A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults
Phase: PHASE1
Conditions: COVID-19
Sponsor: AstraZeneca

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Cli nic al St u d y Pr ot oc ol
A P h ase I D o u ble -bli n d, Pl ace b o -c o ntr olle d St u d y t o E v al u ate 
t he S afet y, Toler a bilit y a n d P h ar m ac o k i netics of A Z D 7 4 4 2 i n 
He alt h y A d ults
P are xel St u d y N o.:
P X L 2 5 2 1 6 6
S p o ns or St u d y C o de:
D 8 8 5 0 C 0 0 0 0 1
E u dr a C T N o:
2 0 2 0- 0 0 3 0 7 6 - 4 0
I n vesti g ati o n al Me dici n al Pr o d uct(s):
A Z D 7 4 4 2 (A Z D 8 8 9 5 + A Z D 1 0 6 1 )
T her a pe utic I n dic ati o n:
Pr o p h y la xis a n d treat me nt of S A R S-C o V -2 i nfecti o n
P h ar m ac ol o gic al Cl ass:
C o m bi ne d m o n ocl o nal a nti b o dies ( m A bs)
De vel o p me nt P h ase:
P hase I
S p o ns or:
Astra Ze neca A B
1 5 1 8 5 S ö dertälje
S we de n
St u d y Ce ntre :
Pare xel Earl y P hase Cli nical U nit ( L o n d o n)
Le vel 7, N ort h wic k Par k H os pital
 H A 1 3 UJ
U n ite d Ki n g d o m
D ate of Pr ot oc ol:
Fi nal , 2 4 J ul y 2 0 2 0 
Pr ot oc ol A me n d me nt N o. 1:
Fi nal, 0 7 A u g ust 2 0 2 0
Pr ot oc ol A me n d me nt N o. 2 :
Fi nal, 2 3 Se pte m ber 2 0 2 0
Pr ot oc ol A me n d me nt N o. 3 :
Fi nal , 0 8 Dece m ber 2 0 2 0
Pr ot oc ol A me n d me nt N o. 4:
Fi nal , 0 8 Fe br uar y 2 0 2 1
Pr ot oc ol A me n d me nt N o. 5:
Fi nal , 1 6 A pr il 2 0 2 1
Pr ot oc ol A me n d me nt N o. 6:
Fi nal, 1 9 J ul y 2 0 2 1
T his cli nical st u d y will be c o n d ucte d acc or di n g t o t he pr ot oc ol a n d i n c o m plia nce wit h t he 
I nter nati o nal C o u ncil f or Har m o nisati o n Tri partite g ui deli ne f or G o o d Cli nical Practice a n d wit h 
ot her a p plica ble re g ulat or y re q uire me nts.
C o nfi de nt iality State m e nt
T his c o nfi de nt ial d oc u me nt is t he pr o pert y of Astra Ze neca. N o u n p u blis he d i nf or mati on 
c o ntai ne d herei n ma y be discl ose d wit h o ut pri or writte n a p pr o val fr o m Astra Ze neca. 
Access t o t his d oc u me nt must be restri cte d t o rele va nt parties.
P P D

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
P R O T O C O L A M E N D M E N T S
Pr ot oc ol A me n d me nt N o. 6 , d ate d 1 9 J u l y 2 0 2 1
T he re vise d C S P date d 1 6 A pril 2 0 2 1 ( Pr ot oc ol A me n d me nt N o. 5 ) was a me n de d t o
i ncl u de a d mi nistrati ve c ha n ges a n d a n u p date t o t he S A R S -C o V -2 ser ol o g y  a n d q R T-P C R
f oot e r i n t he scree ni n g Sc he d ule of Assess me nt.
T he f o ll owi n g sect i ons of t he pr ot oc ol ha ve bee n c ha n ge d:
 
In vest i gat ors a n d st u d y a d mi nistrati ve str uct ure: S p o ns or’s lea d p h ysicia n was u p date d 
fr om 
. Details o n a n a d ditio n al  anal yt ical la b orat or y
( G C L-E U) were a d de d.
 
Ta ble 3- 1 : U p date d f o ot n ote ‘ b’ (S A R S -C o V -2 ser ol o g y  a n d q R T-P C R ) t o incl u de t he 
f oll owi n g: T he C O VI D -1 9 tests at scree ni n g will be perf or me d as part of t he Cli nical 
U nit ’s ge neral scree ni n g. T hese C O VI D 1 9 scree ni n gs will occ ur after t he s u bject has 
c o nse nte d t o t he C O VI D-1 9 scree ni n g a n d bef ore c o nse nt f or t he st u d y  is o btai ne d.
 
Secti o n  1 2. 1 : Details of t he S p o ns or’s l ea d p h ysicia n were u p date d fr o m   
 
 t o 
.
 
A d dit i onal mi n or f or matti n g a n d gra m mat ical c orrecti o ns were ma de.
Pr ot oc ol A me n d me nt N o. 5 , d ate d 1 6 A pril 2 0 2 1
T he re vise d C S P date d 0 8 Fe br uar y 2 0 2 1 ( Pr ot oc ol A me n d me nt N o. 4 ) was a me n de d t o
i ncl u de a t hir d a n d f o urt h i nteri m a nal ysis. T he data fr o m t his a nal ysis will be use d i n a 
re g ulat or y s u b missio n .
T he f o ll owi n g secti ons of t he pr ot oc ol ha ve bee n c ha n ge d:
 
S y n o psis ( Prese ntati o n a n d A nal ysis of E x pl orat or y Data ): U p date d te xt t o state t hat 
e x pl orat or y d at a ma y for m  part of t he C S R.
 
S y n o psis ( I nteri m A nal ysis): A d de d t hat a t hir d a n d f ourt h i nteri m a nal ysis will be
perf or m e d a n d s pecifie d w hat data will be use d f or eac h a nal ysis.
 
I n vesti gat ors a n d St u d y  Ad mi nistr ati ve Str uct ure : A d de d M o n o gra m  Bioscie nces –
La b C or p S pecialt y Test i n g Gr o u p f or e x pl orat or y n e utralisi n g a nt i b o d y a nal ys is.
 
Secti o n 2. 3 : U p date d e x pl orat or y  o utc o me meas ure t o state t hat e x pl orat or y data ma y 
f or m part of t he C S R.
 
Secti o n 4. 4 : A d de d t hat a t hir d a n d f o urt h i nteri m a nal ysis will be perf or me d a n d 
s pecifie d w hat data will be use d f or eac h a nal ysis.
 
Secti o n 6. 6 : Re m o ve d te xt stati n g t hat res ults f or ne utralisi n g a nti b o d y assess me nts 
will be re p orte d se paratel y  fr o m t he C S R.
 
Secti o n 1 1. 2. 6. 2 : A d de d h o w t he res ults f or nasal fl ui d P K will be a nal yse d a n d 
prese nte d.
P P D
P P D
P P D

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Pr ot oc ol A me n d me nt N o. 4 , d ate d 0 8 Fe br u a r y 2 0 21
T he re vise d C S P date d 0 8 Dece m ber 2 0 2 0 ( Pr ot oc ol A me n d me nt N o. 3 ) was a me n de d t o
a d d t he o pti o n f or st u d y partici pa nts t o recei ve a n a p pr o ve d vacci ne f or pr otecti o n a gai nst 
S A R S -C o V -2.
T he f o ll owi n g sect i ons of t he pr ot oc ol ha ve bee n c ha n ge d:
 
S y n o psis ( St u d y  Desi g n): A d de d t hat g ui da nce f or ma na ge me nt of s u bjects w h o wis h 
t o recei ve a n a p pr o ve d vacci ne f or pr otecti o n a gai nst S A R S-C o V - 2 is pr o vi de d.
 
Secti o n 3. 1 : A d de d t hat g ui da nce f or ma na ge me nt of s u bjects w h o wis h t o recei ve a n 
a p pr o ve d vacci ne f or pr otecti o n a gai nst S A R S -C o V -2 is pr o vi de d.
A d de d t hat a n u nsc he d ule d u n bli n di n g visit will be i ncl u de d s h o uld a s u bject wa nt t o 
be u n bli n de d f or vacci nati o n p ur p oses o utsi de t he visit wi n d o w s d uri n g t he F ol l ow- u p 
P erio d.
 
Fi g ure 3- 1 : A d de d f o ot n ote t hat an u nsc he d ule d u n bli n di n g visit will be i ncl u de d 
s h o uld a s u bject wa nt t o be u n bli n de d f or vacci nat i o n p ur p oses o utsi de t he visit 
wi n d o ws.
 
Ta ble 3- 3 : A d de d f o ot n ote t hat a n u nsc he d ule d u n bli n di n g visit will be i ncl u de d 
s h o uld a s u bject wa nt t o be u n bli n de d f or vacci nat i o n p ur p oses o utsi de t he visit 
wi n d o ws.
 
Secti o n 5. 3. 2 : Met h o ds f or u n bli n di n g t he st u d y were u p date d t o pr o vi de g ui da nce i n 
t he e ve nt t hat a partici pa nt wi s hes t o recei ve a n a p pr o ve d vacci ne t o pr otect a gai nst 
i nfecti on wi t h S A R S-C o V -2 or wis hes t o wit h dra w c o m pletel y fr o m t he st u d y  after 
u n bli n di n g .
 
Secti o n 5. 5 : G ui da nce was a d de d re gar di n g t he pr oce d ure t o be f o ll owe d i n t he e ve nt 
t hat a partic i pa nt bec o mes eli gi ble f or t he C O VI D -1 9 vacci ne a gai nst i nfecti o n wit h 
S A R S -C o V - 2.
 
A d dit i onal mi n or f or matti n g a n d gra m mat ical c orrecti o ns were ma de.
Pr ot oc ol A me n d me nt N o. 3 , d ate d 0 8 Dece m ber 2 0 2 0
T he re vise d C S P date d 2 3 Se pte m ber 2 0 2 0 ( Pr ot oc ol A me n d me nt N o. 2 ) was a me n de d t o
c ha n ge t he Pri nci pal I n vest i gat or fr o m Dr M u na Al ba yat y t o Dr Pa bl o F orte S ot o. 
Pr ot oc ol A me n d me nt N o. 2, d ate d 2 3 Se pte m ber 2 0 2 0
T he re vise d Cli nical St u d y  Pr ot oc ol ( C S P) date d 0 7 A u g ust 2 0 2 0 ( Pr ot oc ol A me n d me nt 
N o. 1) was a me n de d t o defi ne C o h ort 4 of t he st u d y f or d osi n g of A Z D 7 4 4 2 3 0 0 0 m g 
i ntra ve n o usl y (I V) wit h c o -a d mi nistrati o n i nstea d of se q ue nt ial a d mi nistrati o n of t he 
i n di vi d ual m o n ocl o nal a nt i b o dies (m A bs ). O btai ni n g safet y a n d p har mac o ki net ic ( P K)
data f or mi xe d, I V c o- a d mi nistrati o n o f t he m A bs will per mit a si m plifie d a d mi nistrati o n 
pr ocess a n d s h orter I V i nf usi on ti mes f or A Z D 7 4 4 2.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
T he f o ll owi n g secti ons of t he pr ot oc ol ha ve bee n c ha n ge d :
 
Secti o n 1. 2 Rati o nale f or C o n d ucti n g T his St u d y (te xt a d de d).
 
Secti o n 2. 2 Se c o n dar y O bject i ves (te xt a d de d).
 
Secti o n 3. 1 O verall St u d y  Desi g n a n d Fl o w C hart (te xt a d de d).
 
Fi g ure 3- 2 O verall Gra p hical Re prese ntati o n of t he St u d y (fi g ure u p date d; e x pla nat or y  
f oot n otes a d de d).
 
Ta ble 3- 2 Sc he d ule of Assess me nts ( Treat me nt Peri o d) (f o ot n otes u p date d ; data of 
Da y 2 m o ve d fr o m  Ta ble 3- 3 t o be di s pla ye d u n der Treat me nt Peri o d rat her t ha n 
u n der F ol l ow - u p Perio d ).
 
Secti o n 3. 2. 5 D o se Escalati o n Strate g y (te xt a d de d).
 
Secti o n 3. 2. 7. 2 Data Re vie we d b y D ose Escalat i on C o m mittee f or D ose Escalati o n 
Decisi o n (te xt a d de d).
 
Secti o n 3. 2. 7. 3 D ose Escalat i on C o m mit tee Decisi o n o n Ne xt D ose (te xt a d de d).
 
Secti o n 3. 3. 2 De gree of U ncertai nt y:  C o-a d mi nistratio n of  M o n oclo nal A nt i b o dies 
( ne w secti on a d de d).
 
Secti o n 4. 4 I nteri m A nal ysis (te xt a d de d).
 
Secti o n 5. 1. 1 Pr oce d ures f or Ra n d o misat i on (te xt re vise d).
 
Secti o n 5. 3. 1 Met h o ds f or E ns uri n g Bli n di n g (te xt a d de d).
 
Ta ble 5- 2 I de ntity of  t he I n vesti gati onal Me dici nal Pr o d uct (te xt a d de d).
 
Secti o n 5. 4. 3 D o se a n d Treat me nt Re gi me ns (te xt a d de d).
 
Secti o n 1 0 E val ua tio n a n d Calc ulat i on of Varia bles (te xt a d de d).
 
Secti o n 1 1. 2 Met h o ds of Statist ical A nal ysis (te xt a d de d).
 
Secti o n 1 1. 4 Deter mi nat i on of Sa m ple Si ze (te xt a d de d).
F urt her m ore, i nc o nsiste ncies i n t he pre vi o us versi o n of t he pr ot oc ol were clarifie d 
t hr o u g h o ut t he pr ot oc ol. Te xt of t he Pr ot oc ol S y n o psis was re vise d i n ali g n me nt wit h 
c orres p o n d i n g secti ons wi t hi n t he pr ot oc ol. T he Ta bles of C o nte nts we re u p dated t o s h o w 
t he hea di n g a n d pa ge n u m ber re visi o ns.
Pr ot oc ol A me n d me nt N o. 1, d ate d 0 7 A u g ust 2 0 2 0
T he f o ll owi n g c ha n ges were ma de t o t he ori gi nal C S P , date d 2 4 J ul y 2 0 2 0, t o i ncl u de 
c ha n ges re q ueste d b y t he Me dici nes a n d Healt hcare P r o d ucts Re g ul at or y Age nc y 
(M H R A ).
 
Pr ot oc ol  S y n opsi s, Secti o n s 3. 1 a n d 1 1. 4 : Te xt re gar di n g t he p ote ntial for a d ditio n of  a 
c o h ort wit h a hi g her d ose of A Z D 7 4 4 2 has bee n re m o ve d .
 
Secti o n 4. 1. 1 : I ncl usi on Cri t erio n 8 u p date d t o state t hat females of c hil d beari n g 
p ote nti al w h o are se x uall y act i ve wit h a n o n-sterilise d male part ner m ust ha ve use d a 
sta ble a n d hi g hl y  effecti ve met h o d of c o ntrace pti o n f or at  least 3 m o nt hs pri or t o 
d osi n g wit h I M P a n d m ust a gree t o c o nti n ue usi n g s uc h preca uti o ns u nt il 3 6 0 da ys 
after t he d ose of I M P.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 
Secti o n 4. 2. 1. 2 : Te xt a d de d t o clarif y t hat t he c o ntrace pti ve re q uire me nts a p pl y t o 
w o m a n of c hil d beari n g p ote ntial a n d t heir n o n- sterilise d male part ners. T hi s is f or 
c o nsiste nc y wit h w or di n g use d i n I ncl usi o n Cri t eri o n 8. 
 
Secti o n 4. 2. 1. 2 : T e xt a d de d stati n g t hat fe male partici pa nts s h o ul d n ot d o nate o va f or
3 6 0 d a y s after t he I M P d ose .
 
Secti o n  4. 2. 1. 3 : Te xt is u p date d t o state t hat  female part ner/s p o use of t he male 
parti ci pa nt s h o uld be sta ble o n t heir c h ose n met h o d of birt h c o ntr ol f or at least 
3 m o nt hs pri or t o d osi n g wit h I M P a n d m ust a gree t o c o nti n ue usi n g s uc h preca uti ons 
u nt il 3 6 0 da ys after t he d ose of I M P.
 
Secti o n 1 1. 3 : Te xt a d de d t o c o nfir m t hat pla n ne d pr ot oc ol de viat i ons are n ot 
acce pta ble a n d t hat t hose s us pecte d or k n o w n t o ha ve t he p ote ntial t o si g nifica nt l y 
i m pact o n a partici pa nt’s safet y, p h ysical or me ntal i nte grit y, or scie nt ific val ue will be 
classifie d as a seri o us breac h .

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
P R O T O C O L S Y N O P SI S
Title of t he St u d y
A P hase I D o u ble -bli n d, Place b o -c o ntr olle d St u d y t o E valuate t he Safet y,  T olera bilit y a n d 
P har mac o ki net ics of A Z D 7 4 4 2 i n Healt h y A d ult s.
Pri nci p al I n vesti g at or ( PI)
Dr Pa bl o F orte S ot o ( M D, M Sc, P h D)
St u d y C ent re
T his st u d y  will be c o n d ucte d at a si n gle st u d y ce ntre.
St u d y R ati o n ale a n d J ustific ati o n of St u d y Desi g n
A Z D 7 4 4 2 m o n ocl o nal a nt i b o dies ( m A bs) are bei n g e val uate d f or a d mi nistrati o n t o pre ve nt 
or treat t he C or o na vir us Disease 2 0 1 9 ( C O VI D - 1 9). T his P hase I st u d y will gat her 
i m p orta nt i nf or mati on o n t he safet y a n d t olera bilit y of  AZ D 7 4 4 2 , as well as rele va nt data 
o n t he p har mac o ki net ic (P K ) pr ofile a n d t he ge nerati o n of a nt i-dr u g a nti b o dies ( A D As) t o 
A Z D 7 4 4 2. I n a d diti on, b ot h se q ue nt ial a n d c o -a d mi nistrati o n of t he m A bs will be 
i n vestigate d t o gat her i m p orta nt i nf or mat i on o n t he P K, t he I V a d mi nistrati o n pr ocess a n d 
i nf usi on ti mes.
N u m ber of P artici p a nt s Pl a n ne d
It is pla n ne d t o e nr ol at least 6 0 healt h y part ici pa nts acr oss 5 d osi n g c o h orts.
St u d y O bjecti ves
T he o bj ect i ves of t he st u d y are:
Pri m ary O bjective:
 
T o e val uate t he safet y a n d t olera bilit y of A Z D 7 4 4 2 a d mi nistere d i ntra ve n o usl y (I V) or 
i ntr a musc ularl y  (I M) t o healt h y a d ult parti ci pa nt s 1 8 t o 5 5 years of a ge.
Sec o n d ary O bjectives:
 
T o e val uate t he si n gle d ose P K of A Z D 7 4 4 2 ( w he n m A bs are a d mi nistere d 
se q ue ntiall y [di vi de d i n se parate i nf usi o n of eac h m A b c o m p o ne nt ], a n d w he n m A bs 
are c o-a d mi nistere d [b ot h m A bs mi xe d i nt o a si n gle i nf usi o n] ) i n ser u m.
 
T o e val uate t he A D A res p o nses t o t he A Z D 7 4 4 2 i n ser u m.
E x pl or at ory O bjectiv es:
 
T o e val uate t he si n gle d ose P K c o nce ntrati o ns of A Z D 7 4 4 2 i n nasal fl ui d.
 
T o e val uate t he f u nct i onal i n hi bit i on of se vere ac ute res pirat or y s y n dr o me 
c or o na vir us 2 ( S A R S -C o V - 2) b y A Z D 7 4 4 2 c o nce ntrati o ns i n ser u m.
St u d y Desi g n
T his is a P hase I, first ti me i n h u ma n ( F TI H), ra n d o mise d, d o u ble-bli n d, 
pl ace b o -c o ntr olle d, d ose escalat i on st u d y  e val uati n g t he safet y, t olera bilit y, a n d P K of 
A Z D 7 4 4 2 i n healt h y a d ult partici pa nt s, 1 8 t o 5 5 years of a ge. A p pr o xi matel y 6 0 healt h y 
parti ci pa nt s will be e nr olle d at o ne st u d y  ce ntre a n d ra n d o mise d 1 0: 2 t o eit her A Z D 7 4 4 2 
or pl ace b o a d mi nistere d I V or I M, acr oss 5 fi xe d-d ose c o h orts. F or partici pa nts w h o will 
recei ve t he i n vesti gati onal me dici nal pr o d uct ( I M P) via I M i njecti on ( C o h ort 1a), t he I M P 
will be a d mi nistere d as se q ue ntial direct gl uteal I M a d mi nistrati o ns starti n g wit h 
A Z D 8 8 9 5/ place b o a n d f o ll owe d b y A Z D 1 0 6 1/ place b o. F or partici pa nt s w h o will recei ve 

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 of 1 0 3
t he I M P via I V i nf usi o n i n t he first 3 c o h orts t o be d ose d via I V i nf usi o n ( C o h orts 1 b, 2, 
a n d 3) , the I M P will be a d mi nistere d i n t wo se q ue ntial I V i nf usio ns at a ma xi mal i nf usi on 
rate of 2 0 m g/ mi n ute, starti n g wit h A Z D 8 8 9 5/ place b o a n d f o ll owe d b y  A Z D 1 0 6 1/ place b o. 
F or partici pa nts w h o will recei ve t he I M P via I V i nf usi o n i n C o h ort 4, t he I M P will be 
c o -a d mi nistere d as a si n gle I V i nf usi o n c o ntai ni n g b ot h m A bs / place b o at a ma xi mal 
i nf usi on rate of 5 0 m g/ mi n ute. A d dit i onal c o h orts ma y be a d de d wit h l o wer or 
i nter me diate d ose s of  A Z D 7 4 4 2 if t he D ose Escalati o n C o m mittee ( D E C) deter mi nes t he y 
are warra nte d.
After t he scree ni n g p eri o d, eac h eli gi ble partici p a nt will be a d mitte d t o earl y p hase cli nical 
u nit ( E P C U) o n Da y -1 ( 1 d a y  prior t o d osi n g) a n d disc har ge d o n Da y  2 ( 1 da y after 
d osi n g , after t he 2 4-h o ur pr oce d ures are c o m plete d ). Parti ci pa nt s will t he n be m o nit ore d
f or a p pr o xi matel y o ne year after d osi n g (Da y 3 6 1 ) f or safety,  incl u di n g rec or di n g of 
a d verse e ve nts ( A Es ) a n d serio us a d verse e ve nts ( S A Es ), a n d c ollecti o n of bl o o d sa m ples
f or P K a n d A D As. Se nti nel d osi n g will be a p plie d f or all d osi n g c o h orts t o e ns ure 
parti ci pa nt safety , as f oll ows: T w o partici pa nt s of  eac h c o h ort will be d ose d at  a rati o of 
1: 1 ( A Z D 7 4 4 2: place b o ) a n d will t he n u n der g o a safet y m o ni t ori n g peri o d for at least 
2 4 h o urs bef ore d osi n g t he rest of t he parti ci pa nt s of t hat co h ort . Escalati on fr o m o ne d ose 
le vel t o t he ne xt d ose le vel, a n d fr o m t he last c o h ort wit h se q ue ntial I V i nf usio ns of  t he 
m A bs ( C o h ort 3) t o t he first c o h ort wit h a c o -a d mi nistere d i nf usi o n of t he m A bs
( C o h ort 4), will be base d o n re vie w o f all a vaila ble safet y data u p t o a n d i ncl u di n g Da y  8. 
I n a d diti on, a n y a vaila ble P K data will als o be re vie we d.
As t he st u d y  will ver y li kel y t a k e place d uri ng t he C O VI D -1 9 pa n de mic, meas ures will be 
p ut i n place t o e ns ure mi ni mal S A R S -C o V -2 e x p os ure f or site staff, as well as st u d y 
parti ci pa nt s. E xclusi o n  a n d wit hdra wal cri t eria are i n place t o e ns ure site staff a n d st u d y 
parti ci pa nt safety.  Re p orti n g of S A R S-C o V -2 p ositi ve res ults d uri n g t he st u d y  c o n d uct 
will be re p orte d as A Es a n d meas ures will be a p plie d at t he discret i on of t he PI t o 
mi ni mi se furt her S A R S -C o V -2 e x p os ure as m uc h as p ossi ble. G ui da nce f or m a na ge me nt 
of  s u bjects w h o wis h t o recei ve a n a p pr o ve d vacci ne f or pr otecti o n a gai nst S A R S-C o V - 2 
is pr o vi de d.
E x pecte d D ur ati o n of t he St u d y
T he st u d y  is e x pecte d t o be a p pr o xi matel y 3 89 da ys i n d urati o n f or eac h parti ci pa nt , 
c o nsist i n g of a Scree ni n g Peri o d of  u p t o 2 7 da ys ( Da y -2 8 t hr o u g h Da y -2), a T reat me nt 
P erio d of  2 d a y s (Da y - 1 t o Da y 1 ) a n d a 3 6 0-da y  s afet y F ol l ow- u p P erio d ( Da y 2 t hr o u g h 
Da y  3 6 1).
T ar get St u d y P o p ul ati o n
T his st u d y  will be c o n d ucte d i n health y male a n d fe male partici pa nt s, 1 8 t o 5 5 years of 
a ge.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
I n vesti g ati o n al Me dici n al Pr o d uct
S u p plier:
A Z D 7 4 4 2 ( A Z D 8 8 9 5 + A Z D 1 0 6 1): Astra Ze neca.
Place b o/ Dil ue nt: 0. 9 % S o di u m C hl ori de ( P h. E ur. , Br itis h
P har mac o p oeia ): Pare xel.
F or m ulati o n:
Eac h vial of A Z D 8 8 9 5 a n d A Z D 1 0 6 1 is f or m ulate d as a sterile, w hite t o 
off -w h ite, l y o p hilise d p o w der, i n a glass vial, 1 5 0 m g. After 
rec o nstit uti o n i n sterile water f or i njecti o n/i nf usi o n; eac h vial yi el ds
m g/ m L of acti ve i n gre die nt ( A Z D 8 8 9 5 or A Z D 1 0 6 1) ,  
m M 
L- histi di ne/ L -histi di ne h y dr oc hl ori de,   
 m M s ucr ose, a n d  
( w/ v) 
p ol y s or bate 8 0, at p H 6. 0.
Stre n gt h/c o nce ntrati o n:
S u p plie d as p o w der f or s ol uti on f or i njecti o n/i nf usi o n . After 
rec o nstit uti o n, eac h vial will c o ntai n   
 A Z D 8 8 9 5 or 
m g/ m L A Z D 1 0 6 1, wit h a u nit d ose stre n gt h of 1 5 0 m g A Z D 8 8 9 5 or 
1 5 0 m g A Z D 1 0 6 1.
D ose:
A Z D 7 4 4 2 d oses (c o m bi ne d d oses of A Z D 8 8 9 5 a n d A Z D 1 0 6 1 eac h 
re prese nts half of t he t otal d ose) t o be a d mi nistere d se q ue ntiall y are 
3 0 0 m g I M ( direct gl uteal I M i njecti o ns) (C o h ort 1a) , 3 0 0 m g I V 
( C o h ort 1 b) , 1 0 0 0 m g I V ( C o h ort 2) , a n d 3 0 0 0 m g I V ( C o h ort 3) at
2 0 m g/ mi n ute f or t he I V i nf usi o ns , a n d t he A Z D 7 4 4 2 d ose t o be 
c o-a d mi nistere d is 3 0 0 0 m g I V at 5 0 m g/ mi n ute ( C o h ort 4) f or t he I V 
i nf usi o n.
R o ute of a d mi nistrati o n:
I V i nf usi o n or I M i njecti o n.
S pecific de vice f or dr u g 
a d mi nistrati o n, if a p plica ble:
I V ba gs, li nes, a n d cat heters f or I V i nf usi o n as well as t he s yri n ges a n d 
nee dles f or i njecti o n will be pr o vi de d b y Pare xel .
Re gi me n:
Si n gle, se parate, se q ue ntial d oses as I V i nf usi o ns will be a d mi nistere d at
ma xi mal i nf usi o n rate of 2 0 m g/ mi n ute or direct I M i njecti o ns of eac h 
m A bs. A c o -a d mi nistere d d ose of b ot h m A bs mi xe d i n a si n gle I V 
i nf usi o n will be a d mi nistere d at a ma xi mal i nf usi o n rate of 5 0 m g/ mi n ute.
S pecial ha n dli n g re q uire me nts:   
Will be pr o vi de d i n a se parate d oc u me nt.
A vaila bilit y of t he i n vesti gati o nal 
me dici nal pr o d uct (I M P) :
Will be s hi p pe d w he n a p pr o vals are i n place.
I M: i ntra m usc ular; m A bs: m o n ocl o nal a nti b o dies: I V: i ntra ve n o us.
D osi n g i nstr ucti o ns a n d dis pe nsi n g details will be pr o vi de d i n t he p har mac y ma n ual .
O utc o me Me as ures
S afety a n d T oler a bility E n d p oi nt s:
S af et y a n d t olera bilit y varia bles will i ncl u de:
 
A Es, S A Es, co nc o mita nt m e dicat i on, safety la b orat or y para meters ( hae mat olo g y , 
cli nical c he mistr y, c oa g ulat i on, a n d uri nal ysis); 1 2 -lea d safety electr ocar di o gra m 
(E C G ); vital si g ns (bl o o d press ure [ B P ], p ulse rate , oral te m perat ure, a n d res pirat or y 
rate), a n d p h ysical e xa mi nat i on.
 
I njecti on site reacti o ns wi t h I M a d mi nistrati o n will be m o ni t ore d (i ncl u di n g 
assess me nt of size, re d ness/er yt he ma, s welli n g, itc hi n g/ pr uritis, pai n or te n der ness, 
i n d urati o n, disc o l ourati o n ) a n d will be d oc u me nte d as an A E a n d a p h ot o gra p h ta ke n,
at t he discreti o n of t he PI , wit h visi ble meas uri n g ta pe.
C CI
C CI
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
I m m u n o ge nicity E n d p oi nts
 
Ve n o us bl o o d sa m ples will be c ollecte d a n d st ore d f or a nal ysis of A D As. 
U nsc he d ule d sa m ples f or A D A a nal ysis s h o uld be c ollecte d i n res p o nse t o s us pecte d 
i m m u ne-r elate d A Es.
Ser u m P h ar m ac o ki netic E n d p oi nts:
W here p ossi ble, P K para meters will be assesse d f or i n di vi d ual m A bs ( A Z D 8 8 9 5 a n d 
A Z D 1 0 6 1):
 
P K para meters:

After I V i nf usi o n: C ma x, T ma x, t ½ λz, A U Clast , A U Ci nf , Vss, Vz, a n d C L.

After I M i nject i on: C ma x, T ma x, t ½ λz, A U Clast , A U Ci nf , e xtra vasc ular s yste mic 
cleara nce ( C L/ F), bi oa vaila bilit y ( F), a n d e xtra vasc ular ter mi nal p hase v ol u me of 
di stri b uti on ( Vz/ F).
A d dit i onal P K para meters ma y  be deter mi n e d w here a p pr o priate.
E x pl or at ory E n d p oi nts:
 
Si n gle d ose A Z D 8 8 9 5 a n d A Z D 1 0 6 1 P K c o nce ntrati o ns i n nasal fl ui d.
 
Assess me nt of S A R S -C o V -2 ne utrali si n g acti vity of  A Z D 7 4 4 2.
St atistic al Met h o ds
A n alysis Sets
T he safet y a nal ysis set will i ncl u de all part ici pa nts w h o were ra n d o mise d a n d recei ve d a n y 
a mo u nt of A Z D 7 4 4 2. T he P K a nal ysis set will c o nsist of all partici pa nts i n t he safet y 
a nal ysis set w h o recei ve d A Z D 7 4 4 2 a n d w h o ha ve e val ua ble ser u m P K data, wit h n o 
i m p orta nt pr ot oc ol de viati ons t h o u g ht t o i m pact o n t he a nal ysis of t he P K data. T he 
Ra n d o mise d Set will c o nsist of all part ici pa nts ra n d o mise d i nt o t he st u d y.
Prese nt ati o n a n d A n alysis of S afety a n d T oler a bility D at a:
T he safet y of  A Z D 7 4 4 2 will pri maril y be assesse d a n d meas ure d b y t he occ urre nces o f all 
A Es a n d S A Es, as well as b y re vie w of safet y cli nical la b orat or y data a n d s u m mar y of 
cli nical la b orat or y meas ure me nts (ie, ser u m c he mistr y, hae mat ol o g y , c oa g ulatio n a n d 
uri nal ysis ).
All A Es a n d S A Es will be s u m maris e d b y s yste m or ga n class, preferre d ter m ( usi n g t he 
latest a vaila ble versi o n of t he Me dical Dict i onar y  f or Re g ulat or y Act i vities [ Me d D R A]), 
a n d b y se verit y a n d relatio ns hi p t o I M P.
Prese nt ati o n a n d A n alysis of Ser u m P h ar m ac o ki netic D at a:
T he ser u m A Z D 7 4 4 2 m A bs ( A Z D 8 8 9 5 a n d A Z D 1 0 6 1) c o nce ntrati o ns a n d P K para meters 
will be liste d a n d prese nte d i n ta b ular a n d gra p hical f or m as a p pr o priate. F or A Z D 7 4 4 2 
m A bs ( A Z D 8 8 9 5 a n d A Z D 1 0 6 1), t he ser u m c o nce ntrati o ns f or eac h sc he d ule d ti me p o i nt 
will be s u m marise d b y treat me nt gr o u p usi n g a p pr o priate descri pti ve statist ics, base d o n 
t he P K a nal ysis set. P K para meters will be deri ve d usi n g n o nc o m part me ntal met h o ds. All 
P K para meters will be s u m marise d b y treat m e nt gr o u p usi n g a p pr o priate descri pt i ve 
statistics, base d o n t he P K a nal ysis set.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Prese nt ati o n a n d A n alysis of A nti -dr u g A nti b o dy D at a:
T he i nci de nce of A D As t o A Z D 7 4 4 2 will be s u m mari se d b y nu m ber a n d perce nta ge of 
parti ci pa nt s w h o are A D A p ositi ve. T he A D A titer will be liste d b y partici pa nt at  differe nt 
ti me p oi nts. T he i m pact of A D A o n P K, a n d ass ociati o n wit h A Es a n d S A Es ma y be 
assesse d.
Prese nt ati o n a n d A n alysis of E x pl or at ory D at a:
Res ults of nasal fl ui d P K a nal ysis a n d t he e valuati o n of t he f u nct i onal i n hi biti on of 
S A R S -C o V -2 b y  AZ D 7 4 4 2 c o nc e ntratio ns i n ser u m ma y f or m part of t he st u d y’s re p ort.
I nteri m A n alysis:
T here will be f our u n bli n de d i nteri m a nal yses. T he first will assess data fr o m C o h ort 1a 
a n d C o h ort 1 b o nce all partici pa nts i n t h ose t w o c o h orts ha ve c o m plete d t heir Da y 8 visit. 
T he sec o n d will assess c u m ulati ve data fr o m all c o h orts o nce all partici pa nts i n C o h ort 4
ha ve c o m p lete d t heir Da y 8 visit. T he t hir d i nteri m a nal ysis will  assess all a vaila ble data
fr om all c o h orts o nce all part ici pa nts i n C o h ort 4 ha ve c o m p lete d t heir Da y 1 5 1 visit . T he 
f ourt h i nteri m a nal ysis will assess data fr o m all c o h orts o nce all partici pa nts ha ve 
c o mplete d t heir Da y 2 1 1 visit a n d parti ci pa nts i n C o h ort 1a a n d C o h ort 1 b ha ve c o mplete d 
t heir Da y 2 7 1 visi t. T he res ults of t hese a nal yses will be use d t o assist Astra Ze neca ’s 
i nter nal o peratio nal pla n ni n g. T he pri mar y  a nal ysis will be c o n d ucte d w he n all treate d 
parti ci pa nts f or eac h pla n ne d a nal ysis ha ve c om p lete d f oll o w-u p t hr o u g h Da y 3 1. All 
a vaila ble data at t he ti me of data c ut-off will be i ncl u de d i n t he i nteri m a nal yses . T he 
u n bli n de d safet y,  P K, A D A data ( A D A data if a vaila ble), ne utralisi n g a nti b o d y  a n d nasal 
fl uid data will be use d t o deter mi ne w het her t o i nit iate a P hase 2/ 3 pr o p h yla xis st u d y in 
br oa der p o p ulat i ons . Astra Ze neca pers o n nel, ass ociate d pers o n nel at t he c o ntract researc h 
or ga ni sat i on c o n d uct i n g t he st u d y a n d t he testi n g la b orat ories will be u n bli n de d as nee de d 
t o perf or m t he a nal ysis a n d pla n ni n g. U n bli n de d data ma y be s hare d wit h re g ulat or y 
a ge ncies a n d ot her parties f or t he de vel o p me nt pr o gra ms, as nee de d, i n re g ulat or y  
a p plicat i ons a n d ot her de vel o p me nt -re q uire d c orres p o n de nce. It is a ntici pate d t hat st ud y 
site pers o n nel a n d parti ci pa nt s will re mai n bli n de d.
T he res ults will be base d o n clea n data a n d n o mi nal t i mes will be use d f or t he deri vati o n of 
t he ser u m P K para meters.
A s u bset of t he o ut p uts t hat will be re q uire d f or t he i nteri m a nal yses will be i de nt ifie d i n 
t he ta bles, list i n gs, a n d fi g ures s hells of t his st u d y a n d t he res ults will be pr o vide d o nl y o n 
w hic he ver data is a vaila ble.
Deter mi n ati o n of S a m ple Size
A p pr o xi matel y  6 0 healt h y a d ult partici pa nt s will be ra n d o mise d t o A Z D 7 4 4 2 or place b o 
acr oss 5 fi xe d-d ose c o h orts i n a se q ue ntial or der (f or details refer st u d y desi g n). Beca use 
all a nal yses will be descri pti ve i n nat ure a n d n o h y p ot hesis is bei n g teste d statisticall y , n o 
f or mal sa m ple size calc ulati o ns were perf or me d, h o we ver, t he sa m ple size is c o nsi dere d 
s ufficie nt f or a n earl y assess me nt of safet y,  t olera bilit y, i m m u n o ge nicity, a n d P K. 
A d dit i onal c o h orts ma y be a d de d wit h lo wer or i nter me diate d oses of  A Z D 7 4 4 2 if t he 
D E C deter mi nes t he y  are warra nte d:
 
C o h ort 1a ( 1 2 partici pa nt s): 3 0 0 mg A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g 
A Z D 1 0 6 1) ( n = 9) or place b o ( n = 1), a d mi nistere d I M,

Se nt i nel d osi n g: 3 0 0 m g A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g A Z D 1 0 6 1) 
( n = 1) or place b o ( n = 1), a d mi nistere d I M.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 
C o h ort 1 b ( 12 partici pa nt s): 3 0 0 m g A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g
A Z D 1 0 6 1) ( n = 9 ) or place b o ( n =1 ), a d mi nistere d IV ,

Se nt i nel d osi n g: 3 0 0 m g A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g A Z D 1 0 6 1) 
( n = 1) or place b o ( n = 1), a d mi nistere d I V.
 
C o h ort 2 ( 1 2 partici pa nt s): 1 0 0 0 m g A Z D 7 4 4 2 ( 5 0 0 m g A Z D 8 8 9 5 a n d 5 0 0 m g 
A Z D 1 0 6 1) ( n = 9 ) or place b o ( n = 1 ), a d mi nistere d IV ,

Se nt i nel d osi n g: 1 0 0 0 m g A Z D 7 4 4 2 ( 5 0 0 m g A Z D 8 8 9 5 a n d 5 0 0 m g A Z D 1 0 6 1) 
( n =1 ) or place b o ( n = 1) , a d mi nistere d I V.
 
C o h ort 3 ( 1 2 partici pa nt s): 3 0 0 0 mg A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1) ( n = 9 ) or place b o ( n =1 ), a d mi nistere d I V,
 
Se nt i nel d osi n g: 30 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1) ( n = 1) or place b o ( n = 1) , a d mi nistere d I V.
 
C o h ort 4 ( 1 2 partici pa nts): 3 0 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1 mi xe d i n si n gle i nf usi o n) ( n = 9) or place b o ( n = 1), a d mi nistere d I V,
 
Se nt i nel d osi n g: 3 0 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g A Z D 1 0 6 1 
mi xe d i n si n gle i nf usi o n) ( n = 1) or place b o ( n = 1), a d mi nistere d I V.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 2 of 1 0 3
T A B L E O F C O N T E N T S
P R O T O C O L A M E N D M E N T S ....................................................................................2
Pr ot oc ol  A me n d me nt N o. 6, date d 1 3 J ul y 2 0 2 1 ...........................................................2
Pr ot oc ol  A me n d me nt N o. 5, date d 1 6 A pril 2 0 2 1 .........................................................2
Pr ot oc ol  A me n d me nt N o. 4, date d 0 8 Fe br uar y 2 0 2 1 ...................................................3
Pr ot oc ol  A me n d me nt N o. 3, date d 0 8 Dece m ber 2 0 2 0 .................................................3
Pr ot oc ol  A me n d me nt N o. 2, date d 2 3 Se pte m ber 2 0 2 0 .................................................3
Pr ot oc ol  A me n d me nt N o. 1, date d 0 7 A u g ust 2 0 2 0......................................................4
P R O T O C O L S Y N O P SI S .............................................................................................6
T A B L E O F C O N T E N T S ...........................................................................................1 2
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S ................................. 1 7
I N V E S TI G A T O R S A N D S TU D Y A D MI NI S T R A TI V E S T R U C T U R E ....................2 2
1. 
I N T R O D U C TI O N ...................................................................................2 5
1. 1. 
Di sease Bac k gr o u n d ................................................................................2 5
1. 2. 
Rati o nale f or C o n d ucti n g T his St u d y .......................................................2 5
1. 3. 
Bac k gr o u n d t o C O VI D - 1 9 .......................................................................2 6
2. 
S T U D Y O BJ E C TI V E S ............................................................................2 7
2. 1. 
Pri mar y O bject i ve....................................................................................2 7
2. 2. 
Sec o n dar y  O bjecti ves...............................................................................2 7
2. 3. 
E x p l orat or y O bjecti ves ............................................................................2 7
3. 
S T U D Y D E SI G N ....................................................................................2 8
3. 1. 
O verall St u d y  Desi g n a n d Fl o w C hart......................................................2 8
3. 1. 1. 
Or der of Assess me nts ..............................................................................3 7
3. 1. 2. 
E n d of St u d y ............................................................................................3 7
3. 1. 3. 
E x pec te d D uratio n of  t he St u d y ...............................................................3 7
3. 2. 
Rati o nales f or St u d y  Desi g n a n d D ose Selecti on ......................................3 8
3. 2. 1. 
Rati o nale f or St u d y  Desi g n......................................................................3 8
3. 2. 2. 
Rati o nale f or E n d p oi nts ...........................................................................3 8
3. 2. 3. 
D ose Rati o nale .........................................................................................3 8
3. 2. 4. 
Rati o nale f or St u d y  P o p ulat i on ................................................................3 9
3. 2. 5. 
D ose Escal atio n Strate g y .........................................................................3 9
3. 2. 6. 
St o p pi n g Criteria f or D ose Escalat i on ......................................................4 0
3. 2. 6. 1. 
St o p pi n g R ules f or a n I n di vi d ual Partici pa nt, at A n y Ti me i n t he St u d y ...4 0
3. 2. 6. 2. 
St o p pi n g R ules f or a W h o le C o h ort, D ose Escalati o n, Pr o gressi o n t o Ne xt 
St u d y  Part a n d Ter mi nati on of St u d y .......................................................4 0
3. 2. 7. 
D ose Escal atio n C o m mi tt e e .....................................................................4 1
3. 2. 7. 1. 
C o m p osi tio n of  D ose Escalatio n C o m mi tt e e ............................................4 1
3. 2. 7. 2. 
Data Re vie we d b y D ose Escalat i on C o m mitte e f or D ose Escalati o n 
Decisi o n ..................................................................................................4 2
3. 2. 7. 3. 
D ose Escal atio n C o m mi ttee Decisio n  o n Ne xt D ose ................................4 2
3. 2. 7. 4. 
Bli n di n g at D ose Escalat i on C o m mittee Meeti n g .....................................4 3
3. 2. 7. 5. 
Assess me nts A da ptati o n ..........................................................................4 3
3. 3. 
De gree of U ncertai nt y ..............................................................................4 3

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
3. 3. 1. 
Se nt i nel D osi n g .......................................................................................4 4
3. 3. 2. 
C o -a d mi nistrati o n of M o n ocl o nal A nti b o dies ...........................................4 4
3. 4. 
Ris k -Be nefi t a n d Et hical Assess me nt .......................................................4 4
3. 4. 1. 
Descri pt i on of A Z D 7 4 4 2 .........................................................................4 4
3. 4. 2. 
M o de of Acti o n ........................................................................................4 4
3. 4. 2. 1. 
Pri mar y P har mac o d y na mics .....................................................................4 4
3. 4. 3. 
T o xic ol o g y  Pre-cli nical Data....................................................................4 4
3. 4. 3. 1. 
T o xic ol o g y ..............................................................................................4 4
3. 4. 4. 
Cli nical St u dies ........................................................................................4 5
3. 4. 5. 
Ris k Assess me nt f or A Z D 7 4 4 2 ................................................................4 5
3. 4. 6. 
Ris k Assess me nt f or C O VI D -1 9 Pa n de mic ..............................................4 6
4.  
S T U D Y P O P U L A TI O N ..........................................................................4 8
4. 1. 
S el ect i on of St u d y  P o p ulatio n ..................................................................4 8
4. 1. 1. 
I ncl usi on Cri t eria .....................................................................................4 8
4. 1. 2. 
E xcl usi o n Cri t eria ....................................................................................4 9
4. 2. 
Restricti o ns D uri n g t he St u d y ..................................................................5 0
4. 2. 1. 
Re pr o d ucti ve Restrict i ons ........................................................................5 1
4. 2. 1. 1. 
W o me n of N o n -C hil d beari n g P ote ntial ....................................................5 1
4. 2. 1. 2. 
W o me n of C hil d beari n g P ote ntial ............................................................5 1
4. 2. 1. 3. 
Male Parti ci pa nts .....................................................................................5 2
4. 3. 
Re place me nt of Partici pa nts .....................................................................5 4
4. 4. 
I nteri m A nal ysis ......................................................................................5 4
5. 
S T U D Y C O N D U C T ................................................................................5 5
5. 1. 
Parti cipa nt E nr ol me nt a n d Ra n d o misat i on ................................................5 5
5. 1. 1. 
Pr oce d ures f or Ra n d o misat i on ................................................................. 5 5
5. 2. 
Pr oce d ures f or Ha n dli n g I nc orrectl y Ra n d o mise d Partici pa nts .................5 6
5. 3. 
Bli n di n g a n d Pr oce d ures f or U n bli n di n g t he St u d y ...................................5 6
5. 3. 1. 
Met h o ds f or E ns uri n g Bli n di n g ................................................................5 6
5. 3. 2. 
Met h o ds f or U n bli n di n g t he St u d y ...........................................................5 7
5. 4. 
St u d y  Treat me nts .....................................................................................5 8
5. 4. 1. 
I de ntity of  t he I n vesti gati onal Me dici nal Pr o d uct .....................................5 8
5. 4. 2. 
S u p pl y  of I n vestig ati o n al  Me dici nal Pr o d uct............................................5 8
5. 4. 3. 
D ose a n d Treat me nt Re gi me ns ................................................................. 5 9
5. 4. 4. 
La belli n g ................................................................................................. 5 9
5. 4. 5. 
St ora ge a n d Ha n dli n g Pr oce d ures .............................................................5 9
5. 5. 
C o nc o mita nt a n d P ost -st u d y Treat me nt(s) ................................................6 0
5. 6. 
Treat me nt C o m plia nce .............................................................................6 1
5. 6. 1. 
Dr u g Acc o u nta bilit y, Dis pe nsi n g a n d Destr ucti o n ....................................6 1
5. 7. 
Di sc o nti n uatio n of  I n vesti gati onal Me dici nal Pr o d uct a n d Wit h dra wal fr o m 
St u d y .......................................................................................................6 1
5. 7. 1. 
Pr oce d ures f or Wit h dra wal o f a Partici pa nt fr o m t he St u d y......................6 1
6. 
C O L L E C TI O N O F S T U D Y V A RI A B L E S ..............................................6 2
6. 1. 
Rec or di n g of Data ....................................................................................6 2
6. 2. 
E nr ol me nt a n d Scree ni n g Pr oce d ures .......................................................6 2
6. 3. 
S af et y ......................................................................................................6 2
6. 3. 1. 
A d verse E ve nts ........................................................................................6 2

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
6. 3. 1. 1. 
Defi nit i on o f A d verse E ve nts ...................................................................6 2
6. 3. 1. 2. 
Defi nit i ons of Seri o us A d verse E ve nt ......................................................6 3
6. 3. 1. 3. 
Ot her Si g nifica nt A d verse E ve nts ............................................................6 3
6. 3. 1. 4. 
Rec or di n g of A d verse E ve nts ...................................................................6 4
6. 3. 1. 5. 
Re p orti n g of Seri o us A d verse E ve nts .......................................................6 6
6. 3. 1. 6. 
Re g ulat or y  Re p orti n g Re q uire me nts f or Seri o us A d verse E ve nts.............6 7
6. 3. 2. 
La b orat or y  Assess me nts ..........................................................................6 7
6. 3. 2. 1. 
Hae mat ol o g y ...........................................................................................6 7
6. 3. 2. 2. 
Ser u m  Cli nical C he mistr y........................................................................6 7
6. 3. 2. 3. 
Uri nal ysis ................................................................................................6 8
6. 3. 2. 4. 
C oa g u lati o n .............................................................................................6 8
6. 3. 2. 5. 
Pre g na nc y Testi n g ...................................................................................6 8
6. 3. 2. 6. 
Vi r al S er olo g y  a n d S A R S-C o V -2 Testi n g ................................................6 8
6. 3. 2. 7. 
Dr u gs of A b use a n d Alc o h o l....................................................................6 8
6. 3. 3. 
Vi t al Sig ns............................................................................................... 6 8
6. 3. 4. 
Electr ocar di o gra p h y .................................................................................6 9
6. 3. 4. 1. 
Rest i n g 1 2-lea d Electr ocar di o gra m ..........................................................6 9
6. 3. 5. 
P h ysical E xa mi nat i on ...............................................................................6 9
6. 3. 6. 
I njecti on Si te Reactio ns ...........................................................................6 9
6. 4. 
P har mac o ki net ics.....................................................................................7 0
6. 4. 1. 
C ollect i on of P har mac o ki net ic Sa m ples...................................................7 0
6. 4. 1. 1. 
Ser u m  S a mples ........................................................................................7 0
6. 4. 1. 2. 
N asal Fl ui d Sa m ples ................................................................................7 0
6. 4. 2. 
P har mac o ki net ic Dr u g Assa ys..................................................................7 0
6. 5. 
I mm u n o ge nicit y .......................................................................................7 0
6. 5. 1. 
C ollect i on of I m m u n o ge nicit y Sa m ples ....................................................7 0
6. 5. 2. 
I mm u n o ge nicit y Assa ys ...........................................................................7 1
6. 5. 3. 
E x pl or at or y  St u d y-Relate d Bi o m ar kers ....................................................7 1
6. 6. 
Ne utralisi n g A nt i b o d y Assess me nts .........................................................7 1
7. 
BI O L O GI C A L S A M P LI N G P R O C E D U R E S ..........................................7 2
7. 1. 
T otal  Blo o d V ol u me ................................................................................7 2
7. 2. 
Ha n dli n g, St ora ge a n d Destr ucti o n of Bi o l ogical Sa m ples ........................7 2
7. 2. 1. 
P har mac o ki net ic Sa m ples ........................................................................7 2
7. 2. 2. 
I mm u n o ge nicit y a n d P har mac o d y na mic Sa m ples .....................................7 3
7. 3. 
La belli n g a n d S hi p me nt of Bi o hazar d Sa m ples ........................................7 3
7. 4. 
C hai n o f C ust o d y  of Biol o gical  Sa m ples..................................................7 3
7. 5. 
Wit h dra wal o f I nf or me d C o nse nt f or D o nate d Bi ol o gical Sa m ples...........7 4
8. 
E T HI C A L A N D R E G U L A T O R Y R E Q UI R E M E N T S .............................7 5
8. 1. 
Et hical C o n d uct of t he St u d y ....................................................................7 5
8. 2. 
Parti cipa nt Data Pr otecti o n .......................................................................7 5
8. 3. 
Et hics a n d Re g ulat or y  Re vie w ................................................................. 7 5
8. 4. 
I nf or me d C o nse nt ....................................................................................7 5
8. 5. 
I ns ura nce ................................................................................................. 7 6
8. 6. 
C ha n ges t o t he Pr ot oc ol a n d I nf or me d C o nse nt F or m ...............................7 6
8. 7. 
A u dits a n d I ns pect i ons .............................................................................7 6
9. 
D A T A Q U A LI T Y A S S U R A N C E A N D D A T A M A N A G E M E N T ..........7 7

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
9. 1. 
Q ualit y C o ntr ol  a n d S o urce Data Verificati on ..........................................7 7
9. 2. 
A u dit/I ns pect i ons .....................................................................................7 7
9. 3. 
St u d y  M o nit ori n g.....................................................................................7 7
9. 4. 
Data C ollect i on ........................................................................................7 7
9. 4. 1.  
Case Re p ort F or ms a n d S o urce D oc u me nts ..............................................7 7
9. 4. 2. 
Access t o S o urce D oc u me nts ...................................................................7 8
9. 5. 
Data Ma na ge me nt ....................................................................................7 8
1 0. 
E V A L U A TI O N A N D C A L C U L A TI O N O F V A RI A B L E S .....................7 9
1 0. 1. 
S af et y Vari a bles .......................................................................................7 9
1 0. 1. 1. 
A d verse E ve nts ........................................................................................7 9
1 0. 1. 2. 
La b orat or y  Assess me nts ..........................................................................8 0
1 0. 1. 3. 
Vi t al Sig ns............................................................................................... 8 1
1 0. 1. 4. 
Rest i ng 1 2 -lea d Electr ocar di o gra m ..........................................................8 1
1 0. 1. 5. 
P h ysical E xa mi nat i on ...............................................................................8 1
1 0. 1. 5. 1. 
I njecti on Si te Reactio n .............................................................................8 1
1 0. 2. 
P har mac o ki net ic Varia bles.......................................................................8 1
1 0. 2. 1. 
Ser u m  P K Para meters ..............................................................................8 2
1 0. 2. 2. 
Calc ulati o n or Deri vat i on of P har mac o ki net ic Para meters........................8 2
1 0. 3. 
I mm u n o ge nicit y a n d P har mac o d y na mics .................................................8 3
1 1. 
S T A TI S TI C A L M E T H O D S A N D S A M P L E SI Z E D E T E R MI N A TI O N . 8 4
1 1. 1. 
Descri pt i on of t he A nal ysis Sets ...............................................................8 4
1 1. 1. 1. 
S af et y A nal ysis Set ..................................................................................8 4
1 1. 1. 2. 
P har mac o ki net ic A nal ysis Set ..................................................................8 4
1 1. 1. 3. 
Ra n d o mise d Set .......................................................................................8 4
1 1. 2. 
Met h o ds of Statist ical A nal yses ...............................................................8 4
1 1. 2. 1. 
Ge neral Pri nci ples ....................................................................................8 4
1 1. 2. 1. 1. 
Missi n g Data ............................................................................................8 5
1 1. 2. 2. 
Pa rticipa nt C haracteristics ........................................................................8 6
1 1. 2. 2. 1. 
De m o gra p hic a n d Baseli ne Data ..............................................................8 6
1 1. 2. 3. 
Pri or a n d C o nc o mi ta nt Me dicati on a n d Dr u g A d mi nistrati o n ...................8 6
1 1. 2. 3. 1. 
Pri or a n d C o nc o mi ta nt Me dicati on ...........................................................8 6
1 1. 2. 3. 2. 
Dr u g A d mi nistrati o n ................................................................................8 7
1 1. 2. 4. 
S af et y a n d T olera bilit y .............................................................................8 7
1 1. 2. 5. 
P har mac o ki net ics.....................................................................................8 8
1 1. 2. 5. 1. 
Ser u m  C o nce ntrati o n Data.......................................................................8 8
1 1. 2. 5. 2. 
Ser u m  P har mac o ki netic Para meter Listi n gs .............................................8 8
1 1. 2. 5. 3. 
Ser u m  P har mac o ki netic Para meter Descri pti ve Statistics .........................8 8
1 1. 2. 5. 4. 
Gra p hical Prese ntati o n f or Ser u m C o nce ntrati o n Data ..............................8 8
1 1. 2. 6. 
I mm u n o ge nicit y a n d P har mac o d y na mics .................................................8 8
1 1. 2. 6. 1. 
A nt i-dr u g A nt i b o d y Tit ers........................................................................8 8
1 1. 2. 6. 2. 
Nasal Fl ui d P har mac o ki net ic A nal ysis .....................................................8 9
1 1. 2. 6. 3. 
Ne utralisi n g A nt i b o d y C o nce ntrati o ns .....................................................8 9
1 1. 3. 
Pr ot oc ol  De viati ons ..................................................................................8 9
1 1. 4. 
De ter mi nati on of Sa m ple Size ..................................................................9 0
1 2. 
I M P O R T A N T M E DI C A L P RO C E D U R E S T O B E F O L L O W E D B Y T H E 
I N V E S TI G A T O R ....................................................................................9 1

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
1 2. 1. 
Me dical E mer ge ncies a n d Astra Ze neca C o ntacts
.....................................9 1
1 2. 2. 
O ver d ose ................................................................................................. 9 1
1 2. 3. 
Pre g na nc y ................................................................................................9 1
1 2. 3. 1. 
Mater nal E x p os ure ...................................................................................9 2
1 2. 3. 2. 
Pater nal  E x p os ure....................................................................................9 2
1 3.  
L E G A L A N D A D MI NI S T R A TI V E A S P E C T S .......................................9 3
1 3. 1. 
Arc hi vi n g of St u d y  D o c u me nts ................................................................9 3
1 3. 2. 
P u blicat i on of St u d y  Res ults ....................................................................9 3
1 3. 3. 
Cli nical St u d y  Re p ort...............................................................................9 3
1 4. 
LI S T O F R E F E R E N C E S .........................................................................9 4
1 5.   
A P P E N DI C E S .........................................................................................9 5
LI S T O F T A B L E S
Ta ble 2- 1 
Pri mar y O bject i ve a n d O utc o me Meas ures......................................2 7
Ta ble 2- 2 
Sec o n dar y  O bjecti ves a n d O utc o me Meas ures ................................2 7
Ta ble 2- 3 
E x pl or at or y  O bjecti ves a n d O utc o me Meas ures..............................2 7
Ta ble 3 - 1 
Sc he d ule of Assess me nts ( Scree ni n g) .............................................3 2
Ta ble 3 - 2 
Sc he d ule of As sess me nts ( Treat me nt Peri o d) ..................................3 3
Ta ble 3 - 3 
Sc he d ule of Assess me nts ( F oll o w - u p).............................................3 5
Ta ble 3- 4 
E x pecte d D urati o n of Eac h St u d y  Part............................................3 7
Ta ble 5 - 1 
Parti cipa nt Ra n d o misat i on ..............................................................5 6
Ta ble 5- 2 
I de ntity of  t he I n vesti gati onal Me dici nal Pr o d uct ............................5 8
Ta ble 7- 1 
T otal  Blo o d V ol u me .......................................................................7 2
LI S T O F FI G U R E S
Fi g ure 3- 1 
St u d y  Flo w C hart ............................................................................3 0
Fi g ure 3- 2 
O verall Gra p hical Re prese ntati o n of t he St u d y ................................3 1
LI S T O F A P P E N DI C E S
A p pe n di x A 
A d dit i onal Safet y I nf or matio n .........................................................9 6
A p pe n di x B 
I nter nati o nal Airli ne Tra ns p ortati o n Ass ociati on 6. 2 G ui da nce 
D oc u m e nt .......................................................................................9 8
A p pe n di x C 
Act i ons Re q uire d i n Cases of C o m bi ne d I ncrease of 
A mi n otra nsferase a n d T otal Bilir u bi n - H y ’s La w...........................9 9

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S
Pl ease n ote t hat defi nit i ons of a b bre viat i ons f or p har mac o ki net ic varia bles are prese nte d i n 
Secti o n 1 0. 2 of  t his pr ot oc ol. 
A b bre vi ati o n or 
s peci al ter m
E x pl a n ati o n
A E
A d verse e ve nt (see defi niti o n i n Secti o n 6. 3. 1. 1 )
A C E
A n gi ote nsi n c o n verti n g e nz y me
A D A
A nti- dr u g a nti b o d y
A L P
Al kali ne p h os p hatase
A L T
Ala ni ne a mi n otra nsferase
A N O V A
A nal y sis of varia nce
a P P T
Acti vate d partial t hr o m bi n ti me
A S T
As partate a mi n otra nsferase
A U C
Area u n der t he c ur ve
A U Ci nf
Area u n der t he ser u m c o nce ntrati o n vers us ti me c ur ve e xtra p olate d t o i nfi nit y
A U Clast
Area u n der t he ser u m c o nce ntrati o n vers us ti me c ur ve fr o m ti me zer o t o ti me of 
last meas ura ble c o nce ntrati o n
A V
Atri o ve ntric ular
A Z Ra n d
Astra Ze neca ra n d o misati o n s yste m
β- h C G
Beta h u ma n c h ori o nic g o na d otr o pi n
B MI
B o d y mass i n de x
B P
Bl o o d press ure
b p m
Beats per mi n ute
CI
C o nfi de nce i nter val 
C F R
C o de of Fe deral Re g ulati o ns
Cli n Base T M
Pare xel's electr o nic s o urce data ca pt uri n g a n d i nf or mati o n ma na ge me nt s yste m
C O VI D - 1 9
C or o na vir us disease - 2 0 1 9
(e) C R F
(electr o nic) Case re p ort f or m
C L
S y ste mic cleara nce
C L/ F 
A p pare nt t otal cleara nce
C ma x
Ma xi m u m ser u m c o nce ntrati o n
C R O
C o ntract researc h or ga nisati o n
C R P
C- reacti ve pr otei n
C S P
Cli nical St u d y Pr ot oc ol
C S R
Cli nical St u d y Re p ort 
C V
C oefficie nt of variati o n
D A E
A d verse e ve nt lea di n g t o t he disc o nti n uati o n of I M P
D C F
Data clarificati o n f or m
D E C
D ose Escalati o n C o m mittee

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
A b bre vi ati o n or 
s peci al ter m
E x pl a n ati o n
D E S
Data E ntr y Site – w h ere seri o us a d verse e ve nt re p orts fr o m Ast ra Ze neca 
Cli nical st u dies are e ntere d o nt o t he Astra Ze neca Patie nt Safet y data base b y 
Tata C o ns ulta nc y Ser vices
d E C G
Di gital electr ocar di o gra m
D G R
Da n ger o us G o o ds Re g ulati o ns
DI LI
Dr u g -I n d uce d Li ver I nj ur y
D M P
Data ma na ge me nt pla n
D N A
De o x yri b o n ucleic aci d
D V S
Data vali dati o n s pecificati o n
E C
Et hics C o m mittee
E C G
Electr ocar di o gra m
E Cl y sis©
User -i nteracti ve, m o d ular c o m p uter-base d s yste m f or d E C G data pr ocessi n g, 
a nal ysis a n d meas ure me nt of E C G i nter vals a n d wa ve a m plit u des, e x p orts a n d 
re p orts, use d b y t he Astra Ze neca E C G Ce ntre 
E L F
E n d ot helial li ni n g fl ui d
E M A
E ur o pea n Me dici nes A ge nc y
E P C U
Earl y  p hase cli nical u nit
E U
E ur o pea n U ni o n
F A A N
Fell o w of t he A merica n Aca de m y of N ursi n g
Fc R n
Ne o natal Fc rece pt or
F D A
F o o d a n d Dr u g A d mi nistrati o n
F S H
F ollicle -sti m ulati n g h or m o ne
F TI H
First ti me i n H u ma n
G C P
G o o d Cli nical Practice
G G T
Ga m ma gl uta m yl tra ns pe pti dase (tra nsferase)
GI
Gastr oi ntesti nal
G L P
G o o d La b orat or y Practice
G M P
G o o d Ma n ufact uri n g Practice
H b
H ae m o gl o bi n
H Bs A g
He patitis B s urface a nti ge n
H C T
H ae mat ocrit
H E D
H u ma n e q ui vale nt d ose
HI V
H u ma n i m m u n o deficie nc y vir us
I A T A
I nter nati o nal Airli ne Tra ns p ortati o n Ass ociati o n
I B
I n vesti gat or’s br oc h ure
I B u n dle bra nc h bl oc k 
I nc o m plete b u n dle bra nc h bl oc k
I C F
I nf or me d C o nse nt F or m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C
I n de pe n de nt Et hics C o m mittee

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 9 of 1 0 3
A b bre vi ati o n or 
s peci al ter m
E x pl a n ati o n
I g G 1
I m m u n o gl o b uli n G 1
I N R
I nter nati o nal n or malise d rati o
I M
I ntra m usc ular
I M P
I n vesti gati o nal Me dici nal Pr o d uct
I R B
I nstit uti onal Re vie w B oar d
I S R B
I n de pe n de nt Safet y Re vie w B oar d
I U D
I ntra uteri ne de vice
I U S
I ntra uteri ne c o ntrace pti ve s yste m
I V
I ntra ve n o us
L D H
Lactate de h y dr o ge nase
L L N
L o wer li mit of n or mal
L L O Q
L o wer li mit of q ua ntificati o n
m A bs
M o n ocl o nal a nti b o dies
M C H
Mea n c or p usc ular h ae m o gl o bi n
M C H C
Mea n c or p usc ular h ae m o gl o bi n c o nce ntrati o n
M C V
Mea n c or p usc ular v ol u me
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Acti vities
M E R S
Mi d dle East Res pirat or y S y n dr o me
M H R A
Me dici nes a n d Healt hcare P r od ucts Re g ulat or y A ge nc y
n
N u m ber of partici pa nts
NI AI D
Nati o nal I nstit ute of Aller g y a n d I nfecti o us Diseases
N A
N ot a p plica ble
N D
N ot deter mi ne d
N O A E L
N o -o bser ve d -a d verse-effect le vel
N R
N o res ult
O S A E
Ot her si g nifica nt a d verse e ve nt
O T C
O ver -t h e-c o u nter
P D
P har mac o d y na mics
P D F
P orta ble D oc u me nt F or mat
P D S
Pr ot oc ol de viati o n s pecificati o n ( d oc u me nt)
p E C G
Pa per pri nt -o ut E C G
P h. E ur.
E ur o pea n P h ar mac o p oeia
P H L
P ote ntial H y’s La w
PI
Pri nci pal I n vesti gat or
P K
P har mac o ki netics
P P E
Pers o nal pr otecti ve e q ui p me nt
P R( P Q)
E C G i nter val meas ure d fr o m t he o nset of t he P wa ve t o t he o nset of t he Q R S 
c o m ple x

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
A b bre vi ati o n or 
s peci al ter m
E x pl a n ati o n
P T
Preferre d ter m
Q R S
E C G i nter val meas ure d fr o m t he o nset of t he Q R S c o m ple x t o t he J p oi nt
q R T -P C R
q ua ntitati ve real -ti me p ol y merase c hai n reacti o n
Q T
E C G i nter val meas ure d fr o m t he o nset of t he Q R S c o m ple x t o t he e n d of t he T 
wa ve
Q Tc B
Q T i nter val c orrecte d f or heart rate usi n g Bazett ’s f or m ula
Q Tc F
Q T i nter val c orrecte d f or heart rate usi n g Fri dericia’s f or m ula
R & D
Researc h a n d De vel o p me nt
R B C
Re d bl o o d cell
R B D
Rece pt or bi n di n g d o mai n
R R
T he ti me bet wee n c orres p o n di n g p oi nts o n t w o c o nsec uti ve R wa ves o n E C G
R S V
Res pirat or y  s yn c y tial vir us
S A D
Si n gle asce n di n g d ose
S A E
Seri o us a d verse e ve nt (see defi niti o n i n Secti o n 6. 3. 1. 2 ).
S A P
Statistical A nal ysis Pla n
S A R S
Se vere ac ute res pirat or y s y n dr o me
S A R S -C o V - 2 
Se vere ac ute res pirat or y s y n dr o me c or o na vir us 2
S D
Sta n dar d de viati o n
S o A
Sc he d ule of assess me nts
S O C
S y ste m Or ga n Class
S O P
Sta n dar d o perati n g pr oce d ure
S U S A R
S us pecte d u ne x pecte d seri o us a d verse reacti o n
T B L
T otal bilir u bi n le vel
T C A
Tric yclic a nti -de pressa nt
T C S
Tata C o ns ulta nc y Ser vices – a n Astra Ze neca part ner w h o c o n d uct data e ntr y 
o nt o Sa p p hire
T E A E
Treat me nt -e mer ge nt a d verse e ve nt
T E S A E
Treat me nt -e mer ge nt seri o us a d verse e ve nt
T S H
T h y r oi d-sti m ulati n g h or m o ne
T M
Tri ple m utati o n
T ma x
Ti me t o reac h ma xi m u m ser u m c o nce ntrati o n
t ½ λz
Ter mi nal eli mi nati o n half -life
U K
U n ite d Ki n g d o m
U L N
U p per li mit of n or mal
U S A
U n ite d States of A merica
Vss
V ol u me of distri b uti o n at stea d y state
Vz/ F
A p pare nt v ol u me of distri b uti o n at ter mi nal p hase
Vz
V ol u me of distri b uti o n at ter mi nal p hase

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
A b bre vi ati o n or 
s peci al ter m
E x pl a n ati o n
W A D
Wi n d o w All o wa nce D oc u me nt
W B C
W hite bl o o d cell
W H O
W orl d Healt h Or ga nisati o n

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
I N V E S TI G A T O R S A N D S TU D Y A D MI NI S T R A TI V E S T R U C T U R E
S p o ns or:
Astra Ze neca A B
1 5 1 8 5 S ö dertälje
S we de n
S p o ns or’s Lea d 
P h y sicia n:
, M D 2 0 8 7 8
U n ite d States of A merica
Tel: 
E- mail : 
S p o ns or’s 
Bi ostatisticia n:
Astra Ze neca P har mace uticals
 M D 2 0 8 7 8
U n ite d States of A merica
Tel: 
Pri nci pal 
I n vesti gat or:
Dr Pa bl o F orte S ot o ( M D, M Sc, P h D)
Pare xel E P C U ( L o n d o n)
 H A 1 3 UJ
U n ite d Ki n g d o m
Tel:
E- mail: 
C o ntract Researc h 
Or ga ni sati on:
Pare xel E P C U L o n d o n
 H A 1 3 UJ
U n ite d Ki n g d o m
Cli nical 
La b orat o r y:
T he D oct ors La b orat or y ( T D L)
 W C 1 H 9 A X
U n ite d Ki n g d o m
Tel: 
Fa x: 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
A nal y tical 
La b orat o r y:
( p har mac o ki netic 
a n d 
p har mac o d y na mic 
sa m ple a nal ysis)
P P D B i oa nal ytical L a bor at or y S er vices
, V A 2 3 2 3 0
U n ite d States of A merica
Tel: 
C o ntact P K: 
E- mail: 
C o ntact A D A: 
E- mail: 
Astra Ze neca S o ut h Sa n Fra ncisc o
, C A 9 4 0 8 0
U n ite d States of A merica
C o ntact: 
E- mail: 
P P D
, V A 2 3 2 3 0
U n ite d States of A merica
Tel: 
E- mail: 
G C L -E U
Sa m ple Ma na ge me nt
Cl uster par k
, Bel gi u m
Tel: 
Fa x: 
C o ntact: 
E- mail
Ser u m Ne utrali si n g A nti b o d y test
Vir ocli nics Bi oscie nces, B. V.
T he Net herla n ds
Tel :
E- mail: 
M o n o gra m Bi oscie nces – La b C or p S pecialt y Testi n g Gr o u p (e x pl orat or y sa m ples)
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
,
 U S A
Tel: 
E- mail: 
A d verse E ve nt 
Re p orti n g:
Astra Ze neca Patie nt Safet y Data E ntr y Site
Tata C o ns ulta nc y Ser vices
Fa x: 
E- mail: 
A list a n d c o ntact details of I n vesti gat ors a n d ot her ke y st u d y tea m me m bers are pr o vi de d 
i n t he Pr oject Pla n i n t he electr o nic I n vesti gat or’s Site File. A list of all partici pati n g 
I n vesti gat ors will be pr o vi de d i n t he Cli nical St u d y Re p ort ( C S R).
P P D
P P D
P P D
P P D
P P D
P P D

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
1. 
I N T R O D U C TI O N
1. 1. 
Dise ase B ac k gr o u n d
C or o na vir uses are a fa mil y of lar ge, si n gle -stra n d, p ositive -se nse R N A vir uses w hic h 
reside i n m ul tiple a ni mal reser v o irs, i ncl u di n g bats. C or o na vir uses are pri maril y 
res pir at or y vir uses, a n d m ost t ypicall y  ca use c o m mo n -c o l d li ke s y m pt o ms o n a n a n n ual 
basi s [ 1]. H o we ver, m ore pat h o ge nic c or o na vir uses ha ve t he ca pacit y t o cr oss fr o m a ni mal 
h osts t o h u m a ns, wit h var yi n g de grees o f h u ma n t o h u ma n tra nsfer , a n d ca n ca use seri o us 
h u ma n disease [ 2]. T he pre vi o us S A R S o ut brea k be ga n i n C hi na ( 2 0 0 2 t hr o u g h 2 0 0 3) a n d 
s prea d t o 3 7 c o u ntries, wit h r o u g hl y 8, 30 0 cases, 7 7 5 deat hs, a n d a case fatalit y rate of 
~ 1 0 %. T he M E R S o ut brea k t hat has bee n o n g oi n g si nce 2 0 1 2 is e ve n m ore dea dl y; w hile 
o nl y  2, 5 1 9 la b orat or y-c o nﬁr me d cases ha ve bee n re p orte d t his has i ncl u de d 8 6 6 ass ociate d 
deat hs wit h a res ult i n g case fatalit y rate of 3 4. 3 % [ 3].
Se vere ac ute res pirat or y  c or o na vir us 2 is a n o vel c or o na vir us t hat a p pears t o ha ve first 
e mer ge d i n C hi na i n N o ve m ber 2 0 1 9 ca usi n g cases of at y pical p ne u m o nia. Si nce t he n, t he 
C O VI D -1 9 pa n de mic has ca use d maj or disr u pt i on t o healt hcare s yste ms wit h si g nifica nt 
s o cioec o n o mic i m pacts. As of 2 0 J ul y 2 0 2 0, t he vir us ha d s prea d t o all c or ners of t he 
gl o be, i n v o l vi n g 1 8 8 c o u ntries/r e gio n s wit h o ver 1 4. 7 milli on c o nfir me d cases re p orte d 
a n d m ore t ha n 6 1 0, 0 0 0 ass ociate d deat hs [ 4, 5]. As a res p o nse t o t he o n g oi n g pa n de mic, 
Astra Ze neca is de vel o pi n g m A bs t o t he S A R S-C o V -2 s pi ke pr otei n. T he S A R S -C o v -2 
s pike pr otei n c o ntai ns t he vir us's rece pt or bi n di n g d o mai n, w hic h e na ble s t he vir us t o bi n d 
t o rece pt ors o n h u ma n cells. B y tar geti n g t his re gi o n of t he vir us's s pi ke pr otei n, a nti b o dies 
ca n bl oc k t he vir us's attac h me nt t o h u ma n cells, a n d, t heref ore, is e x pecte d t o bloc k 
i nfecti on. T w o I g G 1 a nti b o dies t hat ha ve bee n i de ntifie d t o ha ve p ote nt ne utralisi n g 
acti vit y are bei n g c o m bi ne d a n d will be e val uate d f or efficac y i n b ot h pr o p h ylact ic a n d 
t hera pe utic setti n gs. A mi n o aci d s u bst ituti o ns ha ve bee n i ntr o d uce d i nt o t he a nti b o dies t o 
b ot h e xte n d t heir half -li ves, w hic h s h o ul d pr olo n g t hei r p ote ntial pr o p h ylact ic be nefit, a n d 
decrease Fc effect or f u nct i on i n or der t o decrease t he p ote ntial ris k of a nti b o d y-de pe n de nt 
e n ha nce me nt of disease. F or detail please refer t o t he I B [ 6].
1. 2. 
R ati o n ale f or C o n d ucti n g T his St u d y
A Z D 7 4 4 2 is bei n g e val uate d f or a d mi nistrati o n t o pre ve nt a n d/ or treat C O VI D- 1 9. T his 
P hase I st u d y , h o we ver, will gat her i m p orta nt i nf or mat i on o n t he safe t y a n d t olera bilit y of 
A Z D 7 4 4 2 as well as rele va nt data o n t he P K pr ofile a n d t he ge nerat i on of A D As t o t he 
m A bs.
As of Pr ot oc ol  A me n d me nt n o. 2, b ot h se q ue nt ial a n d c o -a d mi nistrati o n of  t he m A bs will 
be i n vesti gate d t o gat her i m p orta nt i nf or mati o n o n t he P K, t he I V a d mi nistrati o n pr ocess
a n d i nf usi o n ti mes.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
1. 3. 
B ac k gr o u n d t o C O VI D - 1 9
T he re g ul at or y a ut h orities ha ve iss ue d ne w g ui deli nes t hat ai m t o pr o vi de 
rec o m me n dati ons f or actio ns f or c o n d uct of cli nical st u dies of me dical pr o d ucts d uri n g 
C O VI D -1 9 pa n de mic [ 7]. Si nce t he pa n de mic sit uati on is e v ol vi n g, g ui deli nes, 
rec o m me n dati ons, nati o nal la ws a n d l ocal restrict i o ns ma y c ha n ge at a ra pi d pace. Gi ve n 
t he circ u msta nces of a p ote nti all y rela psi n g pa n de mic or e pi de mic sit uati on wi t h re gar d t o 
t he s prea d of C O VI D- 1 9 i n t he f ut ure, s pecial atte nt i on will be gi ve n t o pr otect partici pa nt s 
parti ci pat i n g i n t he st u d y a n d site staff i n v ol ve d i n t he i n vesti gati ons a gai nst i nfect i on wi t h 
S A R S -C o V -2 as re q ueste d b y  t he ne wl y iss ue d M H R A g uidel i nes. I n or der t o a d here t o 
t he ne wl y iss ue d M H R A G uida nce o n t he Ma na ge me nt of Cli nical Trials d uri n g t he 
C O VI D -1 9 pa n de mic a n assess me nt of ris k of t he I M P a n d t he st u d y  desi g n has bee n d o ne 
a n d c o ncl u de d t hat A Z D 7 4 4 2 is n ot e x pecte d t o ne gati vel y i nterfere wit h health y 
parti ci pa nt s' res p o nse t o C O VI D- 1 9.
T he parti ci pa nt s e nr olle d i n t his st u d y ca n be S A R S-C o V -2 nai ve b ut s h o ul d n ot be 
p osi tive f or S A R S-C o V -2 m uc osal  s wa bs R T-P C R bef ore all ocat i on i n t he st u d y.
T he E P C U will c o nsi der i ncl u di n g a d dit i onal preca uti o nar y a n d safet y meas ures i n t his 
st u d y, s uc h as s ocial dista nci n g t o re d uce t he ris k of S A R S -C o V -2 i nfect i on, C O VI D -1 9, 
testi n g f or prese nce of viral part icles a n d a nti b o dies a n d t he use of P P E f or b ot h staff a nd 
v o l unt eers g uide d b y l o c al  re q uire me nts a n d c urre nt g o ver n me nt a d vice. I nf or mati on o n 
C O VI D -1 9 c o nsi derat i ons, testi n g a n d preca ut i onar y  u nit meas ures are descri be d i n a U nit 
s pecific c o nse nt f or m w hic h is a p pr o ve d b y t he Ge neric Et hics C o m mittee. T he tr ial 
parti ci pa nt s will be c o nse nte d t o U nit s pecific c o nse nt f or m i n a d dit i on t o t he St u d y  
S pecific c o nse nt f or m. 
Parti cipa nt s will u n der g o C O VI D-1 9 testi n g at scree ni n g , prior t o ra n d o misati o n a nd ca n 
be perf or m e d as per PI’s discret i on d uri n g t he st u d y, i ncl u di n g t he Fol l ow- u p P eri o d. A 
p artici pa nt wit h c urre nt c o nfir me d C O VI D -1 9 i nfecti o n will n ot be i ncl u de d i n t he st u d y . 
C o nfir me d a n d s us pecte d S A R S -C o V -2 i nfect i on a n d C O VI D -1 9 will be rec or de d i n t he 
A Es fiel ds.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
2. 
S T U D Y O B J E C TI V E S
2. 1. 
Pri m ar y O bjecti ve
T a bl e 2- 1 
Pri m ar y O bjecti ve a n d O utc o me Me as ures
Pri m ar y O bjecti ve
O utc o me Me as ures

T o e val uate t he safet y a n d t olera bilit y of 
A Z D 7 4 4 2 a d mi nistere d I V or I M t o healt h y a d ult 
partici pa nt s 1 8 t o 5 5 years of a ge.

A Es, S A Es, safet y la b orat or y para meters 
( hae mat ol o g y, cli nical c he mistr y, c oa g ulati on,
a n d uri nal ysis); 1 2 -lea d safet y E C G; vital si g ns 
( B P, p ulse rate , oral te m perat ure, a n d res pirat or y 
rate), a n d p h ysical e xa mi nati o n.

I njecti o n site reacti o ns will be m o nit ore d f or t he 
I M i njecti o n c o h ort (i ncl u di n g assess me nt of 
size, re d ness/er yt he ma, s welli n g, itc hi n g/ pr uritis, 
pai n or te n der ness, i n d urati o n, disc ol o ur ati o n ) 
a n d will be rec or de d as an A E a n d a p h ot o gra p h
ta ke n , at t he discreti o n of t he PI , wit h visi ble 
meas uri n g ta pe .
A Es : a d verse e ve nts; B P: bl o o d press ure; E C G : electr ocar di o gra m; I M: i ntra m usc ular; I V: i ntra ve n o us; 
S A Es : seri o us a d verse e ve nts.
2. 2. 
Sec o n d ar y O bjecti ves
T a ble 2- 2 
Sec o n d ar y O bjecti ves a n d O utc o me Me as ures
Sec o n d ar y O bjecti ve
O utc o me Me as ures

T o e val uate t he si n gle d ose P K of A Z D 7 4 4 2 
(w h e n m A bs are a d mi nistere d se q ue ntiall y 
[di vi de d i n se parate i nf usi o n of eac h m A b
c o m p o ne nt ], a n d w he n m A bs are c o -
a d mi nistere d [ b ot h m A bs mi xe d i nt o a si n gle 
i nf usi o n]) i n ser u m.

After I V i nf usi o n: C ma x, T ma x, t ½ λz, A U Clast , 
A U Ci nf , Vss, Vz, a n d C L.

After I M i njecti o n: C ma x, T ma x, t ½ λz, A U Clast , 
A U Ci nf , e xtra vasc ular C L/ F, F, a n d 
e xtra vasc ular Vz/ F.

T o e val uate t he A D A res p o nses t o A Z D 7 4 4 2 i n 
ser u m.

I nci de nce of A D A t o A Z D 7 4 4 2 i n ser u m o ver 
ti me.
A D A: a nti -dr u g a nti b o d y; A U Ci nf: Ar ea u n der t he ser u m c o nce ntrati o n vers us ti me c ur ve e xtra p olate d t o 
i nfi nit y; A U Clast: Ar ea u n der t he ser u m c o nce nt rati on vers us ti me c ur ve fr o m ti me zer o t o ti me of last 
meas ura ble c o nce ntrati o n ; C L: s yste mic cleara nce; C L/ F: a p pare nt t otal cleara nce; C ma x: ma xi m u m ser u m 
c o nce ntrati o n; I M: i ntra m usc ular; I V: i ntra ve n o us; P K: p har mac o ki netics; t ½ λz: ter mi nal eli mi nation  
half -life; T ma x: ti me t o reac h ma xi m u m ser u m c o nce ntrati o n; S A Es: seri o us a d verse e ve nts; Vss: v ol u me of 
distri b uti o n at stea d y state; Vz : v ol u me of distri b uti o n at ter mi nal p hase ; Vz/ F: a p pare nt v ol u me of 
distri b uti o n at ter mi nal p hase.
2. 3. 
E x pl or at or y O bjecti ves
T a ble 2- 3 
E x pl or at or y O bjecti ves a n d O utc o me Me as ures
E x pl or at or y O bjecti ve(s)
O utc o me Me as ures

T o e val uate t he si n gle d ose P K c o nce ntrati o ns of 
A Z D 7 4 4 2 i n nasal fl ui d.

Nasal fl ui d a n d bl o o d sa m ples t o be c ollecte d, 
h o we ver, res ults ma y f or m part of t he st u d y’s 
re p ort.

T o e val uate t he f u ncti o nal i n hi biti o n of 
S A R S -C o V -2 b y  A Z D 7 4 4 2 c o nce ntrati o ns i n 
ser u m.
P K: p har mac o ki netics; S A R S -C o V - 2: se vere ac ute res pirat or y s yn dr o me c or o na vir us 2.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Refer t o Secti o n 6. 3 f or safet y varia bles a n d Sect i on 1 0. 2 f or P K para meters.
3. 
S T U D Y D E SI G N
3. 1. 
O ver all St u d y Desi g n a n d Fl o w C h art
T his is a P hase I, F TI H, ra n d o mise d, d o u ble- bli n d, place b o -c o ntr olle d, d ose escalat i on 
st u d y e val uati n g t he safet y, t olera bility,  a n d P K of A Z D 7 4 4 2 i n health y a d ult partici pa nt s,
1 8 t o 5 5 years of a ge. A p pr o xi matel y 6 0 heal t hy p arti ci pa nt s will be e nr olle d at o ne st u d y 
ce ntre a n d ra n d omise d 1 0: 2 t o ei t her A Z D 7 4 4 2 or place b o a d mi nistere d I V or I M, acr oss 
5 fi xe d-d ose c o h orts. F or partici pa nts w h o will recei ve t he I M P via I M i njecti on ( C o h ort 
1a), t he I M P will be a d mi nistere d as se q ue nt ial direct glut e al I M a d mi nistrati o ns starti n g 
wi t h A Z D 8 8 9 5/ place b o a n d f oll owe d b y  A Z D 1 0 6 1/ place b o. F or partici pa nt s w h o will 
recei ve I M P via I V i nf usi on i n t he first 3 c o h orts t o be d ose d via I V i nf usi on ( C o h orts 1 b, 
2, a n d 3) , t he I M P will be a d mi nistere d i n t wo se q ue ntial I V i nf usi ons at a ma xi mal 
i nf usi on rate of 2 0 m g/ mi n ute, starti n g wit h A Z D 8 8 9 5/ place b o a n d f o ll owe d b y  
A Z D 1 0 6 1/ place b o. F or partici pa nts w h o will recei ve t he I M P via I V i nf usi o n i n C o h ort 4, 
t he I M P will be c o -a d mi nistere d as a si n gle I V i nf usi o n c o ntai ni n g b ot h m A bs at a 
ma xi mal i nf usi o n rate of 5 0 m g/ mi n ute. A d dit i onal c o h orts ma y be a d de d wit h l o wer or 
i nter me diate d ose s of  A Z D 7 4 4 2 if t he D E C deter mi nes t he y are warra nte d.
All p arti ci pa nt s will be a d mitte d t o a P hase I u nit o n t heir res pect i ve Da y -1 ( 1 da y  prior t o 
d osi n g ; S A R S -C o V - 2 q R T -P C R res ults m u st be a vaila ble bef ore d osi n g o n Da y 1 ) a n d 
di sc har ge d o n Da y 2 ( 1 da y after d osi n g, after t he 2 4-h o ur pr oce d ures are c o m plete d). 
Parti cipa nt s will t he n be f oll owe d u p u ntil a n d i ncl u di n g Da y 3 6 1 f or s af et y,  incl u di n g 
rec or di n g of A Es a n d S A Es, a n d c ollecti on of bl o o d sa m ples f or P K a n d A D As. Se nti nel 
d osi n g (see Sect i on 3. 3. 1 ) will be a p plie d f or all d osi n g c o h orts t o e ns ure parti ci pa nt
safety.  T w o partici pa nt s of eac h c o h ort will be d ose d at a rati o of 1: 1 ( A Z D 7 4 4 2: place b o) 
a n d will t he n u n der g o a safet y m o nit ori n g peri o d f or at least 2 4 h o urs bef ore d osi n g t he 
rest of t he partici pa nt s of t hat c o h ort. Escalat i on fr o m o ne d ose le vel t o t he ne xt d ose le vel, 
a n d fr o m t he last c o h ort wit h se q ue ntial I V i nf usi ons o f t he m A bs ( C o h ort 3) t o t he first 
c o h ort wit h a c o -a d mi nistere d i nf usi o n of t he m A bs ( C o h ort 4), will be base d o n re vie w o f 
all a vaila ble safet y data u p t o a n d i ncl u di n g Da y 8. I n a d diti o n, a n y  a vailable P K data will 
als o be re vie we d.
As t he st u d y  will ver y li kel y t a k e place d uri n g t he C O VI D -1 9 pa n de mic, meas ures will be 
p ut i n place t o e ns ure mi ni mal S A R S -C o V -2 e x p os ure f or site staff as well as st u d y  
parti ci pa nt s. E xclusi o n  a n d wit hdra wal cri t eria ar e i n place t o e ns ure site staff a n d st u d y 
parti ci pa nt safety.  Re p orti n g of S A R S-C o V -2 p ositi ve res ults d uri n g t he st u d y  c o n d uct 
will be re p orte d as A Es a n d meas ures will be a p plie d at t he discret i on of t he PI t o 
mi ni mi se furt her S A R S -C o V -2 e x p os ure as m uc h as p ossi ble. G ui da nce f or m a na ge me nt 
of  s u bjects w h o wis h t o recei ve a n a p pr o ve d vacci ne f or pr otecti o n a gai nst S A R S-C o V - 2 
is pr o vi de d.
Details o n I M P a d mi nistrati o n are pr o vi de d i n Secti o n 5. 4. 3 .

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
T he st u d y  will c o mprise of:

A Scree ni n g Peri o d of u p t o 2 7 da ys ( Da y -2 8 t hr o u g h Da y -2);

A Treat m e nt Perio d d uri n g w hic h parti ci pa nt s will be resi de nt at t he Cli nical U nit fr o m 
Da y  -1, 1 da y bef ore I M P a d mi nistrati o n ( o n Da y 1) u ntil at least 2 4 h o urs after I M P 
a d mi nistrati o n, will be disc har ge d o n Da y 2 af ter all s af et y e valu ati o ns ha ve bee n 
c o mplete d, a n d

A F ol l ow- u p P erio d last i n g 3 6 0 da ys (t hr o u g h t o Da y 3 6 1) after t he I M P d ose. S h o ul d 
a s u bject wa nt t o be u n bli n de d f or vacci nat i on p ur p oses o utsi de t he visit wi n d o ws
d uri n g t he F oll o w - u p Perio d , an u nsc he d ule d u n bli n di n g visit will be i ncl u de d).
T he st u d y  desi g n is dee me d a p pr o priate f or c o n d uct i n healt h y v o l unt eers d uri n g t he 
C O VI D -1 9 pa n de mic o n g oi n g at t he ti me of writ i n g t his C S P.
T he st u d y  fl ow- c hart is prese nte d i n Fi g ure 3 - 1 a n d t he o verall gra p hical re prese ntati o n of 
t he st u d y sc he me is ill ustrate d i n Fi g ure 3- 2 . T he S o A dis pla yi n g assess me nts/tas ks a n d 
ti me p oi nts is prese nte d i n Ta ble 3- 1 , Ta ble 3- 2 , a n d Ta ble 3- 3.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Fi g ure 3- 1 
St u d y Fl o w C h art
Visit 1 *
E nr ol me nt
Visit 2
Resi de ntial peri o d
Visit 3 t hr o u g h 1 4
F oll o w - u p P eri o d* * *
I nf or me d c o nse nt 
A d missi o n t o Cli nical U nit
Disc har ge fr o m Cli nical 
U nit
F oll o w - u p
Scree ni n g peri o d
Ra n d o mi sati on, f oll o we d b y si n gle d ose a d mi nistrati o n
(I V i nf usi o n or I M i njecti o n)
2 7 da ys
( Da y -2 8 t hr o u g h Da y - 2)
Da y  - 1 * *
Da y 1
Da y  2 
Da y  4 t hr o u g h Da y 3 6 1
* Visit 1 ma y be c o n d ucte d o ver o ne or m ore da ys d uri n g t he Scree ni n g Peri o d
* * Partici pa nts ma y be a d mitte d t o t he Cli nical U nit o n Da y -2 t o all o w f or S A R S -C o V -2 q R T -P C R res ults t o be a vaila ble bef ore d osi n g o n Da y 1.
* * * A n u nsc he d ule d u n bli n di n g visit will be i ncl u de d sh o ul d a s u bject wa nt t o be u n bli n de d f or vacci nati o n p ur p oses o utsi de t he visit wi n d o ws .
I M: i ntra m usc ular; I V: i ntra ve n o us; q R T -P C R: q ua ntitati ve real -ti me p ol y merase c hai n reacti o n; S A R S -C o V- 2: se vere ac ute res pirat or y s y n dr o me c or o na vir us 2.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 2 0 2 1
C O N FI D E N TI A L A N D P R O P R I E T A R Y 
3 1 of 1 0 3
Fi g ure 3- 2 
O ver all Gr a p hic al Re prese nt ati o n of t he St u d y
A Z D 7 4 4 2 will be a d mi nistere d se q ue ntiall y i n C o h orts 1a, 1 b, 2, a n d 3 ( A Z D 8 8 9 5/ place b o f oll o we d b y 
A Z D 1 0 6 1/ place b o) .
I M: i ntra m usc ular; I V: i ntra ve n o us; n: n u m ber of partici pa nts.
See S ectio n 1 1. 4 a n d Secti o n 3. 3. 1 f or furt her details o n deter mi nat i on of sa m ple size a n d 
se nti nel d osi n g , res pecti vel y.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 2 0 2 1
C O N FI D E N TI A L A N D P R O P R I E T A R Y 
3 2 of 1 0 3
T a ble 3- 1 
Sc he d ule of Assess me nts ( Scree ni n g)
Scree ni n g Pr oce d ures
St u d y Peri o d
Scree ni n g
Pr oce d ure / St u d y 
D a y -2 8 t o D a y - 2
Writte n i nf or me d c o nse nt/assi g n me nt of R u n -i n n u m ber
X
Me dical hist or y a n d de m o gra p hics
X
F ull p h ysical e xa mi nati o n, hei g ht, wei g ht a n d B MI
X
1 2 -Lea d E C G
X
Vital si g ns
X
Ser u m c he mistr y
X
Hae mat ol o g y
X
C oa g ulati o n
X
F ollicle sti m ulati n g h or m o ne ( p ostme n o pa usal w o me n o nl y)
X
Ur i nal ysis
X
Pre g na nc y test (ser u m β- h C G) a
X
HI V, he patitis B, he patitis C testi n g
X
U ri ne dr u g a n d alc o h ol scree n
X
Assess me nt of A Es/ S A Es
X
( S A Es o nl y)
C o nc o mita nt me dicati o ns
X
Verif y  eli gi bilit y criteria
X
S A R S -C o V -2 ser ol o g y a n d q R T -P C R
b
X
a. 
Fe male partici pa nt s onl y . Pre g na nc y test m ust be ne gati ve at scree ni n g.
b. 
S A R S -C o V -2 ser ol o g y ca n be d o ne at scree ni n g visit. C o nfir mat or y q R T -P C R ca n be d o ne at t he 
discreti o n of t he PI de pe n di n g o n t he serol o g y res ults at scree ni n g. A q R T -P C R m ust be d o ne at 
a d missi o n a n d res ult s h o w n t o be ne gati ve pri or t o ra n d o misati o n of partici pa nts . T he C O VI D -1 9 tests at 
scree ni n g will be perf or me d as part of t he Cli nical U nit’s ge neral scree ni n g. T h ese C O VI D - 1 9
scree ni n gs will occ ur after t he s u bject has c o nse nte d t o t he C O VI D- 1 9 scree ni n g a n d bef ore c o nse nt f or 
t he st u d y is o btai ne d.
A E: a d verse e ve nt; β- h C G: beta h u ma n c h ori o nic g o na d otr o pi n; E C G = electr ocar di o gra m; HI V = h u ma n 
i m m u n o deficie nc y vir us; PI: pri nci pal i n vesti gat or; q R T -P C R: q ua ntitati ve real -ti me p ol y merase c hai n 
reacti o n; S A E: seri o us a d verse e ve nt.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 2 0 2 1
C O N FI D E N TI A L A N D P R O P R I E T A R Y 
3 3 of 1 0 3
T a ble 3- 2 
Sc he d ule of Assess me nts ( Tre at me nt Peri o d)
Tre at me nt Peri o d St u d y Pr oce d ures 
Pr oce d ure 
Tre at me nt Peri o d
D a y -1  a
D osi n g ( D a y 1)
D a y 2
A d missi o n 
D osi n g
E n d of 
D osi n g
8 h o urs
p ost -d ose
Disc h ar ge
Me dical Hist or y
X  b
P h y sical e xa mi nati o n
X  b
( brief)
Wei g ht
X
1 2 -Lea d E C G  c
X   
X   
X   
X
Vital si g ns
X   
X
d
X
d
X   
X
Ser u m c he mistr y 
X
Hae mat ol o g y
X
C oa g ulati o n
X
Ur i nal ysis
X
Pre g na nc y test ( uri ne h C G)
X
e
U ri ne dr u g a n d alc o h ol scree n
X
P K ser u m sa m ple
X
f
X
g
X   
X
P K nasal fl ui d sa m ple
X
A D A ser u m sa m ple
X
Ne utralisi n g a nti b o d y ser u m 
sa m ple
X
Assess me nt of S A Es a n d A Es
X
( o n g oi n g o bser vati o n a n d q uesti o ni n g)
C o nc o mita nt me dicati o ns
X
( o n g oi n g o bser vati o n a n d q uesti o ni n g)
Verif y  eli gi bilit y criteria
X   
X
A d missi o n t o t he Cli nical U nit
X
h
Ra n d o misati o n after a d missi o n t o 
i nf usi o n u nit
X
Scree n Fail ure 
X
Partici pa nt i de ntificati o n car d
X
I n vesti g ati o n al me dici n al pr o d uct
a d mi nistr ati o n
X
I njecti o n site reacti o n m o nit ori n g
(l ocal t olera bilit y) i
X   
X   
X   
X
a. 
Partici pa nt s ma y be a d mitte d t o t he Cli nical U nit o n Da y  - 2 t o all o w f or S A R S-C o V - 2 q R T -P C R res ults 
t o be a vaila ble bef ore d osi n g o n Da y 1 . F or t hese partici pa nts, a d missi o n assess me nts ma y be perf or me d 
o n Da y - 1.
b. 
U p date scree ni n g me dical hist or y a n d p h ysical e xa mi nati o n (a n y ne w fi n di n gs si nce scree ni n g).
c. 
E C G will be o btai ne d after at least fi ve mi n utes s u pi ne rest ( pre-d ose) i n all c o hor ts. I n t he I V c o h orts 
ti m e p oi nts will i ncl u de pr e-d ose o n Da y 1, at c o m pleti o n of i nf usi o n , 6 0 mi n utes after c o m pleti o n of 
i nf usi o n, 4 a n d 8 h o urs ( ± 1 0 mi n utes) p ost start of I M P a d mi nistrati o n. F or t he I M co h ort E C Gs will be 
o btai ne d at pre-d ose o n Da y 1, a n d at 1, 4, a n d 8 h o urs after t he start of I M P a d mi nistrati o n . O n Da y 2, 
resti n g E C G will be perf or me d bef ore disc har ge f or all c o h orts.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 2 0 2 1
C O N FI D E N TI A L A N D P R O P R I E T A R Y 
3 4 of 1 0 3
d. 
Vital si g ns will be m o nit ore d bef ore a n d after I M a n d I V a d mi nistrati o n of I M P. A pre-d ose B P , p ulse 
rate, te m perat ure a n d res pirat or y rate rea di n gs will be o btai ne d i n all c o h orts. F or I V c o h orts, vital si g ns 
s h o ul d be m o nit ore d at t he start of i nf usi o n a n d e ver y 3 0 mi n utes ( ± 5 mi n utes) d uri n g i nf usi o n, at 
c o m pleti o n of i nf usi o n ( ± 5 mi n utes), 3 0 ( ± 5), a n d 6 0 ( ± 5) mi n utes after c o m pleti o n of i nf usi o n. F or 
t he I M c o h ort, vital si g ns s h o ul d be m o nit ore d at 3 0 ( ± 5) mi n utes a n d 6 0 ( ± 5) mi n utes p ost-d ose.
e. 
Fe male partici pa nt s onl y . Pre g na nc y test m ust be ne gati ve pri or t o d osi n g.
f. 
Pr e -d ose sa m ple f or b ot h I M a n d I V d osi n g c o h ort s. For  I V c o h orts a n a d diti o nal sa m ple is t o be 
c ollecte d w h e n t he i nf usi o n is 5 0 % c o m plete (f or eac h m A b w h e n I V a d mi nistrati o n is se q ue ntial i n 
C o h orts 1 b, 2 a n d 3, a n d o nce d uri n g t he c o -a d mi nistere d si n gle i nf usi o n i n C o h ort 4 ).
g. 
F or I V c o h orts o nl y (e n d of i nf usi o n f or eac h m A b i n C o h orts 1 b, 2 a n d 3 , a n d f or t he c o-a d mi nistere d
i nf usi o n i n C o h ort 4 ).
h. 
Partici pa nt s ma y be a d mitte d t o t he Cli nical U nit 2 da y s pri or t o d osi n g ( Da y - 2) t o all o w f or 
S A R S -C o V -2 q R T -P C R res ults t o be a vaila ble bef ore d osi n g o n Da y 1 . F or t hese partici pa nts, 
a d missi o n sa m ples ma y be c ollecte d o n Da y - 1.
i. 
L ocal t olera bilit y c hec k: f or partici pa nt s i n C o h ort 1a (i ntra m usc ular a d mi nistrati o n o nl y). Assess me nts 
at pre-d ose, i m me diatel y after d osi n g, 0. 5, 1, 8, a n d 2 4 h o urs p ost -d ose .
A E: a d verse e ve nt; A D A: a nti -dr u g a nti b o dies; E C G: electr ocar di o gra m; h C G: h u ma n c h ori o nic 
g o na d otr o pi n; I M P: i n vesti gati o nal me dici nal pr o d uct; I V: i ntra ve n o us; I M: i ntra m usc ular; m A b: a nti b o d y; 
P K: p har mac o ki netic; q R T -P C R: q ua ntitati ve real -ti me p ol y merase c hai n reacti o n; S A E: seri o us a d verse 
e ve nt; S A R S-C o V -2: se vere ac ute res pirat or y s y n dr o me c or o na vir us 2.
N O T E : Wit h t he e xce pti o n of vital si g ns a n d safet y E C Gs c, d, all Da y 1 assess me nts are t o ha ve t heir start 
ti m e ( n o mi nal ti me) matc h t he ti me of “e n d of i nf usi o n”. P ost -d ose assess me nts o n Da y 2 are t o ha ve t heir 
start ti me ( n o mi nal ti me) matc h t he ti me p oi nt of Da y 1 “start of i nf usi o n”.

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
T a ble 3- 3 
Sc he d ule of Assess me nts ( F oll o w -u p)
F oll o w -u p Pr oce d ures
Pr oce d ure
P ost -d ose F oll o w -u p D a y ± Assess me nt Wi n d o w
c
4  
6
8
- 1
1 5
± 1
3 1
- 2
6 1
± 5
9 1
± 5
1 5 1
± 5
2 1 1
± 5
2 7 1
± 1 0
3 6 1
± 1 0
Vital si g ns
a
X
X
X
X   
X   
X   
X   
X
1 2- Lea d safet y E C G
X
X
X
Ser u m c he mistr y
X
X
X
X
Hae mat ol o g y
X
X
X
X
C oa g ulati o n
X
X
X
X
Ur i nal ysis
X
X
X
X
P K ser u m sa m ple
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X
P K nasal fl ui d sa m ple
X
X
X   
X
A D A ser u m sa m ple
X   
X   
X
X   
X   
X
X
Ne utralisi n g a nti b o d y ser u m sa m ple
X
X   
X   
X   
X   
X   
X   
X
Assess me nt of A Es a n d S A Es b
X ( o n g oi n g o bser vati o n a n d q uesti o ni n g)
C o nc o mita nt me dicati o ns
X ( o n g oi n g o bser vati o n a n d q uesti o ni n g)
F ull p h ysical e xa mi nati o n
X
X
X
Wei g ht
X
St u d y c o m pleti o n i nf or mati o n
X

Cli nical St u d y Pr ot oc ol A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
F oll o w -u p Pr oce d ures
Pr oce d ure
P ost -d ose F oll o w -u p D a y ± Assess me nt Wi n d o w
c
4  
6
8
- 1
1 5
± 1
3 1
- 2
6 1
± 5
9 1
± 5
1 5 1
± 5
2 1 1
± 5
2 7 1
± 1 0
3 6 1
± 1 0
Pre g na nc y test ( uri ne h C G ) 
X   
X   
X   
X   
X   
X   
X
Astra Ze neca T ha n k y o u Car d
X
a. 
A n y  a b n or mal vital si g ns m ust be re peate d after t he partici pa nt has bee n at rest f or at least fi ve mi n utes. As part of C O VI D -1 9 m o nit ori n g dail y  or al te m perat ure 
meas ure me nts d uri n g i n -h o use sta y a n d at e ver y o ut patie nt visit will be i m ple me nte d.
b. 
S A R S -C o V -2 q R T -P C R or ser ol o g y t o be perf or me d at t he discreti o n of t he PI.
c. 
A n u nsc he d ule d u n bli n di n g visit will be i ncl u de d s h o ul d a s u bject wa nt t o be u n bli n de d f or vacci nati o n p ur p oses o utsi de t he visit wi n d o ws.
A D A: a nti -dr u g a nti b o dies; A E: a d verse e ve nt; E C G: electr ocar di o gra m; β -h C G: beta -h u ma n c h ori o nic g o na d otr o pi n; P K: p har mac o ki netic; q R T -P C R: q ua ntitati ve real -ti me 
p ol y merase c hai n reacti on; S A E: seri o us a d verse e ve nt; S A R S -C o V -2: se vere ac ute res pirat or y s y n dr o me c or o na vir us 2.
N O T E : All p ost-d ose assess me nts fr o m, a n d i ncl u di n g, Da y 2 are t o ha ve t heir start ti me ( n o mi nal ti me) matc h t he ti me p oi nt of Da y 1 “start of i nf usi o n”.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
3. 1. 1. 
Or der of Assess me nts
It is i m p orta nt t hat P K sa m pli n g occ urs as cl ose as p ossi ble t o sc he d ule d ti me. I n or der t o 
ac hie ve t his, ot her assess me nts sc he d ule d at t he sa me ti me ma y be i nit iate d pri or/f oll owi n g 
t o t he ti me p oi nt. T he se q ue nce at a partic ular ti me p oi nt is:
1 
1 2- Lea d S af et y E C Gs .
2 
Vi t al si g ns (s yst olic a n d diast olic B P a n d p ulse rate, oral  t e mperat ure a n d res pirat or y  
r at e).
3 
P K bl o o d a n d nasal fl ui d sa m pli n g ( will be c o llecte d at t he s pecifie d ti me p oi nt).
4 
S af et y bl o o d a n d uri ne sa m pli n g .
5 
Ot her pr oce d ures .
Details o f acce pta ble t olera nce wi n d o ws f or safet y a n d P K assess me nts will be i ncl u de d i n 
a W A D w hic h will be a gree d u p o n a n d si g ne d off bef ore t he start of t he st u d y .
3. 1. 2. 
E n d of St u d y
T he e n d o f st u d y is defi ne d as t he last partici pa nt ’s last visit t o t he Cli nical U nit.
3. 1. 3. 
E x pecte d D ur ati o n of t he St u d y
Eac h parti ci pa nt will be i n v o l ve d i n t he st u d y for u p t o 3 8 9 d a ys (a n u p t o 2 7-da y  
Scree ni n g Peri o d [ Da y -2 8 t hr o u g h Da y -2 ]; a 2-da y Treat me nt  Perio d [Da y - 1 a n d Da y 1] 
a n d a 3 6 0-d a y  Fol l ow- u p P erio d [ Da y  2 t hr o u g h Da y  3 6 1]).
T a ble 3- 4 
E x pecte d D ur ati o n of E ac h St u d y P art
All P artici p a nt s
Scree ni n g
Peri o d of 2 7 da ys. Da y -2 8 t hr o u g h Da y -2. T w o da ys bef ore 
d osi n g ( Da y 1).
Treat me nt Peri o d
A si n gle Treat me nt Peri o d d uri n g w hic h partici pa nt s will be 
resi de nt at t he Cli nical U nit fr o m 1 da y bef ore d osi n g ( Da y -1) 
u ntil at least 2 4 h o urs after d osi n g ( Da y 2) a n d will be 
disc har ge d o n Da y 2 after t he 2 4 -h o ur assess me nts are 
c o m plete d.
Partici pa nts ma y be a d mitte d t o t he Cli nical U nit o n Da y -2 t o 
all o w f or S A R S-C o V -2 q R T -P C R res ults t o be a vaila ble bef ore 
d osi n g o n D a y 1.
Was h o ut Peri o d
N ot a p plica ble.
F oll o w - u p
A 3 6 0 -da y safet y F oll o w - u p Peri o d (u p t o a n d i ncl u di n g
Da y 3 6 1 ).
T otal D urati o n
U p t o 3 8 9 da ys .
q R T -P C R: q ua ntitati ve real -ti me p ol y merase c hai n reacti o n; S A R S-C o V -2: se vere ac ute res pirat or y 
s yn dr o me c or o na vir us 2.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
3. 2. 
R ati o n ales f or St u d y Desi g n a n d D ose Selecti o n
3. 2. 1. 
R ati o n ale f or St u d y Desi g n
A Z D 7 4 4 2 is bei n g e val uate d f or a d mi nistrati o n t o pre ve nt a n d f or treat me nt of C O VI D -1 9. 
T his P hase I st u d y  will gat her i m p orta nt i nf or mat i on o n t he safet y a n d t olera bilit y of 
A Z D 7 4 4 2 , as well as rele va nt data o n t he P K pr ofile a n d t he ge nerat i on of A D As.
3. 2. 2. 
R ati o n ale f or E n d p oi nts
T he pri mar y  st u d y e n d p oi nts are sta n dar d e n d p oi nts f or safety assess me nt, i ncl u di n g AEs , 
S A Es , a n d safety cli nical la b orat or y meas ure me nts. Use of t he safet y e n d p o i nts is justifie d 
b y t heir a bilit y t o c haracteri se t he safet y a n d t olera bilit y pr ofile of A Z D 7 4 4 2 i n health y 
a d ults prior t o a d mi nistrati o n t o br oa der p o p ulat i ons i n later P hase 2/ 3 st u dies.
T he sec o n dar y  st u d y e n d p o i nts are t h ose re q uire d t o defi ne t he P K a n d i nci de nce of A D As 
t hr o u g h 3 6 0 da ys after a d mi nistrati o n ( Da y 1 t hr o u g h Da y 3 6 1). T he 3 6 0-da y  Fol l ow- u p 
P erio d will all o w f o ll ow- u p of  d ose d parti cipa nt s t hr o u g h a p pr o xi matel y fi ve half -li ves, 
w hic h is e x pecte d t o pr o vi de s ufficie nt safet y f oll ow- u p a n d will als o ma xi mi se t he 
pr o ba bilit y o f detecti n g A D A t o A Z D 7 4 4 2. T he P K e n d p o i nts will descri be t he dis p ositi on 
of  A Z D 7 4 4 2 i n health y a d ults after I V or I M a d mi nistrati o n. A nti-dr u g a nti b o d y res p o nses 
a n d i nci de nce will be meas ure d t o e ns ure t hat t he y are at acce pta ble le vels a n d d o n ot 
affect safet y or P K. I n a n e x pl orat or y  assess me nt, t he f u ncti o nal acti vity of  AZ D 7 4 4 2 will 
als o be assesse d b y t he a bilit y t o ne utralise S A R S -C o V -2 i nfect i on i n a micr o ne utralisat i on 
assa y.
3. 2. 3. 
D ose R ati o n ale
D ose l e vels of A Z D 7 4 4 2 i n F TI H st u d y were selecte d base d o n all a vaila ble p har mac ol o g y 
a n d P K data, w hic h were use d t o pre dict H E D. H u ma n P K para meters f or A Z D 7 4 4 2 were 
pre di cte d base d o n o bser ve d nirse vi ma b ( M E DI 8 8 9 7) h u ma n P K data. Nirse vi ma b is a n 
a nt i-R S V I g G 1 wi t h Y T E s u bstit uti o n t o pr ol o n g half-life. A Z D 7 4 4 2 is a n a nti-C O VI D - 1 9 
I g G 1 wit h b ot h Y T E a n d T M s u bstitut i ons. Si milar P K f or A Z D 7 4 4 2 a n d nirse vi ma b was 
o bser ve d i n h u ma n Fc R n tra ns ge nic mice.   T he si milarity of  P K f or A Z D 7 4 4 2 a n d 
M E DI 8 8 9 7 will be c o nfir me d i n t he m o n ke y st u d y.
H u m a n efficacio us d ose s were pr ojecte d base d o n i n vitr o f u nct i onal p ote nc y  data t hat 
acc o u nts f or p ote ntial s y ner gistic effect of t w o-m A b c o m bi nati o n . T hese d ose le vels were 
selecte d t o e ns ure e x p os ure i n ser u m a n d t he E L F of t he l u n gs t o be a b o ve t he I C8 0 f or 
A Z D 7 4 4 2 t o be a p pr o xi matel y 
f or a d uratio n of  at least 5 mo nt hs p ost -d ose .
T o f urt her s u p p ort t he selecti o n of t he st u d y  d oses, a viral d y na mic m o del was de vel o pe d, 
w hic h allo ws u n dersta n di n g of t he p har mac o d y na mic effects of A Z D 7 4 4 2 o n t he gr o wt h 
of  a S A R S-C o V -2 i nfect i on a n d t he res ult i n g i m m u ne res p o nse. F or pr o p h yla xis, t he viral 
d y na mic m o del i n dicates t hat vir us e ntr y  in hi bit i on greater t ha n a p pr o xi matel y 8 0 % is 
s ufficie nt t o pre ve nt i nfecti on. Ass u mi n g a partit i on rati o of  1 % f or lu n g E L F t o ser u m a n d 
a n I C8 0 f or A Z D 7 4 4 2 t o be a p pr o xi matel y  
, a mi ni m u m effecti ve I M d ose of 
C CI
C CI

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 is re q uir e d for pr o p h yla xis t o pr o vi de pr otecti o n fr o m S A R S -C o V -2 i nfecti o n f or
5 m o nt hs. If t he partiti o n rati o is 0. 1 %, a c o nser vati ve ass u m pti o n, t he n a mi ni m u m 
effect i ve d ose of   
 I M ma y be nee de d f or pr o p h yla xis. With 7 6 % I M 
bi oa vaila bilit y ass u me d, I V d oses w o ul d be pr o p orti o nall y lo wer . F or parti ci pa nts wit h 
acti ve i nfectio n, t he m o d el  in dicates t hat vir us e ntr y i n hi bit i on greater t ha n a p pr o xi matel y 
9 2 % i s s ufficie nt t o ra pi dl y s u p press t he viral l oa d t o less t ha n o ne c o py per s wa b, w hic h is 
a n u merical c ut -off criteria t hat is re gar de d as cli nicall y mea ni n gf ul effect t ha t will 
acc o m pa n y c o mplete nat ural  infect i on cleara nce. Wit h a n e ntr y  in hi bit i on I C8 0 f or 
A Z D 7 4 4 2 t o be a p pr o xi matel y 
a n d a lu n g E L F t o ser u m partiti on ra n ge of 1 % 
t o 0. 1 %, t he mi ni m u m effecti ve d ose t he n ra n ges fr o m 3 0 0 m g I M t o 3 0 0 0 m g I M. T his 
ali g ns wit h t he d ose re q uire d t o ac hie ve t he tar get re d ucti o n of 9 2 % i n vir us e ntr y 
i n hi biti on. Wi t h 7 6 % I M bioa vaila bili t y ass u me d, I V d oses w o ul d be pr o p orti o nall y l o wer.
Pe n di n g c o m plet i on of o n g o i n g t o xic ol og y  st u dies, t he ass u m pt i on is t he d ose teste d i n 
m o n ke y t o xic ol o g y  st u d y ( 
 per A b f or I M a n d   
 per A b f or I V) is t he 
N O A E L. Safet y mar gi ns are pre dicte d usi n g e x pecte d e x p os ures at m o n ke y  N O A E L 
di vi de d b y e x pecte d e x p os ures at h u ma n d oses i n t he P hase 1 st u d y . S ufficient  safety 
mar gi ns are mai ntai ne d f or starti n g a n d t o p d ose le vels i n t he P h ase 1 st u d y . At t he starti n g 
d ose of  
 per A b I M, C ma x-base d safet y ma r gi n is 3 0, A U C-base d a n d H E D -base d 
safety mar gi n is 1 0. At t he starti n g d ose of 1 5 0 m g per A b I V, C ma x- ba se d safety mar gi n 
is 1 2 0, A U C-base d a n d H E D -base d safet y mar gi n is 4 0. At t he t o p d ose of 1 5 0 0 m g per 
A b I V, C m a x-base d safet y mar gi n is 1 2, A U C -base d a n d H E D -base d safet y  mar gi n is 
f our.
3. 2. 4. 
R ati o n ale f or St u d y P o p ul ati o n 
T he p ote nti al tar get p o p ulat i on f or t he de vel o p me nt of A Z D 7 4 4 2 is t he ge neral  p o p ulat i on 
a n d s pecificall y healt hcare w or kers , or i n di vi d uals at i ncrease d ris k of C O VI D - 1 9 or t hose 
w h o are e x pecte d t o ha ve a se vere o utc o me a n d nee d i m me diate pr otecti o n. T h us, t his 
st u d y is bei n g c o n d ucte d i n healt h y a d ult s 1 8 t o 5 5 years of a ge. The P K of A Z D 7 4 4 2 i n 
healt h y a d ults , a ge d 1 8 t o 5 5 years is e x pecte d t o be m ost re prese ntati ve of t hat i n t he 
p ote nti al tar get p o p ulat i ons, m a ki n g t he healt h y p o p ul at i on a p pr o priate f or d ose select i on. 
I n a d diti on, i ni tiall y e val uat i n g A Z D 7 4 4 2 i n healt h y v o l unt eers all o ws safet y data t o be 
gat here d wi t h t he lo west ris k of o bser vi n g c o nf o u n di n g e ve nts relate d t o pre -e xist i n g 
u n derl yi n g ill nesses or pri or C O VI D -1 9 e x p os ure .
3. 2. 5. 
D ose Esc al ati o n Str ate g y
A st u d y s pecific D E C will be res p o nsi ble f or d ose escalat i on decisi o ns , a n d for t he 
decisi o n t o per mit I V c o -a d mi nistrati o n of t he m A bs mi xe d i n a si n gle i nf usi o n, after 
re vie w of u p t o a n d i ncl u di n g Da y 8 safety data fr o m  Co h ort 1 b a n d o n war ds . A n e x pecte d 
mi ni m u m o f 8 partici pa nt s’ w ort h of safety data will b e re q uir e d t o e val uate t he d ose 
escalat i on. T his c o m mittee i ncl u des t he Astra Ze neca Lea d P h ysicia n , t he Astra Ze neca 
Pati e nt Safet y P h ys icia n, a n d t he PI f or t he st u d y. A d h oc me m bers ma y be a d de d or 
c o ns ulte d o n a n as-nee de d basis. T he D E C will re vie w bli n de d data, i ncl u di n g all A Es a n d 
la b orat or y para meters, after all partici pa nt s i n eac h d ose c o h ort ( u nless wit h dra w n or l ost 
C CI
C CI
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
t o f oll ow- u p) ha ve bee n f o ll owe d t hr o u g h t o t he Da y  8 visit. Bli n de d u p date d safet y data 
fro m  lo wer d osi n g c o h orts will als o be re vie we d f or t he d ose escalat i on decisi o ns . Bli n de d 
u p date d safet y data fr o m t he 3 0 0 0 mg I V se q ue ntiall y  d ose d c o h ort will be re vie we d prior 
t o a decisi on t o per mit I V c o -a d mi nistrati o n o f t he 2 m A bs t hat c o m prise A Z D 7 4 4 2. T his 
c o m mittee ma y als o re vie w bli n de d data at ot her ti me p oi nts i n res p o nse t o A Es assesse d 
as me dicall y rele va nt b y t he Lea d P h ysicia n or PI . T he D E C ma y als o re q uest t o re vie w 
u n bli n de d data if t his is c o nsi dere d necessar y  t o full y  e val uate a p ote ntial s af et y si g nal. 
T he 7 -d a y  F ol l ow- u p P erio d s h o ul d pr o vi de a de q uate safet y i nf or mati on f or d ose 
escalat i on, a n d t he tra nsit i on fr om se q ue ntial ad mi nistrati o n t o c o-a d mi nistrati o n of t he 
m A bs, beca use 1) A Z D 7 4 4 2 d oes n ot ha ve h u ma n h ost tiss ue tar gets a n d 2) t here are n o 
s pecific safety c o ncer ns i n li g ht of t he tiss ue cr oss -reacti vity data.
3. 2. 6. 
St o p pi n g Criteri a f or D ose Esc al ati o n
If r ules s pecifie d in t his c ha pter are f ulfille d, d osi n g will be st o p pe d. ( Please refer als o t o 
D E C secti o n f or f urt her i nf or mat i on.)
3. 2. 6. 1. 
St o p pi n g R ules f or a n I n di vi d u al P artici p a nt , at A n y Ti me i n t he St u d y
Eac h parti ci pa nt i n t his st u d y will recei ve a si n gle d ose of IM P ( di vi de d i nto t wo se parate 
d oses f or eac h m A b c o m p o ne nt) . A n i n di vi d ual p arti ci pa nt will n ot recei ve I M P if a n y of 
t he f o ll owi n g occ ur i n t he parti ci pa nt i n q uesti on:

Wit h dra wal o f c o nse nt after si g ni n g i nf or me d c o nse nt.

Parti cipa nt meets o ne or m ore of t he e xcl usi o n cri t eria or fails t o meet all i ncl usi o n 
criteria f or st u d y partici patio n.

A se vere or p ote ntiall y  life-t hreate ni n g seri o us s yste mic, aller gic, or l ocal react i on wi t h 
o nset after d osi n g has bee n i nit iate d. If s uc h a reacti o n is o bser ve d d uri n g I MP 
a d mi nistrati o n, t he i nf usi o n will  be i m me diatel y st o p pe d, n o f urt her I M P will be 
a d mi nistere d, a n d t he Lea d P h ysicia n m ust be c o ntacte d i m me diatel y.
Eac h parti ci pa nt w h o has recei ve d I M P will be f oll o we d f or t he f ull st u d y peri o d u nless 
c o nse nt is wit h dra w n s pecificall y fr o m furt her st u d y  p artici pat i on, or t he parti ci pa nt is l ost 
t o f oll ow- u p. Parti ci pa nt s w h o ha ve n ot recei ve d I M P, re gar dless of reas o n, will n ot be 
fol l owe d . U nless c o nse nt f or f o ll ow- u p i s wit hdra w n, parti ci pa nt s disc o nti n ue d after 
recei vi n g a partial d ose of I M P will be f oll owe d f or t he f ull st u d y  perio d ( u p t o a n d 
i ncl u di n g Da y 3 6 1, 3 6 0 da y s after I M P d osi n g) wit h all la b orat or y a n d cli nical e v aluat i ons 
c ollecte d as defi ne d i n t his C S P.
3. 2. 6. 2. 
St o p pi n g R ules f or a W h ole C o h ort, D ose Esc al ati o n, Pr o gressi o n t o Ne xt 
St u d y P art a n d Ter mi n ati o n of St u d y
St o p pi n g r ul es as detaile d bel o w ( ge neral, car di o vasc ular, la b orat or y , a n d A Z D 7 4 4 2 
s pecific) are a p plica ble for eac h of t he f oll o wi n g sit uati o n:
 
St o p pi n g d osi n g f or a w h ole c o h ort.
 
St o p pi n g d ose escalat i on.
 
Fi nal st o p of st u d y .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Ge ner al Criteri a
T he st u d y  will be p ut o n te mp orar y h o l d ( defi ne d as treat me nt st o p pe d f or e nr olle d 
parti ci pa nt s; a n d st o p of e nr ol me nt of parti ci pa nt s i nt o t he st u d y) pe n di n g f urt her safety 
data a nal ysis if a n y  of t he f oll owi n g cri t eria occ ur i n parti ci pa nt s recei vi n g A Z D 7 4 4 2:
 
A “seri o us” a d verse reacti o n (ie, a S A E [i ncl u di n g deat h]) c o nsi dere d at least p ossi bl y 
r elate d t o t he I M P a d mi nistrati o n) i n a n y o ne partici pa nt ;
 
“ Se vere” n o n-serio us a d verse react i ons (ie, se vere n o n -serio us A Es c o nsi dere d as, at 
least, p ossi bl y relate d t o t he I M P a d mi nistrati o n) i n t wo or m ore partici pa nt s i n t he 
sa me c o h ort, i n de pe n de nt of  wit hi n or n ot wit hi n t he sa me S O C.
T he ri s k t o all parti ci pa nt s will be e val uate d t h or o u g hl y prior t o a decisi o n  as t o w het her t o 
ter mi nate t he st u d y pre mat urel y or c o nti n ue d osi n g i n a gree me nt wit h t he re g ulat or y 
a ut h orities.
T he D E C will caref ull y  r evie w t he t otalit y of  data, ta ki n g i nt o acc o u nt m o derate 
n o n- serio us A Es at l east p ossi bl y relate d t o t he I M P a d mi nistrati o n, t he n u m ber of 
parti ci pa nt s i n w hic h t he y occ ur, a n d c o nc urre nc y of m ore t ha n o ne wit hi n t he sa me 
parti ci pa nt .
C ar di o v asc ul ar Criter i a
 
T w o or m ore partici pa nt s, t hat recei ve A Z D 7 4 4 2, ha ve Q Tc pr ol o n gati on defi ne d as 
Q Tc F > 5 0 0 ms, or a pr ol o n gat i on fr om baseli ne (pre -d ose o n Da y 1) of  > 6 0 ms, 
c o nfir me d ( persiste nt f or at least fi ve mi n utes ) a n d deter mi ne d p ost-d ose eit her d uri n g 
c o ntin u o us 1 2 -lea d E C G m o nit ori n g or o n a re peat 1 2-lea d E C G.
L a b or at or y Fi n di n gs
 
O ne or m or e partici pa nt s, w h o recei ve A Z D 7 4 4 2, f ulfil H y’s La w defi ne d as “ A n 
i ncrease i n A S T or A L T ≥ 3 × U L N a n d T B L ≥ 2 × U L N, w here n o ot her reas o n ca n 
be f ou n d t o e x plai n t he c o m bi nat i on of i ncreases, e g, ele vate d ser u m A L P i n dicat i n g 
c h o lestasis, viral he patitis, a n ot her dr u g”. T he ele vati o ns d o n ot ha ve t o be at t he sa me 
ti me or wit hi n a s pecifie d ti me fra me (see A p pe n di x C f or fol l ow- u p pr oce d ures).
St u d y S pecific St o p pi n g Criteri a Rel ate d t o A Z D 7 4 4 2
1 
A na p h ylactic reactio n ( per NI AI D a n d t he F A A N defi nit i on [ 8]) c o nsidere d relate d t o 
t he I M P i n a n y part ici pa nt.
2 
A n y safet y fi n di n g assesse d as relate d t o t he I M P t hat, i n t he o pi ni on of t he s p o ns or or 
t he PI , warra nts s us pe nsi on of f urt her d osi n g of pa rtici pa nt s u ntil m ore f ull y assesse d.
3. 2. 7. 
D ose Esc al ati o n C o m mittee
3. 2. 7. 1. 
C o m p ositi o n of D ose Esc al ati o n C o m mittee
T he D E C will c o nsist of t he f o ll owi n g c ore me m bers:
 
Pri nci pal I n vest i gat or ( C hair, v oti n g me m ber).
 
Astra Ze neca Lea d P h ysicia n ( v oti n g me m ber) .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 
Astra Ze neca Pati e nt Safet y P h ysicia n ( v oti n g me m ber) .
T he D E C m a y als o re q uest t o ha ve atte n da nce of or off-li ne s u p p ort a n d i n p ut fr o m t he 
f oll owi n g f u nct i ons as re q uire d:
 
Astra Ze neca Cli nical P har mac o ki net icist.
 
Astra Ze neca Tea m P har mac o met ricia n.
 
C o va n ce P har mac o ki net icist.
 
A stra Ze neca Statisticia n.
 
Astra Ze neca a n d/ or Pare xel a n d/ or e xter nal Me dical S pecialists as nee de d .
Astra Ze neca Cli nical Scie nt ist a n d Safet y S ci e nt ist ma y pr o vi de i n p uts as necessar y.
Wr itte n state me nts a n d c o ncl usi o ns b y t he D E C w ill be i n place bef ore all owi n g trial 
pr o gressi o n at t he n ote d ti mes as per C S P. T his i ncl u des d oc u me ntati o n of a p pr o priate 
q ualit y c o ntr ol c hec ks o n t he data re vie we d.
3. 2. 7. 2. 
D at a Re vie we d b y D ose Esc al ati o n C o m mittee f or D ose Esc al ati o n 
Decisi o n
T he D E C will de ci de o n pr o gressio n t o t he ne xt C S P -s pecifie d d ose le vels t hr o u g h o ut t he 
st u d y, a n d f or t he decisi o n t o per mit I V c o -a d mi nistrati o n of t he m A bs mi xe d i n a si n gle 
i nf usi on, c o nsi deri n g at eac h decisi o n p oi nt t he de gree of u ncertai nt y ( Sectio n 3. 3 ).
At  e ver y D E C, c u mulat i ve data f or all c o h orts will be re vie we d. T he f oll owi n g data will be 
re vie we d f or eac h i n di vi d ual c o h ort:
 
S af et y a n d t o lera bility data f or u p t o 2 4 h o urs p ost -d ose f or t he se nt i nel p arti ci pa nt s 
a n d at least 7 da ys’ w ort h of p ost -d ose safet y data f or eac h c o h ort f or d osi n g 
escalat i on bet wee n c o h orts.
E val ua ble parti ci pa nt s are defi ne d as parti ci pa nt s o n A Z D 7 4 4 2/ place b o, w h o ha ve 
c o mplete d all  s af et y fol l ow- u ps, as detaile d a b o ve. A mi ni m u m n u m ber of e val ua ble 
parti ci pa nt s of eig ht o n A Z D 7 4 4 2 will be c o nsi dere d a p pr o priate f or D E C decisi o n; n o 
r e place me nt partici pa nt s are pla n ne d.
A p pr o priate safet y data c ollect i on of  u p t o a n d i ncl u di n g Da y 8 safety data i n a gi ve n 
d osi n g c o h ort s h o ul d be c o m p lete t o pr ocee d t o t he ne xt d ose c o h ort.
3. 2. 7. 3. 
D ose Esc al ati o n C o m mittee Decisi o n o n Ne xt D ose
T he D E C will ma ke t he decisi o n w het her t o escalate t o t he ne xt d ose le vel, or t o per mit I V 
c o- a d mi nistrati o n of t he m A bs, or e x pa n d t he size of t he last d ose d c o h ort, or st o p t he 
st u d y after re vie wi n g all t he perti ne nt safety a n d a n y ot her rele va nt data.
If c o nse ns us a m o n g t he v oti n g D E C me m bers ca n n ot be reac he d t he n t he PI, w h o has t he 
ul timate res p o nsi bilit y f or t he safety of  t he parti ci pa nt s, will ma ke t he fi nal decisi on o n t he 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
ne xt d ose l e vel, ne xt c o h ort, or w het her t o st o p t he st u d y . I n or der t o escalate t o a ne xt 
d ose l e vel or c o h ort a u na ni m o us D E C decisi o n is nee de d.
T he decisi o ns of t he D E C o n t he ne xt d ose le vel or c o h ort will be d oc u m e nte d a n d 
pr o vi de d t o all t he a p pr o priate parties i n v o l ve d with t he st u d y , i ncl u di n g t he P har macist t o 
e na ble I M P pre parati o n f or t he ne xt sc he d u le d d osi n g da y.
 
A d ose i n w hic h t he safet y st o p pin g cri t eria ha ve bee n met ( please refer t o 
Secti o n 3. 2. 6 , St o p pi n g R ules) will n ot be re peate d a n d f urt her d ose escalat i on m ust 
n ot occ ur.
 
I n t his case, t he D E C will re vie w t he t otalit y of  data a n d restart of d osi n g is 
p ossi ble wit h o ut a s u bsta nt ial a me n d me nt (e g, i n t he case of a la b orat or y err or) if 
D E C re vie w c o ncl u des t hat t he rele va nt st o p pi n g criteri o n was n ot f ulfille d. 
 
A l ower d ose l e vel e x pecte d t o be t olera ble a n d n ot t o meet t he st o p pi n g criteria, 
w o ul d be acce pta ble i n t his case.
 
If t he safety st o p pin g cri t eria are met a n d t he D E C deci des t hat t here are reas o ns 
t hat t he d ose le vel s h o ul d be re peate d or f urt her d ose escalat i on is warra nte d a 
s u m mar y of t he data a n d j ust ificati on ( pr ot oc ol a me n d me nt) will be s u b mitte d t o 
t he Astra Ze neca Safet y Re vie w C o m mittee, t he I S R B, t he Re g ulat or y  Aut h ori t y 
a n d E C f or t heir a p pr o val bef ore f urt her d osi n g.
 
I n s o me circ u msta nces, c o nsi derati on ca n be gi ve n t o test fracti o nate d or s plit d oses.
3. 2. 7. 4. 
Bli n di n g at D ose Esc al ati o n C o m mittee Meeti n g
I nitiall y, t he data will be re vie we d bli n de d, b ut if t he PI or t he D E C c o nsi der it necessar y  
d ue t o a safet y c o ncer n, eit her i n di vi d ual p arti ci pa nt s or t he e ntire c o h ort ma y be u n bli n de d 
t o usi n g c o de brea k e n vel o pes t o e na ble decisi o n- ma ki n g. T he c o de will be br o ke n 
acc or di n g t o l ocal S O Ps.
3. 2. 7. 5. 
Assess me nts A d a pt ati o n
F o ll owi n g re vie w of data fr o m a c o h ort of parti ci pa nt s, t he ti mi n g of assess me nts a n d/ or 
bl o o d sa m ple s ma y b e a djuste d f or s u bse q ue nt c o h orts.
A d dit i onal assess me nt or sa m pli n g t i mes ma y be a d de d if i n dicate d b y  t he data; h o we ver, 
t he ma xi m u m bl o o d v ol u me ta ke n fr o m eac h partici pa nt will n ot e xcee d 2 4 0. 2 m L f or 
parti ci pa nts i n t he I V gr o u p a n d 2 3 0. 2 m L f or participa nts i n t he I M gr o u p .
3. 3. 
De gree of U ncert ai nt y
At  t he ti me of t his C S P, n o cli nical st u dies ha ve yet bee n c o n d ucte d wit h A Z D 7 4 4 2. 
O verall, it is c o nsi dere d t hat t he A Z D 7 4 4 2 n o n -cli nical data a vaila ble t o date a n d cli nical 
data fr o m  si milar c o m p o u n ds, al o n g wit h t he se nt i nel d osi n g strate g y a n d a p pr o priate 
cli nical m o nit ori n g a p plie d i n t he st u d y, pr o vide c o nfi de nce t hat t he ris k t o s u bjects will be 
mi ni mi se d. T he n o n -cli nical t o xic ol o g y st u dies are o n g oi n g .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
3. 3. 1. 
Se nti nel D osi n g
D osi n g f or all co h ort s will be i nit iate d wit h t wo partici pa nt s i n a se nti nel c o h ort, s uc h t hat 
o ne partici pa nt will be ra n d o mise d t o recei ve place b o a n d o ne parti ci pa nt will be 
ra n d omise d t o recei ve A Z D 7 4 4 2. T he safety data fr o m  t he se nti nel parti ci pa nt s u p t o 
2 4 h o urs p ost -d ose will be re vie we d b y t he PI bef o re t he re mai ni n g parti ci pa nt s i n t he 
c o h ort are d ose d. T he re mai ni n g 1 0 parti ci pa nt s for eac h c o h ort will be d ose d at least 
2 4 h o urs after t he se nt i nel c o h ort at a rati o of 9: 1 acti ve t o place b o.
3. 3. 2. 
C o- a d mi nistr ati o n of M o n ocl o n al A nti b o dies
Mi xi n g t he m A bs pri or t o d osi n g, a n d c o -a d mi nisteri n g t he m A bs as a si n gle I V i nf usi o n, 
offers a si m plifie d pr ocess f or a d mi nisteri n g A Z D 7 4 4 2 , a n d all o ws f or a faster i nf usi on 
rate, s h orte ni n g t he ti me nee de d f or d osi n g. I ntra ve n o us c o- a d mi nistrati o n of t he m A bs 
will be perf or me d i n t his st u d y  o nl y after t heir se q ue ntial a d mi nistrati o n has bee n teste d 
a n d o bser ve d t o ha ve ha d a n acce pta ble safet y pr ofile. I nstr uctio ns f or d osi n g are pr o vi de d 
i n t he p har mac y m a n ual.
3. 4. 
Ris k -B e n efit a n d Et hic al Assess me nt
3. 4. 1. 
Descri pti o n of A Z D 7 4 4 2
A Z D 7 4 4 2 is a c o m bi nat i on of t wo rec o m bi na nt h u ma n I g G 1 κ m A bs, A Z D 8 8 9 5 a n d 
A Z D 1 0 6 1, di recte d a gai nst t he R B D of t he s pi ke pr otei n of S A R S-C o V - 2. A Z D 7 4 4 2 is 
c o mprise d of t he 2 m A bs t o mi ni mis e t he p ote ntial of vir us mut ati o nal  esca pe. A Z D 8 8 9 5 
a n d A Z D 1 0 6 1 m A bs ha ve bee n e n gi neere d wit h tri ple a mi n o aci d s u bstit uti o ns 
M 2 5 2 Y/ S 2 5 4 T/ T 2 5 6 E ( Y T E) i n t he Fc re gi o n t o pr ol o n g t he t 1/ 2, w hic h is e x pecte d t o 
pr o vi de pr otecti o n f r o m C O VI D- 1 9 f or a d uratio n of  at least 5 mo nt hs. I n a d di tio n, t he 
triple a mi n o aci d s u bst ituti o ns L 2 3 4 F/ L 2 3 5 E/ P 3 3 1 S ( T M) i n t he Fc re gi o n were 
e n gi neere d f or b ot h A Z D 8 8 9 5 a n d A Z D 1 0 6 1 t o a br o gate Fc- me d iate d effect or f u ncti on, 
w hic h is e x pecte d t o re d uce p ote ntial ris k of  a nt i b o d y-de pe n de nt e n ha nce me nt of disease .
3. 4. 2. 
M o de of Acti o n
3. 4. 2. 1. 
Pri m ar y P h ar m ac o d y n a mics
A Z D 7 4 4 2 c o nsist s of  t w o se parate m A bs w hic h bi n d t o dist i nct, n o n-o verla p pi n g sites o n 
t he S A R S -C o V -2's s pi ke pr otei n's rece pt or bi n di n g d o mai n. Bi n di n g t o eit her of t hese sites 
bl oc ks t he vir us's a bilit y t o bi n d t o its h u ma n cell ular rece pt or, A C E 2. B y  bloc ki n g vir us 
e ntr y int o h u ma n cells, A Z D 7 4 4 2 has t he p ote ntial t o pre ve nt or treat ill ness d ue t o 
S A R S -C o V -2 i nfect i on, C O VI D -1 9. A Z D 7 4 4 2 has n o h u ma n tar gets, a n d n o h u ma n 
p har mac o d y na mic effects are e x pecte d.
3. 4. 3. 
T o xic ol o g y Pre -cli nic al D at a
3. 4. 3. 1. 
T o xic ol o g y
A pre -cli nical safet y pr o gra m  incl u di n g assess me nt of tiss ue cr oss- reacti vity i n h u ma n a n d 
c y n o m o l g us m o n ke y t iss ues a n d a si n gle d ose t o xic ol o g y st u d y i n c y n om o l g us m on ke ys. 
As of 2 4 J ul y 2 0 2 0: T o date, n o pre/cli nical fi n di n gs i n dicat i n g ris ks t o partici pati n g 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
parti ci pa nt s were o bser ve d. Assess me nt of tiss ue cr oss-reacti vity of  AZ D 7 4 4 2 a n d t he 
i n di vi d ual a nti b o dies A Z D 8 8 9 5 a n d A Z D 1 0 6 1 t o h u ma n a n d c y n om o l g us m o n ke y tiss ues 
is o n g oi n g. Res ults t o date de m o nstrate d n o bi n di n g of A Z D 7 4 4 2 or its i n di vi d ual 
c o mp o ne nts t o a n y  hu ma n tiss ue. Assess me nt of bi n di n g t o c y n o m ol g us m o n ke y t iss ues is 
pe n di n g. T he si n gle d ose t o xicit y st u d y  in c y n o m o l g us m on ke ys is o n g o i n g.
F urt her i nf o r mat i on o n pre -cli nical fi n di n gs is a vaila ble i n t he I B [ 6].
3. 4. 4. 
Cli nic al St u dies
A Z D 7 4 4 2 has n ot bee n e val uate d i n cli nical st u dies pre vi o usl y. T his is a F T I H cli nical 
st u d y.
3. 4. 5. 
Ris k Assess me nt f or A Z D 7 4 4 2
F or A Z D 7 4 4 2, n o a d verse reacti o ns ha ve bee n i de nt ifie d yet d ue t o n o n -a vaila bilit y of 
cli nical data. A n y a d verse e ve nt t hat is dee me d t o be relate d t o t he I M P b y t he i n vest i gat or 
or t he c o m pa n y , w hic h is als o serio us will be treate d as a S U S A R a n d a p pr o priatel y 
e x pe dite d.
As n o cli nical data o n A Z D 7 4 4 2 is a vaila ble, t he safety preca uti o ns a n d t he st u d y  desi g n 
are base d o n pre vi o us Astra Ze neca e x perie nces of si milar m A bs (m A bs c o ntai ni n g t he 
Y T E s u bstit uti o n: nirse vi ma b , s u vrat o x u ma b, a n d m o ta viz u ma b; m A bs t hat c o ntai n T M 
su bst itut i on: i mfi nzi, a nifr ol uma b, a n d ol ecl u ma b). T he de vel o p me nt pr o gra m f or 
A Z D 7 4 4 2 rese m bles a plat f or m a p pr oac h as t he safety of  I g G 1 m A bs wit h either Y T E or 
T M s u bst ituti o ns has bee n pre vi o usl y  d e mo nstrate d i n cli nical trials.
Astra Ze neca c o nsi ders t hat t he data gat here d i n t he P hase 1 st u dies f or b ot h M E DI 4 8 9 3 
( mA b t hat bi n ds t he St a p hyl oc occ us a ure us alp ha t o xi n; s ur vat o x u ma b) a n d M E DI 8 8 9 7 
( mA b t hat bi n ds t he R S V f usi o n pr otei n; nirse vi ma b) s u p p ort usi n g safety data t o i nit iate 
f ut ure stu dies wit h A Z D 7 4 4 2 . Li ke A Z D 7 4 4 2, b ot h a nti b o dies d o n ot ha ve h u ma n h ost cell 
tar gets, a n d b ot h m A bs als o ha ve t he Y T E s u bstituti o ns i ntr o d uce d f or half -life e xte nsi on. 
S af et y f oll ow- u p i n b ot h st u dies was f or o ne y ear, w hic h is als o t he pla n ne d safet y 
F ol l ow- u p P eri o d f or A Z D 7 4 4 2. I n ge neral, i n b ot h pr o gra ms t he safety pr ofile o f t he 
m A bs, w het her a d mi nistere d I V or I M, was si milar t o t hat see n f or place b o.
I n t he M E DI 4 8 9 3 P hase 1 st u d y, t he i ncide nce of T E A Es was n ot ele vate d i n partici pa nt s 
w h o recei ve d t he m A b c o m pare d t o place b o partici pa nt s. I n a d ditio n, n o gra de 3 or hi g her 
T E A Es or T E S A Es were rec or de d a n d n o partici pa nts di sc o nti n ue d fr om t he st u d y d ue t o a 
T E A E.
I n t he M E DI 8 8 9 7 P hase 1 st u d y, t he o verall i nci de nce of T E A Es was si milar i n m A b 
recipie nts c o m pare d t o pl ace b o recipie nts, a n d w hile t here were t hree e ve nts t hat were 
classifie d as eit her Gra de 3 T E A Es or as T E S A Es i n parti ci pa nt s w h o recei ve d 3 0 0 m g of 
M E DI 8 8 9 7 I M (e y e i nj ur y, g u ns h ot w o u n d a n d a p pe n dicitis), t hese e ve nts were n ot 
c o nsi dere d relate d t o recei pt of I M P. N o partici pa nt s disc o nti n ue d fr om t he st u d y d ue t o a 
T E A E.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Base d o n t his, t he safet y i nf or mati on a vaila ble t o date s u p p orti n g d osi n g i n t he F TI H tri al 
is c o nsi dere d a p pr o priate a n d t he ris k f or a n y u n desire d a d verse effects is c o nsi dere d l o w.
F urt her, t he F TI H st u d y  desi g n wit h t he safet y preca utio ns o utli ne d bel o w is c o nsi dere d 
a p pr o priate a n d i n li ne wit h F TI H g ui deli nes.
T he pl a n ne d d osi n g sc he me f or t his st u d y has bee n desig ne d t o test a ra n ge of d oses bei n g 
c o nsi dere d f or pr o p h yla xis a n d/ or treat me nt, w hile escalati n g d oses i n a c o ntr olle d ma n ner.
O verall, it is c o nsi dere d t hat t he A Z D 7 4 4 2 n o ncli nical data a vaila ble t o date a n d cli nical 
d ata fr o m si milar c om p o u n ds al o n g wit h t he se nt i nel d osi n g strate g y a n d a p pr o priate 
cli nical m o nit ori n g a p plie d i n t he F TI H st u d y pr o vi de c o nfi de nce t hat t he ris k t o healt h y 
v o l unt eers will be mi ni mise d.
3. 4. 6. 
Ris k Assess me nt f or C O VI D -1 9 P a n de mic
T he re g ul at or y a ut h orities ha ve iss ue d ne w g ui deli nes t hat ai m t o pr o vi de 
rec o m me n dati ons f or actio ns f or c o n d uct of cli nical st u dies of me dical pr o d ucts d uri n g 
C O VI D -1 9 pa n de mic [ 9]. Si nce t he pa n de mic sit uati on is e v ol vi n g, g ui deli nes, 
rec o m me n dati ons, nati o nal la ws , a n d l ocal restrict i o ns ma y c ha n ge at hi g h pace. Gi ve n t he 
circ u msta nces of p ote ntiall y rela psi n g pa n de mic or e pi de mic sit uati o n with re gar d t o t he 
s prea d of C O VI D- 1 9 i n f ut ure, s pecial atte nti o n will be pai d t o pr otect partici pa nt s i n t he 
st u d y a n d site staff i n v ol ve d i n t he i n vesti gati o ns a gai nst i nfecti on wi t h S A R S-C o V -2 as 
re q ueste d b y t he ne wl y iss ue d M H R A g ui deli nes.
Meas ures t o mit i gate p ossi ble ris ks ca use d b y S A R S-C o V -2 are:
 
C urre nt nati o nal la ws a n d l ocal rec o m me n dat i ons f or pre ve nt i on of pa n de mic will be 
strict l y a d here d t o.
 
C O VI D -1 9 ser ol o g y  t estin g will be perf or me d at Scree ni n g.
 
Ne gati ve S A R S -C o V - 2 qR T -P C R test is re q uire d f or a d missi o n.
 
F urt her C O VI D -1 9 testi n g d uri n g t he st u d y , i ncl u di n g F ol l ow - u p Perio d ca n be 
perf or m e d as per PI’s discreti o n.
 
Parti cipa nt s will be cl osel y m o nit ore d f or a n y si g ns a n d s y m pt o ms of S A R S -C o V -2, 
i ncl u di n g fe ver, dr y c o u g h, d ys p n oea, s ore t hr oat a n d fati g ue t hro u g h o ut t he st u d y . 
O nce cli nical si g ns o f i nfecti on are re p orte d b y  parti ci pa nt s, t he PI nee ds t o deter mi ne 
w het her sa m ples ca n be c o llecte d, a n d safety data ca n be rec or de d o n site. I n s uc h 
circ u msta nces, if sa m ples ca n n ot be c ollecte d o n site, e ver y eff ort s h o uld be ma de t o 
c ollect sc he d ule d sa m ples off-site i n a ma n ner safe f or staff a n d parti ci pa nt s. If n ot, 
A Es a n d c o nc o mit a nt me dicat i ons will be o btai ne d via p h o ne calls. Dail y or al
t e mperat ure m eas ure me nts d uri n g i n-h o use sta y  a n d o ut patie nt visits will be 
i m ple me nte d.
 
C o nfir mati o n o f S A R S -C o V -2 i nfect i on b y o pti o n al  la b orat or y assess me nt will be 
c o n d ucte d base d o n a vaila bilit y (test ca pacit y a n d t ur nar o u n d ti me) of a p pr o ve d tests
a n d at PI’s discreti o n.
 
T he pr o ba bilit y of  vir us tra ns missi o n will be c o ntr olle d as m uc h as p ossi ble b y:

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 
A d vice f or partici pa nt t o a d here t o l ocal re q uire me nts f or re d ucti o n of t he p u blic 
e x p os ure w hile a m b ulat or y.
 
T he E P C U will i ncl u de a d dit i onal preca ut i onar y  a n d safety me as ures i n t his 
st u d y, s uc h as s ocial dista nci n g, t he use of P P E f or b ot h staff a n d v ol u nteers t o 
re d uce t he ris k of S A R S-C o V -2 i nfect i on g ui de d b y  lo c al re q uire me nts a n d 
c urre nt g o ver n me nt a d vice .
 
I nf or mat i on o n C O VI D -1 9 c o nsi derat i ons, testi n g a n d preca ut i onar y  u nit 
meas ures are descri be d i n U nit s pecific C o nse nt f or m w hic h is a p pr o ve d b y t he 
ge neric E C. T he st u d y parti ci pa nt s will be c o nse nte d wit h t he U nit s pecific 
C o nse nt f or m  in a d dit i on t o t he st u d y s pecific C o nse nt f or m.
 
C o nfir me d a n d s us pecte d S A R S -C o V -2 i nfect i on a n d C O VI D -1 9 will be rec or de d i n 
t he a d verse e ve nt fiel ds.
 
Parti cipa nt s ma y be with dra w n b y t he PI base d o n disc ussi o n wi t h t he S p o ns or a n d 
Lea d P h ysicia n u n der t he f o ll owi n g ci rc u msta nces:
 
A n y c o nfir me d C O VI D -1 9 case t hat warra nts disc o nti n uat i on i n t he j u d ge me nt of  
t he PI or S p o ns or t o pr otect t he safet y of  t he parti ci pa nt , ot her st u d y partici pa nts 
or st u d y  site staff. Parti ci pa nt s t hat are wit h dra w n d ue t o c o nfir me d C O VI D- 1 9 
case will be f o ll owe d u p u nt il t he fi nal o utc o m e of t he A E .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
4. 
S T U D Y P O P U L A TI O N
4. 1. 
Selecti o n of St u d y P o p ul ati o n
T he PI s h o uld kee p a partici pa nt scree ni n g l o g of all p ote ntial parti ci pa nt s w h o c o nse nte d 
a n d were s u bjecte d t o scree ni n g pr oce d ures.
Parti cipa nt s w h o fail t o meet t he i ncl usi o n cri t eria or meet a n y e xcl usio n  crit erio n s h o ul d 
n ot, u n der a n y  circ u msta nces, be ra n d o mise d i nt o t he st u d y. T here ca n be n o e xce pti o ns t o 
t his r ule.
T his st u d y  will be c o n d ucte d o n male a n d fe male parti ci pa nt s. T he st u d y  ma y n ot 
n ecessaril y be bala nce d re gar di n g ge n der. T he st u d y  was n ot f or mall y p o were d t o detect 
differe nces bet wee n ge n ders f or t he pri mar y e n d p oi nt. It is n ot pla n ne d t o perf or m 
s u b-a nal yses o n ge n der.
4. 1. 1. 
I ncl usi o n Criteri a
F or i ncl usi o n i n t he st u d y parti ci pa nt s s h o ul d f ulfil all of t he f o ll owi n g cri t eria:
1 
A ge d 1 8 t hr o u g h 5 5 y ears ( b ot h i ncl usi ve) at t he ti me of scree ni n g.
2 
Wr itte n i nf or me d c o nse nt a n d a n y lo c all y re q uire d a ut h orisat i on o btai ne d fr o m t he 
parti ci pa nt pri or t o perf or mi n g a n y  C S P -r elate d pr oce d ures, i ncl u di n g scree ni n g 
e val uat i ons.
3 
Ne gati ve S A R S -C o V -2 q R T -P C R a n d / or ser ol o g y tests pri or t o ra n d o misati o n.
4 
Wei g ht ≥ 5 0 k g a n d ≤ 1 1 0 k g at scree ni n g, i ncl u di n g a B MI of ≥1 8. 0 t o ≤3 0. 0 k g/ m 2.
5 
Heal t h y b y me dical hist or y, p h ysical e xa mi nati on, a n d baseli ne s afet y la b orat or y 
st u dies, acc or di n g t o t he j u d g e me nt of  t he PI.
6 
Electr ocar di o gra m wit h o ut cli nicall y  si g nifica nt a b n or malit ies at scree ni n g.
7 
A ble t o c o m plete t he F oll o w - u p Perio d t hr o u g h Da y  3 61 as re q uire d b y t he C S P .
8 
Fe males of c hil d beari n g p ote ntial w h o are se x uall y acti ve wit h a n o n-sterilise d male 
part ner m ust ha ve use d a sta ble a n d hi g hl y effect i ve met h o d of c o ntrace pti o n f or at 
least 3 m o nt hs pri or t o d osi n g wit h I M P a n d m ust a gree t o c o nti n ue usi n g s uc h 
preca uti o ns u nt il 3 6 0 da ys after t he d ose of  I M P. Perio di c a bst i ne nce, t he r h yt h m 
met h o d, a n d t he wit h dra wal met h o d are n ot acce pta ble met h o ds of c o ntrace pti o n.

Fe males of n o n- c hil d beari n g p ote ntial are defi ne d as t h ose w h o are s ur gicall y 
sterile (ie, bilateral sal pi n gect o m y, bilateral o o p h orect om y, or c o m plete 
h ysterect o m y) or p ost me n o pa usal defi ne d as 1 2 m o nt hs wit h n o me nses wit h o ut a n 
alter nati ve me dical ca use a n d c o nfir me d b y F S H i n p ost me n o pa usal ra n ge.

A hi g hl y effect i ve met h o d of c o ntrace pti o n is defi ne d as o ne t hat res ults i n a l o w 
fail ure rate (ie, less t ha n 1 % per year) w he n use d c o nsiste nt l y a n d c orrectl y (see 
Secti o n  4. 2. 1. 2 ). 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
4. 1. 2. 
E xcl usi o n Criteri a
Parti cipa nt s m ust n ot be ra n d o mise d i n t he st u d y if a n y of t he foll o wi n g e xcl usi o n criteria 
are f ulfille d:
1 
K n o w n h y perse nsit i vity t o a n y  c o mp o ne nt of t he I M P.
2 
Hi st or y of aller gic disease or reactio ns li kel y  t o be e xacer bate d b y a n y c o mp o ne nt of 
t he I M P.
3 
Pre vi o us h y perse nsit i vity,  inf usi o n -r elate d reactio n or se vere a d verse react i on 
f oll owi n g a d mi nistrati o n of a m A bs .
4 
Ac ute (ti me -li mite d) ill ness, i ncl u di n g fe ver a b o ve 3 7. 5° C ( 9 9. 5 F), o n da y prior t o or 
d a y  of pla n ne d d osi n g; parti ci pa nt s e xcl u de d f or transie nt ac ute ill ness ma y be d ose d 
if ill ness res ol ves wit hi n t he 27 -da y  S cree ni n g P eri o d or ma y be rescree ne d o nce.
5 
A n y dr u g t hera p y  wit hi n 7 da ys pri or t o Da y 1 (e xce pt c o ntrace pti ves or a si n gle use 
of  aceta mi n o p he n, as piri n, a nti hista mi ne, or c o m bi nati on O T C pr o d uct t hat c o ntai ns 
aceta mi n o p he n wit h a n a nt i hista mi ne, or O T C n o nster oi dal a nti-i nfla m mat or y a ge nt at 
a d ose e q ual t o or l o wer t ha n t hat rec o m me n de d o n t he pac ka ge). Vita mi ns a n d ot her 
n utri tio nal s u p ple me nts t hat are n ot ne wl y  int r o d uce d, ie, ha ve bee n ta ke n f or at least 
3 0 da y s prior t o e nr ol m e nt, are n ot e xcl usi o nar y .
6 
Bl o o d dra w n i n e xcess of a t otal of 4 5 0 m L ( 1 u nit) f or a n y  reas o n wit hi n 2 mo nt hs 
pri or t o scree ni n g.
7 
Recei pt of i m m u n o gl o b uli n or bl o o d pr o d ucts wit hi n 6 m o nt hs pri or t o scree ni n g.
8 
S A R S -C o V -2 or C O VI D - 1 9:
a.
Parti cipa nt s wit h a n y c o nfir me d c urre nt or pre vi o us C O VI D-1 9 i nfect i on bef ore 
ra n d omisat i on.
b.
Parti cipa nt has cli nical si g ns a n d s y m pt o ms c o nsiste nt wit h C O VI D -1 9, e g, fe ver, 
dr y  c o u g h, d ys p n oea, s ore t hr oat, fati g ue or c o nfir me d i nfecti on b y a p pr o priate 
la b orat or y test wit hi n t he last 4 wee ks pri or t o scree ni n g or o n a d missi on.
c.
A n y pri or recei pt of  in vest i gati onal or lice nse d vacci ne i n dicate d f or t he pre ve nt i on 
of  S A R S-C o V -2 or C O VI D - 1 9 or e x pecte d recei pt d uri n g t he peri o d of st u d y 
f oll ow- u p.
9 
Recei pt of a n y  I M P i n t he prece di n g 9 0 da ys or e x pecte d recei pt of I M P d uri n g t he 
p eri o d of  st u d y fol l ow -u p, or c o nc urre nt partici pati o n i n a n ot her i nter ve nt i onal st u d y.
1 0
Pre vi o us recei pt of a m A b wi t hi n 6 mo nt hs, or fi ve a nti b o d y  half-li ves ( w hic he ver is 
l on ger), pri or t o st u d y  start.
1 1
I mm u n o deficie nc y  d ue t o ill ness, i ncl u di n g HI V i nfecti on, or d ue t o dr u gs, i ncl u di n g 
a n y c o urse of gl uc oc ortic o i d t hera p y e xcee di n g 2 wee ks of pre d nis one or e q ui vale nt at 
a d ose of 2 0 m g dail y or e ver y ot her day wi t hi n 6 m ont hs pri or t o scree ni n g. HI V 
testi n g m ust be ne gati ve at scree ni n g.
1 2
Ei t her hist or y of acti ve i nfecti on wi t h he pat itis B or C or p ositi ve test f or he patitis C 
or f or he patit is B s urface a nti ge n at scree ni n g.
1 3
Hi st or y of infecti o n wi t h S A R S or M ER S.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
1 4
As partate a mi n otra nsferase , AL T, or ser u m creati ni ne a b o ve t he U L N ; bilir u bi n a n d 
A L P > 1. 5 × U L N .
1 5
Hae m o gl o bi n or pl at elet c o u nt belo w t he L L N at scree ni n g. W hite bl o o d cell or 
ne utr o p hil c o u nt o utside n or m al refere nces ra n ges.
1 6
Hi st or y of mali g na nc y.
1 7
A n y la b orat or y  val ue i n t he scree ni n g pa nel t hat, i n t he o pi ni o n of t he PI, is cli nicall y 
sig nifica nt or mi g ht c o nf o u n d a nal ysis of st u d y  r es ults.
1 8
Pre g na nt or n ursi n g fe male.
1 9
Hi st or y of alc o h ol or dr u g a b use wit hi n t he past 2 years t hat, acc or di n g t o t he PI , 
mi g ht affect assess me nts of safet y or a bili t y of partici pa nt t o c o mpl y  wit h all st u d y 
re q uire me nts O R p ositive uri ne dr u g or al c o h o l scree ni n g.
2 0
A n y c o n dit i on t hat, i n t he o pi ni o n of t he PI , mi g ht c o m pr omise parti ci pa nt safety or 
i nterfere wit h e valu ati o n o f t he I M P or i nter pretati o n of parti ci pa nt safety or s t u d y 
res ults.
2 1
E m pl o y ees of t he s p o ns or, cli nical st u d y site, or a n y ot her i n di vi d uals i n v ol ve d with 
t he c o n d uct of t he st u d y, or i m me diate fa mil y me m bers of s uc h i n di vi d uals.
2 2
A bse nce of s uita ble vei ns f or bl o o d sa m pli n g (I M a n d I V c o h orts) a n d a d mi nistrati o n 
of  I M P (I V c o h orts).
4. 2. 
Restricti o ns D uri n g t he St u d y
T he f o ll owi n g restri ct i ons a p pl y f or t he s pecifie d ti mes d uri n g t he st u d y  perio d:
1 
Parti cipa nt s s h o ul d rest c o mf orta bl y d uri n g t he I V i nf usi o n or lie s u pi ne f or a n h o ur 
after I M a d mi nistratio n. Parti ci pa nt s s h o ul d n ot e n ga ge i n a n y stre n u o us acti vity fr om 
7 2 h o urs pri or t o c hec k -i n u ntil disc har ge a n d 7 2 h o urs bef ore e ver y o ut patie nt visit 
a n d t heir fi nal F ollo w -u p Vi sit.
2 
Pri or t o t he Treat me nt Peri o d a n d o ut patie nt visits, partici pa nt s s h o uld a bstai n fr o m 
alc o h o l f or 7 2 h o urs pri or t o c hec k -i n u ntil after t heir last P K sa mpli n g visi t. 
Parti cipa nt s s h o ul d als o a bstai n fr om alc o h o l f or 7 2 h o urs bef or e t heir fi nal F o ll ow- u p 
Vi sit.
3 
Pri or t o t he Treat me nt Peri o d a n d o ut patie nt visits, partici pa nt s s h o uld a bstai n fr o m 
caffei ne c o ntai ni n g f o o ds a n d be vera ges f or 2 4 h o urs pri or t o c hec k -i n u ntil disc har ge 
fr om t he Cli nical U nit.
4 
D uri n g a d missi o n peri o d, par tici pa nt s will recei ve a sta n dar d diet, w hic h e xcl u des all 
alc o h o l a n d caffei nate d pr o d ucts.
5 
Pri or t o a d missi o n , partici pa nt s h o uld a v o i d f oo d c o ntai ni n g p o p p y  see ds f or at least 
7 2 h o urs .
6 
Parti cipa nt s will be re q uire d t o a bstai n fr o m bl o o d or plas ma d o nati on u ntil 3 m o nt hs 
after t he fi nal me dical e xa mi nati on at t he st u d y  Fol l ow- u p.
7 
Parti cipa nts are n ot re q ui re d t o a bstai n fr om f oo d a n d dri n k i nta ke pri or t o sa mple 
c ollect i on f or safety assess me nts.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
F or m e dicat i on restrict i ons, pl ease refer t o Secti o n 5. 5 .
4. 2. 1. 
Re pr o d ucti ve Restricti o ns
4. 2. 1. 1. 
W o me n of N o n -C hil d be ari n g P ote nti al
W o me n of n o n -c hil d beari n g p ote ntial are defi ne d as fe male parti ci pa nt s w h o are 
p er ma ne nt l y s ur gicall y sterilise d or p ost me n o pa usal.
P er m a ne nt sterilisat i on i ncl u des h ysterect o m y a n d/ or bilateral o o p h orect o m y a n d/ or 
bilateral  sal pi n gect o m y at least si x wee ks bef ore scree ni n g b ut e xcl u des bilateral t u bal 
li gati on. Bilateral o o p h orect o m y alo n e is acce pta ble o nl y w he n t he re pr o d ucti ve stat us of 
t he w o ma n has bee n c o nfir me d b y f o ll ow- u p h or m o ne le vel  assess me nt.
Fe males are c o nsi dere d p ost me n o pa usal if t he y ha ve ha d a me n orr hea f or at least 
1 2 m o nt hs or m or e f ol l owi n g cessat i on of all e x o ge n o us h or m o nal  tr e at me nts a n d wit ho ut 
a n alter nati ve me dical ca use a n d t he F S H le vel is i n t he p ost me n o pa usal ra n ge.
4. 2. 1. 2. 
W o me n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d of c hil d beari n g p ote ntial, ie, fertile, f oll owi n g m e narc he a n d u nt il 
bec o mi n g p ost me n o p a usal u nless per ma ne nt l y sterile. W ome n of c hil d beari n g p ote ntial 
w h o are se x uall y  acti ve must a gree t o use, wi t h t heir n o n- sterilise d male part ner, a n 
a p pr o ve d met h o d of hi g hl y effect i ve c o ntrace pti o n fr om t he ti me of I M P a d mi nistrati o n 
u nt il 3 6 0 da ys after t he d ose of I M P. W o me n s h o ul d be sta ble o n t heir c h ose n met h o d of 
birt h c o ntr ol f or at least 3 m o nt hs bef ore d osi n g.
Hi g hl y  effecti ve c o ntrace ptio n f or m  of birt h c o ntr ol, ie, a f or m of birt h c o ntr ol wit h a 
fail ure rate of less t ha n 1 % per year w he n use d c o nsiste nt l y a n d c orrectl y, w hic h are 
all o we d i n t his cli nical st u d y, are:
Met h o ds t hat ca n ac hie ve a fail ure rate of less t ha n 1 % per y ear w he n use d c o nsiste nt l y 
a n d c orrectl y are c o nsi dere d as hi g hl y effecti ve birt h c o n tr ol met h o ds. S uc h met h o ds 
i ncl u de:
 
C o m bi ne d ( oestr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wi t h in hi bit i on of o v ulati o n:
 
Oral
 
I ntra va gi nal
 
Tra ns der mal
 
Pr o gest o ge n -o nl y h or m o nal  c o ntrace ptio n ass oci ate d wit h in hi bit i on o f o v ul at i on:
 
Oral
 
I njecta ble
 
I mpla nta ble
 
I ntra uteri ne de vice

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
 
I ntra uteri ne h or m o ne- releasi n g s yste m
 
Bilateral t u bal occl usi o n
 
Vasect o mi se d part ner ( o nl y acce pta ble pr o vide d t hat part ner is t he s ole se x ual part ner 
of  t he partici pa nt a n d t hat t he vasect o mise d part ner has recei ve d me dical assess me nt 
of  t he s ur gical s uccess)
 
Se x ual a bst i ne nce is defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he 
e nt ire perio d of  ris k ass ociate d wit h t he st u d y treat me nts. It is o nl y acce pta ble if 
preferre d a n d us ual lifest yle o f t he partici pa nt .
I n a d diti on, a barrier met h o d m ust als o be use d ie, c o n d o m ( wit h o ut s per mici dal 
f oa m/ gel/fil m/crea m/s u p p osit or y or fat - or oil -c o ntai ni n g lu brica nt s); or occl usi ve ca p 
( dia p hra g m or cer vical/ va ult ca ps) wit h s per mici dal f oa m/ gel/fil m/crea m/s u p p osit or y .
Pre g n a nc y Testi n g
W o me n of c hil d beari n g p ote ntial ca n be i ncl u de d o nl y  after a ne gati ve, hi g hl y se nsit i ve 
ser u m pre g na nc y test. A d ditio nall y , uri ne pre g na nc y testi n g will be d o ne as per t he S o A 
(Ta ble 3- 1 , Ta ble 3 - 2, a n d Ta ble 3 - 3).
Pre g n a nc y
If t he parti ci pa nt bec o me s pre g na nt d uri n g t he st u d y t his s h o ul d be re p orte d t o t he PI . T he 
PI s h o ul d als o be n otifie d of pre g na nc y occ urri n g d uri n g t he st u d y b ut c o nfir me d after 
c o mplet i on of t he st u d y . T he pre g na nc y will be f ollo we d, a n d t he stat us of m ot h er a n d/ or 
c hil d will be re p orte d t o t he S p o ns or after deli ver y.
A pre g na nc y  notificat i on f or m a n d fol l ow- u p will be c o m plete d. Pre g na nc y occ urri n g a n d 
re p orte d d uri n g t he st u d y will be f oll owe d u p f or safety fr om t he p ost -d ose a d mi nistrati o n 
t o e n d of t he st u d y or u ntil  t er m t o ide nt if y pre g na nc y o utc o me, w hic he ver is later. Fe male 
parti ci pa nts w h o bec o me pre g na nt after d osi n g will c o nti n ue t o ha ve all safet y, P K (ser u m 
a n d nasal fl ui d), A D A ser u m sa m ple, a n d ne utralisi n g a nti b o d y sa m ples c ollecte d. T hese 
d o n ot re prese nt a safety ris k, a n d ser u m sa m ples are alrea d y bei n g c ollecte d as part of 
safety f oll ow- u p. A n y c o m p licati ons d uri n g t he pla n ne d f o ll ow- u p of  a n y pre g na nt 
parti ci pa nt (if a n y) will be disc usse d bet wee n t he PI a n d Astra Ze neca, a n d a decisi on t o 
hal t or c o nti n ue a n y f urt her sa m pli n g will be ma de o n a case- b y-case basis.
O v a D o n ati o n
Fe m ale partici pa nts s h o uld n ot d o nate o va f or 3 6 0 da ys after t he I M P d ose .
4. 2. 1. 3. 
M ale P artici p a nt s
Restricti o ns f or M ale P artici p a nts
T here i s n o i nf or mati o n a b o ut effects t hat A Z D 7 4 4 2 c o ul d ha ve o n t he de vel o p me nt of t he 
f oet us i n h u ma ns. T heref ore, it is i m p orta nt t hat w o me n of c hil d beari n g p ote ntial, w h o are 
t he part ners of male partici pa nt s, d o n ot bec o me pre g na nt d uri n g t he st u d y a n d f or a t otal 
p eri o d of  3 6 0 da ys after t he male parti ci pa nt has a recei ve d t he I M P.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Male parti ci pa nt s w h o ha ve bee n sterilise d are re q uire d t o use o ne barrier met h o d of 
c o ntrace pti o n (c o n d o m) fr o m t he ti me of I M P a d mi nistrati o n u nt il after t he F ol l ow- u p 
V isit. T he parti ci pa nt m ust ha ve recei ve d me dical assess me nt of t he s ur gical s uccess.
As a preca uti o n, all n o n -sterilise d male parti ci pa nt s s h o ul d a v oi d fatheri n g a c hil d b y 
eit her tr ue a bsti ne nce 1 or use a c o n d o m a n d t heir fe male part ner/s p o use has t o be eit her of 
n o n- c hil d beari n g p ote ntial or has t o use a hi g hl y effecti ve c o ntrace pti o n f or m of birt h 
c o ntr ol, starti n g fr o m t he ti me of I M P a d mi nistrati o n u ntil 3 m o nt hs after t he st u d y 
F ol l ow- u p V isit. T he fe male part ner/s p o use of  t he male partici pa nt s h o ul d be sta ble o n 
t heir c h ose n met h o d of birt h c o ntr ol f or least 3 m o nt hs pri or t o d osi n g with I M P a n d m ust 
a gree t o c o nti n ue usi n g s uc h preca ut i ons u ntil 3 6 0 da ys after t he d ose of I M P .
Hi g hl y  effecti ve c o ntrace pti o n f or m of birt h c o ntr ol, ie, a f or m of birt h c o ntr ol wit h a 
fail ure rate of less t ha n 1 % per year w he n use d c o nsiste nt l y a n d c orrectl y, are:
 
C o m bi ne d ( o estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wi t h in hi bit i on of o v ulati o n:
 
Oral
 
I ntra va gi nal
 
Tra ns der mal
 
Pr o gest o ge n -o nl y h or m o nal  c o ntrace pti o n ass ociate d wit h i n hi bit i on o f o v ul at i on:
 
Oral
 
I njecta ble
 
I mpla nta ble
 
I U D
 
I U S
 
Bilateral t u bal occl usi o n of fe male part ner
S per m D o n ati o n
Male parti ci pa nt s s h o ul d n ot d o nate s per m f or t he d urati o n of t he st u d y a n d for at l east 
3 m o nt hs after t he st u d y F o ll ow- u p Visi t.
Pre g n a nc y
Parti cipa nt s will be i nstr ucte d t hat if t heir part ner bec o mes pre g na nt d uri n g t he st u d y t his 
s h o uld be re p orte d t o t he PI . T he PI s h o ul d als o be n otifie d of pre g na nc y occ urri n g d uri n g 
t he st u d y b ut c o nfir me d after c o mplet i on of  t he st u d y. I n t he e ve nt t hat a partici pa nt ’s 
part ner i s s u bse q ue ntl y f ou n d t o be pre g na nt after t he v ol u nteer is i ncl u de d i n t he st u d y , 
t he n c o nse nt will be s o u g ht fr o m t he part ner a n d if gra nte d a n y pre g na nc y will be 
                                               
1 Se x ual a bsti ne nce is defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k 
ass ociate d wit h t he st u d y treat me nts. It is o nl y acce pta ble if preferre d a n d us ual lifest yle of t he partici pa nt .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
f oll owe d , a n d t he stat us of m ot her a n d/ or c hil d will be re p orte d t o t he S p o ns or after 
deli ver y .
A pre g na nc y  notificat i on f or m a n d fol l ow- u p will be c o m plete d.
4. 3. 
Re pl ace me nt of P artici p a nt s
Parti cipa nt s w h o are wit h dra w n fr o m t he st u d y, for a n y  reas o n, will n ot be re place d.
Rescree ne d partici pa nts will be pr o vi de d wi t h ne w r u n-i n n u m bers, h o we ver, will ha ve t he 
sa me partici pa nt I D.
4. 4. 
I nteri m A n al ysis
T here will be f our u n bli n de d i nteri m a nal yses. T he first will assess data fr o m C o h ort 1a 
a n d C o h ort 1 b o nce all partici pa nts i n th ose t w o c o h orts ha ve c o m plete d t heir Da y  8 visit. 
T he sec o n d will assess c u m ulati ve data fr o m all c o h orts o nce all partici pa nts i n C o h ort 4
ha ve c o m p lete d t heir Da y 8 visit. T he t hi r d i nteri m a nal ysis will  assess all a vaila ble data
fr om all c o h orts o nce all partici pa nts i n C o h ort 4 ha ve c o m p lete d t heir Da y 1 5 1 visit . T he 
f ourt h i nteri m a nal ysis will assess data fr o m all c o h orts o nce all partici pa nts ha ve 
c o mplete d t hei r D a y 2 1 1 visit a n d partici pa nts a n d C o h ort 1a a n d C o h ort 1 b ha ve
c o mplete d t heir Da y 2 7 1 visit . T he res ults of t hese a nal yses will be use d t o assist 
Astra Ze neca ’s i nter nal o perati o nal pla n ni n g. T he pri mar y a nal ysis will be c o n d ucte d w he n 
all treate d partici pa nts f or eac h pla n ne d a nal ysis ha ve c om p lete d f oll ow- u p t hr o u g h 
Da y 3 1. All  a vaila ble data at t he ti me of data c ut -off will be i ncl u de d i n t he i nteri m 
a nal yses. T he u n bli n de d safet y,  P K, A D A data ( A D A data if a vaila ble), ne utralisi n g 
a nt i b o d y a n d nasal fl ui d data will be use d t o deter mi ne w het her t o i nit iate a P hase 2/ 3 
pr o p h yla xis st u d y  in br oa der p o p ulat i ons . Astra Ze neca pers o n nel, ass ociate d pers o n nel at 
t he C R O c o n d ucti n g t he st u d y a n d t he testin g la b orat ories will be u n bli n de d as nee de d t o 
perf or m  t he a nal ysis a n d pla n ni n g. U n bli n de d data ma y be s hare d wit h re g ulat or y a ge ncies 
a n d ot her parties f or t he de vel o p me nt pr o gra ms, as nee de d, i n re g ulat or y a p plicati o ns a n d 
ot her de vel o p me nt -re q uire d c orres p o n de nce. It is a ntici pate d t hat st u d y site pers o n nel a n d 
parti ci pa nt s will re mai n bli n de d.
T he res ults will be base d o n clea n data a n d n o mi nal t i mes will be use d f or t he deri vati o n of 
t he ser u m P K para meters.
A s u bset of t he o ut p uts t hat will be re q uire d f or t he i nteri m a nal yses will be i de nt ifie d i n 
t he ta ble, listi n gs, a n d fi g ures s hells of t his st u d y a n d t he res ults will be pr o vi de d o nl y o n 
w hic he ver data is a vaila ble.
Pare xel will n ot be res p o nsi ble f or t he i nteri m cli nical st u d y  re p orts.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
5. 
S T U D Y C O N D U C T
5. 1. 
P artici p a nt E n r ol me nt a n d R a n d o misati o n
T he PI will e ns ure:
 
Si g ne d i nf or me d c o nse nt is o btai ne d fr o m eac h p ote nt ial parti ci pa nt bef ore a n y st u d y
s pecific pr oce d ures are perf or me d.
 
Eac h p ote ntial partici pa nt is assi g ne d a u ni q ue e nr ol me nt n u m ber at Scree ni n g u p o n
sig ni n g t he I C F.
 
T he eli gi bilit y of  eac h parti ci pa nt is i n acc or da nce wit h t he i ncl usi on a n d e xcl usi o n
criteria.
 
Eac h el i gi ble partici pa nt is assi g ne d a u ni q ue ra n d o misat i on c o de ( partici pa nt
n u m ber).
Ra n d o mi sat i on will be d o ne o n Da y  1.
Ra n d o mi sat i on c o des will be assi g ne d strict l y se q ue ntiall y as parti ci pa nt s bec ome eli gi ble 
f or ra n d o misat i on, starti n g fr o m e g, 1 0 1 (c o de s t o be use d with o ut l ea di n g zer o [s]).
W he n usi n g u ni q ue e nr ol me nt n u m ber, t he s pecific f or mat m ust be f o ll owe d (ie, re d uce d 
e nr o l me nt n u m ber, e g, “ 1 0 0 1” i n Cli n Base ™ a n d o n la bels, f ull e nr ol me nt n u m ber, e g, 
“ E 0 0 0 1 0 0 1” f or o ut p uts).
T here will be n o partici pa nt re place me nts.
5. 1. 1. 
Pr oce d ures f or R a n d o mi sati o n
U p o n c o m plet i on of t he ra n d o mi sat i on re q uire me nts s pecificat i ons f or m , t he 
ra n d omisat i on list a n d c o de brea k e n vel o pes f or eac h parti ci pa nt will be pr o d uce d b y  
Pare xel acc or di n g t o t he A Z Ra n d.
F or all co h ort s, sent i nel d osi n g will be a p plie d. Parti ci pa nt s will be ra n d o mise d t o 
A Z D 7 4 4 2 or place b o i n a rati o of 1: 1 f or t he se nt i nel gr o u p a n d 9: 1 i n t he re mai ni n g 
1 0 partici pa nt s of t he c o h ort s uc h t hat 1 0 o ut of 1 2 parti ci pa nt s i n eac h o verall c o h ort will 
recei ve A Z D 7 4 4 2 a n d 2 o ut of 1 2 will recei ve place b o.
T he ra n d omisat i on will  be c o mplete d f or eac h c o h ort usi n g c o nsec ut i ve ra n d omi satio n 
c o des.
Si nce a d ditio n al  c o h orts ma y be a d de d, ra n d omisati o n will i ncl u de a d dit i onal c o h orts 5, 6
a n d 7.
Parti cipa nt s will be assi g ne d as gi ve n i n Ta ble 5- 1 .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 6 of 1 0 3
T a ble 5- 1  
P artici p a nt R a n d o mi sati o n
C o h ort N u m ber
P artici p a nt s
1a
1 0 1 t o 1 1 2
1 b
2 0 1 t o 2 1 2
2
3 0 1 t o 3 1 2
3
4 0 1 t o 4 1 2
4
5 0 1 t o 5 1 2
5
6 0 1 t o 6 1 2
6
7 0 1 t o 7 1 2
7
8 0 1 t o 8 1 2
O nce a ra n d o mi sat i on n u m ber has bee n all o cate d t o o ne parti ci pa nt , it ma y n ot be assi g ne d 
t o a n ot her parti cipa nt .
5. 2. 
Pr oce d ures f or H a n dli n g I nc orrectl y R a n d o mi s e d P artici p a nt s
Parti cipa nt s w h o fail t o meet t he i ncl usi on cri t eria or meet a n y e xcl usio n  crit erio n s h o ul d 
n ot, u n der a n y  circ u msta nces, be ra n d o mise d i nto t he st u d y . T here ca n be n o e xce pti o ns t o 
t his r ule.
W here a parti ci pa nt , w h o d oes n ot meet t he select i o n criteria, is ra n d o mise d i n err or a n d 
t his is ide ntifie d bef ore d osi n g, t he partici pa nt s h o ul d be wit h dra w n fr om t he st u d y. If a 
parti ci pa nt is wit h dra w n pri or t o d osi n g t he y will be re place d.
If a parti ci pa nt , w h o d oes n ot meet t he select i on cri teria, has bee n d ose d bef ore t he err or is 
i de ntifie d, t he parti ci pa nt s h o uld be a d vise d t o c o nti n ue safet y assess me nts t o e ns ure t heir 
safety.  T he PI will i nf or m t he Astra Ze neca Lea d P h ysicia n o f t he err or.
5. 3. 
Bli n di n g a n d Pr oce d ures f or U n bli n di n g t he St u d y
5. 3. 1. 
Met h o ds f or E ns uri n g Bli n di n g
T his is a bli n de d st u d y  in w hic h t he parti cip a nts a n d I n vest i gat or are bli n de d t o I M P, a n d 
Astra Ze neca staff w h o are i n v ol ve d i n t he st u d y are u n bli n de d. U n bli n de d data ma y be 
s hare d wit h re g ulat or y a ge ncies a n d ot her parties f or t he de vel o p me nt pr o gra ms, as 
nee de d, i n re g ulat or y  a p plicati ons a n d ot her de vel o p m e nt -re q uire d c orres p o n de nce. As t his 
is a d ose escalati on st u d y , t he I n vesti gat or, st u d y site staff a n d partici pa nts will be bli n de d 
t o t he treat me nt all ocati o n ( A Z D 7 4 4 2 or place b o), b ut n ot t o t he d ose. T he D E C 
res p o nsi ble f or t he d ose escalati on decisi o ns after re vie w o f u p t o a n d i ncl u di n g Da y 8
safety data fr o m C o h ort 1 a, C o h ort 1 b, a n d C o h ort 2 wi ll als o re mai n bli n de d. T his 
c o m mittee i ncl u des t he Astra Ze neca Lea d P h ysicia n , t he Astra Ze neca Patie nt Safety 
P h ysicia n, a n d t he PI f or t he st u d y.
A Z D 7 4 4 2 a n d place b o will , as far as p ossi ble, be matc he d f or f or m ulat i on, a p peara nce, 
a n d a m o u nt. Parti ci pa nts ra n d omise d t o place b o will recei ve t he sa me v olu me of s o l uti on 
as parti ci pa nt s o n active treat m e nt. I n cases of t he I M i njecti on, s yrin ge ma s ki n g ma y be 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
re q uire d i n or der t o kee p t he bli n d ( p ossi bility of  sli g ht ye ll o wis h dis c ol o urati o n of  t he 
s us pe nsi o n f or I M i njecti on).
T he C o va nce p har mac o ki net icist will re mai n bli n de d d uri n g t he st u d y c o n d uct, u nless 
ot her wi se re q uire d base d o n st u d y fi n di n gs.
T he f oll owi n g pers o n nel will ha ve access t o t he ra n d omisat i on list fr o m st u d y start:
 
T he Astra Ze ne ca pers o n nel carr yi n g o ut t he la belli n g a n d pac ka gi n g of parti ci pa nt
s pecific treat me nts.
 
P har mac y  st aff pre pari n g t he I M P.
 
Bi oa nal y tic al staff a nal ysi n g perf or mi n g t he bi oa nal ysis of t he P K ser u m sa m ples, P K
nasal fl ui d sa m ples, a n d A D A ser u m sa m ples.
 
De d icate d u n bli n de d C o va nce P K  S cie nt ist perf or mi n g t he P K a nal yses f or t he i nteri m
a nal ysis a n d p ossi ble i n p ut i n t he D E C .
 
De di cate d u n bli n de d tea m ( Biost ati stical pr o gra m mers a n d st u d y Biost ati sticia n) fr om
Pare xel i n v o l ve d i n t he u n bli n de d i nteri m a nal yses.
 
De di cate d u n bli n de d Astra Ze neca pers o n nel i n v o l ve d i n a nal yses, a n d pre paratio n of
o ut p uts f or t he f or mal i nteri m a n d pr oject decisi o ns.
T he ra n d omisat i on list s h o ul d be ke pt i n a sec ure l ocati o n u ntil t he data base is l oc ke d.
5. 3. 2. 
Met h o ds f or U n bli n di n g t he St u d y
T he treat me nt c o de s h o ul d n ot be br o ke n, e xce pt i n me dical e mer ge ncies w he n t he 
a p pr o priate ma na ge me nt of t he partici pa nt re q uires k n o wle d ge of t he treat me nt 
ra n d omisat i on or re g ulat or y  re q uire me nts e xist (e g, f or S A Es), or t o e na ble pr o per 
g ui da nce t o a s u bject w h o wis hes t o recei ve a n a p pr o ve d vacci ne t o pr otect a gai nst 
i nfecti on wi t h S A R S-C o V - 2. If a n e mer ge nc y u n bli n di n g bec omes necessar y, t he PI c o uld 
brea k t he bli n d usi n g c o de brea k e n vel o pes f or a s pecific parti ci pa nt or c o m plete c o h or t 
a n d s h o uld n otif y  t he S p o ns or prior t o u n bli n di n g, if p ossi ble, u nless i de nt ificati on of t he 
I M P is re q uire d f or e mer ge nc y t hera pe utic me as ures. If a PI or partici pa nt is pre mat urel y 
u n bli n de d, t he partici pa nt ma y c o nti n ue t o be f o ll owe d i n t he cli nical st u d y f or safety,  P K, 
ne utralizi n g a nt i b o d y titers, a nti-dr u g a nti b o dies, a n d, i n fe male partici pa nts, m o nit ori n g 
f or de vel o p me nt of pre g na nc y. I n t he e ve nt t hat a partici pa nt wis hes t o wit h dra w 
c o mpletel y fr o m  t he st u d y after u n bli n di n g, ie, t he partici pa nt  wit hdra ws c o nse nt f or 
c o nti n ue d partici pati o n, t he n, de pe n de nt u p o n t he partici pa nt’s a gree me nt, a n d pr oce d ures 
acc o m pa n yi n g wit h dra wal are t o be perf or me d. T he decisi o n t o brea k t he bli n d will be 
ma de o n a case - b y-case basis a n d, if p ossi ble, s uc h e mer ge ncies are t o be disc usse d wit h 
Astra Ze neca pri or t o discl os ure of t he treat me nt all ocati o n. If t he bli n d is br o ke n, t he date, 
ti me a n d reas o n t o get her wit h t he i de ntity of  t he pers o n res p o nsi ble m ust be rec or de d i n 
Cli n Base ™
a n d a n y ass ociate d A E re p ort.
T he PI will d oc u me nt a n d re p ort t he acti o n t o Astra Ze neca staff.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Details o f t he c o de brea ki n g pr oce d ure will be pr o vi de d i n t he Safet y Re vie w a n d 
Ma na ge me nt Pla n.
5. 4. 
St u d y Tre at me nts
5. 4. 1. 
I de ntit y of t he I n vesti g ati o n al Me dici n al Pr o d uct
Details o n t he i de nt ity of  t he I M P are prese nte d i n Ta ble 5- 2.
T a ble 5- 2 
I de ntit y of t he I n vesti g ati o n al Me dici n al Pr o d uct
S u p plier:
A Z D 7 4 4 2 ( A Z D 8 8 9 5 + A Z D 1 0 6 1): Astra Ze neca.
Place b o/ Dil ue nt: 0. 9 % S o di u m C hl ori de ( P h. E ur. , Britis h 
P har mac o p oeia ): Pare xel.
F or m ulati o n:
Eac h vial of A Z D 8 8 9 5 a n d A Z D 1 0 6 1 is f or m ulate d as a sterile, w hite t o 
off -w h ite, l y o p hilise d p o w der, i n a glass vial, 1 5 0 m g. After 
rec o nstit uti o n i n sterile water f or i njecti o n/i nf usi o n; eac h vial yi el ds 
1 0 0 m g/ m L of acti ve i n gre die nt ( A Z D 8 8 9 5 or A Z D 1 0 6 1 ), 2 0 m M 
L- histi di ne/ L -histi di ne h y dr oc hl ori de, 2 4 0 m M s ucr ose, a n d 0. 0 4 % ( w/ v)
p ol y s or bate 8 0, at p H 6. 0.
Stre n gt h/c o nce ntrati o n:
S u p plie d as a p o w der f or s ol uti on f or i njecti o n/i nf usi o n . After 
rec o nstit uti o n, eac h vial c o ntai ns 1 0 0 m g/ m L A Z D 8 8 9 5 or 1 0 0 m g/ m L 
A Z D 1 0 6 1, wit h a u nit d ose stre n gt h of 1 5 0 m g A Z D 8 8 9 5 vial or 1 5 0 m g 
A Z D 1 0 6 1.
D ose:
A Z D 7 4 4 2 d oses ( c o m bi ne d d oses of A Z D 8 8 9 5 a n d A Z D 1 0 6 1 eac h 
re prese nts half of t he t otal d ose) t o be a d mi nistere d se q ue ntiall y are 
3 0 0 m g I M (direct gl uteal I M i njecti o ns) ( C o h ort 1a) , 3 0 0 m g I V 
( C o h ort 1 b) , 1 0 0 0 m g I V ( C o h ort 2) , a n d 3 0 0 0 m g I V ( C o h ort 3) at
2 0 m g/ mi n ute f or t he I V i nf usi o ns , a n d t he A Z D 7 4 4 2 d ose t o be 
c o-a d mi nistere d is 3 0 0 0 m g I V at 5 0 m g/ mi n ute ( C o h ort 4) f or t he I V 
i nf usi o n.
R o ute of a d mi nistrati o n:
I V i nf usi o n or I M i njecti o n.
S pecific de vice f or dr u g 
a d mi nistrati o n, if a p plica ble:
I V ba gs, li nes, a n d cat heters f or I V i nf usi o n as well as t he s yri n ges a n d 
nee dles f or i njecti o n will be pr o vi de d b y Pare xel.
Re gi me n:
Si n gle , se parate, se q ue ntial d oses as I V i nf usi o ns will be a d mi nistere d at
ma xi mal i nf usi o n rate of 2 0 m g/ mi n ute or direct I M i njecti o ns of eac h 
m A bs. A c o -a d mi nistere d d ose of b ot h m A bs mi xe d i n a si n gle I V 
i nf usi o n will be a d mi nistere d at a ma xi mal i nf usi o n rate of 5 0 m g/ mi n ute.
S pecial ha n dli n g re q uire me nts: 
Will be pr o vi de d i n a se parate d oc u me n t.
A vaila bilit y of t he I M P:
Will be s hi p pe d w he n a p pr o vals are i n place.
I M: i ntra m usc ular; I M P: i n vesti gati o nal me dici nal pr o d uct; I V: i ntra ve n o us; m A bs: m o n ocl o nal a nti b o dies.
Details o f t he batc h n u m bers will be i ncl u de d i n t he trial master file, p har mac y ma n ual,
a n d t he fi nal C S R.
5. 4. 2. 
S u p pl y of I n vesti g ati o n al Me dici n al Pr o d uct
T he I M P will be s u p plie d b y Astra Ze neca as l y o p hilis e d vials i n o ne vial kits .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
A tec h nical a gree me nt bet wee n t he PI a n d Astra Ze neca will be i n place t o c o ver all 
p har mac y relat e d acti vit ies, detaili n g r oles a n d res p o nsi bilities pri or t o recei pt of t he I M Ps 
at t he Cli nical U nit.
A release d oc u me nt si g ne d b y a le gall y  a ut h orise d Q ualifie d P ers o n nel at t he Cli nical U nit 
will be place d i n t he a p pr o priate sect i on of t he Trial Master File t o d oc u me nt la belli n g a n d 
di s pe nsi n g of t he I M P t o t he partici pa nt .
5. 4. 3. 
D ose a n d Tre at me nt Re gi me ns
Eac h parti ci pa nt will recei ve a si n gle I V i nf usi o n or I M d ose of A Z D 7 4 4 2 or pl ace b o. 
Parti cipa nt s will n ot be faste d a n d will be all o we d t o dri n k water t o pre ve nt de h y drati o n 
u nt il 1 h o ur bef ore d osi n g. Water will be all o we d a d li bit u m fr o m 1 h o ur after t he start of 
d osi n g ( de pe n di n g o n t he d urati o n of t he I V i nf usi o ns) a n d a sta n dar d meal will be gi ve n 
4 h o urs after t he start of d osi n g.
Parti cipa nts i n t he first c o h ort ( C o h ort 1a) will recei ve a d ose of 3 0 0 m g A Z D 7 4 4 2 or 
pl ace b o t o be a d mi nistere d se q ue ntiall y as direct gl uteal I M a d mi nistrati o ns starti n g wit h 
A Z D 8 8 9 5/ place b o a n d f o ll owe d b y A Z D 1 0 6 1/ place b o.
Parti cipa nts i n t he first 3 c o h orts t o be d ose d via I V i nf usi o n ( C o h orts 1 b, 2, a n d 3 ) will 
recei ve a d ose of 3 0 0 m g/ 1 0 0 0 m g/ 3 0 0 0 m g A Z D 7 4 4 2 or pl ace b o t o be a d mi nistere d 
se q ue ntiall y via I V i nf usi on at a ma xi mal i nf usi on rate of 2 0 m g/ mi n ute starti n g wit h 
A Z D 8 8 9 5/ place b o a n d f o ll owe d b y A Z D 1 0 6 1/ place b o .
Parti cipa nts i n C o h ort 4 will recei ve a d ose of 3 0 0 0 m g A Z D or place b o via c o -
a d mi nist ere d ( b ot h m A bs mi xe d i n a si n gle i nf usi o n ) I V i nf usi on at a ma xi mal inf usi o n  
rate of 5 0 m g/ mi n ute .
T he m a xi m u m d ose will n ot e xcee d 3 0 0 0 m g (t otal d ose, 1 5 0 0 m g per m A b).
Ot her restrict i ons are descri be d i n Sect i on 4. 2 . Data of parti ci pa nt s ma y be e xcl u de d fr o m 
t he P K a nal ysis set.
5. 4. 4. 
L a belli n g
La bels will be pre pare d i n acc or da nce wit h G M P a n d l ocal re g ulat or y  g uideli nes. T he 
la bels will f ulfil G M P A n ne x 1 3 req ui re me nts a n d me dical de vice directi ve f or la belli n g.
5. 4. 5. 
St or a ge a n d H a n dli n g Pr oce d ures
T he I M P will be st ore d i n a sec ure facilit y u n der a p pr o priate st ora ge c o n dit i on of 2 t o 8° C 
a n d pr otect fr o m li g ht wit hi n its ori gi nal pac ka gi n g. Details o f st ora ge c o n diti ons will be 
pr o vi de d o n t he la bel o f t he I M P.
N o s pecial pr oce d ures f or t he safe ha n dli n g of A Z D 7 4 4 2 are re q uire d.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Astra Ze neca will be per mitte d u p o n re q uest t o a u dit t he s u p plies, st ora ge, dis pe nsi n g 
pr oce d ures , a n d rec or ds pr o vi de d t hat t he bli n d of t he st u d y is n ot c o m pr o mise d.
5. 5. 
C o nc o mit a nt a n d P ost -st u d y Tre at me nt(s)
Pl ease see e xcl usi o n cri t eria #5 f or restrict i ons a n d all o we d c o nc o mita nt me dicat i ons.
T he parti ci pa nt s s h o uld be i nstr ucte d t hat n o ot her me dicati on is all owe d, wi t ho ut t he 
c o nse nt of t he PI .
Me dicat i on, w hic h is c o nsi dere d necessar y f or t he parti ci pa nt ’s safety a n d well-bei n g, m a y 
be gi ve n at t he discret i on of t he PI d uri n g t he resi de nt ial perio d.
W he n a n y me dicat i on is re q uire d, it s h o ul d be prescri be d b y t he PI . F oll o wi n g c o ns ultati o n 
wi t h Astra Ze neca Lea d P h ysicia n, t he PI s h o ul d deter mi ne w het her or n ot t he parti cipa nt
s h o uld c o nt i n ue i n the st u d y . A d mi nistratio n of  c o nc omit a nt me dicat i ons t hat ma y 
i nfl ue nce t he meas ure me nt of t he P K e n d p oi nts will be d oc u me nte d as a pr ot oc ol de viat i on 
after c o ns ult atio n of  t he PI wit h Astra Ze neca Lea d P h ysicia n.
W he n
a n i n di vi d ual partici pa nt bec o mes eli gi ble f or t he nat i onall y  de plo y e d C O VI D- 1 9 
vacci ne a n d it is l ocall y a vaila ble, t he partici pa nt ca n be u n bli n de d o n re q uest, after a f ull y 
i nf or me d, o bjecti ve disc ussi o n base d o n all a vaila ble u p -t o-date i nf or mat i on, a n d re mai n i n 
t he st u d y.
 
U n bli n de d p artici pa nts w h o recei ve d place b o s h o ul d be a d vise d t hat n o 
st u d y-ass ociate d c o ntrai n dicat i on t o recei vi n g a vacci ne e xists .
 
U n bli n de d partici pa nts w h o recei ve d A Z D 7 4 4 2 s h o ul d be a d vise d t hat t he 3 0 0 m g 
d ose m a y pr o vide 6 t o 9 m o nt hs of pr otecti o n, t hat t he 1 0 0 0 m g d ose ma y pr o vi de 1 1 
t o 1 4 m o nt hs of pr otecti o n, a n d t hat t he 3 0 0 0 m g d ose ma y pr o vi de u p t o 1 5 t o 
1 8 m o nt hs of pr otecti o n, b ut t hat s uc h pr otecti o n has n ot y et bee n de m o nstrate d. I n 
t hese partici pa nts, t here w o ul d be little or n o ur ge nc y for recei vi n g a vacci ne. I n 
a d ditio n, i n t he prese nce of a de q uate ne utralizi n g a nt i b o d y titers, e x pecte d f or t he 
d urati o ns n ote d, a n a p pr o priate a n d effect i ve res p o nse t o t he vacci ne c o ul d be 
i m paire d. S uc h partici pa nts s h o ul d be a d vise d t o c o nsi der waiti n g a n a p pro pri ate 
le n gt h of ti me, as s u g geste d a b o ve f or t he differe nt d oses, bef ore recei vi n g a n 
a nt i-S A R S -C o V -2 vacci ne. F or A Z D 7 4 4 2, t he n u m ber of m o nt hs i de nt ifie d a b o ve f or 
eac h d ose re prese nt t he a p pr o xi mate n u m ber of eli mi nat i on half -li ves of t he m A bs, 
t hat ma y nee d t o pass bef ore t he p ote ntial of t he m A bs t o pr otect a gai nst C O VI D - 1 9 
s h o uld be re d uce d, a n d after w hic h t heir p ote ntial i nterfere nce wit h a vacci ne ma y  be 
re d uce d. If t he partici pa nt deci des t o recei ve t he vacci nat i on des pite t hese 
c o nsi derati o ns t he s u bject ca n pr ocee d a n d c o nti n ue i n t he st u d y.
 
F or partici pa nts w h o ha ve recei ve d I M P ( bli n de d) a n d de vel o p s y m pt o mat ic 
C O VI D -1 9 at s o me p oi nt i n t he st u d y :
 
T here is n o reas o n t o belie ve t hat a d mi nistrati o n of a vacci ne d uri n g ac ute 
C O VI D -1 9 will a meli o rate t he ill ness.
 
I n al m o st all place b o reci pie nts, a n d i n m ost m A b reci pie nts, a n i nfecti on- i n d uce d 
i m m u ne res p o nse will occ ur, a n d t his res p o nse s h o ul d be pr otecti ve. At t his ti me, 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
t here is n o reas o n t o belie ve t hat t he pr otecti o n aff or de d b y  nat ural i nfecti on is 
less fre q ue nt or less r o b ust t ha n t he pr otecti o n pr o vi de d b y a vacci ne, s o t he 
be nefit of vacci nat i on ma y be li mite d.
 
T he ri s k of recei vi n g a vacci ne after res ol uti on of t he ill ness s h o ul d be l o w.
5. 6. 
Tre at me nt C o m pli a nce
D osi n g will ta ke place at t he Pare xel E P C U.
T he a d mi nistrati o n of all me dicat i ons will be rec or de d i n Cli n Base T M .
C o m plia nce will be ass ure d b y di rect s u per visio n  a n d wit nessi n g of t he I M P 
a d mi nistrati o n.
I n a d diti on, bi oa nal ysis o f A Z D 7 4 4 2 i n ser u m sa m ple at C ma x fr o m all pres u med 
pl ace b o -treate d partici pa nt s ma y be use d t o c o nfir m lac k of A Z D 7 4 4 2 i n t he ser u m.
5. 6. 1. 
Dr u g Acc o u nt a bilit y, Dis pe nsi n g a n d Destr ucti o n
T he I M P pr o vi de d f or t his cli nical st u d y  will be use d o nl y as directe d i n t he C S P.
I n acc or da nce wit h G C P, t he Cli nical U nit will  acc o u nt f or all s u p plies of A Z D 7 4 4 2 a n d 
pl ace b o. Details of recei pt, st ora ge, asse m bl y/ dis pe nsi n g, a n d ret ur n will be rec or de d.
All use d a n d u n use d s u p plies of A Z D 7 4 4 2 ( A Z D 8 8 9 5 , A Z D 1 0 6 1 ) a n d place b o will be 
destr o y e d b y Pare xel at t he e n d of t he st u dy.  T he certificate of deli ver y a n d destr ucti o n 
m ust be si g ne d, i n acc or da nce wit h i nstr ucti o n b y Astra Ze neca. Destr ucti o n m ust n ot ta ke 
pl ace u nless t he res p o nsi ble pers o n at Astra Ze neca has a p pr o ve d it.
5. 7. 
Disc o nti n u ati o n of I n vesti g ati o n al Me dici n al Pr o d uct a n d 
Wit h dr a w al fr o m St u d y
Heal t h y partici pa nt s ma y be disc o nti n ue d fr om I M P i n t he f oll owi n g si t u atio ns:
 
Heal t h y partici pa nt decisi o n. T he healt h y p arti ci pa nt is at a n y ti me free t o disc o nti n ue 
treat me nt, wit ho ut prej u dice t o f urt her treat me nt.
 
Se vere n o n -c o mplia nce t o st u d y  pr ot oc ol.
 
A n y si g nifica nt a n d cli nicall y  rele va nt c ha n ges i n t he safety para meters (e g, E C G, B P , 
p ul se, la b orat or y assess me nts a n d A E) ma ki n g t he c o nti n uati on of I M P a d mi nistrati o n 
u nj ust ifie d.
 
A n y case of P H L acc or di n g t o  A p pe n di x C.
T he a p pr o pri ate A E f or m in t he C R F is t o be c o m plete d.
5. 7. 1. 
Pr oce d ures f or Wit h dr a w al of a P artici p a nt fro m t he St u d y
If a parti ci pa nt wi t hdra ws or is wi t hdra w n fr o m  t he st u d y, t he partici pa nt will be 
e nc o ura ge d t o ret ur n t o t he Cli nical U nit f or a n Earl y Ter mi nati o n Visit (t o f oll o w t he 
pr oce d ures of t he Fi nal F oll o w -u p Visi t) t o e ns ure t he partici pa nt s’ s afet y.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
6. 
C O L L E C TI O N O F S T U D Y V A RI A B L E S
6. 1. 
Rec or di n g of D at a
Sta n dar d meas ures t o assess P K, safet y, a n d t olera bilit y a p pl y d uri n g t he st u d y. F or t he 
si n gle d oses of A Z D 7 4 4 2 pla n ne d t o be gi ve n d uri n g t his st u d y, n o safet y iss ues are 
e x pecte d.
F or ti mi n g o f assess me nts refer t o t he S o A (Ta ble 3- 1 , Ta ble 3 - 2, a n d Ta ble 3- 3 ).
6. 2. 
E nr ol me nt a n d Scree ni n g Pr oce d ures
Vi r al s er olo g y , uri ne dr u gs of a b use, a n d alc o h o l will be assesse d f or eli gi bilit y. F ol licle 
sti m ulati n g h or m o ne (females o nl y), pre g na nc y  testi n g (fe males o nl y ) a n d use of 
c o nc o mita nt me dicat i on will als o be assesse d a n d re p orte d.
6. 3. 
S afet y
S af et y a n d t olera bilit y varia bles will i ncl u de:
 
A Es /S A Es.
 
Vi t al si g ns (s yst olic a n d diast olic B P, p ulse rate, a n d oral te m perat ure ).
 
1 2- Lea d safet y  E C G s.
 
P h ysical e xa mi nat i on.
 
La b orat or y  assess me nts ( hae mat ol o g y, cli nical c he mistr y, c oa g ulat i on, a n d uri nal ysis).
6. 3. 1. 
A d verse E ve nts
6. 3. 1. 1. 
Defi niti o n of A d verse E ve nts
A n A E i s t he de vel o p me nt of a n y u nt o war d me dical occ urre nce i n a parti ci pa nt or cli nical 
st u d y partici pa nt a d mi nistere d a me dici nal pr o d uct a n d w hic h d oes n ot necessaril y ha ve a 
ca usal relat i ons hi p wi t h t his treat me nt. A n A E ca n t heref ore be a n y u nfa v o ura ble a n d 
u ni nte n de d si g n (e g, a n a b n or mal la b orat or y  fi n di n g), s y m pt o m (f or e xa m ple na usea, c hest 
pai n), or disease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot 
c o nsi dere d relate d t o t he me dici nal pr o d uct.
T he ter m  A E is use d t o i ncl u de b ot h seri o us a n d n o n-serio us A Es a n d ca n i ncl u de a 
deteri or ati o n of  a pre-e xist i n g me d ical occ urrence. A n A E ma y occ ur at a n y t i me, 
i ncl u di n g r u n-i n or was h o ut peri o ds, e ve n if n o st u d y treat me nt has bee n a d mi nistere d.
T he ter m A E will be use d f or a n y  e ve nt as descri be d a b o ve t hat is re p orte d pre-d ose a n d 
A E f or all e ve nts p ost-d ose.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
6. 3. 1. 2. 
Defi niti o ns of Ser i o us A d verse E ve nt
A S A E is a n A E occ urri n g d uri n g a n y st u d y  p hase (ie, r u n-i n, treat me nt, was h o ut, 
f oll ow- u p), t hat f ulfils o ne or m ore of t he f oll o wi n g criteria:
 
Res ults i n deat h.
 
Is i m me diatel y life-t hreate ni n g.
 
Re q ui res i n-pat ient h os pi talisat i on or pr ol o n gat i on of e xist i n g h os pi talisat i on.
 
Res ults i n persiste nt or si g nifica nt disa bilit y or i nca paci t y or s u bsta ntial disr u pt i on of 
t he a bilit y t o c o n d uct n or mal life f u nct i ons.
 
Is a c o n ge nital a b n or mality or bi rt h defect.
 
Is a n i m p orta nt me dical e ve nt t hat ma y je o par dise t he partici pa nt or m a y re q uire 
me dical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve.
F or f urt her g ui da nce o n t he defi nit i on of a S A E, see  A p pe n di x A of  t his C S P.
A d verse e ve nts f or mali g na nt t u m o urs re p orte d d uri n g a st u d y  s h o uld ge nerall y be 
assesse d as S A Es. If n o ot her seri o us ness criteria a p pl y, t he “I m p orta nt Me dical E ve nt” 
crit erio n s h o ul d be use d. I n certai n sit u atio ns, h o we ver, me dical j u d ge me nt o n a n 
i n di vi d ual e ve nt basis s h o ul d be a p plie d t o clarif y t hat t he mali g na nt t u m o ur e ve nt s h o ul d 
be assesse d a n d re p orte d as a n o n -serio us A E. F or e xa m ple, if t he t u m o ur is i ncl u de d as 
me dical hist or y  a n d pr o gressi o n occ urs d uri n g t he st u d y , b ut t he pr o gressio n d oes n ot 
c ha n ge treat me nt a n d/ or pr o g n osis of t he mali g na nt t u m o ur, t he A E ma y n ot f ulfil t he 
attri b utes f or bei n g assesse d as seri o us, alt h o u g h re p orti n g o f t he pr o gressi o n of t he 
mali g na nt t u m o ur as a n A E is v ali d a n d s h o uld occ ur. Al s o, s o me t ypes of  mali g na nt 
t u mo urs, w hi c h d o n ot s prea d re m otel y after a r o uti ne treat me nt t hat d oes n ot 
re q uire h os pi talisat i on, m a y be assesse d as n o n -serio us; e xa m ples i ncl u de Sta ge 1 basal 
cell carci n o ma a n d Sta ge 1 A 1 cer vical ca ncer re m o ve d via c o ne bi o ps y.
6. 3. 1. 3. 
Ot her Si g nific a nt A d verse E ve nts
D uri n g t he e val uat i on of t he A E data, a n Astra Ze neca me dicall y q ualifie d e x pert will 
re vie w t he list of A Es t hat were n ot re p orte d as seri o us or w here rele va nt disc o nti n uati o n 
e ve nts a n d wit h dra wal fr o m t he st u d y . Base d o n t he e x pert’s j u d ge me nt, si g nifica nt A Es of 
parti c ular cli nical i m p orta nce ma y, after c o ns ultat i o n wit h t he Gl o bal Safety P h ysicia n, be 
c o nsi dere d O S A Es a n d re p orte d as s uc h i n t he C S R. A si milar re vie w of ot her data fr o m 
lab orat or y  tests, vit al si g ns, E C Gs a n d ot her safety assess me nts will be perf or me d f or 
i de ntificati on of ot her S A Es .
E xa m ples of t hese are mar ke d hae mat ol o gical a n d ot her la b orat or y  a b n or malities, a n d 
certai n e ve nts t hat lea d t o i nter ve nt i on ( ot her t ha n t h os e alrea d y classifie d as seri o us), d ose 
re d uctio n or si g nifica nt a d di tio nal  tr e at me nt.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
6. 3. 1. 4. 
Rec or di n g of A d verse E ve nts
Ti me Peri o d f or C ollecti o n of A d verse E ve nts
A d verse e ve nts will be c ollecte d fr o m t he ti me of I M P a d mi nistratio n t hr o u g h o ut t he 
Treat me nt Peri o d u p t o a n d i ncl u di n g t he F o ll ow- u p Visi t.
S eri o us a d verse e ve nts will be rec or de d fr o m t he ti me of i nf or me d c o nse nt.
F oll o w -u p of U nres ol ve d A d verse E ve nts
A n y A Es t hat are u nres ol ve d at t he partici pa nt ’s last visit in t he st u d y  are f oll owe d u p b y 
t he PI f or as l o n g as me dicall y i n dicate d, b ut wit h o ut f urt her rec or di n g i n Cli n Base ™.
Astra Ze neca retai ns t he ri g ht t o re q uest a d diti o nal i nf or mat i on f or a n y part ici pa nt wit h 
o n g oi n g A Es a n d S A Es at t he e n d of t he st u d y, if j u d ge d necessar y.
V ari a bles
T he f ol l owi n g varia bles will be c ollecte d f or eac h A E , i ncl u di n g w het her treat m e nt of t he 
A E was re q uire d :
 
A E e ve nt dia g n osis/ descri pt i on.
 
T he date a n d ti me w he n t he A E starte d a n d st o p pe d.
 
I nte nsity.
 
W het her t he A E is seri o us or n ot .
 
PI ca usalit y rati n g a gai nst t he I M P ( yes or n o).
 
Act i on ta ke n wit h re gar d t o I M P a d mi nistrati o n .
 
If t he A E ca use d parti ci pa nt ’s wit h dra wal fr om st u d y ( yes or n o) .
 
O utc o m e.
I n a d diti on, t he f o ll owi n g vari a bles will be c ollecte d f or S A Es:
 
Date A E m et crit eria f or S A E.
 
Date PI beca me a ware of S A E .
 
T he ca use lea di n g t o a n A E bei n g c o nsi dere d seri o us .
 
Date of h os pi talisat i on (if h os pitali se d) .
 
Date of disc har ge .
 
Pr o ba ble ca use of deat h (if deat h occ urre d) .
 
Date of deat h .
 
A ut o ps y  p erfor m e d.
 
Ca usalit y assess me nt i n r elat i on t o St u d y  pr oce d ures.
 
Ca usalit y assess me nt t o ot her me dicat i on.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 5 of 1 0 3
T he f o ll owi n g i nte nsit y rati n gs will be use d:
1 
Mil d (a ware ness of si g n or s y m pt o m, b ut easil y t olerate d) .
2 
M o derate ( di sc omf o rt s ufficie nt t o ca use i nterfere nce wit h n or mal acti vities).
3 
Se vere (i nca pacitat i n g, wit h i na bility t o perf or m n or mal acti vities).
It is i m p orta nt t o disti n g uis h bet wee n seri o us a n d se vere A Es:
 
Se verit y is a meas ure of i nte nsity w hereas seri o us ness is defi ne d b y t he criteria i n 
Secti o n 6. 3. 1. 2 .
 
A n A E of se vere i nte nsit y nee d n ot necessaril y be c o nsi dere d seri o us. F or e xa m ple, 
na usea t hat persists f or se veral h o urs m a y be c o nsi dere d se vere na usea, b ut n ot a S A E. 
O n t he ot her ha n d, a str o ke t hat res ults i n o nl y  a li mite d de gree of disa bility ma y be 
c o nsi dere d a mil d str o ke b ut w o ul d be a n S A E.
C a us alit y C ollecti o n
T he PI will assess ca usal relat i ons hi p bet wee n I M P a n d eac h A E, a n d a ns wer “ yes” or 
“ n o” t o t he q uesti o n “ D o yo u c o nsi der t hat t here is a reas o na ble p ossi bilit y t hat t he e ve nt 
ma y ha ve bee n ca use d b y  t he I M P?”
F or S A Es , ca usal relat i ons hi p will als o be assesse d f or ot her me dicat i on, a n y a d dit i onal 
dr u g a n d st u d y  pr oce d ures. N ote t hat f or S A Es t hat c o ul d be ass ociate d wit h a n y st u d y 
pr oce d ure t he ca usal relat i ons hi p is i m plie d as “ yes”.
A g ui de t o t he i nter pretati o n of t he ca usalit y q uest i o n is f o u n d i n A p pe n di x A of  t his C S P.
A d verse E ve nts B ase d o n Si g ns a n d S y m pt o ms
All A Es s p o nta ne o usl y re p orte d b y  t he partici pa nt or re p orte d i n res p o nse t o t he o pe n 
q uesti o n fr o m t he st u d y pers o n nel: “ H ave y o u h a d a ny he alt h pr o ble ms si nce y o u were 
l ast aske d ? ” or re veale d b y o bser vat i on will be c o llecte d a n d rec or de d i n Cli n Base ™.
W he n c o llecti n g A Es, t he rec or di n g of dia g n oses is preferre d ( w he n p ossi ble) t o rec or di n g 
a list of si g ns a n d s y m pt o ms.
H o we ver, if a dia g n osis is k n o w n a n d t here are ot her si g ns or s y m pt o ms t hat are n ot 
ge nerall y part of t he dia g n osis, t he dia g n osis a n d eac h si g n or s y m pt o m will be rec or de d 
se paratel y.
A d verse E ve nts B ase d o n E x a mi n ati o ns a n d Tests
T he res ults fr o m C S P -ma n date d la b orat or y  tests, vital si g ns, E C Gs a n d ot her safety 
assess me nts will be s u m marise d i n t he C S R.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
Deteri or ati o n as c o m pare d t o baseli ne i n C S P -ma n date d la b orat or y  val ues, vital si g ns, 
E C Gs a n d ot her safet y assess me nts s h o ul d t heref ore o nl y be re p orte d as A Es if t he y fulfil 
a n y o f t he S A E crit eria or are t he reas o n f or disc o nti n uat i on of treat me nt wit h t he I M P.
If deteriorati o n i n a la b orat or y  val ue or vit al si g n is ass ociate d wit h cli nical si g ns a n d 
s y m pt o ms, t he si g 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, or vit al si g n will be c o nsi dere d as a d diti onal i nf or mat i on.
W here ver p ossi ble t he re p orti n g PI s h o uld use t he cli nical, rat her t ha n t he la b orat or y  t er m 
(e g, a nae mia vers us l o w hae m o gl obi n val ue).
I n t he a bse nce of cli nical si g ns or s y m pt o ms, cli nicall y rele va nt deteri orati o ns i n 
n o n- C S P -ma n date d para meters s h o ul d be re p orte d as A E s.
A n y ne w or a g gra vate d cli nicall y rele va nt a b n or mal me dical fi n di n g at a p h ysical 
e xa mi nat i on as c o m pare d wit h t he baseli ne assess me nt will be re p orte d as a n A E.
H y' s L a w
Cases w here a parti ci pa nt s h o ws ele vati o ns i n li ver bi oc he mistr y ma y re q uir e furt her 
e val uat i on a n d occ urre nces of A S T or A L T ≥ 3 × U L N t o get her wit h t otal bilir u bi n ≥2 × 
U L N m a y nee d t o be re p orte d as S A Es. Please refer t o  A p pe n di x C f or furt her i nstr ucti o n 
o n cases of i ncreases i n li ver bi oc he mistr y  a n d e val uati on of H y’s La w.
6. 3. 1. 5. 
Re p orti n g of Seri o us A d verse E ve nts
All S A Es ha ve t o be re p orte d, w het her or n ot c o nsi dere d ca usall y relate d t o t he I M P, or t o 
t he st u d y pr oce d ure(s). All S A Es will  be rec or de d i n Cli n Base ™.
If a n y S A E occ urs i n t he c o urse of t he st u d y, t he n t he PI or ot her site pers o n nel will i nf or m 
a p pr o priate Astra Ze neca re prese ntati ves i m me diatel y, or n o l ater t h a n 2 4 h o urs of  w he n 
he or s he bec o me s a ware of it.
T he desi g nate d Astra Ze neca re prese ntati ve will w or k wit h t he PI t o e ns ure t hat all t he 
necessar y  inf o r mat i on is pr o vi de d t o t he Astra Ze neca Patie nt Safety data e ntr y  sit e wit hi n 
1 c ale n d ar d a y of  init ial recei pt f or fat al a n d life-t hreate ni n g e ve nts a n d wit hi n 
5 c ale n d ar d a ys of  init ial recei pt f or all ot her S A Es.
F or fatal  or life-t hreate ni n g A Es w here im p orta nt or rele va nt i nf or mat i on is missi n g, acti ve 
f oll ow- u p will be u n derta ke n i m me diatel y.
PI s or ot her site pers o n nel will i nf or m Astra Ze neca re prese ntati ves of a n y f o ll ow- u p 
i nf or mat i on o n a pre vi o usl y  re p orte d S A E i m me diatel y, or n o l ater t h a n 2 4 h o u rs of  
w he n he or s he bec o me s a ware of it.
T he refere nce d oc u me nt f or defi nit i on o f e x pecte d ness/liste d ness is t he I B f or t he 
Astra Ze neca dr u g.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 0 3
6. 3. 1. 6. 
Re g ul at or y Re p orti n g Re q uire me nts f or Seri o us A d verse E ve nts
Pr o m pt n otificat i on b y t he PI t o t he S p o ns or of a S A E is esse ntial s o t hat le gal o bli gatio ns 
a n d et hical res p o nsi bilit ies t o war ds t he safety of  p artici pa nts a n d t he safet y of  an I M P
u n der cli nical i n vest i gati on are m et.
T he S p o ns or has a le gal res p o nsi bilit y t o n otif y  bot h t he l o c 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 safety of  a st u d y int er ve nt i on u n der cli nical 
i n vesti gati on. T he S p o ns or will c o m p l y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts 
r elat i n g t o safety re p orti n g t o t he Re g ulat or y Aut h ori t y, E C, a n d PI s.
F or all st u dies, e xce pt t h ose utilis i n g me dical de vices, PI safety re p orts must be pre pare d 
f or S U S A Rs acc or di n g t o l ocal re g ulat or y re q uire me nts a n d S p o ns or p olic y a nd f or war de d 
t o t he PI s as necessar y.
A PI w h o recei ves a PI safet y re p ort descri bi n g a S A E or ot her s pecific safet y i nf or mati o n 
(e g, s u m mar y or listi n 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 al o n g wit h 
t he I B a n d will n otif y t he E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
6. 3. 2. 
L a b or at or y Assess m e nts
6. 3. 2. 1. 
H ae m at ol o g y
H ae m at ol o g y 
W hite bl o o d cell ( W B C) c o u nt
Ne utr o p hils a bs ol ute c o u nt 
Re d bl o o d cell ( R B C) c o u nt
L y m p h oc y tes a bs ol ute c o u nt 
Hae m o gl o bi n ( H b)
M o n oc ytes a bs ol ute c o u nt 
Hae mat ocrit ( H C T)
E osi n o p hils a bs ol ute c o u nt 
Mea n c or p usc ular v ol u me ( M C V)
Bas o p hils a bs ol ute c o u nt 
Mea n c or p usc ular hae m o gl o bi n ( M C H)
Platelets
Mea n c or p usc ular hae m o gl o bi n c o nce ntrati o n 
( M C H C)
Retic ul oc ytes a bs ol ute c o u nt 
6. 3. 2. 2. 
Ser u m Cli nic al C he mistr y
Ser u m Cli nic al C he mistr y
S o di u m
Al kali ne p h os p hatase ( A L P)
P otassi u m
Ala ni ne a mi n otra nsferase ( A L T)
Ur ea
As partate a mi n otra nsferase ( A S T)
Creati ni ne
Ga m ma gl uta m yl tra ns pe pti dase ( G G T)
Al b u mi n
T otal Bilir u bi n
Calci u m
U n c o nj u gate d bilir u bi n
P h os p hate
C o nj u gate d bilir u bi n
Gl uc ose
Creati ne Ki nase
C- reacti ve pr otei n ( C R P)

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 8 of 1 0 3
6. 3. 2. 3. 
Uri n al ysis
Uri n al ysis
Gl uc ose
Pr otei n
Bl o o d
Micr osc o p y (if p ositi ve f or pr otei n or bl o o d): R B C, W B C, Casts ( Cell ular, Gra n ular, H yali ne)
6. 3. 2. 4. 
C o a g ul ati o n
C o a g ul ati o n
I nter nati o nal n or malise d rati o (I N R)
Pr ot hr o m bi n Ti me ( P T)
Acti vate d partial t hr o m bi n ti me (a P T T)
6. 3. 2. 5. 
Pre g n a nc y Testi n g
Pre g n a nc y test (fe m ales o nl y)
Ser u m h u ma n -beta c h ori o nic g o na d otr o p hi n
(scree ni n g)
Ur i ne h u ma n-beta c h ori o nic g o na d otr o p hi n ( pre-
a n d p ost -d ose)
6. 3. 2. 6. 
Vir al Ser ol o g y a n d S A R S -C o V -2 Testi n g
Vir al Ser ol o g y
H u ma n i m m u n o deficie nc y vir us ( HI V) I a n d II   
He patitis C Vir us a nti b o d y
He patitis B s urface a nti ge n ( H Bs A g)
S A R S -C o V -2 ser ol o g y
S A R S -C o V -2 q ua ntitati ve real -ti me p ol y merase c hai n reacti o n ( q R T-P C R)
6. 3. 2. 7. 
Dr u gs of A b use a n d Alc o h ol
Dr u gs of A b use a n d Alc o h ol
A m p heta mi ne
Be nz o diaze pi nes
Et ha n ol
Met ha d o ne Meta b olites
Ca n na bi n oi ds
Bar bit urates
C ocai ne
P he nc y cli di ne
O piates 
Ur i ne Creati ni ne
Tric yclic a nti -de pressa nts ( T C A)
Met ha m p heta mi nes
6. 3. 3. 
Vit al Si g ns
T he f o ll owi n g varia bles will be c ollecte d after t he parti ci pa nt has reste d i n t he s u pi ne 
p osi tio n f or at l east 5 mi n utes:
 
S y st olic B P ( m m H g),
 
Di ast olic B P ( m m H g) ,
 
P ul se r at e( beats per mi n ute [ b p m]),
 
Oral  t e mperat ure , a n d 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 9 of 1 0 3
 
R es pirat or y r at e ( breat hs per mi n ute).
T he m eas ure me nt of vital si g ns will be carrie d o ut acc or di n g t o t he rele va nt Pare xel S O Ps.
6. 3. 4. 
Electr oc ar di o gr a p h y
6. 3. 4. 1. 
Resti n g 1 2 -le a d Electr oc ar di o gr a m
At  t he ti me p oi nts s pecifie d i n t he S o A (Ta ble 3- 1 , Ta ble 3- 2 , a n d Ta ble 3- 3 ), a 1 2-lea d 
safety E C G will be o btai ne d after at least 5 mi n utes s u pi ne rest, usi n g t he sites o w n E C G 
mac hi nes.
T he PI will j u d ge t he o verall i nter pretati o n as n or mal or a b n or mal a n d t his e val uat i on will 
be re p orte d i n Cli n Base ™. If a b n or mal, it will be f urt her d oc u me nte d as t o w het her or n ot 
t he a b n or malit y is cli nicall y si g nifica nt b y t he PI. F or all a b n or malities (re gar dless of 
cli nical si g nifica nce) t he s pecific t y pe a n d nat ure of t he a b n or malit y will  be d oc u me nte d i n 
Cli n Base ™. Cli nicall y si g nifica nt fi n di n gs s h o ul d als o be d oc u me nte d o n t he A E pa ge of 
t he C R F if a p plica ble.
T he PI m a y a d d e xtra 1 2-lea d resti n g E C G safety assess me nts if t here are a n y a b n or mal 
fi n di n gs or if t he PI c o nsi ders it is re q uire d for a n y ot her safet y reas o n. T hese assess me nts 
s h o uld be e ntere d as a n u nsc he d ule d assess me nt.
All E C G rea di n gs will be di gitall y st ore d as s o urce d oc u me nts.
6. 3. 5. 
P h ysic al E x a mi n ati o n
F ull
T he c o m plete p h ysical e xa mi nat i ons will i ncl u de a n asses s me nt of t he ge neral a p peara nce, 
s ki n, car di o vasc ular, res pirat or y, a b d o me n, hea d, a n d nec k (i ncl u di n g ears, e yes, n ose, a n d 
t hr oat), l y m p h n o des, t h yr oid, m usc ul os keletal  a n d ne ur ol o gical s yste ms.
Brief ( A b bre vi ate d)
T he brief p h ysical e xa mi nat i ons will i ncl u de a n assess me nt of t he ge neral a p peara nce, 
s ki n, car di o vasc ular s yste m, l u n gs a n d a b d ome n. Site -di recte d p h ysical e x a m s h o uld be 
perf or m e d t o assess s y m pt o ms re p orte d b y parti ci pa nt .
6. 3. 6. 
I njecti o n Site Re acti o ns
I njecti on site reacti o ns will be m o nit ore d ti me p oi nts i n dicate d i n t he S o A (Ta ble 3- 1 , 
Ta ble 3- 2 , a n d Ta ble 3- 3 ), i ncl u di n g assess me nt of er yt he ma, s welli n g, i n d urati o n itc hi n g, 
pai n or te n der ness, a n d disc o l ourati o n . I nject i on sit e reactio ns mi g ht be d oc u m e nte d b y 
p h ot o gra p h y , at t he discreti on of t he PI / Desi g nee, wit h visi ble meas uri n g ta pe a n d be 
d oc u m e nte d i n eac h parti ci pa nt s C R F i n a p pr o priate m o d ules ( n ot t o be deli vere d t o 
Astra Ze neca u nless re q ueste d).

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 0 of 1 0 3
6. 4. 
P h ar m ac o ki netics
6. 4. 1. 
C ollecti o n of P h ar m ac o ki netic S a m ples
6. 4. 1. 1. 
Ser u m S a m ples
Bl o o d sa m pl es f or t he det er mi nati o n of ser u m c o nce ntrati o ns of A Z D 7 4 4 2 m A bs 
(A Z D 8 8 9 5 a n d A Z D 1 0 6 1 ) will be c ollecte d as s pecifie d i n t he S o A (Ta ble 3- 1 , Ta ble 3- 2 , 
a n d Ta ble 3- 3 ).
S a m ples will  be c ollecte d, ha n dle d, la belle d , st ore d, a n d s hi p pe d as detaile d i n t he 
La b orat or y  Ma n ual.
6. 4. 1. 2. 
N as al Fl ui d S a m ples
Nasal fl ui d sa m ples f or t he deter mi nat i on of nasal fl ui d c o nce ntrati o ns o f A Z D 7 4 4 2 m A bs 
( A Z D 8 8 9 5 a n d A Z D 1 0 6 1) will be c ollecte d as s pecifie d i n t he S o A (Ta ble 3- 1 , Ta ble 3- 2 , 
a n d Ta ble 3- 3 ).
S a m ples will  be c ollecte d, ha n dle d, la belle d, st ore d a n d s hi p pe d as detaile d i n t he 
La b orat or y  Ma n ual.
6. 4. 2. 
P h ar m ac o ki netic Dr u g Ass a ys
Bl o o d sa m pl es f or deter mi nat i on of A Z D 7 4 4 2 m A bs ( A Z D 8 8 9 5 a n d A Z D 1 0 6 1)
c o nce ntrati o ns i n ser u m will be a nal yse d usi n g a vali date d assa y c o n d ucte d at P P D. Nasal 
fl uid a nal ysis ma y be perf or me d at Astra Ze neca usi n g a q ualifie d assa y. Ad di tio nal 
a nal yses ma y be c o n d ucte d o n t he bi o l ogical sa m ples t o f urt her i n vest i gate t he prese nce 
a n d/ or i de nt ity of  dr u g meta b o lites.
F ull details o f t he a nal ytical met h o d a n d a nal yses pe rf or me d will be descri be d i n a se parate 
Bi oa nal y tic al Re p ort.
A d dit i onal a nal yses ma y be c o n d ucte d o n t he bi o l ogi cal sa m ples t o f urt her i n vesti gate t he 
prese nce a n d/ or i de ntit y of  dr u g meta b o lites.
Pl ace b o sa mples will n ot be a nal yse d, u nless t here is a ne e d t o c o nfir m t hat c orrect 
treat me nt has bee n gi ve n t o st u d y parti ci pa nt s.
F ull details o f t he a nal ytical met h o d a n d a nal yses perf or me d will be descri be d i n a se parate 
Bi oa nal y tic al Re p ort.
6. 5. 
I m m u n o ge nicit y
6. 5. 1. 
C ollecti o n of I m m u n o ge nicit y S a m ples
Bl o o d sa m ples f or deter mi nati on of A D A a nt i b o dies i n ser u m will be c o n d ucte d at P P D 
a n d a nal yse d b y C o va nce o n be half o f Astra Ze neca, usi n g a vali date d assa y. Bl o o d 
sa m ples f or deter mi nati on of A D A a nti b o dies i n ser u m will be c ollecte d as s pecifie d i n t he 
S o A (Ta ble 3- 1 , Ta ble 3- 2 , a n d Ta ble 3- 3 ). U nsc he d ule d sa m ples f or A D A a nal ysis s h o ul d 
be c o llecte d i n res p o nse t o s us pecte d i m m u ne-relate d A E s.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 1 of 1 0 3
If a parti ci pa nt’s sa m ple at t he last st u d y visit is c o nfir me d A D A p ositive, t he s u bject ma y 
be as ke d t o ret ur n t o t he cli nic f or a d diti o nal sa m pli n g if j u d ge d necessar y b y t he 
Astra Ze neca Lea d P h ysicia n a n d t he PI .
S a m ples will  be c ollecte d, ha n dle d, la belle d, st ore d a n d s hi p pe d as detaile d i n t he 
La b orat or y  Ma n ual.
6. 5. 2. 
I m m u n o ge nicit y Ass a ys
T he prese nce or a bse nce of A D A will be deter mi ne d i n t he ser u m sa m ples usi n g a 
vali date d bi oa nal y tical met h o d. A tiere d testi n g sc he me will be e m pl o ye d, wi t h t he first 
ste p bei n g scree ni n g. Sa m ples f o u n d p ositi ve i n t he scree ni n g ste p will be teste d i n t he 
c o nfir mat or y ste p. Sa mples c o nfi r me d p ositive f or A D A i n t he c o nfir mat or y ste p will 
u n der g o e n d p oi nt titer deter mi nati o n.
F ull details o f t he a nal ytical met h o d a n d a nal yses perf or me d use d will be descri be d i n a 
se parate Bi oa nal ytical Re p ort.
6. 5. 3. 
E x pl or at or y St u d y -Rel ate d Bi o m ar kers
C ollecte d bi os peci me ns ma y  be ut ilise d for e x pl or at or y  st u d y-r elate d bio m ar ker researc h 
(ie, t o i n vesti gate a d dit i onal h u m oral a n d/ or m uc osal i m m u ne res p o nses , as well as 
p ote nti al c orr elates of pr otect i on) as deter mi ne d b y t he S p o ns or base d u p o n e mer gi n g 
safety,  efficac y, a n d i m m u n o ge nicity data. A nal ysis m a y i nclu de, b ut i s n ot li mite d t o, 
 
 
F or st ora ge, re -use, a n d destr ucti o n of bi o mar ker sa m ples see Secti o n 7. 2 .
6. 6. 
Ne u tr alisi n g A nti b o d y Assess me nts
Ser u m  sa m ples t o meas ure f u nct i onal acti vit y of A Z D 7 4 4 2 (ie , S A R S -C o V -2 ne utrali si n g 
a nt i b o d y le vels) will be c ollecte d fr o m partici pa nt s acc or di n g t o t he ti me p oi nts s pecifie d 
i n t he S o A (Ta ble 3- 1 , Ta ble 3- 2 , a n d Ta ble 3- 3) . A ut h orise d la b orat ories will meas ure 
ne utrali si n g a nti b o dies t o S A R S-C o V -2 usi n g vali date d wil d -t ype ne utrali sat i on assa y  or 
pse u d o ne utrali sat i on assa ys.
C CI

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 2 of 1 0 3
7. 
BI O L O GI C A L S A M P LI N G P R O C E D U R E S
All b i ol ogical sa m ples c ollecti o ns will be perf or me d b y  trai ne d staff a n d i n acc or da nce 
wi t h t he Cli nical U nit’s S O Ps.
7. 1. 
T ot al Bl o o d V ol u me
T he a p pr o xi mate t otal a m o u nt of bl o o d t o be c ollecte d fr o m eac h parti ci pa nt i n t his st u d y, 
e xcl u di n g re peat sa m ples, is est i mate d at 2 4 0. 2 m L  for parti ci pa nts i n t he I V gr o u p a n d 
2 3 0. 2 m L f or partici pa nts i n t he I M gr o u p.
T a ble 7- 1 
T ot al Bl o o d V ol u me
V ol u me per S a m ple 
N u m ber of S a m ples 
T ot al
Hae mat ol o g y
2 m L
6
1 2 m L
Cli nical c he mistr y
5 m L
6
3 0 m L
Ser ol o g y  a, b
0 m L
1
0 m L
C oa g ulati o n
2. 7 m L
6
1 6. 2 m L
P K (I V)
2. 5 m L
1 8
4 5 m L
P K (I M)
2. 5 m L
1 4
3 5 m L
A D As
3 . 5 m L
7
2 4. 5 m L
Ne utrali si n g a nti b o dies
1 2 . 5 m L
9
1 1 2. 5 m L
F S H b
0 m L
1
0 m L
Pre g na nc y test (ser u m h C G)
b
0 m L
1
0 m L
T ot al
2 4 0 . 2 m L ( I V)
2 3 0. 2 m L (I M)
a. 
S A R S -C o V - 2 ser ol o g y t o be perf or me d at t he discreti o n of t he PI .
b. 
Ser ol o g y, F S H, a n d Ser u m pre g na nc y test t o be perf or me d o n t he sa me sa m ple as f or cli nical c he mistr y.
A D As: a nti -dr u g a nti b o dies; F S H: f ollicle sti m ulati n g h or m o ne; h C G: h u ma n c h ori o nic g o na d otr o pi n ; 
I M: i ntra m usc ular; I V: i ntra ve n o us; S A R S-C o V -2: se vere ac ute res pirat or y s y n dr o me c or o na vir us 2.
Re peat bl o o d sa m ples ma y be c o llecte d f or safety reas o ns. T he ma xi m u m v ol ume t o be 
dra w n fr o m eac h parti ci pa nt m u st n ot e xcee d 5 0 0 m L o ver a peri o d of  5 6 c o nsec uti ve 
da ys .
7. 2. 
H a n dli n g, St or a ge a n d Destr ucti o n of Bi ol o gic al S a m ples
S a m ples will  be dis p ose d of, o n i nstr ucti o n fr o m Astra Ze neca, after t he C S R has bee n 
fi nalise d, u nless sa m ples are retai ne d f or a d dit i onal or f ut ure a nal yses.
7. 2. 1. 
P h ar m ac o ki netic S a m ples
P har mac o ki net ic sa m ples will be dis p ose d of after t he Bi oa nal ytical Re p ort fi nalisat i on or 
6 m o nt hs after iss ua nce of t he draft Bi oa nal y tical Re p ort ( w hic he ver is earlier), u nless 
re q ueste d f or f ut ure a nal yses.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 3 of 1 0 3
P har mac o ki net ic sa m ples ma y be dis p ose d of or a n o n y mi se d b y p o oli n g. A d ditio n al 
a nal yses ma y be c o n d ucte d o n t he a n o n y mise d, p o ole d p har mac o ki net ic sa m ples t o f urt her 
e val uate a n d vali date t he a nal yt ical met h o d. A n y r es ults fr o m s uc h a nal yses ma y be 
re p orte d se paratel y fr o m t he C S R.
I nc urre d sa m ple re pr o d uci bility a nal ysis, if a n y , will be perf or me d alo n gsi de t he 
bi oa nal ysis o f t he test sa mples. T he res ults fr o m t he e val uat i on will n ot be re p orte d i n t he 
C S R , b ut se paratel y i n a Bi oa nal yt ical Re p ort.
7. 2. 2. 
I m m u n o ge nicit y a n d P h ar m ac o d yn a mic S a m ples
Re mai ni n g ser u m sa m ple ali q u ots f or ne utralis i n g a nti b o d y assess me nts a n d A D A will be 
retai ne d at Astra Ze neca or its desi g nee f or a ma xi m u m of 1 5 years f o ll owi n g t he l ast 
parti ci pa nt ’s last visit in t he st u d y . A d ditio n al use i ncl u des b ut is not li mi t e d t o furt her 
c haracterisatio n of  a n y A D As , fut ure e x pl or ati o n of  c orr elates of pr otectio n, c o nfi r mat i on 
a n d/ or re q ualificat i on of t he assa y , as well as a d diti o nal assa y de velo p me nt w or k base d 
u p o n e m er gi n g safet y,  efficac y, a n d i m m u n o ge nicit y data as deter mi ne d b y t he S p o ns or.
T he res ults fr o m f ut ure a nal ysis will n ot be re p orte d i n t he C S R.
7. 3. 
L a belli n g a n d S hi p me nt of Bi o h az ar d S a m ples
S a m ples will  be la belle d a n d s hi p pe d i n acc or da nce wit h t he La b orat or y Ma n ual a n d t he 
Bi ol o gi cal S u bsta nce, Cate g or y B re g ulat i ons ( materials c o ntai ni n g or s us pecte d t o c o ntai n 
i nfecti ous s u bsta nces t hat d o n ot meet Cate g or y  A criteria), see A p pe n di x B of  t his C S P 
‘I A T A 6. 2 G ui da nce D oc u me nt’.
A n y sa m ples i de nt ifie d as I nfecti ous Cate g or y  A materials will n ot be s hi p pe d a n d n o 
f urt her sa m ples will be ta ke n fr om t he parti ci pa nt u nless a gree d wit h Astra Ze neca a n d 
a p pr o priate la belli n g, s hi p me nt , a n d c o ntai n me nt pr o visi o ns are a p pr o ve d.
7. 4. 
C h ai n of C u st o d y of Bi ol o gic al S a m ples
A f ull c hai n of c ust o d y will be mai ntai ne d f or all sa mples t hr o u g h o ut t heir lifec ycle.
T he PI will e ns ure f ull tracea bilit y of c o llecte d bi ol ogical sa m ples fr o m t he parti ci pa nt s 
w hile i n st ora ge at t he ce ntre u ntil s hi p me nt a n d will kee p d oc u me ntati o n of recei pt of 
arri val.
T he sa m ple recei ver will kee p f ull tracea bilit y of  s a mples w hile i n st ora ge a n d d uri n g use, 
u nt il use d, dis p ose d of, or u ntil f urt her s hi p me nt or dis p osal ( w here a p pr o priate) a n d will 
kee p d oc u me ntati o n of rec ei pt of arri val.
S a m ples retai ne d f or f urt her use will be re gistere d i n t he Astra Ze neca bi o ba n k s yste m 
d uri n g t he e nt ire life c ycle.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 4 of 1 0 3
7. 5. 
Wit h dr a w al of I nf or me d C o nse nt f or D o n ate d Bi ol o gic al 
S a m ples
If a parti ci pa nt wi t hdra ws c o nse nt t o t he use of d o nate d bi o lo gical  sa m ples, t he sa mples 
will be dis p ose d if n ot alrea d y a nal yse d a n d t he acti o n d oc u me nte d.
As c ollect i on of d o nate d bi o l ogi c al sa m ples is a n i nte gral part of t he st u d y, t he n t he 
parti ci pa nt is wit h dra w n fr om f urt her st u d y partici patio n.
Astra Ze neca e n s ures t he ce ntral la b orat or y h o l di n g t he sa m ples is/are i nf or me d a b o ut t he 
wi t hdra w n c o nse nt i m me diatel y a n d t hat sa m ples are dis p ose d of/ destr o y e d, t he actio n 
d oc u m e nte d, a n d t he sig ne d d oc u m e nt ret ur ne d t o t he Cli nical U nit.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 5 of 1 0 3
8. 
E T HI C A L A N D R E G U L A T O R Y R E Q UI R E M E N T S
8. 1. 
Et hic al C o n d uct of t he St u d y
T he st u d y  will be perf or me d i n acc or da nce wit h et hical pri nci ples t hat ha ve t heir ori gi n i n 
t he Declarat i on of Helsi n ki a n d are c o nsiste nt wit h I C H G C P a n d t he Astra Ze neca p olic y 
o n Bi o et hi cs a n d H u ma n Bi o l ogi c al Sa m ples.
8. 2. 
P artici p a nt D at a Pr otecti o n
T he I C F will i nc or p orate ( or, i n s o me cases, be acc o m pa nie d b y a se parate d oc u me nt 
i nc or p orati n g) w or di n g t hat c o m plies wit h rele va nt data pr otecti o n a n d pri vac y le gislati on.
All cli nical st u d y fi n di n gs a n d d oc u me nts will be re gar de d as c o nfi de nt ial. T he PI a n d 
me m bers of his/ her researc h tea m m ust n ot discl ose s uc h i nf or mat i on wi t ho ut pri or wri tte n 
a p pr o val fr o m t he S p o ns or.
T he a n o n y mit y of partici pati n g partici pa nt s m ust be mai ntai ne d. Parti ci pa nt s will be 
s pecifie d i n o ut p uts a n d ot her d oc u me nts c o ntai ni n g partici pa nt data b y  t heir parti ci pa nt
n u m ber, n ot b y  na me. D oc u me nts t hat ide ntif y  t he parti ci pa nt (e g, si g ne d I C F) will be 
mai ntai ne d i n c o nfi de nce b y  t he PI.
St u d y  data will be st ore d i n acc or da nce wit h l ocal a n d gl obal data pr otecti o n l a ws.
8. 3. 
Et hics a n d Re g ul at or y Re vie w
T he st u d y  will be s u b mitte d t o t he N atio nal  Re g ulat or y A ge nc y, M H R A, f or re vie w a n d 
a p pr o val, b y Pare xel i n acc or da nce wit h l ocal re g ulat or y pr oce d ures.
T he st u d y  will be s u b mitte d t o t he I E C f or et hical re vie w a n d a p pr o val b y t he PI i n 
acc or da nce wit h l ocal pr oce d ures.
Pare xel will pr o vi de t he I E C a n d PI wit h safet y u p dates/re p orts acc or di n g t o l ocal 
re q uire me nts, i ncl u di n g S U S A Rs, w here rele va nt.
Astra Ze neca will pr o vi de t he Re g ulat or y  Aut h ori t y wit h s afet y u p dates/re p orts acc or di n g 
t o lo c al  re q uire me nts, i ncl u di n g S U S A Rs, w here rele va nt.
C o m pe nsat i on will be reas o na ble a n d relate d t o t he nat ure a n d de gree of i nc o n ve nie nce 
a n d disc o mf o rt as a res ult of partici pat i on i n t he st u d y. I nf or mat i on o n h o w partic i pa nts 
will be c o m pe nsate d is c o ntai ne d i n t he I C F.
8. 4. 
I nfor me d C o nse nt
T he parti ci pa nt s s hall be i nf or me d of t he nat ure, si g nifica nce, i m plicat i ons a n d ris ks of t he 
trial, a n d i nf or me d c o nse nt will be freel y gi ve n a n d e vi de nce d i n writi n g, date d a n d si g ne d, 
or ot her wise mar ke d, b y t he part ici pa nt as e vi de nce t o i n dicate his/ her free i nf or me d 
c o nse nt, pri or t o t he start of t he st u d y.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 6 of 1 0 3
T he nat ure of t he i nf or me d c o nse nt will c o m p l y wit h t he Declaratio n of  Helsi n ki, t he 
c urre nt re q uire me nts of G C P ( C P M P/I C H/ 1 3 5/ 9 5) a n d l ocal re g ulat i on w hic h e ver offers 
t he greater partici pa nt pr otecti o n.
8. 5. 
I ns ur a nce
T he S p o ns or has c o vere d t his cli nical st u d y  b y mea ns of a n i ns ura nce of t he cli nical st u d y 
acc or di n g t o nati o nal re q uire me nts. T he na me a n d a d dress of t he rele va nt i ns ura nce 
c o mpa n y, t he certificate of i ns ura nce, t he p olic y n u m ber a n d t he s u m i ns ure d are p r o vide d 
i n t he PI ’s Site File.
8. 6. 
C h a n ges t o t he Pr ot oc ol a n d I nf or me d C o nse nt F or m
St u d y  pr oce d ures will n ot be c ha n ge d wit h o ut t he m ut ual a gree me nt of t he PI a n d 
Astra Ze neca.
If t here are a n y s u bsta ntial c ha n ges t o t he st u d y pr ot oc ol, t he n t hese c ha n ges will be 
d oc u m e nte d i n a st u d y pr ot oc ol a me n d me nt a n d w here re q uire d i n a ne w versi on of t he 
st u d y pr ot oc ol.
T he a m e n d me nt s h o uld be a p pr o ve d b y  t he E C /I R B a n d t he N atio nal Re g ulat or y  
A ut h ori t y, b efore i m ple me ntati o n, as a p pr o pri ate. L ocal re q uire me nts s h o uld be f oll owe d 
f or re vise d pr ot oc ols.
If a pr ot oc ol a me n d me nt re q uires a c ha n ge t o t he I C F t he I E C/I R B s h o ul d a p pr o ve t he 
re vise d I C F bef ore t he re vise d f or m is use d.
If l ocal re g ulati ons re q ui re, a n y a d mi nistrati ve c ha n ge will be c o m m u nicate d t o or 
a p pr o ve d b y t he I E C/I R B.
8. 7. 
A u dits a n d I ns pecti o ns
N ot a p plica ble.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 7 of 1 0 3
9. 
D A T A Q U A LI T Y A S S U R A N C E A N D D A T A 
M A N A G E M E N T
9. 1. 
Q u alit y C o ntr ol a n d S o urce D at a Verific ati o n
S o urce data verificati o n will be c o n d ucte d wit h d ue re gar d t o partici pa nt c o nfi de nt iality.
T he Cli nical U nit will all o w t he st u d y  mo ni t or a n d S p o ns or re prese ntati ve direct access t o 
all st u d y d oc u me nts, me dical files a n d s o urce d oc u me nts t o e na ble verificat i on of t he st u d y  
data, w hile mai ntai ni n g t he a n o n y mit y of  t he partici pa nt a n d c o nfi de nt iality of  t he data.
I nter nal q uality c o ntr ol will be perf or me d at all sta ges of t he st u d y b y t he Cli nical U nit.
9. 2. 
A u dit/I ns pecti o ns
T he Cli nical U nit facilit ies a n d all st u d y data/ d oc u me ntatio n m a y be a u dite d/i ns pecte d b y 
i n de pe n de nt a u dit or/i ns pect or/a n y re prese ntati ves of re g ulat or y a ut h orities. T he PI m ust 
all o w t he a p plica ble pers o ns access t o all rele va nt facilit ies a n d data/ d oc u me nts. T he PI 
m ust be a vaila ble t o disc uss a n y fi n di n gs/iss ues.
If a n a u dit was perf or me d, t he a u dit certificate will be i ncl u de d i n t he C S R.
9. 3. 
St u d y M o nit ori n g
T he c o n d uct of t he st u d y  will be mo ni t ore d b y a n i n de pe n de nt Pare xel mo ni t or or a 
s u bc o ntracte d m o nit or t o e ns ure c o m plia nce wit h a p plica ble re g ulat or y re q uire me nts a n d 
G C P. T he s u m mar y  of t he d oc u me ntatio n of  t he m o nit ori n g visits will for m  part of t he 
st u d y d o c u me ntatio n a n d will be arc hi ve d as s uc h.
9. 4. 
D at a C ollecti o n
T he Cli n Base ™ s yste m is a n electr o nic s o urce data ca pt uri n g a n d i nf or mat i on 
ma na ge me nt s yste m. T he s yste m c o m bi nes all as pects of s o urce data ca pt uri n g wit h 
pr oces s c o ntr ol a n d cli nical st u d y ma na ge me nt. All cli nical a n d la b orat or y data, e xce pt 
t hose w hi c h are pa per -base d or pr o vi de d b y  e xter nal ve n d or, will be c ollecte d i n 
Cli n Base ™. O nl y pa per -base d data will be parti ci pa nt t o data e ntr y. F or electr o nic s o urce 
dat a, n o data e ntr y will be perf or me d.
T he res p o nsi ble st u d y  mo ni t or will c hec k data at t he m o nit ori n g visits t o t he Cli nical U nit. 
T he PI will e ns ure t hat t he data c ollecte d are acc urate, c o m plete a n d le gi ble. Data will be 
m o nit ore d wi t hi n Cli n Base ™ b y t he st u d y mo ni t or bef ore bei n g e x p orte d. A n y c ha n ges 
ma de d uri n g m o nit ori n g will be d oc u me nte d wit h a f ull a u dit trail wit hi n Cli n Base ™.
9. 4. 1. 
C ase Re p ort F or ms a n d S o urce D oc u me nts
All data o btai ne d usi n g pa per c ollect i on met h o ds d uri n g t he cli nical st u d y  will be rec or de d 
i n Cli n Base ™. All s o urce d oc u me nts fr o m w hic h Cli n Base ™ e ntries are deri ve d s h o ul d be 
pl ace d i n t he part ici pa nt’s pers o nal rec or ds.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 8 of 1 0 3
T he ori gi nal  Cli n Base ™ e ntries f or eac h parti ci pa nt will be c hec ke d a gai nst s o urce 
d oc u m e nts b y t he st u d y mo ni t or. I nsta nces of missi n g or u ni nter preta ble data will be 
di sc usse d wit h t he PI f or res olut i on.
9. 4. 2. 
Access t o S o urce D oc u me nts
D uri n g t he c o urse of t he cli nical st u d y , a st u d y mo ni t or will ma ke Cli nical U nit visit s t o 
re vie w pr ot oc ol c om p lia nce, c o m pare Cli n Base ™ e ntries a n d i n di vi d ual parti ci pa nt ’s 
pers o nal rec or ds, assess I M P acc o u nta bilit y a n d e ns ure t hat t he cli nical st u d y  is bei n g 
c o n d ucte d acc or di n g t o perti ne nt re g ulat or y re q uir e me nts. Cli n Base ™ e ntries will be 
verifie d a gai nst s o urce d oc u me nts. T he re vie w of m e dical rec or ds will be ha n dle d 
c o nfi de nt iall y t o e ns ure partici pa nt a n o n y mit y.
C hec ki n g of t he Cli n Base ™ e ntries f or c o m plete ness a n d clarit y a n d verif yi n g wit h s o urce 
d oc u m e nts, will be re q uire d t o m o nit or t he cli nical st u d y for c o m plia nce wi t h G C P a n d 
ot her re g ulat i ons. M ore o ver, re g ulat or y  a ut h orities of certai n c o u ntries, I E Cs/I R Bs ma y 
wi s h t o carr y o ut s o urce data ins pect i ons o n -site, a n d t he S p o ns or’s cli nical q uality 
ass ura nce gr o u p ma y wis h t o carr y o ut a u dits. Direct access t o s o urce data will be re q uire d 
f or t hese i ns pecti o ns a n d a u dits; t he y will be carrie d o ut gi vi n g d ue c o nsi derati o n t o data 
pr otecti o n a n d partici pa nt c o nfi de nt iality.  T he PI ass ures t he S p o ns or of t he necessar y 
s u p p ort at all ti mes.
9. 5. 
D at a M a n a ge me nt
Pare xel will utili se sta n dar dise d a n d vali date d pr oce d ures a n d s yste ms t o c ollect, pr ocess 
a n d file t he cli nical data of t his st u d y. A n y s yste m use d will b e c o mplia nt wi t h FD A 2 1 
C F R Part 1 1 re q uire me nts.
A D M P will be pre pare d t o descri be t he pr ocesses a n d data -fl ow wi t hi n t he cli nical st u d y. 
Ti meli nes, versi o ns f or t he c o m p uter s yste ms a n d t he c o di n g will be defi ne d i n t he D M P, 
a n d if a p plica ble, sp o ns or s pecific re q uests will als o be d oc u me nte d wit hi n. T he D M P will 
be fi nalis e d bef ore first d ose w here p ossi ble b ut bef ore data base l oc k.
A D V S will be create d t o o utli ne t he vali dat i on c hec ks t o be perf or me d d uri n g t he st u d y . 
T he D V S m ust be fi nali se d bef ore data vali dat i on.
After t he data has bee n m o nit ore d b y  t he res p o nsi ble st u d y mo ni t or all data recei ve d will 
be re vie we d, l o g ge d a n d file d.
T he ra w data i nte n de d f or f urt her pr ocessi n g will be c hec ke d b y sta n dar d r o uti nes or 
acc or di n g t o t he D V S a n d q ueries will be ge nerate d a n d se nt t o t he PI f or re vie w a n d 
res olut i on. C orrecti o ns res ult i n g fr o m t hese q ueries will be c o nfir me d o n t he DC Fs. T hi s 
pr ocess will be re peate d u ntil n o f urt her discre pa ncies are f o u n d. T he data will t he n be 
decl are d as clea n. A p plica ble d oc u me ntati o n will be st ore d i n t he st u d y files.
O nl y trai ne d st u d y  staff will ha ve access t o t he cli nical data base a n d e ver y cha n ge i n data 
will ha ve a f ull a u dit trail.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 
7 9 of 1 0 3
1 0. 
E V A L U A TI O N A N D C A L C U L A TI O N O F V A RI A B L E S
1 0. 1. 
S afet y V ari a bles
1 0. 1. 1. 
A d verse E ve nts
All A E s will  be c o de d usi n g Me d D R A v oca b ular y a n d will be liste d f or eac h parti ci pa nt .
F or assi g ni n g A E s t o a s pecific treat me nt/ d ose, t he f oll owi n g g ui deli nes s h o ul d be 
f oll owe d:
 
A E s wi t h start date/ti me at t he ti me of or after d osi n g (f or eac h s pecific 
treat me nt/ d ose) u ntil F o ll ow- U p Visi t will be assi g ne d t o t he s pecific treat me nt/ d ose.
 
A E s wi t h u n k n o w n start ti mes, b ut wit h start date k n o w n, will be i m p ute d wit h a ti me 
of  0 0: 0 0, u nless t he start date c orres p o n ds t o a n y gi ve n d osi n g date. I n t his case t he 
start ti me will be i m p ute d wit h t he ti me of d osi n g. If t his res ults i n a start date/ti me 
after e n d date/ti me of t he A E , t he n t he ti me will als o be i m p ute d wit h 0 0: 0 0.
 
A E s wi t h c o mpletel y u n k n o w n start dates will be i m p ute d wit h t he date a n d ti me of 
d osi n g, u nless t he e n d date is k n o w n a n d pri or t o d osi n g; i n t hat case t he start date will 
be i m p ute d as t he date of Scree ni n g a n d a ti me of 0 0: 0 0.
 
A E s wi t h p artiall y k n o w n start dates/ti mes will be treate d as f oll o ws:
 
If o nl y t he da y is missi n g, t he n t he da y will be i m p ute d wit h t he first da y of t he 
m o nt h, u nless t he m o nt h a n d year i n w hic h t he A E starte d is a m o nt h a n d year i n 
w hic h I M P was a d mi nistere d, t he n t he da y will be i m p ute d wit h t he first da y  o n 
w hic h I M P was a d mi nistere d i n t hat m o nt h. If t his res ults i n a start date after t he 
e n d date, t he n t he da y will be i m p ute d wit h t he first d a y of t he mo nt h.
 
If o nl y  t h e mo n t h is missi n g a n d t he ye ar is a year i n w hic h I M P was 
a d mi nistere d, t he n t he m o nt h will be i m p ute d wit h t he first m o nt h i n w hic h I M P 
was a d mi nistere d. If t his res ults i n a start date after t he e n d date of t he A E , t he n 
t he mo nt h will  be i m p ute d wit h J A N. If t he k n o w n year part is n ot a y ear i n w hic h 
I M P was a d mi nistere d, t he n t he m o nt h will als o be i m p ute d wit h J A N.
 
If b ot h t he da y  a n d mo nt h is missi n g a n d t he year is a y ear i n w hic h I M P was 
a d mi nistere d, t he n t he da y a n d mo n t h will be i m p ute d wit h t he da y a n d mo n t h of 
d osi n g. If t his res ults i n a start date after e n d date, t he n t he da y a n d m o nt h will be 
i m p ute d wit h 0 1J A N. If t he year is n ot a year i n w hic h I M P was a d mi nistere d, 
t he n t he da y a n d mo nt h will  als o be i m p ute d wit h 0 1J A N.
 
If o nl y t he year is missi n g, t he n t he y ear will be i m p ute d wit h t he year of d osi n g.
 
Missi n g ti mes will be i m p ute d as 0 0: 0 0 h or wit h t he ti me o f d osi n g f or e ve nts 
starti n g o n a d osi n g da y.
F or p ur p ose of t he A E s u m maries, t he f oll owi n g will  a p pl y:
 
A E s wi t h u n k n o w n i nte nsit y will be treate d as “se vere” f or t he ta b ulati ons.
 
A E s wi t h u n k n o w n relat i ons hi p will be treate d as “relate d” f or t he ta b ulat i ons.
 
A E s wi t h u n k n o w n serio us ness will  be treate d as “serio us” f or t he ta b ul at i ons.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 0 of 1 0 3
T here will be n o i m p utati o n of A E data f or t he data list i n gs. All data will be liste d as 
rec or de d i n Cli n Base ™.
A d verse e ve nts wi t h o nset (start date/ti me) after d osi n g will be s u m marise d b y tr e at me nt 
gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  AZ D 7 4 4 2, t otal  AZ D 7 4 4 2 a n d p o ole d 
pl ace b o). Ta b ulat i ons will i ncl u de ca usalit y a n d se verit y ( mil d, mo derate a n d se vere). All 
ta b ulat i ons will be prese nte d b y S O C a n d P T wi t h t he e xce pti on of t he ca usalit y a n d 
se verity ta bles, w hic h will be prese nte d b y P T o nl y. F urt her m ore, list i n gs of S A E a n d A E s
t hat le d t o wit h dra wal will be ma de a n d t he n u m ber of parti ci pa nt s w h o ha d a n y A E , 
S A E s, a n d disc o nt i n uati on e ve nts will be s u m maris e d. T he A Es t hat occ ur bef ore d osi n g 
will be e xcl u de d fr o m t he s u m mar y ta bles.
A d verse e ve nts will be liste d b y eac h d ose of A Z D 7 4 4 2 a n d p o ole d place b o. T he 
f oll owi n g i nf or mat i on will be i ncl u de d i n t he list i n gs: ver bati m ter m, Me d D R A S O C, P T 
a n d l o west le vel t er m, start date/ti me, e n d date/ti me, ti me fr o m last d ose, ca usality,  acti on 
ta ke n, w het her t he A E was classifie d as seri o us a n d t he o utc o me.
All ta b ulat i ons will i ncl u de t he n u m ber a n d perce nta ge of parti ci pa nt s.
1 0. 1. 2. 
L a b or at or y Assess me nts
Hae mat ol o g y  a n d cli nical c he mistr y val ues will be liste d b y partici pa nt a n d ti me p oi nt 
i ncl u di n g c ha n ges fr om baseli ne a n d re peat/ u nsc he d ule d meas ure me nts. S u m mar y 
ta b ulat i ons will be prese nte d b y treat me nt gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  
A Z D 7 4 4 2, t otal A Z D 7 4 4 2 a n d p o ole d place b o) a n d ti me p o i nt for t he safet y a nal ysis set. 
T he baseli ne f or t he meas ure me nts will be t he last pre -d ose assess me nt perf or me d o n 
a d missi o n . C ha n ges fr o m baseli ne will be calc ulate d a n d prese nte d f or all fol l ow- u p v isits. 
S hift ta bles will als o be prese nte d.
A n y la b orat or y  para meters with res ults fr o m t he la b orat or y gi ve n as ' < x x' or ' > x x' i n t he 
data base will be i m p ute d wit h t he a bs o l ute val ue of t he n u m ber wit h o ut t he si g n (e g, < 2. 2 
will be i m p ute d as 2. 2) f or t he descri pt i ve statistics a n d c ha n ges fr om baseli ne.
T he list i n gs will i ncl ude t he f oll o wi n g i nf or mat i on: test na me, date of meas ure me nt, 
refere nce ra n ge, res ult a n d fla gs f or a n y meas ure me nts t hat are o utsi de t he refere nce ra n ge 
(e g, Astra Ze neca, pr o gra m, or la b orat or y ra n ges). Cli nical la b orat or y data will be re p orte d 
i n t he u nits pr o vide d b y  t he cli nical la b orat or y for t he D E C meet i n g (if a p plica ble), a n d i n 
S y st e m I nter nati onal u nits i n t he C S R.
A d dit i onal listi n gs will be prese nte d f or t he f oll owi n g:
 
Uri nal ysis ( macr osc o pic a n d micr osc o pic, if a p plica ble)
 
Pre g na nc y testi n g (i n cl u di n g F S H)

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 of 1 0 3
1 0. 1. 3. 
Vit al Si g ns
T he res ults of t he vital si g ns meas ure me nts will be liste d b y partici pa nt a n d ti me p oi nt 
i ncl u di n g t he date/ti me of t he assess me nt, c ha n ges fr om baseli ne a n d re peat/ u nsc he d ule d 
meas ure me nts. T he baseli ne f or vital si g ns meas ure me n ts will be t he pre-d ose assess me nt 
o n Da y 1. Descri pt i ve statistics will be prese nte d b y treat me nt gr o u p ( d ose le vel or 
a d mi nistrati o n pr ocess of  A Z D 7 4 4 2, t otal A Z D 7 4 4 2 , a n d p o ole d place b o) a n d ti me p oi nt 
f or b ot h o bser ve d val ues a n d c ha n ges fr om baseli ne.
1 0. 1. 4. 
Resti n g 1 2 -le a d Electr oc ar di o gr a m
T he res ults of t he 1 2-l ea d E C G res ults will be liste d f or eac h parti ci pa nt wi t h int er pretati o n 
b y t he PI as “ N or mal”, “ A b n or mal C S” a n d “ A b n or mal N C S”.
1 0. 1. 5. 
P h ysic al E x a mi n ati o n
T he baseli ne/scree ni n g res ults o f t he p h ysical e xa mi nat i on will be d oc u me nte d i n me dical 
hist or y  for eac h parti ci pa nt .
A n y ne w or a g gra vate d cli nicall y rele va nt a b n or mal me dical p h ysical e xa mi nat i on fi n di n g 
c o mpare d t o t he baseli ne assess me nt will be re p or te d as a n A E.
1 0. 1. 5. 1. 
I njecti o n Site Re acti o n
Res ults of t he i njecti o n site react i on (i ncl u di n g assess me nt of size, re d ness/er yt he ma, 
s welli n g, itc hi n g/ pr urit us, pai n or te n der ness, i n d urati o n, disc ol ourati o n ) will be liste d b y 
parti ci pa nt f or C o h ort 1 b (I M a d mi nistratio n c o h ort).
1 0. 2. 
P h ar m ac o ki netic V ari a bles
W here p ossi ble, t he P K para meters will be est i mate d f or A Z D 7 4 4 2 (eac h m A b: A Z D 8 8 9 5 
a n d A Z D 1 0 6 1) o n ser u m c o nce ntrati o ns. 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 2 of 1 0 3
1 0. 2. 1. 
Ser u m P K P ar a meters
C ma x
O bser ve d ma xi m u m c o nce ntrati o n
t ma x 
Ti me t o reac h ma xi m u m c o nce ntrati o n
A U Clast
Area u n der t he c o nce ntrati o n -c ur ve fr o m ti me zer o t o t he ti me of last q ua ntifia ble 
c o nce ntrati o n
A U Ci nf
Area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me zer o e xtra p olate d t o i nfi nit y 
t ½ λz
Ter mi nal eli mi nati o n half -life, esti mated as (l n 2)/ z
C L 
S y ste mic cleara nce (I V a d mi nistrati o n o nl y)
C L/ F 
A p pare nt t otal cleara nce (I M a d mi nistrati o n o nl y)
Vss
V ol u me of distri b uti o n at stea d y state (I V a d mi nistrati o n o nl y)
Vz
V ol u me of distri b uti o n at ter mi nal p hase (I V a d mi nistrati o n o nl y )
Vz/ F
A p pare nt v ol u me of distri b uti o n at ter mi nal p hase (I M a d mi nistrati o n o nl y)
tlast
Ti me of last q ua ntifia ble c o nce ntrati o n
Bi oa vaila bilit y ( F)
Bi oa vaila bilit y f or e xtra vasc ular a d mi nistrati o n, calc ulate d as A U C rati o of I M 
a d mi nistrati o n t o I V a d mi nistrati o n.
D ose n or m alise d C ma x, A U Ci nf , a n d A U Clast will be calc ulate d f or eac h m A b: A Z D 8 8 9 5 
a n d A Z D 1 0 6 1. 
T he f o ll owi n g para m eters will be calc ulate d f or dia g n ostic p ur p oses a n d will als o be 
s u m marise d.
λz l o wer
L o wer (earlier) t use d f or λz deter mi nati o n
λz u p per
U p per (later) t use d f or λz deter mi nati o n
λz, N
N u m ber of data p oi nts i ncl u de d i n t he l o g -li near re gressi o n a nal ysis
λz s pa n rati o
Ti me peri o d o ver w hic h λz was deter mi ne d as rati o of t ½ λz
Rs q _a dj
Statistical meas ure of fit f or t he re gressi o n use d f or λz deter mi nati o n a dj uste d f or t he 
n u m ber of use d data p oi nts ( n o bs)
λz
Ter mi nal eli mi nati o n rate c o nsta nt
% A U Ce xtr
E xtra p olate d area u n der t he c ur ve fr o m tlast t o i nfi nit y, e x presse d as perce nta ge of 
A U C i nf
A d dit i onal ser u m P K para meters ma y be deter mi ne d w here a p pr o priate.
1 0. 2. 2. 
C alc ul ati o n or Deri v ati o n of P h ar m ac o ki netic P ar a m eters
T he P K a nal yses of t he ser u m c o nce ntrati o n data f or A Z D 7 4 4 2 m A bs ( A Z D 8 8 9 5 a n d 
A Z D 1 0 6 1) will be perf or me d at C o va nce o n be half o f Cli nical P har mac o ki net ic Allia nce, 
Astra Ze neca R & D a n d will be calc ulate d acc or di n g t o t he Astra Ze neca sta n dar ds 
( G uideli ne f or P K E val uat i ons i n Cli nical St u di es, v 3, Fe b 2 0 2 0).
T he P K a nal ysis will, w here data all o w, be carrie d o ut usi n g act ual ela pse d ti mes 
deter mi ne d fr o m t he P K sa m pli n g a n d d osi n g ti mes rec or de d i n t he data base. If act ual 
ela pse d ti mes are missi n g, n o mi nal ti mes ma y be use d

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 3 of 1 0 3
N o mi nal sa m pli n g ti mes will be use d f or i nteri m P K para meter calc ulat i ons.
P K para meters will be deri ve d usi n g n o n c o mpart me ntal met h o ds wi t h P h oe ni x ® 
Wi n N o nli n
® Versi o n  8. 1, or hig her.
1 0. 3. 
I m m u n o ge nicit y a n d P h ar m ac o d y n a mics
T he prese nce or a bse nce of A D A s t o A Z D 7 4 4 2 fr o m Da y 1 pre-d ose t o Da y  3 6 1 will be 
c ollecte d, i ncl u di n g t he titer f or sa m ples c o nfir me d p osit i ve f or A D A.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 4 of 1 0 3
1 1. 
S T A TI S TI C A L M E T H O D S A N D S A M P L E S I Z E 
D E T E R MI N A TI O N
1 1. 1. 
Descri pti o n of t he A n al ysis Sets
1 1. 1. 1. 
S afet y A n al ysis Set
T he safet y a nal ysis set will i ncl u de all part ici pa nts w h o were ra n d o mise d a n d recei ve d a n y 
a mo u nt of A Z D 7 4 4 2.
U nless ot her wise state d, t he safet y a nal ysis set will be use d f or t he prese ntati o n of all 
safety a nal yses a n d i m m u n o ge nicit y. E x p os ure t o I M P will als o be prese nte d usi n g t he 
safety a nal ysis set.
1 1. 1. 2. 
P h ar m ac o ki netic A n al ysis Set
T he P K a nal ysis set will c o nsist of all p arti ci pa nt s i n t he safety a nal ysis set w h o r ecei ve d 
A Z D 7 4 4 2 a n d w h o ha ve e val ua ble ser u m P K data, wit h n o i m p orta nt pr ot oc ol de viati o ns 
t ho u g ht t o i m pact o n t he a nal ysis of t he P K data.
T he e xcl usi o n of a n y  part ici pa nts fr om P K a nal ysis set or a n y  time p oi nts fr o m t he 
calc ulat i on of t he P K para meter s will be d oc u me nte d b y t he P K Scie nt ist incl u di n g t he 
reas o n(s) f or e xcl usi on.
T he a vaila ble c o nce ntrati o n data a n d P K para meter data f or a n y  parti ci pa nt s e xcl u de d fr o m 
t he P K a nal ysis set will be liste d o nl y. C o nce ntrati o n data f or partici pa nt s e xcl u de d fr om 
t he P K a nal ysis set will be prese nte d i n t he i n di vi d ual fi g ures o f c o nce ntrati o n vers us t i me 
pl ots.
1 1. 1. 3. 
R a n d o mi se d Set
T he Ra n d o mi se d Set will c o nsist of all part ici pa nts ra n d o mise d i nto t he st u d y .
1 1. 2.   
Met h o ds of St atistic al A n al yses
1 1. 2. 1. 
Ge ner al Pri nci ples
T he st atistical met h o d ol o g y  belo w descri bes t he stati stical a nal ysis as it is foresee n w he n 
t he st u d y is bei n g pla n ne d.
If circ u msta nces s h o ul d arise d uri n g t he st u d y re n deri n g t he a nal ysis i na p pr o priate, or if i n 
t he mea nt i me i m pr o ve d met h o ds of a nal ysis s h o ul d c o me t o lig ht, differe nt a nal yses ma y  
be perf or m e d. A se parate S A P will n ot be writte n f or t he st u d y . A n y de viati ons fr om t he 
statistical met h o d ol o g y  defi ne d i n t his pr ot oc ol, reas o ns f or s uc h de viati ons a n d all 
alter nati ve/a d diti onal st atistical a nal yses t hat ma y be perf or me d will be descri be d i n t he 
C S R. S uc h c ha n ges t o a nal yses ma y be writte n i nt o a n a b bre viate d S A P, if a p pr o priate. 
T he verificat i on a n d re vie w of all statistical m o delli n g ass u m pt i ons will be d oc u me nte d 
a p pr o priatel y.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 5 of 1 0 3
All ori gi nal  a nd de rive d para meters , as well as de m o gra p hic a n d dis p osit i on data will be 
liste d a n d descri be d usi n g s u m mar y statistics. All safety data (sc he d ule d a n d u nsc he d ule d) 
will be prese nte d i n t he data list i n gs.
De m o gra p hic a n d baseli ne data will be s u m mari se d b y tr e at me nt gr o u p ( d ose le vel or 
a d mi nistrati o n pr ocess of  A Z D 7 4 4 2, t otal A Z D 7 4 4 2 a n d p o ole d place b o). 
P har mac o ki net ic data will be s u m marise d b y treat me nt gr o u p. Safety a n d t olera bilit y data 
will be s u m mari se d b y treat me nt gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  AZ D 7 4 4 2, 
t otal A Z D 7 4 4 2 a n d p o ole d place b o).
Fre q ue nc y c o u nts ( n u m ber of parti ci pa nt s [ n] a n d perce nta ges) will be ma de f or eac h 
q ualitat i ve varia ble. Descri pti ve statistics ( n, mea n, S D, me dia n, mi ni m u m a n d ma xi m u m) 
will be calc ulate d f or eac h q ua nt itati ve varia ble ( u nless ot her wise state d). Descri pt i ve 
statistics will o nl y be prese nte d if n > 3. If n o partici pa nt s ha ve data at a gi ve n ti me p o i nt, 
t he n o nl y n = 0 will be prese nte d. If n < 3, o nl y  t he n, mi ni m u m a n d ma xi m u m will be 
prese nte d , a n d if n = 3, o nl y t he n, me dia n, mi ni m u m a n d ma xi m u m will be prese nte d ; the 
ot her descri pti ve statist ics will be left bla n k.
T he f o ll owi n g r ul es will a p pl y t o a n y re peate d safet y assess me nts occ urri n g wit hi n eac h 
c o h ort:
 
If t he re peate d meas ure me nt of a s pecific para meter occ urs pri or t o I M P 
a d mi nistrati o n ( Da y 1), t he n t he last o btai ne d val ue pri or t o d osi n g will be use d i n t he 
descri pt i ve statistics a n d i n t he calc ulati o n of c ha n ges fr o m baseli ne;
 
If t he re peate d meas ure me nt of a s pecific para meter occ urs after I M P a d mi nistrati o n 
( Da y 1), t he n t he first ( n o n -missi n g) val ue after d osi n g will be use d i n descri pti ve 
statistics a n d i n t he calc ulati on of c ha n ges fr o m baseli ne.
T he pl a n ne d se q ue nce f or meas ure me nt of m ult i ple assess me nts at t he sa me ti me p oi nt is 
descri be d i n Secti o n 3. 1. 1 .
F or safet y assess me nts perf or me d at scree ni n g a n d t he f o ll ow- u p, t he f o ll owi n g r ul es will 
a p pl y f or a n y re peate d assess me nts:
 
If t he re peate d assess me nt occ urs at Scree ni n g, t he last a vaila ble val ue will be use d i n 
t he s u m mar y st atistics;
 
If t he re peate d assess me nt occ urs at t he F oll ow- u p Vi sit, t he first n o n-missi n g 
assess me nt will be use d i n t he s u m mar y statist ics.
All st atistical a nal yses a n d pr o d ucti o n of ta bles, fi g ures a n d listi n gs will be perf or me d 
usi n g S A S ® versi o n 9. 4 or l ater.
1 1. 2. 1. 1. 
Missi n g D at a
Missi n g dates a n d ti mes i n t he A E data will be ha n dle d as descri be d i n Sect i on 1 0. 1. 1 . 
C o nce ntrati o ns t hat are N Q i n t he P K data will be ha n dle d as descri be d i n Secti o n 1 1. 2. 5 .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 6 of 1 0 3
T here will be n o i m p utati o ns of ot her missi n g data. All partici pa nt s will be i ncl u de d i nt o 
t he safet y a nal yses as far as t he data per mit.
1 1. 2. 2. 
P artici p a nt C h ar acteristics
A ra n d omisat i on listi n g will be prese nte d a n d i ncl u de t he f oll owi n g: eac h parti ci pa nt ’s 
ra n d omisat i on n u m ber, t he parti cipa nt ’s f ull e nr ol me nt n u m ber, t he treat me nt t o w hic h t he 
parti ci pa nt has bee n ra n d omise d a n d t he c o u ntr y w here t he st u d y ce ntre is l ocate d.
Parti cipa nt s a n d/ or data e xcl u de d fr om t he P K a nal ysis set will be liste d i ncl u di n g t he 
reas o n f or e xcl usi on. Parti ci pa nt dis p osit i on will be s u m mari se d a n d will i ncl u de t he 
f oll owi n g i nf or mat i on: n u m ber of parti ci pa nt s ra n d o mise d a n d d ose d, n u m ber a n d 
perce nta ge of parti ci pa nt s c o mplet i n g t he st u d y a n d t he n u m ber a n d perce nta ge of 
parti ci pa nt s w h o were wit h dra w n (i ncl u di n g reas o ns f or wit hdra wal ). Dis p ositio n data will 
be prese nte d base d o n all part ici pa nts ra n d o mise d.
Parti cipa nt disc o nti n uati o ns will be liste d i ncl u di n g t he date of st u d y e xit, d urati o n o f 
treat me nt a n d reas o n f or disc o nt i n uati on. A list i n g of i nf or me d c o nse nt res p o nse will als o 
be prese nte d.
1 1. 2. 2. 1. 
De m o gr a p hic a n d B aseli ne D at a
De m o gra p hic vari a bles (a ge, ge n der, race, et h nicit y,  hei g ht, weig ht a n d B MI) will be liste d 
b y p arti ci pa nt . De mo gra p hic c haracteri stics (a ge, ge n der, race a n d et h nicit y) a n d 
parti ci pa nt c haracteristics ( hei g ht, wei g ht a n d B MI) will be s u m mari se d b y treat me nt 
gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  AZ D 7 4 4 2, t otal  AZ D 7 4 4 2 a n d p o ole d 
pl ace b o) f or all ra n d o mise d parti ci pa nt s. T he de n o mi nat or f or perce nta ges will be t he 
n u m ber of ra n d omise d parti ci pa nt s.
Me dical hist or y  data will be liste d b y parti ci pa nt i ncl u di n g visit, descri pti on of t he 
di sease/ pr oce d ure, Me d D R A S O C, Me d D R A P T , start date a n d st o p date ( or o n g oi n g if 
a p plica ble).
1 1. 2. 3. 
Pri or a n d C o nc o mit a nt Me dic ati o n a n d Dr u g A d mi nis tr ati o n
1 1. 2. 3. 1. 
Pri or a n d C o nc o mit a nt Me dic ati o n
Pri or me dicat i ons are t h ose t hat starte d a n d st o p pe d pri or t o si gni n g of t he I C F; all 
me dicat i ons ta ke n after t he I C F si g ni n g are c o nsi dere d as c o nc o mita nt (i ncl u di n g 
me dicat i ons t hat starte d pri or t o d osi n g a n d c o n tin ue d after). Pri or me dicati o n starte d 
wi t hi n 3 mo n t hs prior t o t he first d ose of I M P will be rec or de d als o i n t he c o nc o mita nt 
me dicat i on m o d ule of Cli n Base ™. 
Pri or a n d c o nc o mita nt m e dicat i on will be liste d b y partici pa nt a n d will i ncl u de t he 
f oll owi n g i nf or mat i on: re p orte d na me, P T , t he r o ute of a d mi nistrati o n, d ose, fre q ue nc y, 
start date/ti me, d urati o n a n d i n dicat i on. Pri or a n d c o nc o mita nt me dicat i on will be c o de d 
acc or di n g t o t he S p o ns or’s dr u g dict i onar y .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 7 of 1 0 3
T he d urati o n will be calc ulate d as:
D urati o n = (e n d date/ti me ) – (start date/ti me)
T he d urati o n m a y be prese nte d i n h o urs or da ys i n t he listi n g de pe n di n g o n t he 
a p plica bilit y t o t he e mer gi n g data. F or me dicati ons wit h partial or c o m pletel y missi n g start 
date/ti mes a n d/ or e n d date/ti mes, t he d urati o n will n ot be calc ulate d.
Me dicat i ons wit h missi n g or partial start date/ti me a n d/ or e n d date/ti me s uc h t hat it is n ot 
p ossi ble t o classif y as pri or or c o nc o mita nt will be c o nsi dere d as c o nc o mita nt i n t he 
listi n gs.
1 1. 2. 3. 2. 
Dr u g A d mi nistr ati o n
Dr u g a d mi nistrati o n dates a n d ti mes will be liste d f or eac h partici pa nt .
1 1. 2. 4. 
S afet y a n d T oler a bilit y
All safety data (sc he d ule d a n d u nsc he d ule d) will be prese nte d i n t he data list i n gs, s orte d b y 
treat me nt gr o u p a n d parti ci pa nt . C o nti n u o us varia bles will be s u mmari se d usi n g 
descri pt i ve statistics ( n, mea n, S D, mi ni m u m, me dia n, ma xi m u m) b y treat me nt gr o u p 
( d ose le vel or a d mi nistrati o n pr ocess of  AZ D 7 4 4 2, t otal  AZ D 7 4 4 2 a n d p o ol e d place b o). 
Cate g orical varia bles will be s u m maris e d i n fre q ue nc y ta bles (fre q ue nc y a n d pr o p orti o n) 
b y treat me nt gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  A Z D 7 4 4 2, t otal A Z D 7 4 4 2 a n d 
p o ol e d place b o). T he a nal ysis o f t he safet y varia bles will be base d o n t he safet y a nal ysis 
set.
A d verse e ve nts will be s u m mari se d b y P T a n d S O C usi n g Me d D R A v oca b ular y . 
F urt her m ore, list i n gs of S A Es a n d A Es t hat le d t o wit hdra wal  will be ma de a n d t he 
n u m ber of parti ci pa nt s w h o ha d a n y AE, S A Es, A Es t hat l e d t o wit hdra wal , a n d A Es wit h 
se vere i nte nsity will  be s u m marise d. A d verse e ve nts t hat occ ur bef ore d osi n g will  be 
re p orte d se paratel y.
Ta b ulat i ons a n d list i n gs of data f or vital si g ns, cli nical la b orat or y tests a n d E C Gs (listi n gs 
o nl y), will be prese nte d. A n y ne w or a g gra vate d cli nicall y rele va nt a b n or mal me dical 
p h ysical e xa mi nat i on fi n di n g c om pare d t o t he baseli ne assess me nt will be re p orte d as a n 
A E. Data will be s u m mari se d for t he o bser ve d val ues at eac h sc he d ule d assess me nt, 
t o get her wit h t he c orres p o n di n g c ha n ges fr o m t he baseli ne w he n baseli ne is defi ne d. 
Cli nical la b orat or y  data will be re p orte d i n t he u nit s pr o vi de d b y t he cli nical la b orat or y for 
t he D E C meet i n g, a n d i n S ystè me I nter nati o nal u nits i n t he C S R.
O ut -of -ra n ge val ues f or safety lab orat or y  will be fla g ge d i n i n di vi d ual listi n gs, as well as 
s u m marise d descri pt i vel y usi n g a gree d sta n dar d refere nce ra n ges a n d/ or e xte n de d 
refere nce ra n ges (e g, Astra Ze neca, pr o gra m, or la b orat or y ra n ges).

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 8 of 1 0 3
1 1. 2. 5. 
P h ar m ac o ki netics
T he ser u m A Z D 7 4 4 2 m A bs ( A Z D 8 8 9 5 a n d A Z D 1 0 6 1) c o nce ntrati o ns a n d P K para meters 
will be liste d a n d prese nte d i n ta b ular a n d gra p hical f or m as a p p r o priate acc or din g t o t he 
m o st rece nt versi o n of t he Astra Ze neca C P E ta bles, list i n gs, a n d fi g ures sta n dar ds, t hat 
i ncl u des a p plica ble descri pti ve statistics, ha n dli n g of i n di vi d ual c o nce ntrati o ns bel o w t he 
L L O Q f or list i n gs, descri pti ve statistics a n d fi g ures, a n d precisi on a n d r o u n di n g r ules f or 
c o nce ntrati o ns a n d P K para meter data.
1 1. 2. 5. 1. 
Ser u m C o nce ntr ati o n D at a
F or A Z D 7 4 4 2 m A bs ( A Z D 8 8 9 5 a n d A Z D 1 0 6 1) , t he ser u m c o nce ntratio ns f or eac h 
sc he d ule d ti me p oi nt will be s u m marise d b y treat me nt gr o u p usi n g a p pr o pri ate descript i ve 
statistics, base d o n t he P K a nal ysis set. A listi n g of all c o nce ntrati o n-ti me data, ie, P K 
sc he d ule d ti mes, act ual sa m ple c o llecti on ti mes, sa m ple act ual relat i ve ti mes, as well as 
deri ve d sa m pli n g ti me de viat i ons will be prese nte d b y treatme nt  gr o u p f or all parti ci pa nt s
i n t he safety a nal ysis set . A list i n g of c o nce ntrati o n vers us sc he d ule d ti me data will be 
prese nte d b y treat me nt gr o u p f or t he safety a nal ysis set.
1 1. 2. 5. 2. 
Ser u m P h ar m ac o ki netic P ar a meter Listi n gs 
All re p orta ble A Z D 7 4 4 2 P K para meters, i ncl u di n g i n di vi d ual dia g n ostic a n d λz- r elate d 
para m eters, will be liste d f or eac h parti ci pa nt b y treat me nt gr o u p , base d o n t he safet y
a nal ysis set.
1 1. 2. 5. 3. 
Ser u m P h ar m ac o ki netic P ar a meter Descri pti ve St atistics
All P K para meters will be s u m mari se d b y tr e at me nt gr o u p usi n g a p pr o priate descri pt i ve 
statistics, base d o n t he P K a nal ysis set.
1 1. 2. 5. 4. 
Gr a p hic al Prese nt ati o n f or Ser u m C o nce ntr ati o n D at a
I n di vi d ual c o nce ntratio n -ti me data will be gra p hicall y prese nte d o n li near a n d 
se mi-l og ari t hmic scales, f or all parti ci pa nt s i n t he safet y a nal ysis set . C o m bi ne d i n di vi d ual 
ser u m c o nce ntratio n vers us act ual  ti mes will be pl otte d o n b ot h t he li near a n d 
se mi-l og ari t hmic scale f or all parti ci pa nt s i n t he P K a nal ysis set. Pl ots will  be gr o u pe d b y 
treatme nt  gr o u p. Fig ures f or t he ge o metric mea n ( -/ + g S D) ser u m c o nce ntrati o n-ti me data 
will be prese nte d f or all tr e at me nt gr o u ps o n b ot h a li near a n d se mi -l ogari t h mic scale ( n o 
g S D prese nte d), f or all partici pa nt s i n t he P K a nal ysis set.
All pl ots will be base d o n t he P K a nal ysis set, wit h t he e xce pti o n o f i n di vi d ual pl ots b y 
parti ci pa nt w hic h will be base d o n t he safet y a nal ysis set.
1 1. 2. 6. 
I m m u n o ge nicit y a n d P h ar m ac o d y n a mics
1 1. 2. 6. 1. 
A nti -dr u g A nti b o d y Titers
T he prese nce or a bse nce of A D A t o A Z D 7 4 4 2 (ei t her A Z D 8 8 9 5 a n d/ or A Z D 1 0 6 1) 
c ollecte d, i ncl u di n g t he titer f or sa m ples c o nfir me d p osit i ve f or A D A f or eac h treat me nt 
gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  AZ D 7 4 4 2) will be liste d b y  p arti ci pa nt a n d 
ti me p oi nt. Ta b ul at i ons will be pr o vi de d f or eac h treat me nt gr o u p ( d ose le vel or 

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 9 of 1 0 3
a d mi nistrati o n pr ocess of  A Z D 7 4 4 2). T he res ults will be prese nte d base d o n t he safet y 
a nal ysis set.
T he res ults of t he A D A assess me nts will be liste d f or eac h parti ci pa nt a n d ti me p oi nt. T his 
will i ncl u de t h e classificat i on of t he res p o nse ( p ositi ve/ ne gat i ve) a n d t he meas ure d titers 
w here a p pr o priate. S u m mar y  ta bles will be prese nte d, b y treat me nt gr o u p ( d ose le vel or 
a d mi nistrati o n pr ocess of  A Z D 7 4 4 2 ), for t he n u m ber a n d perce nta ge of parti ci pa nt s wit h 
p osi ti ve/ ne gati ve res ults at eac h ti me p oi nt, base d o n t he Safety a nal ysis set.
I n a d diti on, t he A D A titers ( n, me dia n, mi ni m u m a n d ma xi m u m) will be s u m mari se d b y 
treat me nt gr o u p ( d ose le vel or a d mi nistrati o n pr ocess of  A Z D 7 4 4 2 ) for all partici pa nt s 
wi t h a p ositive c o nfir mat or y  assa y at eac h ti me p oi nt; t his ta b ulati on will i ncl u de a 
s u m mar y of t he hi g hest titer acr oss all t i me p oi nts f or eac h partici pa nt .
T he i m pact of A D A o n P K, a n d ass ociat i on wi t h A Es a n d S A Es ma y be assesse d.
1 1. 2. 6. 2. 
N as al Fl ui d P h ar m ac o ki netic A n a l ysis
S a m ple c ollect i on will ta ke place f or nasal fl uid P K a nal ysis a n d t he res ults will be liste d 
f or eac h partici pa nt a n d ti me p oi nt. S u m mar y ta bles will be prese nte d, b y tr e at me nt gr o u p 
( d ose le vel or a d mi nistratio n pr ocess of A Z D 7 4 4 2), f or t he n u m ber a n d perce nta ge of 
parti ci pa nts at eac h ti me p o i nt, base d o n t he safety a nal ysis set.
1 1. 2. 6. 3. 
Ne utr ali si n g A nti b o d y C o nce ntr ati o ns
S a m ple c ollect i on will ta ke place f or ne utrali si n g a nti b o dies a gai nst S A R S -C o V - 2;
h o we ver, t he e val uat i on of t he f u nct i onal i n hi biti on of  S A R S-C o V -2 b y  AZ D 7 4 4 2 
c o nce ntrati o ns i n ser u m will be re p orte d se paratel y fr o m t he st u d y’s re p ort.
1 1. 3. 
Pr ot oc ol De vi ati o ns
Pr ot oc ol  de viati ons are c o nsi dere d a n y  de viati on fro m  t he C S P relat i n g t o a partici pa nt , 
a n d i ncl u de t he f oll o wi n g:
 
I ncl usi on/e xcl usi o n cri teria de viati ons .
 
D osi n g de viat i ons (e g, i nc orrect treat me nt recei ve d) .
 
Ti me wi n d o w de viat i ons f or safety a n d/ or P K assess me nts .
 
Parti cipa nt s recei vi n g pr o hi bite d c o nc o mita nt me dicat i ons .
 
Ot her pr oce d ural a n d st u d y  c o n d uct de viat i ons rec or de d b y t he Cli nical U nit o n a 
pr ot oc ol  de viati on l og.
Pl a n ne d pr ot oc ol de viat i ons are n ot c o nsi dere d acce pta ble. A pr ot oc ol de viat i on t hat i s 
s us pecte d or k n o w n t o ha ve t he p ote ntial t o si g nifica nt l y i m pact o n a partici pa nt’s safety,  
p h ysical or me n t al int e grit y, or sci e nt ific val ue will be classifie d as a seri o us breac h . T he 
criteria f or t he assess me nt a n d re p orti n g of pr ot oc ol de viati o ns will be sti p ulate d i n a 
se parate st u d y s pecific P D S d oc u me nt. T his will i ncl u de a W A D w hic h sti p ulates 
t olera nce wi n d o ws f or safet y a n d P K assess me nts. Meas ure me nts perf or me d wit hi n t hese 
t olera nce wi n d o ws will n ot be c o nsi dere d as pr ot oc ol de viat i ons a n d will n ot be re p orte d.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 0 of 1 0 3
All pr ot oc ol de viat i ons will be disc usse d at t he data re vie w meet i n g pri or t o data base hard 
l oc k i n or der t o defi ne t he a nal ysis sets f or t he st u d y.
I mp orta nt pr ot oc ol de viat i ons will be liste d b y partici pa nt . Pr ot oc ol de viat i ons ( missi n g 
assess me nts/ visits) relate d t o C O VI D -1 9 will be liste d se paratel y.
Pr ot oc ol  de viati ons will be ha n dle d i n a cc or da nce wit h Pare xel S O Ps.
F or ha n dli n g of pr ot oc ol a me n d me nts, see Secti o n 8. 6 .
1 1. 4. 
Deter mi n ati o n of S a m ple Size
A p pr o xi matel y  6 0 healt h y a d ult partici pa nt s will be ra n d o mise d t o A Z D 7 4 4 2 or place b o 
acr oss 5 fi xe d-d ose c o h orts as bel o w. Beca use all a nal yses will be descri pt i ve i n nat ure a n d 
n o h y p ot hesis is bei n g teste d statist icall y, n o f or mal sa m ple size calc ulati ons were 
perf or m e d, h o we ver, t he sa m ple size is c o nsi dere d s ufficie nt f or a n earl y  assess me nt of 
safety,  t olera bilit y, i m m u n o ge nicit y, a n d P K. A d ditio nal  c o h orts ma y be a d de d wit h lo wer
or i nter me diate d oses of  A Z D 7 4 4 2 if t he D E C deter mi nes t he y are warra nte d:
 
C o h ort 1a ( 1 2 partici pa nt s): 3 0 0 mg A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g 
A Z D 1 0 6 1) ( n = 9) or place b o ( n = 1), a d mi nistere d I M,

Se nt i nel d osi n g: 3 0 0 m g A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g A Z D 1 0 6 1) 
( n = 1) or place b o ( n = 1).
 
C o h ort 1 b ( 1 2 partici pa nt s): 3 0 0 mg A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g 
A Z D 1 0 6 1) ( n = 9) or place b o ( n = 1), a d mi nistere d I V,

Se nt i nel d osi n g: 3 0 0 m g A Z D 7 4 4 2 ( 1 5 0 m g A Z D 8 8 9 5 a n d 1 5 0 m g A Z D 1 0 6 1) 
( n =1) or pl ace b o ( n = 1).
 
C o h ort 2 ( 1 2 partici pa nt s): 1 0 0 0 m g A Z D 7 4 4 2 ( 5 0 0 m g A Z D 8 8 9 5 a n d 5 0 0 m g 
A Z D 1 0 6 1) ( n = 9) or place b o ( n = 1 ), a d mi nistere d I V,

Se nt i nel d osi n g: 1 0 0 0 m g A Z D 7 4 4 2 ( 5 0 0 m g A Z D 8 8 9 5 a n d 5 0 0 m g A Z D 1 0 6 1) 
( n = 1) or place b o ( n = 1).
 
C o h ort 3 ( 1 2 partici p a nt s): 3 0 0 0 mg A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1) ( n = 9) or place b o ( n = 1), a d mi nistere d I V,
 
Se nt i nel d osi n g: 3 0 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1) ( n = 1) or place b o ( n = 1).
 
C o h ort 4 ( 1 2 partici pa nts): 3 0 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g 
A Z D 1 0 6 1 mi xe d i n si n gle i nf usi o n) ( n = 9) or place b o ( n = 1), a d mi nistere d I V,
 
Se nt i nel d osi n g: 3 0 0 0 m g A Z D 7 4 4 2 ( 1 5 0 0 m g A Z D 8 8 9 5 a n d 1 5 0 0 m g A Z D 1 0 6 1 
mi xe d i n si n gle i nf usi o n) ( n = 1) or place b o ( n = 1), a d mi nistere d I V.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 of 1 0 3
1 2. 
I M P O R T A N T M E DI C A L P R O C E D U R E S T O B E 
F O L L O W E D B Y T H E I N V E S TI G A T O R
1 2. 1. 
Me dic al E mer ge ncies a n d Astr a Ze nec a C o nt acts
I n case of me dical e mer ge nc y, t he pri mar y c o ntact is t he PI. T he PI ma y c o ntact t he 
S p o ns or’s Lea d P h ysicia n. If t he PI ca n n ot be reac he d, t he site’s staff will c o ntact t he PI’ s 
de p ut y  or ma y c o ntact S p o ns or’s Lea d P h ysicia n. 
N a me
R ole i n t he St u d y
C o nt act Det ails
Dr Pa bl o F orte S ot o (M D, M Sc, P h D ) 
Pri nci pal I n vesti gat or 
Tel: 
Tel: 
1 2. 2. 
O ver d ose
F or t hi s st u d y, a n y d ose of A Z D 7 4 4 2 greater t ha n 1 5 0 0 m g of eit her i n di vi d ual m A b 
d uri n g t he c o urse of t he st u d y  will be c o nsi dere d a n o ver d ose.
Astra Ze neca d oes n ot rec o m me n d a s pecific treat me nt f or a n o ver d ose. S y m pt o ms of 
o ver d ose s h o ul d be treate d as per cli ni c al ju d ge me nt.
 
A n o ver d ose wit h ass ociate d A Es is rec or de d as t he A E dia g n osis/s y m pt o ms o n t he 
r ele va nt A E mo d ules i n t he C R F a n d o n t he O ver d ose C R F m o d u le.
 
A n o ver d ose wit h o ut ass ociate d s y m pt o ms is o nl y  re p orte d o n t he O ver d ose C R F 
m o d ule .
If a n o ver d ose o n a n Astra Ze neca st u d y dr u g occ urs i n t he c o urse of t he st u d y, t he n t he PI
or ot her si te pers o n nel i nf or m a p pr o priate Astra Ze neca re prese ntati ves i m me diatel y, or n o 
l ater t h a n 2 4 h o urs of  w he n he or s he bec o mes a ware of it.
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he PI t o e ns ure t hat all rele va nt 
i nf or mat i on is pr o vi de d t o t he Astra Ze neca Patie nt Safety data e ntr y  sit e wit hi n 1 or 5 da ys 
f or S A Es, a n d wit hi n 3 0 da ys f or ot her o ver d oses.
1 2. 3. 
Pre g n a nc y
All pre g na ncies a n d o utc o mes of pre g na nc y s h o ul d be re p orte d t o Astra Ze neca e xce pt f or:
 
If t he pre g na nc y is disc o vere d bef ore t he st u d y patie nt has recei ve d a n y I M P.
If a pre g na nc y is re p orte d, t he PI s h o ul d i nf or m t he S p o ns or wit hi n 2 4 h o urs of lear ni n g of 
t he pre g na nc y.
A b n or m al pre g na nc y o utc o mes (e g, s p o nta ne o us a b orti o n, f oetal deat h, still birt h, 
c o n ge nital a n o ma lies, ect o pic pre g na nc y) are c o nsi dere d S A Es.
P P D
P P D
P P D
P P D

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 2 of 1 0 3
Pl ease refer t o Secti o n 4. 2. 1. 2 a n d Secti o n 4. 2. 1. 3 f or furt her details.
1 2. 3. 1.
M ater n al E x p os ure
Pre g na nc y itself is n ot re gar de d as a n A E u nless t here is a s us pici o n t hat t he I M P u n der 
st u d y ma y ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati on. C o n ge nital 
a b n or malities/ birt h defects a n d s p o nta ne o us miscarria ges s h o ul d be re p orte d a n d ha n dle d 
as S A Es. Elect i ve a b orti o ns with o ut c o m plicat i ons s h o ul d n ot be ha n dle d as A Es. T he 
o utc o m e of all pre g na ncies (s p o nta ne o us miscarria ge, electi ve ter mi nati on, ect 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 ul d be f o ll owe d u p a n d 
d oc u m e nte d e ve n if t he patie nt was disc o nti n ue d fr o m t he st u d y .
If a n y pre g na nc y occ urs in t he c o urse of t he st u d y, t he n t he PI or ot her si te pers o n nel 
i nf or ms t he a p pr o priate Astra Ze neca re prese ntati ves wit hi n 1 da y (ie, i m me diatel y b ut n o 
l ater t h a n 2 4 h o urs) of  w he n he or s he bec ome s a ware of it.
T he desi g nate d Astra Ze neca re prese ntati ve w o r ks wit h t he PI t o e ns ure t hat all rele va nt 
i nf or mat i on is pr o vi de d t o t he Astra Ze neca Patie nt Safety data e ntr y  sit e wit hi n 1 or 
5 cale n dar da ys f or S A Es (see C S P pr ocess f or S A E re p orti n g) a n d wit hi n 3 0 da ys f or all 
ot her pre g na ncies.
T he sa me ti meli nes a p pl y w he n o utc o me i nf or mat i o n is a vaila ble.
T he P R E G R E P m o d ule i n t he C R F is use d t o re p ort t he pre g na nc y a n d t he P R E G O U T is 
use d t o re p ort t he o utc o me of t he pre g na nc y .
Pl ease refer t o Secti o n 4. 2. 1. 2 f or furt her details.
1 2. 3. 2.
P ater n al E x p os ure
Male parti ci pa nt s s h o ul d refrai n fr om fatheri n g a c hil d d uri n g t he st u d y  a n d for 3 6 0 da y s 
f oll owi n g t he last d ose.
I n case of pre g na nc y of t he part ner of a male pat ient , t he part ner’s pre g na nc y s h o ul d be 
re p orte d o n t he pre g na nc y f or m (c o nse nt fr om t he part ner must be o btai ne d bef ore t he 
pre g na nc y f or m is c o m plete d) f o ll owi n g t he sa me ti mefra me a n d r o uti n g as descri be d f or 
a n y partici pa nt’s pre g na nc y. Pre g na nc y of t he patie nt’s part ner is n ot c o nsi dere d t o be a n 
A E. T hese pre g na ncies will als o be f o ll owe d u p, a n d t he o utc o me of t he pre g na nc y  
(s p o nta ne o us miscarria ge, electi ve ter mi nati on, ect 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 ul d, if p ossi bl e, be o btai ne d a n d d oc u me nte d.
Pl ease refer t o Secti o n 4. 2. 1. 3 f or furt her details.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 3 of 1 0 3
1 3. 
L E G A L A N D A D MI NI S T R A TI V E A S P E C T S
1 3. 1.   
Arc hi vi n g of St u d y D oc u me nts
All s o urce d oc u me nts ge nerate d i n c o n necti on wi t h t he st u d y will be retai ne d i n t he li mite d 
access file st ora ge area, res pecti n g t he pri vac y a n d c o nfi de nt iality of  all rec or ds t hat c o ul d 
i de ntif y t he parti ci pa nt s. Direct access is all o we d o nl y for a ut h ori se d p e o pl e for m o ni t orin g 
a n d a u dit i n g p ur p oses. S o urce d oc u me nts will be ha n dle d, st ore d a n d arc hi ve d acc or di n g 
t o i n h o use pr oce d ures.
T he I n vesti gat or's Site File will be arc hi ve d b y t he C R O f or 1 5 years after c o m plet i on of 
t he st u d y.
1 3. 2. 
P u blic ati o n of St u d y R es ults
All o f t he st u d y inf or mat i on a n d data c ollecte d d uri n g t he st u d y are c o nfi de nt ial a n d t he 
pr o pert y  of Astra Ze neca. After c o m pleti o n of t he st u d y, Astra Ze neca ma y pre pare a j oi nt 
p u blicat i on wi t h t he PI . T he PI m ust u n derta ke n ot t o s u b mit a n y data f r o m t his C S P f or 
p u blicat i on wi t ho ut pri or c o nse nt of Astra Ze neca at a m ut uall y  a gree d ti me.
A ut h ors hi p will be deter mi ne d b y  mut u al  a gree me nt a n d i n li ne with I nter nat i onal 
C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p re q uire me nts.
1 3. 3. 
Cli nic al St u d y Re p ort
A n i nte grate d C S R will be pre pare d i n acc or da nce wit h t he sta n dar ds of t he I C H g ui deli ne 
f or str uct ure a n d c o nte nt of C S Rs (I C H E 3). C o pies of t he C S R will be pr o vi de d t o t he 
I E C a n d t he N at i on al  Re g ulat or y Aut h ori t y in acc or da nce wit h re g ulat or y  req ui re me nts 
a n d Pare xel S O Ps. I n t he e ve nt of pre mat ure ter mi nat i on of t he st u d y  or ot her c o n diti ons 
s pecifie d i n I C H E 3, a n a b bre viate d C S R ma y be pre pare d.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 4 of 1 0 3
1 4. 
LI S T O F R E F E R E N C E S
1 
Perl ma n S, McI nt os h K. C or o na vir uses, I ncl u di n g Se vere Ac ute Res pirat or y  
S y n dr o me ( S A R S) a n d Mi d dle East Res pirat or y  S y n dr o me ( M E R S). I n: Be n nett J, 
D oli n R, Blaser MJ. Ma n dell, D o u glas, a n d Be n nett's Pri nci ples a n d Pract ice of 
I nfecti o us Diseases, 9t h E d. P hila del p hia: Else vier; 2 0 2 0. P. 2 0 7 2- 2 0 8 0.
2 
Fe hr R , Perl ma n S . C or o na viruses: a n o ver vie w of t heir re plicat i on a n d pat h o ge nesis. 
Met h o ds M ol Bi o l. 2 0 1 5 1 2 8 2: 1 - 2 3.
3 
M E R S -sit u atio n u p date. W H O [cite d Ja n uar y  2 0 2 0]. A vaila ble fr o m:
U R L: ht t p:// w w w.e mr o. w h o.i nt/ pa n de mic-e pi de mic-di seases/ mers-c o v/ mers-
sit u atio n -u p date -jan uar y - 2 0 2 0.ht ml .
4 
C O VI D -1 9 C or o na vir us Pa n de mic cases u p dates [accesse d o n 2 0 J ul y  2 0 2 0]. 
U R L: ht t ps:// w w w. w orl d omet ers.i nf o/c or o na vir us/ #c o u ntries accesse d 2 0 J ul y 2 0 2 0.
5 
C O VI D -1 9 Das h b oar d b y  t he Ce nter f or S yste ms Scie nce a n d E n gi neeri n g ( C S S E) at 
J o h ns H o p ki ns U ni versity [accesse d o n 2 0 J ul y 2 0 2 0] 
U R L: ht t ps:// gisa n d data. ma ps.arc gis.c om/a p ps/ o ps das h b oar d/i n de x. ht ml #/ b da 7 5 9 4 7 4 0
f d 4 0 2 9 9 4 2 3 4 6 7 b 4 8e 9ecf 6 accesse d 2 0 J ul y 2 0 2 0 .
6 
I n vesti gat or’s Br oc h ure f or A Z D 7 4 4 2, versi o n 1. 0 - 2 3 J ul y 2 0 2 0.
7 
M H R A ( 2 0 2 0) M e dici nes a n d Healt hcare pr o d ucts Re g ulat or y  A ge nc y g ui da nce o n 
Ma na gi n g cli nical trials d uri n g C or o na vir us ( C O VI D- 1 9), U p date d o n 2 1 Ma y  2 0 2 0;
U R L:  ht t ps:// w w w. g o v. u k/ g ui da nce/ ma na gi n g-cli nical-trials-d uri n g -c or o na vir us-
c o vid- 1 9 , accesse d o n 0 8 J u n 2 0 2 0.
8 
Ma ni va n na n V , Dec ker W W , Lat ha G et al. Vis ual re prese ntati o n of Nati o nal I nst itute 
of  Aller g y a nd I nfecti o us Disease a n d F o o d Aller g y  a nd A na p h yla xis Net w or k c riteria 
f or a na p h yla xis. I nt J E mer g Me d. 2 0 0 9 A pr; 2( 1): 3– 5.
9 
G ui da nce o n t he Ma na ge me nt of Cli nical Trials d uri n g t he C O VI D 1 9 ( C or o na vir us) 
pa n de mic, E M A, Versi o n 3 ( 2 8/ 0 4/ 2 0 2 0)
U R L: ht t ps://ec.e ur o pa.e u/ healt h/sites/ health/ files/files/e u drale x/ v ol-
1 0/ g ui da ncecli nicaltri als _c o vid 1 9 _e n. p df .

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 5 of 1 0 3
1 5. 
A P P E N DI C E S

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 6 of 1 0 3
A p pe n di x A
A d diti o n al S afet y I nf or m ati o n
F urt her G ui d a nce o n t he Defi niti o n of a Seri o us A d verse E ve nt
Life -t hre ate ni n g
‘ Life-t hreate ni n g’ mea ns t hat t he parti ci pa nt was at i m me diate ris k of deat h fr o m t he A E 
as it occ urre d, or it is s us pecte d t hat use or c o nti n ue d use of t he pr o d uct w o ul d res ult i n t he 
parti ci pa nt ’s deat h. ‘ Life-t hreate ni n g’ d oes n ot mea n t hat ha d a n A E occ urre d i n a m ore 
se vere f or m it mi g ht ha ve ca use d deat h (e g, he patitis t hat res ol ve d wit h o ut he patic fail ure).
H os pit ali sati o n
O ut pati e nt treat me nt i n a n e mer ge nc y r o o m is n ot i n itself a S A E, alt h o u g h t he reas o ns f or 
it ma y be (e g, br o nc h os pas m, lar y n geal oe de ma). h os pital a d missi o ns a n d/ or s ur gical 
o perati o ns pla n ne d bef ore or d uri n g a st u d y  are n ot c o nsidere d A Es if t he ill ness or di sease 
e xiste d bef ore t he parti ci pa nt was e nr olle d i n t he st u d y , pr o vide d t hat i t did n ot deteri orate 
i n a n u ne x pecte d wa y d uri n g t he st u d y.
I m p ort a nt Me dic al E ve nt or Me dic al I nter ve nti o n
Me dical a n d scie ntific j u d ge me nt s h o ul d be e xercise d i n deci di n g w het her a case is seri o us 
i n sit u atio ns w here i m p orta nt me dical e ve nts ma y n ot be i m me diatel y  life-t hreate ni n g or 
res ult i n deat h, h os pi talisat i on, di sa bilit y or i nca pacit y b ut ma y je o par dise t he parti ci pa nt
or m a y re q uire me dical int er ve nt i on t o pre ve n t 1 or m ore o utc o mes liste d i n t he defi nit i on 
of  serio us. T hese s h o ul d us uall y  be c o nsi dere d as serio us.
Si m pl y st o p pi n g t he s us pect dr u g d oes n ot mea n t hat it is a n i m p orta nt me dical e ve nt; 
me dical j u d ge me nt m ust be use d.
E xa m ples of s uc h e ve nts are:
 
A n gi oe de ma n ot se vere e n o u g h t o re q uire i nt u bati o n b ut re q uiri n g i ntra ve n o us 
h y dr oc ortis o ne treat me nt.
 
He pat ot o xicit y ca use d b y paraceta m o l/aceta mi n o p he n o ver d ose re q uiri n g treat me nt 
wi t h N-acet yl c ystei ne.
 
I nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me for aller gic br o nc h os pas m.
 
Bl o o d d y scrasias (e g, ne utr o pe nia or a nae mia re q uiri n g bl o o d tra nsf usi o n) or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pi talisat i on.
 
De vel o p me nt of dr u g de pe n de nc y or dr u g a b use.
A G ui de t o I nter preti n g t he C a us alit y Q uesti o n
T he f o llo wi n g f act ors s h o uld be c o nsi dere d w he n deci di n g if t here is a “reas o na ble 
p ossi bilit y” t hat a n A E ma y ha ve bee n ca use d b y t he I M P.
 
Ti me C o urse / E x p os ure t o s us pect dr u g:
Has t he parti ci pa nt act uall y recei ve d t he s us pect dr u g? Di d t he A E occ ur i n a 
reas o na ble te m p oral relati ons hi p t o t he a d mi nistrati o n of t he s us pect dr u g?

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 7 of 1 0 3
 
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 vi o us k n o wle d ge of t he s us pect dr u g 
( p har mac ol og y a n d t o xic o l og y ) or dr u gs of t he sa me p har mac ol o gical class? O R, 
c o uld t he A E be a nt ici pate d fr om it s p har mac ol ogical  pr o perties ?
 
Dec halle n ge e x perie nce:
Di d t he A E res ol ve or i m pr o ve o n st o p pi n g or re d uci n g t he d ose of t he s us pect dr u g?
 
N o al ter nati ve cause:
T he A E ca n n ot be reas o na bl y e x plai ne d b y  ot her etiol o g y  s uc h as t he u n derl yi n g 
di sease, ot her dr u gs, ot her h ost or e n vir o n me ntal fact ors.
 
Rec halle n ge e x perie nce:
Di d t he A E re occ ur if t he s us pecte d dr u g was rei ntr o d uce d after ha vi n g bee n st o p pe d?
N o te: Astr a Ze nec a wo ul d n ot n or m ally rec o m me n d or s u p p ort a rec h alle n ge.
 
La b orat or y  tests:
A s pecific la b orat or y  in vest i gati on (if perf or me d) has c o nfir me d t he relati o ns hi p?
I n diffic ult cases, ot her fact ors c o ul d be c o nsi dere d s uc h as:
 
Is t his a rec o g nis ed f eat ure of o ver d ose of t he dr u g?
 
Is t here a k n o w n mec ha nis m?
Ca usalit y of  ‘relate d’ is ma de if f o ll owi n g a re vie w of t he rele va nt data, t here is e vi de nce 
f or a ‘reas o na ble p ossi bility’ of a ca usal relat i ons hi p f or t he i n di vi d ual case. T he 
e x pressi o n ‘re as o na ble p ossi bilit y’ of a ca usal relati o ns hi p is mea nt t o c o n ve y, i n ge neral, 
t hat t here are facts (e vi de nce) or ar g u me nts t o s u g gest a ca usal relat i ons hi p.
T he ca usalit y assess me nt is perf or me d base d o n t he a vaila ble data i ncl u di n g e n o u g h 
i nf or mat i on t o ma ke a n i nf or me d j u d ge me nt. Wit h li mite d or i ns ufficie nt i nf or mat i on i n 
t he case, it is li kel y t hat t he e ve nt(s) will be assesse d as ‘ n ot relate d’.
Ca usal relat i ons hi p i n cases w here t he disease u n der st u d y  has deteriorate d d ue t o l ac k of 
effect s h o uld be classifie d as n o reas o na ble p ossi bilit y.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 8 of 1 0 3
A p pe n di x B
I nter n ati o n al Airli ne Tr a ns p ort ati o n Ass oci ati o n 6. 2 
G u i d a nce D oc u me nt
L a belli n g a n d S hi p me nt of Bi o h az ar d S a m ples
I nter nati o nal Airli ne Tra ns p ortati o n Ass ociati on (I A T A) classifies bi o hazar d o us a ge nts 
i nto 3 cate g ories ( htt p:// w w w.iata. or g/ w hat we d o/car g o/ da n ger o us _ g o o ds/i nfect i ous
_s u bsta nces. ht m) . F or tra ns p ort p ur p oses, t he classificat i on of i nfect i ous s u bsta nces 
acc or di n g t o ris k gr o u ps was re m o ve d fr om t he D G R i n t he 4 6t h e dit i on ( 2 0 0 5). I nfecti o us 
s u bsta nces are n o w classifie d either as Cate g or y  A, Cate g or y B or E xe mpt. T here is n o 
di rect relat i ons hi p bet wee n Ris k Gr o u ps a n d Cate g ories A a n d B.
C ate g or y A I nfecti ous S u bst a nces are i nfect i ous s u bsta nces i n a f or m t hat, w he n 
e x p os ure t o it occ urs, is ca pa ble o f ca usi n g per ma ne nt disa bilit y,  life-t hreate ni n g or fatal 
di sease i n ot her wise health y h u ma ns or a ni mals. Cate g or y A pat h o ge ns are f or e xa m ple, 
E b ola a n d Lassa Fe ver vir uses:
 
Are t o be pac ke d a n d s hi p pe d i n acc or da nce wit h I A T A I nstr ucti o n 6 0 2.
C ate g or y B I nfecti o us S u bst a nces are i nfect i ous s u bsta nces t hat d o n ot meet t he criteria 
f or i ncl usi on i n Cate g or y A. Cate g or y B pat h o ge ns are f or e xa m ple, he patit is A, B, C, D 
a n d E vir uses, a n d HI V t ypes 1 a n d 2. T he y  are assi g ne d t he f oll o wi n g U N n u m ber a n d 
pr o per s hi p pi n g na me:
 
U N 3 3 7 3 – Bi o l ogi cal S u bsta nce, Cate g or y B .
 
Are t o be pac ke d i n acc or da nce wit h U N 3 3 7 3 a n d I A T A 6 5 0.
E xe m pt r efers t o all ot her materials wit h mi ni mal ri s k of c o ntai ni n g pat h o ge ns.
 
Cli nical trial sa m ples will fall i nt o Cate g or y B or E xe m pt u n der I A T A re g ulati o ns.
 
Cli nical trial sa m ples will r o uti nel y be pac ke d a n d tra ns p orte d at a m bie nt te m perat ure 
i n I A T A 6 5 0 c o m plia nt pac ka gi n g.
( htt p:// w w w.iata. or g/ w hat we d o/car g o/ da n ger o us _ g o o ds/i nfecti ous _s u bsta nces. ht m)
 
Bi ol o gic al s a m ples tr a ns p orte d i n dr y ice re q uire a d diti o n al d a n ger o us g o o ds 
s pecific ati o n f or t he dr y ice c o nte nt.
 
A n I A T A c o m p lia nt c o urier a n d pac ka gi n g materials s h o ul d be use d f or pac ki n g a n d 
tra ns p ortati o n. Pac ki n g s h o ul d be d o ne b y a n I A T A certifie d pers o n, as a p plica ble.
 
S a m ples r o uti nel y tra ns p orte d b y r oa d or rail are parti ci pa nt t o lo c al  re g ulat i ons w hic h 
re q uire t hat t he y are als o pac ke d a n d tra ns p orte d i n a safe a n d a p pr o priate wa y t o 
c o ntai n a n y ris k of i nfecti on or c o nta mi nat i on b y usi n g a p pr o ve d c o uriers a n d 
pac ka gi n g / c o ntai n me nt materials at all ti mes. T he I A T A 6 5 0 bi o l ogical  sa m ple 
c o ntai n me nt sta n dar ds are e nc o ura ge d w here ver p ossi ble w he n r oa d or rail tra ns p ort is 
use d.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 9 of 1 0 3
A p pe n di x C
Acti o ns Re q uire d i n C ases of C o m bi ne d I ncre ase of 
A mi n otr a nsfer ase a n d T ot al Bilir u bi n - H y’s L a w
C 1
I ntr o d ucti o n
T his A p p e n di x descri bes t he pr ocess t o be f o ll owe d i n or der t o i de nt if y a n d a p pr o priatel y 
re p ort P H L cases a n d Hy’s La w ( H L) cases. It is n ot i nte n de d t o be a c o m pre he nsi ve g ui de 
t o t he ma na ge me nt of ele vate d li ver bi oc he mistries.
D uri n g t he c o urse of t he st u d y  t he PI will re mai n vi gila nt f or i ncreases i n li ver 
bi oc he mistr y . T he PI is res p o nsi ble f or deter mi ni n g w het her a partici pa nt meets p ote ntial 
P H L cri t eria at a n y p oi nt d uri n g t he st u d y.
All s o urces of la b orat or y data are a p pr o priate f or t he deter mi nat i on of P H L a n d H L e ve nts; 
t his i ncl u des sa m ples ta ke n at sc he d ule d st u d y visits a n d ot her visits i ncl u di n g ce ntral a n d 
all l ocal la b orat or y e val uati ons e ve n if c o llecte d o utsi de of t he st u d y visits; for e xa m ple, 
P H L cri teria c o uld be m et b y a n ele vate d A L T fr o m a ce ntral la b orat or y a n d/ or ele vate d 
T B L fr o m a l ocal la b orat or y . 
T he PI will als o re vie w A E data (f or e xa m ple, f or A Es t hat ma y i n dicate ele vat i ons i n li ver 
bi oc he mistr y ) for p ossi ble P H L e ve nts.
T he PI partici pates, t o get her wit h Astra Ze neca cli nical pr oject re prese ntati ves, i n re vie w 
a n d assess me nt of cases meeti n g P H L criteria t o a gree w het her H L criteria are met. H L 
criteria are met if t here is n o alter nati ve e x pla nati o n f or t he ele vati ons i n li ver b i oc he mistr y 
ot her t ha n DI LI ca use d b y  t he I M P. 
T he PI is res p o nsi ble f or rec or di n g data pertai ni n g t o P H L/ H L cases a n d f or re p orti n g 
S A Es a n d A Es acc or di n g t o t he o utc o me of t he re vie w a n d assess me nt i n li ne wit h 
sta n dar d safety re p orti n g pr ocesses.
C 2
Defi n iti o ns
P ote nti al H y’s L a w ( P H L)
As partate a mi n otra nsferase ( A S T) or ala ni ne a mi n otra nsferase ( A L T) ≥3 × U L N t o get her 
wit h T B L ≥2 × U L N at a n y p oi nt d uri n g t he st u d y f o ll owi n g t he start of st u d y  me dicat i on 
irres pecti ve of a n i ncrease i n A L P.
H y’s L a w ( H L)
A S T or A L T ≥3 × U L N t o get her wit h T B L ≥2 × U L N, w here n o ot her reas o n, ot her t ha n 
t he I M P, ca n be f o u n d t o e x plai n t he c o m bi nat i on of i ncreases, e g, ele vate d A L P i n dicati n g 
c h o lestasis, viral he patitis, a n ot her dr u g.
F or P H L a n d H L t he ele vat i on i n tra nsa mi nases m ust prece de or be c oi nci de nt wit h (ie, o n 
t he sa me da y) t he ele vat i on i n T B L, b ut t here is n o s pecifie d ti mefra me wit hi n w hic h t he 
ele vat i ons i n tra nsa mi nases a n d T B L m ust occ ur.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 0 of 1 0 3
C 3
I de ntific ati o n of P ote nti al H y’s L a w C ases
I n or der t o ide ntif y  c ases of P H L it is i m p orta nt t o perf or m a c o m pre he nsi ve re vie w of 
la b orat or y data f or a n y part ici pa nt w h o meets a n y of t he f o ll owi n g i de ntificat i on cri t eria i n 
is olati on or i n c o m bi nat i on:
 
A S T ≥3 × U L N
 
A L T ≥3 × U L N
 
T B L ≥2 × U L N
If Ce ntr al L a b or at ories Bei n g Use d:
W he n a parti ci pa nt meets a n y of t he P H L i de nt ificati o n criteria, i n is olati on or i n 
c o m bi nat i on, t he ce ntral la b orat or y  will i m me diatel y se n d a n alert t o t he PI (als o se n d t o 
Astra Ze neca re prese ntati ve).
T he PI will als o re mai n vi gila nt f or a n y lo c al  la b orat or y re p orts w here t he P H L 
i de ntificati on cri teria are met, w here t his is t he case t he PI will:
 
N otif y  t he Astra Ze neca re prese ntati ve.
 
Re q uest a re peat of t he test ( ne w bl o o d dra w) b y  t he ce ntral la b orat or y wit ho ut dela y .
 
C o m plete t he a p pr o priate u nsc he d ule d la b orat or y C R F m o d ule(s) wit h t he ori gi nal 
l ocal la b orat or y test res ult.
W he n t he i de ntificat i on cri t eria are met fr o m ce ntral or lo c al  la b orat or y res ults t he PI will 
wi t ho ut dela y :
 
Deter mi ne w het her t he partici pa nt meets P H L crite ria (see Secti o n 2 wi t hi n t his 
a p pe n di x f or defi nit i on) b y re vie wi n g la b orat or y  re p orts fr o m all pre vi o us visits 
(incl u di n g b ot h ce ntral a n d l ocal la b orat or y  res ults).
If L oc al L a b or at ories Bei n g Use d:
T he PI will wi t ho ut d el a y re vie w eac h ne w la b orat or y re p ort a n d if t he i de ntificati on 
criteria are met will:
 
N otif y  t he Astra Ze neca re prese ntati ve.
 
Deter mi ne w het her t he partici pa nt meets P H L criteria (see Secti o n 2 wi t hi n t his 
a p pe n di x f or defi nit i on) b y re vie wi n g la b orat or y  re p orts fr o m all pre vi o us visits.
 
Pr o m pt l y e nter t he la b orat or y data i nt o t he la b orat or y C R F mo d ul e(s) .
C 4
F oll o w -U p
C 4. 1
P ote nti al H y’s L a w Criteri a n ot met
If t he parti ci pa nt d oes n ot meet P H L criteria t he PI will:

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 1 of 1 0 3
 
I nf or m t he Astra Ze neca re prese ntati ve t hat t he partici pa nt has n ot m et P H L crit eria.
 
Perf or m  fol l ow- u p o n s u bse q ue nt la b orat or y  res ults acc or di n g t o t he g ui da nce 
pr o vi de d i n t he C S P .
C 4. 2
P ote nti al H y’s L a w Criteri a met
If t he parti ci pa nt d oes m eet P H L crit eria t he PI will:
 
N otif y  t he Astra Ze neca re prese ntati ve w h o will t he n i nf or m t he ce ntral St u d y Tea m .
 
Wit hi n 1 da y of P H L criteria bei n g met, t he PI will re p ort t he case as a n S A E of P H L; 
serio us cri teria “I m p orta nt Me dical E ve nt” a n d ca usality assess me nt ‘ y es/relate d’ 
acc or di n g t o C S P pr ocess f or S A E re p orti n g .
 
F or partici pa nt s t hat met P H L criteria pri or t o starti n g I M P, t he PI is n ot re q uire d t o 
s u b mit a P H L S A E u nless t here is a si g nifica nt c ha n ge 2 i n t he partici pa nt ’s c o n diti on.
 
T he St u d y  P h ysicia n c o ntacts t he PI , t o pr o vi de g ui da nce, disc uss a n d a gree a n 
a p pr o ac h f or t he st u d y part ici pa nts’ f oll ow- u p (i ncl u di n g a n y f urt her la b orat or y  
testi n g) a n d t he c o nti n u o us re vie w of data.
 
S u bse q ue nt t o t his c o ntact t he PI will:
o 
M o ni t or t he parti ci pa nt u ntil li ver bi oc he mistr y p ar a meters a n d a p pr o priate 
cli nical s y m pt o ms a nd si g ns ret ur n t o n or mal or baseli ne le vels, or as l o n g as 
me dicall y i n dicate d. C o m pletes f o ll ow- u p S A E F or m  as re q uire d.
o 
I n vesti gate t he aetiol o g y  of t he e ve nt a n d perf or m dia g n ostic i n vesti gati ons 
as disc usse d wit h t he St u d y P h ysicia n. T his i ncl u des decidi n g w hic h t he tests 
a vaila ble i n t he H L la b orat or y kit s h o uld be use d (if a p plica ble).
o 
C o m plete t he t hree li ver C R F m o d ules as i nf or mati on bec o mes a vaila ble.
C 5
Re vie w a n d Assess me nt of P ote nti al H y’s L a w C ases
T he i nstr ucti o ns i n t his sect i on s h o ul d be f o ll owe d f or all  cases w here P H L criteria are 
met.
As s o o n as p ossi ble after t he bi oc he mistr y  a b n or mality was i ni tiall y detecte d, t he St u d y 
P h ysicia n c o ntacts t he PI i n or der t o re vie w a vaila ble data a n d a gree o n w het her t here is a n 
alter nati ve e x pla nati on f or meet i n g P H L criteria ot her t ha n DI LI ca use d b y t he I M P, t o 
e ns ure ti mel y a nal ysis a n d re p orti n g t o healt h a ut h orities wit hi n 1 5 cale n dar da ys fr o m t he 
date t he P H L criteria were met. T he Astra Ze neca Gl o bal Cli nical Lea d or e q ui vale nt a n d 
                                               
2 A ‘si g nifica nt’ c ha n ge i n t he part ici pa nt’s c o n diti o n refers t o a cli nicall y rele va nt c ha n ge i n a n y of t he 
i n di vi d ual li ver bi oc he mistr y para meters ( A L T, A S T or t otal bilir u bi n) i n is olati o n or i n c o m bi nati o n, or a 
cli nicall y rele va nt c ha n ge i n ass ociate d s y m pt o ms. T he deter mi nati o n of w het her t here has bee n a si g nifica nt 
c ha n ge will be at t he discreti o n of t he I n vesti gat or, t his ma y be i n c o ns ultati o n wit h t he St u d y P h ysicia n if 
t here is a n y u ncertai nt y.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 2 of 1 0 3
Gl o bal Safet y P h ysicia n will als o be i n v o l ve d i n t his re vie w t o get her wit h ot her partici pa nt
matter e x perts as a p pr o priate.
Acc or di n g t o t he o utc o me of t he re vie w a n d assess me nt, t he PI will f o ll ow t he i nstr ucti o ns 
bel o w.
W here T here Is a n A gree d Alter n ati ve E x pl a n ati o n
f or t he A S T or A L T a n d T B L 
Ele vat i ons, a Deter mi nati o n o f W het her t he Alter nati ve E x pla nat i on Is a n A E Will Be 
Ma de a n d S u bse q ue ntl y W het her t he A E Meets A n y Criteria f or a S A E:
 
If t he alter nati ve e x pla nati on is n ot a n A E, rec or d t he alter nati ve e x pla nati o n o n t he 
a p pr o priate C R F m o d ule(s) .
 
If t he alter nati ve e x pla nati on is a n A E/ S A E: u p date t he pre vi o usl y s u b mitte d P H L 
S A E a n d A E C R F e ntries acc or di n gl y wit h t he ne w i nf or mat i on (reassessi n g e ve nt 
ter m; ca usality a n d s erio us ness cri teria) f oll owi n g t he Astra Ze neca sta n dar d pr ocesses .
If it is a gree d t hat t here is n o e x pla nat i on t hat w o ul d e x plai n t he A S T or A L T a n d T B L 
ele vat i ons ot her t ha n t he I M P:
 
Se n d u p date d S A E (re p ort ter m ‘ H y’s La w’) acc or di n g t o Astra Ze neca s ta n dar d 
pr ocesses .
 
T he ‘ Me dicall y  I m p orta nt’ serio us ness criteri o n s h o ul d be use d if n o ot her 
serio us ness cri t eria a p pl y.
 
As t here is n o alter nat i ve e x pla nati o n f or t he H L case, a ca usality assess me nt of 
‘relate d’ s h o ul d be assi g ne d.
If t here is a n u na v oida ble dela y  of o ver 1 5 cale n dar da ys i n o btai ni n g t he i nf or mat i on 
necessar y  t o assess w het her t he case meets t he criteria f or H L, t he n it is ass u me d t hat t here 
is n o alter nat i ve e x pla nati on u nt il s uc h ti me as a n i nf or me d decisi on ca n be ma de:
 
Pr o vi de a n y f urt her u p date t o t he pre vi o usl y  s u b mitte d S A E of P H L (re p ort ter m n o w 
‘ H y’s La w case’), e ns uri n g ca usality assess me nt is ‘relate d t o I M P’ a n d seri o us ness 
crit erio n is ‘ me dicall y i m p orta nt’, acc or di n g t o C S P pr ocess f or S A E re p orti n g .
 
C o nti n ue f o ll ow- u p a n d re vie w acc or di n g t o a gree d pla n. O nce t he necessar y 
s u p ple me ntar y inf or mat i on is o btai ne d, re peat t he re vie w a n d assess me nt t o deter mi ne 
w het her H L criteria are still met. U p date t he pre vi o usl y s u b mitte d P H L S A E re p ort 
f oll owi n g C S P pr ocess f or S A E re p ort i n g, acc or di n g t o t he o utc o me of t he re vie w a n d 
a me n di n g t he re p orte d ter m if a n alter nat i ve e x pla nati on f or t he li ver bi oc he mistr y 
ele vat i ons is deter mi ne d.
C 6
L a b or at or y Tests
T he list bel o w re prese nts t he sta n dar d, c o m pre he nsi ve list of f o ll ow- u p tests w hi c h are 
rec o m me n de d b ut n ot ma n dat or y w he n usi n g a ce ntral la b orat or y. F or st u dies usi n g a lo c al  
la b orat or y, t he list ma y be mo difie d base d o n cli nical  ju d ge me nt. A n y  test res ults nee d t o 
be rec or de d.

Cli nical St u d y Pr ot oc o l A me n d me nt 6
Astra Ze neca
A Z D 7 4 4 2 – D 8 8 5 0 C 0 0 0 0 1
1 9 J ul y 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 3 of 1 0 3
H y’s L a w l a b or at or y kit f or ce ntr al l a b or at ories ( 1 8 Dec e m ber 2 0 1 8)
A d diti o nal sta n dar d bi oc he mistr y a n d 
c oa g ulati on tests
G G T
L D H
Pr ot hr o m bi n ti me
I N R
Viral he patitis
I g M a nti-H A V 
a nti-H C V
I g M a n d I g G a nti-H Bc 
H C V R N A *
H Bs A g
I g M a nti-H E V
H B V D N A
H E V R N A
Ot her viral i nfecti o ns
I g M & I g G a nti-C M V
I g M & I g G a nti-H S V
I g M & I g G a nti-E B V
Alc o h olic he patitis
Car b o h y drate deficie nt tra nsferri n ( C D -tra nsferri n) * *
A ut oi m m u ne he patitis
A nti n uclear a nti b o d y ( A N A)
A nti- Li ver/ Ki d ne y Micr os o mal A b ( A nti -L K M)
A nti- S m o ot h M uscle A b ( A S M A)
Meta b olic diseases
al p ha - 1-a ntitr ypsi n
Cer ul o plas mi n
Ir on
Ferriti n
Tra nsferri n * *
Tra nsferri n sat urati o n
* H C V R N A is o nl y teste d w he n a nti -H C V is p ositi ve or i nc o ncl usi ve
* * Car b o h y dr ate deficie nt tra nsferri n ( C D -tra nsferri n) is n ot a vaila ble i n C hi na. St u d y tea ms s h o ul d a me n d 
t his list acc or di n gl y.
R E F E R E N C E S
Ait hal G P, Wat ki ns P B, A n dra de RJ, et al. Case defi nit i on a n d p he n ot y pe sta n dar di sat i on 
i n dr u g-i n d uce d li ver i nj ur y. Cli nical P har mac ol o g y & T hera pe utics 2 0 1 1; 8 9( 6): 8 0 6– 1 5.

SI G N A T U R E P A G E
T his is a re prese nt ati o n of a n electr o nic rec or d t h at w as si g ne d
electr o nic ally a n d t his p a ge is t he m a nifest ati o n of t he electr o nic si g n at ure
D oc u me nt N a me: d 8 8 5 0c 0 0 0 0 1-cs p-a me n d me nt- 6
D oc u me nt Title:
D 8 8 5 0 C 0 0 0 0 1 Cli nical St u d y Pr ot oc ol A me n d me nt 6
D oc u me nt I D:
D oc I D- 0 0 4 3 1 6 8 7 3
Versi o n L a bel:
7. 0 C U R R E N T L A T E S T A P P R O V E D
Ser ver D ate
( d d- M M M- y y y y H H: m m ‘ U T C’ Z)
Si g ne d b y
Me a ni n g of Si g n at ure
3 0-J ul- 2 0 2 1 1 2: 4 7 U T C
C o nte nt A p pr o val
2 8-J ul- 2 0 2 1 1 7: 0 1 U T C
Q ualifie d Pers o n A p pr o val
2 7-J ul- 2 0 2 1 0 7: 2 9 U T C
C o nte nt A p pr o val
2 6-J ul- 2 0 2 1 2 0: 2 2 U T C
Ma na ge me nt A p pr o val
N otes: ( 1) D oc u me nt details as st ore d i n A N G E L, a n Astra Ze neca d oc u me nt ma na ge me nt s yste m.
P P D
P P D
P P D
P P D