A Phase 2 Multinational, Randomized, Double-blind, Parallel-group, 16-week Placebo-controlled Study With a 36-Week Extension to Investigate the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis Despite Treatment With Topical Medications (The HILLIER Study)
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: AstraZeneca

Clinical Study Protocol 
AstraZeneca 
D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
Clinical Study Protocol 
Study Intervention 
Benralizumab 
Study Code 
D3256C00001 
Version 
3 
Date 
04 May 2021 
A Phase 2 Multinational, Randomized, Double-blind, Parallel-
group, 16-week Placebo-controlled Study with a 36–week 
Extension to Investigate the Use of Benralizumab for Patients with 
Moderate to Severe Atopic Dermatitis Despite Treatment with 
Topical Medications (The HILLIER Study) 
 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
S p o ns or N a me: Astr a Ze nec a A B  
Le gal Re gistere d A d dress:  Astra Ze neca A B, 1 5 1 8 5 S ö dertälje, S we de n  
L ocal S p o ns or i n Ja pa n: Astra Ze neca K K, 3 -1 Of u ka -c h o, Kita-k u, Osa ka 5 3 0 -0 0 1 1, Ja pa n  
Re g ul at or y A ge nc y I de ntif yi n g N u m ber(s):  
E u dra C T n u m ber 2 0 2 0 -0 0 0 2 8 5 -4 2; I N D 
 
T his Cli nical St u d y Pr ot oc ol has bee n s u bject  t o a peer re vie w acc or di n g t o Astra Ze neca 
Sta n dar d pr oce d ures. T he Cli nical St u d y Pr ot oc ol is p u blicl y re gistere d a n d t he res ults are 
discl ose d a n d/ or p u blis he d acc or di n g t o t he Astra Ze neca Gl o bal P olic y o n Bi oet hics a n d i n 
c o m plia nce wit h pre vaili n g la ws  a n d re g ulati o ns.  
Pr ot oc ol N u m ber: D 3 2 5 6 C 0 0 0 0 1  
A me n d me nt N u m ber: 2  
St u d y I nter ve nti o n: Be nraliz u ma b  
St u d y P hase: 2  
S h ort Title:  
A p hase 2 st u d y t o i n vesti gate t he use of be nraliz u ma b i n patie nts wit h m o derate t o se vere 
at o pic der matitis  
T he HI L LI E R St u d y  
St u d y P h ysici a n N a me a n d C o nt act I nf or m ati o n will be pr o vi de d se p ar atel y  
I nter n ati o n al C o-or di n ati n g I n vesti g at or:   
N Y 1 0 0 2 9  
U S A  
 
C CI
P P D

Clinical Study Protocol 
AstraZeneca 
D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2 
04 May 2021 
Amendment 1 
18 June 2020 
Original Protocol 
19 March 2020 
 
Amendment 2 (04 May 2021) 
This amendment is considered to be non-substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is to align the contents of the clinical study protocol with the 
updated project specific safety requirements for benralizumab studies. Other changes were made as 
points of clarification, alignment with the updated protocol template, and correction of minor errors or 
omissions.   
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial/ 
Non-substantial 
Throughout 
The term “medical monitor” was replaced by 
“study physician”. 
To ensure 
consistency with 
the latest protocol 
template. 
Non-substantial 
Throughout 
The term “congenital abnormalities” was amended 
to “congenital anomalies”. 
To ensure 
consistency with 
the latest protocol 
template. 
Non-substantial 
Throughout 
The term “women” was amended to “females”. 
To ensure 
consistency 
throughout the 
protocol and to 
reflect the 
adolescent 
population. 
Non-substantial 
Throughout 
Minor editorial changes. 
To ensure 
consistency with 
the latest protocol 
template. 
Non-substantial 
Title Page 
The IND number was updated and the amendment 
number changed to amendment 2.  
The IND number 
was updated on 
request from the 
FDA. 
Non-substantial 

Clinical Study Protocol 
AstraZeneca 
D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial/ 
Non-substantial 
Title Page 
The Coordinating Investigator address was 
updated. 
To update to the 
current 
Coordinating 
Investigator 
address.  
Non-substantial 
1.2 
Schema 
The study schematic was replaced with an updated 
version. 
The updated 
version of the 
schematic is 
provided for 
additional clarity. 
Non-substantial 
1.3 
Schedule of 
Activities 
The healthcare resource utilization assessment at 
run-in was removed.  
This was 
previously 
included at run-in 
in error. 
Non-substantial 
 
The electrocardiogram assessment was moved 
from Visit 2 to Visit 1. 
To ensure that 
electrocardiogram 
results are 
available no later 
than 
randomization. 
Non-substantial 
 
A hematology assessment to include eosinophils 
only was added to Visit 3. 
Previously 
omitted from the 
table in error. 
Non-substantial 
 
The following samples were removed from the 
follow-up visit: 
• 
Pharmacokinetic sample prior to IP 
administration  
• 
Immunogenicity sample.  
These 
assessments are 
not needed for the 
follow-up visit 
and thus were 
removed. 
Non-substantial 
2.3.2  
Risk 
Assessment, 
6.1.1 
Investigational 
Products,  
8.3.12 
Management 
of 
Investigational 
Product-related 
Drug 
Reactions 
Removal of ‘one hour’ in relation to the duration of 
observation following IP administration, and 
addition of the more general statement of ‘in line 
with clinical practice’. 
Updated based on 
benralizumab 
safety data 
Non-substantial  

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
Secti o n # a n d 
N a me  
Descri pt i o n of C h a n ge 
Brief R ati o n ale  
S u bst a nti al/  
N o n -s u bst a nti al 
4. 1. 1  
St u d y C o n d uct 
Miti gati o n 
D uri n g 
Disr u pti o ns  
Ne w w or di n g was a d de d t o clarif y t hat if 
partici pa nt testi n g is perf or me d d ue t o t he p u blic 
healt h crisis, t he res ults ma y be d oc u me nte d f or 
t his st u d y.  
U p date d i n 
c o nsiste nc y wit h 
ot her st u dies of 
t he sa me pr o gra m 
a n d t o better 
clarif y miti gati o n 
pr oce d u res d uri n g 
disr u pti o ns.  
N o n -s u bsta ntial 
5. 1  
I ncl usi o n 
Criteri o n  
Criteri o n 3 “ b o d y wei g ht ≥ 3 5  k g” was re m o ve d.   
Be nraliz u ma b 
e x p os ure is n ot 
affecte d b y wei g ht 
a n d t heref ore t his 
criteri o n is n ot 
re q uire d.  
N o n -s u bsta ntial 
 
Criteri o n 9 was a me n de d t o c orrect t he refere nce t o 
e xcl usi o n criteri o n 2 3 t o state e xcl usi o n 
criteri o n 1 1.  
T o c orrect 
pre vi o us err or.  
N o n -s u bsta ntial 
5. 2  
E xcl usi o n 
Criteri o n  
Criteri o n 6 “ hist or y of G uillai n -Barré s y n dr o me” 
was re m o ve d.  
G uillai n -Barré 
s y n dr o me is n ot a 
re q uire d e xcl usi o n 
criteri o n f or 
be nraliz u ma b a n d 
was pre vi o usl y 
i ncl u de d i n err or. 
N o n -s u bsta ntial 
 
Criteri o n 1 3 was re place d wit h t he f oll o wi n g “ Use 
of i m m u n os u p pressi ve me dicati o n, i ncl u di n g, b ut 
n ot li mite d t o: met h otre xate, c ycl os p ori ne, 
azat hi o pri ne, s yste mic c ortic oster oi ds wit hi n 4 
wee ks or 5 half -li ves pri or t o t he date i nf or me d 
c o nse nt/asse nt is o btai ne d, w hic he ver is l o n ger.”  
Te xt a me n de d t o 
ali g n wit h t he 
u p date d pr oject 
s pecific safet y 
re q uire me nts f or 
t he be nraliz u ma b 
de vel o p me nt  
pr o gra m.  
N o n -s u bsta ntial 
 
Criteri o n 2 1 was u p date d t o clarif y t hat electi ve 
maj or s ur gical pr oce d ures d uri n g t he c o n d uct of 
t he st u d y lea d t o partici pa nt e xcl usi o n. 
U p date d f or 
i m pr o ve d clarit y. 
N o n -s u bsta ntial 
5. 3  
Lifest yle 
c o nsi derati o ns  
T he i ncl usi o n criteri o n n u m ber referri n g t o t he 
defi niti o n of fe males of c hil d beari n g p ote ntial was 
u p date d fr o m 1 3 t o 1 1.  
U p date d t o reflect 
t he c orrect 
n u m ber i n t his 
pr ot oc ol versi o n.  
N o n -s u bsta ntial 
6. 3. 2  
Bli n di n g  
It was clarifie d t hat 
 
assess me nts will be ma de i n a ce ntral la b orat or y.  
U p date d f or 
i m pr o ve d clarit y. 
N o n -s u bsta ntial 
C CI

Clinical Study Protocol 
AstraZeneca 
D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial/ 
Non-substantial 
6.5 
Concomitant 
Medications 
Clarified in the text that any prior biologic 
medication(s) are to be collected in the electronic 
case report form. 
Updated to clarify 
that prior biologic 
medication(s) are 
to be collected. 
Non-substantial 
6.5.4 
Restrictions 
Topical anti-inflammatory medications were 
removed from the list of restricted medications. 
This bullet has 
been included in 
duplicate. 
Non-substantial 
 
The following bullet was added to the restrictions: 
• 
Receipt of inactive/killed vaccinations (eg, 
inactive influenza) is allowed provided they 
are not administered within 1 week 
before/after any IP administration; 
additionally, it is recommended to rotate the 
next IP site injection to a site distant from the 
vaccine site injection. 
 
Exclusion of 
inactive vaccines 
was inadvertently 
not included in 
the previous 
versions and has 
been added so as 
to align with the 
current 
benralizumab 
safety 
information.   
Non-substantial  
8 
Study 
assessments 
and procedures 
A note was added, stating that if not all laboratory 
kits are available at a given visit, the Investigator 
should contact the Study Physician to confirm 
whether the assessment is critical or may be 
postponed until supplies are available.  
 
To allow for 
improved 
feasibility and to 
conduct study 
visits, in case 
specific 
laboratory kits are 
not available at a 
given time point. 
Non-substantial 
8.2.1.1 
Pregnancy 
tests 
The inclusion criterion number referring to the 
definition of females not of childbearing potential 
was updated from 11 to 12. 
Updated to reflect 
the correct 
number in this 
protocol version. 
Non-substantial 
8.2.3 
Vital signs 
Wording was updated to clarify that pulse rate and 
blood pressure will be (instead of “should be”) 
measured after the participant has been resting for 
at least 5 minutes, and that the pulse rate should be 
(instead of “will be”) obtained before blood 
pressure. 
Updated for 
improved clarity. 
Non-substantial 
8.3.2 
Follow-up of 
AEs and SAEs 
“Description of AE” was included as one of the 
variables to be collected for SAEs. 
Omitted 
previously from 
the protocol by 
error. 
Non-substantial 
8.3.9 
Device 
Section was added to provide details of actions 
required in the case of a deficiency in the drug 
Section was 
updated to meet 
Non-substantial 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
Secti o n # a n d 
N a me  
Descri pt i o n of C h a n ge 
Brief R ati o n ale  
S u bst a nti al/  
N o n -s u bst a nti al 
C o nstit ue nt 
Deficie ncies  
de vice c o nstit ue nts. I n c o nse q ue nce, t he pre vi o us 
Secti o n  8. 3. 9 “ malf u ncti o n of 
 
” was re m o ve d.  
ne w re g ulat or y 
re q uire me nts. 
8. 3. 1 0  
Seri o us 
A d verse 
De vice Effect 
Re p orti n g  
T his secti o n was a d de d t o pr o vi de details of 
re p orti n g re q uire me nts i n case of S A D E. 
Secti o n was 
u p date d t o meet 
ne w re g ulat or y 
re q uire me nts. 
N o n -s u bsta ntial 
A p pe n di x A 1 
Re g ulat or y a n d 
Et hical 
C o nsi derati o ns  
T he f oll o wi n g te xt has bee n i ncl u de d:  
“ T he i n vesti gat or will be res p o nsi ble f or pr o vi di n g 
o versi g ht of t he c o n d uct of t he st u d y at t he site a n d 
a d here nce t o re q uire me nts of 2 1 C F R, I C H 
g ui deli nes, t he I R B/I E C, E ur o pea n Re g ulati o n 
5 3 6/ 2 0 1 4 f or cli nical st u dies (if a p plica ble), 
E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h (if a p plica ble), a n d all 
ot her a p plica ble l ocal re g ulati o ns.”  
T o ali g n wit h t he 
u p date d pr ot oc ol 
te m plate. 
N o n -s u bsta ntial 
A p pe n di x A 3 
I nf or me d 
C o nse nt/ Asse n
t Pr ocess 
T he f oll o wi n g se nte nce was re m o ve d “If a 
partici pa nt’s part ner bec o mes pre g na nt d uri n g or 
wit hi n 1 2 wee ks after t he last d ose of st u d y dr u g, 
t he part ner will be as ke d t o si g n t he “ Ad ult St u d y 
I nf or me d C o nse nt/ Asse nt F or m f or Pre g na nt 
Part ners of St u d y Partici pa nts” a n d pr o vi de 
i nf or mati o n a b o ut t he pre g na nc y acc or di n gl y.” 
Te xt a me n de d t o 
ali g n wit h t he 
u p date d pr oject 
s pecific safet y 
re q uire me nts f or 
t he be nraliz u ma b 
de vel o p me nt 
pr o g ra m. 
N o n -s u bsta ntial 
A p pe n di x A 6 
Disse mi nati o n 
of Cli nical 
St u d y Data  
T he li n k htt p://astraze necacli nicaltrials.c o m  was 
re place d wit h 
htt p://astraze neca gr o u ptrials. p har mac m.c o m .  
T o ali g n wit h t he 
u p date d pr ot oc ol 
te m plate. 
N o n -s u bsta ntial 
A p pe n di x A 7 
Data Q ualit y 
Ass ura nce  
Te xt u p date d t o clarif y t hat t he I n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are 
acc urate a n d c orrect b y electr o nicall y si g ni n g t he 
electr o nic case re p ort f or m.  
T o ali g n wit h t he 
u p date d pr ot oc ol 
te m plate an d 
pr oce d ures.  
N o n -s u bsta ntial 
C F R, C o de of Fe deral Re g ulati o ns; F D A,  F o o d a n d Dr u g A d mi nistrati o n; I E C,  I n de pe n de nt Et hics C o m mittee; 
I C H, I nter nati o nal C o u ncil f or Har m o nisati o n; I N D, I n vesti gati o nal Ne w Dr u g; I P, i n vesti gati o nal pr o d uct; 
I R B, I nstit utio nal Re vie w B oar d S A D E,  seri o us a d verse de vice effects. 
 
 
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Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ................................................................................... 13 
1.1 
Synopsis ................................................................................................................ 13 
1.2 
Schema .................................................................................................................. 20 
1.3 
Schedule of Activities ........................................................................................... 22 
2 
INTRODUCTION ................................................................................................ 28 
2.1 
Study Rationale ..................................................................................................... 28 
2.2 
Background ........................................................................................................... 28 
2.3 
Benefit/risk Assessment ....................................................................................... 30 
2.3.1 
Benefit Assessment ............................................................................................... 30 
2.3.2 
Risk Assessment ................................................................................................... 31 
2.3.3 
Overall Benefit:Risk Conclusion .......................................................................... 32 
3 
OBJECTIVES AND ENDPOINTS ...................................................................... 34 
4 
STUDY DESIGN ................................................................................................. 36 
4.1 
Overall Design ...................................................................................................... 36 
4.1.1 
Study Conduct Mitigation During Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis .................................................. 38 
4.1.2 
Investigational Product Dosing Regimen ............................................................. 39 
4.2 
Scientific Rationale for Study Design .................................................................. 41 
4.3 
Justification for Dose ............................................................................................ 42 
4.4 
End of Study Definition ........................................................................................ 43 
5 
STUDY POPULATION ....................................................................................... 43 
5.1 
Inclusion Criteria .................................................................................................. 44 
5.2 
Exclusion Criteria ................................................................................................. 45 
5.3 
Lifestyle Considerations ....................................................................................... 48 
5.4 
Screen Failures ..................................................................................................... 48 
5.4.1 
Re-screening ......................................................................................................... 48 
6 
STUDY INTERVENTION .................................................................................. 49 
6.1 
Study Interventions Administered ........................................................................ 49 
6.1.1 
Investigational Products ....................................................................................... 49 
6.1.2 
Investigational Product Administration Re-scheduling ........................................ 51 
6.2 
Preparation/handling/storage/accountability ........................................................ 52 
6.2.1 
Preparation and Handling of Investigational Product ........................................... 52 
6.2.2 
Shipping and Storage ............................................................................................ 53 
6.2.3 
Accountability ...................................................................................................... 53 
6.3 
Measures to Minimize Bias: Randomization and Blinding .................................. 54 
6.3.1 
Randomization ...................................................................................................... 54 
6.3.2 
Blinding ................................................................................................................ 54 
6.3.3 
Methods for Unblinding ....................................................................................... 56 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
St u d y I nter ve nti o n C o m plia nce  ............................................................................ 5 6  
6. 5  
C o nc o mita nt T hera p y  ........................................................................................... 5 7  
6. 5. 1  
Bac k gr o u n d Me dicati o n  ....................................................................................... 5 7  
6. 5. 2  
Ot her C o nc o mita nt Treat me nt  .............................................................................. 5 7  
6. 5. 3  
Resc ue Me dicati o n  ............................................................................................... 5 8  
6. 5. 4  
Restricti o ns  ........................................................................................................... 5 8  
6. 6  
D ose M o dificati o n  ................................................................................................ 5 9  
6. 7  
I nter ve nti o n After t he E n d of t he St u d y ............................................................... 5 9  
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ............................................................ 5 9  
7. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n  ................................................................. 5 9  
7. 1. 1  
Pr oce d ures f or Earl y Disc o nti n uati o n of St u d y I nter ve nti o n a n d at E n d of 
St u d y  ..................................................................................................................... 6 0  
7. 1. 1. 1  
Earl y Disc o nti n uati o n of St u d y I nter ve nti o n  ........................................................ 6 0  
7. 1. 1. 2  
Disc o nti n uati o n of St u d y I nter ve nti o n u p o n N otificati o n of Cl os ure of St u d y  .... 6 1  
7. 1. 2  
Pr oce d ures f or Ha n dli n g I nc orrectl y E nr olle d or Ra n d o mize d Partici pa nts  ........ 6 1  
7. 2  
Partici pa nt Wit h dra wal fr o m t he St u d y  ................................................................ 6 1  
7. 2. 1  
Disc o nti n uati o n or S us pe nsi o n of t he W h ole St u d y Pr o gra m  .............................. 6 2  
7. 3  
L ost t o F oll o w -u p  ................................................................................................. 6 2  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ............................................... 6 3  
8. 1  
Efficac y Assess me nts  ........................................................................................... 6 4  
8. 1. 1  
I n vesti gat or Gl o bal Assess me nt ........................................................................... 6 4  
8. 1. 2  
Ecze ma Area a n d Se verit y I n de x  .......................................................................... 6 4  
8. 1. 3  
Sc ori n g At o pic Der matitis  .................................................................................... 6 5  
8. 1. 4  
B o d y S urface A rea I n v ol ve me nt of At o pic Der matitis ........................................ 6 5  
8. 1. 5  
S ki n P h ot o gra p h y  ................................................................................................. 6 6  
8. 1. 6  
Patie nt -re p orte d O utc o mes ................................................................................... 6 6  
8. 1. 6. 1  
Pea k Pr urit us N u meric Rati n g Scale  .................................................................... 6 7  
8. 1. 6. 2  
Patie nt -Orie nte d Ecze ma Meas ure  ....................................................................... 6 7  
8. 1. 6. 3  
Der m at ol o g y Life Q ualit y I n de x  .......................................................................... 6 7  
8. 1. 6. 4  
C hil dre n’s Der mat ol o g y Life Q ualit y I n de x ......................................................... 6 8  
8. 1. 6. 5  
H os pital A n xiet y a n d De pressi o n Scale  ............................................................... 6 8  
8. 1. 6. 6  
Patie nt Gl o bal I m press i o n of Se verit y .................................................................. 6 8  
8. 1. 6. 7  
S F -3 6 ( Versi o n 2), Ac ute Recall  .......................................................................... 6 8  
8. 1. 6. 8  
E ur o pea n Q ualit y of Life -5 Di me nsi o ns  .............................................................. 6 9  
8. 1. 7  
Patie nt -Re p orte d E x perie nce  ................................................................................ 7 0  
8. 2  
Safet y Assess me nts  ............................................................................................... 7 0  
8. 2. 1  
Cli nical Safet y La b orat or y Assess me nts  .............................................................. 7 0  
8. 2. 1. 1  
Pre g na nc y Tests  .................................................................................................... 7 1  
8. 2. 1. 2  
Ser ol o g y  ................................................................................................................ 7 2  
8. 2. 2  
P h ysical E xa mi nati o ns  .......................................................................................... 7 2  
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Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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. 3  
Vital Si g ns  ............................................................................................................ 7 3  
8. 2. 4  
Electr ocar di o gra ms  ............................................................................................... 7 3  
8. 3  
A d verse E ve nts a n d Seri o us A d verse E ve nts  ....................................................... 7 3  
8. 3. 1  
Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or mati o n  ................. 7 4  
8. 3. 2  
F oll o w -u p of A Es a n d S A Es  ................................................................................ 7 4  
8. 3. 3  
Ca usalit y C ollecti o n  ............................................................................................. 7 5  
8. 3. 4  
A d verse E ve nts Base d o n Si g ns a n d S y m pt o ms  .................................................. 7 5  
8. 3. 5  
A d verse E ve nts Base d o n E xa mi nati o ns a n d Tests  .............................................. 7 6  
8. 3. 6  
Disease U n der St u d y  ............................................................................................ 7 6  
8. 3. 7  
Re p orti n g of Seri o us A d verse E ve nts  ................................................................... 7 6  
8. 3. 8  
Pre g na nc y  ............................................................................................................. 7 7  
8. 3. 8. 1  
Mater nal E x p os ure  ................................................................................................ 7 7  
8. 3. 9  
De vice C o nstit ue nt Deficie ncies  .......................................................................... 7 8  
8. 3. 1 0  
Seri o us A d verse De vice Effect Re p orti n g  ............................................................ 7 8  
8. 3. 1 1  
Me dicati o n Err or  ................................................................................................... 7 9  
8. 3. 1 2  
Ma na ge me nt of I n vesti gati o nal Pr o d uct -relate d Dr u g Reacti o ns ......................... 7 9  
8. 4  
O ver d ose  ............................................................................................................... 8 0  
8. 5  
H u ma n Bi ol o gical Sa m ples  .................................................................................. 8 0  
8. 5. 1  
P har mac o ki netics  .................................................................................................. 8 1  
8. 5. 1. 1  
Deter mi nati o n of Dr u g C o nce ntrati o n  .................................................................. 8 1  
8. 5. 2  
I m m u n o ge nicit y Assess me nts .............................................................................. 8 2  
8. 5. 3  
P har mac o d y na mics  ............................................................................................... 8 2  
8. 6  
H u ma n Bi ol o gical Sa m ple Bi o mar kers  ................................................................ 8 2  
8. 8  
Healt hcare Res o urce Utilizati o n  ........................................................................... 8 5  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................. 8 6  
9. 1  
Statistical H y p ot heses  ........................................................................................... 8 6  
9. 2  
Sa m ple Size Deter mi nati o n  .................................................................................. 8 7  
9. 3  
P o p ulati o ns f or A nal yses  ...................................................................................... 8 9  
9. 4  
Statistical A nal yses  ............................................................................................... 9 0  
9. 4. 1  
Ge neral C o nsi derati o ns  ......................................................................................... 9 0  
9. 4. 2  
Efficac y  ................................................................................................................. 9 1  
9. 4. 2. 1  
Pri mar y E n d p oi nt  .................................................................................................. 9 1  
9. 4. 2. 2  
Ke y Sec o n dar y E n d p oi nts  .................................................................................... 9 2  
9. 4. 2. 3  
Sec o n dar y E n d p oi nts  ............................................................................................ 9 3  
C CI

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9.4.2.4 
Tertiary/exploratory Endpoints ............................................................................. 95 
9.4.3 
Safety Analyses .................................................................................................... 95 
9.4.4 
Immunogenicity Analyses .................................................................................... 97 
9.4.5 
Other Analyses ..................................................................................................... 97 
9.4.5.1 
Skin Photography ................................................................................................. 97 
9.4.6 
Methods for Multiplicity Control ......................................................................... 97 
9.4.7 
Sensitivity Analyses ............................................................................................. 98 
9.4.8 
Subgroup Analysis ................................................................................................ 98 
9.5 
Interim Analyses ................................................................................................... 98 
9.6 
Data and Safety Monitoring Board ....................................................................... 99 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................ 99 
11 
REFERENCES ................................................................................................... 130 
 
LIST OF TABLES 
Table 1 
Primary and Secondary Objectives ............................................................. 14 
Table 2 
Number of Patients Randomized by Stratification Factors ......................... 17 
Table 3 
Schedule of Site Visit Activities ................................................................. 23 
Table 4 
Schedule of PRO Assessments .................................................................... 27 
Table 5 
Objectives and Endpoints ............................................................................ 34 
Table 6 
Investigational Products .............................................................................. 49 
Table 7 
Investigator Global Assessment Score ........................................................ 64 
Table 8 
Patient-Oriented Eczema Measure Score Bands ......................................... 67 
Table 9 
Threshold Values for the SF-36v2 Scale and Summary Measures ............. 69 
Table 10 
Laboratory Safety Variables ....................................................................... 71 
Table 11 
Randomization Stratification ...................................................................... 88 
Table 12 
Populations for Analyses ............................................................................. 89 
 
LIST OF FIGURES 
Figure 1 
Investigational Product Administered Q4W by Randomized Treatment 
Sequence ..................................................................................................... 18 
Figure 2 
Study Design ............................................................................................... 21 
Figure 3 
Investigational Product Administered Q4W by Randomized Treatment 
Sequence ..................................................................................................... 40 
Figure 4 
Injection Sites and Examples of Rotation Scheme ..................................... 50 

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LIST OF APPENDICES 
Appendix A 
Regulatory, Ethical, and Study Oversight Considerations ........................ 100 
Appendix B 
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting ........................................................................ 105 
Appendix C 
Handling of Human Biological Samples ................................................... 110 
Appendix D 
Optional Genomics Initiative Sample ....................................................... 112 
Appendix E 
Anaphylaxis: Definition, Signs, Symptoms, and Management ................ 116 
Appendix F 
Changes Related to Mitigation of Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis .............................. 119 
Appendix G 
Abbreviations ............................................................................................ 121 
Appendix H 
Protocol Amendment History ................................................................... 124 
 

Clinical Study Protocol 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: 
A Phase 2 Multinational, Randomized, Double-blind, Parallel-group, 16-week Placebo-
controlled Study with a 36–week Extension to Investigate the Use of Benralizumab for 
Patients with Moderate to Severe Atopic Dermatitis Despite Treatment with Topical 
Medications (The HILLIER Study) 
Short Title: 
A Phase 2 study to investigate the use of benralizumab in patients with moderate to severe 
atopic dermatitis despite treatment with topical medications (The HILLIER Study) 
Rationale:The aim of this study is to investigate the use of benralizumab as treatment for 
patients with moderate to severe atopic dermatitis (AD) who remain symptomatic despite 
treatment with topical medications. It is proposed that benralizumab will deplete eosinophils 
from affected skin, improve symptoms of AD, and improve AD-related quality of life. This 
Phase 2 study is designed to compare the efficacy of 16 weeks of treatment with benralizumab 
30 mg versus placebo and compare benralizumab maintenance dosing regimens (every 8 
weeks [Q8W] versus every 4 weeks [Q4W]) in the 36-week extension period. 
Objectives and Endpoints: 
The primary and secondary objectives and associated endpoints are detailed below. For 
tertiary/exploratory objectives and endpoints, see Section 3 of this protocol. 

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Table 1 
Primary and Secondary Objectives 
Primary objective: 
Estimand description/endpoints 
To compare the clinical efficacy of 
benralizumab 30 mg with placebo in 
patients with AD despite treatment with 
topical medications a. 
• 
Population: Full analysis set 
• 
Endpoint: A binary response giving the proportion of patients 
with an IGA 0/1 and a decrease in IGA of ≥ 2 points at Week 
16 relative to baseline 
• 
Intercurrent events:  Participants who withdraw from the 
study or require rescue therapy b will be considered as non-
responders from the time these events occur up to Week 16.  
• 
Summary measure: Difference in proportions   between 
benralizumab and placebo at Week 16 
Secondary objectives: 
Endpoint/variable: 
To compare the effect of benralizumab 
with placebo on supportive measures of 
clinical efficacy in patients with AD 
despite treatment with topical 
medications a. 
• 
Key secondary endpoint c: proportion of patients with skin 
clearance (EASI-75) at Week 16 
• 
Key secondary endpoint c: proportion of patients with an 
improvement of ≥ 4 or more points in peak pruritus weekly 
score at Week 16 
• 
Key secondary endpoint c: proportion of patients with skin 
clearance (EASI-90) at Week 16 
• 
Proportion of patients with skin clearance (EASI-50) at 
Week 16 
• 
Proportion of patients with skin clearance (EASI-100) at 
Week 16 
• 
Change from baseline in EASI score at Week 16 
• 
Change from baseline in peak pruritus score at Week 2 
• 
Change from baseline in POEM score at Week 16 
• 
Change from baseline in SCORAD score at Week 16 
To compare benralizumab with placebo 
on patient-reported health-related quality 
of life measures in patients with AD 
despite treatment with topical 
medications a. 
• 
Change from baseline in DLQI and CDLQI at Week 16 
To estimate the PK and immunogenicity 
of benralizumab 30 mg in patients with 
AD despite treatment with topical 
medications a. 
• 
Serum benralizumab concentration 
• 
ADA 
To compare long-term treatment with 
benralizumab 30 mg Q8W versus 
benralizumab 30 mg Q4W up to Week 
52 in patients with AD despite treatment 
with topical medications a. 
• 
Change from baseline in EASI total score at Week 52. 
• 
Proportion of patients with an IGA 0/1 and a decrease in IGA 
of ≥ 2 points at Week 52 relative to baseline 
• 
Proportion of patients with EASI-75 at Week 52 
• 
Other supportive efficacy assessments at Week 52 as 
appropriate. 

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Table 1 
Primary and Secondary Objectives 
Safety  
To compare the safety and tolerability of 
benralizumab with placebo in patients 
with AD despite treatment with topical 
medications a. 
Safety and tolerability will be evaluated in terms of AEs, Vital 
signs, and Clinical laboratory values. 
Assessments related to AEs cover: 
• 
Occurrence/frequency 
• 
Relationship to IP as assessed by Investigator 
• 
Intensity 
• 
Seriousness 
• 
Death 
• 
AEs leading to discontinuation of IP 
 
Vital signs parameters include systolic and diastolic blood 
pressure, and pulse, as well as respiration rate, body temperature, 
body weight, and height. 
Assessments related to vital signs cover: 
• 
Observed value 
• 
Absolute and percent change from baseline values over time 
a 
The locally-approved regimen of topical medication. 
b 
Rescue therapy is defined in Section 6.5.3. 
c 
The key secondary endpoints will use the same estimand as outlined for the primary endpoint. For all other 
endpoints, the estimands will be detailed in the SAP. 
AD, atopic dermatitis; ADA, anti-drug antibodies; AE, adverse event; CDLQI, The Children’s Dermatology Life 
Quality Index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, 
Investigator Global Assessment; IP, investigational product; PK, pharmacokinetics; POEM, Patient Oriented 
Eczema Measure; Q4W, every 4 weeks; Q8W, every 8 weeks; SAP, Statistical Analysis Plan; SCORAD, 
SCORing Atopic Dermatitis. 
 
Overall Design 
This is a Phase 2 multinational, randomized, double-blind, placebo-controlled, parallel-group 
study to compare the efficacy and safety of benralizumab 30 mg monotherapy with placebo in 
patients ≥ 12 years of age with moderate to severe AD who remain symptomatic despite 
treatment with standard of care treatment with topical medications. The purpose of the study is 
to compare the efficacy and safety of benralizumab 30 mg subcutaneously (SC) Q4W versus 
placebo SC Q4W for 16 weeks and to compare benralizumab 30 mg Q4W and Q8W 
maintenance dosing regimens during a 36-week extension period. 
The study comprises the following consecutive periods: 

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• 
A 1- to 4-week run-in period, which includes a 7-day washout period of topical 
medications prior to randomization 
• 
A 16-week placebo-controlled, double-blind treatment period  
• 
A 36-week blinded-to-dosing regimen extension period for maintenance treatment. 
 
Following informed consent/assent, all eligible participants will enter a run-in period of 1 to 4 
weeks during which inclusion/exclusion criteria will be assessed, medical history taken, and a 
complete physical exam will be conducted. Potentially eligible participants will enter a 7-day 
washout period (prior to randomization) during which all topical medications for AD except 
the stable emollient moisturizer regimen must be discontinued. Randomization will be 
stratified by baseline blood eosinophil and age subgroups. 
An independent Data and Safety Monitoring Board (DSMB) will be utilized. 
Disclosure Statement: 
This is a Phase 2 parallel-group, placebo-controlled study with 3 treatment sequences that are 
participant- and investigator-blinded. 
Number of Participants: 
Approximately 270 participants are expected to be enrolled/screened in order to achieve at 
least 160, and a maximum of 200, eligible study participants randomly assigned to study 
intervention to ensure that a broad distribution of participants is recruited across the range of 
ages and blood eosinophil levels to allow potential identification of responding subpopulations 
and appropriate cut-offs for future studies, if necessary. 
Note: "Enrolled" is defined as a participant's agreement to participate in a clinical study 
following completion of the informed consent/assent process. Potential participants who are 
screened for the purpose of determining eligibility for the study but are not randomized to the 
study will be considered “screen failures”, unless otherwise specified by the protocol. 
Intervention Groups and Duration: 
Following a 1- to 4-week run-in period, a minimum of approximately 160 participants will be 
randomized in a ratio of 1:1:2, respectively, to 1 of the following 3 treatment sequences (refer 
also to Figure 1 and Figure 2): 
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q4W administered until Week 52 (n = 40) 
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q8W administered until Week 52 (n = 40) 

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• 
Placebo Q4W until Week 16, followed by an extension period with benralizumab 30 
mg Q4W administered until Week 28, and then benralizumab 30 mg Q8W administered 
until Week 52 (n = 80). 
 
Up to Week 16 (ie, prior to the start of the 36-week extension period evaluating the 
benralizumab 30 mg Q4W and Q8W maintenance regimens), participants who receive 
benralizumab 30 mg Q4W initially will be grouped together and considered as a single 
treatment group. Randomization will be stratified by blood eosinophils at baseline 
(< 300 cells/μL, ≥ 300 cells/μL) and age (≥ 12 to < 18 years and ≥ 18 years). Participants will 
be randomized in minimum cohort sizes across the baseline blood eosinophil and age 
subgroups; the intended distribution of participants in total across the treatment groups for 
each combination of these factors is summarized in Table 2. If the minimum recruitment 
target in any cohort is achieved, that cohort may remain open in order to fulfill minimum 
recruitment targets for the remaining cohorts. Thus, minimum recruitment targets may be 
exceeded in cohorts that remain open while fulfilling recruitment targets for other cohorts. 
Recruitment will stop when a maximum of 200 participants in total is achieved. 
Table 2 
Number of Patients Randomized by Stratification Factors 
 
Baseline blood eosinophils 
<300 cells/μL 
≥300 cells/μL 
Adolescents (≥ 12 to < 18 years), n 
30 
50 
Adults (≥ 18 years), n 
30 
50 
 
Blinded investigational product (benralizumab or placebo) will be administered by SC 
injection at the investigational site Q4W for up to 48 Weeks. 
In order to maintain blinding to the benralizumab Q4W treatment regimen in the extension 
period, participants randomized to receive benralizumab Q8W will also receive Q8W placebo 
injections at intervening visits where they are not scheduled to receive benralizumab (Figure 
1). 
The final dose of benralizumab/placebo will be administered at Week 48.  

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and a 5% significance level and assumes a response rate of 40% for benralizumab 30 mg 
Q4W and 10% for placebo.   
Subgroup analyses:  As a benchmark, a minimum of 35 participants per treatment will provide 
at least 80% power to detect a 30% difference between benralizumab 30 mg Q4W and 
placebo. (As for the primary analysis, these calculations are based on a 2-sided test and a 5% 
significance level and assumes the same response rates for benralizumab 30 mg Q4W and 
placebo.) Thus, there is a high probability of detecting differences between treatments in the 
baseline blood eosinophils ≥ 300 cells/μL subgroup (with 50 participants per treatment), in the 
adult subgroup (with 40 participants per treatment), and in the adolescent subgroup (with 40 
participants per treatment). Note that in the baseline blood eosinophils < 300 cells/μL 
subgroup, 30 participants per treatment group will provide an adequate amount of data to 
explore treatment differences, and will allow different cut-offs between ‘low’ and ‘high’ 
eosinophils at baseline to be assessed. 
Assessing consistency of effect:  Consistency of effect will be assessed between adults and 
adolescents in the overall population and in any identified subgroup for baseline blood 
eosinophils.  By aiming for 25 adults and 25 adolescents per treatment in the baseline blood 
eosinophils ≥ 300 cells/μL subgroup, the probability of detecting consistent effects between 
adults and adolescents is high. That is, assuming the true increase in response rate between 
benralizumab 30 mg Q4W and placebo is 30%, there is > 85% chance of observing a 
treatment difference for adolescents of at least half of the treatment difference observed for 
adults. 
Assessment of the First 16 Weeks of Treatment Intervention 
The primary efficacy analysis will be based on the initial 16-week, double-blind, placebo-
controlled phase of the study, and will compare benralizumab 30 mg Q4W versus placebo. 
The primary estimand will be based on the full analysis set (refer to Table 12). Intercurrent 
events will consist of participants who withdraw from the study or require rescue therapy 
(defined in Section 6.5.3). The primary estimand will regard these participants as non-
responders from the time such events occur up to Week 16. A participant with missing data at 
a specific time point will also be considered as a non-responder at that time point. 
The primary endpoint is a binary response, identifying responders with IGA 0/1 (ie, clear or 
almost clear) and a decrease in IGA of 2 or more points at Week 16, relative to baseline.  For 
the primary analysis, a logistic regression model will be fitted to the primary endpoint using a 
logit link function. The model will include treatment group and baseline covariates for age 
(adolescents; adults) and blood eosinophils (< 300 cells/μL; ≥ 300 cells/μL). The model will be 
used to estimate the proportion of responders for benralizumab 30 mg Q4W and placebo, the 
difference between these proportions (benralizumab 30 mg Q4W – placebo), and an odds 

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ratio, with corresponding 95% confidence limits. A p-value, corresponding to a 2-sided test, 
will be presented to compare the benralizumab 30 mg Q4W and placebo treatment groups.  
The first and third key secondary endpoints will be derived from the Eczema Area and 
Severity Index (EASI) and will include the proportion of patients with EASI-75 at Week 16 
and the proportion of patients with EASI-90 at Week 16, respectively. The second key 
secondary endpoint will be the proportion of patients with an improvement of 4 or more points 
in peak pruritus weekly score at Week 16 relative to baseline. 
1.2 
Schema 
The general study design is summarized in Figure 2. 
 

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Figure 2
Study Design
a
To maintain blinding, patients will receive investigational product every Q4W during the extension period. Placebo will be administered Q8W, occurring 
4 weeks after each benralizumab administration.
n, number; Q4W, every 4 weeks; Q8W, every 8 weeks.

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1.3 
Schedule of Activities  
The Schedule of Activities (SoA) at each site visit for this study is provided in Table 3. 
Details of the schedule for home and site visit patient-reported outcome (PRO) assessments 
are provided in Table 4. 

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Table 3 
Schedule of Site Visit Activities 
Procedure 
Run-
in  
Double-blind placebo-
controlled treatment 
period 
Double-blind extension period (to EoT) 
Follow-
up 
 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 15 
16 
Unsch 
Visit c 
IP 
Disc. d 
CSP section or 
appendix with 
details 
Week a  
-4 to -
1 b 
0 
4 
8 
12 16 20 
24 
28 
32 
36 
40 
44 
48 52 
60 
General procedures 
Informed consent/assent  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Appendix A 3 
Demography/medical 
history 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Sections 5.1 and 
5.2 
Inclusion/exclusion 
criteria 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Sections 5.1 and 
5.2 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.5 
Randomization 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Section 6.3.1 
Efficacy assessments 
Handheld device 
distribution for PRO 
collection 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Section 8.1.4 
Review compliance of  
at-home PRO assessments 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.1 and 
Table 4 
At-site PRO assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.1 and 
Table 4 
IGA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.1.1 
EASI, BSA, SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.1.2 and 
Section 8.1.3 

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Table 3 
Schedule of Site Visit Activities 
Procedure 
Run-
in  
Double-blind placebo-
controlled treatment 
period 
Double-blind extension period (to EoT) 
Follow-
up 
 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 15 
16 
Unsch 
Visit c 
IP 
Disc. d 
CSP section or 
appendix with 
details 
Week a  
-4 to -
1 b 
0 
4 
8 
12 16 20 
24 
28 
32 
36 
40 
44 
48 52 
60 
Other assessments in-office 
Patient reported 
experience (free text entry) 
X 
- 
X 
X 
X 
X 
- 
- 
X 
- 
- 
X 
- 
- 
X 
- 
- 
- 
Section 8.1.7 
Healthcare resource 
utilization  
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
X 
Section 8.8 
Photographic skin 
assessment 
- 
X 
- 
X 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Section 8.1.5 
Safety assessments 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.3 
Complete (Brief) physical 
exam 
X 
(X) (X) (X) (X) X (X) (X) (X) (X) (X) (X) (X) (X) X 
- 
X 
- 
Section 8.2.2 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.2.3 
Weight and height 
X 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
X 
- 
- 
- 
Section 8.2.2 
ECG 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Section 8.2.4 
Laboratory assessments 
Hematology, clinical 
chemistry, and urinalysis 
X 
X e X e 
- 
- 
X 
- 
-  
X 
- 
- 
X 
- 
- 
X 
- 
- 
X 
Section 8.2.1 
Serum pregnancy test  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Section 8.2.1.1 
Urine dipstick pregnancy 
test 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
X 
Section 8.2.1.1 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
T a ble 3  
Sc he d ule of Site Visit Acti vities  
Pr oce d ure  
R u n -
i n  
D o u ble -bli n d pl ace b o -
c o ntr olle d tre at me nt 
peri o d  
D o u ble -bli n d e xte nsi o n peri o d (t o E o T)  
F oll o w -
u p  
 
Visit  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
1 1  
1 2  
1 3  
1 4  1 5  
1 6  
U nsc h 
Visit c 
I P 
Disc. d  
C S P secti o n or 
a p pe n di x wit h 
det ails  
Wee k 
a  
-4 t o -
1 b  
0  
4  
8  
1 2  1 6  2 0  
2 4  
2 8  
3 2  
3 6  
4 0  
4 4  
4 8  5 2  
6 0  
P ost -me n o pa use 
c o nfir mati o n  
( F S H) 
X  
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Secti o n 8. 2. 1. 1  
He patitis/ HI V scree ni n g  
X  
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Secti o n 8. 2. 1. 2  
P har mac o ki netics sa m ple 
pri or t o I P a d mi nistrati o n f 
- 
X  
- 
X  
- 
X  
- 
- 
X  
- 
- 
X  
- 
- 
X  
- 
- 
X  
Secti o n 8. 5. 1  
I m m u n o ge nicit y sa m ple 
( A D A)  
- 
X  
- 
X  
- 
X  
- 
- 
X  
- 
- 
X  
- 
- 
X  
- 
- 
X  
Secti o n 8. 5. 2  
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
T a ble 3  
Sc he d ule of Site Visit Acti vities  
Pr oce d ure  
R u n -
i n  
D o u ble -bli n d pl ace b o -
c o ntr olle d tre at me nt 
peri o d  
D o u ble -bli n d e xte nsi o n peri o d (t o E o T)  
F oll o w -
u p  
 
Visit  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
1 1  
1 2  
1 3  
1 4  1 5  
1 6  
U nsc h 
Visit c 
I P 
Disc. d  
C S P secti o n or 
a p pe n di x wit h 
det ails  
Wee k 
a  
-4 t o -
1 b  
0  
4  
8  
1 2  1 6  2 0  
2 4  
2 8  
3 2  
3 6  
4 0  
4 4  
4 8  5 2  
6 0  
I n vesti gati o nal pr o d uct a d mi nistrati o n 
I P a d mi nistrati o n g  
- 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
- 
- 
- 
- 
Secti o n 4. 1. 1  
Secti o n 6. 1  
a 
T he wi n d o w f or Visits 3 t hr o u g h 1 6 will be  ±  3 da ys.  
b 
T he r u n -i n peri o d is a ma xi m u m of 4 wee ks a n d a mi ni m u m of 1 wee k. T he was h o ut peri o d is 7 da ys pri or t o ra n d o mizati o n d uri n g w hic h partici pa nts m ust 
disc o nti n ue use of t o pical me dicati o ns f or A D.  
c 
U nsc he d ule d Visit: ma y be i nitiate d as nee de d; pr oce d ures s h o ul d be perf or me d as cli nicall y i n dicate d at t he discreti o n of t h e I n vesti gat or.  
d 
I n vesti gati o nal Pr o d uct Disc o nti n uati o n: I n case of earl y disc o nti n uati o n fr o m i n vesti gati o nal pr o d uct, visit pr oce d ures s h o ul d be perf or me d 4 
wee ks  ±  7  da ys after t he last d ose of I P or as s o o n as feasi ble if t his i nter val is misse d (e g, if decisi o n o n disc o nti n uati o n was ma de  later). N ote: T he I P D 
visit  re places t he nearest re g ular visit. 
e 
O nl y a bs ol ute e osi n o p hil c o u nts will be meas ure d at t his visit.  
f 
N o I P will be a d mi nistere d at Wee k 5 2.  
g 
Re vie w of self -a d mi nistrati o n of I P pr oce d ures ma y be offere d at Visits 2 a n d 3.  
A D, At o pic der matitis; A D A, A nti -dr u g a nti b o dies; A E, A d verse E ve nt; B S A, b o d y s urface area; C S P, Cli nical St u d y Pr ot oc ol; E A SI, Ecze ma Area a n d Se verit y 
I n de x;  E C G, Electr ocar di o gra m; 
; E o T, E n d of treat me nt; F S H, F ollicle-sti m ulati n g h or m o ne; HI V, H u ma n 
i m m u n o deficie nc y vir us; I G A, I n vesti gat or Gl o bal Assess me nt; I P, I n vesti gati o nal pr o d uct; I P D, I n vesti gati o nal pr o d uct disc o nti n uati o n; P R O, Patie nt-re p orte d 
o utc o mes; 
; S C O R A D, S C O Ri n g At o pic Der matitis; U nsc h, u nsc he d ule d. 
 
C CI
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
If a n at-h o me P R O is a vaila ble acc or di n g t o t he assess me nt sc he d ule i n Ta ble 4  b ut has n ot 
bee n c o m plete d pri or t o t he site visit, t h e n site staff will direct t he partici pa nt t o c o m plete t he 
assess me nt at t he site bef ore a n y ot her st u d y pr oce d ures are c o n d ucte d.  
T a ble 4  
Sc he d ule of P R O Assess me nts  
I nstr u me nts 
Sc he d ule  
Dail y P R O at h o me: Pea k Pr urit us N R S  
E ver y e ve ni n g a. First assess me nt at h o me t he da y of 
V 1.  
Peri o dic P R Os: 
, E Q-5 D -5 L, 
S F -3 6 v 2  
At site at V 1 a n d V 2. At h o me e ver y 2 8 ± 3 da ys after 
V 2 u ntil V 6 is c o nfir me d. At site at V 6, V 7, V 1 2, a n d 
V 1 6. Re q uire d at I P D visit. O pti o nal at  u nsc he d ule d 
visit.  
Peri o dic P R Os: P O E M, D L QI/ C D L QI, H A D S, P GI -
S, Patie nt -re p orte d e x perie nce (free te xt e ntr y) 
At site at V 1, V 2, V 3, V 4, V 5, V 6, V 9, V 1 2, V 1 5, 
a n d V 1 6. Re q uire d at I P D visit. O pti o nal at 
u nsc he d ule d visit. C D L QI will be assesse d i n 
parti ci pa nts ≤ 1 6 years of a ge at V 1; D L QI will be 
assesse d i n all ot her patie nts >  1 6 years of a ge.  
P R O at site: 
 
At site at V 6 a n d V 1 5. Re q uire d at I P D visit.  
a 
E ve ni n g is defi ne d as 1 7: 0 0 t o 2 3: 5 9.  
 
  
 C D L QI, T he C hil dre n’s Der mat ol o g y Life Q ualit y I n de x; D L QI, 
Der mat ol o g y Life Q ualit y I n de x; E Q -5 D -5 L, E ur o pea n Q ualit y of  Life -5 Di me nsi o ns; H A D S, H os pital A n xiet y 
a n d De pressi o n Scale; I P D, I n vesti gati o nal pr o d uct disc o nti n uati o n; N R S, N u merical Rati n g Scale; 
 
; P GI-S, Patie nt Gl o bal I m pressi o n of Se verit y; P O E M, Patie nt 
Orie n te d Ecze ma Meas ure; P R O, Patie nt-re p orte d o utc o me; S F-3 6 v 2, S h ort F or m 3 6 -ite m Healt h S ur ve y 
Versi o n 2; 
; V, Visit. 
 
C CI
C CI
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
I N T R O D U C TI O N 
2. 1  
St u d y R ati o n ale  
At o pic der matitis ( A D), als o referre d t o as ecze ma, is c hara cterize d b y i nte nse itc h a n d 
ecze mat o us s ki n lesi o ns. It is t he m ost c o m m o n c hr o nic i nfla m mat or y s ki n disease, affecti n g 
bet wee n 2. 1 % a n d 4. 9 % of a d ults ( Bar bar ot et al 2 0 1 8 ), a n d u p t o 2 0 % of c hil dre n i n s o me 
c o u ntries ( N utte n 2 0 1 5 ). T he disease ofte n prece des t he de vel o p me nt of f o o d aller g y, ast h ma, 
a n d aller gic r hi nitis (referre d t o as t he ‘at o pic marc h’), a n d p oses a si g nifica nt b ur de n o n 
healt h -care res o urces a n d pat ie nts’ q ualit y of life (Le u n g a n d G utt ma n -Yass k y 2 0 1 4 , N utte n 
2 0 1 5 ); h o we ver, treat me nt o pti o ns f or patie nts wit h m o derate t o se vere A D are li mite d (Le u n g 
a n d G utt ma n -Yass k y 2 0 1 4 ). 
Patie nts wit h A D are  c o m m o nl y c ol o nize d wit h Sta p h yl oc occ us a ure us a n d ha ve bee n s h o w n 
t o ha ve m ore se vere disease, aller ge n se nsitizati o n, barrier disr u pti o n, lactate de h y dr o ge nase 
le vel ele vati o n a n d hi g her le vels of t y pe 2 bi o mar kers (e osi n o p hil c o u nt, t otal I g E , C C L 1 7, 
an d peri osti n) t ha n n o nc ol o nize d patie nts wit h A D ( Si m ps o n et al 2 0 1 8 ). W hile bl o o d 
e osi n o p hilia is varia ble i n t he ge neral p o p ulati o n of patie nts wit h A D , it i ncreases wit h disease 
se verit y, t here b y s u p p orti n g t he e osi n o p hilic nat ure of t he disease (Je ner o wicz et al 2 0 0 7). 
S ki n bi o psies ofte n d o n ot de m o n strate mar ke d e osi n o p hil prese nce; e osi n o p hils are m ore 
li kel y t o be prese nt i n ac utel y disease d s ki n sa m ples t ha n i n c hr o nicall y disease d sa m ples. 
H o we ver, t he mar kers of e osi n o p hil acti vati o n a n d de gra dati o n (e g, e osi n o p hil per o xi dase, 
maj or basic pr otei n [ M B P], e osi n o p hil cati o nic pr otei n a n d 
 
,]), as re veale d b y i m m u n ofl u oresce nce a n d e osi n o p hil me m bra ne disr u pti o n b y 
electr o n micr osc o p y, are pr o mi ne nt wit hi n A D s ki n sa m ples pr o vi di n g f urt her e vi de nce of 
e osi n o p hil i n v o l ve me nt i n t he pat h o p h ysi ol o g y of A D (Ott et al 1 9 9 4  a n d Ras hee d et al 2 0 1 8 ). 
T his e vi de nce f or a r ole of e osi n o p hils i n t he pat h o p h ysi ol o g y of A D s u g gests t hat a direct 
e osi n o p hil -de pleti n g a p pr oac h, as pr o vi de d b y be nraliz u ma b, ma y pr o ve be neficial i n t he 
treat me nt of A D. A d diti o nall y, res ults fr o m a pil ot st u d y of patie nts wit h h y pere osi n o p hilic 
s y n dr o me ( H E S) s h o we d i m pr o ve me nts i n s ki n-relate d s y m pt o ms, wit h a n a bse nce of 
e osi n o p hils i n s ki n bi o psies after 1 2 wee ks of treat me nt wit h be nraliz u ma b ( K ua n g et al 
2 0 1 9 ). Base d o n t hese res ults, f urt her i n vesti gati o n of t he efficac y a n d safet y of be nraliz u ma b 
i n treati n g m o derate t o se vere A D is warra nte d. 
2. 2  
B ac k gr o u n d  
A D is c haracterize d b y itc h y lesi o ns wit h a n i ncrease d n u m ber of i nfla m mat or y cells i n t he 
s ki n. T he pat h o p h ysi ol o g y of A D is c o m ple x a n d t he dri vers of t he disease pr ocess are 
u n k n o w n. It has bee n s u g geste d t hat t he i nteracti o n of a d ysf u ncti o nal e pi der mal barrier i n 
ge neticall y pre dis p ose d i n d i vi d uals wit h har mf ul effects of e n vir o n me ntal a ge nts lea ds t o t he 
de vel o p me nt of t he disease ( N utte n 2 0 1 5 ). A c o m bi nati o n of ge netic, e n vir o n me ntal, a n d 
i m m u n ol o gic fact ors li kel y acc o u nt f or t he heter o ge neit y of A D o nset a n d t he se verit y a n d 
C CI

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
natural history of the disease. Thus, effective control of local and systemic immune activation 
is necessary for optimal management of AD (Leung and Guttman-Yassky 2014). There are 
few effective medications available for long-term use and current treatments target symptom 
control rather than a cure. These treatments attempt to manage skin barrier integrity or 
impairment and include topical corticosteroids (TCS), emollients, antibiotics and, in refractory 
disease, short course systemic corticosteroids, phototherapy, and immunosuppressants (Leung 
and Guttman-Yassky 2014). Cyclosporine A is approved in some countries for treatment of 
severe AD but generally only as a short-term rescue therapy (≤ 1 year) due to cumulative 
nephrotoxicity (Megna et al 2017). Dupilumab is approved for treatment of moderate to 
severe AD; however, ≤ 40% of patients achieved clear or almost clear skin (as defined by 
≥ 90% improvement in Eczema Area and Severity Index [EASI-90] or Investigator Global 
Assessment of 0 or 1 [IGA 0/1]) (Blauvelt et al 2017, Simpson et al 2016, and Thaci et al 
2016). The lack of approved treatments has led to recommendations for use of other agents 
not approved for AD (eg, methotrexate and azathioprine) (Boguniewicz et al 2018). Thus, 
there remains an unmet medical need for more effective, long-term treatments for AD that 
target both local and systemic immune activation. 
The role of eosinophils in the pathophysiology of AD suggests that a direct eosinophil-
depleting approach may prove beneficial in the treatment of AD. Eosinophilic diseases are in 
large part driven by T2 cytokines, including IL-4, interleukin-5 (IL-5,), and IL-13, which are 
produced by type-2 T helper cells, innate lymphocyte type 2 cells, and mast cells (Valent et al 
2012); serum IL-13 and blood eosinophil levels have been shown to be significantly increased 
in children with early-onset AD (Lee et al 2016). Benralizumab is a humanized, recombinant 
IgG1k monoclonal antibody that binds to the alpha subunit of human alpha chain of the IL-5 
receptor (IL-5Rα.). This receptor is selectively expressed by mature eosinophils, eosinophil 
progenitor cells, and basophils. The antibody has been engineered to be afucosylated, or 
without a fucose sugar residue in the Fc domain, which also facilitates binding to FcɣRIII 
receptors on immune effectors cells, such as natural killer cells, leading to apoptosis of 
eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity 
(ADCC). In asthmatic patients, the enhanced ADCC activity of benralizumab results in the 
rapid and nearly complete depletion of eosinophils in the blood as well as depletion of 
eosinophils in the lung tissue, sputum and bone marrow (Busse et al 2013, Kolbeck et al 2010, 
Laviolette et al 2013). Thus, benralizumab may potentially be effective in AD and 
eosinophilic-driven skin diseases (Simon and Simon 2019; Eberle et al 2019). 
This Phase 2 study is designed to investigate the efficacy and safety of benralizumab 30 mg 
subcutaneously (SC) in treating patients with moderate to severe AD who remain 
symptomatic despite treatment with at least approved doses of topical medications.  
A detailed description of the chemistry, pharmacology, efficacy, and safety of benralizumab is 
provided in the Investigator’s Brochure. 

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
2.3 
Benefit/risk Assessment 
2.3.1 
Benefit Assessment 
AD is a chronic inflammatory disease that most commonly affects children and has a marked 
impact on quality of life measures (Section 2.1). The development of AD in infancy is also a 
major risk factor for later development of other chronic allergic diseases such as allergic 
rhinitis and asthma, which is referred to as atopic march (Bantz et al 2014). Infections are 
frequent complications of AD and can result in severe restrictions and further psychological 
stresses (Werfel et al 2016). Studies have shown that 10% to 20% of children with AD 
continue to suffer with the disease in adolescence (Ricci et al 2012). AD persistence during 
adolescence is correlated with psychological disorders such as anxiety and depression, 
feelings of isolation, sleep disturbance and general feelings of physical and emotional illness 
(Ricci et al 2012). Stress and the psychological problems represent a serious burden on both 
the adolescents living with the disease and the family members who care for them. 
Furthermore, due to the associated risks with its chronic recurrent course, there remains an 
unmet medical need for efficacious and safe treatments in this subpopulation of patients with 
AD (Section 2.2). Expected benefits of benralizumab over placebo include clinically 
significant improvement in symptoms and quality of life measures related to AD in both adult 
and adolescent participants in this study. 
The direct eosinophil-depleting ability of benralizumab has been shown to be effective in the 
treatment of eosinophilic asthma in patients 12 to 75 years of age (SIROCCO 
[Bleecker et al 2016] and CALIMA [FitzGerald et al 2016]) and steroid-dependent asthma 
(Nair et al 2017). In Phase 3 studies in patients with severe asthma, the pharmacodynamic 
(PD) profile of benralizumab was similar in adolescent (≥ 12 to < 18 years) and adult patients, 
with both populations demonstrating near complete depletion of blood eosinophils that was 
maintained throughout the treatment period. Refer to the Investigator Brochure for details of 
results of these studies. 
Results from 2 clinical studies provide additional evidence of benralizumab’s eosinophil-
depleting mechanism of action specifically in skin and tissue. A Phase 2 double-blind, 
placebo-controlled study was conducted in 20 adult patients with HES. HES is a group of 
diseases with persistent blood eosinophilia and eosinophil-related end-organ involvement, 
which commonly involves the skin, heart, lungs, central nervous system, or gastrointestinal 
tract (Andreae et al 2016 and Kuang et al 2019). The study enrolled patients with high 
baseline eosinophil counts (≥ 1000 cells/µL) and included 4 patients with dermatological 
involvement (Kuang et al 2019 and Legrand et al 2017). Two of these patients had previous 
evidence of eosinophilia in skin-biopsy samples and had repeated biopsies during the course 
of the study to evaluate new or worsening rash. Eosinophils were absent in biopsy samples 
following treatment with benralizumab, and the rash resolved in these 2 patients. The overall 
study results showed eosinophil reduction (at least 50% reduction in the absolute eosinophil 

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
count at Week 12) occurred in more patients in the benralizumab group than in the placebo 
group (between-group difference of 60 percentage points); furthermore, clinical and 
hematologic responses were sustained for 48 weeks in benralizumab-treated patients and were 
associated with clinical improvement and the ability to taper background therapy in these 
patients. In the second study, a small single-blinded, placebo run-in study in 12 patients with 
chronic idiopathic urticaria, benralizumab treatment resulted in significant reductions in 
weekly Urticaria Activity Scores (assessing hives and itch) and improvements in Chronic 
Urticaria Quality of Life Questionnaire Scores (Bernstein and Singh 2019). Improvements in 
skin conditions following benralizumab treatment have also been reported in a patient with 
chronic symptomatic dermographism (Bergmann et al 2019). These results support the benefit 
of benralizumab’s significant eosinophil-depleting capabilities in the skin and suggest that 
benralizumab will also be effective for the treatment of AD. 
2.3.2 
Risk Assessment 
The efficacy and safety of benralizumab have been established in patients 12 to 75 years of 
age with asthma (Bleecker et al 2016 and FitzGerald et al 2016); in the United States, it is 
indicated as an add-on therapy for patients 12 years of age and older with severe eosinophilic 
asthma (approved 14 November 2017).  
Phase 3 studies confirmed the efficacy and safety of benralizumab 30 mg every 8 weeks 
(Q8W) and every 4 weeks (Q4W) in both adult and adolescent patients with severe asthma 
(SIROCCO [Bleecker et al 2016] and CALIMA [FitzGerald et al 2016]). The results of these 
Phase 3 studies demonstrated that benralizumab 30 mg Q4W was well-tolerated during the 
treatment period of up to 112 weeks with no unexpected safety findings and the safety profile 
was maintained through Extension Week 56. In adolescents, benralizumab 30 mg Q4W was 
well-tolerated with no unexpected safety findings over the 108-week on-treatment period and 
the 12-week post-treatment period. The most commonly reported adverse events (AEs) with 
benralizumab treatment included nasopharyngitis, asthma, and upper respiratory tract 
infections. Most AEs were mild to moderate in nature. Fewer patients in the benralizumab 
group reported serious adverse events (SAEs) compared with placebo. Long-term safety and 
tolerability of benralizumab 30 mg Q4W and Q8W were demonstrated in adolescent patients 
in an extension study (BORA), which included a treatment period of approximately 2 years. In 
general, the safety results of the long-term extension study (BORA) were commensurate with 
the previous studies (Busse et al 2013). Refer to the Investigator Brochure for the details of 
study design and results of these studies. 
In a more recent Phase 3 study to evaluate efficacy, safety, pharmacokinetic (PK) and 
immunogenicity of a fixed dose of benralizumab 30 mg administered following seasonal 
influenza virus vaccination (ALIZE) in patients 12 to 21 years of age with severe asthma, a 
total of 72 adolescent patients received 3 doses of benralizumab 30 mg Q4W. In this study, 
benralizumab 30 mg was well-tolerated with no unexpected safety findings. There was no 

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
observable pattern or notable differences in AEs in adolescent and young adult patients. No 
discontinuations of investigational product (IP) or from the study due to an AE or SAE and no 
AEs with fatal outcome were reported in this study. Refer to the Investigator Brochure for the 
details of study design and results. 
Overall, the AE profile in adolescents was generally similar to the overall population in Phase 
3 studies conducted with benralizumab; few SAEs were reported for adolescent patients. 
Additionally, during the benralizumab Phase 3 asthma exacerbation studies, extensive 
evaluation of immunoglobulins and flow cytometric assessment of cell subtypes demonstrated 
no differences between adolescent patients receiving benralizumab compared with placebo. Of 
note, mepolizumab had an acceptable AE profile in children with eosinophilic esophagitis as 
young as 2 years, and the PK in children was similar to adults (Assa’ad et al 2011).  
In summary, there have been no safety signals detected in previous clinical studies with 
benralizumab or other monoclonal antibodies (mepolizumab) that deplete eosinophils that 
would preclude administration of benralizumab to adolescent participants ≥ 12 years of age.  
Serious hypersensitivity reactions (including anaphylaxis) are an identified risk of biologic 
therapy, including benralizumab. Anaphylaxis may be life-threatening. Risk minimization 
includes observation in line with clinical practice following IP administration for the 
appearance of any acute drug reactions. Refer to Appendix E for further information and 
guidance. 
Serious infections have been reported for benralizumab. A relationship between eosinophil 
depletion and serious infection has not been established.  
Development of anti-drug antibodies (ADA) to benralizumab has been documented. Potential 
risks of developing ADA include decreased drug efficacy and hypersensitivity reactions (eg, 
anaphylaxis or immune complex disease). To date, no confirmed cases of immune complex 
disease have been observed and no appearance of a relationship between ADA and treatment-
emergent AEs has been established. There was no impact of ADA on overall benralizumab 
safety or efficacy in the previous Phase 3 studies in asthma. 
Eosinophils are a prominent feature of the inflammatory response to helminthic parasitic 
infections, and the presence of infiltrating eosinophils has been circumstantially associated 
with a positive prognosis in certain solid tumors. Helminthic parasitic infections and 
malignancy will continue to be monitored as part of routine pharmacovigilance practices. 
(Refer to Section 5.2, exclusion criteria). 
2.3.3 
Overall Benefit:Risk Conclusion 
Given the clinical evidence to date to support the use of benralizumab 30 mg Q4W in 
eosinophilic diseases and the established PK, PD, and safety profile in adolescent and adult 

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
patients with severe asthma, the benefit-risk assessment of the use of benralizumab for AD in 
adult and adolescent patients appears favorable. Data from the approved severe asthma 
indication demonstrate that benralizumab 30 mg Q4W is safe and well tolerated among 
adolescent patients, and treatment with placebo posed no serious risks in adolescent patients. 
The favorable benefit/risk assessment of benralizumab supports the inclusion of adolescents in 
this Phase 2 study. 
Based on the extensive safety data already available, the benefit risk profile in patients with 
AD is expected to be commensurate with that observed in the benralizumab asthma pivotal 
trials. Risk minimization measures include exclusion of patients with allergy or reaction to 
any component of the IP formulation, untreated parasitic infection, a history of anaphylaxis to 
any biologic therapy, active or recent malignancy, and exclusion of pregnant females. Risk 
minimization measures will be maintained during the conduct of this study, in conjunction 
with the performance of AstraZeneca’s routine pharmacovigilance activities.  
An independent Data and Safety Monitoring Board (DSMB) will provide oversight, with 
particular focus on the adolescent participants, to ensure safe and ethical conduct of the study. 
The DSMB will have the responsibility of evaluating cumulative safety and other clinical trial 
data at regular intervals and making appropriate recommendations based on the available data. 
During the study, the benefit/risk assessment will be continuously monitored by the DSMB to 
ensure that the balance remains favorable. Refer to Appendix A 5 and the DSMB Charter for 
information regarding the independent DSMB. 
Participants with AD in this Phase 2 study will be monitored for AEs throughout treatment 
with benralizumab or placebo and for 12 weeks following the last dose. This study will be 
conducted under applicable International Conference on Harmonisation Good Clinical 
Practice (GCP) Guidelines.  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of benralizumab may be found in the Investigator’s Brochure. 

Clinical Study Protocol 
AstraZeneca 
Benralizumab - D3256C00001 
04 May 2021 
CONFIDENTIAL AND PROPRIETARY 
 
3 
OBJECTIVES AND ENDPOINTS 
Table 5 lists the objectives of this study and the endpoints for each objective. 
Table 5 
Objectives and Endpoints 
Objectives 
Estimand description / Endpoints 
Primary 
To compare the clinical efficacy of benralizumab 
30 mg with placebo in patients with AD despite 
treatment with topical medications a. 
• Population: Full analysis set 
• Endpoint: A binary response giving the proportion 
of patients with an IGA 0/1 and a decrease in IGA 
of ≥ 2 points at Week 16 relative to baseline 
• Intercurrent events: Participants who withdraw from 
the study or require rescue therapy b will be 
considered as non-responders from the time these 
events occur up to Week 16 
• Summary measure: Difference in proportions 
between benralizumab and placebo at Week 16 
Secondary 
To compare the effect of benralizumab with placebo 
on supportive measures of clinical efficacy in patients 
with AD despite treatment with topical medications a. 
• Key secondary endpoint c: proportion of patients 
with skin clearance (EASI-75) at Week 16 
• Key secondary endpoint c: proportion of patients 
with an improvement of ≥ 4 or more points in peak 
pruritus weekly score at Week 16 
• Key secondary endpoint c: proportion of patients 
with skin clearance (EASI-90) at Week 16 
• Proportion of patients with skin clearance (EASI-
50) at Week 16 
• Proportion of patients with skin clearance (EASI-
100) at Week 16 
• Change from baseline in EASI score at Week 16 
• Change from baseline in peak pruritus score at 
Week 2 
• Change from baseline in POEM score at Week 16 
• Change from baseline in SCORAD at Week 16 
To compare benralizumab with placebo on patient-
reported health-related quality of life measures in 
patients with AD despite treatment with topical 
medications a. 
• Change from baseline in DLQI and CDLQI at Week 
16  
To estimate the PK and immunogenicity of 
benralizumab 30 mg in in patients with AD despite 
treatment with topical medications a. 
• Serum benralizumab concentration 
• ADA 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
T a ble 5  
O bjecti ves a n d E n d p oi nts  
T o c o m pare l o n g -ter m treat me nt wit h be nraliz u ma b 
3 0 m g Q 8 W vers us be nraliz u ma b 3 0 m g Q 4 W u p t o 
Wee k 5 2 i n patie nts wit h A D des pite  treat me nt wit h 
t o pical me dicati o ns a. 
• C ha n ge fr o m baseli ne i n E A SI t otal sc ore at Wee k 
5 2.  
• Pr o p orti o n of patie nts wit h a n I G A 0/ 1 a n d a 
decrease i n I G A of ≥ 2 p oi nts at Wee k 5 2 relati ve t o 
baseli ne  
• Pr o p orti o n of patie nts wit h E A SI-7 5 at Wee k 5 2  
• Ot her s u p p orti ve efficac y assess me nts at Wee k 5 2 
as a p pr o priate.  
Safet y  
T o c o m pare t he safet y a n d t olera bilit y of 
be nraliz u ma b wit h place b o i n patie nts wit h A D 
des pite treat me nt wit h t o pical me dicati o ns a. 
Safet y a n d t olera bilit y will be e val uate d i n ter ms of 
A Es, Vital si g ns, a n d Cli nical la b orat or y val ues.  
Assess me nts relate d t o A Es c o ver:  
• 
Occ urre nce/fre q ue nc y  
• 
Relati o ns hi p t o I P as assesse d b y I n vesti gat or  
• 
I nte nsit y 
• 
Seri o us ness  
• 
Deat h  
• 
A Es lea di n g t o disc o nti n uati o n of I P  
 
Vital si g ns para meters i ncl u d e s yst olic a n d diast olic 
bl o o d press ure, a n d p ulse, as well as res pirati o n rate, 
b o d y te m perat ure, b o d y wei g ht, a n d hei g ht.  
Assess me nts relate d t o vital si g ns c o ver:  
• 
O bser ve d val ue  
• 
A bs ol ute a n d perce nt c ha n ge fr o m baseli ne 
val ues o ver ti me  
Tertiar y/e x pl orat or y  
T o e x pl ore t he effect of be nraliz u ma b c o m pare d t o 
place b o o n healt hcare res o urce utilizati o n d ue t o A D.  
Rate of A D -relate d healt hcare res o urce utilizati o n 
d uri n g t he st u d y  
T o e x pl ore t he effect of be nraliz u ma b c o m pare d t o 
place b o o n patie nt -re p orte d healt h-relate d q ualit y of 
life meas ures i n patie nts wit h A D des pite treat me nt 
wit h t o pical me dicati o ns a. 
C ha n ge fr o m baseli ne i n sc ores f or:  
• H A D S  
• P GI -S  
• S F -3 6 v 2 Healt h S ur ve y  
• E Q -5 D -5 L  
• 
 
• Patie nt -re p orte d e x perie nce (free te xt e ntr y) 
C CI
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
T a ble 5  
O bjecti ves a n d E n d p oi nts  
T o e x pl ore t he use of s ki n p h ot o gra p h y t o i nf or m 
cli nical efficac y assess me nts  
• C o nc or da nce wit h i n -pers o n assess me nts of cli nical 
efficac y. 
a 
T he l ocall y -a p pr o ve d re gi me n of t o pical me dicati o n.  
b 
Resc ue t hera p y is defi ne d i n Secti o n 6. 5. 3 . 
c 
T he ke y sec o n dar y e n d p oi nts will use t he sa me esti ma n d as o utli ne d f or t he pri mar y e n d p oi nt. F or all ot her 
e n d p oi nts, t he esti ma n ds will be detaile d i n t he S A P.  
; A D, At o pic der matitis; A D A, a nti-dr u g a nti b o dies; A E, a d verse e ve nt;  
C D L QI, T he C hil dre n’s Der mat ol o g y Life Q ualit y I n de x; D L QI, Der mat ol o g y Life Q ualit y I n de x; E A SI, 
Ecze ma Area a n d Se verit y I n de x; E Q -5 D -5 L, E ur o pea n Q ualit y of Life -5 Di me nsi o ns; H A D S, H os pital A n xiet y 
a n d De pressi o n Scale; I G A, I n vesti gat or Gl o bal Assess me nt; I P, i n vesti gati o nal pr o d uct; 
 
; P GI-S, Patie nt Gl o bal I m pressi o n of Se verit y; P K, p har mac o ki netics;  P O E M, Patie nt 
Orie nte d Ecze ma Meas ure;  Q 4 W, e ver y 4 wee ks; Q 8 W, e ver y 8 wee ks; 
; S A P, Statistical 
A nal ysis Pla n; S C O R A D, S C O Ri n g At o pic Der matitis; S F -3 6 v 2, S h ort F or m 3 6 -ite m Healt h S ur ve y Versi o n 2; 
 
 
4  
S T U D Y D E SI G N  
4. 1  
O ver all Desi g n  
T his is a P hase 2 m ulti nati o nal, ra n d o mize d, d o u ble -bli n d, parallel -gr o u p, 1 6 -wee k place b o -
c o ntr olle d st u d y wit h a 3 6 – wee k e xte nsi o n. T he st u d y will e val uate t he efficac y a n d safet y of 
be nraliz u ma b 3 0 m g i n male a n d fe male partici pa nts  ≥ 1 2 years of a ge wit h m o derate t o 
se vere A D w h o re mai n s y m pt o matic des pite treat me nt wit h sta n dar d of care treat me nt wit h 
t o pical me dicati o ns. T he st u d y is desi g ne d t o c o m pare t he safet y a n d efficac y of be nraliz u ma b 
3 0 m g wit h place b o a n d i de ntif y t he a p pr o priate mai nte na n ce a d mi nistrati o n fre q ue nc y ( Q 4 W 
vers us Q 8 W).  
T his st u d y c o nsists of t he f oll o wi n g c o nsec uti ve peri o ds:  
•  
A 1 - t o 4-wee k r u n -i n peri o d, i ncl u di n g a 7-da y was h o ut peri o d of t o pical me dicati o ns 
pri or t o ra n d o mizati o n  
C CI
C CI
C CI
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• 
A 16-week placebo-controlled, double-blind treatment period  
• 
A 36-week blinded-to-dosing regimen extension period for maintenance treatment. 
 
Following informed consent/assent, all eligible participants will enter a run-in period of 1 to 4 
weeks during which inclusion/exclusion criteria will be assessed, medical history taken, and 
complete physical exam will be conducted (Visit 1,Table 3). Potentially eligible participants 
will enter a 7-day washout period during which all topical medications for AD except the 
stable emollient moisturizer regimen must be discontinued. Participants will be provided with 
a handheld device to respond to PRO questionnaires during the study. 
Following the 1- to 4-week run-in period, including the 7-day washout period, a minimum of 
approximately 160 participants will be randomized at Visit 2, in a ratio of 1:1:2, respectively, 
to 1 of the following 3 treatment sequences (refer also to Figure 1 and Figure 2): 
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q4W administered until Week 52 (n = 40) 
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q8W administered until Week 52 (n = 40) 
• 
Placebo Q4W until Week 16, followed by an extension period with benralizumab 30 
mg Q4W administered until Week 28, and then benralizumab 30 mg Q8W administered 
until Week 52 (n = 80). 
 
Randomization will be stratified by blood eosinophils (< 300 cells/μL; ≥ 300 cells/μL), and age 
(≥ 12 to < 18 years; ≥ 18 years).  Participants will be randomized in minimum cohort sizes 
across the baseline blood eosinophil and age subgroups. If the minimum recruitment target in 
any cohort is achieved, the cohort may remain open to further recruitment in order to fulfill 
minimum recruitment targets for the remaining cohorts for a maximum total study size of 200 
participants.  
Up to Week 16, participants receiving benralizumab 30 mg Q4W will be considered as a 
single treatment group (total n = 80). 
Blinded IP (benralizumab or placebo) will be administered by SC injection at the 
investigational site Q4W for up to 48 weeks. 
Throughout the study, participants will be required to maintain a stable regimen of their 
topical emollient (moisturizer) for AD. If medically necessary (ie, to control intolerable AD 
symptoms), rescue treatment for AD may be provided to study participants at the discretion of 
the investigator (refer to Section 6.5.3). 

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The primary database lock (DBL) is targeted to occur when all participants have completed 
the 16-week double-blind treatment period (Figure 2). The final DBL will occur when all 
participants have completed the 52-week treatment period and the Week 60 follow-up visit 
and/or the IP discontinuation/ (IPD)/end-of treatment visit (Table 3). An additional lock, 
between the primary and final DBL, may be performed to report data accumulated during the 
extension part of the study to support end of Phase 2 decision making. Participants and 
investigators will remain blinded to treatments and dosing regimens (refer to Section 4.1.2) 
until the final DBL. 
For an overview of the study design, see Figure 2. For details of the treatments administered 
and dosing regimens used during the study, see Section 4.1.2 and Figure 3. For details of the 
efficacy and safety endpoints, see Section 3. 
4.1.1 
Study Conduct Mitigation During Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis 
The guidance given below supersedes instructions provided elsewhere in this clinical study 
protocol (CSP) and should be implemented only during cases of civil crisis, natural disaster, 
or public health crisis (eg, during quarantines and resulting site closures, regional travel 
restrictions, and considerations if site personnel or study participants become infected with 
SARS-CoV-2 or similar pandemic infection) which would prevent the conduct of 
study-related activities at study sites, thereby compromising the study site staff or the 
participant’s ability to conduct the study. The investigator or designee should contact the 
study Sponsor representative to discuss whether the mitigation plans below should be 
implemented. The study participants will be required to complete the screening and 
randomization visits on site prior to having the option to participate in the mitigation plans.   
To ensure continuity of the clinical study during a civil crisis, natural disaster, or public health 
crisis, changes may be implemented to ensure the safety of study participants, maintain 
compliance with Good Clinical Practice, and minimize risks to study integrity.  
Where allowable by local health authorities, ethics committees, healthcare provider guidelines 
(eg, hospital policies) or local government, these changes may include the following options:  
• 
Obtaining consent/assent for the mitigation procedures (note, in the case of verbal 
consent/assent, the Informed Consent Form (ICF) should be signed at the participant’s 
next contact with the study site).  
• 
Rescreening: Additional rescreening for screen failure and to confirm eligibility to 
participate in the clinical study can be performed in previously screened participants. The 
investigator should confirm this with the designated study physician. 
• 
Home or Remote visit: Performed by a site qualified Health Care Professional (HCP) or 
HCP provided by a third-party vendor (TPV). 

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• 
Telemedicine visit: Remote contact with the participants using telecommunications 
technology including phone calls, virtual or video visits, and mobile health devices.  
• 
At-home IP administration: Performed by a site qualified HCP or HCP provided by a 
TPV, or by the participant or the participant’s caregiver, if possible. Additional 
information related to the visit can be obtained via telemedicine. 
• 
If participant testing is performed due to the public health crisis, the results may be 
documented for this study. 
  
For further details on study conduct during civil crisis, natural disaster, or public health crisis, 
refer to Appendix F. 
4.1.2 
Investigational Product Dosing Regimen 
Participants who meet entry criteria will be randomized 1:1:2 by the interactive voice/web 
response system (IxRS) to 1 of the 3 treatment sequences described in Section 4.1. 
Figure 3 presents an overview of the IP that will be administered for each randomized 
treatment sequence. 
 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
D osi n g Re gi me n at Visits 2, 3, 4, a n d 5 (I niti al 1 6 -Wee k D o u ble -bli n d Tre at me nt Peri o d)  
All partici pa nts will recei ve ra n d o mize d d o u ble -bli n d I P Q 4 W at Wee ks 0, 4, 8, a n d 1 2 
(Fi g ure 3 ). 
D osi n g Re gi me n at Visits 6 T hr o u g h E O T, Be nr aliz u m a b 3 0 m g  
At Wee k 1 6, partici pa nts i nitiall y ra n d o mize d t o be nraliz u ma b 3 0 m g will recei ve 
be nraliz u ma b 3 0 m g Q 4 W or Q 8 W acc or di n g t o t heir ori gi nal ra n d o mizati o n at Visit  2 ( Wee k 
0). Partici pa nts ra n d o m ize d t o t he Q 8 W re gi me n will recei ve place b o at t he Wee k 1 6 visit a n d 
be nraliz u ma b 3 0 m g at t he Wee k 2 0 visit, a n d will c o nti n ue t o alter nate bet wee n t hese 
treat me nts Q 4 W u ntil Wee k 4 8 (Fi g ure 3 ). 
D osi n g Re gi me n at Visits 6 T hr o u g h E O T, Pl ace b o  
At Wee ks 1 6, 2 0, a n d 2 4, partici pa nts i nitiall y ra n d o mize d t o place b o will recei ve 
be nraliz u ma b 3 0 m g Q 4 W. At Wee k 2 8, t hese partici pa nts will tra nsiti o n t o recei ve 
be nraliz u ma b 3 0 m g Q 8 W; t he y will recei ve place b o at t he Wee k 2 8 visit a n d be nraliz u ma b 
3 0 m g at t he Wee k 3 2 visit, a n d will c o nti n ue t o alter nate bet wee n t hese treat me nts Q 4 W u ntil 
Wee k 4 8 ( Fi g ure 3 ). 
T he fi nal d ose of be nraliz u ma b or place b o will be a d mi nistere d at Wee k 4 8.  
4. 2  
Scie ntific R ati o n ale f or St u d y Desi g n  
T his is a P hase 2 st u d y desi g ne d t o e val uate t he efficac y a n d safet y of be nraliz u ma b i n t he 
treat me nt of patie nts wit h m o derate t o se vere A D. 
T his st u d y’s i ncl usi o n/e xcl usi o n criteria a n d r u n -i n peri o d (i ncl u di n g a 7-da y was h o ut of 
t o pical me dicati o ns f or A D) are desi g ne d t o ca pt ure a p o p ulati o n a p pr o priate f or treat me nt 
wit h be nraliz u ma b,  w hic h is patie nts wit h A D w h o re mai n s y m pt o matic des pite treat me nt 
wit h t o pical me dicati o ns. B ot h patie nt -re p orte d s y m pt o ms a n d hist ol o gical fi n di n gs (ie, 
e osi n o p hil c o u nts i n bi o psies) will be ca pt ure d t o e ns ure t he patie nt p o p ulati o n is a p pr o priate 
f or t he st u d y a n d t o esta blis h baseli ne meas ure me nts f or deter mi ni n g cli nical a n d P D 
treat me nt effect. 
L oss of s ki n barrier f u ncti o n a n d i ncrease d se verit y of A D pre dis p oses patie nts’ s ki n t o 
micr o bial c ol o nizati o n a n d c hr o nic s ki n i nfla m mati o n ( Le u n g a n d G utt ma n -Yass k y 2 0 1 4 ). 
P ote ntial s u b p o p ulati o ns wit h m ore e vi de nt e osi n o p hil -dri ve n A D ha ve bee n n ote d i n t he 
literat ure a n d i ncl u de Sta p h yl oc occ us a ure us-c ol o nize d a d ult patie nts wit h m ore se vere 
disease a n d a disti nct p he n ot y pe (ie, ele vate d bl o o d e osi n o p hils, maj or basic pr otei n,  
 i n 
s ki n, e osi n o p hil cell l ysis b y Sta p h yl oc occ us a ure us α-he m ol ysi n i ncreasi n g tiss ue i nj ur y) a n d 
c hil dre n a n d a d olesce nts, w h ose disease pr ocess is m ore i nfla m mat or y i n nat ure a n d dri ve n 
m ore s o b y t he i n nate i m m u ne s yste m ( Si m ps o n et al 2 0 1 8 ). T heref ore, t his st u d y will i ncl ude 
mi ni m u m c o h ort sizes f or b ot h a d ults ( ≥ 1 8 years of a ge) a n d a d olesce nts ( ≥ 1 2 t o <  1 8 years 
C CI

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of age) and baseline blood eosinophil cohorts (< 300 versus ≥ 300) to ensure a broad 
distribution of patients across these characteristics to enable exploration of potential responder 
populations. 
The study’s 16–week randomized, double-blind, placebo-controlled, parallel-group treatment 
period is designed to compare the efficacy and safety of benralizumab 30 mg with placebo. 
This design is considered appropriate for demonstrating efficacy and safety without bias in a 
clinical trial (Leshem et al 2019). The study treatment duration is considered appropriate for 
this disease and was based on the treatment duration for previous studies in patients with AD 
(Blauvelt et al 2017, Guttman-Yassky et al 2019, Simpson et al 2016, and Thaci et al 2016). 
The primary endpoint chosen is the proportion of patients with a binary response of IGA 0/1 
and a decrease of ≥ 2 points from baseline in IGA at Week 16. The IGA assesses the overall 
inflammatory signs of AD (erythema, induration/papulation, lichenification, oozing/crusting) 
and is recommended by international guidelines to be used in clinical practice to determine 
disease activity and response to treatment. It has also been used in clinical trials for the 
registration of other products for the treatment of AD. Additional secondary endpoints are 
included to provide a complete picture of the efficacy achieved with benralizumab treatment.  
The 36-week extension period will provide an opportunity to evaluate long-term benralizumab 
treatment in patients with AD. The effect of benralizumab 30 mg Q8W as a maintenance 
dosing regimen will be compared with benralizumab 30 mg Q4W. Participants who received 
placebo during the initial 16 weeks of the study will switch to benralizumab 30 mg; these 
participants will receive 3 doses of benralizumab 30 mg Q4W followed by benralizumab 
30 mg Q8W for the remainder of the extension period. This regimen has been included in the 
extension period to provide a preliminary evaluation of the efficacy and safety of the approved 
dosing regimen for patients with severe asthma, when administered to patients with AD. 
4.3 
Justification for Dose 
The PK of benralizumab are well-characterized (Wang et al 2017), and benralizumab is 
expected to demonstrate consistent PK across different disease populations. The safety and 
tolerability of a range of doses of benralizumab have been demonstrated. In Phase 3 asthma 
studies, over 3500 patients have received benralizumab 30 mg. In Phase 2 and 3 studies in 
patients with chronic obstructive pulmonary disease, over 1100 patients have received 
benralizumab 30 mg, and over 1100 patients have received benralizumab 100 mg. No dose-
limiting safety issues have been identified with dosing in clinical studies up to 100 mg Q8W 
for 52 weeks (refer to the Investigator Brochure for details). 
The approved dosing regimen of benralizumab in severe asthma is 30 mg Q4W for the first 3 
doses, followed by 30 mg Q8W thereafter. In adult and adolescent patients with severe asthma 
(SIROCCO [Bleecker et al 2016] and CALIMA [FitzGerald et al 2016]), treatment with 

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benralizumab 30 mg Q8W and Q4W resulted in near complete blood eosinophil depletion for 
both the Q8W and Q4W dosing regimens. Since the PK/PD relationship of adolescents with 
asthma has been shown to be consistent with those of adults (SIROCCO and CALIMA) and 
given PK/PD relationships are consistent across disease populations, the same benralizumab 
treatment regimen will be administered to adults and adolescents in this study. Treatment with 
benralizumab 30 mg Q4W has also been shown to reduce blood and tissue eosinophilia in GI 
tissue of patients with varied clinical subtypes of HES where patients have higher blood 
eosinophils and significant organ manifestations of eosinophilic inflammation (Kuang et al 
2019). 
Based on results for the asthma studies, participants will receive benralizumab 30 mg or 
placebo Q4W during the initial 16-week treatment period. A 16-week treatment period was 
chosen based on previous studies in patients with AD (Simpson et al 2016) in order to 
maximize the chances of demonstrating efficacy. Participants will subsequently either 
transition to a 30 mg Q8W dosing regimen or remain on a 30 mg Q4W regimen during the 
blinded extension period to evaluate the effect of a Q8W maintenance dosing regimen relative 
to Q4W over the longer-term treatment period. 
4.4 
End of Study Definition 
The end of study is defined as the last expected visit/contact of the last participant 
participating in the study.  
A participant is considered to have completed the study when he/she has completed his/her 
last scheduled visit/telephone contact. 
See Appendix A 6 for guidelines for the dissemination of study results. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to inclusion or exclusion criteria, also known as 
protocol waivers or exemptions, is not permitted. 
Each participant should meet all of the inclusion criteria and none of the exclusion criteria for 
this study in order to be randomized to IP. Under no circumstances can there be exceptions to 
this rule. Participants who do not meet the entry requirements are screen failures (Section 5.4). 
In this protocol, “enrolled” is defined as a participant’s agreement to participate in a clinical 
study following completion of the informed consent/assent process. “Randomized” 
participants are defined as those who undergo randomization and receive a randomization 
number. 
For procedures for withdrawal of incorrectly enrolled participants, refer to Section 7.1.2. 

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5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Informed Consent/Assent/age/gender/weight 
1 
Provision of the signed and dated written informed consent/assent of the participant prior 
to any mandatory study-specific procedures, sampling, and analyses. The informed 
consent/assent process is described in Appendix A 3. 
2 
Male and female participants ≥ 12 years of age at the time of signing the ICF. 
 
Type of Patients and Disease 
3 
Physician-confirmed diagnosis of AD (according to American Academy of Dermatology 
Consensus Criteria) that is not adequately controlled with topical medications. 
4 
EASI score of ≥ 12 at screening and ≥ 16 at randomization.  
5 
IGA score of ≥ 3 (on a scale of 0 to 4, in which 3 is moderate and 4 is severe) at screening 
and at randomization.   
6 
AD involvement of ≥ 8% body-surface area at screening and ≥ 10% body-surface area at 
randomization.  
7 
A pruritus numerical rating scale average score for maximum itch intensity of ≥ 4, based 
on the average of daily pruritus numerical rating scale scores for maximum itch intensity 
reported during the 7 days prior to randomization. 
8 
Documented recent history (within 6 months prior to screening) of inadequate response to 
treatment with topical medications, or patients for whom topical treatments are otherwise 
medically inadvisable (eg, because of important side effects or safety risks). 
9 
Participants that have applied a stable dose of topical emollient (moisturizer) twice daily 
for ≥ 7 consecutive days immediately before the randomization visit.  (NOTE: See 
exclusion criterion 11 for limitations regarding emollients). 
10 Participants must be willing and able to complete daily PRO assessments: 
(a) Complete at least 70% of daily PRO assessments between Visit 1 and Visit 2 and 
(b) Complete at least 5 of 7 daily PRO assessments in the 7 days prior to Visit 2. 
 
Reproduction 
11 Females of childbearing potential (FOCBP) must agree to use a highly effective method 
of birth control (confirmed by the Investigator) from randomization, throughout the study 
duration, and within 12 weeks after last dose of IP and have a negative serum pregnancy 
test result on Visit 1. 
Highly effective methods of birth control (defined as those that can achieve a failure rate 
of less than 1% per year when used consistently and correctly) include: 

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(a) Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: oral, intravaginal, or transdermal. 
(b) Progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable, or implantable. 
(c) Intrauterine device. 
(d) Intrauterine hormone-releasing system. 
(e) Bilateral tubal occlusion or ligation. 
(f) Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the clinical 
study and the preferred and usual lifestyle of the participant). 
(g) Vasectomized sexual partner (provided that partner is the sole sexual partner of the 
FOCBP study participant and that the vasectomized partner has received medical 
assessment of the surgical success). 
12 Females not of childbearing potential are defined as females who are either permanently 
sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are 
postmenopausal. Females will be considered postmenopausal if they have been 
amenorrheic for ≥ 12 months prior to the planned date of randomization without an 
alternative medical cause. The following age-specific requirements apply: 
(a) Females < 50 years old will be considered postmenopausal if they have been 
amenorrheic for 12 months or more following cessation of exogenous hormonal 
treatment and with follicle-stimulating hormone (FSH) levels in the postmenopausal 
range. Until FSH is documented to be within menopausal range, the participant 
should be treated as a FOCBP. 
(b) Females ≥ 50 years old will be considered postmenopausal if they have been 
amenorrheic for 12 months or more following cessation of all exogenous hormonal 
treatment. 
 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1 
Participants with active dermatological conditions (eg, psoriasis, seborrheic dermatitis, 
cutaneous lymphoma) other than AD that, in the investigator’s opinion, may interfere 
with the study assessments. 
2 
Known active allergic or irritant contact dermatitis that, in the investigator’s opinion, may 
interfere with the study assessments. 
3 
Current malignancy, or history of malignancy, with the exception of: 

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CONFIDENTIAL AND PROPRIETARY 
 
(a) Participants who have had basal cell carcinoma, localized squamous cell carcinoma 
of the skin, or in situ carcinoma of the cervix are eligible provided that the participant 
is in remission and curative therapy was completed at least 12 months prior to the 
date informed consent/assent, was obtained. 
(b) Participants who have had other malignancies are eligible provided that the 
participant is in remission and curative therapy was completed at least 5 years prior to 
the date informed consent/assent, was obtained. 
4 
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, 
neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 
psychiatric, or major physical impairment that is not stable in the opinion of the 
Investigator and could: 
(a) Affect the safety of the participant throughout the study. 
(b) Influence the findings of the studies or their interpretations. 
(c) Impede the participant’s ability to complete the entire duration of study. 
5 
History of anaphylaxis to any biologic therapy or vaccine. 
6 
A helminth parasitic infection diagnosed within 24 weeks prior to the date informed 
consent/assent is obtained that has not been treated with, or has failed to respond to 
standard of care therapy. 
7 
Any clinically significant abnormal findings in physical examination, vital signs, 
haematology, clinical chemistry, or urinalysis during screening/run-in period which, in 
the opinion of the Investigator, may put the participant at risk because of his/her 
participation in the study, or may influence the results of the study, or the participant’s 
ability to complete entire duration of the study. 
8 
Current active liver disease: 
(a) Chronic stable hepatitis B and C (including positive testing for hepatitis B surface 
antigen or hepatitis C antibody), or other stable chronic liver disease are acceptable if 
participant otherwise meets eligibility criteria. Stable chronic liver disease should 
generally be defined by the absence of ascites, encephalopathy, coagulopathy, 
hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis. 
(b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 times 
the upper limit of normal, confirmed by repeated testing during the run-in period. 
Transient increase of AST/ALT level that resolves by the time of randomization is 
acceptable if in the Investigator’s opinion the participant does not have an active liver 
disease and meets other eligibility criteria. 
9 
A history of known immunodeficiency disorder including a positive human 
immunodeficiency virus (HIV) test. 
 

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Prior/concomitant Therapy 
10 Participants who have received treatment for AD with TCS, topical calcineurin inhibitors 
(TCI), or topical phosphodiesterase-4 (PDE4) inhibitors within the 7 days prior to the 
randomization visit. 
11 Initiation of treatment of AD with prescription moisturizers or moisturizers containing 
additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products 
during the screening period (patients may continue using stable doses of such 
moisturizers if initiated before the screening visit). 
12 Regular use (2 visits per week) of a tanning booth/parlor or phototherapy for AD within 4 
weeks prior to the randomization visit.  
13 Use of immunosuppressive medication, including, but not limited to: methotrexate, 
cyclosporine, azathioprine, systemic corticosteroids within 4 weeks or 5 half-lives prior to 
the date informed consent/assent is obtained, whichever is longer.  
14 Known history of allergy or reaction to any component of the IP formulation. 
 
Other 
15 Receipt of immunoglobulin or blood products within 30 days prior to the date informed 
consent/assent is obtained.  
16 Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior 
to the date informed consent/assent is obtained, whichever is longer. 
17 Receipt of live attenuated vaccines 30 days prior to first dose of IP. 
18 Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date 
informed consent/assent is obtained, whichever is longer. 
19 Previously received benralizumab (MEDI-563, FASENRA). 
20 Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior 
to the date of informed consent/assent and anticipated changes in immunotherapy 
throughout the study. 
21 Planned elective major surgical procedures during the conduct of the study. 
22 Previous randomization in the present study. 
23 Concurrent enrollment in another clinical trial. 
24 AstraZeneca staff involved in the planning and/or conduct of the study. 
25 For females only: Currently pregnant, breastfeeding, or lactating females. 
(a) A serum pregnancy test will be done for FOCBP at Visit 1 and a urine pregnancy test 
must be performed for FOCBP at each subsequent treatment visit prior to IP 
administration. A positive urine test result must be confirmed with a serum 
pregnancy test. If serum test is positive, the participant should be excluded. 
 

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5.3 
Lifestyle Considerations 
Female participants of childbearing potential must use highly effective contraceptive methods 
throughout the study and at least for 12 weeks after last administration of the IP, as stated in 
inclusion criterion 11, Section 5.1. 
Participants must abstain from donating blood, plasma, or platelets from the time of informed 
consent/assent and for 12 weeks after last dose of IP. 
5.4 
Screen Failures 
Screen failures are defined as patients who consent/assent to participate in the clinical study 
but are not subsequently randomly assigned to study intervention/entered in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the Consolidated Standards of Reporting Trials publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria not fulfilled, and any SAE. A 
pregnancy test is not required for FOCBP who are screen failures. 
These participants should have the reason for study withdrawal recorded as ‘Screen Failure’ 
(ie, patient does not meet the required inclusion/exclusion criteria) in the electronic case report 
form (eCRF.). This reason for study withdrawal is only valid for screen failures and not 
randomized participants. 
5.4.1 
Re-screening 
If the reason for screen failure was transient (including but not limited to study-supplied 
equipment failure, unforeseen personal events that mandate missed screening visits, transient 
events during the screening period that contraindicate IP dosing, etc), participants may 
potentially be re-screened. These cases must be discussed with the study physician prior to 
randomization and documented in the Investigator Study File. 
Re-screening of a participant for any reason will also be allowed only upon approval of the 
study physician and allowed only once per participant. A documented approval for re-
screening should be filed in the Investigator Study File. 
Re-screened participants should be assigned the same participant number as for the initial 
screening, meaning that the participant should keep the same E-code as was originally 
assigned. 
Re-screened participants should sign a new ICF. All procedures from the screening period 
should be repeated (eg, a serum pregnancy test must be completed for FOCBP). 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
S T U D Y I N T E R V E N TI O N  
St u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s) or 
place b o i nte n de d t o be a d mi nistere d t o or me dical de vice(s) utilize d b y a st u d y partici pa nt 
acc or di n g t o t he st u d y pr ot oc ol. St u d y i nter ve nti o n i n t his st u d y refers t o be nraliz u ma b a n d 
place b o, 
. 
6. 1  
St u d y I nter ve nti o ns A d mi nistere d  
6. 1. 1  
I n vesti g ati o n al Pr o d ucts 
Descri pti o ns of t he I Ps are pr o vi de d i n Ta ble 6 . 
T a ble 6  
I n vesti g ati o n al Pr o d ucts 
 
St u d y i nter ve nti o n  
 
Be nr aliz u m a b  
Pl ace b o  
D osa ge 
f or m ulati o n 
R o ute of 
A d mi nistrati o n  
S u bc uta ne o us i njecti o n  
S u bc uta ne o us i njecti o n  
D osi n g 
I nstr ucti o ns 
Be nraliz u ma b acti ve s ol uti o n will be 
a d mi nistere d s u bc uta ne o usl y t o partici pa nts 
b y healt h care pr ofessi o nals 
 
Place b o s ol uti o n will be a d mi nistere d 
s u bc uta ne o usl y t o partici pa nts b y healt h 
care pr ofessi o nals 
 
Use  
E x peri me ntal  
Place b o -c o m parat or 
I M P a n d NI M P 
I M P 
I M P 
S o urci n g  
Astra Ze neca  
Astra Ze neca  
Pac ka gi n g a n d 
La beli n g  
St u d y i nter ve nti o n will be pr o vi de d  
 
. 
Eac h  
 will be la bele d i n acc or da nce 
wit h G M P A n ne x 1 3 a n d per c o u ntr y 
re g ulat or y re q uire me nt. 
St u d y i nter ve nti o n will be pr o vi de d  
 
 
Eac h  
 will be la bele d i n acc or da nce 
wit h G M P A n ne x 1 3 a n d per c o u ntr y 
re g ulat or y re q uire me nt. 
 G M P, G o o d Ma n ufact uri n g Practice; I M P I n vesti gati o nal Me dici nal 
Pr o d uct; NI M P N o n -I n vesti gati o nal Me dici nal Pr o d uct; w/ v, wei g ht b y v ol u me. 
 
Bef ore I P A d mi nistr ati o n  
All a p plica ble visit pr oce d ures, i ncl u di n g c ollecti o n of bi o mar ker, P K, a n d A D A sa m ples a n d 
o n -site P R O assess me nts, s h o ul d be co m plete d pri or t o I P a d mi nistrati o n.  
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Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
Pri or t o eac h I P a d mi nistrati o n:  
•  
F or F O C B P, t he uri ne pre g na nc y test m ust be perf or me d; I P will be a d mi nistere d o nl y 
w he n t he res ult of t he test is ne gati ve (refer t o Secti o n 8. 2. 1. 1 ). 
•  
I n vesti gat or, or desi g nee, will e val uate t he partici pa nt's c o n diti o n f or p ote ntial 
c o ntrai n dicati o ns f or d osi n g (refer t o Secti o n 6. 5. 4 ). 
•  
I n vesti gat or, or desi g nee, will assess t he i njecti o n site as per sta n dar ds of me dical care. 
 
I P A d mi nistr ati o n 
T he I P will be a d mi nistere d S C as a si n gle i njecti o n via t he 
 
 b y t he I n vesti gat or, or desi g nee ( Secti o n 4. 1. 2 ). 
It is a d vise d t hat t he site of I P i njecti o n be r otate d s uc h t hat t he partici pa nt recei ves I P at a 
differe nt a nat o mical site at eac h treat me nt visit. S u g geste d i njecti o n site r otati o n se q ue nc e is 
prese nte d  bel o w ( Fi g ure 4 ). T he i njecti o n site m ust be d oc u me nte d i n t he s o urce at eac h 
treat me nt visit a n d rec or de d i n t he e C R F. T he date a n d ti me of all I P a d mi nistrati o ns, as well 
as a n y misse d d oses (I P i nterr u pti o ns), s h o ul d be rec or de d i n t he a p pr o priate secti o n of t he 
e C R F.  
Fi g ure 4  
I njecti o n Sites a n d E x a m ples of R ot ati o n Sc he me  
 
 
If r otati o n of t he i njecti o n site is n ot p ossi ble, t he reas o n f or t his m ust be d oc u me nte d i n t he 
s o urce. 
At Visits 2 a n d 3, a p pr o priate partici pa nts a n d/ or t heir care gi ver ma y be trai ne d i n I P 
a d mi nistrati o n b y t he i n vesti gat or or desi g nee. If n ot p ossi ble at Visits 2 a n d 3 t his ma y occ ur 
at later visits. T his trai ni n g will be pr o vi de d t o ha ve partici pa nts pre pare d i n case tele me dici ne 
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visits may be required secondary to study disruptions as described in Section 4.1.1. 
Participants may still participate in the study if they do not consent/assent to this training. 
The specific details for IP administration are provided in the IP Handling Instruction. The IP 
administration must be carried out in line with these instructions. 
After IP Administration 
It is strongly recommended that the participant is observed after IP administration for the 
appearance of any acute drug reactions in line with clinical practice. 
6.1.2 
Investigational Product Administration Re-scheduling 
Every effort should be taken to keep IP administration within the scheduled window. 
If a participant presents with a condition that contraindicates dosing, IP will be withheld and 
administered as soon as possible after the contraindicating condition resolves. 
The IP should not be administered, and the dosing is to be re-scheduled in the presence of the 
following conditions: 
• 
The participant has an intercurrent illness that, in the opinion of the Investigator, may 
compromise the safety of the participant in the study. 
• 
The participant has signs of a clinically significant infection. Benralizumab should not be 
administered to a participant with a clinically significant active infection treated with oral 
or intravenous (IV) antimicrobials, antivirals, or antifungals until it is confirmed by the 
Investigator that the infection has resolved. 
• 
The participant is febrile (≥ 38°C; ≥ 100.4°F) within 72 hours prior to IP administration. 
• 
Any event or laboratory abnormality that, in the opinion of the Investigator or 
AstraZeneca, contraindicates dosing or could result in complications. 
 
It is recommended that the study physician, or designee, be contacted in case of any questions. 
When IP dosing needs to be postponed, it is recommended that all scheduled treatment visit 
procedures (except for pregnancy test and IP administration) are still performed within the 
visit window. 
Re-scheduled IP dose can then be administered at an unscheduled visit along with the 
pregnancy test. The vital signs assessments are the minimum procedures to be performed at 
this visit. It may also include remaining visit procedures (not performed at the scheduled visit) 
and additional assessments as deemed necessary by the Investigator. 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
If t he visit pr oce d ures ca n n ot be c o n d ucte d wit hin t he wi n d o w (e g, t he partici pa nt is u na ble t o 
atte n d t he st u d y site), t he n t he e ntire visit will be re -sc he d ule d al o n g wit h I P d ose. 
If a d ose is si g nifica ntl y dela ye d, it is rec o m me n de d t o kee p at least a 2-wee k i nter val bef ore 
t he ne xt d ose. If a p ost p one d d ose o verla ps wit h t he ne xt treat me nt visit wi n d o w, t he 
p ost p o ne d d ose will be s ki p pe d, a n d t he ne xt d ose of I P gi ve n at t he re g ularl y sc he d ule d visit. 
T he visit sc he d ule will al wa ys be calc ulate d fr o m t he ra n d o mizati o n visit date.  
If 2 or m ore d oses (c o nsec uti ve or n o n -c o nsec uti ve) of I P are misse d, a c o n versati o n bet wee n 
t he I n vesti gat or a n d t he st u d y p h ysicia n s h o ul d ta ke place t o re vie w treat me nt c o m plia nce a n d 
deci de o n t he partici pa nt's f urt her dis p ositi o n. All partici pa nts, re gar dless of w het her t he y 
re mai n o n I P or n ot, will be e nc o ura ge d t o re mai n i n t he st u d y t hr o u g h t he e n d of t he 
treat me nt peri o d ( Visit 1 6). Disc o nti n uati o n pr oce d ures are descri be d i n Secti o n 7. 1. 1 ). 
6. 2  
Pre p ar ati o n/ h a n dli n g/st or a ge/ acc o u nt a bilit y  
T he I n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y treat me nt recei ve d a n d a n y discre pa ncies are re p orte d 
an d res ol ve d bef ore use of t he st u d y treat me nt.  
O nl y partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y treat me nt a n d o nl y a ut h orize d site 
staff ma y s u p pl y or a d mi nister st u d y treat me nt. All st u d y treat me nts m ust be st ore d i n a 
sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mate d) area i n acc or da nce 
wit h t he la bele d st ora ge c o n diti o ns wit h access li mite d t o t he I n vesti gat or a n d a ut h orize d site 
staff. 
T he I n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u d y treat me nt acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na nce (ie, 
recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). 
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y i nter ve nti o ns are 
pr o vi de d i n  t he P har mac y Ma n ual. 
6. 2. 1  
Pre p ar ati o n a n d H a n dli n g of I n vesti g ati o n al Pr o d uct  
T he I P will be a d mi nistere d at t he st u d y site, o n treat me nt visits, a n d wit hi n visit wi n d o ws as 
s pecifie d i n t he S o A (Ta ble 3 ). T he I P will be s u p plie d t o t he site i n kits wit h  
 of 
eit her be nraliz u ma b or place b o. Eac h kit will ha ve a u ni q ue i de ntifier (I D) t hat i s pri nte d o n 
all la bels wit hi n t he kit (ie, t he o uter cart o n la bel a n d t he la bel of eac h c o ntai ner wit hi n t he 
cart o n). 
O nl y partici pa nts ra n d o mize d t o t he st u d y ma y recei ve I P a n d o nl y a ut h orize d site staff ma y 
dis pe nse a n d a d mi nister I P.  
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Cli nical St u d y Pr ot oc ol  
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Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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. 2  
S hi p pi n g a n d St or a ge  
All s hi p me nts of I P i ncl u de a data l o g ger w hic h will all o w t he I n vesti gat or, or desi g nee, t o 
c o nfir m t hat a p pr o priate te m perat ure c o n diti o ns ha ve bee n mai ntai ne d d uri n g tra nsit f or all I P 
recei ve d. A n y discre pa ncies m ust be re p orte d a n d res ol ve d bef ore use of t he I P. 
I n t he f oll o wi n g cases, t he site staff s h o ul d n ot use affecte d I P a n d s h o ul d i m me diatel y c o ntact 
t he Astra Ze neca re prese ntati ve f or f urt her g ui da nce: 
•  
Te m perat ure e xc ursi o n u p o n recei pt or d uri n g st ora ge at t he st u d y site  
•  
Da ma ge d kit u p o n recei pt  
•  
/cartri d ge 
 
Da ma ge d I P s h o ul d be d oc u me nte d usi n g a n I x R S (refer t o I x R S ma n ual a n d t he P har mac y 
Ma n ual f or f urt her details).  
6. 2. 3  
Acc o u nt a bilit y  
T he I n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or I P acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na nce (ie, recei pt, 
rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). 
A n Astra Ze neca re prese ntati ve site m o nit or will acc o u nt f or all I P recei ve d at t he sit e, f or 
u n use d I P, a n d f or a p pr o priate destr ucti o n of u n use d st u d y treat me nts. A n y u n use d kits will be 
destr o ye d l ocall y (f or f urt her details, refer t o t he P har mac y Ma n ual). D oc u me ntati o n of I P 
deli ver y a n d destr ucti o n s h o ul d be mai ntai ne d acc or di n g t o a p pl ica ble Astra Ze neca a n d 
i nstit uti o n pr oce d ures. 
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y treat me nt are 
pr o vi de d i n t he P har mac y Ma n ual ( pr o vi de d t o t he sites). I n t he case of a malf u ncti o ni n g I P 
, t he site s h o ul d c o ntact t he Astra Ze neca re prese ntati ve st u d y m o nit or t o i nitiate a 
pr o d uct c o m plai nt pr ocess acc or di n g t o a p plica ble g ui deli nes.  
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6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Randomization 
All participants will be centrally assigned to randomized IP using an IxRS. Randomization 
codes will be assigned strictly sequentially in each stratum as participants become eligible for 
randomization. Randomization will be stratified by age (≥ 12 years to < 18 years; ≥ 18 years) 
and baseline blood eosinophils (< 300 cells/ μL; ≥ 300 cells/ μL) collected at screening into 
the following strata: 
• 
≥ 12 years to < 18 years and < 300 cells/μL 
• 
≥ 12 years to < 18 years and ≥ 300 cells/μL  
• 
≥ 18 years and < 300 cells/μL   
• 
≥ 18 years and ≥ 300 cells/μL 
 
Participants who fail to meet the inclusion/exclusion criteria should not, under any 
circumstances, be randomized or receive IP. There can be no exceptions to this rule. 
Participants may be rescreened under certain conditions (Section 5.4.1). 
If a participant withdraws from the study, then his/her randomization code cannot be reused. 
Withdrawn participants will not be replaced. 
6.3.2 
Blinding 
Benralizumab and placebo will not be visually distinct from each other. All packaging and 
labeling of the IP will be done in such a way as to ensure blinding for all AstraZeneca and 
investigational site staff. Neither the participant nor any of the Investigators or AstraZeneca 
staff who are involved in the treatment, clinical evaluation, and monitoring of the participants 
will be aware of the treatment received. Since benralizumab and placebo are not visually 
distinct, IP will be handled by an appropriately qualified member of the study team (eg, 
pharmacist, Investigator, or designee) at the site. 
All participants will receive one SC injection through Visit 16 (EOT). During the extension 
period, participants receiving benralizumab 30 mg Q8W will receive a placebo injection at 
every other site visit; thus, the investigational staff, participants, and AstraZeneca will remain 
blinded to the participant’s dosing regimen (refer to Section 4.1.2 for details on dosing 
regimens). 
A site monitor will perform IP accountability. If the treatment allocation for a participant 
becomes known to the Investigator or other study staff involved in the management of study 
participants or needs to be known to treat an individual participant for an AE, AstraZeneca 
must be notified promptly by the Investigator and before unblinding (if possible). 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
T he f oll o wi n g pers o n nel will ha ve access t o t he ra n d o mizati o n list d uri n g t he st u d y, pri or t o 
t he pri mar y D B L: 
•  
T h ose ge nerati n g t he ra n d o mizati o n list  
•  
Pers o n nel at t he I nteracti ve V oice Res p o nse S yste m (I V R S)/ I nteracti ve We b Res p o nse 
S yste m (I W R S) ( hereafter referre d t o as I x R S) c o m pa n y  
•  
T he Astra Ze neca s u p pl y c hai n de part me nt  
•  
Partici pa nt  safet y de part me nt at AstraZe neca  
•  
Bi oa nal ytical la b orat or y perf or mi n g t he P K a n d A D A sa m ple a nal ysis  
 
T he i nf or mati o n i n t he ra n d o mizati o n list will be ke pt fr o m ot her pers o n nel i n v ol ve d i n t he 
c o n d uct of t he st u d y i n a sec ure l ocati o n u ntil after t he pri mar y D B L; restricte d me m bers  of 
t he st u d y tea m will bec o me u n bli n de d after t he pri mar y D B L. N o ot her me m ber of t he 
e xte n de d st u d y tea m, i ncl u di n g Astra Ze neca, or a n y C o ntract Researc h Or ga nizati o n ha n dli n g 
data, will ha ve access t o t he ra n d o mizati o n sc he me d uri n g t he c o n d uct of t he s t u d y. 
M ai nt ai ni n g t he Bli n d t o t he P artici p a nt’s Bl o o d E osi n o p hil a n d B as o p hil C o u nts a n d 
 
Partici pa nts o n acti ve be nraliz u ma b treat me nt are e x pecte d t o ha ve l o wer e osi n o p hil a n d 
bas o p hil bl o o d c o u nts a n d l o wer le vels of  
 t ha n partici pa nts o n place b o base d o n 
its esta blis he d mec ha nis m of acti o n. Pr oce d ures t o pre ve nt u n bli n di n g base d o n e osi n o p hil a n d 
bas o p hil c o u nts a n d 
 will be i n place d uri n g t he i n d ucti o n, mai nte na nce, a n d 
e xte nsi o n treat me nt peri o ds (fr o m We e k 0 t hr o u g h Wee k 5 2):  
•  
He mat ol o g y assess me nts will be c o n d ucte d b y a ce ntral la b orat or y. P ost -ra n d o mizati o n 
( be gi n ni n g at Visit 2, Wee k 0), Astra Ze neca, st u d y site pers o n nel, a n d partici pa nts will be 
bli n de d t o t he e osi n o p hil a n d bas o p hil c o u nts. T he a bs ol ute e osi n o p hil, bas o p hil, a n d 
m o n oc yte c o u nts, a n d perce nta ges will be re dacte d fr o m t he he mat ol o g y re p orts pr o vi de d 
t o t he i n vesti gati o nal sites. 
•  
If t he I n vesti gat or or ders a n y l ocal safet y la b orat or y assess me nts, t he re q ueste d tests 
s h o ul d be restricte d t o t he q uesti o n at ha n d. F or e xa m ple, if he m o gl o bi n is desire d, t he 
I n vesti gat or s h o ul d a v oi d or deri n g a c o m plete bl o o d cell c o u nt wit h a differe ntial c o u nt. 
•  
I n cases w here t he I n vesti gat or re q uires a n e osi n o p hil, bas o p hil, or m o n oc yte c o u nt f or 
ma na gi n g s afet y iss ues, he/s he ma y or der t hese tests as per re g ular site practice. 
Astra Ze neca s h o ul d be n otifie d of all s uc h cases wit h o ut bei n g re veale d a bs ol ute 
e osi n o p hil c o u nts, a bs ol ute bas o p hil c o u nts, or a bs ol ute m o n oc yte c o u nts . 
•  
Site staff w h o are directl y i n v ol ve d i n t he partici pa nt’s ma na ge me nt s h o ul d re mai n 
bli n de d t o a n y e osi n o p hil, bas o p hil, a n d m o n oc yte res ults i ncl u de d as part of a n o utsi de 
la b orat or y re p ort or electr o nic me dical rec or d. T o hel p e ns ure t his, eac h i n vesti gati o nal 
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
site will desi g nate a n i n di vi d ual (e g, a d mi nistrat or or a n ot her a ncillar y pers o n) n ot 
directl y i n v ol ve d i n partici pa nt ma na ge me nt, t o recei ve a n d re dact a n y e osi n o p hil, 
bas o p hil, a n d m o n oc yte res ults pri or t o t he re p ort bei n g ha n de d o ver t o t he site staff 
i n v ol ve d i n t he partici pa nt’s ma na ge me nt a n d pri or t o fili n g t he la b orat or y re p ort as a 
s o urce d oc u me nt. Si milarl y, e osi n o p hil, bas o p hil, a n d m o n oc yte res ults m ust be re dacte d 
fr o m all c o m m u nicati o ns wit h Astra Ze neca. 
•  
 
After t he pri mar y D B L, restricte d me m bers of t he st u d y tea m will bec o me u n bli n de d t o all 
partici pa nts' bl o o d a n d bi o ps y cell c o u nts o btai ne d d uri n g t he d o u ble -bli n d treat me nt peri o d.  
6. 3. 3  
Met h o ds f or U n bli n di n g  
T he I x R S will pr o vi de t he I n vesti gat or(s) or p har macists t he kit I D n u m ber(s) t o be all ocate d 
t o t he partici pa nt at t he st u d y site visit. R o uti nes f or t his will be descri be d i n t he I x R S user 
ma n ual a n d t he u n bli n di n g pla n t hat will be pr o vi de d t o eac h site.  
T he ra n d o mizati o n 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 o mizati o n. T he I n vesti gat or will d oc u me nt a n d re p ort t he acti o n t o Astra Ze neca 
re prese ntati ve, wit h o ut re veali n g t he partici pa nt’s treat me nt ra n d o mizati o n t o Astra Ze neca 
re prese ntati ve or Astra Ze neca staff. 
E mer ge nc y u n bli n di n g s h o ul d als o be a vaila ble t o a t hir d -part y p h ysicia n/ me dical pr ofessi o nal 
w h o is n ot partici pati n g i n t he st u d y (e g, staff i n h os pital E R). As s o o n as p ossi ble, t he 
I n vesti gat or s h o ul d first c o ntact t he St u d y P h ysicia n t o disc uss t he me dical e mer ge nc y a n d t he 
reaso n f or re veali n g t he act ual treat me nt recei ve d b y t hat partici pa nt; h o we ver, t his ma y n ot be 
ma n dat or y a n d s h o ul d n ot ca use a n y dela y i n u n bli n di n g i n case of e mer ge ncies. T he 
treat me nt assi g n me nt will be u n bli n de d b y t he I n vesti gat or t hr o u g h I x R S. 
Astra Ze neca retai ns t he ri g ht t o brea k t he c o de f or S A Es t hat are u ne x pecte d a n d are 
s us pecte d t o be ca usall y relate d t o I P a n d t hat p ote ntiall y re q uire e x pe dite d re p orti n g t o 
re g ulat or y a ut h orities. Ra n d o mizati o n c o des will n ot be br o ke n f or t he pla n ne d a nal yses of 
data u ntil all decisi o ns o n t he e val ua bilit y of t he data fr o m eac h i n di vi d ual partici pa nt ha ve 
bee n ma de a n d d oc u me nte d.  
6. 4  
St u d y I nter ve nti o n C o m pli a nce  
Partici pa nts are d ose d at t he site, recei vi n g st u d y i nter ve nti o n directl y fr o m t he I n vesti gat or or 
de si g nee, u n der me dical s u per visi o n. T he a d mi nistrati o n of all I P s h o ul d be rec or de d i n t he 
C CI

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appropriate section of the eCRF. The study treatment provided for this study will be used only 
as directed in this CSP. 
The IP will be administered at the study site on treatment visits and within visit windows as 
specified in the SoA (Table 3). Any change from the dosing schedule, dose interruptions, or 
dose discontinuations must be recorded in the eCRF; dose modifications are prohibited. Sites 
should call participants 1 to 2 days before each visit to remind the participant of the visit. 
6.5 
Concomitant Therapy 
Any prior biologic medication(s) and concomitant medication(s), including herbal 
preparations, taken during the study will be recorded in the eCRF, along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
• 
Investigator, or designee, will collect and record information about concomitant 
medications and treatments as follows: 
− 
Stable basic skin care (cleansing and bathing, including bleach baths), emollients 
(required as background treatment), topical anesthetics, antihistamines, and topical 
and systemic anti-infective medications for any duration 
− 
All other medications or procedures taken for any reason in the 3 months prior to 
Visit 1 (except for prior biologic medication[s], which will be collected regardless of 
the time of administration) 
− 
Concomitant treatments given during the study (at each study visit). 
 
6.5.1 
Background Medication 
Throughout the study, participants will be required to maintain stable doses of their topical 
moisturizer for AD. 
6.5.2 
Other Concomitant Treatment 
Medication other than that described in Section 6.5.1 (AD therapy), which is considered 
necessary for the participant’s safety and well-being, may be given at the discretion of the 
Investigator and must be recorded in the appropriate sections of the eCRF. 
Brief course(s) of topical antibiotics will be permitted for treatment of local skin infections at 
the discretion of the Investigator and must be recorded in the appropriate sections of the 
eCRF. 

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6.5.3 
Rescue Medication 
If medically necessary (ie, to control intolerable AD symptoms), rescue treatment for AD may 
be provided to study participants at the discretion of the investigator.  
If medically necessary for intolerable AD symptoms that occur during the treatment or follow-
up periods, rescue therapy with otherwise prohibited concomitant medications or therapies 
may be prescribed to participants at the discretion of the investigator. Rescue therapy is not 
permitted until at least Visit 3 (Week 4). Rescue therapy should only be prescribed after 
assessment of the participant in the clinic, either at a scheduled or unscheduled visit. A 
justification for each participant who commences rescue therapy must be documented by the 
investigator in the clinical notes.  
Rescue therapy should initially be restricted to topical therapies (ie, TCSs or TCIs, or any 
other topical anti-inflammatory treatment [eg, PDE4 inhibitor]). TCSs should be prescribed at 
the lowest potency appropriate for the situation. TCIs should be reserved for problem areas 
only (eg, face, neck, or intertriginous and genital areas). Systemic rescue therapy should be 
reserved for participants who do not adequately respond to topical rescue therapy after ≥ 7 
days of treatment. If a participant receives rescue treatment with systemic corticosteroids or 
non-steroidal systemic immunosuppressive drugs (cyclosporine, methotrexate, mycophenolate 
mofetil, azathioprine, etc.) study treatment will be immediately discontinued. After the 
treatment with these medications is completed, study treatment may be resumed if deemed 
appropriate by the Investigator and the Study Physician, but not sooner than 5 half-lives after 
the last dose of systemic rescue medication. All participants will complete the schedule of 
study visits and assessments whether or not they complete study treatment and whether or not 
they receive rescue treatment for AD. 
Participants who require any rescue therapy during the study will be classified as non-
responders from the time of rescue use up until week 16 in the primary analysis (see section 
9.4.1). Sensitivity analyses will explore the impact of potential rescue use on the statistical 
analyses. 
6.5.4 
Restrictions 
Use of any of the following concomitant treatments or procedures will not be permitted 
throughout the study duration, unless otherwise specified: 
• 
Topical corticosteroids, TCIs, and topical PDE4 inhibitors (unless required for rescue 
medication; refer to Section 6.5.3) 
• 
Steroids/nonsteroidal systemic immunosuppressive drugs (eg, cyclosporine, methotrexate, 
mycophenolate-mofetil, azathioprine) (other than for treatment for AEs where no 
alternative treatment is available) 
• 
Major elective surgical procedures 

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• 
Phototherapy  
• 
Regular tanning in a bed/booth from 4 weeks prior to randomization and throughout the 
study 
• 
Receipt of live attenuated vaccines is disallowed 30 days prior to first dose of IP, during 
IP administration, and for 12 weeks after last dose of IP  
• 
Receipt of inactive/killed vaccinations (eg, inactive influenza) is allowed provided they 
are not administered within 1 week before/after any IP administration; additionally, it is 
recommended to rotate the next IP site injection to a site distant from the vaccine site 
injection 
• 
Any marketed or investigational biologic (monoclonal or polyclonal antibody) is not 
allowed within 4 months or 5 half-lives (whichever is longer) prior to randomization, 
during the treatment period, and is not ideally recommended within 4 months or 5 half-
lives (whichever is longer) after the last dose of the IP 
• 
Other IPs for 30 days or 5 half-lives (whichever is longer) prior to randomization and 
during the study period 
• 
New moisturizers containing additives including ceramide, hyaluronic acid, urea, or 
filaggrin degradation products may not be initiated after screening. 
 
Participants should not receive allergen immunotherapy on the same day as the IP 
administration. 
6.6 
Dose Modification 
Modification of the dose (benralizumab or placebo) is not permitted.  
6.7 
Intervention After the End of the Study 
After the end of the study, the participant should be given standard of care therapy according 
to local practice, at the discretion of the Investigator. 
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
Participants who prematurely discontinue from IP will be asked to come in for all visits and 
complete the study assessments at the IPD/EOT visit. 
Discontinuation from IP does NOT automatically lead to a complete withdrawal from the 
study. Participants discontinuing from IP are strongly encouraged to continue in the study up 
to the study completion (Visit 16, Week 60) as described in Section 7.1.1. 

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Participants will be discontinued from IP in the following situations: 
• 
Participant decision. The participant is at any time free to discontinue treatment, without 
prejudice to further treatment. The participant should always be asked about the reason(s) 
and presence of any AEs. 
• 
AE that, in the opinion of the Investigator, contraindicates further dosing. 
• 
Severe non-compliance with the CSP. 
• 
Risk to participant as judged by the Investigator or AstraZeneca. 
• 
Pregnancy.  
• 
IP unblinding. 
• 
Development of any of the following study-specific criteria for discontinuation: 
− 
Anaphylactic reaction to IP administration, in the opinion of the Investigator, 
requiring administration of epinephrine. 
− 
Development of helminth parasitic infestation requiring hospitalization. 
 
Refer to the SoA (Table 3) and Section 7.1.1 (IPD visit) for data to be collected at the time of 
IPD and follow-up and for any further evaluations that need to be completed.  
The reason for premature discontinuation of IP should be documented in the source 
documentation and recorded in the eCRF. 
7.1.1 
Procedures for Early Discontinuation of Study Intervention and at End 
of Study 
A participant who decides to discontinue IP should always be asked about the reason(s) and 
the presence of any AEs. The reason for discontinuing treatment and the date of last IP 
administration should be recorded in the eCRF. Participants permanently discontinuing IP 
administration should be given locally available standard of care therapy, at the discretion of 
the Investigator. Discontinuation of IP will be registered in the IxRS. 
See the SoA (Table 3) for data to be collected at the IPD visit and for any further evaluations 
to be completed. 
7.1.1.1 
Early Discontinuation of Study Intervention 
All participants who prematurely discontinue IP should return to the study site for the IPD 
visit 4 weeks (± 7 days) after the last dose of IP for procedures, or as soon as feasible if this 
interval is missed (eg, if decision on discontinuation was made later), as specified in Table 3. 
At the IPD visit, the participant will be offered the following options for further follow-up: 

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• 
Participants are encouraged to return to all scheduled site visits and perform all 
procedures (including PRO completion and blood draws), but without IP administration, 
until the end of the study (Visit 16). 
• 
If the participant is unwilling or unable to attend the scheduled site visits until the end of 
the double-blind treatment period, he/she will be offered a follow-up option that includes 
monthly telephone contact instead. During follow-up telephone contact, the Investigator 
will collect information about concomitant medications, information on AD symptoms, 
and AE/SAE(s) (Section 8.3). 
 
7.1.1.2 
Discontinuation of Study Intervention upon Notification of Closure of Study 
The IPD visit (4 weeks [± 7 days] after the last dose of IP) should be conducted for all 
ongoing participants within 3 months of notification from AstraZeneca of closure of the study 
(Section 7.2.1). 
7.1.2 
Procedures for Handling Incorrectly Enrolled or Randomized 
Participants 
Participants who fail to meet the eligibility criteria should not, under any circumstances, be 
randomized or receive IP. Participants who are enrolled but subsequently found not to meet all 
the eligibility criteria must not be randomized and must be withdrawn (screen failed) from the 
study. 
Where a participant does not meet all the eligibility criteria but is randomized in error, or 
incorrectly started on IP, the Investigator should inform the study physician or designee 
immediately, and a discussion should occur between the study physician and the Investigator 
regarding whether to continue or discontinue the participant from IP. 
If the agreed decision is to discontinue IP, participants should be encouraged to remain in the 
study and continue to be followed-up until the end of the study (ie, Week 60). 
The decision to discontinue/continue IP must be appropriately documented, including 
rationale, particularly if the agreed decision is to continue IP treatment. 
7.2 
Participant Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioural, 
compliance, or administrative reasons. This is expected to be uncommon. 
• 
A participant who considers withdrawing from the study must be informed by the 
Investigator about modified follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records). 

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• 
At the time of withdrawal from the study, if possible, the IPD visit should be conducted. 
See the SoA (Table 3) for data to be collected at the time of study withdrawal and follow-
up and for any further evaluations that need to be completed. 
− 
The participant will discontinue the study intervention and be withdrawn from the 
study at that time. 
• 
If the participant withdraws consent/assent for disclosure of future information, 
AstraZeneca may retain and continue to use any data collected before such a withdrawal 
of consent/assent. 
 
If a participant withdraws from the study, it should be confirmed if he/she still agrees for 
existing samples to be used in line with the original consent/assent. If he/she requests 
withdrawal of consent/assent for use of samples, destruction of any samples taken and not 
tested should be carried out in line with what was stated in the informed consent/assent and 
local regulations. The Investigator must document the decision on use of existing samples in 
the site study records and inform the AstraZeneca representative. 
Participants who withdraw from the study will return the handheld electronic PRO device. 
7.2.1 
Discontinuation or Suspension of the Whole Study Program 
If AstraZeneca decides to prematurely terminate or suspend the study, the Investigator and 
regulatory authorities should receive written notification of the reasons for the premature 
termination or suspension. The Investigator will immediately notify the decision to the 
participants and, if relevant, give appropriate medical treatment, take necessary measures, and 
document these in the source notes. 
There are no pre-specified stopping rules or criteria for this study. 
7.3 
Lost to Follow-up 
A participant will be considered potentially lost to follow-up if he or she fails to return for 
scheduled visits and is unable to be contacted by the study site.  
To prevent a participant being lost to follow-up, it is recommended that the study sites 
maintain up-to-date contact details for participants, including next of kin or other emergency 
contacts (if allowed by national regulation). 
The Investigator should educate the participant on the importance of maintaining contact with 
the Investigator/study site throughout the study. 
The following actions must be taken if a participant fails to return to the site for required study 
visits: 

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• 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule. 
• 
Repeated attempts must be made to regain contact with the participant or next of 
kin/emergency contact by repeat telephone calls, emails, and/or certified letter. These 
contact attempts should be documented in the participant’s medical record. 
 
Efforts to reach the participant should continue until the end of the study. 
The participant will be classified as lost to follow-up only if he/she has failed to return for the 
required study visits and his/her vital status remains unknown at the end of the study (ie, 
Week 60), despite all above listed efforts. For the primary analysis purposes, a participant will 
be classified as lost to follow-up if he/she has failed to return for the required study visits and 
his/her vital status remains unknown at the time of primary DBL (ie, after the Week 16 visit). 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Table 3).  
The Investigator will ensure that data are recorded on the eCRFs. The Web Based Data 
Capture system will be used for data collection and query handling. 
The Investigator ensures the accuracy, completeness, legibility, and timeliness of the data 
recorded and of the provision of answers to data queries according to the Clinical Study 
Agreement. The Investigator will sign the completed eCRFs. A copy of the completed eCRFs 
will be archived at the study site. 
Immediate safety concerns should be discussed with the AstraZeneca representative 
immediately upon occurrence or awareness to determine if the participant should continue or 
discontinue IP. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood test, 
echocardiography, biopsy, etc.) and obtained before signing of the ICF may be utilized for 

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screening or baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA. 
Note: for laboratory assessments, if not all laboratory kits are available at a given visit, the 
Investigator should contact the Study Physician to confirm whether assessment is critical or 
may be postponed until supplies are available. 
8.1 
Efficacy Assessments 
8.1.1 
Investigator Global Assessment 
The IGA is an instrument used in clinical studies to rate the severity of AD globally, based on 
a 5-point scale ranging from 0 (clear) to 4 (severe). The IGA uses clinical characteristics of 
erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity 
assessment. The validated IGA scale for AD will be completed by the investigator on an 
electronic device supplied to the site according to the SoA (Table 3) to capture these key 
measures of AD disease activity and describe the overall appearance of AD lesions (Table 7).  
Table 7 
Investigator Global Assessment Score 
Score 
Morphological description 
0 – Clear 
No inflammatory signs of atopic dermatitis (no erythema, no induration/papulation, 
no lichenification, no oozing/crusting). Post-inflammatory hyperpigmentation and/or 
hypopigmentation may be present. 
1 -- Almost clear 
Barely perceptible erythema, barely perceptible induration/papulation, and/or 
minimal lichenification. No oozing or crusting. 
2 -- Mild 
Slight but definite erythema (pink), slight but definite induration/papulation, and/or 
slight but definite lichenification. No oozing or crusting. 
3 -- Moderate 
Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, 
and/or clearly perceptible lichenification. Oozing and crusting may be present. 
4 -- Severe 
Marked erythema (deep or bright red), marked induration/papulation, and/or marked 
lichenification. Disease is widespread in extent. Oozing or crusting may be present. 
 
8.1.2 
Eczema Area and Severity Index 
The EASI is a validated tool used in clinical practice and clinical trials to assess the severity 
and extent of AD (Hanifin et al 2001). The EASI including percentage body surface area 
(BSA) affected by AD will be assessed according to the SoA (Table 3). The EASI is a 
composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, 
thickness [induration, papulation, edema], scratching [excoriation], and lichenification) will 
each be assessed by the investigator or designee at visits specified in the SoA (Table 3). The 
severity score is assessed on a scale of 0 (absent) to 3 (severe) in each of 4 body regions 
(head, trunk, upper limbs, and lower limbs). In addition, the area of AD involvement will be 
assessed as a percentage by body area in the 4 anatomic areas and converted to a score of 0 to 

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6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 
49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).  
The percentage of participants achieving a 50% reduction from baseline in EASI score (EASI-
50), 75% reduction from baseline in EASI score (EASI-75), 90% reduction from baseline in 
EASI score (EASI-90), and 100% reduction from baseline in EASI score (EASI-100) will be 
calculated from the total EASI scores. 
The EASI will be completed by the investigator on an electronic device supplied to the site, 
which will calculate the domain and total scores for the subject.  
8.1.3 
Scoring Atopic Dermatitis 
SCORing Atopic Dermatitis (SCORAD) is a clinical tool for assessing the severity of AD that 
evaluates the extent and intensity of AD lesions, in addition to subjective symptoms (Kunz et 
al 1997). There are 3 components to the assessment: A = extent or affected body surface area, 
B = severity, and C = subjective symptoms. The extent of AD is assessed as a percentage of 
each defined body area (see Section 8.1.4) and reported as the sum of all areas, with a 
maximum score of 100% (assigned as “A” in the overall SCORAD calculation). The severity 
of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin 
thickening/lichenification, dryness) is assessed using the following scale: none (0), mild (1), 
moderate (2), or severe (3) (for a maximum of 18 total points, assigned as “B” in the overall 
SCORAD calculation). Subjective assessment of itch and sleeplessness is recorded for each 
symptom by the participant or relative on a visual analogue scale (VAS), where 0 is no itch 
(or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum 
possible score of 20. This parameter is assigned as “C” in the overall SCORAD calculation. 
The maximum total score is 103, with higher values indicating more severe disease. SCORAD 
will be assessed at the visits specified in the SoA (Table 3) and will be completed on the 
electronic device supplied to the site.   
A suitable area of non-lesional skin will be designated at screening for SCORAD assessments 
of skin dryness at Visit 1. To allow for the assessment of skin dryness, moisturizers should not 
be applied to the designated area for ≥ 8 hours before visits when SCORAD will be assessed. 
These instructions should be explained to participants at Visit 1. 
8.1.4 
Body Surface Area Involvement of Atopic Dermatitis 
Body surface area affected by AD will be assessed for each section of the body using the 
Palmar method with rule of nine. The possible highest score for each region is: head and neck 
[9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals 
[1%], and will be reported as a percentage of all major body sections combined. Participants 
will undergo this assessment at time points according to the SOA (Table 3). The BSA affected 
scoring will also be calculated on the electronic device that is supplied to the site. 

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8.1.5 
Skin Photography 
Clinical skin photography is a method to capture and document images of the skin. To 
evaluate alternative methods of clinical assessments, skin photography will be used in this 
study. Full body photographs will be taken as outlined in the photography manual and 
according to the SoA (Section 1.3).  
At visits when clinical skin photography is to be performed and assessed before the 
Investigator sees the participant for the study visit, the photographs should be taken by a 
trained site personnel and not by the Investigator performing efficacy assessments on the 
participant. The site Investigator will then review the photographs and perform the clinical 
efficacy assessments (IGA, EASI, SCORAD, and BSA) based on review of the photographs. 
The Investigator photograph assessment will be recorded in the eCRF. The same site 
Investigator should then see the participant and perform the usual in-person visit assessments 
including the in-person assessment of efficacy parameters and document the data. The first 
assessments (based on skin photography) should not be altered even if differences are 
observed after assessing the participant in person. The final in-person Investigator assessment 
documented should reflect the Investigator’s overall clinical judgment. Photographic 
equipment will be provided to the sites.  
8.1.6 
Patient-reported Outcomes 
Participants will complete all patient-reported outcomes (PRO) assessments using a handheld 
device. The handheld device will be the only accepted source of PRO data. 
The Investigator will ensure that participants are properly trained on the use of this device and 
the importance of completing assessments as scheduled. 
The handheld PRO device will be programmed at Visit 1 with reminder alarms for the daily 
diary. Study site staff will be able to adjust alarms for specific participant needs as needed. 
The participant will be required to complete a training module (at the site) before taking the 
device home. 
The Investigator or designee will be responsible for ensuring that the participant is completing 
the daily diary and follow-up as necessary to minimize missing data. Participant compliance 
should be checked weekly (at a minimum) to ensure that the participant is completing the 
assessments as scheduled. Monitoring of participant compliance with completion of the diary 
is especially critical between Visit 1 and Visit 2 to ensure that the participant meets applicable 
criteria for randomization. If the participant does not meet the randomization requirements, 
the device will be deactivated and retained at the site for future use. 

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Review of participant compliance with the assessment schedule, completion of any available 
assessments, and logging of the visit on the handheld device should be completed prior to 
other study procedures. 
Compliance with the assessment schedule should be completed weekly throughout the study 
and follow-up with participants via phone and at the visits. Compliance review is required to 
ensure sufficient data are available for supporting the primary endpoint of this study. 
The timing and frequency for each PRO is provided in Table 3. 
8.1.6.1 
Peak Pruritus Numeric Rating Scale 
The Peak Pruritus Numeric Rating Scale is a one-item daily assessment of the worst itch the 
patient experienced over the past 24 hours. The score ranges from 0 to 10, with 0 being “no 
itch” and 10 being “worst itch imaginable.” 
8.1.6.2 
Patient-Oriented Eczema Measure 
The Patient-Oriented Eczema Measure (POEM) is a 7-item assessment of AD symptoms 
(itchiness, sleep disturbance, bleeding, weeping, cracking, flaking, and dryness) that 
characterizes severity as a function of symptom frequency. The participant responds to each 
question by selecting the approximate number of days during the past week when they 
experienced the symptom (no days, 1 to 2 days, 3 to 4 days, 5 to 6 days, or every day).  
For scoring, the frequency is converted to a 0 to 4 scale, with “no days” being 0 and “every 
day” being 4. The seven items are summed, resulting in a score ranging from 0 to 28 (Table 
8). Higher scores represent more severe AD symptoms. 
Table 8 
Patient-Oriented Eczema Measure Score Bands 
Score range 
Clinical interpretation 
0 to 2 
Clear or almost clear 
3 to 7 
Mild atopic dermatitis 
8 to 16 
Moderate atopic dermatitis 
17 to 24 
Severe atopic dermatitis 
25 to 28 
Very severe atopic dermatitis 
 
8.1.6.3 
Dermatology Life Quality Index 
The Dermatology Life Quality Index (DLQI) is a 10-item assessment of dermatology-specific 
health-related quality of life in participants age 17 and older (Finlay and Khan 1994). 
Participants are asked to rate their symptoms and the impact of their symptoms on several 
domains: symptoms and feelings, daily activities, leisure, work and school, personal 
relationships, and treatment. Both the overall score and domain scores will be calculated. 

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The DLQI will only be administered to participants who are age 17 or older at Visit 1. 
8.1.6.4 
Children’s Dermatology Life Quality Index 
The Children’s Dermatology Life Quality Index (CDLQI) is a 10-item assessment of 
dermatology-specific health-related quality of life in children and adolescents ages 5 to16 
(Lewis-Jones and Finlay 1995). Participants are asked to rate their symptoms and the impact 
of their symptoms on several domains: symptoms and feelings, leisure, school and holidays, 
personal relationships, sleep, and treatment. Both the overall score and domain scores will be 
calculated. 
The CDLQI will only be administered to participants who are age 16 or younger at Visit 1. 
8.1.6.5 
Hospital Anxiety and Depression Scale 
The Hospital Anxiety and Depression Scale (HADS) is a mental health assessment comprising 
7 items on anxiety and 7 items on depression. All questions are rated on a 0 to 3 scale, with 
higher scores representing worse mental health; scores for the 2 subscales thus range from 0 to 
21. Scores between 0 and 7 are considered normal. Scores between 8 and 10 are possible cases 
of anxiety/depression. Scores 11 or greater are considered likely cases of anxiety/depression.  
8.1.6.6 
Patient Global Impression of Severity 
The Patient Global Impression of Severity (PGI-S) is a single item assessment of the 
participant’s perception of overall symptom severity at the time of completion. The 
assessment uses a 6-point categorical response scale (ranging from "no symptoms” to “very 
severe”). 
8.1.6.7 
SF-36 (Version 2), Acute Recall 
The Short Form 36-item Health survey Version 2 (acute recall) (SF-36v2) is a 36-item, self-
report survey of functional health and well-being, with a 1-week recall period.  Responses to 
35 of the 36 items are used to compute an 8-domain profile of functional health and 
well-being scores. The remaining item, referred to as the ‘Health Transition’ item, asks 
participants to rate how their current state of health compared to their state of health 1 week 
ago and is not used to calculate domain scores. The 8-domain profile consists of the following 
subscales: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily 
Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role 
Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-
based physical and mental health component summary scores (PCS and MCS, respectively) 
are computed from subscale scores to give a broader metric of physical and mental health-
related quality of life. 
Two types of thresholds have been developed for interpretation of SF-36v2 scores. The first 
type is suitable for comparing group mean scores and is generally referred to as the minimal 
clinically important difference. The second type is suitable for interpreting change at the 

Cli nical St u d y Pr ot oc ol  
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0 4 Ma 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  
 
i n di vi d ual le vel a n d is referre d t o as t he res p o n der t hres h ol d or res p o n der defi niti o n; t hres h ol d 
val ues f or t he S F -3 6 v 2 scale a n d s u m mar y meas ures are pr o vi de d i n Ta ble 9 . 
T a ble 9  
T hres h ol d V al ues f or t he S F -3 6 v 2 Sc ale a n d S u m m ar y Me as ures  
T hres h ol d  
S F -3 6 v 2 sc ore  
P C S  
M C S  
P F  
R P  
B P  
G H  
V T  
S F  
R E  
M H  
Gr o u p 
differe nce  
2  
3  
3  
3  
3  
2  
2  
3  
4  
3  
I n di vi d ual 
c ha n ge 
3. 4  
4. 6  
4. 3  
3. 4  
6. 2  
7. 2  
6. 2  
6. 9  
4. 5  
6. 2  
B P, B o dil y Pai n; G H, Ge neral Healt h Perce pti o ns; M C S, me ntal healt h c o m p o ne nt s u m mar y; M H, Me ntal 
Healt h; P C S, p h ysical c o m p o ne nt s u m mar y; P F, P h ysical F u ncti o ni n g; R E, E m oti o nal Pr o ble ms; R P, R ole 
Li mitati o ns d ue t o P h ysical Healt h; S h ort F or m 3 6 -ite m Healt h S ur ve y Versi o n 2; V T, Vitalit y. 
 
8. 1. 6. 8  
E ur o pe a n Q u alit y of Life -5 Di me nsi o ns  
T he E ur o pea n Q ualit y of Life -5 Di me nsi o ns ( E Q -5 D) q uesti o n naire asse sses 5 di me nsi o ns: 
m o bilit y, self -care, us ual acti vities, pai n/ disc o mf ort, a n d a n xiet y/ de pressi o n. Eac h di me nsi o n 
has 5 res p o nse o pti o ns ( n o pr o ble ms, sli g ht pr o ble ms, m o derate pr o ble ms, se vere pr o ble ms, 
a n d e xtre me pr o ble ms) t hat reflect i ncreasi n g le vels  of diffic ult y.  
T he partici pa nt will be as ke d t o i n dicate his/ her c urre nt healt h state b y selecti n g t he m ost 
a p pr o priate le vel i n eac h of t he 5 di me nsi o ns. T he q uesti o n naire als o i ncl u des a V A S, w here 
t he partici pa nt will be as ke d t o rate c urre nt healt h stat us o n a scale of 0 t o 1 0 0, wit h 0 bei n g 
t he w orst i ma gi na ble healt h state. 
C CI

Cli nical St u d y Pr ot oc ol  
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0 4 Ma 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. 7  
P atie nt -Re p orte d E x perie nce  
Partici pa nts will be as ke d t o res p o n d i n writi n g (free te xt) t o 3 o pe n -e n de d q uesti o ns a b o ut 
t heir e x perie nce wit h A D a n d t heir st u d y i nter ve nti o n. T he assess me nt will be c o n d ucte d 
d uri n g t he site visits s pecifie d i n t he S o A ( Ta ble 3 ), usi n g a pr o visi o ne d ta blet t o access t he 
sec ure we b f or m. 
Data fr o m t he free te xt c ollecti o n will be use d f or e x pl orat or y descri pti ve a nal ysis u si n g 
mac hi ne lear ni n g tec h n ol o gies. D ue t o t he q ualitati ve nat ure of t he data a n d t he a nal ysis, t he 
res ults will be prese nte d i n a se parate re p ort ( n ot i n t he Cli nical St u d y Re p ort [ C S R]) a n d t he 
data will n ot be e ntere d i nt o t he st u d y data base.  
8. 2  
S afet y Ass ess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A ( Ta ble 3 ). 
8. 2. 1  
Cli nic al S afet y L a b or at or y Assess me nts  
Ta ble 1 0  lists t he cli nical safet y la b orat or y tests t o be perf or me d. Refer t o t he S o A (Ta ble 3 ) 
f or t he ti mi n g a n d fre q ue nc y. All pr ot oc ol-re q uire d la b orat or y assess me nts, as defi ne d i n t he 
ta ble, m ust be c o n d ucte d i n acc or da nce wit h t he La b orat or y Ma n ual a n d t he S o A (Ta ble 3 ).  
T he I n vesti gat or s h o ul d ma ke a n assess me nt of t he a vaila ble res ults wit h re gar d t o cli nicall y 
rele va nt a b n or malities. T he la b orat or y res ults s h o ul d be si g ne d a n d date d a n d retai ne d at t he 
site as s o urce data f or la b orat or y varia bles.  
C CI

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For information on how AEs based on laboratory tests should be recorded and reported, see 
Section 8.3.5. 
Additional safety samples may be collected if clinically indicated at the discretion of the 
Investigator. The date, time of collection and results (values, units, and reference ranges) will 
be recorded in the participant’s medical records. 
The clinical chemistry, hematology, and urinalysis will be performed at a central laboratory. 
Instructions for sample collection, processing, storage, and shipment are provided in the 
central laboratory manual. 
Table 10 
Laboratory Safety Variables 
Clinical chemistry 
Hematology 
Urinalysis 
Alkaline phosphatase 
Gamma-GT (gamma-
glutamyl transpeptidase) 
Hematocrit 
Appearance 
ALT (alanine 
aminotransferase) 
Glucose 
Hemoglobin 
Blood 
AST (aspartate 
aminotransferase) 
Phosphorus 
Mean corpuscular 
volume (MCV) 
Color 
BUN (blood urea 
nitrogen) 
Potassium 
Platelet count 
Ketones 
Calcium 
Sodium 
Red blood cell (RBC) 
count 
Microscopy including 
White blood cell 
(WBC)/high power field 
(HPF), RBC/HPF 
Chloride 
Total bilirubin 
WBC count (absolute 
and differential) a 
pH 
CO2 (carbon dioxide) b 
Uric acid 
 
Specific gravity 
Creatinine 
Creatine kinase 
 
 
a 
Eosinophil, basophil, and monocyte counts will be redacted from the central laboratory reports starting from 
Visit 2 (refer to Section 6.3.2). 
b 
Measured as bicarbonate. 
 
8.2.1.1 
Pregnancy Tests 
The following tests are applicable to female participants only and will be conducted in 
accordance with the schedules provided in the SoA (Table 3). 
• 
Serum beta-human chorionic gonadotropin (HCG): To be performed for all female 
participants at Visit 1 except for those who are NOT of childbearing potential as defined 
in inclusion criterion 12. This test is to be sent to and analyzed at the central laboratory. 

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• 
FSH: To be performed at Visit 1 only for female participants < 50 years who have been 
amenorrhoeic for ≥ 12 months prior to the planned date of randomization to confirm 
postmenopausal status. This test is to be sent to and analyzed at the central laboratory; all 
females should be treated as pre-menopausal until results are received from the central 
laboratory. 
• 
Urine HCG (dipstick): To be performed locally at the study site before each IP 
administration (starting at Visit 2 through the EOT), and at IPD visits for all female 
participants except for those who are NOT of childbearing potential as defined in 
inclusion criterion 12. A positive urine test result must be confirmed with serum beta-
HCG. 
 
8.2.1.2 
Serology 
Hepatitis B surface antigen and hepatitis C antibody tests will be assessed in accordance with 
the SoA (Table 3); tests are to be performed at the central laboratory. 
In case of positive result of hepatitis B surface antigen or hepatitis C virus antibody, additional 
testing (eg, hepatitis C ribonucleic acid [RNA] polymerase chain reaction test) may be 
performed. 
HIV-1 and HIV-2 antibodies (along with p24 Antigen): To be performed only at screening; 
test to be performed at the central laboratory. 
Instructions for sample collection, processing, storage, and shipment are provided in the 
laboratory manual. 
8.2.2 
Physical Examinations 
Physical examinations (complete or brief), including height and weight, will be conducted in 
accordance with the schedule provided in Table 3. Baseline data will be collected at the 
randomization visit (Visit 2) before administration of the first dose of IP. Any new findings or 
aggravated existing abnormalities, judged as clinically significant by the Investigator, will be 
reported as an AE as described in Section 8.3.5. 
The complete physical examination will include an assessment of the following: general 
appearance, skin, head and neck (including eyes/conjunctivitis, ears, nose, mouth, and throat), 
lymph nodes, abdomen, musculoskeletal (including spine and extremities), cardiovascular, 
respiratory, and neurological systems. 
The brief physical examination will include an assessment of the general appearance, head 
and neck (including eyes/conjunctivitis, nose), abdomen, cardiovascular, and respiratory 
system. For the brief physical examination, only information on whether the assessment was 
performed or not is to be recorded. 

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Weight measurements will be performed in light clothing and without shoes and will be 
recorded in kilograms. 
8.2.3 
Vital Signs 
Pre-dose vital signs (pulse rate, blood pressure, respiratory rate, and body temperature) will be 
assessed in accordance with the SoA (Table 3). 
It is recommended that vital signs are assessed before any interventional study procedures 
(blood test collection, IP administration). 
Body temperature will be measured in Celsius in accordance with local standards. 
Blood pressure and pulse measurements will be assessed while sitting with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available. The pulse rate and blood pressure will be measured after the participant has been 
resting for at least 5 minutes in a quiet setting without distractions (eg, television, cell 
phones). The pulse rate should be obtained before blood pressure. 
The respiration rate will be obtained after the participant has been resting for at least 5 
minutes, by counting the number of breaths (how many times the chest rises) for 1 minute. 
8.2.4 
Electrocardiograms 
Single 12-lead electrocardiogram (ECG) will be obtained locally during screening (Table 3) 
using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and 
QT intervals. The ECG results will be interpreted locally.  
The Investigator or authorized delegate will be responsible for the overall interpretation and 
determination of clinical significance of any potential ECG findings. The ECG printouts will 
be signed and dated by the Investigator and stored at the study site. Any findings will be 
recorded in the eCRF. 
ECG will be taken in the supine position, after the participant has been resting for at least 
5 minutes. The assessment should be performed before interventions with the participant 
(eg, IP administration). 
8.3 
Adverse Events and Serious Adverse Events 
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section. 
The definitions of an AE or SAE can be found in Appendix B. 

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AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE. For information on how to follow up AEs 
refer to Section 8.3.2. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information  
All AEs will be collected starting from Visit 1, throughout the treatment period, and including 
the follow-up period last contact with participant. 
Serious AEs will be recorded from the time the participant signs the ICF, throughout the 
duration of the study. All SAEs will be recorded and reported to the AstraZeneca 
representative within 24 hours, as indicated in Appendix B. The Investigator will submit any 
updated SAE data to the AstraZeneca representative within 24 hours of it being available. 
If the Investigator becomes aware of a SAE with a suspected causal relationship to the 
investigational medicinal product that occurs after the end of the clinical study in a participant 
treated by him or her, the Investigator shall, without undue delay, report the SAE to the 
AstraZeneca representative. 
8.3.2 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
Any AEs that are unresolved at the end of the study (final DBL) will be followed-up by the 
Investigator for as long as medically indicated, but without further recording in the eCRF. 
AstraZeneca retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary. 
Adverse Event Variables 
The following variables will be collected for each AE: 
• 
AE (verbatim) 
• 
The date when the AE started and stopped 
• 
Maximum intensity 

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• 
Whether the AE is serious or not 
• 
Investigator causality rating against the IP (yes or no) 
• 
Action taken with regard to the IP 
• 
AE caused participant’s withdrawal from study (yes or no) 
• 
Outcome 
 
In addition, the following variables will be collected for SAEs: 
• 
Description of AE 
• 
Date AE met criteria for SAE 
• 
Date Investigator became aware of SAE 
• 
AE is serious due to (see definition of SAE in Appendix B 2)  
• 
Date of hospitalization 
• 
Date of discharge 
• 
Probable cause of death 
• 
Date of death 
• 
Autopsy performed 
• 
Causality assessment in relation to study procedure(s) 
• 
Causality assessment to other medication 
 
8.3.3 
Causality Collection 
The Investigator will assess causal relationship between IP and each AE, and answer ‘yes’ or 
‘no’ to the question ‘Do you consider that there is a reasonable possibility that the event may 
have been caused by the IP?’ 
For SAEs, causal relationship will also be assessed for other medication and study procedures. 
Note that for SAEs that could be associated with any study procedure, the causal relationship 
is implied as ‘yes’. 
A guide to the interpretation of the causality question is found in Appendix B. 
8.3.4 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the participant or care provider or reported in response to 
the open question from the study site staff: ‘Have you had any health problems since the 
previous visit/you were last asked?’, or revealed by observation will be collected and recorded 
in the eCRF. When collecting AEs, the recording of diagnoses is preferred (when possible) to 
recording a list of signs and symptoms. However, if a diagnosis is known and there are other 

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signs or symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom will be recorded separately. 
8.3.5 
Adverse Events Based on Examinations and Tests 
The results from the protocol-mandated laboratory tests and vital signs will be summarized in 
the CSR. Deterioration as compared to baseline in protocol-mandated laboratory values and 
vital signs should therefore only be reported as AEs if they fulfill any of the SAE criteria, are 
the reason for discontinuation of treatment with the investigational product, or are considered 
to be clinically relevant as judged by the Investigator (which may include but not limited to 
consideration as to whether treatment or non-planned visits were required or other action was 
taken with the study intervention, eg, drug interruption). 
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible the reporting Investigator 
uses the clinical, rather than the laboratory term (eg, anemia versus low hemoglobin value). In 
the absence of clinical signs or symptoms, clinically relevant deteriorations in non-mandated 
parameters should be reported as AE(s). 
Deterioration of a laboratory value, which is unequivocally due to disease progression, should 
not be reported as an AE/SAE. 
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE unless unequivocally 
related to the disease under study. 
8.3.6 
Disease Under Study 
Symptoms of disease under study are those which might be expected to occur as a direct result 
of AD (eg, erythema, induration/papulation, lichenification, oozing/crusting, pruritus). Events 
which are unequivocally due to AD should not be reported as an AE during the study unless 
they meet SAE criteria or lead to discontinuation of the IP. 
8.3.7 
Reporting of Serious Adverse Events 
All SAEs have to be reported, whether or not considered causally related to the IP, or to the 
study procedure(s). All SAEs will be recorded in the eCRF. 
If any SAE occurs in the course of the study, Investigators or other site personnel will inform 
the appropriate AstraZeneca representatives within one day, ie, immediately but no later than 
24 hours of when he or she becomes aware of it. 

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The designated AstraZeneca representative will work with the Investigator to ensure that all 
the necessary information is provided to the AstraZeneca Patient Safety data entry site within 
one calendar day of initial receipt for fatal and life-threatening events and within 5 calendar 
days of initial receipt for all other SAEs. 
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
within one calendar day ie, immediately but no later than 24 hours of when he or she becomes 
aware of it). 
If the electronic data capture system is not available, then the Investigator or other study site 
staff reports an SAE to the appropriate AstraZeneca representative by telephone. 
The AstraZeneca representative will advise the Investigator/study site staff how to proceed. 
The reference document for definition of expectedness/listedness is the Investigator's 
Brochure for benralizumab.  
For further guidance on the definition of an SAE, see Appendix B. 
8.3.8 
Pregnancy 
All pregnancies and outcomes of pregnancy should be reported to the AstraZeneca 
representative unless the pregnancy is discovered before the study participant has received any 
IP. 
If a pregnancy is reported, the Investigator should inform the AstraZeneca representative 
within 24 hours of learning of the pregnancy. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, foetal death, stillbirth, congenital 
anomalies, and ectopic pregnancy) are considered SAEs. 
8.3.8.1 
Maternal Exposure 
If a participant becomes pregnant during the course of the study, IP should be discontinued 
immediately. 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IP under study 
may have interfered with the effectiveness of a contraceptive medication. Congenital 
anomalies/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. The outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth or congenital anomaly/birth defect) should be followed-up and documented even if the 
participant was discontinued from the study. 

Cli nical St u d y Pr ot oc ol  
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0 4 Ma 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  
 
If a n y pre g na nc y occ urs i n t he c o urse of t he st u d y, t he n t he I n vesti gat or or ot her site pers o n nel 
i nf or ms t he a p pr o priate Astra Ze neca re prese ntati ve wit hi n o ne da y (ie, i m me diatel y b ut n o 
later t ha 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 I n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt Safet y data e ntr y site wit hi n 1 or 5 
cale n dar da ys f or S A Es ( Secti o n 8. 3. 7 ) 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 mati o n is a vaila ble.  
8. 3. 9  
De vice C o nstit ue nt De ficie ncies 
•  
I n a c o m bi nati o n dr u g-de vice I P  
 t he De vice C o nstit ue nt deficie nc y is a n 
i na de q uac y of a de vice c o nstit ue nt wit h res pect t o its i de ntit y, q ualit y, d ura bilit y, 
relia bilit y, safet y, or perf or ma nce. T hese deficie ncies i ncl u de malf u ncti o ns, use err ors, 
a n d i nf or mati o n s u p plie d b y t he ma n ufact urer.  
•  
Seri o us a d verse de vice effect ( S A D E) is defi ne d as a n y De vice C o nstit ue nt Deficie nc y 
t hat mi g ht ha ve le d t o a n S A E if a p pr o priate acti o n ha d n ot bee n ta ke n, i nter ve nti o n ha d 
n ot occ urre d, or circ u msta nces ha d bee n less f ort u nate.  
•  
F or de vice c o nstit ue nt deficie ncies, it is ver y i m p orta nt t hat t he i n vesti gat or descri bes a n y 
c orrecti ve or re me dial acti o ns ta ke n t o pre ve nt rec urre nce of t he deficie nc y.  
•  
A re me dial acti o n is a n y acti o n ot her t ha n r o uti n e mai nte na nce or ser vici n g of a de vice 
c o nstit ue nt w here s uc h acti o n is necessar y t o pre ve nt rec urre nce of a de vice c o nstit ue nt 
deficie nc y. T his i ncl u des a n y a me n d me nt t o t he de vice c o nstit ue nt desi g n t o pre ve nt 
rec urre nce. 
•  
T he i n vesti gat or is o bli gate d t o  perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d t o el uci date t he nat ure a n d/ or 
ca usalit y of t he de vice c o nstit ue nt deficie nc y as f ull y as p ossi ble. T his ma y i ncl u de 
a d diti o nal la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or 
c o ns ultati o n wit h ot her healt h care pr ofessi o nals.  
 
8. 3. 1 0  
Seri o us A d verse De vice Effect Re p orti n g  
N O T E: T here are a d diti o nal re p orti n g o bli gati o ns f or de vice c o nstit ue nt deficie ncies t hat are 
p ote ntiall y relate d t o S A Es t hat m ust f ulfill t he le gal res p o nsi bilit y t o n otif y a p pr o priate 
re g ulat or y a ut h orities a n d ot her e ntities a b o ut certai n safet y i nf or mati o n relati n g t o de vice 
c o nstit ue nts bei n g use d i n cli nical st u dies.  
•  
A n y de vice c o nstit ue nt deficie nc y t hat is as s ociate d wit h a n S A E m ust be re p orte d t o t he 
s p o ns or wit hi n 2 4 h o urs after t he i n vesti gat or deter mi nes t hat t he e ve nt meets t he 
defi niti o n of a de vice c o nstit ue nt deficie nc y.  
•  
T he s p o ns or will re vie w all de vice c o nstit ue nt deficie ncies a n d deter mi ne a n d d oc u me nt 
i n writi n g w het her t he y c o ul d ha ve le d t o a n S A E. T hese de vice c o nstit ue nt deficie ncies 
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will be reported to the regulatory authorities and Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) as required by national regulations. 
 
8.3.11 
Medication Error 
If a medication error occurs in the course of the study, then the Investigator or other site 
personnel informs the AstraZeneca representative within one day (ie, immediately but no later 
than 24 hours of when he or she becomes aware of it). 
The designated AstraZeneca representative works with the Investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within one 
(initial fatal/life-threatening or follow-up fatal/life-threatening) or 5 (other serious initial and 
follow-up) calendar days if there is an SAE associated with the medication error (Section 
8.3.1) and within 30 days for all other medication errors. 
The definition of a Medication Error can be found in Appendix B. 
8.3.12 
Management of Investigational Product-related Drug Reactions 
Appropriate drugs, such as epinephrine, H1 and H2 antihistamines, and corticosteroids, as well 
as medical equipment to treat acute anaphylactic reactions must be immediately available 
when IP is administered and study site personnel must be trained to recognize and treat 
anaphylaxis (Lieberman et al 2010). Details on anaphylaxis management are provided in 
Appendix E. 
Anaphylaxis will be defined as a serious reaction that is rapid in onset and may cause death 
(Sampson et al 2006). Anaphylaxis typically manifests as 1 of 3 clinical scenarios: 
1 
The acute onset of a reaction (minutes to hours) with involvement of the skin, mucosal 
tissue, or both and at least one of the following: 
(a) respiratory compromise; or 
(b) reduced blood pressure or symptoms of end-organ dysfunction; or 
2 
Two or more of the following that occur rapidly after exposure: involvement of the 
skin/mucosal tissue, respiratory compromise, reduced blood pressure or associated 
symptoms and/or persistent gastrointestinal symptoms; or 
3 
Reduced blood pressure after exposure. 
 
Further details on the clinical criteria for defining anaphylaxis and immune complex disease 
are provided in Appendix E 2. 

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Participants will have had a pre-assessment (ie, vital signs) prior to IP administration. 
Participants should be observed in line with clinical practice after each IP administration for 
the appearance of any acute drug reactions. 
Serum tryptase or other blood or urine testing relevant to the diagnosis of anaphylaxis may be 
obtained at a local laboratory at the discretion of the Investigator. 
8.4 
Overdose 
For this study, any administration greater than 200 mg of benralizumab will be considered an 
overdose. 
There is no specific treatment for an overdose with benralizumab. If overdose occurs, the 
participant should be treated supportively with appropriate monitoring as necessary. 
• 
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the case report form (CRF) and on the Overdose CRF module. 
• 
An overdose without associated symptoms is only reported on the Overdose CRF module. 
 
If an overdose on an AstraZeneca IP occurs in the course of the study, then the Investigator or 
other site personnel inform the AstraZeneca representative immediately, or no later than 24 
hours of when he or she becomes aware of it. 
The AstraZeneca representative works with the Investigator to ensure that all relevant 
information is provided to the AstraZeneca Patient Safety data entry site. 
For overdoses associated with an SAE, the standard reporting timelines apply, see 
Section 8.3.2. For other overdoses, reporting must occur within 30 days. 
8.5 
Human Biological Samples 
Instructions for the collection and handling of biological samples will be provided in the study 
specific laboratory manual. Samples should be stored in a secure storage space with adequate 
measures to protect confidentiality. For further details on Handling of Human Biological 
Samples, refer to Appendix C. 
Samples will be stored for a maximum of 15 years from the date of the issue of the CSR in 
line with consent/assent and local requirements, after which they will be destroyed/repatriated.  
• 
PK samples will be disposed of after the Bioanalytical Report finalization or 6 months 
after issuance of the draft Bioanalytical Report (whichever is earlier), unless 
consented/assented for future analyses. 
− 
PK samples may be disposed of or anonymized by pooling. Additional analyses may 
be conducted on the anonymized, pooled PK samples to further evaluate and validate 

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the analytical method. Any results from such analyses may be reported separately 
from the CSR. 
• 
Remaining ADA sample aliquots will be retained at AstraZeneca or its designee for a 
maximum of 15 years following issue of the CSR. Additional use includes but is not 
limited to further characterization of any ADAs, confirmation and/or requalification of 
the assay as well as additional assay development work. The results from future analysis 
will not be reported in the CSR. 
 
8.5.1 
Pharmacokinetics 
All PK samples will be collected before administration of IP according to the SoA (Table 3). 
Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
AstraZeneca and site study files but will not constitute a protocol amendment. The IRB/IEC 
will be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 
For the PK analysis, it is important that the date, time, and location of each SC injection is 
recorded for each participant. 
Instructions for sample collection, processing, storage, and shipment are provided in the 
Laboratory Manual. 
Full details of the analytical method used will be described in a separate Bioanalytical 
Validation Report. 
8.5.1.1 
Determination of Drug Concentration 
Samples for determination of benralizumab concentration in serum will be assayed by 
bioanalytical test sites operated by or on behalf of AstraZeneca, using an appropriately 
validated bioanalytical method. Full details of the analytical method used will be described in 
a separate report. Only samples from the benralizumab treatment arm will be analyzed. 
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate Bioanalytical Report. 

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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. 2  
I m m u n o ge nicit y Assess me nts 
Bl o o d sa m ples f or deter mi nati o n of A D A i n ser u m will be assa ye d at t he discreti o n of 
Astra Ze neca b y bi oa nal ytical test sites o perate d b y or o n be half of Astra Ze neca, usi n g a n 
a p pr o priatel y vali date d bi oa nal ytical met h o d. F ull details of t he met h o ds us e d will be 
descri be d i n a se parate re p ort.  
A D A sa m ples ma y als o be f urt her teste d f or c haracterizati o n of t he A D A res p o nse.  
Sa m ples will be c ollecte d, la bele 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.  
8. 5. 3  
P h ar m ac o d y n a mics  
Bl o o d a n d tiss ue e osi n o p hil a n d bas o p hil le vels are a n i m p orta nt mar ker of t he P D effect of 
be nraliz u ma b a n d bl o o d le vels will be assesse d as part of t he he mat ol o g y safet y testi n g 
( Secti o n 8. 2. 1 ). 
 
 
8. 6  
H u m a n Bi ol o gic al S a m ple Bi o m ar kers  
8. 6. 1  
C ollecti o n of M a n d at or y S a m ples f or Bi o m ar ker A n al ysis  
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Cli nical  St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
Detaile d i nstr ucti o ns f or c ollecti o n of t hese sa m ples are pr o vi de d i n t he La b orat or y Ma n ual.  
8. 6. 2  
C ollecti o n of A d diti o n al Bi o m ar ker S a m pl es 
C CI
C CI

Cli nical St u d y Pr ot oc ol  
Astra Ze neca  
Be nraliz u ma b  - D 3 2 5 6 C 0 0 0 0 1  
0 4 Ma 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  
 
•  
 
Detaile d i nstr ucti o ns f or c ollecti o n of t hese sa m ples are pr o vi de d i n t he La b orat or y Ma n ual.  
8. 6. 3  
St or a ge, Re -use a n d Destr ucti o n of Bi o m ar ker S a m ples  
8. 7  
O pti o n al Ge n o mics I niti ati ve S a m ple  
8. 8  
He alt hc are Res o urce Utiliz ati o n  
A D -relate d healt hcare res o urce utilizati o n i nf or mati o n will be c ollecte d b y t he I n vesti gat or, or 
desi g nee, i n acc or da nce wit h t he S o A ( Ta ble 3 ) a n d rec or de d i n t he a p pr o priate e C R F m o d ule. 
Pr ot oc ol -ma n date d pr oce d ures, tests, a n d e nc o u nters are n ot i ncl u de d.  
At ra n d o mizati o n, retr os pect i ve A D-relate d healt hcare res o urce utilizati o n i nf or mati o n will be 
c ollecte d wit h a o ne -year recall peri o d. At all s u bse q ue nt visits, A D -relate d healt hcare 
res o urce utilizati o n i nf or mati o n will be c ollecte d wit h a recall peri o d of ‘si nce last sc he d ule d 
vis it’. 
T he data c ollecte d ma y be use d t o c o n d uct e x pl orat or y ec o n o mic a nal yses a n d i ncl u de:  
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• 
Number and duration of hospitalization (length of stay, overall and by wards [eg, general 
ward, intensive care unit]) 
• 
Number and type of diagnostic and therapeutic tests and procedures 
• 
Number of outpatient medical encounters and interventions (including GP, specialists, or 
emergency room visits, and medications) 
 
Note: Cases of hospitalization occurring after signing of the ICF must be reported as an SAE 
(Section 8.3). 
9 
STATISTICAL CONSIDERATIONS 
The primary DBL will occur after all randomized participants have completed the initial 16-
week treatment period. The final DBL will occur when all participants have completed the 52-
week treatment period and/or the IPD/end-of-treatment/Week 60 follow-up visit. An 
additional analysis may be performed between the primary and final DBLs, to report data 
accumulating during the extension part of the study if needed to support end of Phase 2 
decision making. Participants and investigators will remain blinded to the dosing regimens 
until the final DBL. 
The CSR will be based on the final DBL and will include all data for the study. 
9.1 
Statistical Hypotheses 
The primary endpoint is the proportion of participants with IGA 0/1 (ie, clear or almost clear) 
and a decrease in IGA of 2 or more points at Week 16, relative to baseline. The null 
hypothesis is: the proportion of participants on benralizumab 30 mg Q4W is equal to the 
proportion of participants on placebo. Whereas, the alternative hypothesis is: the proportion of 
participants on benralizumab 30 mg Q4W is not equal to the proportion of participants on 
placebo. That is, 
H0: Difference in proportions (benralizumab 30 mg Q4W – placebo) = 0 
H1: Difference in proportions (benralizumab 30 mg Q4W – placebo) ≠ 0 
The first and third key secondary endpoints are derived from the EASI and they are: the 
proportion of patients with EASI-75 at Week 16; and the proportion of participants with 
EASI-90 at Week 16. The second key secondary endpoint is the proportion of participants 
with an improvement of 4 or more points in peak pruritus weekly score at Week 16, relative to 
baseline. For each of these endpoints, the null hypothesis is: the proportion of participants on 
benralizumab 30 mg Q4W is equal to the proportion of participants on placebo. Whereas, the 
alternative hypothesis is: the proportion of participants on benralizumab 30mg Q4W is not 
equal to the proportion of participants on placebo.  That is, 

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H0: Difference in proportions (benralizumab 30 mg Q4W – placebo) = 0 
H1: Difference in proportions (benralizumab 30 mg Q4W – placebo) ≠ 0 
For the primary and key secondary endpoints, the primary estimand will be based on the full 
analysis set (Table 12). Intercurrent events will consist of participants who withdraw from the 
study or require rescue therapy (defined in Section 6.5.3). The primary estimand will regard 
these participants as non-responders from the time such events occur up to Week 16. A 
participant with missing data at a specific time point will also be considered as a non-
responder at that time point. 
Hypothesis testing for the primary and key secondary endpoints will be based on a 2-sided test 
and carried out using a 5% significance level. If a p-value is less than 0.05, the treatment 
effect favors benralizumab 30 mg Q4W and the decision will be to reject the null hypothesis 
(H0) and the alternative hypothesis (H1) will be accepted. 
A hierarchical testing procedure will be used to control the overall Type I error rate at 5% 
across the primary and key secondary endpoints (Section 9.4.2). The variables will be tested 
sequentially in the following order using a 2-sided test and a 5% significance level: 
1 
Proportion of participants with IGA 0/1 (ie, clear or almost clear) and a decrease in IGA 
of 2 or more points at Week 16, relative to baseline 
2 
Proportion of participants with EASI-75 at Week 16 
3 
Proportion of participants with an improvement of 4 or more points in peak pruritus 
weekly score at Week 16, relative to baseline 
4 
Proportion of participants with EASI-90 at Week 16 
 
9.2 
Sample Size Determination 
As a minimum, approximately 160 participants will be recruited into the study and will be 
randomized to one of the following treatment sequences in a ratio of 1:1:2 (respectively):  
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q4W administered until Week 52 (n = 40) 
• 
Benralizumab 30 mg Q4W until Week 16, followed by an extension period with 
benralizumab 30 mg Q8W administered until Week 52 (n = 40) 
• 
Placebo Q4W until Week 16, followed by an extension period with benralizumab 30 
mg Q4W administered until Week 28, and then benralizumab 30 mg Q8W administered 
until Week 52 (n = 80). 
 
For the initial 16-week treatment period, the aim is to recruit a minimum of 80 participants 
into the placebo group and a minimum of 80 participants into the benralizumab 30 mg Q4W 

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group. (Note that participants who receive benralizumab 30 mg Q4W during the first 16 
weeks will be grouped together and considered as a single treatment group.)  
To identify responding subpopulations, the randomization will be stratified by age (≥ 12 to 
< 18 years and ≥ 18 years) and baseline blood eosinophils (< 300 cells/μL, ≥ 300 cells/μL). In 
total, the aim is to recruit a minimum number of participants per strata across the treatment 
groups as outlined in Table 11. 
Table 11 
Randomization Stratification 
 
Baseline blood eosinophils 
< 300 cells/μL 
≥ 300 cells/μL 
Adolescents (≥ 12 to < 18 years), n 
30 
50 
Adults (≥ 18 years), n 
30 
50 
n, number 
 
The study will continue to recruit participants until the minimum number of participants per 
strata is achieved, up to a maximum of 200 patients in total. The purpose of this method of 
recruitment is to ensure that a broad distribution of participants is recruited across the range of 
ages and blood eosinophil levels to allow potential identification of responding subpopulations 
and appropriate cut-offs for future studies, if necessary. 
The sample size calculations that follow are based on the primary endpoint, ie, the proportion 
of patients with an IGA 0/1 and a decrease in IGA of ≥ 2 points relative to baseline. The 
calculations are associated with differences between benralizumab 30 mg Q4W and placebo at 
Week 16 during the initial double-blind, placebo-controlled phase of the study (Figure 2). For 
the primary analysis, the sample size calculation will power the study to detect a difference 
between benralizumab 30 mg Q4W and placebo in the overall population. Additional 
calculations have been provided to ensure that the study is adequately powered to detect 
treatment differences and consistency of effect in potential subgroups, should efficacy be 
limited to a subset of the population. 
Primary analysis:  In the overall population, a minimum of 80 participants per treatment group 
will provide a high level of power (> 95%) to detect a 30% difference between benralizumab 
30 mg Q4W and placebo for the primary endpoint. This calculation is based on a 2-sided test 
and a 5% significance level and assumes a response rate of 40% for benralizumab 30 mg 
Q4W and 10% for placebo.   
Subgroup analyses:  As a benchmark, a minimum of 35 participants per treatment will provide 
at least 80% power to detect a 30% difference between benralizumab 30 mg Q4W and 
placebo. (As for the primary analysis, these calculations are based on a 2-sided test and a 5% 

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significance level, and assumes the same response rates for benralizumab 30 mg Q4W and 
placebo.) Thus, there is a high probability of detecting differences between treatments in the 
baseline blood eosinophils ≥ 300 cells/μL subgroup (with 50 participants per treatment), in the 
adult subgroup (with 40 participants per treatment), and in the adolescent subgroup (with 40 
participants per treatment). Note that in the baseline blood eosinophils < 300 cells/μL 
subgroup, 30 participants per treatment group will provide an adequate amount of data to 
explore treatment differences, and will allow different cut-offs between ‘low’ and ‘high’ 
eosinophils at baseline to be assessed. 
Assessing consistency of effect:  Consistency of effect will be assessed between adult and 
adolescent participants in the overall population and in any identified subgroup for baseline 
blood eosinophils. By aiming for 25 adults and 25 adolescents per treatment in the baseline 
blood eosinophils ≥ 300 cells/μL subgroup, the probability of detecting consistent effects 
between adults and adolescents is high. That is, assuming the true increase in response rate 
between benralizumab 30 mg Q4W and placebo is 30%, there is > 85% chance of observing a 
treatment difference for adolescents of at least half of the treatment difference observed for 
adults. 
9.3 
Populations for Analyses 
The populations for purposes of analyses are defined in Table 12: 
Table 12 
Populations for Analyses 
Population 
Description 
All participants analysis set  
All participants who sign the ICF 
Full analysis set 
The full analysis set will comprise all randomized participants who receive 
at least one dose of IP, irrespective of their protocol adherence and 
continued participation in the study. Participants will be analyzed according 
to their randomized treatment irrespective of whether or not they were 
prematurely discontinued, according to the ITT principle. Data for 
participants who withdraw consent/assent to participate in the study will be 
included up to the date of permanent discontinuation. 
Safety analysis set 
The safety analysis set will comprise all participants who receive at least 
one dose of IP. Erroneously-treated participants (eg, those randomized to 
treatment A but actually given treatment B) are accounted for in this 
analysis set by assigning them to the treatment they actually received. A 
participant who receives at least one dose of active IP will be classified as 
active and included in the active IP treatment group/sequence. Safety and 
ADA data will be based on this analysis set and for whom any post-dose 
data are available. 

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Table 12 
Populations for Analyses 
Population 
Description 
Pharmacokinetic analysis set 
All participants who received benralizumab and from whom PK blood 
samples are assumed not to be affected by factors such as protocol 
violations (eg, received wrong dose) and who had at least one quantifiable 
serum PK observation post first dose. All PK summaries will be based on 
this analysis set. 
Placebo-to-benralizumab 
extension analysis set 
All participants who received benralizumab at the start of the extension 
period who were previously on placebo. 
ADA, Anti-drug antibodies; ICF, Informed consent/assent form; IP, Investigational product; ITT, Intent-to treat; 
PK, Pharmacokinetic. 
 
9.4 
Statistical Analyses 
A comprehensive statistical analysis plan (SAP) will be developed and finalized prior to the 
primary DBL and will include a more technical and detailed description of the statistical 
analyses described below. The SAP will describe the participant populations to be included in 
the analyses and the procedures for accounting for missing, unused, and spurious data. Any 
deviations from this plan will be reported in the CSR. 
This section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
All personnel involved in the analyses of the study will remain blinded until the primary DBL 
and protocol deviations are identified. 
Analyses will be performed by AstraZeneca or its representatives. 
Categorical variables will be summarized using frequency and percentages, where the 
denominator for calculation is the underlying analysis set population unless otherwise stated. 
Continuous variables will be summarized with descriptive statistics of number of available 
observations, mean, standard deviation, median, minimum and maximum, and quartiles where 
more appropriate. 
All point estimates will be presented together with 95% confidence intervals. Nominal p-
values, corresponding to a 2-sided test, will be presented for comparisons between treatments. 
Methods for controlling multiplicity across the primary and key secondary endpoints are 
discussed in Section 9.4.6. 
9.4.1 
General Considerations 
The primary analysis will be based on the initial 16-week, double-blind, placebo-controlled 
phase of the study, and will compare 2 treatment groups comprising all participants 

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randomized to benralizumab 30 mg Q4W until Week 16 (n = 80) and all participants 
randomized to placebo until Week 16 (n = 80). 
The primary estimand will be based on participants in the full analysis set (Table 12) and will 
be used for the analysis of primary and key secondary endpoints. The set of incurrent events 
for this estimand consists of participants who withdraw from the study and participants who 
require rescue therapy (refer to Section 6.5.3). The primary estimand will regard these 
participants as non-responders from the time such events occur up to Week 16. The amount of 
missing data for this study is expected to be low, as participants who prematurely discontinue 
IP will be asked to come in for all visits and complete all study assessments up to the end of 
the study. Any participant with missing data at a specific time point will be considered as a 
non-responder at that time point. 
Additional estimands will be specified in the SAP for the primary and key secondary 
endpoints to carry out sensitivity analyses for assessing the robustness of results. These 
sensitivity analyses will explore different methods for handling intercurrent events and 
different assumptions for missing data. Estimands for secondary, exploratory, and tertiary 
endpoints will also be specified in the SAP, which will include how intercurrent events will be 
handled for continuous endpoints. Sensitivity analyses may be carried out for specific 
secondary endpoints, if deemed necessary to strengthen conclusions drawn from the primary 
and key secondary endpoints. Full details will be provided in the SAP. 
Full details of the analyses and methods to be used for the extension period will be provided in 
the SAP. 
Demography and baseline characteristics will be summarized by treatment for the Full 
Analysis Set (FAS). If there are major differences between the FAS and safety analysis set, 
the summaries will also be repeated and presented for the safety analysis set. 
9.4.2 
Efficacy 
9.4.2.1 
Primary Endpoint 
Proportion of Patients with Skin Clearance at Week 16 Using the IGA Data 
The primary endpoint is a binary response that classifies a participant’s skin clearance at 
Week 16 using the IGA score. Participants will be classified as responders if IGA 0/1 (ie, 
clear or almost clear) and they have a decrease in IGA of 2 or more points relative to baseline. 
Otherwise, participants will be classified as non-responders. 
For the primary analysis, a logistic regression model will be fitted to the primary endpoint 
using a logit link function. The model will include treatment group and baseline covariates for 
age (adolescents; adults) and blood eosinophils (< 300 cells/μL; ≥ 300 cells/μL). Sensitivity 
analyses may also explore the effect of including baseline covariates such as severity of 

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disease (moderate; severe), presence of staphylococcus aureus (absent; present) and asthma 
comorbidity (yes; no). The model will be used to estimate the proportion of responders for 
benralizumab and placebo, the difference between these proportions (benralizumab – placebo) 
and an odds ratio, with corresponding 95% confidence limits. A p-value, corresponding to a 2-
sided test, will be presented to compare the benralizumab and placebo treatment groups. Note 
that if the logistic regression model does not converge to a solution due to low response rates 
in certain strata, these data will be analyzed using a Cochran–Mantel–Haenszel test. 
To support this analysis, the observed proportion of responders will be summarized using 
descriptive statistics by treatment group and each scheduled visit up to Week 16. Full details 
will be provided in the SAP. 
9.4.2.2 
Key Secondary Endpoints 
Proportion of Patients with Skin Clearance at Week 16 Using the EASI Data 
The first and third key secondary endpoints are binary responses that classify a participant’s 
skin clearance at Week 16 using the EASI:  
• 
EASI-75 response rate: Participants will be classified as responders if they achieve at 
least a 75% reduction from baseline in their EASI score at Week 16. Otherwise, 
participants will be classified as non-responders. 
• 
EASI-90 response rate: Participants will be classified as responders if they achieve at 
least a 90% reduction from baseline in their EASI score at Week 16. Otherwise, 
participants will be classified as non-responders. 
 
The statistical analysis described for the primary analysis will be carried out for these key 
secondary endpoints. To support this analysis, the observed proportion of responders will be 
summarized for each endpoint using descriptive statistics by treatment group and each 
scheduled visit up to Week 16. Full details will be provided in the SAP. 
Proportion of Patients with Itch at Week 16, Using the Peak Pruritus Numerical Rating Scale 
(NRS) Data 
The second key secondary endpoint is a binary response that will classify a participant as a 
responder if there is an improvement of 4 or more points in peak pruritus weekly score at 
Week 16 relative to baseline. Otherwise, participants will be classified as a non-responder.  
(Note that daily peak pruritus scores are averaged to give a weekly score.) 
The statistical analysis described for the primary analysis will be carried out for this key 
secondary endpoint. To support this analysis, the observed proportion of responders will be 
summarized using descriptive statistics by treatment group and each scheduled visit up to 
Week 16. Full details will be provided in the SAP. 

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Note that a hierarchical testing procedure will be used to control the overall Type I error rate 
at 5% across the primary and key secondary endpoints. Refer to Section 9.4.6 for more details. 
9.4.2.3 
Secondary Endpoints 
Proportion of Patients with Skin Clearance at Week 16 Using the EASI Data 
Two additional binary responses that classify a participant’s skin clearance at Week 16 will be 
derived from the EASI:  
• 
EASI-50 response rate: Participants will be classified as responders if they achieve at 
least a 50% reduction from baseline in their EASI score at Week 16. Otherwise, 
participants will be classified as non-responders. 
• 
EASI-100 response rate: Participants will be classified as responders if they achieve at 
least a 100% reduction from baseline in their EASI score at Week 16. Otherwise, 
participants will be classified as non-responders. 
 
The statistical analysis described for the primary analysis will be carried out for each of these 
endpoints. (The p-values will be nominal, as secondary objectives are not controlled for 
multiplicity and do not appear in the testing hierarchy.) To support this analysis, the observed 
proportion of responders will be summarized for each endpoint using descriptive statistics by 
treatment group and each scheduled visit up to Week 16. Full details will be provided in the 
SAP. 
Assessing Changes in Atopic Dermatitis at Week 16 Using the EASI 
The EASI is a continuous outcome that will be completed at the visits specified in the SoA 
(Table 3) during the initial 16-week treatment period. This endpoint will be analyzed by a 
Mixed Model Repeated Measures (MMRM) model. 
The model will include change from baseline as the dependent variable (derived for each 
participant and every scheduled visit up to Week 16); baseline as a continuous covariate; 
treatment, age (adolescents; adults), baseline blood eosinophils (< 300 cells/μL; ≥ 300 cells/μL) 
and visit as categorical covariates; treatment-by-visit as an interaction term. An unstructured 
variance-covariance matrix will be used to model within-subject errors, and the Kenward-
Roger approximation will be used to estimate denominator degrees of freedom and to adjust 
standard errors.  (If the model fails to converge, alternative variance-covariance models will 
be tried in the following order: Toeplitz, first-order regressive, compound symmetry.) For 
each visit, the model will be used to estimate the mean change from baseline for each 
treatment group and the difference versus placebo, with corresponding 95% confidence limits. 
A p-value, corresponding to a 2-sided test, will be presented to compare the benralizumab and 
placebo treatment groups at each visit. (The p-values will be nominal, as secondary objectives 
are not controlled for multiplicity and do not appear in the testing hierarchy.)  

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The distributional assumptions of the MMRM model will be checked by examining plots of 
residuals. If the residuals suggest that it is unreasonable to assume that data follow a Normal 
distribution (eg, data are skewed and the constant variance assumption is not met), alternative 
models will be explored. For example, data may be log transformed prior to fitting the model, 
or a non-parametric method may be deemed more appropriate.  
To support this analysis, observed means and mean changes from baseline will be summarized 
using descriptive statistics by treatment group and each scheduled visit up to Week 16. Full 
details will be provided in the SAP. 
Assessing Itch at Week 2, Using the Peak Pruritus Numerical Rating Scale (NRS) Data 
Daily peak pruritus scores are continuous outcomes that will be averaged for each participant 
to give a value at baseline and values for Week 1 through to Week 16 (inclusive) during the 
initial 16-week treatment period. The statistical analysis described above for the EASI will be 
carried out for this secondary endpoint, where the same MMRM model will be fitted to these 
data. To support this analysis, observed means and mean changes from baseline will be 
summarized using descriptive statistics by treatment group and each timepoint up to Week 16. 
Full details will be provided in the SAP. 
Assessing Skin Severity at Week 16, Using the Patient Orientated Eczema Measure data 
The POEM is a continuous outcome that will be completed at the visits specified in the SoA 
(Table 3) during the initial 16-week treatment period. The statistical analysis described above 
for the EASI will be carried out for this secondary endpoint, where the same MMRM model 
will be fitted to these data. To support this analysis, observed means and mean changes from 
baseline will be summarized using descriptive statistics by treatment group and each 
scheduled visit up to Week 16. Full details will be provided in the SAP. 
Assessing Quality of Life at Week 16, Using the Dermatology Life Quality Index and the 
Children’s Dermatology Life Quality Index 
The DLQI and CDLQI are continuous outcomes that will be completed by participants aged 
> 16 years and ≤ 16 years (respectively) at the visits specified in the SoA (Table 3) during the 
initial 16-week treatment period. The statistical analysis described above for the EASI will be 
carried out for each of these secondary endpoints, where the same MMRM model will be 
fitted to DLQI and CDLQI separately. To support these analyses, observed means and mean 
changes from baseline will be summarized for DLQI and CDLQI using descriptive statistics 
by treatment group and each scheduled visit up to Week 16. Full details will be provided in 
the SAP. 
Assessing Atopic Dermatitis at Week 16, Using the SCORAD Index 
SCORAD is a continuous outcome that will be completed at the visits specified in the SoA 
(Table 3) during the initial 16-week treatment period. The statistical analysis described above 
for the EASI will be carried out for this secondary endpoint, where the same MMRM model 

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will be fitted to these data. To support this analysis, observed means and mean changes from 
baseline will be summarized using descriptive statistics by treatment group and each 
scheduled visit up to Week 16. Full details will be provided in the SAP. 
Assessing the Efficacy of Q8W Relative to Q4W Dosing Out to Week 52 
The long-term efficacy of the Q8W dosing regimen will be assessed against the Q4W dosing 
regimen as the benchmark.  The efficacy endpoints described above will be assessed until 
Week 52, where trends over time will be assessed for the 3 treatment sequences described in 
Section 4.2.   
The focus of this analysis will assess results at Week 52 for participants that (i) remain on 
benralizumab 30 mg Q4W throughout the study and (ii) switch from benralizumab 30 mg 
Q4W to benralizumab 30 mg Q8W at Week 16. The third group of participants that receive 
placebo followed by benralizumab at Week 16 will also be presented in the analyses; 
however, they will not be formally compared against the other 2 treatment sequences. Results 
observed at Week 52 will be interpreted relative to changes already observed at Week 16 to 
assess if preliminary efficacy appears to be maintained with either treatment regimen.  
Primarily, long-term efficacy will be assessed using the EASI, which is a continuous endpoint 
measured at baseline and at scheduled visits during the study until Week 52 (Table 3). Change 
from baseline values will be derived for every scheduled visit up to Week 52 and analysed by 
an MMRM model, which will include the 3 treatment sequences as a categorical covariate.  
Similar analyses may be performed for additional efficacy endpoints. Full details will be 
provided in the SAP. 
9.4.2.4 
Tertiary/exploratory Endpoints 
Analyses for exploratory objectives will be specified in the SAP or in an exploratory analysis 
plan. 
9.4.3 
Safety Analyses 
Safety analyses will be performed using the safety analysis set. Analyses will be presented for 
the overall study period divided by the 3 treatment sequences and presented separately for the 
first 16 weeks comparing the single benralizumab group with placebo. 
Participants will be analyzed according to the treatment they received.  
In general, the baseline value for statistical analysis is the last non-missing value prior to 
administration of the first dose of IP. Details will be described in the SAP. 

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Adverse Events 
Adverse events will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA) that will have been released for execution at 
AstraZeneca/designee. 
Safety data will be presented using descriptive statistics unless otherwise specified in the SAP. 
Adverse events will be presented for each treatment by system organ class and preferred term, 
including the number and percentage of participants reporting at least one event, number of 
events and exposure-adjusted rates, where appropriate. 
An overview of AEs will be presented for each treatment, including the number and 
percentage of participants with any AE, AEs with outcome of death, serious AEs, and AEs 
leading to discontinuation of IP. 
Separate AE tables will be provided taking into consideration the relationship as to IP 
assessed by the Investigator, maximum intensity, seriousness, death and events leading to 
discontinuation of IP, as well as other action taken related to IP. 
Key participant information will be presented for participants with AEs with outcome of 
death, serious AEs, and AEs leading to discontinuation of IP. 
An AE listing for the safety analysis set will cover details for each individual AE. 
Full details of AE analyses will be provided in the SAP. 
Treatment Emergent 
The following events are considered treatment emergent: 
• 
Adverse events with an onset date on or after the first dose of IP 
• 
Worsening of pre-existing events on or after first dose of IP 
 
Clinical Laboratory Safety Assessments 
Laboratory data for hematology and clinical chemistry will be summarized. The frequency of 
changes with respect to normal ranges between baseline and each post-treatment time point 
will be tabulated. Frequencies of clinically noteworthy values (defined in the SAP) occurring 
during the clinical study will also be given. Shifts from normal to abnormal between baseline 
and each post-baseline time point will be evaluated for urinalysis. 

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Vital Signs 
Vital sign parameters will be presented for each treatment. Summary statistics for continuous 
variables cover n, mean, standard deviation, Minimum, Q1, median, Q3, and Maximum.  
Frequency tables cover number and percentage of participants in the respective category. 
For each scheduled post-baseline visit, descriptive statistics for all vital sign parameters will 
be presented for observed values and change from baseline. 
Changes in vital signs will be examined at each visit. Frequencies of clinically noteworthy 
values (defined in the SAP) occurring during the clinical study will be presented. 
Details of vital sign analyses will be provided in the SAP. 
Physical Examination 
Shifts from normal to abnormal between baseline and follow-up will be evaluated for the 
physical examination. 
9.4.4 
Immunogenicity Analyses 
Anti-drug antibodies to benralizumab will be summarized using descriptive statistics at each 
visit by treatment. The ADA titres-time profiles of benralizumab may be generated. The 
impact of ADA on PK and eosinophil level will be assessed. The potential association of 
ADA with safety and efficacy will be evaluated. Further details will be provided in the SAP. 
9.4.5 
Other Analyses 
Pharmacokinetic and PD exploratory analyses will be described in the SAP, or in an 
exploratory SAP, which will be finalized before DBL. 
9.4.5.1 
Skin Photography 
To support clinical efficacy assessments, skin photography will be performed and these results 
will be compared with in-person completed clinical assessments.  
Treatment effects for efficacy endpoints when informed by photography assessments may be 
compared to those based on in-person efficacy assessments. Concordance between 
photography efficacy assessments and in-person assessments for a given endpoint/visit will be 
summarized as appropriate. Details will be specified in the SAP. 
9.4.6 
Methods for Multiplicity Control 
A hierarchical testing procedure will be used to control the overall Type I error rate at 5% 
across the primary and key secondary endpoints. The variables will be tested sequentially in 
the following order using a 2-sided test and a 5% significance level: 

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1 
Proportion of participants with IGA 0/1 (ie, clear or almost clear) and a decrease in IGA 
of 2 or more points at Week 16, relative to baseline 
2 
Proportion of participants with EASI-75 at Week 16 
3 
Proportion of participants with an improvement of 4 or more points in peak pruritus 
weekly score at Week 16, relative to baseline 
4 
Proportion of participants with EASI-90 at Week 16 
 
If the treatment comparison for (1) is statistically significant, testing will proceed to (2). If the 
treatment comparison for (2) is statistically significant, testing will proceed to (3). If the 
treatment comparison for (3) is statistically significant, testing will proceed to (4). If, at any 
point in this hierarchy, a null hypothesis cannot be rejected at the 5% significance level in 
favor of benralizumab, further testing will stop, and no subsequent null hypotheses will be 
rejected. 
9.4.7 
Sensitivity Analyses 
Sensitivity analyses will be explored to assess the robustness of treatment effects for the 
primary and key secondary endpoints.  Different missing data mechanisms (eg, values missing 
at random and values missing not at random) will be considered to assess the robustness of the 
treatment effect for these endpoints. The use of multiple imputation approaches will be 
considered.  Full details of the sensitivity analyses will be specified in the SAP and 
documented prior to the primary DBL. 
9.4.8 
Subgroup Analysis 
For the primary and secondary efficacy variables, subgroup analyses will be conducted to 
explore the consistency of the overall estimated treatment effect and will include (but not 
limited to) age and baseline blood eosinophils. Subgroup analyses will include assessing 
different cut-offs for baseline blood eosinophil levels to understand if benralizumab is 
effective in different responding subpopulations. Details of these analyses will be provided in 
the SAP.   
9.5 
Interim Analyses 
No formal interim analysis is planned for the study.  
The first set of analyses will be run at the primary DBL, which will occur after all randomized 
participants have completed the initial 16-week treatment period. The final set of analyses will 
be produced at the final DBL, which will occur when all participants have completed the 52-
week treatment period and/or the IPIPD/end-of-treatment/Week 60 follow-up visit. An 
additional analysis may be performed between the primary and final DBLs to report data 
accumulating during the extension part of the study if needed to support end of phase 2 

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decision making. Participants and investigators will remain blinded to the dosing regimens 
until the final DBL. 
9.6 
Data and Safety Monitoring Board 
An independent DSMB will be utilized for this study. The DSMB will provide oversight, with 
particular focus on the adolescent participants, to ensure safe and ethical conduct of the study. 
For details on the rationale for and the remit of the committee, refer to Appendix A 5. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 

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11 
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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 3 2 5 6c 0 0 0 0 1-cs p- v 3
D oc u me nt Title:
D 3 2 5 6 C 0 0 0 0 1 Cli nical St u d y Pr ot oc ol versi o n
D oc u me nt I D:
Versi o n L a bel:
3. 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
1 0- Ma y- 2 0 2 1 1 1: 3 1 U T C
C o nte nt A p pr o val
1 0- Ma y- 2 0 2 1 1 2: 3 3 U T C
Ma na ge me nt A p pr o val
1 0- Ma y- 2 0 2 1 1 6: 1 8 U T C
C o nte nt A p pr o val
1 0- Ma y- 2 0 2 1 1 5: 1 6 U T C
C o nte nt A p pr o val
N otes: ( 1) 
C CI
C CI
P P D