A Postmarketing, Phase 4, Multicentre, Prospective, Single-arm Study to Assess the Safety of Fasenra® (Benralizumab) in Adult Patients of Severe Asthma With Eosinophilic Phenotype in India.
Phase: PHASE4
Conditions: In Adult Patients of Severe Asthma With Eosinophilic Phenotype in India
Sponsor: AstraZeneca

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
1 of 6 7  
Cli ni c al St u dy Pr ot oc ol  
St u d y I nt er ve nti o n  Fas e nra ®  ( Be nralizu ma b) 
St u d y Co d e   
D 3 2 5 0 C0 0 0 9 3  
Versi o n   
Versi o n  1. 0  
Dat e  
0 9  M ar  2 0 2 1  
A P ost mar keti ng, P has e 4, M ultice nt re , Pr os pe cti ve , Si ngle -a r m 
St u dy t o Ass ess t he S af et y of Fas e nr a ®  (Be nr aliz u ma b ) i n A d ult  
P atie nts of  Se ve re Ast h ma  wit h  E osi no p hilic  P he not y pe i n I n di a 
S p o ns o r N a me:  Astr a Ze ne c a P h ar m a I n di a Li mite d   
Le gal Re gistere d A d dress: Bloc k N 1, 1 2t h Flo or, 
Ma n yata E m bass y B usiness P ar k 
Ra c he na halli, O uter Rin g R oa d, Ba n galore -5 6 0 0 4 5  
T his Clinic al St u d y Pr ot oc ol has be e n s u bje ct t o a pe er re vie w a c c or din g t o Astra Ze ne c a 
Sta n dar d pr oc e d ures. T he Clinic al St u d y Pr ot oc ol is p u blicly re gistere d a n d t he res ults are 
dis clos e d a n d/ or p u blis he d a c c or din g t o t he Astra Ze ne c a Glo bal P olic y o n Bioet hics a n d in 
c o m plia nc e wit h pre vailin g la ws a n d re g ulatio ns.  
A me n d me nt N u m ber: N ot A p plic a ble  
St u d y I nter ve ntio n: Fas e nra ® ( Be nraliz u ma b)  
St u d y P has e: 4  
R e d a ct e d f or P u bli c Di s cl o s ur e

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
2 of 6 7  
 
S h o rt Title:  
P ost mar ketin g, P has e 4, Safet y St u d y of Fas e nra ( Be nraliz u ma b) in I n dia  
A c r o n y m:   
F A S T: F A s e nra S afet y T rial in I n dia  
St u d y P h ysici a n N a me a n d C o nt act I nfo r m ati o n will be pr o vi de d s e p ar atel y  
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
3 of 6 7  
 
T A B L E O F C O N T E N T S 
TI T L E P A G E  ..................................................................................................................... 1  
T A B L E O F C O N T E N T S  .................................................................................................... 3  
1  
P R O T O C O L S U M M A R Y ................................................................................. 6  
1. 1  
S y n o psis  ........................................................................................................... 6  
1. 2  
Sc he ma ............................................................................................................11  
1. 3  
Sc he d ule of A ctivities  ..................................................................................... 1 2  
2  
I N T R O D U C TI O N .......................................................................................... 1 4  
2. 1  
St u d y Ratio nale  .............................................................................................. 1 4  
2. 2  
Ba c k gr o u n d  .................................................................................................... 1 5  
2. 3  
Be nefit/ Ris k Ass ess me nt  ................................................................................. 1 6  
2. 3. 1  
Ris k Ass ess me nt  ............................................................................................. 1 6  
2. 3. 2  
Be nefit Ass ess me nt  ......................................................................................... 1 8  
2. 3. 3  
O verall Be nefit: Ris k C o nclusi o n  .................................................................... 1 8  
3  
O BJ E C TI V E S A N D E N D P OI N T S .................................................................. 1 9  
4  
S T U D Y D E SI G N  ........................................................................................... 2 0  
4. 1  
O verall D esi g n ................................................................................................ 2 0  
4. 2  
Scie ntific Rati o nale f or St u d y D esig n  .............................................................. 2 0  
4. 3  
J ustific ati o n f or D os e ...................................................................................... 2 0  
4. 4  
E n d of St u d y D efiniti o n  .................................................................................. 2 1  
5  
S T U D Y P O P U L A TI O N  .................................................................................. 2 2  
5. 1  
I ncl usio n Criteria ............................................................................................ 2 2  
5. 2  
E xcl usio n Criteria  ........................................................................................... 2 2  
5. 3  
Lifest yle C o nsi derati o ns .................................................................................. 2 3  
5. 4  
Scre e n Failures  ............................................................................................... 2 3  
6  
S T U D Y I N T E R V E N TI O N .............................................................................. 2 4  
6. 1  
St u d y I nter ve nti o n A d mi nistere d  ..................................................................... 2 4  
6. 1. 1  
St u d y Dr u g  ..................................................................................................... 2 4  
6. 2  
Pre paratio n/ H a n dli n g/ St ora ge/ A c c o u nta bilit y  .................................................. 2 4  
6. 3  
Me as ures t o Mi ni mis e Bias  ............................................................................. 2 5  
6. 4  
Li mitati o ns of t he St u d y  .................................................................................. 2 5  
6. 5  
St u d y I nter ve nti o n C o m plia nc e  ....................................................................... 2 6  
6. 6  
C o nc o mita nt T hera p y ...................................................................................... 2 6  
6. 6. 1  
Ba c k gr o u n d Me dic ati o n  .................................................................................. 2 6  
7  
DI S C O N TI N U A TI O N 
O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L .......................................................... 2 8  
7. 1  
Dis c o ntin uatio n of St u d y I nter ve ntio n  ............................................................. 2 8  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
4 of 6 7  
 
7. 2  
P artici pa nt Wit h dra w al Fr o m t he St u d y  ........................................................... 2 9  
7. 3  
L ost t o F oll o w u p ............................................................................................ 2 9  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ............................................. 3 0  
8. 1  
Safet y Ass ess me nts  ......................................................................................... 3 0  
8. 1. 1  
P h ysic al E xa minati o ns  .................................................................................... 3 0  
8. 1. 2  
Vital Si g ns  ...................................................................................................... 3 0  
8. 1. 3  
Cli nic al Safet y La b orat or y Ass ess me nts  .......................................................... 3 1  
8. 1. 4  
Ot her Safet y Ass ess me nts  ............................................................................... 3 1  
8. 1. 5  
A d vers e E ve nts a n d Serio us A d vers e E ve nts  .................................................... 3 1  
8. 1. 6  
Ti me P erio d a n d Fre q ue nc y f or C olle ctin g A d vers e E ve nt a n d Serio us A d vers e 
E ve nt I nf or mati o n  ........................................................................................... 3 2  
8. 2  
F oll o w- u p of A d vers e E ve nts a n d Serio us A d vers e E ve nts  ............................... 3 2  
8. 2. 1  
Ca us alit y C olle ctio n ........................................................................................ 3 3  
8. 2. 2  
A d vers e E ve nts Bas e d o n Sig ns a n d S y m pt o ms  ............................................... 3 3  
8. 2. 3  
A d vers e E ve nts Bas e d o n E xa mi nati o ns a n d Tests ............................................ 3 3  
8. 2. 4  
Re p ortin g of Seri o us A d vers e E ve nts  ............................................................... 3 3  
8. 2. 5  
Pre g na nc y ....................................................................................................... 3 4  
8. 2. 5. 1  
Mater nal E x p os ure .......................................................................................... 3 4  
8. 2. 5. 2  
P ater nal E x p os ure  ........................................................................................... 3 5  
8. 3  
Effe ctive ness Ass ess me nts  .............................................................................. 3 5  
8. 3. 1  
Ass ess me nt of Ast h ma E xa c er batio ns  .............................................................. 3 5  
8. 3. 2  
Pre br o nc h o dilat or F E V 1 T hr o u g h S pir o metr y  .................................................. 3 6  
8. 3. 3  
C ha n ge in Bl o o d E osi n o p hils  .......................................................................... 3 6  
8. 3. 4  
Me dic ati o n Err or  ............................................................................................ 3 6  
8. 3. 5  
D e vic e C o nstit ue nt D eficie ncies  ...................................................................... 3 6  
8. 4  
O ver d os e  ........................................................................................................ 3 7  
8. 5  
H u ma n Bi olo gic al Sa m ples  ............................................................................. 3 7  
8. 5. 1  
P har ma c o kinetics ............................................................................................ 3 8  
8. 5. 2  
I m m u n o ge nicit y Ass ess me nts .......................................................................... 3 8  
8. 5. 3  
P har ma c o d y na mics  ......................................................................................... 3 8  
8. 6  
C olle cti o n of H u ma n Biol o gic al Sa m ple Bio mar kers ........................................ 3 8  
8. 7  
C olle cti o n of O pti o nal Ge n o mics I nitiati ve Sa m ple  .......................................... 3 8  
8. 8  
H e alt h Ec o n o mics O R Me dic al Res o urc e Utilis atio n a n d H e alt h Ec o n o mics  ..... 3 8  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  .............................................................. 3 9  
9. 1  
Statistic al H y p ot hes es  ..................................................................................... 3 9  
9. 2  
Sa m ple Size D eter mi natio n  ............................................................................. 3 9  
9. 3  
P o p ulati o ns f or A nal ys es  ................................................................................. 3 9  
9. 4  
Statistic al A nal ys es  ......................................................................................... 4 0  
9. 4. 1  
Ge neral C o nsi derati o ns  ................................................................................... 4 0  
9. 4. 2  
Safet y  ............................................................................................................. 4 1  
9. 4. 2. 1  
Pri mar y E n d p oi nts  .......................................................................................... 4 1  
9. 4. 2. 2  
Ot her Safet y E n d p oi nts  ................................................................................... 4 1  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
5 of 6 7  
 
9. 4. 3  
Effe ctive ness  .................................................................................................. 4 1  
9. 4. 4  
Ot her A nal ys es  ............................................................................................... 4 2  
9. 5  
I nteri m A nal ys es ............................................................................................. 4 2  
9. 6  
D ata M o nit ori n g C o m mitte e ............................................................................ 4 2  
1 0  
S U P P O R TI N G   
D O C U M E N T A TI O N   
A N D   
O P E R A TI O N A L 
C O N SI D E R A TI O N S  ...................................................................................... 4 3  
11  
R E F E R E N C E S  ............................................................................................... 6 1  
A S T R A Z E N E C A SI G N A T U R E( S)  ................................................................................... 6 4  
A S T R A Z E N E C A SI G N A T U R E( S)  ................................................................................... 6 5  
A S T R A Z E N E C A SI G N A T U R E( S)  ................................................................................... 6 6  
A S T R A Z E N E C A SI G N A T U R E( S)  ................................................................................... 6 7  
 
LI S T O F FI G U R E S 
Fig ure 1   
St u d y D esi g n ......................................................................................... 1 1  
 
LI S T O F T A B L E S 
Ta ble 1   
Sc he d ule of A ctivities ............................................................................ 1 2  
Ta ble 2   
O bje cti ves a n d E n d p oi nts ....................................................................... 1 9  
Ta ble 3   
St u d y Dr u g ............................................................................................ 2 4  
Ta ble 4   
P o p ulati o ns f or A nalysis ......................................................................... 4 0  
 
LI S T O F A P P E N DI C E S 
A p pe n di x A    
Re g ulat or y, Et hic al, a n d St u d y O versi g ht C o nsi derati o ns ........................ 4 3  
A p pe n di x B    
A d vers e E ve nts: D efinitio ns a n d Pr oc e d ures f or Re c or din g, E valuatin g, 
F oll o w- u p, a n d Re p orti n g ....................................................................... 4 8  
A p pe n di x C    
H a n dlin g of H u ma n Biol o gic al Sa m ples ................................................. 5 3  
A p pe n di x D    
Be nraliz u ma b, prefille d s yrin ge (I n dia-s pe cific pa c ka ge ins ert) Fas e nra ™
.............................................................................................................. 5 4  
A p pe n di x E    
C or o na vir us Dis e as e- 1 9 V a c cinatio n G ui da nc e ....................................... 5 8  
A p pe n di x F    
A b bre viati o ns ........................................................................................ 5 9  
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
6 of 6 7  
 
1   
P R O T O C O L S U M M A R Y 
1. 1  
S y n o psis 
Pr ot o c ol Title:  A P ost mar ketin g, P has e 4, M ultic e ntre, Pr os pe ctive, Sin gle-a r m St u d y t o Ass ess 
t he Safet y of Fas e nra ® ( Be nraliz u ma b) in A d ult P atie nts of  Se vere Ast h ma Wit h E osin o p hilic 
P he n ot y pe in I n dia 
S h o rt Title:   
P ost mar ketin g , P has e 4, Safet y St u d y of Fas e nra ® ( Be nraliz u ma b) in I n dia 
R ati o n ale:  
T he tre at me nt o ptio ns f or  patie nts wit h s e vere ast h ma wit h e osin o p hilic p he n ot y pe w h o re mai n 
u nc o ntr olle d o n in hale d c ortic oster oids (I C S) a n d lo n g-a ctin g beta-a g o nists ( L A B A) are li mit e d. 
Fas e nra ( be nraliz u ma b) is a h u ma nis e d, af uc os ylate d, m o n oclo nal a ntib o d y t hat bin ds s pe cific all y 
t o t he h u ma n interle u kin- 5 (I L- 5) re c e pt or alp ha s u b u nit (I L-5 R α) of e osin o p hils a n d bas o p hils. 
A d ministratio n of be nraliz u ma b res ults in ra pid a n d ne ar-c o m plete de pletio n of e osin o p hils in t he 
perip heral blo o d a n d in t he air w a ys wit h ass ociate d clinic al i m pr o ve me nt in patie nts wit h s e vere 
e osin o p hilic ast h ma. Be nraliz u ma b w as a p pr o ve d as a n a d d- o n mainte na nc e tre at me nt f or patie nts 
of s e vere ast h ma wit h a n e osin o p hilic p he n ot y pe b y t he U nite d States ( U S) F o o d a n d Dr u g 
A d ministratio n ( F D A) in N o ve m ber 2 0 1 7 (f or t h os e a ge d 1 2 ye ars a n d older), a n d b y t he E ur o pe a n 
Me dicines A ge nc y ( E M A) in J a n uar y 2 0 1 8 (f or a d ult  patie nts). As o n A u g ust 2 0 2 0, be nraliz u m a b 
has be e n a p pr o ve d in 5 8 c o u ntries.    
T he re c e nt E ur o pe a n Res pirat or y S ociet y/ A meric a n T h ora cic S ociet y g uida nc e re c o m me n ds a nti ‒
I L-5 a n d a nti‒ I L-5 R α a ge nts  f or s e vere u nc o ntr olle d a d ult e osin o p hilic ast h ma p he n ot y pes, a n d 
re c o g nises t he lo n g-ter m s afet y of t hes e t hera pies. T he Glo bal I nitiative f or Ast h ma ( GI N A) 2 0 2 0 
g uidelines re c o m me n d a d d -o n a nti-I L-5 a n d a nti‒ I L-5 R α tre at me nt f or s e vere e osin o p hilic ast hma 
t hat is u nc o ntr olle d o n ste p 4-5 tre at me nt ( E vide nc e le vel A). T he s afet y of be nraliz u ma b is w ell 
esta blis he d bas e d o n t he piv otal SI R O C C O, C A LI M A , a n d Z O N D A trials. Inte grate d a nalys es 
( B O R A) of a p pr o xi mately 1 6 0 0  patie nts wit h ast h ma ( a b o ut 1 0 0 0  of w h o m w ere e x p os e d t o 
be nraliz u ma b f or u p t o 2  ye ars) s u g gest t hat e osin o p hil de pletio n b y be nraliz u ma b tre at me nt d oes 
n ot incre as e ris k of infe ctio ns or malig na ncies . T he M E L T E MI st u d y ( o pe n-la bel s afet y e xte nsio n 
st u d y of B O R A) re p orte d t hat be nraliz u ma b w as w ell t olerate d a n d t he m ost fre q ue ntly re p orte d 
tre at me nt-e mer ge nt a d vers e e ve nts ( T E A Es) w ere nas o p har y n gitis, ast h ma, he a da c he, viral u p per 
res pirat or y tra ct infe ctio n, a n d br o nc hitis, re p orte d b y 1 3 1 ( 2 9. 4 %), 5 5 ( 1 2. 3 %), 5 3 ( 11. 9 %), 4 8 
( 1 0. 8 %), a n d 4 5 ( 1 0. 1 %) patie nts, res pe ctively(M E L T E MI D 3 2 5 0 C 0 0 0 3 7 
clinic al st u d y re p ort  
[ C S R], 2 0 2 0). T he c u m ulative w orld wide p ost-a p pr o val patie nt e x p os ure t o be nraliz u ma b sinc e 
la u nc h is esti mate d t o be 7 9,3 0 7 patie nt- ye ars, a n d t he c o m bine d a nalys es of t he c u m ulati v e 
effic a c y a n d s afet y data a vaila ble c o ntin ue t o in dic ate a p ositive 
be nefit-ris k bala nc e of 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
8 of 6 7  
 
Dis cl os ure St ate me nt : T his is a sin gle-a r m, p ost mar ketin g s afet y, t olera bilit y, a n d eff e ctive ness  
st u d y wit h n o mas kin g . 
N u m be r of P artici p a nts: 
C o nsiderin g a dr o p o ut rate of 5 %, a t otal of 1 4 7  participa nt s fr o m 1 0 c e ntres a cr oss I n dia will be  
e nr olle d int o t he st u d y, f or t he p ur p os e of o btainin g data fr o m at le ast 1 3 9  participa nts.  
( Refer t o Se ctio n 9. 2  f or details). 
I ncl usi o n Criteri a 
P atie nts are eligible t o be inclu de d in t he st u d y o nly if all of t he f ollo win g criteria a p ply:  
1.  Male or fe male patie nts 1 8 t o 7 5 ye ars of a ge inclusive, at t he ti me of sig nin g t he inf or m e d 
c o ns e nt 
2.  P atie nts wit h p h ysicia n’s c o nfir me d dia g n osis of s e vere ast h ma wit h a n e osin o p hilic 
p he n ot y pe, ie, a dia g n osis of s e vere ast h ma in pre c e din g at le ast 1 2 m o nt hs, 
wit h a n 
e osin o p hil c o u nt of ≥3 0 0 c ells/ µ L at s cre e nin g, re q uirin g tre at me nt wit h hig h- d os e I C S 
( > 5 0 0 μ g  flutic as o ne pr o pio nate dr y p o w der f or m ulatio n, or  > 8 0 0 μ g  b u des o nide dr y p o w der 
f or m ulatio n, or  e q uivale nt t otal daily d os e) a n d a L A B A as mainte na nc e tre at me nt f or at 
le ast 3 m o nt hs prior t o e nr ol me nt 
3.  A de cre as e d lu n g f u nctio n wit h pre br o nc h o dilat or ( Pre- B D ) f orc e d e x pirat or y v olu me in 1 
s e c o n d ( F E V 1) of < 8 0 % pre dicte d, de m o nstrate d b y s pir o metr y at s cre e nin g  
4.  At le ast 2 d oc u me nte d ast h ma e xa c er batio ns in t he pre c e e din g 1 2  m o nt hs, e xc e pt in 3 0 da ys 
bef ore t he date of inf or me d c o ns e nt, t hat re q uire d t he us e of a s yste mic c ortic oster oid or 
te m p orar y incre as e fr o m t he patie nt’s us ual mainte na nc e d os e of oral c ortic oster oid ( O C S) 
5.  D oc u me nte d p ost br o nc h o dilat or ( p ost- B D ) re versibilit y in F E V 1 of ≥1 2 % a n d ≥2 0 0 m L  i n 
F E V 1 wit hin 1 2 m o nt hs bef ore first d os e. If hist oric al d oc u me ntatio n is n ot a vaila ble, 
re versibilit y 
m ust be de m o nstrate d a n d d oc u me nte d at s cre e nin g or D a y 1 bef ore first d os e 
6.  Be nraliz u ma b naïve patie nts w h o ha ve n ot pre vio usly re c eive d be nraliz u ma b prior t o t he 
start of t his st u d y 
7.  P a tie nts w h o are willin g a n d c a pa ble of givin g sig ne d inf or me d c o ns e nt as des cribe d i n 
A p pe n dix A , w hic h inclu des c o m plia nc e wit h t he re q uire me nts a n d restrictio ns liste d in t he 
inf or me d c o ns e nt f or m (I C F) a n d in t his pr ot oc ol. 
 
E x cl usi o n Criteri a  
P a tie nts will be e xclu de d fr o m t he st u d y if a n y of t he f ollo win g criteria a p ply: 
1.  Clinic ally i m p orta nt p ul m o nar y dis e as e ot her t ha n ast h ma (e g, a ctive lu n g infe ctio n, c hr o nic 
o bstr uctive p ul m o nar y dis e as e, br o nc hie ctasis, p ul m o nar y fibr osis, c ystic fibr osis etc.) or 
e ver be e n dia g n os e d 
wit h p ul m o nar y or s yste mic dis e as e, ot her t ha n ast h ma, t hat are 
ass ociate d wit h ele vate d perip heral e osin o p hil c o u nts (e g, aller gic br o nc h o p ul m o n ar y 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
9 of 6 7  
 
as per gillosis/ m yc osis, 
C h ur g- Stra uss s y n dr o me, h y pere osin o p hilic s y n dr o me), w hic h c a n 
c o nf o u n d t he o utc o me ass ess me nt 
2.  P atie nts c urre ntly e nr olle d in a n inter ve ntio nal clinic al st u d y in parallel inclu din g t h os e wit h 
a n y biolo gic tre at me nt 
3.  P atie nts w h o ha ve re c eive d a n y biolo gic wit hin 3 0 da ys prior t o t he date of inf or me d c o ns e nt. 
4.  K n o w n hist or y of aller g y or re a ctio n t o t he be nraliz u ma b f or m ulatio n 
or e xcipie nts 
( L- histidine, L- histidine h y dr oc hloride 
m o n o h y drate, α-tre halos e dih y drate, p olys or bate 2 0, 
w ater f or inje ctio n)  
5.  Hist or y of a na p h yla xis t o a n y biolo gic t hera p y  
6.  A hel mint h parasitic infe ctio n dia g n os e d wit hin 2 4 w e e ks bef ore t he date inf or me d c o ns e nt 
is o btaine d t hat has n ot be e n tre ate d wit h, or has faile d t o res p o n d t o, sta n dar d of c are t hera p y  
7.  A c ute ast h ma e xa c er batio n 3 0  da ys bef ore t he date inf or me d c o ns e nt  
8.  A c ute ast h ma e xa c er batio n bet w e e n s cre e nin g a n d first d os e of st u d y d os e a d ministrati o n. 
9.  A c ute u p per or lo w er res pirat or y infe ctio ns re q uirin g a ntibiotics or a ntiviral 
me dic ati o n 
wit hin 3 0 da y s bef ore t he date inf or me d c o ns e nt  
1 0.  P atie nts wit h malig na nc y wit hin 5 ye ars prior t o e nr ol me nt, wit h t he e xc e ptio n of a de q uatel y 
tre ate d in-sit u c arcin o ma of t he c er vix, uteri, bas al, or s q ua m o us c ell c arcin o ma or n o n-
mela n o mat o us s kin c a nc er wit h a ctive or re c e nt malig na nc y 
1 1.  A n y clinic all y 
sig nific a nt 
a b n or mal fin din gs in 
p h ysic al 
e xa minatio n, 
vital sig ns, 
ha e mat olo g y, clinic al c he mistr y, or urinalysis, w hic h, in t he o pinio n of t he in vestigat or, ma y 
p ut t he participa nt at ris k be c a us e of his/ her participatio n in t he st u d y 
1 2.  Hist or y of c urre nt alc o h ol, dr u g, or c he mic al a b us e or past a b us e t hat w o uld i m pair or ris k 
t he participa nt’s f ull participatio n in t he st u d y, in t he o pinio n of t he in vestigat or 
1 3.  Fe male patie nts w h o are pre g na nt or la ctatin g or pla n nin g a fa mily d urin g t he st u d y perio d. 
 
I nte r v e nti o n Gr o u ps a n d D ur ati o n: 
A d ult patie nt s of  s e vere ast h ma wit h e osin o p hilic p he n ot y pe re q uirin g hig h d os e of I C S plus 
L A B A, w h o are pres cribe d Fas e nra ( be nraliz u ma b) 3 0  m g , s u bc uta ne o usly, as a n a d d- o n t hera p y 
in line wit h t he loc al pres cribin g inf or matio n a n d are s c he d ule d t o initiate tre at me nt wit h Fas e nra 
( be nraliz u ma b) wit hin 2 w e e ks will be e nr olle d in t he st u d y. T he re c o m me n de d d os e of Fas e nra 
(be nraliz u m a b ) is 3 0 m g  a d ministere d o nc e e ver y 4 w e e ks f or t he first 3  d os es, a n d t he n o nc e e ver y 
8  w e e k s t here after b y s u bc uta ne o us inje ctio n int o t he u p per ar m, t hig h, or a b d o me n as per loc al 
pres cribin g inf or matio n  (A p pe n dix  D ). T he st u d y dr u g, Fas e nra ( be nraliz u ma b ), will be pr o vid e d 
b y Astra Ze ne c a P har ma I n dia Lt d. f or t he d uratio n of t he st u d y.  
T he t otal st u d y d uratio n will be 2 4 w e e ks, inclu din g 1 6  w e e ks of st u d y tre at me nt. 
 Scre e nin g d uratio n: 2 w e e ks 
 St u d y perio d: 2 4 w e e ks 
o  Tre at me nt d uratio n ( 4 d os es) : 1 6  w e e ks ( D a y 1, We e k 4,  We e k 8,  a n d We e k 1 6) 
o  P ost-tre at me nt f ollo w- u p d uratio n: 8 w e e ks ( We e k 2 4 ) 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 0  of 6 7  
 
D at a M o nit o ri n g C o m mitte e : N o  
St atistic al M et h o ds 
Statistic al a nalys es will be pri marily des criptive in nat ure. D ata fr o m all participatin g sites will be 
p o ole d f or a nalysis. Sta n dar d met h o d of i m p utatio n will be a p plie d f or a n y missin g/ partial dates.  
A c c or din g t o t he o bje ctives, t he rele va nt para meters will be s u m maris e d des criptively 
wit h 
a p pr o priate statistic al 
met h o ds: c ate g oric al varia bles 
will 
be pres e nte d usin g fre q ue ncies, 
perc e nta ges, a n d c orres p o n din g 9 5 % c o nfide nc e inter vals ( CIs ) ( usin g Clo p per- P e ars o n e xa ct 
met h o d, w here a p pr o priate) a n d c o ntin u o us varia bles usin g n u m ber of o bs er vatio ns, arit h metic 
me a n, sta n dar d de viatio n ( S D), me dia n, 2 5 t h a n d 7 5t h perc e ntiles, a n d mini m u m a n d ma xi m u m 
values. T he last me as ure me nt prior t o first d os e of st u d y tre at me nt will s er ve as t he bas elin e 
me as ure me nt.  
T he s afet y para meters inclu di n g 
A Es, de at hs, tre at me nt dis c o ntin uatio n/ m o dific atio n,  patie nt 
dis c o ntin uati o n, la b orat or y data, etc. will be re p orte d usin g s afet y a nalysis s et.  
T he ti me- t o-e ve nt e n d p oint s hall be s u m maris e d usin g K a pla n- Meier ( K M) met h o d alo n g wit h t he 
c orres p o n din g 9 5 % CIs (as a p pr o priate) a n d t he K M c ur ve will be plotte d.  

Clinic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versio n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y 
1 1  of 6 7  
 
1. 2  
Sc he m a 
Fi g ure 1   
St u d y D e si g n 
 
 
 
 
E O S = e n d of st u d y  
 

Clinic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versio n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y 
1 3  of 6 7  
 
a Re c h e c k cli nic al st at us bef or e first d ose of be nr aliz u m a b. 
b C li nic al saf et y la b or at or y assess m e nt will i n cl u de cli nic al c h e mistr y, h a e m at ol o g y, a n d uri n al ysis. Cli nic al c h e mistr y will i n cl u de ser u m al k ali n e p h os p h at ase, ala ni n e 
a mi n otr a nsf er ase, as p art ate a mi n otr a nsf er ase, ga m m a- gl ut a m yl tr a nsf er ase, la ct ate de h y dr o ge n ase, t ot al pr otei n, t otal bilir u bi n, al b u mi n, a n d ser u m cr e ati ni n e. Ha e m at ol o g y will 
i n cl u de h a e m at o crit, le uc o c yt e c o u nt, le uc o c yt e diff er e ntial c o u nt ( a bs ol ut e c o u nt), plat elet c o u nt, a n d h a e m o gl o bi n. Uri n al ysis ( di pstic k) will assess uri n e 
h a e m o gl o bi n/er yt hr o c ytes/ bl o o d, pr ot ei n/al b u mi n, a n d gl uc ose.  
c Ser u m pr e g n a n c y t est will be d o n e at baseli n e a n d U P T will be d o n e at Da y 1, We e k 4, 8, 1 6, 2 4 .  
d T h e vit al si g ns ( p ulse, bl o o d pr ess ur e, r es pir ati o n r at e, a n d b o d y t e m p er at ur e) will be t a k e n bef or e be nr aliz u m a b a d mi nistr ati o n, a n d, if p ossi ble, bl o o d dr a wi n g a n d us ual ast h m a 
c o ntr oller m e dic ati o n. If it is n ot l o gistic all y p ossi ble, s ufficie nt ti m e as p er cli nicia n discr eti o n s h o ul d be all ott e d bet we e n p hle b ot o m y a n d vit al si g ns assess m e nt. F or det ails, 
ple ase r ef er t o Se cti o n 8. 1. 3 . 
e W h e n hist oric al pr o of of p ost br o nc h o dilat or r e v ersi bilit y i n F E V1 is n ot d o c u m e nt e d wit hi n 1 2
 m o nt hs bef or e Visit  1, t h e r e v ersi bilit y t est b y s pir o m etr y will n e e d t o be 
p erf or m e d eit h er d uri n g scr e e ni n g or o n Da y 1 bef or e first d ose.  
f W hile o n st u d y dr u g tr e at m e nt a n d wit hi n 2  m o nt h s aft er t h e e n d of st u d y tr e at m e nt/ disc o nti n uati o n of t h e st u d y dr u g . 
g P artici p a nts will be pr o vi de d a p atie nt diar y t o r e c or d a n y u n desir a ble h e alt h-r elat e d e x p erie n c e or a d v erse e v e nt s o c c urri n g d uri n g t h e st u d y. A d v erse e v e nt s a n d seri o us a d v erse 
e v e nt s m e nti o n e d b ot h i n t h e p atie nt diar y a n d v er ball y c o m m u nic at e d b y t h e p artici p a nt will be r e c or de d.  
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 4  of 6 7  
 
2   
I N T R O D U C TI O N 
Be nraliz u ma b is a h u ma ni se d, af uc os ylate d, m o n oclo nal a ntib o d y t hat bin ds s pe cific ally t o t he 
h u ma n interlu kin-5 ( I L-5 ) re c e pt or alp ha s u b u nit (I L-5 R α ) of tar get c ells s uc h as e osin o p hils a n d 
bas o p hils ( Ta kats u et al, 1 9 9 4; To ba et al, 1 9 9 9 ; P elaia et al, 2 0 2 0 ).  
I nterlu kin-5 , 
major pr o-infla m mat or y c yt o kine, bin ds t o I L-5 R  a n d res ults in a n incre as e d 
e osin o p hilic re cr uit me nt a n d a ctivatio n res ultin g in air w a y infla m matio n  (Ta kats u et al, 1 9 9 4; To ba 
et al, 1 9 9 9; P elaia et al, 2 0 2 0 ). Tar getin g I L-5 R  b y m o n oclo nal a ntib o dies s uc h as be nraliz u ma b is 
a n o vel w a y t o de cre as e e osin o p hilic air w a y infla m matio n  (GI N A , 2 0 2 0 ).  
Se vere e osin o p hilic ast h ma a c c o u nts f or o ver 5 0 % of c as es  wit h s e vere ast h ma , a n d is ass ociate d 
wit h incre as e d dis e as e s e verit y, e xa c er batio n fre q ue nc y, a n d de cre as e d lu n g f u nctio n  (P a v or d, 
2 0 1 3;  Walf or d et al, 2 0 1 4 ; Go nzale z et al, 2 0 1 9). C urre nt g uideli nes re c o m me n d t he a d ditio n of 
a nti-I L-5  t hera pies s uc h as me p oliz u ma b 
or resliz u ma b or a nti-I L-5 re c e pt or t hera p y s uc h as 
be nraliz u ma b f or  patie nts wit h s e vere e osin o p hilic ast h ma ( GI N A, 2 0 2 0 ). Be nraliz u ma b 
w as 
a p pr o ve d as a n a d d- o n mainte na nc e tre at me nt f or patie nts of s e vere ast h ma wit h a n e osin o p hilic 
p he n ot y pe b y t he U nite d States ( U S) F o o d a n d Dr u g A d ministratio n ( F D A) in N o ve m ber 2 0 1 7 
(f or t h os e a ge d 1 2 ye ars a n d older) (Fas e nra ® [ be nraliz u ma b] 
U nite d State d Pres cribin g 
I nf or matio n [ U S PI], 2 0 1 7), a n d b y t he E ur o pe a n Me dicines A ge nc y ( E M A) in J a n uar y 2 0 1 8 (f or 
a d ult patie nts) ( Fas e nra T M  [ be nraliz u ma b] S u m mar y of Pr o d uct C hara cteristics [ S m P C], 2 0 1 9). As 
o n A u g ust 2 0 2 0 it has be e n a p pr o ve d in 5 8 c o u ntries . 
Be nraliz u ma b  w as ge nerally w ell  t olerate d b y patie nts in clinic al trials, wit h n o a p pare nt s afet y 
c o nc er ns.  
2. 1  
St u d y R ati o n ale 
T he tre at me nt o ptio ns f or  patie nts wit h s e vere e osin o p hilic ast h ma w h o re main u nc o ntr olle d o n 
in hale d c ortic oster oids (I C S)/lo n g-a ctin g beta-a g o nists ( L A B A) are e xtre mely li mite d. I n clinic al 
st u dies, be nraliz u ma b 
a d ministratio n res ulte d in ra pid a n d ne arly c o m plete de pletio n 
of 
e osin o p hils in t he perip heral blo o d a n d in t he air w a ys of  patie nts wit h s e vere e osin o p hilic ast h ma, 
wit h ass ociate d i m pr o ve me nts in clinic al s y m pt o ms a n d lu n g f u nctio n ( K olbe c k et al, 2 0 1 0; 
Ble e c ker et al, 2 0 1 6; Fitz gerald et al, 2 0 1 6; B uss e et al, 2 0 1 9).  
T he re c e nt E ur o pe a n Res pirat or y S ociet y/ A meric a n T h ora cic S ociet y g uida nc e re c o m me n ds a nti ‒
I L-5 a n d a nti‒ I L-5 R α a ge nts f or s e vere u nc o ntr olle d a d ult e osin o p hilic ast h ma p he n ot y pes, a n d 
re c o g nises t he lo n g-ter m s afet y of t hes e t hera pies. T he Glo bal I nitiative f or Ast h ma ( GI N A) 2 0 2 0 
g uidelines re c o m me n d a d d -o n a nti-I L-5 a n d a nti‒ I L-5 R α tre at me nt f or s e vere e osin o p hilic ast h ma 
t hat is u nc o ntr olle d o n ste p 4-5 tre at me nt ( E vide nc e le vel A). T he s afet y of be nraliz u ma b is w ell 
esta blis he d bas e d o n t he piv otal SI R O C C O, C A LI M A, a n d Z O N D A trials. I nte grate d a nalys es 
( B O R A) of a p pr o xi mately 1 6 0 0 patie nts wit h ast h ma (a b o ut 1 0 0 0  of w h o m w ere e x p os e d t o 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5  of 6 7  
 
be nraliz u ma b f or u p t o 2  ye ars) s u g gest t hat e osin o p hil de pletio n b y be nraliz u ma b tre at me nt d oes 
n ot incre as e ris k of infe ctio ns or malig na ncies. (J a c ks o n et al, 2 0 2 0). T he re c e ntly c o m plete d 
M E L T E MI st u d y ( o pe n -la bel s afet y e xte nsio n st u d y of B O R A) re p orte d t hat be nraliz u ma b 
w as 
w ell t olerate d a n d t he m ost fre q ue ntly re p orte d mild t o m o derate tre at me nt-e mer ge nt a d vers e 
e ve nts ( T E A Es) w ere nas o p har y n gitis, ast h ma, he a da c he, viral u p per res pirat or y tra ct infe cti o n, 
a n d br o nc hitis, re p orte d b y 1 3 1 ( 2 9. 4 %), 5 5 ( 1 2. 3 %), 5 3 ( 11. 9 %), 4 8 ( 1 0. 8 %), a n d 4 5 ( 1 0. 1 %) 
patie nts, res pe ctively (M E L T E MI D 3 2 5 0 C 0 0 0 3 7 C S R, 2 0 2 0 ). T he c u m ulative w orld -wide p ost -
a p pr o val patie nt e x p os ure  t o be nraliz u ma b sinc e la u nc h is esti mate d t o be 7 9,3 0 7 patie nt-ye ars , 
a n d t he c o m bine d a nalys es of t he c u m ulative  effic a c y a n d s afet y data a vaila ble c o ntin ue t o in dic at e 
a p ositive be nefit -ris k bala nc e of be nraliz u ma b  ( P erio dic Be nefit-Ris k E valuatio n Re p ort, 2 0 2 0) . 
A n o n g oin g 
pr os pe ctive, 
o bs er vatio nal, 
pre g na nc y re gistr y 
( D 3 2 5 0 R 0 0 0 2 6) will e xa min e 
pre g na nc y a n d infa nt o utc o mes in w o me n wit h ast h ma e x p os e d t o be nraliz u ma b a n yti me d uri n g 
pre g na nc y, a n d a n o n g oin g malig na nc y p ost-a ut h orisatio n s afet y st u d y ( D 3 2 5 0 R 0 0 0 4 2) will ass ess 
incide nc e of malig na ncies in s e vere ast h ma patie nts re c eivin g be nraliz u ma b c o m pare d wit h t h os e 
re c eivin g n o n-be nraliz u ma b biolo gics a n d t h os e n ot re c eivin g biolo gics . 
Fas e nra ( b e nraliz u ma b) has be e n re c e ntly a p pr o ve d in I n dia wit h t he c o n ditio n t o c o n d uct a 
P has e 4 p ost mar ketin g st u d y in t he I n dia n p o p ulatio n, as pre vio us st u dies did n ot inclu de patie nts 
fr o m I n dia. T he  c urre nt pr os pe ctive , inter ve ntio nal, p ost mar ketin g  s afet y st u d y is pla n ne d t o 
me et t he re g ulat or y ma n date a n d ass ess t he s afet y of be nraliz u ma b  o ver a perio d of 2 4 w e e ks  in 
a d ult patie nt s of  s e vere ast h ma wit h e osin o p hilic p he n ot y pe in I n dia.  
2. 2  
B ac k gro u n d 
Ast h ma affe cts a b o ut 3 3 9  millio n pe o ple w orld wide a n d a n esti mate d 5 % t o 1 0 % ha ve dis e as e t hat 
re mains s e vere a n d u nc o ntr olle d des pite ma xi mal tre at me nt wit h I C S a n d L A B A ( C h u n g et al, 
2 0 1 4 ; GI N A, 2 0 2 0 ). P atie nts w h o s uffer fr o m s e vere or u nc o ntr olle d ast h ma ha ve a re d uc e d q ualit y 
of life, wit h incre as e d ris k of h os pitalis ati o n a n d m ortalit y, in a d ditio n t o incre as e d he alt h c are 
c osts (R o glia ni et al, 2 0 2 0 ). T he c urre nt a p pr oa c h t o a nti-infla m mat or y c o ntr oller t hera p y i n 
ast h ma is bas e d o n a ste p- wis e inte nsific atio n of a daily mainte na nc e re gi me n a n d pri marily c e ntres 
o n  I C S, tiotr o piu m, le u k otrie ne re c e pt or a nta g o nists wit h a d ditio n of L A B A in s e vere ast h ma 
(GI N A, 2 0 2 0 ). D es pite tre at me nt ma na ge me nt as per g uideli nes, a sig nific a nt n u m ber of  patie nt s 
ha ve ast h ma t hat is n ot w ell c o ntr olle d, a n d t herein lies t he u n met me dic al ne e d wit hin t his 
t hera pe utic are a.  
Wit h ide ntific ati o n of s pe cific bio mar kers f or differe nt ast h ma p he n ot y pes, biolo gic al dr u gs 
are 
c urre ntly in dic ate d f or s e vere e osin o p hil ic ast h ma n ot c o ntr olle d o n ma xi mal d os es of IC S  plus 
L A B A  (GI N A , 2 0 2 0 ). B y tar getin g infla m mat or y 
m ole c ules , t hes e n o vel m o n oclo nal a ntib o die s 
are pr o ve n t o re d uc e ast h ma e xa c er batio ns, maintain s y m pt o m c o ntr ol, a n d re d uc e us e of s yste mic 
ster oids (R o glia ni et al, 2 0 2 0 ). 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 6  of 6 7  
 
Be nraliz u ma b is a n a nti-e osin o p hil, h u ma nis e d af uc os ylate d, m o n oclo nal a ntib o d y (I g G1, ka p pa). 
Be nraliz u ma b bin ds t o t he alp ha s u b u nit of t he h u ma n interle u kin- 5 re c e pt or (I L- 5 R α) wit h hi g h 
affinit y ( 1 6 p M) a n d s pe cificit y. T he I L- 5 re c e pt or is s pe cific ally e x press e d o n t he s urfa c e of 
e osin o p hils a n d bas o p hils. T he a bs e nc e of f uc os e in t he Fc d o main of be nraliz u ma b res ults in hi g h 
affinit y ( 4 5. 5 n M) f or Fc ɣ RIII re c e pt ors o n i m m u ne effe ct or c ells s uc h as nat ural killer ( N K) c ells 
le a din g t o a p o pt osis of e osin o p hils a n d bas o p hils t hr o u g h e n ha nc e d a ntib o d y- de pe n de nt c ell-
me diate d c yt ot o xicit y ( A D C C) ( Be nraliz u ma b I n dia pa c ka ge ins ert ( PI )). 
T he s afet y a n d effic a c y of be nraliz u ma b ha ve be e n de m o nstrate d in 3  P has e  3 ra n d o mis e d trials, 
SI R O C C O, C A LI M A, a n d Z O N D A. Be nraliz u ma b 
w as w ell t olerate d as s h o w n b y lo w 
dis c o ntin uati o n rate ( 2 %) in b ot h t he piv otal 
SI R O C C O a n d C A LI M A st u dies, 
wit h 9 0 % 
of  patie nts assig ne d t o be nraliz u ma b still re c eivin g tre at me nt at 4 8  w e e ks in SI R O C C O . T he 
lo n g-ter m effic a c y a n d s afet y of be nraliz u ma b w as e valuate d in a P has e 3, 5 6- w e e k  e xte nsio n trial, 
B O R A, a n d t he M E L T E MI trial ( o pe n-la bel s afet y e xte nsio n st u d y of B O R A) . The re d uctio n i n 
a n n ual rate of ast h ma e xa c er batio ns o bs er ve d in SI R O C C O a n d C A LI M A w ere maintaine d o ver 
t he s e c o n d ye ar of tre at me nt. I n a d ditio n, n o ne w c o ns e q ue nc es of lo n g-ter m e osin o p hil de pleti o n 
oc c urre d, a n d incide nc es of A E inclu di n g o p p ort u nistic infe ctio ns w ere si milar d urin g t he s e c o n d 
ye ar ( B uss e et al, 2 0 1 8 ). 
H o w e ver,  pre vio us st u dies did n ot inclu de patie nts fr o m I n dia. Fas e nra has be e n re c e ntly a p pr o ve d 
in I n dia wit h t he c o n ditio n t o c o n d uct a P has e 4 p ost mar ketin g st u d y in t he I n dia n p o p ulatio n . T his 
pr os pe ctive p ost mar ketin g s afet y st u d y will ge nerate s afet y data t o  me et t he re g ulat or y ma n date i n 
I n dia.  
A detaile d des criptio n of t he c he mistr y, p har ma c olo g y, effic a c y, a n d s afet y of be nraliz u ma b is 
pr o vide d in t he PI . 
2. 3  
Be nefit/ Ris k Assess me nt 
2. 3. 1  Ris k Ass ess me nt 
Be nraliz u ma b has be e n w ell t olerate d,  wit h t he m ost fre q ue ntly o bs er ve d a d vers e e ve nts ( A Es) 
fr o m t he P has e 3 c o ntr olle d st u dies bein g ge nerally refle ctive of ast h matic patie nt p o p ulatio n. 
P ote ntial ris ks of be nraliz u ma b are as f ollo ws:  
 Serio us infe ctio ns ha ve be e n re p orte d f or be nraliz u ma b. A relatio ns hip bet w e e n e osin o p hil 
de pletio n a n d s erio us infe ctio n has n ot be e n esta blis he d. 
 Malig na ncies ha ve be e n re p orte d at a lo w incide nc e in t he c o m plete d a n d o n g oin g st u die s 
of be nraliz u ma b. E osin o p hils ha ve be e n f o u n d in ass ociatio n wit h s olid t u m o urs, es pe ciall y 
t u m o urs of e pit helial origin ( bre ast a n d c olo n), a n d ma y pla y a n a ctive r ole in t u m o ur 
defe nc e b y m o d ulatin g h ost defe nc es, or ma y be a b ysta n der effe ct. H o w e ver, t he c a use 
a n d c o ns e q ue nc es (ie, 
pr o-t u m o urige nic 
vers us a nti-t u m o uri ge nic) 
of e osin o p hil 
re cr uit me nt a n d a c c u m ulatio n int o t u m o urs are u ncle ar (J a c o bs e n et al, 2 0 1 2 ). T he o verall 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 7  of 6 7  
 
incide nc e of 
malig na nt 
ne o plas ms 
A Es in be nraliz u ma b-tre ate d 
patie nts d urin g t he 
SI R O C C O/ C A LI M A st u dies a n d t he B O R A e xte nsio n w as lo w ( <   1%), wit h n o a p pare nt 
tre n ds in or ga ns or tiss ue t y pes affe cte d. (J a c ks o n et al, 2 0 2 0).  Ris k mini mis ati o n me as ures 
inclu de 
e xclusio n 
of 
patie nts 
wit h 
a ctive 
or re c e nt 
malig na nc y 
a n d r o utin e 
p har ma c o vigila nc e a ctivities. 
 Serio us h y pers e nsitivit y re a ctio ns (inclu din g a na p h yla xis) are a n ide ntifie d ris k of biol o gic 
t hera p y, inclu din g be nraliz u ma b. A na p h yla xis ma y be life-t hre ate nin g. Ris k mini mis ati o n 
inclu des o bs er vatio n perio d at t he clinic al site f ollo win g be nraliz u ma b a d ministratio n i n 
line wit h clinic al pra ctic e f or t he a p pe ara nc e of a n y a c ut e dr u g re a ctio ns. 
 D e velo p me nt of a ntidr u g a ntib o dies ( A D A) t o be nraliz u ma b 
has be e n d oc u me nte d. 
T he oretic al ris ks of de velo pin g 
A D A 
ma y inclu de 
de cre as e d dr u g effic a c y a n d 
h y pers e nsitivit y re a ctio ns (e. g. a na p h yla xis or i m m u ne c o m ple x dis e as e). T here w as n o 
a p pare nt i m pa ct of A D A o n o verall be nraliz u ma b s afet y or effic a c y in t he pre vio us P has e◦3 
st u dies in s e vere e osin o p hilic ast h ma patie nts. 
 E osin o p hils are a pr o mine nt fe at ure of t he infla m mat or y res p o ns e t o hel mint hic parasitic 
infe ctio ns. T heref ore, t here is a t he oretic al ris k t hat pr olo n ge d e osin o p hil de pletio n 
ma y 
di minis h t he a bilit y t o defe n d a gainst hel mint hic parasites. Ris k mini mis atio n 
me as ures 
inclu de e xclusio n of patie nts wit h a n u ntre ate d parasitic infe ctio n, in c o nju nctio n wit h t he 
perf or ma nc e of r o utine p har ma c o vigila nc e a ctivities.

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 8  of 6 7  
 
2. 3. 2  B e nefit Ass ess me nt 
P atie nts wit h s e vere u nc o ntr olle d ast h ma, e nr olle d in t his trial are e x pe cte d t o be nefit fr o m t he 
be nraliz u ma b t hera p y f or s y m pt o matic relief, i m pr o ve d lu n g f u nctio n, fe w er e xa c er batio ns a n d 
fe w er h os pital visits. F or e nr ollin g in t his st u d y, t he p h ysicia n w o uld ha ve alre a d y deter mine d t he 
eligibilit y of t he patie nt w h o w o uld be pres cribe d a n d derive be nefit fr o m be nraliz u ma b. T he c ost 
of t he st u d y tre at me nt will be b or ne b y Astra Ze ne c a f or 4  d os es . D ata ge nerate d fr o m t his st u d y 
will help e valuate t he s afet y of be nraliz u ma b in clinic al s ettin gs in I n dia. It will help pr o vide a 
s afer alter native t o patie nts wit h s e vere u nc o ntr olle d ast h ma, re d ucin g t heir de pe n de nc y o n hi g h 
d os es of lo n g-ter m s yste mic ster oids.  
2. 3. 3  O ve rall B e nefit: Ris k C o ncl usi o n 
Ta kin g int o a c c o u nt t he o verall be nefit-ris k pr ofile of be nraliz u ma b, a n d t he u n met ne e d of 
t he patie nt s of s e vere ast h ma wit h e osin o p hilic p he n ot y pe, t he a nticipate d be nefits o ut w eig h t he 
ris ks f or the  participa nts in t he st u d y.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 0  of 6 7  
 
4   
S T U D Y D E SI G N 
4. 1  
O verall Desi g n 
T his is a P has e 4, sin gle-ar m, pr os pe ctive, m ultic e ntr e , inter ve ntio nal st u d y, desig ne d t o ass ess t he 
s afet y, t olera bilit y, a n d effe ctive ness of be nraliz u ma b in a d ult patie nts of  s e vere ast h ma wit h 
e osin o p hilic p he n ot y pe in I n dia. T he st u d y is pla n ne d t o me et t he p osta p pr o val c o m mit me nt as a 
re g ulat or y re q uire me nt. 
Te n c e ntres a cr oss I n dia will participate in t his st u d y. T he in vestigat ors will be p ul m o n olo gists or 
c hest p h ysicia ns tre atin g ast h ma  patie nt s. Inf or me d c o ns e nt will be o btaine d fr o m  all t he patie nt s 
at s cre e nin g bef ore a n y st u d y-relate d pr oc e d ures are perf or me d. A d ult patie nts of  s e vere ast h ma 
wit h e osin o p hilic p he n ot y pe , w h o are pres cribe d be nraliz u ma b as a n a d d- o n t hera p y b y t he tre atin g 
p h ysicia n, will be e nr olle d in t he st u d y.  
T he t otal st u d y d uratio n will be 2 4 w e e ks, inclu din g 1 6  w e e ks of st u d y tre at me nt, a n d 8 w e e ks 
f ollo w-u p (Fig ure 1 ). 
 Scre e nin g d uratio n: 2 w e e ks 
 St u d y perio d: 2 4 w e e ks 
o  Tre at me nt d uratio n ( 4 d os es): 1 6 w e e ks ( Da y 1, We e k 4,  We e k 8,  a n d We e k 1 6)  
o  P ost-tre at me nt f ollo w- u p d uratio n: 8 w e e ks ( We e k 2 4)  
Be nraliz u ma b will be pr o vide d b y Astra Ze ne c a P har ma I n dia Lt d. f or t he d uratio n of t he st u d y.  
P a rticipa nts will be maintaine d o n t heir c urre ntly pres cribe d t hera pies inclu din g I C S- L A B A 
t hera p y(ies), t hr o u g h o ut t he st u d y d uratio n. 
4. 2  
Scie ntific R ati o n ale f o r St u d y Desi g n 
T his pr o p os e d P has e  4 sin gle-ar m st u d y will f ulfil t he re g ulat or y re q uire me nt as a p ost mar keti n g 
st u d y t o ass ess t he s afet y of 3 0 - m g be nraliz u ma b a d ministere d s u bc uta ne o usly in I n dia n patie nt s 
of  s e vere ast h ma wit h e osin o p hilic p he n ot y pe w h o re main u nc o ntr olle d o n hig h d os es of I C S plus 
L A B A. O win g t o t he re c e nt mar ketin g a p pr o val, t here are n o  data a vaila ble fr o m re al-life st u die s 
in t he I n dia n p o p ulatio n. P articipa nts inclu de d in t his st u d y will be as per t he in dic ate d patie nt 
pr ofile in t he loc al 
pres cribin g inf or matio n, 
s pe cific ally ta kin g int o c o nsideratio n t he 
c o ntrain dic atio ns, w ar nin gs, a n d s pe cial pre c a utio ns f or us e.  
4. 3  
J ustific ati o n f o r D ose  
T he st u d y will e nr ol  patie nts w h o ha ve be e n pres cribe d be nraliz u ma b as per t he loc al pres cribi n g 
inf or matio n. T he re c o m me n de d d os e is 3 0 m g  a d ministere d o nc e e ver y 4 w e e ks f or t he first 3 
d os es, a n d t he n o nc e e ver y 8  w e e ks t here after b y s u bc uta ne o us inje ctio n int o t he u p per ar m, t hi g h, 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 1  of 6 7  
 
or a b d o me n b y t he st u d y p h ysicia n. F o ur  d os es of be nraliz u ma b will be a d ministere d as part of t he 
st u d y. 
4. 4  
E n d of St u d y Defi niti o n 
A  participa nt is c o nsidere d t o ha ve c o m plete d t he st u d y w he n he/s he has c o m plete d his/ her e n d of 
st u d y ( E O S) visit at We e k 2 4, 8  w e e ks after e n d of tre at me nt ( E O T) , as per t he s c he d ule of 
a ctivities ( S o A) in Se ctio n  1. 3 . 
T he E O S is define d as t he last e x pe cte d visit of t he last  participa nt u n der g oin g t he st u d y.  
Se e A p pe n dix  A  f or g uideli nes a b o ut diss e minatio n of st u d y res ults. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 2  of 6 7  
 
5   
S T U D Y P O P U L A TI O N 
St u d y p o p ulatio n 
will inclu de a d ult ( 1 8  t o 7 5  ye ars of a ge) male or fe male  patie nt s w h o ha ve 
s e vere ast h ma wit h e osin o p hilic p he n ot y pe re q uirin g hig h d os e of I C S a n d L A B A.  
Ea c h  participa nt s h o uld me et all t he inclusio n criteria a n d n o ne of t he e xclusio n criteria t o be 
eligible f or t he st u d y. U n der n o circ u msta nc es c a n t here be e xc e ptio ns t o t his r ule. P articipa nts  
w h o d o n ot me et t he e ntr y re q uire me nts are s c re e n failures, refer t o Se ctio n  5. 4 . 
“ E nr olle d” me a ns a  participa nt's, or t heir le gally a c c e pta ble re pres e ntative’s, a gre e me nt t o 
participate in a clinic al st u d y after c o m pletio n of t he inf or me d c o ns e nt pr oc ess. Pr os pe ctive 
a p pr o val of pr ot oc ol de viatio ns t o re cr uit me nt a n d e nr ol me nt criteria, als o k n o w n as pr ot oc ol 
w aivers or e xe m ptio ns, is n ot per mitte d.  
5. 1  
I ncl usi o n Criteri a 
P atie nts are eligible t o be inclu de d in t he st u d y o nly if all of t he f ollo win g criteria a p ply:  
1.  Male or fe male patie nts 1 8  t o 7 5  ye ars of a ge inclusive, at t he ti me of sig nin g t he inf or m e d 
c o ns e nt 
2.  P atie nts wit h  p h ysicia n ’s c o nfir me d dia g n osis of s e vere ast h ma wit h a n e osin o p hilic 
p he n ot y pe , ie, dia g n osis of s e vere ast h ma  in pre c e din g at le ast 1 2  m o nt hs , wit h a n  e osin o p hil 
c o u nt of ≥3 0 0 c ells/ µ L at s cre e nin g, re q uirin g tre at me nt wit h hig h -d os e I C S ( > 5 0 0 μ g 
fluticas o ne pr o pio nate dr y p o w der f or m ulatio n, 
or > 8 0 0 μ g b u des o nide dr y p o w der 
f or m ulatio n, or e q uivale nt t otal daily d os e) a n d a L A B A as mainte na nc e  tre at me nt f or at le ast 
3 m o nt hs prior t o e nr ol me nt  
3.  A de cre as e d lu n g f u nctio n wit h pre br o nc h o dilat or ( Pre- B D ) f orc e d e x pirat or y v olu me i n 
1  s e c o n d ( F E V 1) of < 8 0 % pre dicte d, de m o nstrate d b y s pir o metr y at s cre e nin g  
4.  At le ast 2 d oc u me nte d ast h ma e xa c er batio ns in t he pre c e e din g 1 2  m o nt hs, e xc e pt in 3 0 da ys 
bef ore t he date of inf or me d c o ns e nt, t hat re q uire d t he us e of a s yste mic c ortic oster oid or 
te m p orar y incre as e fr o m t he patie nt’s us ual mainte na nc e d os e of O C S 
5.  D oc u me nte d p ost br o nc h o dilat or ( p ost- B D ) re versibilit y in F E V 1 of ≥1 2 % a n d ≥2 0 0 m L  i n 
F E V 1 wit hin 1 2 m o nt h s bef ore first d os e. If hist oric al d oc u me ntatio n is n ot a vaila ble, 
re versibilit y 
m ust be de m o nstrate d a n d d oc u me nte d at s cre e nin g or D a y 1 bef ore first d os e 
6.  Be nraliz u ma b naive patie nts w h o ha ve n ot pre vio usly re c eive d be nraliz u ma b prior t o t he 
start of t his st u d y 
7.  P a tie nts w h o are willin g a n d c a pa ble of givin g sig ne d inf or me d c o ns e nt as des cribe d i n 
A p pe n dix A , w hic h inclu des c o m plia nc e wit h t he re q uire me nts a n d restrictio ns liste d in t he 
inf or me d c o ns e nt f or m (I C F) a n d in t his pr ot oc ol. 
5. 2  
Excl usi o n Criteri a  
P a tie nts will be e xclu de d fr o m t he st u d y if a n y of t he f ollo win g criteria a p ply: 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 3  of 6 7  
 
1.  Clinic ally i m p orta nt p ul m o nar y dis e as e ot her t ha n ast h ma (e g, a ctive lu n g infe ctio n, c hr o nic 
o bstr uctive p ul m o nar y dis e as e, br o nc hie ctasis, p ul m o nar y fibr osis, c ystic fibr osis etc.) or 
e ver be e n dia g n os e d 
wit h p ul m o nar y or s yste mic dis e as e, ot her t ha n ast h ma, t hat are 
ass ociate d wit h ele vate d perip heral e osin o p hil c o u nts (e g, aller gic br o nc h o p ul m o n ar y 
as per gillosis/ m yc osis, 
C h ur g- Stra uss s y n dr o me, h y pere osin o p hilic s y n dr o me), 
w hic h c a n 
c o nf o u n d t he o utc o me ass ess me nt 
2.  P atie nts c urre ntly e nr olle d in a n inter ve ntio nal clinic al st u d y in parallel inclu din g t h os e wit h 
a n y biolo gic tre at me nt 
3.  P atie nts w h o ha ve re c eive d a n y biolo gic wit hin 3 0 da ys prior t o t he date of inf or me d c o ns e nt. 
4.  K n o w n hist or y of aller g y or re a ctio n t o t he be nraliz u ma b f or m ulatio n 
or e xcipie nts 
( L- histidine, L- histidine h y dr oc hloride 
m o n o h y drate, α-tre halos e dih y drate, p olys or bate 2 0, 
w ater f or inje ctio n)  
5.  Hist or y of a na p h yla xis t o a n y biolo gic t hera p y  
6.  A hel mint h ic parasitic infe ctio n dia g n os e d wit hin 2 4 w e e ks bef ore t he date inf or me d c o ns e nt 
is o btaine d t hat has n ot be e n tre ate d wit h, or has faile d t o res p o n d t o, sta n dar d of c are t hera p y  
7.  A c ute ast h ma e xa c er batio n 3 0  da ys bef ore t he date inf or me d c o ns e nt  
8.  A c ute ast h ma e xa c er batio n bet w e e n s cre e nin g a n d first d os e of st u d y d os e a d ministrati o n. 
9.  A c ute u p per or lo w er res pirat or y infe ctio ns re q uirin g a ntibiotics or a ntiviral 
me dic ati o n 
wit hin 3 0 da y s bef ore t he date inf or me d c o ns e nt  
1 0.  P atie nts wit h malig na nc y wit hin 5 ye ars prior t o e nr ol me nt, wit h t he e xc e ptio n of a de q uatel y 
tre ate d in-sit u c arcin o ma of t he c er vix, uteri, bas al, or s q ua m o us c ell c arcin o ma or n o n-
mela n o mat o us s kin c a nc er wit h a ctive or re c e nt malig na nc y 
1 1.  A n y clinic all y 
sig nific a nt 
a b n or mal fin din gs in 
p h ysic al 
e xa minatio n, 
vital sig ns, 
ha e mat olo g y, clinic al c he mistr y, or urinalysis, w hic h, in t he o pinio n of t he in vestigat or, ma y 
p ut t he participa nt at ris k be c a us e of his/ her participatio n in t he st u d y 
1 2.  Hist or y of c urre nt alc o h ol, dr u g, or c he mic al a b us e or past a b us e t hat w o uld i m pair or ris k 
t he participa nt’s f ull participatio n in t he st u d y, in t he o pinio n of t he in vestigat or 
1 3.  Fe male patie nts w h o are pre g na nt or la ctatin g or pla n nin g a fa mily d urin g t he st u d y perio d. 
 
5. 3  
Lifest yle C o nsi derati o ns 
N o restrictio ns are re q uire d.  
5. 4  
Scree n Fail ures 
Scre e n failures are define d as  participa nts w h o c o ns e nt t o participate in t he clinic al st u d y b ut are 
n ot s u bs e q ue ntly e ntere d in t he st u d y. A mini mal s et of s cre e n failure inf or matio n is re q uire d t o 
e ns ure tra ns pare nt re p ortin g of s cre e n f ailure  participa nts t o me et t he C o ns olidate d Sta n dar ds of 
Re p ortin g Trials ( C O N S O R T) p u blis hin g re q uire me nts a n d t o res p o n d t o q ueries fr o m re g ulat or y 
a ut h orities. 
Mini mal inf or matio n inclu des de m o gra p h y, s cre e n failure details, eligibilit y criteria, 
a n d a n y s erio us a d vers e e ve nt ( S A E).  
F or patie nts w h o w ere e xclu de d d ue t o ast h ma e xa c er batio n, res cre e nin g c a n be d o ne p ost 3 0 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 4  of 6 7  
 
da ys of c o m pletio n of tre at me nt of ast h ma e xa c er batio n pr o vide d ot her inclusio n criteria are met. 
Res cre e ne d participa nts s h o uld be assig ne d t he s a me participa nt n u m ber as f or t he initial 
s cre e nin g 
6   
S T U D Y I N T E R V E N TI O N 
6. 1  
St u d y I nterve nti o n A d mi nistere d 
6. 1. 1   
St u dy D r ug  
St u d y dr u g inf or matio n is pr o vide d in Ta ble 3 . 
Ta ble 3   
St u d y D r u g  
I nte r ve nti o n n a me  
Be nralizu ma b  
Ty pe  
Bi ol o gic  
D os e f or m ul ati o n   
Prefille d s yri n g e  
Unit dos e str e n gt h   
3 0  mg / m L 
D os a g e l e vels  
3 0  mg  a d mi nist ere d o n ce e v er y 4 we e k s f or t h e first 3 d os es a n d t he n o n ce e v er y 
8  we e k s t h ere aft er 
R o ute of a d mi nistr ati o n   
S u b c ut an eo us  i nje cti o n i nt o t h e arm, u p p er ar m, t hi g h, or a b d o me n  
S o ur ci n g  
Be nralizu ma b  will b e pr o vi d e d b y Astra Zene c a P h ar ma I n dia Lt d. f or t h e d urati o n 
of t h e st u d y  (4  d os es)  
P ac k a g i n g a n d l a belli n g 
Be nralizu ma b will b e pr o vi d e d i n si n gle-d ose prefille d s yri n ge. Ea c h s yri n ge will 
b e la b elle d i n a c c or d a n ce wit h Go o d M a n ufa ct uri n g Pra cti c es ( G M P) A n n ex 1 3 an d 
as p er I n dia n re g ulat or y re q uire me nt  
C ur r e nt/f or me r n a mes   
Fas e nra ®, M E DI -5 6 3  
  
All d os es of t he st u d y dr u g will be a d ministere d at t he st u d y clinics. Serio us h y pers e nsitivit y 
re a ctio ns (inclu din g a na p h yla xis) are a n ide ntifie d ris k f or be nraliz u ma b. After a d ministratio n of 
t he st u d y dr u g, t he patie nts will be o bs er ve d at t he clinic al site in line wit h clinic al pra ctic e f or 
t he a p pe ara nc e of a n y a c ute dr u g re a ctio ns. 
6. 2  
Pre p arati o n/ H a n dli n g/ Stora ge/ Acco u nt a bility 
1.  T he in vestigat or or desig ne e m ust c o nfir m a p pr o priate te m perat ure c o n ditio ns ha ve be e n 
maintaine d d urin g tra nsit f or all st u d y inter ve ntio n re c eive d a n d a n y dis cre pa ncies are 
re p orte d a n d res olve d bef ore us e of t he st u d y inter ve ntio n. 
2.  O nly participa nts e nr olle d in t he st u d y ma y re c eive st u d y inter ve ntio n a n d o nly a ut h oris e d 
site staff ma y s u p ply or a d minister st u d y inter ve ntio n. All st u d y inter ve ntio n m ust be 
st ore d in a s e c ure, e n vir o n me ntally c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mate d) are a 
in a c c or da nc e wit h t he la belle d st ora ge c o n ditio ns wit h a c c ess li mite d t o t he in vestigat or 
a n d a ut h oris e d site staff. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 5  of 6 7  
 
3.  T he in vestigat or, instit uti o n, or t he he a d of t he me dic al instit utio n ( w here a p plic a ble) is 
res p o nsible f or st u d y inter ve ntio n a c c o u nta bilit y, re c o nciliatio n, a n d re c or d mainte na nc e 
(ie, re c eipt, re c o nciliatio n, a n d final dis p ositi o n re c or ds). 
4.  Be nraliz u ma b is t o be st ore d at t he st u d y c e ntre in a s e c ure d fa cilit y wit h li mite d a c c e ss 
a n d c o ntr olle d te m perat ure. T he te m perat ure s h o uld be m o nit ore d o n a daily basis a n d 
d oc u me nte d in t he te m perat ure- m o nit orin g lo g. 
5.  Be nraliz u ma b m ust be ke pt in t he original pa c ka ge a n d u n der c o n ditio ns s pe cifie d o n t he 
la bel ( bet w e e n 2° C t o 8° C ( 3 6° F t o 4 6° F), pr ote cte d fr o m t he lig ht). 
6.  T he s yrin ge ma y be ke pt at r o o m te m perat ure u p t o 2 5 ° C f or a ma xi m u m of 1 4 da ys. After 
re m o val fr o m t he refrigerat or, be nr aliz u ma b m ust be us e d wit hin 1 4 da ys or dis c ar de d. 
7.  Bef ore a d ministratio n, w ar m t he s yrin ge b y le a vin g c art o n at r o o m te m perat ure ge nerally 
f or 3 0 min utes. Vis ually ins pe ct f or partic ulate matter a n d dis c olo uratio n a n d if clo u d y a n d 
dis c olo ure d, s h o uld n ot be us e d. 
8.  D o n ot us e in t he f ollo win g c as es: 
 te m perat ure e xc ursio n o n re c eipt or d urin g st ora ge at t he st u d y 
 da ma ge d kit o n re c eipt 
 da ma ge d s yrin ge 
T he c e ntre staff s h o uld n ot us e affe cte d be nraliz u ma b a n d s h o uld i m me diately c o nta ct a n 
Astra Ze ne c a re pres e ntative f or f urt her g uida nc e.  
M ore detaile d inf or matio n a b o ut t he d os a ge, pre paratio n, a n d a d ministratio n of be nraliz u ma b 
ma y be f o u n d in t he a brid ge d pres cribin g inf or matio n of be nraliz u ma b  (A p pe n dix  D ).  
6. 3  
Me as ures t o Mi ni m ise Bi as 
T his is a n o pe n-la bel st u d y; p ote ntial bias will be re d uc e d b y e nr ollin g c o ns e c utive participa nt s 
fittin g int o t he inclusio n criteria fr o m t he res pe ctive sites in a n eff ort t o re d uc e t he s ele ctio n bias. 
If a participa nt wit h dra ws fr o m t he st u d y, t he y will n ot be re pla c e d.  
Astra Ze ne c a or desig ne e ma y a c c ess  participa nt le vel data f or m o nit ori n g p ur p os es.  
6. 4  
Li mit ati o ns of t he St u d y 
T his st u d y has n o c o ntr ol gr o u p a n d will f ollo w a b o ut 1 4 7 patie nts d urin g t he perio d of 2 4  w e e ks. 
Give n t hes e c o n ditio ns, t he s afet y a n d effe ctive ness data a vaila ble f or c olle ctio n ma y be li mit e d 
c o m pare d wit h ra n d o mis e d clinic al trials. T he data ge nerate d b y t he st u d y will be us e d t o me et t he 
p ost-a p pr o val c o m mit me nt a n d pres e nte d in des criptive 
w a y. T he des criptive data will be 
p u blis he d o nly loc ally. T his st u d y will ge nerate res ults fr o m a wider ra n ge of data t ha n t h os e 
pre vio usly derive d fr o m t he m ore li mite d clinic al trial s ettin g. T his st u d y will pr o vide inf or mati o n 
o n t he I n dia n patie nt p o p ulatio n t hat is tre ate d wit h F as e nra.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 6  of 6 7  
 
6. 5  
St u d y I nterve nti o n C o m pli a nce 
T he a d ministratio n of t he st u d y inter ve ntio n s h o uld be re c or de d in t he a p pr o priate s e ctio ns of t he 
ele ctr o nic c as e re p ort f or m (e C R F ). 
T he st u d y inter ve ntio n will be a d ministere d at t he st u d y c e ntre o n tre at me nt visits a n d wit hin visit 
win d o ws as s pe cifie d in Ta ble  1 . P articipa nts will re c eive st u d y inter ve ntio n dire ctly fr o m t he 
in vestigat or/ desi g ne e, 
u n der 
me dic al s u per visio n. 
T he date a n d ti me if a p plic a ble, of d os e 
a d ministere d in t he clinic will be re c or de d in t he s o urc e d oc u me nts a n d re c or de d in t he e C R F . T he 
d os e of st u d y inter ve ntio n a n d st u d y  participa nt ide ntific atio n 
will be c o nfir me d at t he ti me of 
d osin g b y a me m ber of t he st u d y site staff ot her t ha n t he pers o n a d ministerin g t he st u d y 
inter ve ntio n. 
6. 6  
C o nc o mit a nt T hera p y 
I nf or matio n a b o ut an y  tre at me nt in t he 3 m o nt h s bef ore  t he date of inf or me d c o ns e nt, a n d all 
c o nc o mita nt tre at me nts  inclu din g tre at me nt/ me dic atio ns f or ast h ma t hat t he participa nt is 
re c eivin g at t he ti me of e nr ol me nt or re c eives d urin g t he st u d y, m ust be re c or de d in t he e C R F 
alo n g wit h: 
 
re as o n f or us e 
 
dates of a d ministratio n inclu din g start a n d e n d dates 
 
d os a ge inf or matio n inclu din g d os e a n d fre q ue nc y 
T he st u d y p h ysicia n s h o uld be c o nta cte d if t here are a n y q uestio ns re gar din g c o nc o mita nt or prior 
t hera p y. 
6. 6. 1   
B ac k gro u n d 
M e dic ati o n 
P articipa nts in t he st u d y are re q uire d t o be tre ate d wit h hig h- d os e I C S ( > 5 0 0 μ g flutic as o n e 
pr o pio nate dr y p o w der f or m ulatio n, or > 8 0 0 μ g b u des o nide dr y p o w der f or m ulatio n, or e q uivale nt 
t otal daily d os e) a n d a L A B A as mainte na nc e f or at le ast 3 m o nt hs prior t o e nr ol me nt. S yste mic or 
I C S s h o uld n ot be a br u ptly dis c o ntin ue d u p o n initiatio n of t hera p y wit h be nraliz u ma b. Re d ucti o n 
in c ortic oster oid d os es, if a p pr o priate, s h o uld be gra d ual. 
T he ai m of t his st u d y is t o re vie w t he s afet y a n d effe ctive ness of be nraliz u ma b as a d d- o n t hera p y 
in u p  t o 1 4 7 patie nts in I n dia in t he p ost mar ketin g s ettin g. T heref ore, t he ba c k gr o u n d ast h ma 
c o ntr oller me dic atio ns s h o uld be maintaine d at a sta ble d os e fr o m Visit  1 u ntil t he e n d of t he st u d y. 
If c ha n gin g t he I C S- L A B A d os e is ju d ge d as ne c ess ar y b y t he in vestigat or, t he justific atio n s h o ul d 
be d oc u me nte d in t he s o urc e a n d t he c ha n ge in t he d os es s h o uld be refle cte d in t he e C R F.  
Ba c k gr o u n d me dic atio n will n ot be pr o vide d b y Astra Ze ne c a.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 7  of 6 7 
 
 
A d ditio nal c o ntr ollers t hat are la belle d f or ast h ma a n d allo w e d as per pr ot oc ol will n ot be 
pr o vide d b y Astra Ze ne c a.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 8  of 6 7  
 
7   
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L 
7. 1  
Disc o nti n u ati o n of St u d y I nterve nti o n 
It ma y be ne c ess ar y f or a participa nt t o per ma ne ntly dis c o ntin ue ( definitive dis c o ntin uati o n) t he 
st u d y inter ve ntio n. If st u d y inter ve ntio n is per ma ne ntly dis c o ntin ue d, t he  participa nt  will  re mai n 
in t he st u d y t o be e valuate d f or s afet y a n d effe ctive ness  para meters. E valuatio ns a n d s afet y 
ass ess me nts at t he ti me of dis c o ntin uati o n of st u d y inter ve ntio n 
ma y be perf or me d as per st u d y 
p h ysicia n  dis cretio n .  
N ote t hat dis c o ntin uati o n fr o m st u d y inter ve ntio n is N O T t he s a me t hin g as a wit h dra w al fr o m t he 
st u d y. P articipa nts will be dis c o ntin ue d fr o m be nraliz u ma b in t he f ollo win g sit uatio ns: 
 P articipa nt is fre e t o dis c o ntin ue tre at me nt at a n y p oint of ti me, wit h o ut preju dic e t o f urt her 
tre at me nt (s e e Se ctio n  7. 2 ) 
 D e velo p me nt of a n y st u d y- s pe cific criteria f or dis c o ntin uati o n :  
a. a na p h yla ctic re a ctio n t o be nraliz u ma b re q uirin g a d ministratio n of e pine p hrine  
b.  de velo p me nt of hel mint h parasitic infestatio ns re q uirin g h os pitalis ati o n  
c. inte nsive c are u nit a d missio n wit h pr olo n ge d int u batio n a n d me c ha nic al ve ntilati o n 
f or ast h ma-relate d e ve nt 
 Se vere n o n-c o m plia nc e t o st u d y pr ot oc ol inclu di n g if a n y d os e of be nraliz u ma b is miss e d 
d urin g t he c o urs e of t he st u d y  
 Eligibilit y re q uire me nt f o u n d n ot t o be f ulfille d (s e e Se ctio n  5. 1 , Se ctio n  5. 2 ) 
 Pre g na nc y (s e e Se ctio n  8. 2. 5 ) 
 L ost t o f ollo w- u p  
 
Bef ore a de cisio n t o dis c o ntin ue a participa nt fr o m be nraliz u ma b instit ute d, t he in vestigat or s h o ul d 
c aref ully c o nsider w het her c o ntin uatio n o n be nraliz u ma b or dis c o ntin uatio n of be nraliz u ma b will 
be in t he best interest of t he patie nt, a n d w het her t he iss ue c a n be mitigate d b y p ost p o nin g or 
s kip pin g t he d os e. It is hig hly re c o m me n de d t hat t he Astra Ze ne c a st u d y p h ysicia n be c o ns ulte d 
bef ore t he be nraliz u ma b dis c o ntin uati o n tra ns a ctio n ta kes pla c e. I n c as e of s afet y c o nc er ns 
be nraliz u ma b a d ministrati o n 
ma y be i m me diately wit h held u ntil t he final de cisio n is ma de.  
Se e t he S o A f or data t o be c olle cte d at t he ti me of inter ve ntio n dis c o ntin uati o n a n d f ollo w- u p a n d 
f or a n y f urt her e valuatio ns t hat ne e d t o be c o m plete d. 
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 9  of 6 7  
 
7. 2  
P artici p a nt Wit h dra wal Fro m t he St u d y 
 A participa nt ma y wit h dra w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest, or ma y be 
wit h dra w n at a n y ti me at t he dis cretio n of t he in vestigat or f or s afet y, be ha vio ur al, 
c o m plia nc e, or a d ministrative re as o ns. T his is e x pe cte d t o be u nc o m m o n. 
 A participa nt 
w h o c o nsiders 
wit h dra win g fr o m t he st u d y 
m ust be inf or me d b y t he 
in vestigat or a b o ut m o difie d f ollo w- u p o ptio ns (e g, tele p h o ne c o nta ct, a c o nta ct wit h a 
relative or tre atin g p h ysicia n, or inf or matio n fr o m me dic al re c or ds). 
 If t he participa nt wit h dra ws c o ns e nt f or dis clos ure of f ut ure inf or matio n, t he S p o ns or ma y 
retain a n d c o ntin ue t o us e a n y data c olle cte d bef ore s uc h a wit h dra w al of c o ns e nt. 
 If a participa nt wit h dra ws fr o m t he st u d y, it s h o uld be c o nfir me d if he/s he still a gre es f or 
e xistin g s a m ples t o be  us e d in line wit h t he original c o ns e nt. If he/s he re q uests wit h dra w al 
of c o ns e nt f or us e of s a m ples, destr uctio n of a n y s a m ples ta ke n a n d n ot teste d s h o uld be 
c arrie d o ut in line wit h w hat w as state d in t he inf or me d c o ns e nt a n d loc al re g ulatio n. T he 
in vestigat or m ust d oc u me nt t he de cisio n o n us e of e xistin g s a m ples in t he site st u d y re c or ds 
a n d inf or m t he S p o ns or. 
Dis c o ntin uatio n of s pe cific sites or of t he st u d y as a w h ole are ha n dle d as part of A p pe n dix  A . 
7. 3  
L ost t o Foll o w u p 
P articipa nt is c o nsidere d lost t o f ollo w- u p w he n a n y of t he f ollo win g atte m pts of c o nta ct ha ve 
faile d: 
3 atte m pts of tele p h o ne c alls, fa xes, or e mails; ha vin g s e nt 1  c ertifie d 
mail; o ne 
u ns uc c essf ul eff ort t o c he c k t he vital stat us of t he  participa nt usin g p u blicly a vaila ble s o urc es, if 
allo w e d b y loc al re g ulatio ns.  
At t hat visit,  participa nts s h o uld be e nc o ura ge d t o re main in t he st u d y t o c o m plete all s u bs e q ue nt 
st u d y visits, pr oc e d ures a n d ass ess me nts or alter natively a gre e t o be c o nta cte d b y p h o ne c alls 
at m o nt hly inter vals t o c olle ct A Es/ S A Es, c ha n ges in c o nc o mita nt 
me dic atio n, 
he alt h c are 
utilis ati o n, a n d ast h ma e xa c er batio n inf or matio n.  
Re as o ns f or wit h dra w al of be nraliz u ma b s h o uld be re c or de d in t he e C R F.  
 
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 0  of 6 7  
 
8   
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S 
 St u d y pr oc e d ures a n d t heir ti min g are s u m maris e d in t he S o A. Pr ot oc ol w aivers or 
e xe m ptio ns are n ot allo w e d. 
 T he in vestigat or will e ns ure t he a c c ura c y a n d c o m plete ness of t he data re c or de d o n t he 
e C R F. 
 T he in vestigat or will sig n t he c o m plete d e C R F. A c o p y of t he c o m plete d e C R F will be 
arc hive d at t he st u d y site. 
 A d here nc e t o t he st u d y desig n re q uire me nts, inclu din g t h os e s pe cifie d in t he S o A, is 
ess e ntial a n d re q uire d f or st u d y c o n d uct. 
 All 
s cre e nin g 
e valuatio ns  
m ust 
be c o m plete d 
a n d re vie w e d t o 
c o nfir m t hat 
p ote ntial participa nts me et all eligibilit y criteria. T he in vestigat or will maintain a s cre e nin g 
lo g t o re c or d details of all participa nts s cre e ne d a n d t o c o nfir m eligibilit y or re c or d re as o ns 
f or s cre e nin g failure, as a p plic a ble. 
 Blo o d s a m ple c olle ctio n a n d pre g na nc y test will be perf or me d as per S o A. 
 P ost br o nc h o dilat or s pir o metr y will be perf or me d at s cre e nin g f or participa nts wit h o ut prior 
d oc u me ntatio n ( d oc u me ntatio n wit hin 1 2 m o nt hs bef ore Visit 1)  of re versibilit y.  
 Pr oc e d ures c o n d ucte d as part of t he participa nt’s r o utine clinic al 
ma na ge me nt (e g, blo o d 
c o u nt) a n d o btaine d bef ore sig nin g of t he I C F ma y be us e d f or s cre e nin g or bas elin e 
p ur p os es pr o vide d t he pr oc e d ures met t he pr ot oc ol-s pe cifie d criteria a n d w ere perf or me d 
wit hin t he ti me fra me define d in t he S o A. 
8. 1  
S afet y Assess me nts 
Pla n ne d ti me p oints f or all s afet y ass ess me nts are pr o vide d in t he S o A.  
8. 1. 1   
P hysic al E x a mi nati o ns 
 A tar gete d p h ysic al e xa minatio n will be perf or me d inclu di n g ass ess me nts of t he 
f ollo win g: ge neral a p pe ara nc e, res pirat or y, c ar dio vas c ular, a b d o me n, s kin, he a d a n d ne c k 
(inclu din g e ars, e yes, n os e, a n d t hr oat), ly m p h n o des, t h yr oid, m us c ulos keletal (inclu din g 
s pine a n d e xtre mities) a n d ne ur olo gic al s yste ms.  
 A n y ne w fin din g(s) or a g gra vate d e xistin g fin din g(s), ju d ge d as clinic all y sig nific a nt b y 
t he in vestigat or, will be re p orte d as a n A E as des cribe d in Se ctio n 8. 2. 2  a n d Se ctio n 
8. 2. 3 . 
P h ysic al e xa minatio n will be perf or me d at ti me p oints as s pe cifie d in t he S o A.  
8. 1. 2   
Vit al Si g ns 
Vital sig ns ( p uls e, blo o d press ure, res piratio n rate, a n d b o d y te m perat ure) a n d ele ctr oc ar dio gra m 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 1  of 6 7  
 
( E C G) will be o btaine d in a c c or da nc e wit h s c he d ule pr o vide d in Ta ble  1 .  
T he vital sig ns will be ta ke n bef ore be nraliz u ma b a d ministratio n, a n d, if p ossible, blo o d dra win g 
a n d us ual ast h ma c o ntr oller me dic atio n.  
A n y ne w fin din g(s) or a g gra vate d e xistin g fin din g(s), ju d ge d as clinic all y sig nific a nt b y t he 
in vestigat or, will be re p orte d as a n A E as des cribe d in Se ctio n  8. 2. 2  a n d Se ctio n 8. 2. 3 . 
8. 1. 3   
Cli nic al S afet y L a borat ory Ass ess me nts 
Blo o d a n d urine s a m ples f or deter minatio n of clinic al c he mistr y, ha e mat olo g y, a n d urinalysis will 
be c olle cte d at s cre e nin g a n d at E O S ( D a y 1 6 8 ± 7) as in dic ate d in t he S o A.  
Clinic al c he mistr y will inclu de s er u m alkaline p h os p hatas e, ala nine a min otra nsferas e, as partate 
a min otra nsferas e, ga m ma gluta m yl tra nsferas e, la ctate de h y dr o ge nas e, t otal pr otein, t otal 
bilir u bi n, alb u min, a n d s er u m cre atinine. H a e mat olo g y will inclu de ha e mat ocrit, le uc oc yte c o u nt, 
le uc oc yte differe ntial c o u nt (a bs olute c o u nt), platelet c o u nt, a n d ha e m o glo bin. 
Urinalysis 
( dipstic k) will ass ess urine ha e m o glo bi n/er yt hr oc ytes/ blo o d, pr otein/alb u mi n, a n d gluc os e.  
A d ditio nal s afet y s a m ples 
ma y be c olle cte d if clinic ally in dic ate d at t he dis cretio n of t he 
in vestigat or. T he date, ti me of c olle ctio n, a n d res ults ( values, u nits, a n d refere nc e ra n ges) will be 
re c or de d o n t he a p pr o priate e C R F. 
T he clinic al c he mistr y, ha e mat olo g y, a n d urinalysis will be perf or me d at a loc al la b orat or y at or 
ne ar t he in vestigat or site. Sa m ple t u bes ma y var y de pe n din g o n la b orat or y met h o d us e d a n d r o utin e 
pra ctic e at t he site.  
8. 1. 4   
Ot he r S afet y Ass ess me nts 
N ot a p plic a ble.  
8. 1. 5   
A dve rs e E ve nts a n d Se ri o us A dve rs e E ve nts 
T h e Principal in vestigat or is res p o nsible f or e ns urin g t hat all staff in v olve d in t he st u d y are fa miliar 
wit h t he c o nte nt of t his s e ctio n.  
T he definitio ns of a n A E or S A E c a n be f o u n d in A p pe n dix  B . 
A d vers e e ve nts will be re p orte d b y t he  participa nt ( or w he n a p pr o priate b y a c are giver, s urr o gate, 
or t he  participa nt's le gally a ut h oris e d re pres e ntative). P articipa nts will be pr o vide d a patie nt diar y 
t o re c or d a n y u n desira ble he alt h-relate d e x perie nc e or a d vers e e ve nts oc c urrin g d urin g t he st u d y. 
A d vers e e ve nts a n d s erio us a d vers e e ve nts me ntio ne d b ot h in t he patie nt diar y a n d ver ball y 
c o m m u nic ate d b y t he participa nt will be re c or de d.  
T he in vestigat or a n d a n y desig ne es are res p o nsible f or dete ctin g, d oc u me ntin g, a n d re c or din g 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 2  of 6 7  
 
e ve nts t hat me et t he definitio n of a n A E.  
8. 1. 6   
Ti me Pe ri o d a n d Fre q ue nc y f or C olle cti ng A dve rs e E ve nt a n d 
Se ri o us A dve rs e E ve nt I nf or mati o n 
A d vers e e ve nts a n d s erio us a d vers e e ve nts will be c olle cte d fr o m ti me of sig nat ure of t he I C F, 
t hr o u g h o ut t he tre at me nt perio d a n d inclu din g t he f ollo w- u p perio d ( We e k 2 4) . 
If t he in vestigat or be c o mes a w are of a n y S A E wit h a s us pe cte d c a us al relatio ns hip t o 
be nraliz u ma b t hat oc c urs after t he e n d of t he clinic al st u d y in a  participa nt tre ate d b y hi m or her, 
t he in vestigat or s hall, wit h o ut u n d ue dela y, re p ort t he S A E t o t he s p o ns or. 
8. 2  
Foll o w- u p of A d verse Eve nts a n d Seri o us A d verse Eve nts 
A n y A Es t hat are u nres olve d at t he f ollo w- u p in t he st u d y are f ollo w e d u p b y t he in vestigat or f or 
as lo n g as me dic ally in dic ate d, b ut wit h o ut f urt her re c or din g in t he e C R F. Astra Ze ne c a retains 
t he rig ht t o re q uest a d ditio nal inf or matio n f or a n y participa nt wit h o n g oin g A E(s)/ S A E(s) at t he 
e n d of t he st u d y, if ju d ge d ne c ess ar y.  
A d v e rs e E v e nt Vari a ble s 
' T he f ollo win g varia bles will be c olle cte d f or e a c h A E: 
 a d vers e e ve nt ( ver bati m) 
 t he date w he n t he A E starte d a n d st o p pe d 
 ma xi m u m inte nsit y of t he A E 
 w het her t he A E is s erio us or n ot 
 in vestigat or c a us alit y ratin g a gainst Fas e nra ( be nraliz u ma b) ( yes or n o) 
 a ctio n ta ke n wit h re gar d t o Fas e nra ( be nraliz u ma b) 
 a d vers e e ve nt c a us e d participa nt’s wit h dra w al fr o m st u d y ( yes or n o) 
 o utc o me 
I n a d ditio n, t he f ollo win g varia bles will be c olle cte d f or S A Es: 
 date A E met criteria f or S A E 
 date in vestigat or be c a me a w are of S A E 
 a d vers e e ve nt is s erio us d ue t o 
 date of h os pitalis ati o n 
 date of dis c har ge 
 pr o ba ble c a us e of de at h 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 3  of 6 7  
 
 date of de at h 
 a ut o ps y perf or me d 
 c a us alit y ass ess me nt in relatio n t o st u d y pr oc e d ure(s) 
 c a us alit y ass ess me nt t o ot her me dic atio n 
8. 2. 1   
C a us alit y C olle cti o n 
T he in vestigat or s h o uld ass ess c a us al relatio ns hip bet w e e n Fas e nra ( be nraliz u ma b) a n d e a c h A E 
a n d S A E, a n d a ns w er ‘ yes ’ or ‘ n o ’ t o t he q uestio n ‘ D o y o u c o nsider t hat t here is a re as o na ble 
p ossibilit y t hat t he e ve nt ma y ha ve be e n c a us e d b y Fas e nra ( be nraliz u ma b)?’  
A g uide t o t he inter pretatio n of t he c a us alit y q uestio n is f o u n d in A p pe n dix  B  t o t he Clinic al St u d y 
Pr ot oc ol.  
8. 2. 2   
A dve rs e E ve nts B as e d o n Si g ns a n d S y m pt o ms 
All A Es s p o nta ne o usly re p orte d b y t he  participa nt or re p orte d in res p o ns e t o t he o pe n q uesti o n 
fr o m t he st u d y site staff: ‘ H a ve y o u ha d a n y he alt h pr o ble ms sinc e t he pre vio us visit/ y o u w ere last 
as ke d?’, or re ve ale d b y o bs er vatio n will be c olle cte d a n d re c or de d in t he e C R F. W he n c olle cti n g 
A Es, t he re c or din g of dia g n os es is preferre d ( w he n p ossible) t o re c or din g a list of sig ns a n d 
s y m pt o ms. H o w e ver, if a dia g n osis is k n o w n a n d t here are ot her sig ns or s y m pt o ms t hat are n ot 
ge nerally part of t he dia g n osis, t he dia g n osis a n d e a c h sig n or s y m pt o m will be re c or de d s e parately.  
8. 2. 3   
A dve rs e E ve nts B as e d o n E x a mi nati o ns a n d Tests 
T he res ults fr o m t he Clinic al St u d y Pr ot oc ol ma n date d la b orat or y tests a n d vital sig ns will be 
s u m maris e d in t he C S R.  
D eterioratio n as c o m pare d t o bas eline in pr ot oc ol- ma n date d la b orat or y values, vital sig ns  s h o ul d 
t heref ore o nly be re p orte d as A Es if t he y f ulfil a n y of t he S A E criteria, are t he re as o n f or 
dis c o ntin uati o n of tre at me nt wit h Fas e nra ( be nraliz u ma b) or are c o nsidere d clinic all y rele va nt as 
ju d ge d b y t he in vestigat or ( w hic h ma y inclu de b ut n ot li mite d t o c o nsideratio n as t o w het her 
tre at me nt or n o n- pla n ne d visits w ere re q uire d or ot her a ctio n w as ta ke n wit h t he st u d y inter ve nti o n, 
e g, d os e a djust me nt or dr u g interr u ptio n).   
If deterioratio n in a la b orat or y value/ vital sig ns is ass ociate d wit h clinic al sig ns a n d s y m pt o ms, t he 
sig n or s y m pt o m will be re p orte d as a n A E a n d t he ass ociate d la b orat or y res ult/ vital sig ns will be 
c o nsidere d as a d ditio nal inf or matio n.  
8. 2. 4   
R e porti ng of Se ri o us A dve rs e E ve nts 
All S A Es ha ve t o be re p orte d, w het her or n ot c o nsidere d c a us ally relate d t o t he be nraliz u ma b, or 
t o t he st u d y pr oc e d ure(s). All S A Es will be re c or de d in t he e C R F. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 4  of 6 7  
 
If a n y S A E oc c urs in t he c o urs e of t he st u d y, in vestigat ors or ot her site pers o n nel will inf or m t he 
a p pr o priate Astra Ze ne c a re pres e ntatives wit hin o ne  da y ie, i m me diately 
b ut n o l ate r t h a n 
2 4  h o urs of w he n he or s he be c o mes a w are of it.  
T he desig nate d Astra Ze ne c a re pres e ntative will w or k wit h t he in vestigat or t o e ns ure t hat all t he 
ne c ess ar y inf or matio n is pr o vide d t o t he Astra Ze ne c a P atie nt Safet y data e ntr y site wit hi n 
o ne  c ale n d ar d a y  
of initial 
re c eipt f or fatal a n d life-t hre ate nin g 
e ve nts a n d 
wit hi n 
5  c ale n d ar da y s of initial re c eipt f or all ot her S A Es.  
F or fatal or life-t hre ate nin g A Es w here i m p orta nt or rele va nt inf or matio n is missin g, a ctive f ollo w -
u p will be u n derta ke n i m me diately. I n vestigat ors or ot her site pers o n nel will inf or m Astra Ze ne ca 
re pres e ntatives of a n y f ollo w- u p inf or matio n 
o n a pre vio usly re p orte d S A E 
wit hin 
o ne 
c ale n dar  da y, ie, i m me diately b ut n o l ate r t h a n 2 4  h o urs of w he n he or s he be c o mes a w are of it.  
O nc e t he in vestigat ors or ot her site pers o n nel in dic ate a n A E is s erio us in t he ele ctr o nic data 
c a pt ure ( E D C) s yste m, a n a ut o mate d e mail alert is s e nt t o t he desig nate d 
Astra Ze ne ca 
re pres e ntative or  in vestigat or/ dele gate d 
st u d y site staff re p orts a S A E t o t he a p pr o priat e 
Astra Ze ne c a re pres e ntative b y tele p h o ne.  
T he Astra Ze ne c a re pres e ntative will a d vis e t he in vestigat or/st u d y site staff h o w t o pr oc e e d.  
T he refere nc e d oc u me nt f or definitio n of e x pe cte d ness/liste d ness is t he I n vestigat or’s Br oc h ure 
f or t he Astra Ze ne c a dr u g. 
8. 2. 5   
Pre g na nc y 
All pre g na ncies a n d o utc o mes of pre g na nc y s h o uld be re p orte d t o Astra Ze ne c a e xc e pt f or t he st u d y 
participa nt w h os e pre g na nc y is dis c o vere d bef ore re c eivin g a n y st u d y dr u g.   
8. 2.5.1   
M ate r n al E x p os ure 
If a participa nt 
be c o mes pre g na nt d urin g t he st u d y, be nraliz u ma b s h o uld be dis c o nti n u e d 
i m me diately. 
Pre g na nc y its elf is n ot re gar de d as a n A E u nless t here is a s us picio n t hat be nraliz u ma b 
ma y ha ve 
interfere d wit h t he effe ctive ness of a c o ntra c e ptive me dic atio n. C o n ge nital a b n or malities/ birt h 
defe cts a n d s p o nta ne o us 
mis c arria ges s h o uld be re p orte d a n d ha n dle d as S A Es. Ele ctiv e 
ter minatio n of pre g na nc y wit h o ut c o m plic atio ns s h o uld n ot be ha n dle d as A Es. T he o utc o me of all 
pre g na ncies (s p o nta ne o us mis c arria ge, ele ctive ter minatio n, e ct o pic pre g na nc y, n or mal birt h or 
c o n ge nital a b n or malit y) s h o uld be f ollo w e d u p a n d d oc u me nte d e ve n if t he  participa nt 
w as 
dis c o ntin ue d fr o m t he st u d y.  
If a n y pre g na nc y oc c urs in t he c o urs e of t he st u d y, t he n t he in vestigat or or ot her site pers o n nel 
inf or ms t he a p pr o priate Astra Ze ne c a re pres e ntatives wit hin 1  d a y , ie, i m me diately b ut n o l ate r 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 5  of 6 7  
 
t h a n 2 4 h o urs of w he n he or s he be c o mes a w are of it.  
T he desig nate d Astra Ze ne c a re pres e ntative w or ks wit h t he in vestigat or t o e ns ure t hat all rele va nt 
inf or matio n is pr o vide d t o t he Astra Ze ne c a P atie nt Safet y data e ntr y site wit hi n 1 o r 
5  c ale n d ar d a ys  f or S A Es (s e e Se ctio n  8. 2. 4 ) a n d wit hi n 3 0  d a ys  f or all ot her pre g na ncies. 
T he s a me ti melines a p ply w he n o utc o me inf or matio n is a vaila ble.  
8. 2.5.2   
P ate r n al E x p os ure  
Pre g na nc y of t he  participa nt’s part ners will n ot be c o nsidere d a n A E. H o w e ver, t he o utc o me of 
all pre g na ncies (s p o nta ne o us mis c arria ge, ele ctive ter minatio n, e ct o pic pre g na nc y, n or mal birt h, 
or c o n ge nital a b n or malit y) s h o uld be f ollo w e d u p a n d d oc u me nte d in t he Pre g na nc y Re p ort 
F or m. C o ns e nt fr o m t he part ner m ust be o btaine d bef ore t he Pre g na nc y Re p ort F or m is 
c o m plete d.  
8. 3  
Effecti ve ness Assess me nts 
8. 3. 1   
Ass ess me nt of Ast h ma E x ace r bati o ns 
F or t he pr ot oc ol, a n ast h ma e xa c er batio n will be define d as a w ors e nin g of ast h ma t hat le a ds t o 
a n y of t he f ollo win g: 
 Us e of s yste mic c ortic oster oids ( or a te m p orar y incre as e in a sta ble O C S ba c k gr o u n d d os e) 
f or at le ast 3 da ys; a sin gle de p ot-inje cta ble d os e of c ortic oster oids 
will be c o nsidere d 
e q uivale nt t o a 3- da y c o urs e of s yste mic c ortic oster oids.  
 A n E R / Ur ge nt c are visit ( define d as e valuatio n a n d tre at me nt f or < 2 4 h o ur s in a n 
e mer ge nc y de part me nt or ur ge nt c are c e ntre) d ue t o ast h ma t hat re q uire d s yste mic 
c ortic oster oids (as per a b o ve).  
 A n in patie nt h os pitalis ati o n ( define d as a d missio n t o a n in patie nt fa cilit y a n d/ or e valuati o n 
a n d tre at me nt in a he alt hc are fa cilit y f or ≥2 4 h o ur s) d ue t o ast h ma. 
Ti me t o first ast h ma e xa c er batio n will be c alc ulate d fr o m bas eline ( Da y 1) t o ti me of first 
e xa c er batio n. T he start of a n e xa c er batio n is define d as t he start date of s yste mic c ortic oster oi ds , 
E R  or ur ge nt c are visits re q uirin g s yste mic c ortic oster oids, or h os pital a d missio ns d ue t o ast h ma, 
w hic he ver oc c urs e arlier. T he e n d date is define d as t he last da y of s yste mic c ortic oster oids or 
E R/ Ur ge nt c are/ h os pital dis c har ge, w hic he ver oc c urs later.  
I n or der t o c alc ulate t he n u m ber of e xa c er batio ns e x perie nc e d b y a patie nt d urin g t he st u d y perio d, 
t he f ollo win g r ule will be a p plie d. T he start of a n e xa c er batio n is define d as t he start date of 
s yste mic c ortic oster oids or start date of a te m p orar y incr e as e in a sta ble O C S ba c k gr o u n d d os e, or 
start date of h os pital a d missio n, w hic he ver oc c urs e arlier. T he e n d date is define d as t he last da y 
of  s yste mic c ortic oster oids or t he last da y of a te m p orar y incre as e in a sta ble O C S ba c k gr o u n d 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 6  of 6 7  
 
d os e, or t he date of dis c har ge fr o m a h os pital, 
w hic he ver oc c urs later. A d ditio nal s yste mic 
c ortic oster oid tre at me nts, E R / ur ge nt c are visits re q uirin g us e of s yste mic c ortic oster oids, or 
in patie nt h os pitalis ati o n d ue t o ast h ma oc c urrin g d urin g a n e xa c er batio n s h o uld n ot be re gar de d as 
a ne w e xa c er batio n. I n or der t o be c o u nte d f or as a ne w e xa c er batio n it m ust be pre c e de d b y at 
le ast 7 da ys in w hic h neit her criterio n is f ulfille d. 
Ma xi m u m f ollo w- u p ti me f or a participa nt is a p pr o xi mately 2 4 w e e ks; define d a s t he ti me fr o m 
e nr ol me nt t o t he date of E O S visit. F or a participa nt lost t o f ollo w- u p, t his will be define d as t he 
ti me fr o m e nr ol me nt t o t he ti me p oint after w hic h a n e xa c er batio n c o uld n ot be ass ess e d, (ie, t he 
last c o nta ct date). A n y e xa c er batio ns after t his ti me p oint will n ot be inclu de d in a nalys es. 
Pr o p ortio n of participa nts wit h ≥ 1 ast h ma e xa c er batio n(s) bet w e e n bas eline a n d e n d of st u d y will 
be s u m maris e d.  
8. 3. 2   
Pre bro nc ho dil at o r F E V 1 T hro ug h S piro met ry 
Pre- B D F E V 1 will be re c or de d b y s pir o metr y a n d perf or me d at s cre e nin g t o c o nfir m t he 
dia g n osis of s e vere ast h ma. 
8. 3. 3   
C ha nge i n Bl o o d E osi no p hils 
C ha n ge in blo o d e osin o p hil le vels fr o m bas eline at We e k 4 , We e k 1 6 , a n d We e k 2 4 will be 
ass ess e d.  
8. 3. 4   
M e dic ati o n Error 
If a me dic atio n err or oc c urs in t he c o urs e of t he st u d y, t he n t he in vestigat or or ot her site 
pers o n nel inf or ms t he a p pr o priate Astra Ze ne c a re pres e ntatives wit hin 1  d a y , ie, i m me diately b ut 
n o l ate r t h a n 2 4  h o urs  of w he n he or s he be c o mes a w are of it. 
T he desig nate d Astra Ze ne c a re pres e ntative w or ks wit h t he in vestigat or t o e ns ure t hat all rele va nt 
inf or matio n is c o m plete d wit hin 1  (I nitial Fatal/ Life- T hre ate nin g or f ollo w- u p Fatal/ Life-
T hre ate nin g) o r 5  ( ot her s erio us initial a n d f ollo w- u p) c ale n d ar d a ys  if t here is a n S A E 
ass ociate d wit h t he me dic atio n err or (s e e Se ctio n  8. 2. 4 ) a n d wit hi n 3 0  d a ys  f or all ot her 
me dic atio n err ors.  
T he definitio n of a me dic atio n err or c a n be f o u n d in A p pe n dix  B . 
8. 3. 5   
D e vice C o nstit ue nt D eficie ncies 
 I n a c o m binatio n dr u g- de vic e st u d y dr u g (e. g. a c c ess oris e d prefille d s yrin ge), t he de vic e 
c o nstit ue nt deficie nc y is a n ina de q ua c y of a de vic e c o nstit ue nt wit h res pe ct t o its ide ntit y, 
q ualit y, d ura bilit y, relia bilit y, s afet y, or perf or ma nc e. T hes e deficie ncies inclu de 
malf u nctio ns, us e err ors, a n d inf or matio n s u p plie d b y t he ma n ufa ct urer. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 7  of 6 7  
 
 F or de vic e c o nstit ue nt deficie ncies, it is ver y i m p orta nt t hat t he in vestigat or des cribes a n y 
c orre ctive or re me dial a ctio ns ta ke n t o pre ve nt re c urre nc e of t he deficie nc y. 
 A re me dial a ctio n is a n y a ctio n ot her t ha n r o utine mainte na nc e or s er vicin g of a de vic e 
c o nstit ue nt w here s uc h a ctio n is ne c ess ar y t o pre ve nt re c urre nc e of a de vic e c o nstit ue nt 
deficie nc y. T his inclu des a n y a me n d me nt t o t he de vic e c o nstit ue nt desig n t o pre ve nt 
re c urre nc e. 
 T he in vestigat or is o bligate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
me as ure me nts a n d/ or e valuatio ns as me dic ally in dic ate d t o elucidate t he nat ure a n d/ or 
c a us alit y of t he de vic e c o nstit ue nt deficie nc y as f ully as p ossible. T his ma y inclu de 
a d ditio nal la b orat or y tests or in vestigatio ns, hist o pat h olo gic al e xa minatio ns, or 
c o ns ultatio n wit h ot her he alt h c are pr ofessio nals.  
8. 4  
O ver d ose 
F or t his st u d y, a n y d os e of be nraliz u ma b gre ater t ha n  3 0  m g  wit hin 4  w e e ks will be c o nsidere d 
a n o ver d os e . As  be nraliz u ma b is give n b y a he alt hc are pr ofessio nal in a me dic al s ettin g, a n 
o ver d os e is u nlikely t o oc c ur.  
 A n o ver d os e wit h ass ociate d A Es is re c or de d as t he A E dia g n osis/s y m pt o ms o n t he 
rele va nt A E m o d ules in t he e C R F a n d o n t he O ver d os e e C R F m o d ule. 
 A n o ver d os e wit h o ut ass ociate d s y m pt o ms is o nly re p orte d o n t he O ver d os e e C R F 
m o d ule. 
If a n o ver d os e o n a n Astra Ze ne c a st u d y inter ve ntio n oc c urs in t he c o urs e of t he st u d y, t he 
in vestigat or or ot her site pers o n nel m ust inf or m a p pr o priate Astra Ze ne c a re pres e ntatives 
i m me diately, b ut n o l ate r t h a n 2 4  h o urs  of w he n he or s he be c o mes a w are of it. 
T he desig nate d Astra Ze ne c a re pres e ntative w or ks wit h t he in vestigat or t o e ns ure t hat all rele va nt 
inf or matio n is pr o vide d t o t he Astra Ze ne c a P atie nt Safet y data e ntr y site wit hi n o ne o r 
5  c ale n d ar d a ys  f or o ver d os es ass ociate d wit h a n S A E (s e e Se ctio n  8. 2. 4 ) a n d wit hi n 3 0  d a ys  
f or all ot her o ver d os es. 
T here is n o s pe cific tre at me nt f or a n o ver d os e wit h be nraliz u ma b. If o ver d os e oc c urs, t he  patie nt 
s h o uld be tre ate d s u p p ortively wit h a p pr o priate m o nit ori n g as ne c ess ar y.  
8. 5  
H u m a n Bi ol o gic al S a m ples 
I nstr uctio ns f or t he c olle ctio n a n d ha n dlin g of biolo gic al s a m ples will be pr o vide d in t he 
st u d y- s pe cific la b orat or y ma n ual. Sa m ples s h o uld be st ore d in a s e c ure st ora ge s pa c e wit h 
a de q uate me as ures t o pr ote ct c o nfide ntialit y. F or f urt her details o n H a n dlin g of H u ma n 
Biolo gic al Sa m ples s e e A p pe n dix C . 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 8  of 6 7  
 
8. 5. 1   
P har mac o ki netics 
P har ma c o kinetic para meters will n ot be e valuate d in t his st u d y.  
8. 5. 2   
I m m u n o ge ni cit y Ass ess me nts 
I m m u n o ge nicit y ass ess me nts will n ot be d o ne in t his st u d y. 
8. 5. 3   
P har mac o dy n a mics 
P har ma c o d y na mic para meters will n ot be e valuate d in t his st u d y . 
8. 6  
C ollecti o n of H u m a n Bi ol o gic al S a m ple Bi o m ar kers 
Bio mar kers will n ot be e valuate d in t his st u d y.  
8. 7  
C ollecti o n of O pti o n al Ge n o mics I niti ative S a m ple 
O ptio nal Ge n o mics I nitiative res e arc h is n ot a p plic a ble t o t his st u d y. 
8. 8  
He alt h Ec o n o mics O R Me dic al Res o urce Utilis ati o n a n d He alt h 
Ec o n o mics 
H e alt h Ec o n o mics/ Me dic al Res o urc e Utilis atio n a n d H e alt h Ec o n o mics para meters will n ot  be  
e valuate d in t his st u d y.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 9  of 6 7  
 
9   
S T A TI S TI C A L C O N SI D E R A TI O N S 
9. 1  
St atistic al H y p ot heses 
T here is n o statistic al h y p ot hesis t o be teste d in t his st u d y.  
9. 2  
S a m ple Size Deter mi n ati o n 
T he pri mar y o bje ctive of t his st u d y is t o ass ess s afet y a n d t olera bilit y of be nraliz u ma b in  a d ult 
( 1 8 t o 7 5  ye ars of a ge) male or fe male  patie nts w h o ha ve s e vere ast h ma wit h e osin o p hilic 
p he n ot y pe re q uirin g hig h d os e of I C S a n d L A B A. Bas e d o n t he literat ure re vie w, t he belo w ta ble 
is cre ate d f or listin g t he ke y A Es ( he a da c he, p yre xia, p har y n gitis a n d inje ctio n site re a ctio ns) a n d 
h y pers e nsitivit y re a ctio ns  (e. g. a na p h yla xis, a n gioe de ma, urtic aria, urtic aria pa p ular, ras h) w hic h 
w ere inclu de d in t he U S PI, S m P C a n d t he I n dia PI, all in t he ra n ge of 1 % t o 1 0 %.  
 
 
I nci de nc e R ate ( %) 
K e y A E Te r ms   
S m P C/ I n di a l a bel   
U S PI   
SI R O C C O  
H e a da c he  
C o m m o n ( 1 % -1 0 %)  
8 %   
7 % -9 %  
P har y n gitis  
5 %   
4 % -6 %  
P yre xia  
3 %   
3 % -4 %  
I nje ctio n site re a ctio ns 
2. 2 %   
2 % -4 %  
H y pers e nsitivit y  
3 %  
3 %  
 
effe ctive ness 𝑛=
𝑍2 𝑃 ( 1 −𝑃)
𝑑2
 
w here n = c alc ulate d s a m ple size, Z = ta b ulate d Z statistic value f or α le vel of c o nfide nc e, 
P  =  e x pe cte d pr o p ortio n of A Es a n d d = a bs olute pre cisio n le vel ( half- widt h of t he c o nfide nc e 
inter val [ CI]). 
C o nsiderin g t he ma xi m u m li mit of t he incide nc e rate of A Es t o be 1 0 %, a p pr o xi mately 1 3 9 
e valua ble  participa nts will be re q uir e d t o pres e nt 9 5 % CI ar o u n d t he esti mate d A E incide nc e rate 
wit h a bs olute pre cisio n le vel of 0. 0 5. C o nsiderin g dr o p o ut rate of 5 %, a t otal of 1 4 7  participa nts 
will be re q uire d t o be e nr olle d int o t he st u d y.  
9. 3  
P o p ul ati o ns f o r A n al yses 
F or p ur p os e of a nalysis, t he f ollo win g p o p ulatio ns/a nal ysis s ets are define d, as pres e nte d in Ta ble 
4  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 0  of 6 7  
 
Ta ble 4   
P o p ul ati o ns fo r A n al ysis  
P o p ul ati o n/ A n al ysis s et   
Des c ri pti o n  
Enr olle d  
" Enr olle d" me a ns a  p artici p a nt 's, or t h eir le g all y a ut h oris ed re prese nt ati ve ’s, 
a gre e me nt b y si g ni n g t he I C F t o p artici p at e i n a cli nic al st u d y f oll o wi n g 
c o mpleti o n of t h e i nf or me d c o nse nt pr oc ess.  
A s si g n ed t o st u d y int er v enti o n  
P ot e ntial  p artici p ant s w h o f ulfil t h e eli gi bilit y crit eria a n d are as si g ne d wit h 
t h e st u d y i d e ntific ati o n n u mb er.  
Ev al u a ble  
All  p artici p a nt s assi g ned t o st u d y i nt er venti o n a n d re c ei vi n g at le ast 1 d os e of 
st u d y i nt er ve nti o n  a n d pr o vi d e at le ast o n e p ost b aseli n e assess me nt . 
Safet y  
All  p artici p a nt s assi g ned t o st u d y i nt er venti o n a n d w h o t a ke at le ast 1 d os e of 
st u d y i nt er ve nti o n. 
A b br e viati o n: I C F = I nf or m e d C o nse nt F or m  
9. 4  
St atistic al A n al yses 
T he statistic al a nalysis pla n ( S A P) will be finalis e d bef ore  data bas e loc k.  It will inclu de a m ore 
te c h nic al a n d detaile d des criptio n of t he statistic al a nalys es des cribe d in t his s e ctio n. T his s e ctio n 
is a s u m mar y of t he pla n ne d statistic al a nalys es of t he m ost i m p orta nt e n d p oints inclu din g 
pri ma r y a n d ke y s e c o n dar y e n d p oints. 
9. 4. 1   
Ge ne ral C o nsi de rati o ns 
Statistic al a nalys es will be pri marily des criptive in nat ure. All ta b ulatio ns, fig ures, a n d listin gs 
will be pr o d uc e d usin g t he Statistic al A nalysis S oft w are ( S A S) S yste m ( Versio n  9. 2 or hig her). 
D ata fr o m all participatin g sites will be p o ole d f or a nalysis. Sta n dar d met h o d of i m p utatio n will 
be a p plie d f or a n y missin g/ partial dates.  
A c c or din g t o t he o bje ctives, t he rele va nt para meters will be s u m maris e d des criptively wit h 
a p pr o priate statistic al met h o ds: c ate g oric al varia bles will be pres e nte d usin g fre q ue ncies, 
perc e nta ges a n d c orres p o n din g 9 5 % CI  (usin g Clo p per -P e ars o n e xa ct met h o d, w here 
a p pr o priate)  a n d c o ntin u o us varia bles usin g n u m ber of o bs er vatio ns, arit h metic me a n, sta n dar d 
de viatio n  ( S D), me dia n, 2 5t h a n d 7 5 t h perc e ntiles,  a n d mini m u m a n d ma xi m u m values.  T he last 
me as ure me nt prior t o first d os e of st u d y tre at me nt will s er ve as t he bas eline me as ure me nt . 
T he s afet y para meters inclu din g A Es, S A Es, de at hs, tre at me nt 
dis c o ntin uati o n/ m o dific ati o n,  patie nt dis c o ntin uatio n, la b orat or y data, etc. will be re p orte d usin g 
s afet y a nalysis s et. 
T he ti me- t o-e ve nt e n d p oint will be s u m maris e d usin g K a pla n- Meier ( K M) met h o d alo n g wit h 
t he c orres p o n din g 9 5 % CIs (as a p pr o priate) a n d t he K M c ur ve will be plotte d.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 1  of 6 7  
 
9. 4. 2   
S afet y 
9. 4.2.1   
Pri m ar y E n d p oi nts 
I n or der t o ass ess s afet y a n d t olera bilit y of be nraliz u ma b in participa nts wit h s e vere e osin o p hilic 
ast h ma, f ollo win g res ults will be pres e nte d: 
Fre q ue nc y, perc e nta ge, a n d 9 5 % CIs ( usin g Clo p per- P e ars o n e xa ct met h o d) will be re p orte d f or 
t he f ollo win g: 
 A Es  
 S A Es  
 T E A Es  
 P articipa nts wit h u ne x pe cte d A d vers e Dr u g Re a ctio ns ( A D Rs)  
 P articipa nts wit h A Es t hat le a d t o st u d y tre at me nt dis c o ntin uati o ns or m o dific atio ns.  
T he A E pr ofiles in participa nts will be pres e nte d as s u m maries s h o win g t he n u m ber 
of  participa nts ( n, %) alo n g wit h n u m ber of e ve nts b y S yste m Or ga n Class a n d Preferre d Ter ms 
assig ne d t o t he e ve nt b y Me dic al Dictio nar y f or Re g ulat or y A ctivities ( Me d D R A) f or t he 
f ollo win g:  
 T E A Es  
 S A Es  
 Relate d a n d n o n-relate d T E A Es  
 Serio us a n d n o n -s erio us T E A Es 
 T E A Es bas e d o n s e verit y ( Mild, 
M o derate, Se vere)  
 U ne x pe cte d A D Rs bas e d o n s e verit y ( Mild, 
M o derate, Se vere)  
T he p h ysic al e xa minatio n, vital sig ns, a n d la b orat or y para meters (if a vaila ble) will be 
s u m maris e d des criptively f or a ct ual values a n d c ha n ge fr o m bas eline values f or e a c h visit usin g 
t he n u m ber of o bs er vatio ns, arit h metic me a n, S D, me dia n, 2 5t h a n d 7 5t h perc e ntiles, a n d 
mini m u m a n d ma xi m u m values.  
9. 4.2.2   
Ot he r S afet y E n d p oi nts 
N o ne  
9. 4. 3   
Effe cti ve ness 
I n or der t o ass ess effe ctive ness of be nraliz u ma b in participa nts of  s e vere ast h ma of e osin o p hilic 
p he n ot y pe, f ollo win g res ults will be pres e nte d usin g E valua ble A nalysis Set: 
A n n ualis e d e xa c er batio n rate per 2 4- w e e k perio d will be re p orte d as perc e nta ge, a n d 9 5 % CI 
(e xa ct P oiss o n met h o d), a n d will be pres e nte d in t he S A P. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 2  of 6 7  
 
T he pr o p ortio n of participa nts wit h ≥1 ast h ma e xa c er batio n d urin g t he st u d y perio d will be 
des cribe d usin g t he fre q ue nc y a n d t he perc e nta ge. T he pr o p ortio n of s uc h participa nts will be 
c alc ulate d as: ( n u m ber of participa nts wit h ≥1 ast h ma e xa c er batio n d urin g t he 2 4 w e e k st u d y 
perio d)/(t otal n u m ber of participa nts in t he st u d y). 
O verall in vestigat or’s ass ess me nt o n t he o utc o me of st u d y tre at me nt will be s u m maris e d usin g 
fre q ue nc y a n d perc e nta ge. 
Ti me fr o m first d os e of st u d y tre at me nt t o t he first ast h ma e xa c er batio n will be c alc ulate d as 
f ollo ws: Start D ate of first ast h ma e xa c er batio n min us D ate of first d os e of st u d y tre at me nt plus 
1. T he ti me t o first ast h ma e xa c er batio n f or  participa nts w h o d o n ot e x perie nc e a n ast h ma 
e xa c er batio n d urin g t he st u d y perio d will be c e ns ore d at 2 4 w e e ks, or at t he ti me p oint after 
w hic h a n e xa c er batio n c o uld n ot be ass ess e d (f or lost- t o-f ollo w-u p  participa nts). T he data will be 
s u m maris e d t hr o u g h me dia n ti me t o t he first ast h ma e xa c er batio n alo n g wit h t he 9 5 % CI of 
me dia n (as per a vaila bilit y of data) a n d dis pla ye d gra p hic ally usin g a K M plot.  
T he a bs olute values of blo o d e osin o p hil le vels a n d t he c ha n ge fr o m bas eline at We e k 4, We e k 1 6 , 
a n d We e k 2 4 will be s u m maris e d des criptively usin g n u m ber of o bs er vatio ns, arit h metic me a n, 
S D, me dia n, 2 5 t h a n d 7 5t h perc e ntiles, a n d mini m u m a n d ma xi m u m values. 
9. 4. 4   
Ot he r A nal ys es  
N o ne  
9. 5  
I nteri m A n al yses  
N o interi m a nalys es is pla n ne d f or t his st u d y.  
9. 6  
D at a M o nit o ri n g C o m mittee 
N ot a p plic a ble 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 3  of 6 7  
 
1 0   
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S 
A p pe n di x A  Re g ul at o ry, Et hic al, a n d St u d y O versi g ht C o nsi derati o ns 
A 1  
Re g ul at o ry a n d Et hic al C o nsi derati o ns 
 
T his st u d y will be c o n d ucte d in a c c or da nc e wit h t he pr ot oc ol a n d wit h t he f ollo win g: 
 
C o ns e ns us et hic al principles derive d fr o m inter natio nal g uidelines inclu din g t he 
D e claratio n of H elsin ki a n d C o u ncil f or I nter natio nal Or ga nizatio ns of Me dic al 
Scie nc es ( CI O M S) I nter natio nal Et hic al Guideli nes 
 
A p plic a ble I nter natio nal C o u ncil f or H ar m o nis atio n (I C H) Go o d Clinic al Pra ctic e 
( G C P) Guidelines 
 
A p plic a ble la ws a n d re g ulatio ns 
 
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, pres cribin g inf or matio n, a n d ot her rele va nt 
d oc u me nts (e g, a d vertis e me nts) m ust be s u b mitte d t o a n I nstit utio nal Re vie w B oar d 
(I R B)/I n de pe n de nt Et hics C o m mitte e (I E C) b y t he in vestigat or a n d re vie w e d a n d a p pr o ve d 
b y t he I R B/I E C bef ore t he st u d y is initiate d. 
 
A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C a n d a p plic a ble Re g ulat or y A ut h orit y 
a p pr o val bef ore i m ple me ntati o n of c ha n ges ma de t o t he st u d y desig n, e xc e pt f or c ha n ges 
ne c ess ar y t o eli minate a n i m me diate ha zar d t o st u d y participa nt s. 
 
Astra Ze ne c a will be res p o nsible f or o btainin g t he re q uire d a ut h oris atio ns t o c o n d uct t he 
st u d y fr o m t he c o nc er ne d Re g ulat or y A ut h orit y. T his res p o nsibilit y 
ma y be dele gate d t o a 
C R O b ut t he a c c o u nta bilit y re mains wit h Astra Ze ne c a. 
 
T he in vestigat or will be res p o nsible f or pr o vidin g o versig ht of t he c o n d uct of t he st u d y at 
t he site a n d a d here nc e t o re q uire me nts of 2 1 C o de of Fe deral Re g ulatio ns, I C H g uidelines, 
t he I R B/I E C, a n d all ot her a p plic a ble loc al re g ulatio ns. 
R e g ul at o r y R e p o rti n g R e q uire me nts fo r Se ri o us A d v e rs e E ve nts 
 
Pr o m pt n otific atio n b y t he in vestigat or t o t he s p o ns or of a S A E is ess e ntial s o t hat le gal 
o bligatio ns a n d et hic al res p o nsibilities t o w ar ds t he s afet y of participa nts a n d t he s afet y of a 
st u d y inter ve ntio n u n der clinic al in vestigatio n are met. 
 
T he s p o ns or has a le gal res p o nsibilit y t o n otif y b ot h t he loc al re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he s afet y of a st u d y inter ve ntio n u n der clinic al in vestigatio n. T he 
s p o ns or will c o m ply wit h c o u ntr y-s pe cific r e g ulat or y re q uire me nts relatin g t o s afet y 
re p ortin g t o t he re g ulat or y a ut h orit y, I R B/I E C, a n d in vestigat ors. 
 
F or all st u dies e xc e pt t h os e utilisi n g 
me dic al de vic es, in vestigat or s afet y re p orts m ust be 
pre pare d f or s us pe cte d u ne x pe cte d s erio us a d vers e re a ctio ns ( S U S A R) a c c or din g t o loc al 
re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d f or w ar de d t o in vestigat ors as ne c ess ar y. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 4  of 6 7  
 
 
A n in vestigat or w h o re c eives a n in vestigat or s afet y re p ort des cribin g a S A E or ot her s pe cific 
s afet y inf or matio n (e g, s u m mar y or listin g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n 
file it alo n g wit h t he I n vestigat or’s Br oc h ure or Pres cribin g I nf or matio n a n d will n otif y t he 
I R B/I E C, if a p pr o priate a c c or din g t o loc al re q uire me nts. 
A 2  
Fi n a nci al Discl os ure 
I n vestigat ors a n d s u b-in vestigat ors 
will pr o vide t he s p o ns or wit h s ufficie nt, a c c urate fina ncial 
inf or matio n as re q ueste d t o allo w t he s p o ns or t o s u b mit c o m plete a n d a c c urate fina ncial 
c ertific atio n or dis clos ure state me nts t o t he a p pr o priate re g ulat or y a ut h orities. I n vestigat ors are 
res p o nsible f or pr o vidin g inf or matio n o n fina ncial interests d urin g t he st u d y a n d f or 1 ye ar after 
c o m pletio n of t he st u d y. Astra Ze ne c a is res p o nsible f or f ur nis hin g t he details of t he c o ntra ct wit h 
t he in vestigat or a b o ut fina ncial s u p p ort, fe es, h o n orariu m a n d p a y me nts ma de in kin d, t o t he 
a p pr o priate re g ulat or y a ut h orities.  
A 3  
I nf o r me d C o nse nt Pro cess 
 
T he in vestigat or or his/ her re pres e ntative will e x plain t he nat ure of t he st u d y t o t he participa nt 
or his/ her le gally a ut h oris e d re pres e ntative a n d a ns w er all q uesti o ns re gar din g t he st u d y. 
 
P articipa nts m ust be inf or me d t hat t heir participatio n is v olu ntar y a n d t he y are fre e t o ref use 
t o participate a n d ma y wit h dra w t heir c o ns e nt at a n y ti me a n d f or a n y re as o n d urin g t he st u d y. 
P articipa nts or t heir le gally a ut h oris e d re pres e ntative will be re q uire d t o sig n a state me nt of 
inf or me d c o ns e nt t hat me ets t he re q uire me nts of, loc al re g ulatio ns, I C H g uidelines, 
w here 
a p plic a ble, a n d t he I R B/I E C or st u d y c e ntre. 
 
T he me dic al re c or d m ust inclu de a state me nt t hat writte n inf or me d c o ns e nt w as o btaine d 
bef ore t he participa nt w as e nr olle d in t he st u d y a n d t he date t he writte n c o ns e nt w as o btaine d. 
T he a ut h oris e d pers o n o btainin g t he inf or me d c o ns e nt m ust als o sig n t he I C F. 
 
P articipa nts m ust be re-c o ns e nte d t o t he m ost c urre nt versio n of t he I C F(s) d urin g t heir 
participatio n in t he st u d y. 
 
A c o p y of t he I C F(s) m ust be pr o vide d t o t he participa nt or t he participa nt’s le gally a ut h oris e d 
re pres e ntative. 
A 4  
D at a Protecti o n 
 
P articipa nts will be assig ne d a u niq ue ide ntifier b y t he s p o ns or. A n y participa nt re c or ds or 
datas ets t hat are tra nsferre d t o t he s p o ns or will c o ntain t he ide ntifier o nly; participa nt na mes 
or a n y inf or matio n w hic h w o uld ma ke t he participa nt ide ntifia ble will n ot be tra nsferre d. 
 
T he participa nt m ust be inf or me d t hat his/ her pers o nal st u d y-relate d data will be us e d b y t he 
s p o ns or in a c c or da nc e wit h loc al data pr ote ctio n la w. T he le vel of dis clos ure a n d us e of t heir 
data m ust als o be e x plaine d t o t he participa nt in t he inf or me d c o ns e nt.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 5  of 6 7  
 
 
T he participa nt m ust be inf or me d t hat his/ her me dic al re c or ds ma y be e xa mine d b y Clinic al 
Q ualit y 
Ass ura nc e a u dit ors or ot her a ut h oris e d pers o n nel a p p ointe d b y t he s p o ns or, b y 
a p pr o priate I R B/I E C me m bers, a n d b y ins pe ct ors fr o m re g ulat or y a ut h orities. 
A 5  
C o m mittees Str uct ure 
T he s afet y of all Astra Ze ne c a clinic al st u dies is clos ely 
m o nit ore d o n a n o n g oin g basis b y 
Astra Ze ne c a re pres e ntatives in c o ns ultatio n 
wit h P atie nt Safet y. Iss ues ide ntifie d 
will 
be 
a d dress e d; f or insta nc e, t his c o uld in v olve a me n d me nts t o t he Clinic al St u d y Pr ot oc ol a n d letters 
t o in vestigat ors. 
A 6  
Disse mi n ati o n of Cli nic al St u d y D at a 
A des criptio n of t his clinic al trial will be a vaila ble o n htt p://astra ze ne c a clinic altrials. c o m a n d 
htt p://ctri. nic.in/ Clinic altrials/l o gi n. p h p as will t he s u m mar y of t he st u d y res ults w he n t he y are 
a vaila ble. T he clinic al trial a n d/ or s u m mar y of t he st u d y res ults ma y als o be a vaila ble o n ot her 
w e bsites a c c or din g t o t he loc ally pre vale nt re g ulatio ns in I n dia.  
A 7  
D at a Q u alit y Ass ura nce 
 
All participa nt data relatin g t o t he st u d y will be re c or de d o n e C R F u nless tra ns mitte d t o t he 
s p o ns or or desig ne e ele ctr o nic ally (e g, la b orat or y data). T he in vestigat or is res p o nsible f or 
verif yin g t hat data e ntries are a c c urate a n d c orre ct b y ele ctr o nic ally sig nin g t he e C R F. 
 
T he in vestigat or 
m ust 
maintain a c c urate d oc u me ntatio n (s o urc e data) t hat s u p p orts t he 
inf or matio n e ntere d in t he e C R F. 
 
T he in vestigat or 
m ust per mit st u d y-relate d 
m o nit orin g, 
a u dits, I R B/I E C re vie w, a n d 
re g ulat or y a ge nc y ins pe ctio ns a n d pr o vide dire ct a c c ess t o s o urc e data d oc u me nts. 
 
M o nit orin g details des cribin g strate g y, met h o ds, res p o nsibilities a n d re q uire me nts, inclu di n g 
ha n dlin g of n o nc o m plia nc e iss ues a n d m o nit orin g te c h niq ues (c e ntral, re m ote, or o n-site 
m o nit orin g) are pr o vide d in t he m o nit orin g pla n.  
 
T he s p o ns or or desig ne e is res p o nsible f or t he data ma na ge me nt of t his st u d y inclu din g q ualit y 
c he c kin g of t he data. 
 
T he s p o ns or ass u mes a c c o u nta bilit y f or a ctio ns dele gate d t o ot her in divid uals (e g, C o ntra ct 
Res e arc h Or ga nis atio ns). 
 
St u d y m o nit ors will perf or m o n g oin g s o urc e dat a verific atio n t o c o nfir m t hat data e ntere d int o 
t he e C R F b y a ut h oris e d site pers o n nel are a c c urate, c o m plete, a n d verifia ble fr o m s o urc e 
d oc u me nts; t hat t he s afet y a n d rig hts of participa nts are bein g pr ote cte d; a n d t hat t he st u d y is 
bein g c o n d ucte d in a c c or da nc e wit h t he c urre ntly a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gre e me nts, I C H G C P, N e w Dr u gs a n d Clinic al 
Trial 
R ules 2 0 1 9, a n d all a p plic a ble 
re g ulat or y re q uire me nts. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 6  of 6 7  
 
 
Re c or ds a n d d oc u me nts, inclu di n g sig ne d I C Fs, pertainin g t o t he c o n d uct of t his st u d y m ust 
be retaine d b y t he in vestigat or f or 1 0  ye ars after st u d y c o m pletio n u nless loc al re g ulatio ns or 
instit utio nal p olicies re q uire a lo n ger rete ntio n perio d. N o re c or ds ma y be destr o ye d d uri n g 
t he rete ntio n perio d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o re c or ds ma y be tra nsferre d 
t o a n ot her loc atio n or part y wit h o ut writte n n otific atio n t o t he s p o ns or. 
A 8  
S o urce D o c u me nts 
 
S o urc e d oc u me nts pr o vide e vide nc e f or t he e xiste nc e of t he participa nt a n d s u bsta ntiate t he 
inte grit y of t he data c olle cte d. S o ur c e d oc u me nts are file d at t he in vestigat or’s site. 
 
D ata e ntere d in t he e C R F t hat are tra ns cribe d fr o m s o urc e d oc u me nts m ust be c o nsiste nt wit h 
t he s o urc e d oc u me nts or t he dis cre pa ncies m ust be e x plaine d. T he in vestigat or 
ma y ne e d t o 
re q uest pre vio us me dic al re c or ds or tra nsfer re c or ds, de pe n din g o n t he st u d y. Als o, c urre nt 
me dic al re c or ds m ust be a vaila ble. 
A 9  
St u d y a n d Site St art a n d Cl os ure 
T he st u d y start date is t he date o n w hic h t he clinic al st u d y will be o pe n f or re cr uit me nt 
of  participa nt s. 
T he first a ct of re cr uit me nt is t he first site initiatio n visit ( SI V) a n d will be t he st u d y start date.  
T he s p o ns or desig ne e res er ves t he rig ht t o clos e t he st u d y site or ter minate t he st u d y at a n y ti m e 
f or a n y re as o n at t he s ole dis cretio n of t he s p o ns or. St u d y sites will be clos e d o n st u d y c o m pleti o n. 
A st u d y site is c o nsidere d clos e d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve be e n 
c olle cte d a n d a st u d y-site clos ure visit has be e n perf or me d.  
T he in vestigat or ma y initiate st u d y-site clos ure at a n y ti me, pr o vide d t here is re as o na ble c a us e a n d 
s ufficie nt n otic e is give n in a d va nc e of t he inte n de d ter minatio n.  
Re as o ns f or t he e arly clos ure of a st u d y site b y t he s p o ns or or in vestigat or ma y inclu de b ut are n ot 
li mite d t o: 
 
Failure of t he in vestigat or t o c o m ply wit h t he pr ot oc ol, t he re q uire me nts of t he I R B/I E C or 
loc al he alt h a ut h orities, t he s p o ns or's pr oc e d ures, or G C P g uidelines 
 
I na de q uate re cr uit me nt of participa nts b y t he in vestigat or 
 
Dis c o ntin uatio n of f urt her st u d y inter ve ntio n de velo p me nt 
If t he st u d y is pre mat urely ter minate d or s us pe n de d, t he s p o ns or s hall pr o m ptly inf or m t he 
in vestigat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) us e d in t he st u d y of t he 
re as o n f or ter minatio n or s us pe nsio n, as s pe cifie d b y t he a p plic a ble re g ulat or y re q uir e me nts. T he 
in vestigat or s hall pr o m ptly inf or m t he participa nt a n d s h o uld ass ure a p pr o priate  participa nt 
t hera p y a n d/ or f ollo w-u p.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 7  of 6 7  
 
P articipa nts fr o m ter minate d sites will be dis c o ntin ue d fr o m t he st u d y a n d will be pr o vide d wit h 
sta n dar d of c are as deter mine d a p pr o priate b y t he st u d y in vestigat or. 
A 1 0  
P u blic ati o n P olic y  
 
T he res ults of t his st u d y ma y be p u blis he d or pres e nte d at s cie ntific 
me etin gs. If t his is 
f ores e e n, t he in vestigat or a gre es t o s u b mit all ma n us cripts or a bstra cts t o t he s p o ns or bef ore 
s u b missio n. 
T his allo ws t he s p o ns or t o pr ote ct pr o prietar y inf or matio n a n d t o pr o vid e 
c o m me nts. 
 
T he s p o ns or will c o m ply wit h t he re q uire me nts f or p u blic atio n of st u d y res ults. I n a c c or da nce 
wit h sta n dar d e dit orial a n d et hic al pra ctic e, t he s p o ns or will ge nerally s u p p ort p u blic atio n of 
m ultic e ntre st u dies o nly in t heir e ntiret y a n d n ot as in divid ual site data. I n t his c as e, a 
c o or dinatin g in vestigat or will be desig nate d b y m ut ual a gre e me nt. 
 
A ut h ors hip will be deter mine d b y m ut ual a gre e me nt a n d in line wit h I nter natio nal C o m mitte e 
of Me dic al J o ur nal E dit ors a ut h ors hip re q uire me nts. 
 
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 8  of 6 7  
 
A p pe n di x B  A d verse Eve nts: Defi niti o ns a n d Pro ce d ures f o r Rec o r di n g, 
Ev al u ati n g, Foll o w- u p, a n d Re p o rti n g 
B 1  
Defi niti o n of A d verse E ve nts  
A n a d vers e e ve nt ( A E) is t he de velo p me nt of a n y u nt o w ar d me dic al oc c urre nc e in a  patie nt or 
clinic al st u d y participa nt a d ministere d a me dicinal pr o d uct a n d w hic h d oes n ot ne c ess arily ha ve a 
c a us al relatio ns hip wit h t his tre at me nt. A n A E c a n t heref ore be a n y u nfa v o ura ble a n d u ninte n d e d 
sig n (e g, a n a b n or mal la b orat or y fin din g), s y m pt o m (f or e xa m ple na us e a, c hest pain), or dis e as e 
te m p orally ass ociate d wit h t he us e of a me dicinal pr o d uct, w het her or n ot c o nsidere d relate d t o t he 
me dicinal pr o d uct .  
T he ter m A E is us e d t o inclu de b ot h s erio us a n d n o n-s erio us A Es a n d c a n inclu de a deteriorati o n 
of a pre-e xistin g me dic al oc c urre nc e. A n A E ma y oc c ur at a n y ti me, inclu din g r u n-in or w as h o ut 
perio ds, e ve n if n o st u d y inter ve ntio n has be e n a d ministere d.  
B 2  
Defi niti o n of Seri o us A d verse E ve nt s 
A n S A E is a n A E oc c urrin g d urin g a n y st u d y p has e (ie, r u n-in, tre at me nt, w as h o ut, f ollo w- u p), 
t hat f ulfils o ne or m ore of t he f ollo win g criteria: 
 
Res ults in de at h 
 
Is i m me diately life-t hre ate nin g 
 
Re q uires in- participa nt h os pitalis ati o n or pr olo n gatio n of e xistin g h os pitalis atio n  
 
Res ults in persiste nt or sig nific a nt dis a bilit y or inc a pa cit y  
 
Is a c o n ge nital a b n or malit y or birt h defe ct 
 
Is a n i m p orta nt 
me dic al e ve nt t hat ma y je o par dis e t he participa nt or ma y re q uire me dic al 
tre at me nt t o pre ve nt o ne of t he o utc o mes liste d a b o ve 
A d vers e e ve nts f or m ali g n a nt t u m o urs  re p orte d d urin g a st u d y s h o uld ge nerally be ass ess e d as 
Se ri o us A Es . If n o ot her s erio us ness criteria a p ply, t he ‘I m p orta nt Me dic al E ve nt’ criterio n s h o ul d 
be us e d. I n c ertain sit uatio ns, h o w e ver, me dic al ju d ge me nt o n a n in divi d ual e ve nt basis s h o uld be 
a p plie d t o clarif y t hat t he malig na nt t u m o ur e ve nt s h o uld be ass ess e d a n d re p orte d as a n o n -s e rio us 
A E . F or e xa m ple, if t he t u m o ur is inclu de d as me dic al hist or y a n d pr o gressio n oc c urs d urin g t he 
st u d y, b ut t he pr o gressio n d oes n ot c ha n ge tre at me nt a n d/ or pr o g n osis of t he malig na nt t u m o ur, 
t he A E ma y n ot f ulfil t he attrib utes f or bein g ass ess e d as s erio us, alt h o u g h re p ortin g of t he 
pr o gressio n of t he malig na nt t u m o ur as a n A E is valid a n d s h o uld oc c ur.  Als o, s o me t y pes of 
malig na nt t u m o urs, w hic h d o n ot s pre a d re m otely after a r o utine tre at me nt t hat d oes n ot re q uire 
h os pitalis ati o n, 
ma y be ass ess e d as n o n -s erio us; e xa m ples in a d ults inclu de Sta ge 1 bas al c ell 
c arcin o ma a n d Sta ge 1 A 1 c er vic al c a nc er re m o ve d via c o ne bio ps y.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 9  of 6 7  
 
Life-t hre ate ni n g 
‘ Life-t hre ate nin g’ me a ns t hat t he  participa nt w as at i m me diate ris k of de at h fr o m t he A E as it 
oc c urre d or it is s us pe cte d t hat us e or c o ntin ue d us e of t he pr o d uct w o uld res ult in t he  participa nt’ s 
de at h. ‘ Life-t hre ate nin g ’ d oes n ot me a n t hat ha d a n A E oc c urre d in a m ore s e vere f or m it mig ht 
ha ve c a us e d de at h (e g, he patitis t hat res olve d wit h o ut he patic failure).  
H os pit alis ati o n 
O ut patie nt tre at me nt in a n e mer ge nc y r o o m ( E R) is n ot in its elf a s erio us A E, alt h o u g h t he re as o ns 
f or it 
ma y be (e g, br o nc h os pas m, lar y n ge al oe de ma). H os pital a d missio ns a n d/ or s ur gic al 
o peratio ns pla n ne d bef ore or d urin g a st u d y are n ot c o nsidere d A Es if t he illness or dis e as e e xiste d 
bef ore t he  participa nt 
w as e nr olle d in t he st u d y, pr o vide d t hat it did n ot deteriorate in a n 
u ne x pe cte d w a y d urin g t he st u d y.  
I m p o rt a nt M e dic al E v e nt o r M e dic al Tre at me nt 
Me dic al a n d s cie ntific ju d ge me nt s h o uld be e xercis e d in de cidin g 
w het her a c as e is s erio us i n 
sit uatio ns w here i m p orta nt me dic al e ve nts ma y n ot be i m me diately life- t hre ate nin g or res ult i n 
de at h, h os pitalis atio n, dis a bilit y or inc a pa cit y b ut ma y je o par dis e t he  participa nt or ma y re q uire 
me dic al tre at me nt t o pre ve nt o ne or m ore o utc o mes liste d in t he definitio n of s erio us. T hes e s h o ul d 
us ually be c o nsidere d as s erio u s. 
Si m ply st o p pin g t he s us pe ct dr u g d oes n ot me a n t hat it is a n i m p orta nt me dic al e ve nt; me dic al 
ju d ge me nt m ust be us e d. 
 
A n gioe de ma n ot s e vere e n o u g h t o re q uire int u batio n b ut re q uirin g intra ve n o us h y dr oc ortis o n e 
tre at me nt 
 
H e pat ot o xicit y c a us e d b y para c eta m ol (a c eta min o p he n) o ver d os e re q uirin g tre at me nt wit h N-
a c et ylc ysteine 
 
I nte nsive tre at me nt in a n E R  or at h o me f or aller gic br o nc h os pas m 
 
Blo o d d ys crasias (e g, ne utr o pe nia or a na e mia re q uirin g blo o d tra nsf usio n, etc.) or c o n v ulsi o ns 
t hat d o n ot res ult in h os pitalis atio n 
 
D e velo p me nt of dr u g de pe n de nc y or dr u g a b us e 
I nte nsit y R ati n g Sc ale: 
As s ess me nt of Se v e rit y 
T he in vestigat or will be as ke d t o pr o vide a n ass ess me nt of t he s e verit y of t he A E usin g t he 
f ollo win g c ate g ories:  
 
Mild: Us ually tra nsie nt a n d ma y re q uire o nly mini mal tre at me nt or t hera pe utic inter ve nti o n. 
T he e ve nt d oes n ot ge nerally interfere wit h us ual a ctivities of daily livin g. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 0  of 6 7  
 
 
M o derate: Us ually alle viate d 
wit h a d ditio nal s pe cific t hera pe utic inter ve ntio n. T he e ve nt 
interferes wit h us ual a ctivities of daily livin g, c a usin g dis c o mf ort b ut p os es n o sig nific a nt or 
per ma ne nt ris k of har m t o t he s u bje ct. 
 
Se vere: I nterr u pts us ual a ctivities of daily livin g, or sig nific a ntl y affe cts clinic al stat us, or ma y 
re q uire inte nsive t hera pe utic inter ve ntio n. 
It is i m p orta nt t o distin g uis h bet w e e n s erio us a n d s e vere A Es. Se verit y is a me as ure of inte nsit y 
w here as s erio us ness is define d b y t he criteria in A p pe n dix  B . A n A E of s e vere inte nsit y ne e d n ot 
ne c ess arily be c o nsidere d s erio us. F or e xa m ple, na us e a t hat persists f or s e veral  h o ur s ma y be 
c o nsidere d s e vere na us e a, b ut n ot a S A E u nless it me ets t he criteria s h o w n in A p pe n dix  B . O n t he 
ot her ha n d, a str o ke t hat res ults in o nly a li mite d de gre e of dis a bilit y 
ma y be c o nsidere d a mil d 
str o ke b ut w o uld be a S A E w he n it s atisfies t he criteria s h o w n in A p pe n dix  B . 
B 3  
Defi niti o n of Tre at me nt-e merge nt A d verse Eve nt 
A tre at me nt-e mer ge nt a d vers e e ve nt ( T E A E) is define d as a n y e ve nt n ot pres e nt prior t o t he 
initiati o n of t he dr u g tre at me nt or a n y e ve nt alre a d y pres e nt t hat w ors e ns in eit her inte nsit y or 
fre q ue nc y f ollo win g e x p os ure t o t he dr u g tre at me nt. 
B 4  
A G ui de t o I nter preti n g t he C a us alit y Q uesti o n 
W he n ma kin g a n ass ess me nt of c a us alit y c o nsider t he f ollo win g fa ct ors w he n de cidin g if t here is 
a ‘re as o na ble p ossibilit y’ t hat a n A E ma y ha ve be e n c a us e d b y t he dr u g. 
 
Ti me C o urs e. E x p os ure t o s us pe ct dr u g. H as t he participa nt a ct ually re c eive d t he s us pe ct 
dr u g? Did t he A E oc c ur in a re as o na ble te m p oral relatio ns hip t o t he a d ministratio n of t he 
s us pe ct dr u g? 
 
C o nsiste nc y wit h k n o w n dr u g pr ofile. Was t he A E c o nsiste nt wit h t he pre vio us k n o wle d ge of 
t he s us pe ct dr u g ( p har ma c olo g y a n d t o xic olo g y) or dr u gs of t he s a me p har ma c olo gic al class? 
Or c o uld t he A E be a nticipate d fr o m its p har ma c olo gic al pr o perties ? 
 
D e -c halle n ge e x perie nc e. Did t he A E res olve or i m pr o ve o n st o p pin g or re d ucin g t he d os e of 
t he s us pe ct dr u g? 
 
N o alter native c a us e. T he A E c a n n ot be re as o na bly e x plaine d b y a n ot her a etiolo g y s uc h as t he 
u n derlyin g dis e as e, ot her dr u gs, ot her h ost or e n vir o n me ntal fa ct ors. 
 
Re -c halle n ge e x perie nc e. Did t he A E re oc c ur if t he s us pe cte d dr u g w as reintr o d uc e d after 
ha vin g be e n st o p pe d? Astra Ze ne c a w o uld n ot n or mally re c o m me n d or s u p p ort a re-c halle n ge. 
 
La b orat or y tests. A s pe cific la b orat or y in vestigatio n (if perf or me d) has c o nfir me d t he 
relatio ns hip. 
I n diffic ult c as es, ot her fa ct ors c o uld be c o nsidere d s uc h as: 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 1  of 6 7  
 
 
Is t his a re c o g nis e d fe at ure of o ver d os e of t he dr u g? 
 
Is t here a k n o w n me c ha nis m? 
Ca us alit y of ‘relate d ’ is ma de if after a re vie w of t he rele va nt data, t here is e vide nc e f or a 
‘re as o na ble p ossibilit y’ of a c a us al relatio ns hip f or t he in divi d ual c as e. T he e x pressio n ‘re as o na ble 
p ossibilit y ’ of a c a us al relatio ns hip is me a nt t o c o n ve y, in ge neral, t hat t here are fa cts (e vide nc e) 
or ar g u me nts t o s u g gest a c a us al relatio ns hip.  
T he c a us alit y ass ess me nt is perf or me d bas e d o n t he a vaila ble data inclu din g e n o u g h inf or mati o n 
t o ma ke a n inf or me d ju d ge me nt. 
Wit h n o a vaila ble fa cts or ar g u me nts t o s u g gest a c a us al 
relatio ns hip, t he e ve nt(s) will be ass ess e d as ‘ n ot relate d’. 
Ca us al relatio ns hip in c as es w here t he dis e as e u n der st u d y has deteriorate d d ue t o la c k of effe ct 
s h o uld be classifie d as n o re as o na ble p ossibilit y.  
B 5  
Me dic ati o n Erro r 
F or t he p ur p os es of t his clinic al st u d y a me dic atio n err or is a n u ninte n de d failure or mista ke in t he 
tre at me nt pr oc ess f or a n Astra Ze ne c a st u d y inter ve ntio n t hat c a us es har m t o t he participa nt or has 
t he p ote ntial t o c a us e har m t o t he participa nt .  
A me dic atio n err or is n ot la c k of effic a c y of t he dr u g, b ut rat her a h u ma n or pr oc ess relate d failur e 
w hile t he dr u g is in c o ntr ol of t he st u d y site staff or  participa nt.  
Me dic atio n err or inclu des sit uatio ns w here a n err or.  
 
O c c urre d 
 
Was ide ntifie d a n d interc e pte d bef ore t he participa nt re c eive d t he dr u g 
 
Did n ot oc c ur, b ut circ u msta nc es w ere re c o g nis e d t hat c o uld ha ve le d t o a n err or 
E xa m ples of e ve nts t o be re p orte d in clinic al st u dies as me dic atio n err ors:  
 
Dr u g na me c o nf usio n 
 
Dis pe nsin g err or e g, me dic atio n pre pare d inc orre ctly, e ve n if it w as n ot a ct ually give n t o 
t he participa nt 
 
Dr u g n ot a d ministere d as in dic ate d, f or e xa m ple, wr o n g r o ute or wr o n g site of a d ministrati o n 
 
Dr u g n ot ta ke n as in dic ate d e g, ta blet diss olve d in w ater w he n it s h o uld be ta ke n as a s oli d 
ta blet  
 
Dr u g n ot st ore d as instr ucte d e g, ke pt in t he frid ge w he n it s h o uld be at r o o m te m perat ure  
 
Wr o n g participa nt re c eive d t he me dic atio n  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 2  of 6 7  
 
 
Wr o n g dr u g a d ministere d t o participa nt  
E xa m ples of e ve nts t hat d o n ot  re q uire re p ortin g as me dic atio n err ors in clinic al st u dies: 
 
P articipa nt a c cide ntally miss e d dr u g d os e(s) e g, f or g ot t o ta ke me dic atio n 
 
A c cide ntal o ver d os e ( will be c a pt ure d as a n o ver d os e) 
 
P articipa nt faile d t o ret ur n u n us e d me dic atio n or e m pt y pa c ka gin g 
 
Err ors relate d t o ba c k gr o u n d a n d res c ue me dic atio n, or sta n dar d of c are me dic atio n in o pe n- 
la bel st u dies, e ve n if a n Astra Ze ne c a pr o d uct  
Me dic atio n err ors are n ot re gar de d as A Es b ut A Es ma y oc c ur as a c o ns e q ue nc e of t he me dic ati o n 
err or.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 3  of 6 7  
 
A p pe n di x C  H a n dli n g of H u m a n Bi ol o gical S a m ples 
C 1  
C h ai n of C ust o d y 
A f ull c hain of c ust o d y is maintaine d f or all s a m ples t hr o u g h o ut t heir life c ycle.  
T he in vestigat or at e a c h c e ntre  ke e ps f ull tra c e a bilit y of c olle cte d biolo gic al s a m ples fr o m 
t he participa nts w hile in st ora ge at t he c e ntre u ntil s hip me nt or dis p os al ( w here a p pr o priate) a n d 
re c or ds rele va nt pr oc essin g inf or matio n relate d t o t he s a m ples w hilst at site.  
T he s a m ple re c eiver ke e ps f ull tra c e a bilit y of t he s a m ples w hile in st ora ge a n d d urin g us e u ntil 
us e d or dis p os e d of or u ntil f urt her s hip me nt a n d ke e ps re c or d of re c eipt of arrival a n d o n w ar d 
s hip me nt or dis p os al. 
Astra Ze ne c a or dele gate d re pres e ntatives will ke e p o versig ht of t he e ntire life c ycle t hr o u g h 
inter nal pr oc e d ures, 
m o nit ori n g 
of st u d y sites, a u ditin g 
or pr oc ess c he c ks, a n d c o ntra ct ual 
re q uire me nts of e xter nal la b orat or y pr o viders 
C 2  
Wit h dra wal of I nf o r me d C o nse nt f o r D o n ate d Bi ol o gical S a m ples  
If a participa nt wit h dra ws c o ns e nt t o t he us e of d o nate d biolo gic al s a m ples, t he s a m ples will be 
dis p os e d of/ destr o ye d/re patriate d, a n d t he a ctio n d oc u me nte d. If s a m ples are alre a d y a nalys e d, 
Astra Ze ne c a is n ot o blige d t o destr o y t he res ults of t his res e ar c h.  
F ollo win g 
wit h dra w al of c o ns e nt f or biolo gic al s a m ples, f urt her st u d y participatio n s h o uld be 
c o nsidere d in relatio n t o t he wit h dra w al pr oc ess es o utline d in t he inf or me d c o ns e nt.  
T he in vestigat or:  
 
E ns ures participa nt’s 
wit h dra w al of inf or me d c o ns e nt t o t he us e of d o nate d s a m ples is 
hig hli g hte d i m me diately t o Astra Ze ne c a or dele gate. 
 
E ns ures t hat rele va nt h u ma n biolo gic al s a m ples fr o m t hat participa nt, if st ore d at t he st u d y 
site, are i m me diately ide ntifie d, dis p os e d of as a p pr o priate, a n d t he a ctio n d oc u me nte d. 
 
E ns ures t hat t he participa nt a n d Astra Ze ne c a are inf or me d a b o ut t he s a m ple dis p os al. 
Astra Ze ne c a e ns ures t he or ga nis atio n(s) h oldin g t he s a m ples is/are inf or me d a b o ut t he wit h dra w n 
c o ns e nt i m me diately a n d t hat s a m ples are dis p os e d of or re patriate d as a p pr o priate, a n d t he a ctio n 
is d oc u me nte d a n d st u d y site is n otifie d. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 4  of 6 7  
 
A p pe n di x D  Be nraliz u m a b, prefille d s yri n ge (I n di a- s pecific p ac k a ge i nsert) 
Fase nra ™ 
T he r a pe utic i n dic ati o ns 
Fas e nra ™ is in dic ate d as a n a d d- o n mainte na nc e tre at me nt f or s e vere ast h ma wit h a n e osin o p hilic 
p he n ot y pe in a d ult patie nt s. 
P os ol o g y a n d met h o d of a d mi nistr ati o n 
P os olo g y 
T he re c o m me n de d d os e is 3 0 m g  of Fas e nra ™ b y s u bc uta ne o us inje ctio n e ver y 4 w e e ks f or t he 
first 3 d os es, a n d t he n e ver y 8 w e e ks t here after. 
El d erly p atie nts 
N o d os e a djust me nt is re q uire d f or elderly patie nts (s e e Se ctio n 5. 2 ). 
Re n al a n d h e p atic i mp air me nt 
N o d os e a djust me nt is re q uire d f or patie nts wit h re nal or he patic i m pair me nt (s e e Se ctio n 5. 2 ). 
A d mi nistr ati o n 
Fas e nra ™ is a d ministere d as a s u bc uta ne o us inje ctio n b y a he alt hc are pr ofessio nal. I n line wit h 
clinic al pra ctic e, m o nit orin g of  patie nts after a d ministratio n of biolo gic a ge nts is re c o m me n de d.  
A d minister Fas e nra ™ int o t he u p per ar m, t hig hs, or a b d o me n. D o n ot a d minister int o are as w here 
t he s kin is te n der, br uis e d, er yt he mat o us, or har de ne d (A p pe n dix D ). 
C o ntr ai n dic ati o ns 
Fas e nra ™ is c o ntrain dic ate d in patie nts w h o ha ve k n o w n h y pers e nsitivit y t o be nraliz u ma b or a n y 
of its e xcipie nts. 
S pe ci al war ni n gs a n d s pe ci al pre c a uti o ns fo r us e 
Fas e nra ™ s h o uld n ot be us e d t o tre at a c ute ast h ma e xa c er batio ns. 
P atie nts s h o uld be instr ucte d t o s e e k me dic al a d vic e if t heir ast h ma re mains u nc o ntr olle d or 
w ors e ns after initiati o n of tre at me nt. 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 5  of 6 7  
 
A br u pt 
dis c o ntin uatio n 
of c ortic oster oids 
after initiati o n 
of 
Fas e nra ™ t hera p y is 
n ot 
re c o m me n de d. Re d uctio n in c ortic oster oid d os es, if a p pr o priate, s h o uld be gra d ual a n d perf or me d 
u n der t he s u per visio n of a p h ysicia n. 
H y p ers e nsitivity r e a cti o ns 
H y pers e nsitivit y re a ctio ns (e. g. a na p h yla xis, a n gioe de ma, urtic aria, urtic aria pa p ular, ras h) ha ve 
oc c urre d after a d ministratio n 
of Fas e nra ™. T hes e re a ctio ns 
ma y oc c ur 
wit hin h o ur s of 
a d ministratio n, b ut in s o me insta nc es, ha ve a dela ye d o ns et (ie, da ys). 
I n t he e ve nt of a h y pers e nsitivit y re a ctio n, Fas e nra ™ s h o uld be dis c o ntin ue d. 
P ar asitic ( Hel mi nt h) I nf e cti o n 
E osin o p hils ma y be in v olve d in t he i m m u n ol o gic al res p o ns e t o s o me hel mint h infe ctio ns. P atie nts 
wit h k n o w n hel mint h infe ctio ns w ere e xclu de d fr o m participatio n in clinic al trials. It is u n k n o w n 
if Fas e nra ™ ma y influe nc e a patie nt’s res p o ns e a gainst hel mint h infe ctio ns. 
Tre at patie nts wit h pre-e xistin g hel mint h infe ctio ns bef ore initiati n g t hera p y wit h Fas e nra ™. 
If patie nts be c o me infe cte d w hile re c eivin g tre at me nt wit h Fas e nra ™ a n d d o n ot res p o n d t o 
a ntihel mint h tre at me nt, dis c o ntin ue tre at me nt wit h Fas e nra ™ u ntil infe ctio n res olves. 
Effe cts o n a bilit y t o dri v e a n d us e m ac hi ne s 
Fas e nra ™ has n o or ne gligible influe nc e o n t he a bilit y t o drive a n d us e ma c hines. 
S pe ci al pre c a uti o ns fo r st o r a g e 
St ore in a refrigerat or ( 2° C t o 8° C). St ore t he prefille d s yrin ge in t he original pa c ka ge t o pr ote ct 
fr o m lig ht. D o n ot fre e ze. 
N at ure a n d c o nte nts of c o nt ai ne r 
O ne m L  s olutio n in a sterile, sin gle- us e prefille d s yrin ge ma de fr o m t y pe I glass wit h a sta ke d 2 9 
ga u ge ½ inc h stainless ste el ne e dle, rigid ne e dle s hield, a n d Flu or ote c-c oate d st o p per in a passive 
s afet y de vic e. 
Fas e nra ™ is a vaila ble in a pa c k c o ntainin g 1 sin gle d os e prefille d s yrin ge. 
I nstr ucti o ns fo r us e, h a n dli n g a n d dis p os al 
D o n ot s ha ke. D o n ot us e if fr oze n. 
I nstr uctio ns f or a d ministratio n 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 7  of 6 7  
 
 
 
 
 
 
 
re c o m me n de d inje ctio n  site  (ie , u p per ar m, t hig h, or 
a b do m e n)  
 
4  
 
 
I nje ct all of t he me dic atio n b y p us hin g in t he plu n g er 
all t he w a y  u ntil t he  p lu n ger he a d is  c o m pletely 
bet we e n  th e  ne e dle  g uar d  a ctivatio n clips.  T his is 
ne c e ss ar y t o acti v ate t he ne e dle g u ar d.  
 
5  
 
 
Afte r inje ctio n , m aintain press ure o n t he plu n ger he a d 
a n d re m o ve t he ne e dle fro m  th e s kin. Rele as e press ure 
o n  t he  p lu n ger he a d t o allo w t he ne e dle g uar d t o c o ver 
th e  ne e dle.  D o  n ot r e -c a p t he prefille d s yri n g e.  
 
6   
D is c ard  t he  us e d  syrin ge int o a s har ps c o ntainer.  
 
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 8  of 6 7  
 
A p pe n di x E  C o ro n a vir us Dise ase- 1 9 V acci n ati o n G ui d a nce 
I n res p o ns e t o t he c urre nt pa n de mic a n d a p pr o val/ e mer ge nc y us e a ut h orizatio n ( E U A) of n o vel 
S A R S- C o V- 2 ( C O VI D- 1 9) va c cines, Astra Ze ne c a has de velo pe d t he f ollo win g g uida nc e f or 
be nraliz u ma b ( Fas e nra) trials:  
 T he trials c o ntin ue as per a p pr o ve d Clinic al St u d y Pr ot oc ol.  
 O n g oin g participa nts in clinic al  trials ma y re c eive a n a p pr o ve d/E U A C O VI D -1 9 va c cine 
w he n ma de a vaila ble t o t he m.  
 Va c cine a d ministratio n 
m ust be at le ast 7  da ys a part fr o m I P inje ctio n, lo n ger inter val is 
a d vis e d w he n p ossible. If ne e de d, I P d os e c a n be re-s c he d ule d t o allo w f or s ufficie nt 
inter val prior/ p ost C O VI D va c cinatio n. 
 S u bs e q ue nt I P d os e s h o uld be give n a differe nt loc atio n fr o m t he va c cine.  
 P atie nts w h o re c eive d C O VI D -1 9 va c cinatio n prior t o t he st u d y start s h o uld n ot be 
ra n d o mize d u ntil > 3 0  da ys after t he last va c cine d os e.  
 C O VI D va c cinatio n m ust be re c or de d o n C o nc o mita nt 
Me dic atio n m o d ule in e C R F cle arl y 
in dic atin g t he va c cine bra n d. T hat a p plies t o a n y C O VI D -1 9 va c cine re c eive d prior  t o or 
d urin g t he st u d y.  
 Us e of e x peri me ntal a n d/ or n o n -a p pr o ve d a n d / or n o n-a ut h oris e d C O VI D -1 9 va c cines is 
dis allo w e d.  
 T he de cisio n t o va c cinate s h o uld be bas e d o n t he ris ks a n d be nefits f or e a c h in divi d u al 
patie nt a n d o n w hat is in t he patie nt ’s best interest a c c or din g t o t he I n vestigat or ’s clinic al 
ju d ge me nt.  
 A n y q uestio ns s h o uld be a d dress e d t o t he st u d y Me dic al Te a m t hr o u g h t he Q A lo g, or dire ct 
c o m m u nic atio n if ur ge nt.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 9  of 6 7  
 
A p pe n di x F  A b bre vi ati o ns 
A b br e vi ati o n or s pe ci al 
te r m 
Ex pl a n ati o n  
A D A  
a nti dr u g a nti b o d y  
A D R  
a d v ers e dr u g re a cti o n  
A E  
a d v ers e e v e nt 
CI  
c o nfi d e n ce i nt er val 
C O P D  
c hr o nic o bstr u cti v e p ul mo nar y dise ase  
C R O  
c o ntra ct res e arc h or g anisati o n  
E C G  
ele ctr o c ar di o gra m 
E D C  
ele ctr o nic d at a c a pt ure  
E R  
E mer g e n c y Ro o m  
e C R F 
ele ctr o nic c ase re p ort for m 
E O S  
En d of St u d y  
F E V1  
f orc e d e xpirat or y v ol u me i n 1 s e c o n d  
G C P  
Go o d Cli nic al Pra ctic e  
GI N A  
Gl o b al I nitiati v e f or Ast h ma  
I C S 
i n h ale d c ortic ost er oi d 
I C F 
i nf or me d c o ns ent f or m 
I C H 
I nt er n ati o nal Co u n cil f or Har mo nis ati o n 
I E C 
I n d e p e n d ent Et hics Co m mitt e e 
I L-5  
i nt erl u ki n-5  
I L-5 R α  
i nt erl u ki n-5 re c e pt or al p h a s u b u nit  
I M P 
I n v esti gati o nal M e dici n al Pr o d uct 
I R B 
I nstit uti o nal Re vie w Bo ar d 
K M  
Ka pla n – Meier  
L A B A  
lo n g -a cti n g b eta -a g o nist 
O C S  
8. 1. st er oi d 
PI  
Pa c ka g e I ns ert  
Pre -B D  
pre br o n ch o dilat or  
P ost -B D  
p ost br o nch o dilat or  
S A E  
s eri o us a d v erse e v ent  
S D  
st a n dar d d e viati o n 
S A P  
st atistic al a n al ysis pla n 
S m P C  
S u m mar y of pr o d u ct c hara ct eristics  
S o A  
s c h e d ule of a cti vities 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 0  of 6 7  
 
A b br e vi ati o n or s pe ci al 
te r m 
Ex pl a n ati o n  
T E A E  
tre at me nt-e mer g ent a d verse e v e nt 
U S PI  
U nit e d St at es Pres cri bi n g I nf or mati o n  
 

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 1  of 6 7  
 
1 1   
R E F E R E N C E S 
Astr a Ze ne c a F as e nr a T M ( be nr aliz u m a b) S u m m ar y of Pr o d uct C h ar acte ristics  
Astra Ze ne c a. Fas e nra ™ ( be nraliz u ma b) s u m mar y of pr o d uct c hara cteristics. 2 0 1 9. Availa ble 
at w w w. e ma. e ur o pa. e u/e n/ d oc u me nts/ pr o d uct-inf or matio n/fas e nra-e par- pr o d uct-
inf or matio n _ e n. p df. A c c ess e d 0 4 Se p 2 0 2 0 . 
Astr a Ze ne c a F as e nr a ® ( be nr aliz u m a b) U S Pre s c ri bi n g I nfo r m ati o n  
Astra Ze ne c a. U S F D A 2 0 1 9. Availa ble at  
htt ps:// w w w. a c c ess data.f da. g o v/ dr u gs atf da _ d ocs/la bel/ 2 0 1 9/ 7 6 1 0 7 0s 0 0 5lbl. p df. A c c ess e d 0 4 
Se p 2 0 2 0 . 
Astr a Ze ne c a  
A Safet y E xte nsio n St u d y wit h Be nraliz u ma b f or Ast h matic A d ults o n I n hale d C ortic oster oid 
Plus L o n g-a ctin g β 2 A g o nist ( M E L T E MI): N C T 2 8 0 8 8 1 9 . Availa ble 
at  htt ps://clinic altrials. g o v/ct 2/s h o w/ N C T 2 8 0 8 8 1 9.  A c c ess e d 1 4 D e c e m ber 2 0 2 0 . 
Astr a Ze ne c a  
O bs er vatio nal St u d y of C hara cteristics, Tre at me nt a n d O utc o mes Wit h Se vere Ast h ma in t he 
U nite d States ( C H R O NI C L E): N C T 0 3 3 7 3 0 4 5 . Availa ble 
at  htt ps://clinic altrials. g o v/ct 2/s h o w/ N C T 0 3 3 7 3 0 4 5.  A c c ess e d 1 4 D e c e m ber 2 0 2 0 . 
B a g n as c o et al, 2 0 1 7  
Ba g nas c o D, Ferra n d o M, Varric c hi G, et al. A nti-interle u ki n 5 (I L- 5) a n d I L- 5 Ra biolo gic al  
dr u gs: effic a c y, s afet y, a n d f ut ure pers pe ctives in s e vere e osin o p hilic ast h ma. Fr o nt Me d 
( La us a n ne). 2 0 1 7; 4:1 3 5. 
Ble e c ke r et al, 2 0 1 6 
Ble e c ker E R , Fitz Gerald J M, C ha ne z P, P a pi A, Weinstein S F , Bar ker P, et al. E ﬃc a c y a n d s afet y 
of be nraliz u ma b f or  patie nts wit h s e vere ast h ma u nc o ntr olle d wit h hig h- d os a ge in hale d 
c ortic oster oids a n d lo n g-a ctin g β 2 -a g o nists ( SI R O C C O): a ra n d o mis e d, m ultic e ntre, pla c e b o-
c o ntr olle d p has e 3 trial. La nc et 2 0 1 6; 3 8 8:2 1 1 5 -2 7  
B us s e et al, 2 0 1 9  
B uss e W W, Ble e c ker E R, Fitz gerald J M, Fer g us o n G T, Bar ker P, S pr o ule S, et al. L o n g -ter m 
s afet y a n d effic a c y of be nraliz u ma b in patie nts wit h s e vere, u nc o ntr olle d ast h ma: 1- ye ar res ults 
fr o m t he B O R A p has e 3 e xte nsio n trial. La nc et Res pir Me d 2 0 1 9; 7:4 6- 5 9  
C h u n g et al, 2 0 1 4  
C h u n g K F, We nzel S E, Br ozel J L, B us h A, Castr o M, Ster k PJ, et al. I nter natio nal E R S/ A T S 
g uidelines o n definitio n, e valuatio n a n d tre at me nt of s e vere ast h ma. E ur Res pir J 2 0 1 4; 4 3: 3 4 3-
3 7 3  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 2  of 6 7  
 
 
Clinic al St u d y Re p ort D 3 2 5 0 C 0 0 0 3 7 . A M ultic e nter, O pe n-la bel, Safet y E xte nsio n St u d y wit h 
Be nraliz u ma b ( M E DI- 5 6 3 ) f or Ast h matic A d ults o n I n hale d C ortic oster oid Plus L o n g-a ctin g 
β 2  A g o nist ( M E L T E MI). Astra Ze ne c a. 2 6  O ct,  2 0 2 0.  
 
Fitz g e r al d et al, 2 0 1 6  
Fitz gerald J M, Ble e c ker E R, N air P, K or n S, O hta K, L o m mats zc h M, et al. Be nraliz u ma b, a n 
a nti-interle u kin- 5 re c e pt or α m o n oclo nal a ntib o d y, as a d d- o n tre at me nt f or  patie nts wit h s e vere, 
u nc o ntr olle d, e osin o p hilic ast h ma ( C A LI M A): a ra n d o mis e d, d o u ble- bli n d, pla c e b o-c o ntr olle d 
p has e 3 trial. La nc et 2 0 1 6; 3 8 8 : 2 1 2 8-4 1  
GI N A 2 0 2 0  
Glo bal I nitiative f or Ast h ma. Glo bal Strate g y f or Ast h ma Ma na ge me nt a n d Pre ve ntio n 2 0 2 0. 
A vaila ble fr o m: w w w. gina ast h ma. or g  
 G o nz ale z et al , 2 0 1 9  
Go nzale z I D, Be nite z F M, Q uirc e S. Be nraliz u ma b: A N e w A p pr oa c h f or t he Tre at me nt of 
Se vere E osin o p hilic Ast h ma . J I n vestig Aller g ol Clin I m m u n ol 2 0 1 9; 2 9:8 4 -9 3.  
I S A R 
I nter natio nal Se vere Ast h ma Re gistr y (I S A R). Availa ble at htt ps://is are gistries. or g/  A c c ess e d 1 4 
D e c e m ber 2 0 2 0.  
J ac ks o n et al, 2 0 2 0  
J a c ks o n DJ, K or n S, Mat h ur S K, et al, Safet y of E osin o p hil- D e pletin g T hera p y f or Se vere, 
E osin o p hilic Ast h ma: F oc us o n Be nraliz u ma b. Dr u g Saf . 2 0 2 0; 4 3:4 0 9- 4 2 5. 
 K ol be c k et al, 2 0 1 0  
K olbe c k R, K oz hic h A, K oike M, P e n g L, A n derss o n C K, D a ms c hr o der M M, et al. M E DI- 5 6 3, a 
h u ma nize d a nti- I L- 5 re c e pt or alp ha m A b wit h e n ha nc e d a ntib o d y- de pe n de nt c ell- me diate d 
c yt ot o xicit y f u nctio n. J Aller g y Clin I m m u n ol 2 0 1 0; 1 2 5: 1 3 4 4- 1 3 5 3 
P a v o r d et al, 2 0 1 3   
P a v or d I D. E osin o p hilic p he n ot y pes of air w a y dis e as e. A n n A m T h ora c S oc 2 0 1 3; 1 0 
S u p pl: S 1 4 3- 9  
Pel ai a et al, 2 0 2 0  
P elaia C, B us c eti M T, Cri mi C, Car pa g na n o G E, L o m bar d o N, Terra c cia n o R, et al. Re al- Life 
e ﬀe cts of be nraliz u ma b o n e xa c er batio n n u m ber a n d lu n g h y perin ﬂatio n in at o pic  patie nts wit h 
s e vere e osin o p hilic ast h ma. Bio me d P har ma c ot her 2 0 2 0; 1 2 9: 1 1 0 4 4 4 d oi: 
1 0. 1 0 1 6/j. bio p ha. 2 0 2 0. 1 1 0 4 4 4.  O nline a he a d of print.  
P erio dic Be nefit- Ris k E valuatio n Re p ort. Fas e nra ™ ( be nraliz u ma b). Astra Ze ne c a. 1 9 D e c,  2 0 2 0.  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 3  of 6 7  
 
R o gli a ni et al, 2 0 2 0  
R o glia ni P, Calzetta L, Matera M G, Laita n o R, Rit o n d o B L, H a na nia N A, et al. Se vere Ast h ma 
a n d Biolo gic al T hera p y: W he n, W hic h, a n d f or W h o. P ul m T her 2 0 2 0 ; 6:4 7-6 6  
T a k ats u et al, 1 9 9 4  
Ta kats u K, Ta ka ki S, Hit os hi Y. I nterle u kin- 5 a n d its re c e pt or s yste m: i m plic ati o ns in t he 
i m m u ne s yste m a n d infla m matio n. A d v I m m u n ol. 1 9 9 4; 5 7:1 4 5- 9 0. 
To b a et al, 1 9 9 9  
To ba K, K oike T, S hibata A, H as hi m ot o S, Ta ka has hi M, Mas u k o M, et al. N o vel te c h niq ue f or 
t he dire ct flo w c yt oflu ori metric a nalysis of h u ma n bas o p hiles in u ns e parate d blo o d a n d b o ne 
marr o w, a n d t he c hara cterizatio n of p he n ot y pe a n d per o xidas e of h u ma n bas o p hiles. C yt o metr y. 
1 9 9 9; 3 5:2 4 9- 5 9  
Walfo r d et al, 2 0 1 4  
Walf or H H, D o hert y T A. Dia g n osis a n d ma na ge me nt of e osin o p hilic ast h ma: a U S pers pe ctive. J 
Ast h ma Aller g y 2 0 1 4; 7:5 3- 6 5  

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 4  of 6 7  
A S T R A Z E N E C A SI G N A T U R E( S)  
A P ost m ar keti n g, P h ase 4, M ultice ntre, Pros pecti ve, Si n gle -ar m St u dy 
t o Assess the S afet y of Fase nra ® ( Be nraliz u m a b) i n A d ult P atie nts of 
Se vere Ast h m a wit h Eosi n o p hilic P he n oty pe i n I n di a  
T his Cli nic al St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Z e nec a revie w 
I a gr ee t o t he ter ms of t his St u d y pr ot oc ol. 
Astr a Ze ne c a r e pr es e nt ati ve  
  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Na m e a n d Affili ati o n  
 Dat e ( Da y M o nt h Ye ar)  
( St u d y Dir ect or) 
V P - Me dic al Aff airs & Re g ulat or y  
Astr a Ze nec a P har ma I n dia Lt d.  
Bloc k N 1, 1 2 t h Flo or,  
Ma n yata E m bass y Business P ar k,  
Ba n galor e, Kar nata ka 5 6 0 0 4 5  
T his d oc u me nt c o nt ai ns c o nfi de nti al i nf or m ati o n, w hic h s h o ul d n ot be c o pie d, ref erre d t o, 
rele ase d or p u blis he d 
wit h o ut writte n a p pr ov al f r o m Astr a Z e nec a. I nv esti g at ors are 
c a uti o ne d t h at t he i nf or m ati o n i n t his pr ot oc ol m ay be s u bject t o c h a n ge a n d revisi o n.  
M a r  1 1 ,  2 0 2 1
P P D
P P D

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 6  of 6 7  
 
A S T R A Z E N E C A SI G N A T U R E( S)   
 
 
 
 
A P ost m ar keti n g, P h ase 4, M ultice ntre, Pros pecti ve, Si n gle -ar m St u dy 
t o Assess t he S afet y of Fase nra ® ( Be nraliz u m a b) i n A d ult P atie nts of 
Se vere Ast h m a wit h Eosi n o p hilic P he n oty pe i n I n di a  
  
 
 
 
T his Cli nic al St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Z e nec a revie w  
 
I a gr ee t o t he ter ms of t his St u d y pr ot oc ol.  
 
 
Astr a Ze ne c a r e pr es e nt ati ve                  
                                                        
        _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Na m e a n d Affili ati o n                             Dat e ( Da y M o nt h Ye ar)  
 
( St u d y Deliver y T ea m Lea der) 
S e nior Ma na ger -Trials, P u blic atio ns & Me dic al E xc elle nc e  
Astr a Ze nec a P har ma I n dia Lt d.  
Bloc k N 1, 1 2t h Flo or,  
Ma n yata E m bass y Business P ar k,  
Ba n galor e, Kar nata ka 5 6 0 0 4 5  
M o bile n o. -
 
  
 
 
 
T his d oc u me nt c o nt ai ns c o nfi de nti al i nf or m ati o n, w hic h s h o ul d n ot be c o pie d, ref erre d t o, 
rele ase d or p u blis he d 
wit h o ut writte n a p pr ov al f r o m Astr a Z e nec a. I nv esti g at ors are 
c a uti o ne d t h at t he i nf or m ati o n i n t his pr ot oc ol m ay be s u bject t o c h a n ge a n d revisi o n.  
 
M a r  1 0 ,  2 0 2 1
P P D
P P D
P P D

Cli nic al St u d y Prot o col 
Astra Zen ec a 
Dr u g S u bst anc e: Fas e nra ® ( Be nralizu ma b) 
St u d y Co d e: D 3 2 5 0 C0 0 0 9 3 
Versi o n: 1. 0 Dat e d 0 9  M ar 2 0 2 1  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 7  of 6 7  
 
A S T R A Z E N E C A SI G N A T U R E( S)   
 
 
 
A P ost m ar keti n g, P h ase 4, M ultice ntre, Pros pecti ve, Si n gle -ar m St u dy 
t o Assess t he Safet y of Fase nra ® ( Be nraliz u m a b) i n A d ult P atie nts of 
Se vere Ast h m a wit h Eosi n o p hilic P he n oty pe i n I n di a  
  
 
 
 
T his Cli nic al St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Z e nec a revie w  
 
I a gr ee t o t he ter ms of t his St u d y pr ot oc ol.  
 
 
Astr a Ze ne c a r e pr es e nt ati ve                  
                                                        
        _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Na m e a n d Affili ati o n                             Dat e ( Da y M o nt h Ye ar)  
 
( St u d y P h ysicia n) 
Me dic al Aff airs  
Astr a Ze nec a P h ar ma I n dia Lt d.  
Bloc k N 1, 1 2t h Flo or,  
Ma n yata E m bass y Business P ar k,  
Ba n galor e, Kar nata ka 5 6 0 0 4 5  
M o bile N o: 
 
  
 
 
 
T his d oc u me nt c o nt ai ns c o nfi de nti al i nf or m ati o n, w hic h s h o ul d n ot be c o pie d, ref erre d t o, 
rele ase d or p u blis he d 
wit h o ut writte n a p pr ov al f r o m Astr a Z e nec a. I nv esti g at ors are 
c a uti o ne d t h at t he i nf or m ati o n i n t his pr ot oc ol m ay be s u bject t o c h a n ge a n d revisi o n.  
 
M a r  1 0 ,  2 0 2 1
P P D
P P D
P P D