A Phase I, Open-label Study to Evaluate the Pharmacokinetics of Tezepelumab in Children ≥ 5 to 11 Years of Age With Mild, Moderate, or Severe Asthma (TRAILHEAD)
Phase: PHASE1
Conditions: Asthma
Sponsor: AstraZeneca

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
1
Clinical Study Protocol 
Study Intervention
Tezepelumab
Study Code
D5180C00025
Version
4.0
Date
06 January 2022
A Phase I, Open Label Study to Evaluate the Pharmacokinetics of 
Tezepelumab in Children ≥5 to 11 Years of Age with Mild, 
Moderate, or Severe Asthma (TRAILHEAD)
Sponsor Name: AstraZeneca
Legal Registered Address: AstraZeneca AB, 151 85 Södertälje, Sweden
Regulatory Agency Identifier Number(s):
2020-000554-97 (EudraCT)
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
Standard procedures. The Clinical Study Protocol is publicly registered, and the results are 
disclosed and/or published according to the AstraZeneca Global Policy on Bioethics and in 
compliance with prevailing laws and regulations. 

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2
P r ot oc ol N u m ber: D 5 1 8 0 C 0 0 0 2 5
A me n d me nt N u m ber: 3
St u d y  I nter ve nti on: Te ze pel u ma b
St u d y  P hase: P hase I
S h ort Title: A St u d y  t o E val uate t he P har mac o ki netics of T eze pel u ma b i n C hil dre n 
≥5 t o 1 1 Ye ars of A ge wit h Ast h ma
Me dic al M o nit or  N a me a n d C o nt act I nf or m ati o n will be pro vi de d se p ar atel y
N ati o n al C o- or di n ati n g I n vesti g at or:
U nite d Ki n g d o m
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E
D O C U M E N T HI S T O R Y
D oc u me nt
D ate
A me n d me nt 3 ( Versi o n 4. 0)
0 6 Ja n 2 0 2 2
A me n d me nt 2 ( Versi o n 3. 0)
1 3 Ma y  2 0 2 1
A me n d me nt 1 ( Versi o n 2. 0)
2 1 J ul y  2 0 2 0
Ori gi nal Pr ot oc ol ( Versi o n 1. 0)
2 5 Fe br uar y 2 0 2 0
A me n d me nt 3 ( 0 6 J a n u ar y 2 0 2 2)
T his a me n d me nt is c o nsi dere d t o be s u bsta nt ial base d o n t he cri t eria set f ort h i n Article 1 0(a) 
of  Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n. 
O ver al l R ati o n ale f or A me n d me nt 3:
T he rati o nale f or t his a me n d me nt is t o u p date safet y  inf or m at i on base d o n t he m ost rece nt 
I n vesti gat or’s Br oc h ure, Versio n 5. 0, date d 2 1 Oct 2 0 2 1 a n d t o incl u de a d di tio nal c ha n ges t o 
u p da t e i ncl usi on a n d e xcl usi o n cri t eria t o be more reflect i ve of t he cli nical c haracteristics of 
pae di atric s u bjects wit h mil d, mo derate, or se vere ast h ma w h o w o ul d be a p pr o priatel y s uite d 
f or a p har mac o ki netic ( P K) st u d y, w hilst mi ni misi n g ris ks t o t he partici pa nt a n d t o t he st u d y 
i nte grit y, a n d mai ntai ni n g c o mplia nce wi t h G o o d Cli nical Practice ( G C P).
P P D

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
3
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial/
Non-substantial
Version 4.0, 06 Jan 2022
Changes to the protocol are summarised below.
Section 1.1 
Synopsis
Updated location 
where 
TRAILHEAD will 
be conducted to 
include 
approximately 10 
study sites globally.
Additional sites to participate in 
TRAILHEAD in order to increase 
enrolment.
Substantial
Section 2.2 
Background
Section 2.3.2 
Benefit 
Assessment
Updated to reflect 
new information 
based on 
Investigator’s 
Brochure (IB) V 5.0
IB V5.0 has been updated to 
reflect new data from Phase 2 and 
Phase 3 asthma studies which were 
completed since the last IB update. 
Substantial
Section 4.1: 
Overall Design
Updated location 
where 
TRAILHEAD will 
be conducted to 
include 
approximately 10 
study sites globally
Additional sites to participate in 
TRAILHEAD in order to increase 
enrolment.
Substantial
Section 5.1 
Inclusion 
Criteria
Appendix F
Removed inclusion 
(Inclusion Criterion 
#12) for body mass 
index for age at 
both Screening and 
Day 1 that is 
between 5th and 
95th percentile and 
associated 
Appendix F
By allowing the full span of 
growth percentiles, this will aid in 
PK predictions that span across 
BMI ranges in this age group. This 
approach ensures a study 
population appropriate for a PK 
study.
Substantial
Section 5.2 
Exclusion 
Criteria
Changed exclusion 
(Exclusion 
Criterion #2) for 
history of a 
deterioration in 
asthma or asthma 
exacerbation that 
required a burst of 
systemic 
glucocorticosteroids 
within 3 months 
prior to Visit 1, up 
As systemic corticosteroid use 
does not impact tezepelumab PK 
levels and TRAILHEAD is not an 
efficacy study, prohibiting use of 
systemic corticosteroids for 
3 months prior to V1 is not 
required. This approach ensures a 
study population appropriate for a 
PK study.
Substantial

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
4
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial/
Non-substantial
to and including 
Visit 2 (Day 1) to 
decrease time 
restriction from 3 
months to 6 weeks. 
Section 5.2 
Exclusion 
Criteria
Changed exclusion 
(Exclusion 
Criterion #4) for 
history of 
hospitalisation 
(overnight 
admission) for 
asthma within 
6 months of Visit 1, 
up to and including 
Visit 2 (Day 1) to 
decrease time 
restriction from 
6 months to 
3 months.
To align with changes to other 
exclusion criteria while still 
ensuring safety and a study 
population appropriate for a PK 
study.
Substantial
Section 5.2 
Exclusion 
Criteria
Changed exclusion 
(Exclusion 
Criterion #6) for 
systemic 
corticosteroid use 
for the maintenance 
treatment of asthma 
within 3 months of 
Visit 1, up to and 
including Visit 2 
(Day 1) and 
discouraged until 
EOS to decrease 
time restriction 
from 3 months to 
6 weeks.
To align with changes to other 
exclusion criteria while still 
ensuring safety and a study 
population appropriate for a PK 
study.
Substantial
Section 5.2
Exclusion 
Criteria
Addition of 
Exclusion Criterion 
(#33) Receipt of 
any COVID-19 
vaccine 28 days 
prior to Visit 2 
(Day 1).
To provide guidance to 
Investigators regarding permitted 
timing for COVID-19 vaccination.
Substantial

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
5
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial/
Non-substantial
Table 1 
Schedule of 
Activities
Section 2.3.1.3 
COVID-19 
Risk 
Mitigations
Section 5.2 
Exclusion 
Criteria
Table 8 Volume 
of Blood to be 
Drawn from 
each Subject
Table 9 
Laboratory 
Safety 
Variables
Section 8.2.5.2 
COVID- 19 
Testing
Updated to reflect 
Coronavirus 
Disease 2019 
(COVID-19) 
antibody testing 
will no longer be 
required (Exclusion 
Criterion #23) and 
added additional 
criteria (Exclusion 
Criteria #31 and 
#32) to exclude 
participants who 
have had a 
confirmed COVID-
19 infection and 
have not fully 
recovered for at 
least 8 weeks prior 
to Visit 1 and those 
participants with a 
history of severe 
COVID-19 
infection requiring 
hospitalization.
COVID-19 antibody testing has 
been removed, as vaccine 
development in this age group is 
moving forward, making antibody 
testing for exclusion criteria 
clinically irrelevant and additional 
information is available regarding 
MIS-C. New exclusion criterion to 
confirm absence of COVID-19 
infection in recent past. This 
approach will ensure participant 
safety and simplify procedures for 
study participants and sites. 
Substantial
Table 5
Restricted 
Medications
COVID-19 
vaccination added 
to allow 
administration 
during study 
conduct (within 28 
days before and 14 
days after IP 
administration/Visit 
2)
To provide guidance to 
Investigators regarding permitted 
timing for COVID-19 vaccination
Section 8.6
Human 
Biological 
Sample 
Biomarkers
Updated to reflect 
that serum samples 
will be collected to 
be analysed for 
total 
immunoglobulin E.
Updated to correct an omission.

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
6
TABLE OF CONTENTS
TITLE PAGE........................................................................................................................ 1
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 2
TABLE OF CONTENTS ...................................................................................................... 6
1
PROTOCOL SUMMARY ................................................................................ 10
1.1
Synopsis ........................................................................................................... 10
1.2
Schema............................................................................................................. 13
1.3
Schedule of Activities ....................................................................................... 14
2
INTRODUCTION............................................................................................ 17
2.1
Study Rationale ................................................................................................ 17
2.2
Background ...................................................................................................... 17
2.3
Benefit/Risk Assessment................................................................................... 21
2.3.1
Risk Assessment ............................................................................................... 21
2.3.1.1
Study Conduct During COVID-19 Pandemic.................................................... 21
2.3.1.2
Requirements During the COVID-19 Pandemic................................................ 21
2.3.1.3
COVID-19 Risk Mitigations ............................................................................. 22
2.3.2
Benefit Assessment........................................................................................... 26
2.3.3
Overall Benefit: Risk Conclusion...................................................................... 26
3
OBJECTIVES AND ENDPOINTS................................................................... 27
4
STUDY DESIGN ............................................................................................. 28
4.1
Overall Design.................................................................................................. 28
4.2
Scientific Rationale for Study Design ............................................................... 28
4.3
Justification for Dose........................................................................................ 29
4.4
End of Study Definition.................................................................................... 29
5
STUDY POPULATION.................................................................................... 29
5.1
Inclusion Criteria .............................................................................................. 30
5.2
Exclusion Criteria ............................................................................................. 31
5.3
Lifestyle Considerations ................................................................................... 33
5.3.1
Meals and Dietary Restrictions ......................................................................... 33
5.3.2
Activity............................................................................................................. 33
5.4
Screen Failures ................................................................................................. 33
6
STUDY INTERVENTION ............................................................................... 34
6.1
Study Intervention(s) Administered................................................................... 34
6.1.1
Investigational Product ..................................................................................... 34
6.2
Preparation/Handling/Storage/Accountability of Interventions.......................... 35
6.2.1
Dose Preparation............................................................................................... 36
6.2.2
Dose Administration ......................................................................................... 37
6.2.3
Procedures for Handling Incorrectly Enrolled Subjects ..................................... 38

Clinical Study Protocol – 4.0
AstraZeneca
Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
8
8.4
Overdose .......................................................................................................... 58
8.5
Human Biological Samples............................................................................... 58
8.5.1
Pharmacokinetics.............................................................................................. 59
8.5.1.1
Pharmacokinetic Drug Assays........................................................................... 59
8.5.2
Immunogenicity Assessments ........................................................................... 59
8.5.2.1
Immunogenicity Testing.................................................................................... 59
8.5.3
Pharmacodynamics........................................................................................... 60
8.6
Human Biological Sample Biomarkers (Not applicable) ................................... 60
8.7
Optional Genomics Initiative Sample (Not applicable)...................................... 60
8.8
Health Economics (Not applicable)................................................................... 60
8.9
Pandemic Impact Assessment ........................................................................... 60
9
STATISTICAL CONSIDERATIONS................................................................ 61
9.1
Statistical Hypotheses....................................................................................... 61
9.2
Sample Size Determination............................................................................... 61
9.3
Populations for Analyses................................................................................... 61
9.4
Statistical Analyses ........................................................................................... 61
9.4.1
General Considerations..................................................................................... 61
9.4.2
Efficacy ............................................................................................................ 63
9.4.2.1
Primary Endpoints ............................................................................................ 63
9.4.2.2
Secondary Endpoints ........................................................................................ 63
9.4.2.3
Exploratory Endpoints ...................................................................................... 63
9.4.3
Safety ............................................................................................................... 64
9.4.4
Other Analyses.................................................................................................. 64
9.5
Interim Analyses............................................................................................... 64
9.6
Data Monitoring Committee ............................................................................. 65
10
REFERENCES................................................................................................. 66
11
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ........................................................................................ 70
LIST OF FIGURES
Figure 1
Study design............................................................................................ 13
Figure F2 Individual Growth Chart 3rd, 5th, 10th, 25th, 50th, 70th, 90th, 95th, 97th 
Percentiles, 2 to 20 Years: Boys Body Mass Index-for-Age ..................... 89
Figure F3 Individual Growth Chart 3rd, 5th, 10th, 25th, 50th, 70th, 85th, 95th, 97th 
Percentiles, 2 to 20 Years: Girls Body Mass Index-for-Age ..................... 90

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LI S T O F T A B L E S
Ta ble 1
Sc he d ule of Act i vities..............................................................................1 4
Ta ble 2
O bject i ves a n d E n d p oi nts.........................................................................2 7
Ta ble 3
I n vesti gati onal Pr o d uct ............................................................................3 4
T a ble 4
I n vesti gati onal Pr o d uct D ose Pre parati o n .................................................3 7
Ta ble 5
Restricte d Me dicat i ons .............................................................................3 9
Ta ble 6
Pr o hi bite d Me dicati o ns ............................................................................4 0
Ta ble 7
Ma xi m u m V o l ume of  Blo o d t o be Dra w n fr o m  a S u bject.........................4 3
Ta ble 8
V ol u me of Bl o o d t o be Dra w n fr o m  Eac h S u bject....................................4 4
Ta ble 9
La b orat or y  S afet y Varia bles .....................................................................5 1
Ta ble 1 0
P o p ul at i ons f or A nal ysis ..........................................................................6 1
Ta ble H 1 1
Esti mate d Dail y D oses of I n hale d C ortic oster oi ds f or C hil dre n A ge d 
6 t o 1 1 Years ...........................................................................................9 5
Ta ble H 1 2
L o w Dail y D oses of I n hale d C ortic oster oi ds f or C hil dre n A ge d 
≤5 Years ................................................................................................. 9 5
LI S T O F A P P E N DI C E S
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Cli nical St u d y Pr ot oc ol – 4 . 0
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1
P R O T O C O L S U M M A R Y
1. 1
S y n o psis
P r ot oc ol Title: A P hase I, O pe n La bel St u d y  t o E valuate t he P har m ac o ki net ics of 
Te ze pel u ma b i n C hil dre n ≥5 t o 1 1 Ye ars of A ge wit h Mil d, M o derate, or Se vere Ast h ma.
S h ort Title: A St u d y  t o E valuate t he P har mac o ki neti cs of Teze pel u ma b i n C hil dre n 
≥5 t o 1 1 Ye ars of A ge wit h Ast h ma.
R ati o n ale:
T he pri mar y  ai m of t his st u d y is t o e val uate t he p har mac o ki netic ( P K) pr ofile f oll o wi n g a 
si n gle s u bc uta ne o us ( S C) 
 d ose of teze pel u ma b i n c hil dre n a ge d ≥5 t o 1 1 years wi t h 
mil d, m o derate, or se vere ast h ma ( Gl o bal I nit iati ve f or Ast h ma [ GI N A] 2 0 2 0 Ste p 2 t o Ste p 4) 
re q uirin g dail y  c o ntr oller me dicat i ons.
A d dit i onal ai ms are t o e val uate t he safet y,  t olera bilit y,  im m u n o ge nicit y a n d 
p har mac o d y na mics ( P D) of a si n gle S C 
 d ose of teze pel u ma b.
C CI
C CI

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T he 9 9 -d a y  st u d y c o nsists of: 

A c o nse nt/scree ni n g peri o d of u p t o 1 4 da ys

Treat me nt a n d f oll ow- u p peri o d of  8 5 da ys.
T his is a n o pe n la bel n o n -ra n d o mise d st u d y. S u bjects will be all ocate d t o recei ve teze pel u ma b 
if t he y f ulfil t he eli gi bility cri t eria. 
Discl os ur e St ate me nt : T his is a n o pe n la bel si n gle ar m st u d y.
N u m ber of S u bjects:
A p pr o xi matel y 2 4 s u bjects will be e nr olle d a n d a p pr o xi matel y 1 4 s u bjects will recei ve I P s uc h 
t hat at least 1 2 s u bjects c o m plete t he st u d y.
N ote : ‘E nr olle d ’ mea ns a s u bject ’s, a n d t heir le gall y acce pta ble re prese ntati ve’s a gree me nt t o 
parti ci pate i n a cli nical st u d y fol l owi n g c o m plet i on of t he i nf or me d c o nse nt pr ocess. P ote ntial 
s u bjects w h o are scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y b ut are n ot 
assi g ne d i n t he st u d y, are c o nsi dere d ‘scree n fail ures’, u nless ot her wise s pecifie d b y  t he 
pr ot oc ol . 
I nter ve nti o n Gr o u ps a n d D ur ati o n:
T his is a 9 9 -d a y  st u d y. Scree ni n g assess me nts s h o ul d be c o m plete d wit hi n 1 4 da ys ( Da y -1 4 t o 
D a y -1). S u bj ects w h o meet eli gi bilit y criteria will recei ve a si n gle S C 
 d ose of 
teze pelu ma b o n Da y 1. T he s u bjects will t he n ret ur n f or F oll o w -u p visit s o n Da ys 3, 7, 1 1, 1 5, 
2 9, 5 7 a n d 8 5 ( E n d of St u d y  [ E O S]). T he st u d y will b e c o mplete d after t he E O S visit o n 
D a y 8 5.
D at a M o nit ori n g C o m mittee: N o
St atistic al met h o ds
All data will be prese nte d usi n g descri pt i ve statistics. N o f or mal statistical h y p ot hesis tests 
will be ma de.
I n di vi d ual teze pel u ma b ser u m c o nce ntrati o n data will be ta b ulate d al o n g wit h descri pt i ve 
statistics. T he f oll owi n g P K para meters will be est i mate d b y n o nc om part me nt al a nal ysis: area 
u n der t he c o nce ntrati o n- ti me c ur ve fr om ti me zer o t o i nfi nity ( AU C 0- i nf), area u n der t he 
c o nce ntrati o n-ti me c ur ve fr om ti me zer o t o t he ti me of t he last meas ure d c o nce ntratio n 
( A U C0- last), ma xi m u m c o nce ntrati o n ( Cma x ), ti me t o Cma x (tma x ), ter mi nal half-life (t1/ 2), 
a p pare nt cleara nce ( C L/ F) a n d a p pare nt stea d y-state v ol ume of distri b ut i on ( V ss/ F). A d dit i on al  
P K para meters ma y be re p orte d if a p pr o priate.
S af et y will be assesse d b y s u m marisi n g a d verse e ve nts ( A Es) a n d seri o us A Es ( S A Es). Ot her 
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Clinical Study Protocol – 4.0
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Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
14
1.3
Schedule of Activities
The schedule of activities (SoA) is presented in Table 1.
Table 1
Schedule of Activities
Consent/ 
Screening
Treatment Day
Follow-up period
Details in CSP Section or 
Appendix
Visit number
V1*
V2**
V3
V4
V5
V6
V7
V8
V9
Study day
Procedure
Day -14 to -1
Day 1
Day 3
Day 7
(± 1)
Day 11
(± 1)
Day 15
(± 1)
Day 29 
(± 2)
Day 57
(± 2)
Day 
85/EOS
(± 3)
Written informed 
consent and assent
X
Section 5.1, Appendix A 3
Assignment of SID 
number
X
Section 6.3
Verify eligibility 
criteria
X
X
Sections 5.1, 5.2
Demography
X
Section 5.1
Medical history
X
Section 5.1
Physical examination
  X a
  X a
  X b
  X b
  X b
  X a
Section 8.2.1
Weight 
X
X
X
X
Sections 5.1, 8.2.1.1, 
Appendix F
Height
X
X
Section 8.2.1.1
12-lead ECG
X
X
X
X
Section 8.2.3
Assessment of 
AEs/SAEs
X
X
X
X
X
X
X
X
X
Section 8.3
Assessment of 
COVID-19 signs and 
symptoms n
X
X
X
X
X
X
X
X
X
Section 2.3.1.3
Concomitant 
medications
X
X
X
X
X
X
X
X
X
Section 6.5

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Ta ble 1
Sc he d ule of Acti vities
C o nse nt/ 
Scree ni n g
Tre at me nt D a y
F oll o w -u p peri o d
Det ails i n C S P Secti o n or 
A p pe n di x
Visit n u m ber
V 1 *
V 2 * *
V 3  
V 4  
V 5  
V 6  
V 7  
V 8  
V 9
St u d y d a y
Pr oce d ure
D a y -1 4 t o - 1
D a y 1  
D a y 3  
D a y 7
( ± 1)
D a y 1 1
( ± 1)
D a y 1 5
( ± 1)
D a y 2 9 
( ± 2)
D a y 5 7
( ± 2)
D a y 
8 5/ E O S
( ± 3)
Secti o n 8. 1. 3
Vital si g ns
X
X c
X  
X  
X  
X  
X  
X  
X
Secti o n 8. 2. 2
Ser u m c he mistr y a n d 
hae mat ol o g y d
X
X
X  
X
X
Secti o ns 8. 2. 4 , 8. 5. 3
Secti o n 8
Uri nal ysis m
X
X
X  
X
X
Secti o n 8. 2. 4
Pre g na nc y test (ser u m 
β- H C G)
  X e
Secti o n 8. 2. 4. 1
Uri ne pre g na nc y test 
( di pstic k)
  X e
  X e
  X e
Secti o n 8. 2. 4. 1
Uri ne dr u g scree n
X
Secti o n 8. 2. 4
Vir ol o g y: H Bs A g, 
H C A b; HI V -1, HI V - 2
X
Secti o n 8. 2. 5. 1
C O VI D -1 9 viral ra pi d 
test via l ocal 
la b orat or y 
X
  X
m
Secti o n  8. 2. 5. 2
Bl o o d sa m ple f or P K 
a nal ysis f
  X g
X  
X  
X  
X  
X  
X  
X
Secti o n 8. 5. 1
Ser u m f or 
i m m u n o ge nicit y 
a nal ysis h, i
  X j
X
X
Secti o n 8. 5. 2
   
   
Secti o n 8. 1. 1
 
  
Secti o n 8. 1. 2
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2
I N T R O D U C TI O N
Te ze pel u ma b is a f ull y h u ma n i m m u n o gl o b uli n G (I g G) 2 λ m o n o cl o nal a nt i b o d y ( m A b) 
di recte d a gai nst t h y mic str o mal l y m p h o p oieti n ( T S L P), a n e pit helial cell-deri ve d c y t o ki ne t hat 
is pr o d uce d i n res p o nses t o pr oi nfla m mat or y sti m uli. Teze pel u ma b is c urre ntl y bei n g 
de vel o pe d as a p ote ntial treat me nt f or se vere ast h ma, m o derate t o se vere at o pic der matit is a n d 
m o derate t o ver y  se vere c hr o nic o bstr ucti ve p ul m o nar y  disease.
2. 1
St u d y R ati o n ale
Te ze pel u ma b is c urre nt l y i n P hase III de velo p m e nt a n d a pi v otal P hase III safety a n d efficac y 
st u d y ( D 5 1 8 0 C 0 0 0 0 7) is bei n g c o n d ucte d i n a d o lesce nts a n d a d ults wit h se vere ast h ma ( GI N A 
Ste ps 4 a n d 5). T he st u d y is o n g o i n g a n d has ra n d o mise d/ d ose d a p pr o xi matel y 8 0 a d olesce nts 
a ge d 1 2 t o 1 7 ye ars, i ncl usi ve. To date, t here are n o i de ntifie d ris ks a n d n o safet y data ha ve 
bee n recei ve d t hat w o u l d ne gat i vel y i m pact t he be nefit: ris k of teze pel u ma b.
T he pri mar y  ai m of t his st u d y is t o e val uate t he P K pr ofile f oll o wi n g a si n gle S C 
 d ose 
of  teze pelu ma b i n c hil dre n a ge d ≥5 t o 1 1 years wit h mil d, m o derate, or se vere ast h ma 
( GI N A 2 0 2 0 Ste p 2 t o S t e p 4) re q uiri n g dail y c o ntr oller me dicat i ons. T his is a necessar y ste p 
bef ore be gi n ni n g safet y a n d efficac y st u dies i n c hil dre n a ge d ≥5 t o 1 1 y ears t o deter mi ne t he 
a p pr o priate teze pel u ma b d osi n g.
A d dit i onal ai ms are t o e val uate t he safet y,  t olera bilit y, i m m u n o ge nicity a n d P D of a si n gle S C 
 d ose of teze pel u ma b.
2. 2
B ac k gr o u n d
Bi ol o gi c t hera pies ha ve bee n s h o w n t o re d uce t he a n n ualise d ast h ma e xacer bat i on rate 
( A A E R) i n s u bjects wit h se vere ast h ma w h o are u nc o ntr olle d wit h me di u m t o hi g h-d ose 
i n hale d c ortic ost er oids (I C S) a n d a d dit i onal ast h ma c o ntr oller me dicat i ons. O maliz u ma b 
( X O L AI R® , Ge ne ntec h, I nc) pr o vi de d be nefit f or a s u b gr o u p of s u bjects wit h pr o ve n 
reacti vity t o a n aer oaller ge n a n d ele vate d ser u m i m m u n o gl o b uli n E (I g E) le vels w h o re mai n 
i na deq uatel y c o ntr olle d wit h a n I C S pl us a l o n g -acti n g β 2 -a g o nist ( L A B A) 
(X ol air U S Prescri bi n g I nf or mat i on 2 0 1 9 ). F o ur a d diti onal bi o l ogics, me p oliz u ma b 
( N UC A L A ® , Gla x o S mit hKli ne), resliz u ma b ( CI N Q AI R ® , Te va Res pirat or y), be nraliz u ma b 
( FA S E N R A ® , Astra Ze neca A B) a n d d u pil u ma b ( D U PI X E N T ® , Re ge ner o n P har mace uticals, 
I nc) ha ve rece ntl y bee n a p pr o ve d f or se vere ast h ma wit h a n e osi n o p hilic p he n ot y pe 
(Ci n qair U S Prescri bi n g I nf or matio n 2 0 1 6 , D u pi xe nt U S Prescri bi n g I nfor m at i on 2 0 1 9 , 
Fase nra U S Prescri bi n g I nf or mati o n 2 0 1 7 , N ucal a U S Prescri bi n g I nf or mati o n 2 0 1 9 ). 
Bi ol o gi cs tar geti n g i nterle u ki n -5 a n d I g E are n o w i ncl u de d i n i nter nat i onal treat me nt 
g ui deli nes (GI N A 2 0 2 0 ) as a n a d d-o n treat me nt t o s u bjects u nc o ntr olle d wit h I C S/ L A B A 
treat me nt. H o we ver, e ve n w he n usi n g c urre nt l y a vaila ble bi o l ogics, s u bsta nt ial pr o p orti o ns of 
s u bjects c o nti n ue t o e x perie nce e xacer bat i ons a n d ma y be nefit fr o m a ge nts t hat tar get differe nt 
C CI
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 8
m o lec ular pat h wa ys (Fr o i d ure et al 2 0 1 6 , S o n a n d Frie d ma n 2 0 2 1
S o n M B F , Frie d ma n K. C O VI D -1 9: M ul tis yste m i nfla m mat or y s y n dr o me i n c hil dre n ( MI S -C) 
cli nical feat ures, e val uat i on, a n d dia g n osis. U p To Date A pril 2 0 2 1 
S we di n et al 2 0 1 7 , We nzel 2 0 1 6 ). T heref ore, des pite t hese a d diti onal t hera pe ut ic o pti o ns, 
t here is still a clear u n met me dical nee d a m o n g s u bjects wit h se vere ast h ma, i n de pe n de ntl y o f 
I g E stat us or e osi n o p hil le vel, w h o are u na ble t o gai n c o m p lete ast h ma c o ntr ol usi n g c urre ntl y 
a vaila ble t hera pies.
T h y mic str o mal l y m p h o p oiet i n is a n e pit helial cell-deri ve d c y t o ki ne t hat is pr o d uce d i n 
res p o nses t o pr oi nfla m mat or y sti m uli (e g, i nfecti o us, aller gic a n d e n vir o n me ntal sti m uli) a n d 
tra u ma. T h y mic str o mal l y m p h o p oiet i n has a n u pstrea m a n d ce ntral r ole i n t he i nitiati on of 
i m m u ne res p o nses a n d ca n acti vate a br oa d ra n ge of cell ty pes i ncl u di n g e osi n o p hils, mast 
cells, T cells, de n drit ic cells, t y pe 2 i n nate l y m p h oi d cells a n d bas o phils 
(Wa ts o n a n d Ga u vrea u 2 0 1 4 ). Classicall y , T S L P ma y be a critical c o mp o ne nt i n t he i nit iati o n 
a n d per pet uati o n of t he T hel per 2 ( T h 2) res p o nse a n d t he res ult i n g casca de of c yt o ki nes 
ass ociat e d wit h T h 2 dri ve n ast h ma (Ka ur a n d Bri g ht li n g 2 0 1 2 ). Ast h ma is rec o g nise d as a 
heter o ge ne o us disease, t h o u g h, a n d t here are s u bsets of s u bj ects t hat d o n ot e x hi bit 
T h 2 -ass ociate d disease (We nzel 2 0 1 2 ). E mer gi n g data i n dicates t hat T S L P ma y als o me diate 
n o n -aller gic ( n o n-T h 2) i nfla m mat i on (Ta na ka et al 2 0 0 9, Zie gler et al 2 0 1 3 ).
Te ze pel u ma b is a f ull y h u ma n I g G 2 λ m A b directe d a gai nst T S L P. Teze pel u ma b bi n ds t o 
h u ma n T S L P a n d pre ve nts its i nteracti o n wit h t he T S L P rece pt or . O wi n g t o t he ce ntral r ole of 
T S L P as a n u pstrea m a n d plei otr o pic c yt o ki ne i n me diat i n g ast h ma pat h o p h ysi ol og y, 
a nt i-T S L P t hera p y is a nt ici pate d t o ha ve br oa d i m pact o n t he s pectr u m of i nfla m mat or y 
res p o nses see n i n ast h ma.
Res ults of a c o m p lete d i n hale d aller ge n c halle n ge st u d y i n 3 1 a d ult s u bjects wit h mil d at o pic 
ast h ma ( St u d y 2 0 1 0 11 8 3) de m o nstrate d t hat teze pel u ma b atte n uate d t he late aller gic res p o nse 
a n d t he earl y aller gic res p o nse t o aller ge n c halle n ge, as meas ure d b y t he A U C f or t he 
perce nta ge fall i n t he f orce d e x pirat or y  v ol ume i n o ne sec o n d ( F E V 1) a n d t he ma xi m u m 
perce nta ge fall i n F E V 1. Teze pel u ma b als o atte n uate d t he i ncrease i n 
 
 val ue o n t he p ost-aller ge n da y c o m pare d wit h t he pre- aller ge n da y. M ultiple 
d oses of teze pel u ma b 7 0 0 m g a d mi nistere d i ntra ve n o usl y de m o nstrate d a n acce pta ble safet y 
pr ofile i n s u bjects wit h mil d at o pic ast h ma. N o s u bjects de vel o pe d A D A  after recei vi n g 
teze pelu ma b (Ga u vrea u et al 2 0 1 4). Base d u p o n t hese data, Me dI m m u ne/ Astra Ze neca 
perf or m e d a ra n d o mise d, d o u ble -bli n d, pl ace b o -c o ntr olle d, d ose -ra n ge fi n di n g st u d y in 
ast h matics w h o were i na de q uatel y c o ntr olle d wit h me di u m or hi g h -d ose I C S/ L A B A wit h or 
wi t ho ut ot her c o ntr oller me dicati o ns.
St u d y  C D-RI -M E DI 9 9 2 9 -1 1 4 6 ( PA T H W A Y ) was a P hase II b mul tice ntre, mul tinat i onal, 
C CI

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CONFIDENTIAL AND PROPRIETARY
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dose-ranging, double-blind, randomised, parallel-group, placebo-controlled study to evaluate 
the effect of 3 dose levels of tezepelumab on the AAER in adult subjects with 
inadequately-controlled severe asthma. Subjects were randomised in a 1:1:1:1 ratio to one of 3 
dose levels of SC tezepelumab (70 mg every 4 weeks [Q4W], 210 mg Q4W, 280 mg every 
2 weeks [Q2W]) or placebo (Q2W) for 52 weeks. A total of 584 subjects received at least 
1 dose of tezepelumab or placebo. Anomalous data at a single site were identified following 
completion of the study and due to Good Clinical Practice (GCP) non-compliance, all data 
related to 34 subjects from this site were excluded and the Clinical Study Report (CSR) 
revised. Consequently, a total of 550 subjects received at least one dose of tezepelumab or 
placebo. An AAER reduction of 62%, 71% and 66% for the 70 mg Q4W, 210 mg Q4W and 
280 mg Q2W tezepelumab groups, respectively, compared with placebo were observed in the 
intent-to-treat population (p<0.001). After repeated SC administration, mean serum trough 
concentration increased over time and achieved steady-state by Week 12. Tezepelumab 
exhibited linear PK across the 3 doses. A total of 6 (4.3%) placebo subjects and 7 (1.7%) 
tezepelumab subjects who had no detectable ADA at baseline had detectable ADA 
post-treatment; no subjects developed neutralising ADA in the study. The results of this study 
did not identify safety concerns associated with tezepelumab for any dosing regimen. The 
frequencies of treatment-emergent AEs (TEAEs) were similar between the placebo (65.9%) 
and the total tezepelumab (66.0%) dose groups and a majority of subjects had TEAEs that 
were mild or moderate in severity and not related to investigational product (IP). Few subjects 
had TEAEs that resulted in permanent discontinuation of IP. Overall, tezepelumab was 
well-tolerated with an acceptable safety profile and no identified safety risks were noted 
(Corren et al 2017).
Study D5180C00002 was a Phase I open label study to evaluate the PK of a single SC 140 mg 
dose of tezepelumab in adolescents with mild to moderate asthma aged 12 to 17 years 
(inclusive). Tezepelumab was slowly absorbed with a time to achieve maximum observed 
serum concentration (tmax) ranging from approximately 4 to 6 days postdose and a mean 
maximum observed serum concentration (Cmax) of 24.0 ± 6.59 µg/mL. Mean CL/F was 
0.159 ± 0.0443 L/day and the t1/2 was estimated to be 25.3 ± 4.70 days, similar to that 
previously observed in the adult population. The younger adolescent subjects 
(aged 12 to 14 years, inclusive) had higher exposure and lower CL/F compared with the older 
subjects (aged 15 to 17 years, inclusive), consistent with lower average body weight in the 
younger subjects and the impact of body weight on the PK of tezepelumab. Overall, the PK 
was consistent with previous experiences with this molecule and typical of human mAbs 
directed towards soluble antigens. Tezepelumab treatment was well-tolerated with an 
acceptable safety profile and supported further clinical development in this subject population. 
In safety assessments, 4 subjects in each cohort experienced at least one TEAE. There were no 
treatment-emergent SAEs. All TEAEs were mild or moderate in severity. One subject had 
ADAs both before treatment and postbaseline. No neutralising ADAs were detected in any 
subject. 

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Study D5180C00007 (NAVIGATOR) was a Phase 3, multicenter, global, randomized, 
double-blind, placebo-controlled study to assess the efficacy and safety of 210 mg of 
tezepelumab administered SC Q4W for 52 weeks. The population of interest was adults and 
adolescents with severe, uncontrolled asthma between the ages of 12 and 80 years and both 
overall and across a broad spectrum of asthma phenotypes as determined by subjects with 
blood eosinophils above and below 300 cells/μL, FeNO above and below 25 ppb, as well as 
allergic and non-allergic status. A total of 1061 subjects were randomized in a 1:1 ratio to 
tezepelumab or placebo and 1059 subjects received at least one dose of IP. Tezepelumab 
treatment resulted in a statistically significant and clinically meaningful reduction in AAER by 
56% (p < 0.001) compared with placebo in the overall population and by 41% compared with 
placebo in subjects with baseline blood eosinophils < 300 cells/μL (p < 0.001). The mean 
serum trough concentration of tezepelumab increased over time and approached steady state 
by 12 weeks. Treatment-emergent ADAs were detected at any time during the study in 4.9% 
(26) of subjects treated with tezepelumab. Neutralizing antibodies to tezepelumab were 
detected in only one (0.2%) of the subjects treated with tezepelumab. On-treatment AEs were 
similar between the placebo (80.8%) and the total tezepelumab (77.1%) dose groups and a 
majority of subjects had on-treatment AEs that were mild or moderate in severity and not 
related to investigational product (IP). The percentage of subjects who discontinued the trial 
regimen was 6.8% in the tezepelumab group and 10.7% in the placebo group. On-treatment 
AEs that resulted in permanent discontinuation of IP was 2.1% in the tezepelumab group and 
3.6% in the placebo group. Overall, tezepelumab was well tolerated with an acceptable safety 
profile and no safety signals in subjects with severe, uncontrolled asthma. (Menzies-Gow et al 
2021).
Eighty-two adolescent subjects aged 12 to 17 years were included in the NAVIGATOR safety 
set; duration of exposure was similar for the adolescents in the tezepelumab and placebo 
groups. The overall incidence of AEs in adolescent subjects during the on-treatment period 
was similar between the tezepelumab (73.2%) and placebo (70.7%) groups. The most 
common AEs in adolescent subjects (reported in ≥ 5% of subjects) in the tezepelumab group 
were: nasopharyngitis (19.5% in the tezepelumab group vs 12.2% in the placebo group), upper 
respiratory tract infection (14.6% and 7.3%), rhinitis (9.8% and 2.4%), pharyngitis (7.3% and 
4.9%), and viral upper respiratory tract infection (7.3% and 4.9%). The incidence of SAEs 
was low and similar between the tezepelumab and placebo groups (one subject [2.4%] in the 
tezepelumab group and 2 subjects [4.9%] in the placebo group, all of which were PT asthma). 
There were no AEs leading to discontinuation of IP for adolescents in either treatment group.  
In conclusion, tezepelumab was well tolerated in adolescent subjects in NAVIGATOR with an 
AE profile that appears generally similar to that seen in adult subjects with severe 
uncontrolled asthma.
Additional studies with tezepelumab have been completed. These include a mechanistic study 
(D5180C00013; CASCADE) conducted in adults with inadequately controlled asthma, study 

Clinical Study Protocol – 4.0
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Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
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D5180C00009 (SOURCE) conducted in adults with oral corticosteroid (OCS)-dependent 
asthma, study D5180C00011 (PATH-HOME), an at-home use study in adults and adolescents 
with severe asthma, and study D5180C00019 (NOZOMI), a Japanese long-term safety study 
in subjects with inadequately controlled asthma.
A detailed description of the above-mentioned additional studies and chemistry, 
pharmacology, efficacy and safety of tezepelumab is provided in the Investigator’s Brochure 
(IB).
2.3
Benefit/Risk Assessment
More detailed information about the known and expected benefits and potential risks of 
tezepelumab may be found in the IB.
2.3.1
Risk Assessment
Clinical and nonclinical experience with tezepelumab demonstrates no safety or tolerability 
concerns to date. Potential risks based on the mechanism of action of tezepelumab include 
serious infections, helminth infections, and serious hypersensitivity reactions. Risk 
minimisation strategies associated with tezepelumab have been identified, described in the 
current IB and are included in this protocol. The risk mitigation strategies include but are not 
limited to: monitoring the subject for vital signs for a minimum of 2 hours post-IP, following
each subject at every visit for AEs, as well as frequent study visits in the days following the 
administration of IP allowing for more intense monitoring of the subject by eg, physical 
examinations, ECGs, urinalysis, serum chemistry and haematology. Additional risks 
associated with the conduct of the study (eg, collection of blood for safety, PK and PD 
assessments, and spirometry testing) have a minimal impact on subjects in the study. 
2.3.1.1
Study Conduct During COVID-19 Pandemic
Coronavirus disease 2019 (COVID-19) has emerged as a worldwide pandemic disease with 
significant implications for public health. AstraZeneca will monitor the participating countries 
and sites, and the study will not begin until local and national guidelines and clinical sites 
have indicated that it is acceptable to conduct clinical studies and the safety of site staff and 
subjects can be ensured. 
2.3.1.2
Requirements During the COVID-19 Pandemic
Please Note: Changes below should only be implemented if study site is closed or travel 
restrictions are in place due to the COVID-19 pandemic.
During the COVID-19 pandemic, changes are being implemented in order to ensure the safety 
of study subjects, to minimise the risk to subjects of COVID-19 exposure, to maintain 
compliance with GCP, and to minimize risks to data integrity. 

Clinical Study Protocol – 4.0
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Tezepelumab - D5180C00025
CONFIDENTIAL AND PROPRIETARY
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Visit 1 and Visit 2 must be performed on-site.
If an on-site visit for Visits 3 through 9 cannot occur due to pandemic related study site 
closure or travel restrictions, alternative visits should be performed, where allowable by local 
health authorities, ethics committees and healthcare provider guidelines (e.g. hospital 
policies), at the site’s discretion in agreement with the Sponsor. The options are specified 
below:
1. Visit(s) to be performed at an alternate site (where applicable): Study visits including 
study assessments and bloodwork according to the SoA can take place at an alternative 
location away from infection risk zones, or closer to the subject’s home, provided this 
is acceptable within local regulation/guidance.  
2. Visit(s) to be performed at home by study site staff. Study visits including study 
assessments and bloodwork according to the SoA can take place at home, provided this 
is acceptable within local regulation/guidance.
3. Visit(s) to be performed at home by qualified third-party vendor. Study visits including 
study assessments and bloodwork according to the SoA can take place at home, 
provided this is acceptable within local regulation/guidance.
For further details, please refer to Appendix I.
2.3.1.3
COVID-19 Risk Mitigations
Severe asthma may be a risk-factor for severe COVID-19 illness. Subjects with suspicion of 
current or recent (within 8 weeks of Visit 1) COVID-19 infection or positive local COVID-19 
viral rapid test during screening will not be included in the study (Section 5.2, Exclusions #22 
and #23).  
Paediatric cases of COVID-19 have been reported. However, there have historically been 
relatively fewer cases of COVID-19 among children compared with cases among adult 
patients.
Among cases in children reported from China, most had exposure to household members with 
confirmed COVID-19 (CDC 2020a).
Data on the incubation period for COVID-19 in the paediatric population is limited, it is 
thought to be similar to adult patients with COVID-19. In studies from China, the reported 
incubation period among paediatric patients ranged from 2 to 10 days.
Paediatric patients with COVID-19 may experience the following signs or symptoms over the 
course of the disease:

Clinical Study Protocol – 4.0
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CONFIDENTIAL AND PROPRIETARY
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
Fever

Cough

Nasal congestion or rhinorrhoea

Sore throat

Shortness of breath

Diarrhoea

Nausea or vomiting

Fatigue

Headache

Myalgia

Poor feeding or poor appetite
The predominant signs and symptoms of COVID-19 reported to date among all patients are 
similar to other viral respiratory infections, including fever, cough, and shortness of breath. 
Although these signs and symptoms may occur at any time during the overall disease course, 
children with COVID-19 may not initially present with fever and cough as often as adult 
patients. In a report of 9 hospitalised infants in China with confirmed COVID-19, only half 
presented with fever. Gastrointestinal symptoms, including abdominal pain, diarrhoea, nausea, 
and vomiting, were reported in a minority of adult patients. In 1 paediatric case of COVID-19, 
diarrhoea was the only symptom reported.
There have been multiple reports to date of children with asymptomatic COVID-19 infection. 
The prevalence of asymptomatic COVID-19 infection and duration of pre-symptomatic 
infection in children are not well understood, as asymptomatic individuals are not routinely 
tested. 
One of the complications of COVID-19 infection in children is multisystem inflammatory 
syndrome (MIS-C) (CDC 2020b). Patients with MIS-C can present with a persistent fever, 
fatigue, and a variety of signs and symptoms including multiorgan (eg, cardiac, 
gastrointestinal, renal, hematologic, dermatologic, neurologic) involvement, and elevated 
inflammatory markers. Not all children will have the same signs and symptoms, and some 
children may have other symptoms. MIS-C symptoms typically appear two to six weeks 
(although occasionally longer) after a child has been infected with SARS-CoV-2 (Son and 
Friedman 2021). 
Sites will be required to provide documentation of a COVID-19 screening and mitigation plan 
that describes how and where subjects would be tested if they are suspected of being infected 
with COVID-19. The plans should also describe mitigation activities designed to protect site 
staff and others at the site, including other subjects and patients.
To ensure the safety of the subject, caregiver, and site staff, every visit will follow these 
guidelines:

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 4
All s u bjects will ha ve a C O VI D-1 9 scree ni n g assess me nt perf or me d b y tele p h o ne wit hi n 
2 4 h o urs pri or t o e ver y  st u d y visit, w het her visit is o n-site or re mote. Q uesti o ns s h o ul d 
i ncl u de, b ut n ot be li mite d t o, si gns a n d s y m pt o ms of acti ve C O VI D- 1 9 i nfect i on, i n a d dit i on 
t o tra vel, k n o w n c o ntacts, a n d testi n g. T he q uesti o n naire will i ncl u de q uest i ons a b o ut 
e x p os ures a n d h o use h o l d health. T he site will deter mi ne t he a p pr o priate c o urse of acti o n 
base d o n t he res p o n ses t o t he q uesti o ns. 
Scree ni n g V 1:

If t here is n o s us pici o n of C O VI D -1 9 i nfect i on base d o n q uesti o n naire res p o nses, t he 
s u bject ca n pr ocee d wit h t he sc he d ule d site visit, ha ve te m perat ure a n d vital si g ns 
rec or de d, a n d, if afe brile, pr ocee d wit h Visit 1 a n d C O VI D -1 9 testi n g. 
o
A n y s us pici o n o f C O VI D -1 9 i nfect i on base d o n q uesti o n naire res p o nses s h o ul d 
be ma na ge d acc or di n g t o l ocal a n d nat i onal g ui deli nes a n d s u bject s h o ul d be 
scree n faile d. T hese s u bjects ca n be rescree ne d wit hi n 2 t o 4 wee ks, as l o n g as 
the y are C O VI D -1 9 ne gat i ve a n d rescree n is a p pr o ve d b y t he C o ntract 
Researc h Or ga nisat i on ( C R O) Me dical M o nit or a n d A Z st u d y  p h ysicia n. 

If l ocal C O VI D-1 9 vi r al ra pi d test is p ositive at V 1, t he s u bject s h o ul d be scree n faile d.   
Tre at me nt D a y V 2:

If t here is n o s us pici o n of C O VI D -1 9 i nfect i on base d o n q uesti o n naire res p o nses, t he 
s u bject ca n pr ocee d wit h t he sc he d ule d site visit, ha ve te m perat ure a n d vital si g ns 
rec or de d, a n d, if afe brile, pr ocee d wit h Visit 2 a n d C O VI D-1 9 testi n g. 
o
A n y s us pici o n o f C O VI D -1 9 i nfect i on base d o n q uesti o n naire res p o nses s h o ul d 
be ma na ge d acc or di n g t o l ocal a n d nat i onal g ui deli nes a n d s u bject s h o ul d be 
scree n faile d. T hese s u bjects ca n be rescree ne d wit hi n 2 t o 4 wee ks, as l o n g as 
t he y are C O VI D-1 9 ne gat i ve a n d a p pr o val b y t he C R O Me dical M o nit or a n d 
A Z st u d y  p h ysicia n. 

L ocal  C O VI D-1 9 vi ral ra pi d test s h o ul d be perf or me d wit h ne gati ve res ults pri or t o 
s pir o metr y,  
, a n d st u d y I P a d mi nistrati o n. 
o
If l ocal C O VI D-1 9 vi r al ra pi d test is p ositive at V 2, t he s u bject s h o ul d be 
scree n faile d.   
All ot her st u d y visits:

If t here is n o s us pici o n of C O VI D -1 9 i nfect i on base d o n q uesti o n naire res p o nses, t he 
s u bject ca n pr ocee d wit h t he sc he d ule d site visit, ha ve te m perat ure a n d vital si g ns 
rec or de d, a n d, if afe brile, pr ocee d wit h t he sc he d ule d st u d y visit. 
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25
o
Any suspicion of COVID-19 infection based on questionnaire responses should 
be managed according to local and national guidelines. 

Study sites may perform a local COVID-19 viral rapid test or central viral test after 
Visit 2 and throughout the study if it is considered clinically appropriate by the 
Investigator. If test results are positive, the subject may or may not be withdrawn from 
the study, depending on extent of illness and Investigator judgement, and the CRO 
Medical Monitor and AZ study physician must be notified. 
It is recognised that depending on the location and facilities of a clinical site, study visit 
attendance may place subjects at risk of exposure to COVID-19. Furthermore, it is recognised 
that more general population-level measures to reduce infection rates (eg, travel restrictions) 
may inhibit the ability of subjects to attend study visits. Necessary healthcare responses at 
sites to the pandemic (eg, additional infection control measures) may also inhibit the ability of 
a clinical site to effectively and properly conduct the study. Study visit attendance for dosing 
and for clinical assessments are critical for the scientific value of the study.
Therefore, investigators should not enrol subjects unless they have reasonable confidence that 
throughout the duration of the study:

Subjects and caregivers will be able to attend study visits, whilst avoiding contact with 
concentrations of COVID-19 patients (eg, hospital entrances used by such patients); and

The site will be able to conduct the study effectively and safely, considering relevant 
national and local factors; and

Subjects and caregivers agree to alternate site visits or home visits as an alternative to on-
site visits if pandemic restrictions are in place
If, for reasons related to the COVID-19 pandemic, a subject/caregiver is not able to attend 
their scheduled study visit at the site, refer to CSP Section 1.2 and Appendix I for alternative 
study visit options. 
The Sponsor will monitor the number of discontinuations, withdrawals, missed visits and 
other missing data and collect such information in the eCRF.
Subjects may be tested for COVID-19 infection by local viral rapid test at any time during 
study conduct if it is considered clinically appropriate by the investigator (Table 1). 
Subjects with a suspicion of COVID-19 infection or active COVID-19 infection detected 
during study conduct may be withdrawn from the study based on severity of illness and 
Investigator discretion. An AE should be recorded in the eCRF to capture the event. Such 
subjects may be replaced at the Sponsor’s discretion. Each situation is likely to be unique, 
therefore the CRO Medical Monitor and AZ study physician must be notified.

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 6
All sit e st aff s h o uld wear pers o nal pr otecti ve e q ui p me nt i n acc or da nce wit h l ocal or nati o nal 
g ui deli nes.
2. 3. 2
Be nefit Assess me nt
I n t he P hase 3 a n d 2 b st u dies, cli nical be nefits a n d i m pr o ve me nts o n bi omar kers were alrea d y 
o bser ve d at t he first assess me nt 2 wee ks a n d 4 wee ks after t he first d ose, res pecti vel y. 
H o we ver, i n t he c o nte xt of t his st u d y , t he pr o ba bilit y of t hera pe utic be nefit f oll o wi n g a si n gle 
S C d ose of teze pel u ma b 
 ca n n ot be pre dicte d. Ne vert heless, it ma y be a nt ici pate d t hat 
s u bjects will deri ve be nefit fr o m t he re g ular re vie w b y healt hcare pr ofessi o nals d uri n g t he 
st u d y.
2. 3. 3
O ver all Be nefit: Ris k C o ncl usi o n
Ta ki n g i nt o acc o u nt t he meas ures ta ke n t o mi ni mise ris k t o s u bjects i n t his st u d y, t he c urre nt 
be nefit: ris k pr ofile a p pears fa v o ura ble a n d j ust ifies t he a d mi nistrati o n of teze pel u ma b i n t his 
st u d y.
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 8
4
S T U D Y D E SI G N
4. 1
O ver all Desi g n
T his is a m ult ice ntre, o pe n la bel st u d y desi g ne d t o e val uate t he PK pr ofile of teze pel u ma b 
f oll owi n g a si n gle S C 
 d ose i n c hil dre n a ge d ≥5 t o 1 1 years wit h mil d, m o derate, or 
se vere ast h ma. 
T he st u d y  will be c o n d ucte d glo ball y  wit h a p pr o xi matel y 1 0 st u d y sit es. 
A p pr o xi matel y  2 4 s u bjects will be e nr olle d a n d a p pr o xi matel y 1 4 pae diatric s u bjects a ge d 
≥5 t o 1 1 years (i ncl usi ve) will recei ve a si n gle S C 
 d ose of teze pel u ma b i n a n atte m pt 
t o ha ve at least 1 2 pae diatric s u bjects c o m plete t he st u d y. At  least 4 s u bjects will ha ve b o d y 
w ei g ht < 2 5 k g a n d a mi ni m u m of  3 s u bjects will ha ve b o d y wei g ht ≥2 5 k g t o < 4 0 k g.
S u bjects w h o are eli gi ble t o partici pate b ut d o n ot g o o n t o recei ve teze pel u ma b, or s u bjects 
w h o d o n ot c o m plete t he re q uire d e val uat i ons t hr o u g h t o Da y 8 5 m a y be re place d t o mai ntai n 
t he stip ulat e d n u m ber of e val ua ble s u bjects, at t he discreti o n of t he S p o ns or. 
T he 9 9 -d a y  st u d y c o nsists of: 

A c o nse nt/scree ni n g peri o d of u p t o 1 4 da ys

Treat me nt a n d f o ll ow- u p peri o d of  8 5 da ys.
T he st u d y  desi g n is s u m marise d i n Fi g ure 1.
S u bjects will atte n d t he st u d y  site a n d i nf or me d c o nse nt will be o btai ne d fr o m t he le gal 
re prese ntati ve a n d i nf or me d asse nt will be o btai ne d fr om t he s u bject. Scree ni n g assess me nts 
s h o uld be c o m plete d wi t hi n 1 4 da ys ( Da y --1 4 t o Da y --1). S u bjects w h o meet eli gi bilit y 
criteria will recei ve a si n gle S C 
 d ose of teze pel u ma b, a d mi nistere d i n t he a nteri or t hi g h 
b y a healt hcare pr ofessi onal o n Da y 1 a n d re m ai n at t he st u d y ce ntre f or 2 h o urs af ter d osi n g. 
T he s u bjects will t he n ret ur n t o t he ce ntre f or o ut patie nt F oll o w -u p visi ts o n Da ys 3, 7, 1 1, 1 5, 
2 9, 5 7 a n d 8 5 ( E O S). T he st u d y will be c o m p lete d after t he E O S visit o n Da y 8 5.
4. 2
Scie ntific R ati o n ale f or St u d y Desi g n
T his st u d y  desi g n has bee n re vie we d a n d a p pr o ve d b y t he Pae diatric C o m mittee of t he 
E ur o pea n Me dici nes A ge nc y as part of t he teze pel u ma b Pae diatric I n vest i gati on Pl a n.
T his is a n o pe n la bel st u d y . A place b o gr o u p is n ot c o nsi dere d re q uire d f or t his st u d y si nce t he 
pri mar y  o bjecti ve is t o deter mi ne t he P K of a si n gle S C 
 d ose of teze pel u ma b i n 
c hil dre n a ge d ≥5 t o 1 1 y ears wi t h mil d, mo derate, or se vere ast h ma a n d n o f or mal assess me nt 
of  efficac y will be ma de. T he assess me nt of t he safet y a n d t olera bility of  teze pelu ma b ca n be 
ma d e wit ho ut a pl ace b o gr o u p.
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 9
T he pri mar y , sec o n dar y a nd 
 were c h ose n t o e val uate w het her P K, 
i m m u n o ge nicity,  safety a n d  
of teze pel u ma b i n c hil dre n are si milar t o t he a d ult a n d 
a d olesce nt p o p ulatio ns. All P K t i me p oi nts i n t his st u d y are base d o n t he P K i nf or mati on 
o btai ne d i n pre vi o us a d ult a n d a d o lesce nt st u dies.
4. 3
J u stific ati o n f or D ose
A si n gle S C 
 d ose has bee n selecte d f or t his st u d y t o e valuate t he P K/ P D of teze pel u ma b 
i n c hil dre n a ge d ≥5 t o 1 1 years . T his was esta blis he d fr om e x p os ure c o mpara bilit y bet wee n 
t he pr o p ose d effect i ve d ose a n d safe e x p os ure i n t he a d ult p o p ulati on base d o n P hase II b data. 
P o p ul at i on P K m o delli n g base d o n P hase I a n d P hase II data s u g geste d b o d y w eig ht was a 
sig nifica nt c o variate f or t he P K of teze p elu ma b. Usi n g t he p o p ulat i on P K m o d el , si m ulati ons 
were c o n d ucte d t o pre dict t he teze pel u ma b e x p os ure i n c hil dre n a ge d ≥5 t o 1 1 years, ta ki n g 
i nto acc o u nt t he differe nce i n b o d y  wei g ht distri b utio n bet wee n t he a d ult a n d pae diatric 
p o p ul at i ons. Base d o n t h e si m ulat i on, t he pre dicte d e x p os ure f o ll owi n g 
 S C Q 4 W d ose 
i n c hil dre n a ge d ≥5 t o 1 1 years is c o m para ble t o t hat i n a d ults at 2 1 0 m g S C Q 4 W , w hic h was 
selecte d as t he o pti mal d ose i n a d ult patie nts wit h se vere ast h ma base d o n t he P hase II b data 
a n d use d i n t he o n g o i n g 5 2-wee k P hase III st u d y in a d ults a n d a d olesce nts. T he P hase II b data 
s h o we d t he d ose of 2 1 0 m g S C Q 4 W  for 5 2 wee ks was well t olerate d a n d le d t o near 
ma xi m u m 
i m pr o ve me nt, as well as re d ucti o n i n  
 a n d 
, 
4 wee ks after t he first d ose. He nce, gi ve n t he li near P K of teze pel u ma b a n d si milar e x p os ure 
t o 2 1 0 mg si n gle S C d ose i n a d ults, a si n gle S C 
 d ose is pre dicte d t o be safe a n d ac hie ve 
near ma xi m u m P D effects w hile bei n g s ufficie nt t o c haracterise P K i n c hil dre n a ge d ≥5 t o 
1 1 years.
4. 4
E n d of St u d y Defi niti o n
A s u bject is c o nsi dere d t o ha ve c o m plete d t he st u d y if he/s he has c o mplete d his/ her l ast 
sc he d ule d c o ntact.
T he e n d o f st u d y is defi ne d as t he date of t he last visit of t he last s u bject i n t he st u d y.
5
S T U D Y P O P U L A TI O N
Pr os pecti ve a p pr o val o f pr ot oc ol  de viatio ns t o recr ui t me nt a n d e nr o l me nt criteria, als o k n o w n 
as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
C CI
C CI
C CI
C CI
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C CI
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Clinical Study Protocol – 4.0
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CONFIDENTIAL AND PROPRIETARY
30
5.1
Inclusion Criteria
Subjects are eligible to be included in the study only if all of the following criteria apply:
Informed Consent
1
Written informed consent and written informed assent and any locally required 
authorisation obtained from the subject and legal representative prior to any study-related 
procedure taking place.
The informed consent form (ICF) process is described in Appendix A 3.
Age
2
Age 5 to 11 years (inclusive) at Visit 1 and Visit 2 (Day 1).
Type of Subject and Disease Characteristics
3
Documented physician diagnosed asthma, defined by the regional guidelines (ie, National 
Institutes of Health [NIH], GINA, American Thoracic Society [ATS], European 
Respiratory Society [ERS], etc), for at least 6 months prior to Visit 1. If the subject is 
naïve to the study site, the participant/guardian must self-report a physician diagnosis of 
asthma and the investigator must confirm by review of medical history with the 
participant/guardian.
4
Documented treatment with total daily dose of either low, medium, or -high-dose ICS 
(≥100 μg fluticasone propionate dry powder inhaler [DPI] or equivalent; see 
Appendix H) for at least 6 months, as described in Step 2 to Step 4 of GINA guidelines 
(GINA 2020) with stable dose for at least 3 months prior to Visit 1.
5
Additional controller medication according to standard practice of care is permitted 
(LABA, leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist 
[LAMA] only) and must be documented and stable for at least 3 months prior to Visit 1. 
6
Inclusion criterion 6 (historical or current airway reversibility) removed with version 3.0 
of Clinical Study Protocol.
7
Pre-bronchodilator (BD) FEV1 of ≥50% of predicted normal value at Visit 1.
8
If on allergen immunotherapy, subjects must be on stable maintenance dose and schedule 
≥1 month prior to Visit 1.
9
Able and willing to comply with the requirements of the protocol.
10 Acceptable inhaler and spirometry techniques during screening/run-in period as assessed 
by the Investigator.

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Weight
11 Body weight ≥16 kg at Visit 1 and Visit 2 (Day 1).
12 Inclusion criterion 12 (Body mass index for age and percentiles) removed with version 
4.0 of Clinical Study Protocol.
Sex
13 Male or female.
Reproduction
14 Females of childbearing potential who are sexually active, as judged by the Investigator, 
must use a highly effective method of contraception from screening, and must agree to 
continue using such precautions for 16 weeks after the final dose of IP.
5.2
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply:
Medical Conditions
1
History of any clinically significant disease or disorder other than asthma which, in the 
opinion of the Investigator, may either put the subject at risk because of participation in 
the study, or influence the results or the subject’s ability to participate in the study.
2
History of a deterioration in asthma or asthma exacerbation that required a burst of 
systemic corticosteroids within 6 weeks of Visit 1, up to and including Visit 2 (Day 1).
3
Exclusion criterion 3 (previous exclusion for intra-articular glucocorticosteroids for 
conditions other than asthma) removed with version 3.0 of Clinical Study Protocol. 
4
History of hospitalisation (overnight admission) for asthma within 3 months of Visit 1, up 
to and including Visit 2 (Day 1).
5
History of a life threatening asthma exacerbation requiring intubation or mechanical 
ventilation.
6
History of systemic corticosteroid use for the maintenance treatment of asthma within 
6 weeks of Visit 1, up to and including Visit 2 (Day 1) and discouraged until EOS.
7
A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not 
been treated with, or has failed to respond to, standard of care therapy.
8
History of a clinically significant infection, including upper or lower respiratory tract 
infection (with or without treatment of antibiotics or systemic antivirals) within 2 weeks 
of Visit 1 or during screening.
9
Tuberculosis requiring treatment within 12 months prior to Visit 1.

Clinical Study Protocol – 4.0
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CONFIDENTIAL AND PROPRIETARY
32
10 Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of 
Visit 2 (Day 1).
11 History of cancer.
Prior/Concomitant Therapy
12 Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives 
(whichever is longer) prior to Visit 1, up to and including Visit 2 (Day 1).
13 Receipt of any investigational nonbiologic agent within 30 days or 5 half-lives 
(whichever is longer) prior to Visit 1, up to and including Visit 2 (Day 1).
14 Receipt of immunoglobin or blood products within 30 days prior to Visit 1, up to and 
including Visit 2 (Day 1).
15 Receipt of live attenuated vaccines 30 days prior to Visit 1, up to and including Visit 2 
(Day 1).
Prior/Concurrent Clinical Study Experience
16 Subjects with known hypersensitivity to tezepelumab or any excipients of the product.
17 History of hypersensitivity or anaphylactic reaction to any biologic therapy. 
18 Concurrent enrolment in another drug-related interventional clinical trial.
Diagnostic assessments
19 Any clinically relevant abnormal findings in physical examination, ECG, vital signs, 
haematology, clinical chemistry, or urinalysis during screening, which in the opinion of 
the Investigator, may put the subject at risk because of his/her participation in the study, 
or may influence the results of the study, or the subject’s ability to complete entire 
duration of the study.
20 Evidence of active liver disease, including jaundice or aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), or alkaline phosphatase (ALP) > 2 × the upper limit of
normal (ULN) at Visit 1. Subjects with ongoing liver disease or inexplicably elevated 
liver chemistry values should be excluded from the study.
21 Positive hepatitis B surface antigen or hepatitis C virus antibody serology at Visit 1, or a 
positive medical history for hepatitis B or C. Subjects with a history of hepatitis B 
vaccination without history of hepatitis B are allowed to enrol.
22 Any clinical signs, symptoms, or abnormal findings during screening that may be 
indicative of past or present MIS-C.
23 Positive local COVID-19 viral rapid test at Visit 1. 
24 Positive local COVID-19 viral rapid test results at Visit 2. 

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
3 3
2 5
A hist or y  of k n o w n i m m u n o deficie nc y dis or der, i nclu di n g a p osi tive h u ma n 
i m m u n o deficie nc y vir us ( HI V) test at Visit 1, or t he s u bject i s ta ki n g a nt iretr o viral 
me dicat i ons as deter mi ne d b y  me dical hist or y a n d/ or s u bject’s ver bal re p ort.
Ot her E xcl usi o ns
2 6
Pare nt/ g uar dia n/s u bject has a hist or y  of ps yc hiatric disease, i ntellect ual deficie nc y, 
s u bsta nce a b use, or ot her c o n dit i on (e g, i na bilit y t o rea d, c o m pre he n d, or write) w hic h 
will li mit t he vali dit y of  c o nse nt t o participate i n t his st u d y . 
2 7
C hil dre n w h o are war ds of t he state or g o ver n me nt.
2 8
Pare nt/ g uar dia n i n v o l ve me nt i n t he pla n ni n g a n d/ or c o n d uct of t he st u d y (a p plies t o 
Astra Ze neca staff, C o ntrac t Researc h Or ga nisati o n [ C R O] staff a n d/ or staff at t he st u d y 
sit e).
2 9
J u d ge me nt b y t he I n vesti gat or t hat t he s u bject s h o ul d n ot partici pate i n t he st u d y if t he 
s u bject is u nli kel y t o c o mpl y  wit h st u d y pr oce d ures, restricti ons a n d re q uire me nts.
3 0
Pre vi o us e nr o l me nt i n t he prese nt st u d y. 
3 1
P arti cipa nts w h o ha ve ha d a c o nfir me d C O VI D -1 9 i nfect i on a n d ha ve n ot f ull y rec o vere d 
( base d o n I n vesti gat or j u d ge me nt) f or at least 8 wee ks pri or t o Visit 1.
3 2
P arti cip a nts wi t h a hist or y of se vere C O VI D-1 9 i nfecti o n re q uiri n g h os pi talisati on. 
3 3
Recei pt of a n y  C O VI D-1 9 vacci ne 2 8 da ys pri or t o Visit 2 ( Da y  1).
5. 3
Lifest yle C o nsi der ati o ns
5. 3. 1
Me als a n d Diet ar y Restricti o ns
S u bjects s h o ul d a v o i d eati n g a lar ge meal f or at least 2 h o urs pri or t o all l u n g f u ncti o n 
assess me nts at t he ce ntre.
S u bjects s h o ul d n ot eat or dri n k o ne h o ur pri or t o ha vi n g t he  
 test.
5. 3. 2
Acti vit y
S u bjects s h o ul d a v o i d e n ga gi n g i n stre n u o us e xerti o n f or at least 3 0 mi n utes pri or t o all l u n g 
f u ncti on assess me nts at t he ce ntre.
5. 4
Scree n F ail ures
Scree n fail ures are defi ne d as s u bjects w h o si g ne d t he I C F t o partici pate i n t he cli nical st u d y  
b ut are n ot s u bse q ue ntl y assi g ne d t o st u d y  tr e at me nt. A mi ni mal set of scree n fail ure 
i nf or mat i on is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects t o meet t he 
C o ns o li date d Sta n dar ds of Re p orti n g Trials ( C O N S O RT) p u blis hi n g re q uire me nts a n d t o 
res p o n d t o q ueries fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, 
scree n fail ure details, eli gi bility cri t eria a n d a n y S A E.
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
3 4
I n di vi d uals w h o d o n ot meet t he criteria f or partici patio n i n t his st u d y  (scree n fail ure) ma y be 
rescree ne d. Rescree n atte m pts are all o we d i n t he st u d y o nl y if o nl y if t he reas o n f or scree n 
fail ure was tra nsie nt (i ncl u di n g b ut n ot li mite d t o e q ui p me nt fail ure, e xcl usi on cri t erio n # 8 
[ Sectio n  5. 2 ], or ot her tra nsie nt c o n diti ons) a n d t he St u d y  P h ysicia n has dee me d t hat t he 
reas o n f or t he rescree n is vali d a n d has a p pr o ve d t he rescree n.
Rescree ne d s u bjects s h o uld be assi g ne d t he sa me s u bject n u m ber as f or t he i nit ial scree ni n g 
a n d be re-c o nse nte d.
Rescree ni n g s h o ul d be disc usse d wit h t he C R O Me dical M o nit or . If rescree ni n g is perf or me d 
wi t hi n 3 0 da ys of i nitial scree ni n g, assess me nts fr o m i nitial scree ni n g ma y be use d, h o we ver 
cli nicall y si g nifica nt fi n di n gs m ust be reassesse d, a n d t he s u bject m ust meet all e ntr y  crit eria 
n ote d i n t he pr ot oc ol. S u bjects rescree ne d m ore t ha n 3 0 da ys after i nit ial scree ni n g m ust 
re peat all assess me nts a n d meet all e ntr y crit eria n ote d in t he pr ot oc ol.
6
S T U D Y I N T E R V E N TI O N
St u d y  int er ve nt i on is defi ne d as a n y i n vesti gati onal i nter ve nt i on(s), m ar kete d pr o d uct(s), 
pl ace b o, or me dical de vice(s) i nte n de d t o be a d mi nistere d t o a st u d y  s u bject acc or di n g t o t he 
Cli nical St u d y  Prot oc ol  ( C S P). St u d y int er ve nt i on i n t his st u d y refers t o teze pel u ma b.
6. 1
St u d y I nter ve nti o n(s) A d mi nistere d
6. 1. 1
I n vesti g ati o n al Pr o d uct
I n vesti gati onal pr o d uct details are pr o vi de d i n  Ta ble 3.
Ta ble 3
I n vesti g ati o n al Pro d uct
Ar m  N a me
Treat me nt 1
I nter ve nti o n N a me
T e ze pel u ma b
T y pe 
Dr u g
D ose F or m ul ati o n
D os a ge Le vel
R o ute of A d mi nistr ati o n
S C i njecti o n
Use
E x peri me ntal
I M P a n d NI M P
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or
P ac k a gi n g a n d L a belli n g
St u d y i nter ve nti o n will be pr o vi de d i n si n gle use 
5 m L vials. Eac h vial will be la belle d i n acc or da nce 
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Table 3
Investigational Product
with GMP Annex 13 per country regulatory 
requirement. 
Former Names
MEDI9929 and AMG 157
GMP Good Manufacturing Practice; IMP Investigational medical product; NIMP Non-investigational 
medical product; SC Subcutaneous.
6.2
Preparation/Handling/Storage/Accountability of Interventions
1
The Investigator or designee must confirm appropriate temperature conditions of 2°C to 
8°C have been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention.
2
Only subjects enrolled in the study may receive study intervention and only authorised 
site staff may administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to the Investigator and 
authorised site staff.
3
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation and record maintenance 
(ie, receipt, reconciliation and final disposition records).
The IP will be supplied to the site in cartons with one vial of tezepelumab in each carton. Each 
vial as well as each carton will be labelled.
The IP kit will be allocated to the subject on a random basis by the site based on the available 
unused kits in the pharmacy.
The Investigator(s) will: 
1
Obtain signed assent from the potential subject and consent from their guardian/legal 
representative, before any study specific procedures are performed.
2
Determine subject eligibility.
3
Assign the potential subject a unique enrolment number, ie, ‘subject identification (SID) 
number’.
All unused supplies of IP will be destroyed by the site in accordance with their local Standard 
Operating Procedure (SOP). Investigational product destruction is not to be performed until 
approval has been granted by the sponsor. 
Upon request by the site or following database lock (DBL), IQVIA will ask the sponsor for 
approval for the sites to destroy their IP. Approval from the sponsor will be forwarded to the 

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
3 6
sites b y t he I Q VI A sit e mo ni t or.
6. 2. 1
D ose Pre p ar ati o n
Eac h vial s h o uld be vis uall y  ins pecte d pri or t o d ose pre parati o n. T he I P will be pr o vi de d t o t he 
st u d y sites as a c olo url ess t o sli g ht l y yell o w clear s ol ut i on c o ntai ne d i n a 5 m L si n gle use glass 
vial t o be st ore d at 2° C t o 8° C u nt il use d. If defects are n ote d wit h t he I P, t he I n vesti gat or a n d 
sit e mo ni t or s h o uld be n otifie d i m me diatel y. Pre paratio n of  I P must be perf or m e d b y a 
q ualifie d pers o n (e g, p har macist, I n vest i gat or or q ualifie d desi g nee) at t he site.
Pre parati o n of  t he I P is t o be perf or me d ase pt icall y. Tot al i n-use st ora ge ti me fr o m  nee dle 
p u nct ure of t he I P vial t o start of a d mi nistrati o n s h o ul d n ot e xcee d 4 h o urs at r o o m 
t e mperat ure. If st ora ge ti me e xcee ds t his li mit, a ne w d ose m ust be pre pare d fr o m a ne w vial.
D ose pre parati o n ste ps:
1.
All o w t he vial t o e q uili brate at r o o m te m perat ure (a b o ut 3 0 mi n utes t o o ne h o ur). 
E ns ure t hat t he vial is a de q uatel y pr otecte d fr o m li g ht d uri n g t he war mi n g pr ocess. 
Ge nt l y s wirl t he vial t o e ns ure t he c o nte nts are mi xe d t o a clear, h om o ge ne o us 
s olut i on. D o n ot s ha ke.
2.
T o pr e pare I P f or a d mi nistrati o n re m o ve t he ta b p orti o n of t he vial ca p a n d clea n t he 
st o p per wit h 7 0 % et h yl alc o h ol or e q ui vale nt.
3.
At tac h a 2 1 G 1 ½-i nc h sterile dis p osa ble nee dle t o a 1 m L sterile s yri n ge.
4.
5.
Re m o ve a n d discar d t he 2 1 G 1 ½ -i nc h sterile dis p osa ble nee dle fr o m t he s yri n ge.
6.
At tac h a ne w 2 7 G ½-i nc h sterile dis p osa ble nee dle t o t he sa me s yri n ge i n ste p 5.
7.
A p pl y t he a p pr o priate la bel t o t he s y rin ge acc or di n g t o l o c al  sta n dar d practice.
T he assi g ne d vial s h o ul d be use d o nl y  o nce t o pre pare a si n gle d ose re q uire d at t he d osi n g 
visit. T he I P d oes n ot c o ntai n preser vat i ves a n d a n y u n use d pr o d uct i n o pe ne d a n d dis pe nse d 
vials s h o ul d n ot be use d f or s u bse q ue nt d osi n g a n d s h o ul d be st ore d u ntil I P acc o u nta bilit y has 
be e n c o mplete d as per t he site ’s S O P. If t he o pe ne d a n d dis pe nse d vials m ust be discar de d 
i m me diatel y after d ose pre parati o n as per t he site’s S O P, t he vial la bels al on g wit h t he cart o ns 
m ust be retai ne d f or I P acc o u nta bilit y.  
T he I P will be a d mi nistere d b y o ne S C i nject i on (see  Ta ble 4 ) acc or di n g t o sta n dar d practice. 
Sta n dar d n u m bi n g me dicat i ons/ de vices a n d/ or distracti o n tec h ni q ues ma y be use d wit h 
a d mi nistrati o n of I P.
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C O N FI D E N TI A L A N D P R O P RI E T A R Y
3 7
Ta ble 4
I n vesti g ati o n al Pro d uct D ose Pr e p ar ati o n
D ose
N u m ber of vi al(s) 
re q uire d
S yri n ge size re q uire d
T ot al v ol u me 
a d mi nistere d
1
1 m L
T he v o l ume of I P dra w n u p a n d i njecte d as well as a n y d osi n g iss ues e nc o u ntere d will be 
rec or de d i n t he electr o nic case re p ort f or m (e C R F).
6. 2. 2
D ose A d mi nistr ati o n
If a n y of t he fol l owi n g has occ urre d, t he I P s h o ul d n ot be a d mi nistere d:

T he s u bject recei ve d aller ge n i m m u n ot hera p y  inje ctio n wi t hi n 7 da ys of sc he d ule d I P 
a d mi nistr atio n.

T he s u bject has a n i nterc urre nt ill ness t hat i n t he o pi ni o n of t he I n vest i gat or ma y 
c o mpr o mise t he safet y of  t he s u bject i n t he st u d y (e g, vir al ill nesses).

T he s u bject is fe brile ( ≥3 8° C; ≥1 0 0. 4° F) wi t hi n 7 2 h o urs prior t o I P a d mi nistrati o n.
T h e visit s h o ul d be resc he d ule d t o a n ot her date a n d I P s h o ul d be a d mi nistere d at t hat visit. 
D el a y of t he d osi n g visit ca n be e xte n de d f or a n a d diti onal 1 4 da ys.
T he I P will be a d mi nistere d i n t he a nteri or t hi g h b y a q ualifie d healt hcare pr ofessi o nal (e g, 
I nvest i gat or or q ualifie d desi g nee) at t he site. T he i njecti on site m ust be rec or de d i n t he s o urce 
d oc u m e nts a n d i n t he e C R F. T he pers o n a d mi nisteri n g t he d ose will wi pe t he s ki n s urface of 
t he a nteri or t hi g h wit h alc o h o l a n d all o w t o ai r dr y. T he s ki n will be pi nc he d t o is o late t he S C 
tiss ue fr o m t h e muscle. T he nee dle will be i nserte d at a 9 0 -de gree a n gle a p pr o xi matel y 
half wa y i nt o t he S C tiss ue. T he I P will be sl o wl y i njecte d ( n o l o n ger t ha n 5 sec o n ds d urati o n 
is rec om me n de d) i nt o t he S C tiss ue usi n g ge nt le press ure. T he area s h o ul d n ot be massa ge d 
after i njecti on.
N ote: Ti me o f di s pe nsi n g of I P, ti me I P ta ke n o ut of t he fri d ge a n d ti me of I P a d mi nistrati o n 
s h o uld be rec or de d i n a s pecific l o g. T his l o g m ust be a part of t he s u bject ’s s o urce 
d oc u m e nts.
S u bj ects s h o uld be o bser ve d f or a mi ni m u m of 2 h o urs after a d mi nistrati o n o f t he I P for t he 
a p peara nce of a n y ac ute dr u g reactio ns (see  A p pe n di x G ). 
If t he s u bject/ pare nt/le gal re prese ntati ve re p orts a n i njecti o n site react i on, t he I n vesti gat or or 
q ualifie d desi g nee will c o m p lete t he A E e C R F pa ge.
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6.2.3
Procedures for Handling Incorrectly Enrolled Subjects
Subjects who fail to meet the eligibility criteria should not, under any circumstances, receive 
study IP. There can be no exceptions to this rule. 
If a subject does not meet all the eligibility criteria but is enrolled in error, or incorrectly 
receives IP, the Investigator should inform the AstraZeneca Study Physician immediately. All 
subjects who receive study IP should remain in the study and the subjects should continue to 
be followed up in accordance with defined study procedures.
6.3
Measures to Minimise Bias: Randomisation and Blinding (Not 
applicable)
Blinding is not applicable as this is an open label, non-randomised study. 
6.4
Study Intervention Compliance
When subjects are dosed at the site, they will receive study intervention directly from the 
Investigator or designee, under medical supervision. The date, and time if applicable, of dose 
administered in the clinic will be recorded in the source documents and recorded in the eCRF. 
The dose of study intervention and study subject identification will be confirmed at the time of 
dosing by a member of the study-site staff other than the person administering the study 
intervention.
The IP Storage Manager is responsible for managing the IP from receipt by the study site until 
the destruction of all unused IP. The date and time of all IP administrations should be recorded 
in the appropriate section of the eCRF.
6.5
Concomitant Therapy
Throughout the study, Investigators may prescribe concomitant medications or treatments 
(including rescue medication as required) deemed necessary to provide adequate supportive 
care. All use of concomitant medications and supplements (nutritional and prophylactic) will 
be recorded on the concomitant medication eCRF.
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins 
and/or herbal supplements) that the subject is receiving at the time of enrolment or receives 
during the study must be recorded along with:

Reason for use

Dates of administration including start and end dates

Dosage information including dose and frequency.
Refer to Section 8.1.1.1 for details of maintenance therapy restrictions on the days when lung 

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
3 9
f u ncti on testi n g is perf or m e d a n d t o Sectio n 8. 1. 2 f or restricti ons pri or t o t he  
 test.
Ast h ma w orse ni n gs/e xacer bat i ons s h o ul d be treate d wit h oral, i n hale d, or ot her me dicat i ons 
(incl u di n g c ortic oster oi ds a n d resc ue me dicat i on) acc or di n g t o sta n dar d practi ce. T he decisi o n 
a n d t he a d mi nistrati o n ma y be at t he discreti on of t he I n vest i gat or a n d/ or pare nt/le gal 
g uar di a n/s u bject u p o n te m p orar y w orse ni n g of ast h ma si g ns a n d s y m pt o ms. I n cases of 
ast h ma w orse ni n g/e xacer bat i on, s u bjects s h o ul d be e val uate d at t he st u d y ce ntre w he n 
feasi ble. 
All me dicati o ns ta ke n f or ast h ma or ot her c o n diti o ns i n t he 6 m o nt hs pri or t o Visit 1 m ust be 
rec or de d i n t he e C R F al on g wit h reas o n f or treat me nt b y t he I n vest i gat or/a ut h orise d dele gate 
at eac h visit.
T he C R O Me dical M o ni t or s h o uld be c o ntacte d if t here are a n y  q uesti ons re gar di n g 
c o nc o mita nt or pri or t hera p y.
6. 5. 1
Restricte d Me dic ati o ns
Restricte d me dicati o ns are s h o w n i n  Ta ble 5.
Ta ble 5
Restricte d Me dic ati o ns
Restricte d me dic ati o n/cl ass of dr u g
Us a ge
Ast h ma mai nte na nce treat me nts
C ha n ges i n eit her d ose or re gi me n are disc o ura ge d fr o m 
Visit 1 a n d t hr o u g h o ut t he st u d y, u nless t here is a n 
a bs ol ute me dical nee d as j u d ge d b y t he I n vesti gat or.
O nce dail y L A B A a n d L A M A s h o ul d be wit h hel d f or at 
least 2 4 h o urs pri or sc he d ule d s pir o metr y a n d  
 at site 
visits a part fr o m a n y u nsc he d ule d visits d ue t o ast h ma 
w orse ni n g.
T wice dail y L A B A - a n d L A M A-c o ntai ni n g t hera pies 
s h o ul d be wit h hel d f or at least 1 2 h o urs pri or t o sc he d ule d 
s pir o metr y a n d  
at site.
L T R A s h o ul d be restricte d f or at least 2 4 h o urs pri or t o 
sc he d ule d s pir o metr y a n d  
 at site.
S h ort -acti n g β 2-a g onists ( S A B A) 
Re g ular sc he d ule d use is n ot all o we d fr o m Visit 1 a n d 
prefera bl y t hr o u g h o ut t he st u d y, u nless t here is a n a bs ol ute 
me dical nee d as j u d ge d b y t he I n vesti gat or. As re q uire d 
( P R N) use is all o we d; h o we ver, atte nti o n s h o ul d be pai d t o 
t he f oll o wi n g restricti o n:
•
If p ossi ble, S A B A s h o ul d be wit h hel d at least 6 h o urs 
pri or t o sc he d ule d s pir o metr y,  
 a n d E C G.
Ma y  be use d f or ma na gi n g a n ast h ma e xacer bati o n e ve nt.
S h ort -acti n g a nti m uscari nics ( S A M A; i pratr o pi u m)
If p ossi ble, S A M A s h o ul d be wit h hel d at least 6 h o urs 
pri or t o sc he d ule d s pir o metr y,  
 a n d E C G. 
I nacti ve/ kille d vacci nati o ns (e g, i nacti ve i nfl ue nza)
All o we d, pr o vi de d t he y are n ot a d mi nistere d wit hi n 7 da y s 
bef ore or after I P a d mi nistrati o n/ Visit 2.
C CI
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Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 0
Ta ble 5
Restricte d Me dic ati o ns
Restricte d me dic ati o n/cl ass of dr u g
Us a ge
C O VI D -1 9 vacci nati o n
All o we d, pr o vi de d t hat vacci nati o n is n ot a d mi nistere d 
wit hi n 2 8 da ys bef ore a n d 1 4 da ys after I P 
a d mi nistrati o n/ Visit 2
Aller ge n i m m u n ot hera p y
All o we d, if o n sta ble t hera p y f or at least 1 m o nt h pri or t o 
Visit 1 wit h n o a ntici pate d c ha n ge d uri n g t he st u d y.
T his s h o ul d n ot be a d mi nistere d wit hi n 7 da ys bef ore or 
after I P a dmi nistrati o n/ Visit 2.
E C G Electr ocar di o gra m; 
; I P I n vesti gati o nal pr o d uct; L A B A L o n g-acti n g 
β 2 -a g o nist; L A M A L o n g -acti n g m uscari nic a nta g o nist; L T R A Le u k otrie ne rece pt or a nta g o nist.
6. 5. 2
Pr o hi bite d Me dic ati o ns
T hera pies e xcl u de d at scree ni n g a n d t hr o u g h o ut t he st u d y ( Sectio n 5. 2 ) are pr o hi bite d a n d 
ma y o nl y be a d mi nistere d if necessar y , t o pr o vide a de q uate s u p p orti ve care (Ta ble 6 ).
Ta ble 6
P r o hi bite d Me dic ati o ns
Pr o hi bite d me dic ati o n/cl ass of dr u g
Us a ge
Li ve Atte n uate d Vacci nes
N ot all o we d 3 0 da ys pri or t o Visit 1 a n d prefera bl y 
t hr o u g h o ut t he st u d y. If t here is a n a bs ol ute me dical nee d 
as j u d ge d b y t he I n vesti gat or, d o n ot a d mi nister pri or t o 
4 wee ks after d ose of I P.
A n y  s yste mic i m m u n o m o d ulat ors or 
i m m u n os u p pressi ves
N ot all o we d t hr o u g h o ut t he st u d y, u nless t here is a n 
a bs ol ute me dical nee d as j u d ge d b y t he I n vesti gat or. 
S y ste mic c ortic oster oi ds ma y be use d f or ma na gi n g a n 
ast h ma w orse ni n g/e xacer bati o n e ve nt.
I m m u n o gl o b uli n or bl o o d pr o d ucts
N ot all o we d 3 0 da ys pri or t o Visit 1 a n d t hr o u g h o ut t he 
st u d y, u nless t here is a n a bs ol ute me dical nee d as j u d ge d 
b y t he I n vesti gat or.
A n y  mar kete d (e g, o maliz u ma b, me p oliz u ma b, 
resliz u ma b) or t o be mar kete d, or i n vesti gati o nal 
bi ol o gic treat me nt
N ot all o we d 4 m o nt hs or 5 half -li ves ( w hic he ver is l o n ger) 
pri or t o Visit 1 a n d t hr o u g h o ut t he st u d y.
Ot her i n vesti gati o nal pr o d ucts
(i ncl u di n g i n vesti gati o nal use of a n a p pr o ve d dr u g)
N ot all o we d 3 0 da ys or 5 half -li ves ( w hic he ver is l o n ger) 
pri or t o Vis it 1 a n d t hr o u g h o ut t he st u d y, u nless t here is a n 
a bs ol ute me dical nee d as j u d ge d b y t he I n vesti gat or.
Me dicati o ns n ot c urre ntl y lice nse d f or use i n t he 
treat me nt of ast h ma i n c hil dre n, (e g, t he o p h ylli ne), 
a n d n ot part of c urre nt sta n dar d of care
N ot all o we d fr o m Visit 1 a n d t hr o u g h o ut t he st u d y, u nless 
t here is a n a bs ol ute me dical nee d as j u d ge d b y t he 
I n vesti gat or.
I P I n vesti gati o nal pr o d uct.
6. 6
D ose M o dific ati o n ( N ot a p plic a ble)
6. 7
I nter ve nti o n after t he E n d of t he St u d y
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Subjects who complete Day 85/EOS should be given standard of care therapy at the discretion 
of the Investigator. 
7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1
Discontinuation of Study Intervention
This is a single-dose study, therefore discontinuation from IP treatment is not applicable.
7.2
Participant Withdrawal from the Study

A subject may withdraw from the study at any time at his/her or parent/legal 
representative’s 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 subject who considers withdrawing from the study should be encouraged to remain in 
the study and attend all study visits to have a minimum of AEs, SAEs and concomitant 
medication information collected. If the subject or parent/guardian does not agree to 
continue in-person study visits, modified follow-up options (eg, telephone contact with 
the subject or parent/guardian) should be arranged to ensure the collection of safety 
information through the Day 85 time point.

At the time of withdrawal from the study, if possible, an EOS visit should be conducted, 
as shown in the SoA (Table 1). See SoA for data to be collected at the time of study 
withdrawal and follow-up and for any further evaluations that need to be completed.

If the subject withdraws consent for disclosure of future information, the sponsor may
retain and continue to use any data collected before such a withdrawal of consent.

If a subject withdraws from the study, it should be confirmed if he/she or their 
parent/legal representative still agrees for existing samples to be used in line with the 
original consent. If he/she requests withdrawal of consent for use of samples, destruction 
of any samples taken and not tested should be carried in line with what was stated in the 
informed consent and local regulation. The Investigator must document the decision on 
use of existing samples in the site study records and inform the Global Study Team.
7.2.1
Replacement of Subjects
Subjects who are eligible to participate but do not go on to receive tezepelumab, or subjects 
who do not complete the required evaluations through to Day 85 may be replaced to maintain 
the stipulated number of evaluable subjects, at the discretion of the Sponsor. 
7.3
Lost to Follow-up
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 

Clinical Study Protocol – 4.0
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CONFIDENTIAL AND PROPRIETARY
42
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit:

The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject/parent/legal representative on the importance of 
maintaining the assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study.

Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject/parent/legal representative (where possible, 
3 telephone calls and, if necessary, a certified letter to the subject/parent/legal 
representative’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the subject’s medical record.
Discontinuation of specific sites or of the study are handled as part of Appendix A.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarised in the SoA (Table 1). Protocol waivers 
or exemptions are not allowed.

Immediate safety concerns should be discussed with the IQVIA Global Therapeutic 
Medical Adviser immediately upon occurrence or awareness to determine if the subject 
should continue or discontinue in the study.

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 
subjects meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Planned sampled blood volume will be compliant with recommendations relating to GCP in 
the conduct of clinical trials (European Commission 2008, Howie 2011); the maximum 
amount of blood collected, including any losses in the manoeuvre, from each subject should 
not exceed 3% of the total blood volume during a period of 4 weeks and should not exceed 
1% at any single time during the study (Table 7). Repeat or unscheduled samples may be 
taken for safety reasons or for technical issues with the samples.

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Table 7
Maximum Volume of Blood to be Drawn from a Subject
Subject weight (kg)
Total blood volume 
(mL) a
Maximum blood 
volume (mL) to be 
drawn at any visit
Maximum blood 
volume (mL) to be 
drawn within a 
4-week period
15-20
1200-1600
12.0-16.0
36.0-48.0
21-25
1680-2000
16.8-20.0
50.4-60.0
26-30
2080-2400
20.8-24.0
62.4-72.0
31-35
2480-2800
24.8-28.0
74.4-84.0
36-40
2880-3200
28.8-32.0
86.4-96.0
41-45
3280-3600
32.8-36.0
98.4-108.0
46-50
3680-4000
36.8-40.0
110.8-120.0
51-55
4080-4400
40.8-44.0
122.4-132.0
56-60
4480-4800
44.8-48.0
134.4-144.0
61-65
4880-5200
48.8-52.0
146.4-156.0
66-70
5280-5600
52.8-56.0
158.4-168.0
71-75
5680-6000
56.8-60.0
170.4-180.0
76-80
6080-6400
60.8-64.0
182.4-192.0
81-85
6480-6800
64.8-68.0
194.4-204.0
86-90
6880-7200
68.8-72.0
206.4-216.0
91-95
7280-7600
72.8-76.0
218.4-228.0
96-100
7680-8000
76.8-80.0
230.4-240.0
a
The total blood volume is estimated at 80 mL/kg body weight.
The total volume of blood to be drawn from each subject at each study visit is shown in 
Table 8.

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Table 8
Volume of Blood to be Drawn from Each Subject
Visit (Study day)
Sample
Sample blood 
volume (mL)
Visit total blood 
volume (mL)
Screening
Chemistry (including β-HCG if required)
3.5
10.5
Haematology
2.0
Serology (HIV)
2.5
Hepatitis B/Hepatitis C
2.5
V2 (Day 1)
Chemistry
3.5
15.5
Haematology
2.0
PK
2.5
ADA
5.0
IgE
2.5
V3 (Day 3)
PK
2.5
2.5
V4 (Day 7)
PK
2.5
2.5
V5 (Day 11)
PK
2.5
2.5
V6 (Day 15)
Chemistry
3.5
8.0
Haematology
2.0
PK
2.5
V7 (Day 29)
Chemistry
3.5
15.5
Haematology
2.0
PK
2.5
ADA
5.0
IgE
2.5
V8 (Day 57)
PK
2.5
2.5
V9 (Day 85/EOS)
Chemistry
3.5
15.5
Haematology
2.0
PK
2.5
ADA
5.0
IgE
2.5
Total blood volume (mL)
75.0
Volumes exclude serum pregnancy testing (with the exception of Visit 1) and exclude any re-testing 
requirements. If serum pregnancy testing is needed at any other visits, then an additional 2.5 mL blood collection 
will be required.
ADA Anti-drug antibodies; β-HCG Beta-human chorionic gonadotrophin; EOS End of Study; HIV Human 
immunodeficiency virus; IgE Immunoglobulin E; PK Pharmacokinetic; V Visit.
8.1
Efficacy Assessments
Planned time points for all efficacy assessments are provided in the SoA (Table 1).

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 5
8. 1. 1
S pir o metr y
C CI

C li nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 6
8. 1. 1. 2
S pir o metr y Testi n g
S pi r o metr y testi n g ca n be c om p lete d at a n y time d uri n g t he da y  a n d wit hi n ± 1. 5 h o urs of t he 
ti me t he scree ni n g s pir omet r y was c o mpl ete d. F or e xa m ple, if t he scree ni n g s pir o met r y is at 
0 8 0 0, t he n all s pir o met r y t estin g at s u bse q ue nt visits nee d t o be c o m plete d bet wee n 0 6 3 0 a n d 
0 9 3 0. O n Da y  1, s pir o metr y testi n g will be perf or me d bef ore a d mi nistrati o n of I P.
T he s u bject s h o ul d wear c o mf ort a bl e clot hi n g w hic h d oes n ot restrict t he c hest or a b d o me n. 
T he s u bject s h o ul d rest f or at least 1 5 mi n utes pri or t o t he test a n d s h o ul d be sitti n g d uri n g 
s pir o metr y t estin g. F orce d e x pirat or y  ma n oe u vres s h o ul d be perf or me d wit h t he s u bject seate d 
i n a n u pri g ht p osi tio n. If t his is n ot c o mf orta ble f or t he s u bject, sta n di n g is per mitte d. T he 
sa me p ositio n s h o ul d be use d b y t he s u bject f or eac h f orce d e x pirat or y  ma n oe u vre t hr o u g h o ut 
t he st u d y. A n ose -cli p s h o uld be use d f or t he ma n oe u vre a n d t he hea d m ust n ot be tilte d d uri n g 
ma n oe u vres. M o ut h pieces of t he sa me di me nsi o n a n d s ha pe s h o ul d be use d b y t he s u bject 
t hr o u g h o ut t he st u d y.
T he f orce d e x pirat or y  ma n oe u vre ( F E V 1) s h o ul d start wit h a ma xi mal i ns pirati on a n d t he n be 
f oll owe d b y a fast a n d f orcef ul e x pirati on t hat s h o ul d l ast for at l east 6 sec o n ds. It is i m p orta nt 
t o e nc o ura ge t he s u bject t o c o nti n ue t he e x pirati on t o be fast a n d f orcef ul t hr o u g h o ut t he 
ma n oe u vre. E ns ure t hat n o ne of t he f o ll owi n g has occ urre d:

C o u g hi n g d uri n g t he first sec o n d

Gl otti s clos ure

Lea k, or

O bstr ucti o n of t he m o ut h piece ( b y  t he t o n g ue).
M ul tipl e f orce d e x pirat or y  eff orts (at least 3 b ut n o m ore t ha n 8) will be perf or me d f or eac h 
s pir o metr y sessio n  a n d t he 2 best eff orts t hat meet A T S/ E R S acce pta bilit y a n d re pr o d uci bi lity 
criteria will be rec or de d i n t he e C R F. T he best eff orts will be base d o n t he hi g hest F E V1. T he 
ma xi m u m F E V 1 of  t he 2 best eff orts will be use d f or t he a nal ysis. T he perce nta ge of pre dicte d 
n or m al val ue f or F E V 1 will be rec or de d usi n g t he l ocal s pir o me ter at t he site wit h pre dicte d 
val ues deri ve d fr o m t he a p pr o priate refere nce val ue of c h o ice, e g, N H A N E S III 2 0 1 0 , 
Q ua njer et al 2 0 1 2 , etc. 
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 7
8. 2
S afet y Assess me nts
Pl a n ne d ti me p o i nts f or all safety assess me nts are pr o vi de d i n t he S o A (Ta ble 1 ).
C CI

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8.2.1
Physical Examinations
Physical examinations will be performed at timelines as specified in the SoA (Table 1). 

A complete physical examination will be performed and include assessments of the 
following: general appearance, respiratory, cardiovascular, abdomen, skin, head and neck 
(including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal (including 
spine and extremities) and neurological systems. 

A brief physical examination will include, at a minimum, assessments of the following: 
general appearance, respiratory, cardiovascular and abdominal systems.
See Section 8.3.5 for reporting AEs based on physical examinations.
8.2.1.1
Weight and Height
Weight and height will be measured in accordance with the SoA (Table 1). 
The subject’s weight will be recorded in kilograms, and height will be recorded in 
centimeters. Weight and height measurements will be performed in light clothing and with 
shoes off.
8.2.2
Vital Signs
Vital signs will be performed at timelines as specified in the SoA (Table 1). If required, this 
may be done by a study nurse at the subject’s home on the Day 11 visit, if previously 
approved and agreed with AstraZeneca.
Vital signs (blood pressure [BP], heart rate, respiratory rate and body temperature) will be 
obtained in accordance with SoA. 
On Day 1, vital signs will be assessed within 1 hour prior to and at 1 hour and 2 hours post-IP 
administration.
Vital signs will be taken prior to blood drawing, and, if possible, usual asthma controller 
medication. 
Blood pressure and pulse measurements will be assessed in sitting position with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available.
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for 
the subject in a quiet setting without distractions (eg, television, cell phones). 
Pulse rate will be obtained before BP, if the manual measurement technique is used.

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Respiration rate will be obtained after the subject has been resting for at least 5 minutes, by 
counting number of breaths (ie, how many times the chest rises) for one minute.
Body temperature will be measured prior to IP administration, in accordance with local 
standards.
See Section 8.3.5 for reporting AEs based on vital signs.
8.2.3
Electrocardiograms
A 12-lead ECG will be performed at timelines as specified in the SoA (Table 1), using local 
site equipment.
Electrocardiograms will be taken in supine position, prior to blood draw and spirometry.
Electrocardiograms should be preceded by at least 5 minutes of rest for the subject in a quiet 
setting without distractions (eg, television, cell phones).
The Investigator or authorised delegate will be responsible for the overall interpretation and 
determination of clinical significance of any potential ECG findings. In case of discrepancy 
between the Investigator’s interpretation and that provided by the ECG machine (if 
applicable), the Investigator’s interpretation will take precedence and should be noted on the 
printout and recorded in the eCRF. A copy of the ECG will be produced, and quality checked 
and kept in case of further need for re-evaluation.
It is highly recommended that the same machine is used for assessment of the subject 
throughout the study.
The ECG data and evaluation will be recorded in the eCRF.
See Section 8.3.5 for reporting AEs based on vital signs.
8.2.4
Clinical Safety Laboratory Assessments
Blood and urine samples for determination of clinical chemistry, haematology and urinalysis 
will be taken at the visits indicated in the SoA (Table 1).
Local clinical routine procedures to reduce pain and discomfort from blood sampling in 
children will be followed, eg, offering topical anaesthesia, coordinated sampling to avoid 
repeated punctures as appropriate in accordance with ethical and instruction guidelines for 
paediatric blood sampling.
Additional safety samples may be collected if clinically indicated at the discretion of the 
Investigator. The date of collection will be recorded on the appropriate eCRF.

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Instructions for sample collection, processing, storage and shipment will be provided in a 
separate Laboratory Manual provided to the sites.
The clinical chemistry, haematology and urinalysis will be performed at a central laboratory.
Table 9 shows the laboratory variables to be measured.

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Table 9
Laboratory Safety Variables
Haematology (CBC with differential)
Clinical chemistry (serum or plasma)
B-Haemoglobin (Hb)
S-Alkaline phosphatase (ALP)
B-Basophil differential count (absolute count)
S-Alanine aminotransferase (ALT)
B-Lymphocyte differential count (absolute count)
S-Aspartate aminotransferase (AST)
B-Platelet count
S-Bilirubin, total
B-Eosinophil differential count (absolute count)
S-Blood urea nitrogen
B-Monocyte differential count (absolute count)
S-Calcium, total
B-Neutrophil differential count (absolute count)
S-Chloride
White blood cell (WBC) count
S-Creatinine
S-Creatinine kinase (CK)
Urinalysis (dipstick) a
S-C-reactive protein (CRP)
U-Hb/Erythrocytes/Blood 
S-Glucose
U-Protein/Albumin 
S-beta-Human chorionic gonadotrophin (β-HCG) 
U-Glucose 
S-Potassium
U-Microscopy and culture as requiredb
S-Sodium
Virology screen
COVID-19 testing
Hepatitis B surface antigen (HBsAg)
Local viral rapid test 
Hepatitis C virus (HCV)
Human immunodeficiency virus (HIV)
B Blood; CBC Complete blood count; COVID-19 Coronavirus disease 2019; S Serum; U Urine.
a The urine dipstick test is not only limited to blood, protein, and glucose, but also additional test analytes as 
defined by central laboratory.
b Urine samples will be analysed locally with the urine dipstick test and sent to the central laboratory only for 
further microscopy and culture analysis when an abnormal dipstick result for any parameter is observed. 
NB. In case a subject shows an AST or ALT ≥3 × ULN together with total bilirubin (TBL) 
≥2 × ULN, please refer to Appendix D ‘Actions required in cases of increases in liver 
biochemistry and evaluation of Hy’s Law’ (HL), for further instructions. See Section 8.3.5 for 
reporting AEs based on laboratory values.
8.2.4.1
Pregnancy Test
The following tests will be performed for female subjects of childbearing potential 
(determined at the discretion of the Investigator), as specified in the SoA (Table 1).

Serum beta-human chorionic gonadotrophin (β-HCG) at Visit 1.

Urine pregnancy test (dipstick) at Visit 2 (treatment day) and EOS visit. A positive urine 
test result must be confirmed with a serum pregnancy test.

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8.2.5
Other Safety Assessments
8.2.5.1
Virology
Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCAb), HIV-1 and HIV-2 
antibodies will be assessed at Visit 1 only. All testing for these will be performed at a central 
laboratory.
Local COVID-19 viral rapid test results must be recorded in the eCRF.
Instructions for sample collection, processing, storage and shipment will be provided in a 
separate Laboratory Manual provided to the sites.
8.2.5.2
COVID-19 Testing
Due to the changing landscape surrounding COVID-19 testing, a local COVID-19 rapid test 
has become available during study conduct and is permitted for site use per the SoA (Table 1) 
provided: 

Test turnaround time is less than 60 minutes in order to minimise subject/caregiver 
time spent at site visits

Sensitivity and specificity are at least 95%

Test is approved by the Sponsor
After local COVID-19 viral rapid testing at V1 and V2, repeat testing may be performed at 
any time for a subject suspected of having COVID-19 using either viral rapid testing or testing 
via the central laboratory.
Local COVID-19 viral rapid test results must be recorded in the eCRF.
Instructions for sample collection, processing, storage and shipment will be provided in a 
separate Laboratory Manual provided to the sites.
8.3
Adverse Events and Serious Adverse Events
The 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.
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, 
surrogate, or the subject’s legally authorised representative). 

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The Investigator and any designees are responsible for detecting, documenting and recording 
events that meet the definition of an AE. For information on how to follow-up AEs, see 
Section 8.3.2.
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
Adverse Events will be collected from time of signature of ICF throughout the treatment day 
and the follow-up period.
Serious AEs will be recorded from the time of signing of the ICF.
If the Investigator becomes aware of an SAE with a suspected causal relationship to the IP that 
occurs after the end of the clinical study in a subject treated by him or her, the Investigator 
shall, without undue delay, report the SAE to the sponsor.
8.3.2
Follow-up of AEs and SAEs
Any AEs that are unresolved at the subject’s last AE assessment or other assessment/visit as 
appropriate in the study are 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 subject 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)

Severity

The date when the AE started and stopped

Whether the AE is serious or not

Investigator causality rating against the IP (yes or no)

Action taken with regard to IP

AE caused subject’s withdrawal from study (yes or no)

Outcome.
In addition, the following variables will be collected for SAEs:

Date AE met criteria for serious AE

Date Investigator became aware of serious AE

AE is serious due to

Date of hospitalisation

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
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 should 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 investigational product?’
For SAEs, causal relationship should 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 provided in Appendix B.
8.3.4
Adverse Events Based on Signs and Symptoms
All AEs spontaneously reported by the subject or care provider or reported in response to the 
open question from the study-site staff: ‘Have you/the child 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 
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 CSP mandated laboratory tests and vital signs will be summarised 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 fulfil any of the SAE criteria, are the reason 
for discontinuation of treatment with the IP, 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, dose adjustment or drug interruption).
If deterioration in an unscheduled (non-protocol mandated) laboratory value/vital sign is 

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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, anaemia versus low haemoglobin value). In the absence of clinical signs or symptoms, 
clinically relevant deteriorations in non-mandated parameters should be reported as AE(s).
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
Hy’s Law
Cases where a subject shows elevation in liver biochemistry may require further evaluation 
and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may need to be 
reported as SAEs. Please refer to Appendix D for further instruction on cases of increases in 
liver biochemistry and evaluation of HL.
8.3.7
Adverse Events of Special Interest
An AE of special interest (AESI) is an event of scientific and medical interest towards 
improving the understanding of the IP. An AESI may be serious or non-serious. For this study, 
AESIs include:

Anaphylactic reactions 

Immune complex disease (Type III hypersensitivity reactions)

Malignancy

Helminth infections 

Severe infections which are defined as:

SAEs or 

Requiring treatment with systemic antiviral medications, intravenous antibiotics or 
medications for helminth parasitic infection.

Injection site reactions 

Opportunistic infections

Guillain Barre Syndrome.
8.3.8
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, then Investigators or other site personnel inform 

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the appropriate AstraZeneca representatives 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 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 is undertaken immediately. Investigators or other site personnel 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.
Once the Investigators or other site personnel indicate an AE is serious in the web-based data 
capture (WBDC) system, an automated email alert is sent to the designated AstraZeneca 
representative.
If the WBDC system is not available, then the Investigator or other study-site staff reports a 
SAE to the appropriate AstraZeneca representative by telephone.
The AstraZeneca representative will advise the Investigator/study-site staff how to proceed.
For further guidance on the definition of a SAE, see Appendix B.
The reference document for definition of expectedness/listedness is the IB for tezepelumab.
8.3.9
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca except for:

If the pregnancy is discovered before the study subject has received any IP.
8.3.9.1
Maternal Exposure
If a subject becomes pregnant during the course of the study, she should be discontinued from 
the study 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 
abnormalities/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 abnormality) should be followed up and documented even if the subject 

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was discontinued from the study.
If any pregnancy occurs in the course of the study, then the Investigator or other site personnel 
informs the appropriate AstraZeneca representatives 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 
or 5 calendar days for SAEs (see Section 8.3.8) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available.
The PREGREP module in the eCRF is used to report the pregnancy and the PREGOUT is 
used to report the outcome of the pregnancy.
8.3.10
Medication Error
If a medication error occurs in the course of the study, then the Investigator or other site 
personnel informs the appropriate AstraZeneca representatives 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 completed 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 (see Section 8.3.8) and within 30 days for all other 
medication errors.
The definition of a medication error can be found in Appendix B. 
8.3.11
Management of Anaphylaxis
Appropriate drugs (eg, epinephrine, H1 and H2 antihistamines, and corticosteroids), and 
medical equipment to treat acute anaphylactic reactions must be immediately available at the 
clinical research site where IP is administered. Study personnel must be trained to recognise 
and treat anaphylaxis (Lieberman et al 2010). Details on anaphylaxis management are 
provided in Appendix G.
Anaphylaxis will be defined as a serious reaction that is rapid in onset (minutes to hours) and 
that may result in death (Sampson et al 2006). Anaphylaxis to an IP that the subject has not 
been previously exposed to (such as tezepelumab) is deemed highly likely when Sampson 
criterion 1 is fulfilled. Sampson criteria 2 and 3 are also listed for completeness:
1
The acute onset of a reaction (minutes to hours) with involvement of the skin, mucosal 
tissue or both, AND AT LEAST 1 of the following:

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(a) respiratory compromise or
(b) reduced BP or symptoms of end-organ dysfunction.
2
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient including: involvement of the skin/mucosal tissue, respiratory compromise, 
reduced BP or associated symptoms and/or persistent gastrointestinal symptoms.
3
Reduced BP after exposure.
Patients will have had a pre-assessment (ie, vital signs) prior to IP administration and the 
sponsor recommends that patients should be observed after IP administration for a minimum 
of 2 hours 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 dose of tezepelumab greater than 140 mg will be considered an overdose.

An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.

An overdose without associated symptoms is only reported on the Overdose eCRF 
module
If an overdose on an AstraZeneca study drug occurs at Visit 2, the Investigator or other site 
personnel inform appropriate AstraZeneca representatives 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 or 5 calendar days for overdoses associated with an SAE (see section 8.3.8) and within 
30 days for all other overdoses.
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 see 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 and local requirements, after which they will be destroyed/repatriated. 

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
Pharmacokinetic (PK) samples will be disposed of after the Bioanalytical Report 
finalisation or six months after issuance of the draft Bioanalytical Report (whichever is 
earlier), unless consented for future analyses. 

Pharmacokinetic samples may be disposed of or anonymised by pooling. Additional 
analyses may be conducted on the anonymised, pooled PK samples to further 
evaluate and validate 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 characterisation 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.
Standard numbing medications/devices and/or distraction techniques may be used with blood 
draws.
8.5.1
Pharmacokinetics
Blood samples for the determination of serum concentrations of tezepelumab will be collected 
as specified in the SoA (Table 1). A serum sample for PK analysis will be collected within 
± 1 hour of the time the baseline Day 1 sample was collected, across the different study days. 
On Day 1, the serum sample for PK analysis will be taken 1 hour prior to IP administration.
If required, blood samples for PK analysis may be taken by a study nurse at the subject’s 
home on the Day 11 visit, if previously approved and agreed with AstraZeneca.
Samples will be collected, handled, labelled, stored and shipped as detailed in the Laboratory 
Manual.
8.5.1.1
Pharmacokinetic Drug Assays
Blood samples for determination of tezepelumab concentrations in serum will be analysed by 
a designated third party on behalf of AstraZeneca, using a validated assay.
Full details of the analytical method and analyses performed will be described in a separate 
Bioanalytical Report.
8.5.2
Immunogenicity Assessments
8.5.2.1
Immunogenicity Testing
Blood samples for determination of anti-tezepelumab antibodies in serum will be analysed by 
a designated third party on behalf of AstraZeneca, using a validated assay. 

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
6 0
Bl o o d sa m pl es f or deter mi nat i on of a nti -teze pelu ma b a nt i b o dies i n ser u m will be c ollecte d as 
s pecifie d i n t he S o A (Ta ble 1 ). A ser u m sa m ple f or i m m u n o ge nicit y a nal ysis will be c o llecte d 
wi t hi n ± 1 h o ur of t he ti me t he baseli ne Da y 1 sa m ple was c o llecte d, o n Da y 2 9 a n d 
D a y 8 5/ E O S. O n Da y  1, t he ser u m sa m ple f or i m m u n o ge nicit y a nal ysis will be ta ke n wit hi n 
1 h o ur pri or t o I P a d mi nistrati o n.
I n t he e ve nt of a s us pecte d i m m u n ol ogi call y-relate d A E, a n u nsc he d ule d A D A sa m ple will be 
c ollecte d.
S a m ples will  be c o llecte d, ha n dle d, la belle d, st ore d a n d s hi p pe d as detaile d i n t he La b orat or y 
Ma n ual. 
T he prese nce or a bse nce of A D As will be deter mi ne d i n t he ser u m sa m ples. A  tiere d testi n g 
sc he me will be e m pl oye d, wi t h t he first ste p bei n g scree ni n g. Sa m ples f o u n d p ut ative p osi tive 
i n t he scree ni n g ste p will be teste d i n t he c o nfir mat or y ste p. Sa mples c o nfir me d p osit i ve f or 
A D A  in t he c o nfir mat or y  ste p will u n der g o titre deter mi nati o n. Sa m ples c o nfir me d p ositi ve 
f or A D A  will be arc hi ve d f or p ossi ble testi n g f or ne utralisi n g a nti b o dies ( n A b). 
F ull details o f t he a nal ytical met h o d a n d a nal yses perf or me d will be descri be d i n a se parate 
Bi oa nal y tic al R e p ort.
8. 5. 3
P h ar m ac o d y n a mics
 
 
8. 6
H u m a n  Bi ol o gic al S a m ple Bi o m ar kers ( N ot a p plic a ble)
S er u m  sa m ples will be c ollecte d t o be a nal yse d f or t otal i m m u n o gl o b uli n E (I g E). T he 
a nal ysis will be perf or me d at t he ce ntral la b orat or y.
8. 7
O pti o n al Ge n o mics I niti ati ve S a m ple ( N ot a p plic a ble)
O pti o nal  Ge n o mics I nitiat i ve researc h is n ot a p plica ble i n t his st u d y.
8. 8
He alt h Ec o n o mics ( N ot a p plic a ble)
8. 9
P a n de mic I m p act Assess me nt
To  assess t he i m pact of t he C O VI D-1 9 pa n de mic o n t he st u d y, sites will be as ke d t o c o m plete 
t he pa n de mic relate d i nf or mat i on i n t he e C R F at eac h st u d y visit.
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
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C O N FI D E N TI A L A N D P R O P RI E T A R Y
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9
S T A TI S TI C A L C O N SI D E R A TI O N S
9. 1
St atistic al H y p ot heses
N o f or m al st atistical h y p ot hesis tests will be ma de. Data will be s u m marise d descri pt i vel y.
9. 2
S a m ple Size Deter mi n ati o n
N o f or m al sa m ple size calc ulati on was c o n d ucte d f or t his st u d y. T he n u m ber of s u bjects was 
base d o n t he desire t o o btai n a de q uate P K a n d safet y  data w hile e x p osi n g as fe w pae diatric 
s u bjects as p ossi ble t o teze pel u ma b a n d st u d y pr oce d ures. A t otal of 1 2 s ubjects i s c o nsidere d 
s ufficie nt t o pr o vi de a de q uate data t o c haracterise P K of teze pel u ma b i n c hil dre n a ge d ≥5 t o 
1 1 years. At  least 4 s u bjects will ha ve b o d y wei g ht < 2 5 k g a n d a mi ni m u m o f 3 s u bjects will 
ha ve b o d y  wei g ht ≥2 5 k g a n d < 4 0 k g. A p pr o xi mat el y 1 4 s u bjects will recei ve teze pel u ma b i n 
a n atte mpt t o ha ve at l east 1 2 s u bjects c o mplete t he st u d y.
9. 3
P o p ul ati o ns f or A n al yses
T he f o ll owi n g p o p ul at i ons are defi ne d (Ta ble 1 0 ):
Ta ble 1 0
P o p ul ati o ns f or  An al ysis
P o p ul ati o n/ a n al ysis set
Descri pti o n
E nr olle d 
All s u bjects w h o si g n t he I C F.
Safet y
All s u bjects w h o recei ve at least o ne d ose of teze pel u ma b.
P K 
S u bjects i n t he Safet y A nal ysis set t hat ha ve at least o ne detecta ble 
teze pel u ma b ser u m c o nce ntrati o n fr o m a sa m ple c ollecte d p ost-d ose t hat is 
ass u me d n ot t o be affecte d b y fact ors s uc h as i m p orta nt pr ot oc ol de viati o ns 
(e g, i nc orrect d ose of st u d y I P recei ve d).
I C F I nf or me d c o nse nt f or m; P K P har mac o ki netic.
All P K s u m maries will be base d o n t he P K a nal ysis set. A nt i-dr u g a nti b o dies a n d 
 
 s u m maries a n d safet y prese ntatio ns will be base d o n t he safet y a nal ysis set.
9. 4
St atistic al A n al yses
A c o m pre he nsi ve statist ical a nal ysis pla n will be de vel o pe d a n d fi nalise d pri or t o D B L a n d it 
will i ncl u de a m ore tec h nical a n d detaile d descri pt i o n of t he statistical a nal yses descri be d i n 
t his sectio n. T his secti o n is a s u m mar y  of t he pla n ne d statistical anal yses of t he m ost 
i m p orta nt e n d p oi nts i ncl u di n g pri mar y a n d ke y sec o n dar y e n d p oi nts. A n y de viat i ons fr om t his 
pl a n will be re p orte d i n t he C S R.
9. 4. 1
Ge ner al C o nsi der ati o ns
N o f or m al st atistical h y p ot hesis tests will be ma de. Data will be pr o vi de d i n data list i n gs 
C CI

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sorted by subject number. Tabular summaries will be presented. Categorical data will be 
summarised by the number and percentage of subjects in each category. Continuous variables 
will be summarised by descriptive statistics, including number of subjects, mean, standard 
deviation, median, minimum and maximum for non-PK data. Median will be presented 
together with first and third quartile if appropriate. For the summary of PK concentration 
levels, in addition, geometric mean and coefficient of variation (CV%) based on 
log-transformed data will be presented. Unless otherwise stated, all summary tables will 
present descriptive statistics and/or frequency by visit. 
Frequency and percentages of subject disposition and reasons for withdrawal from the study 
will be presented. Subjects who withdraw from the study will be listed along with the reason 
for discontinuation. 
Frequency and percentages of subjects in each analysis population will be provided.
Demographics and subject characteristics will be summarised using frequency and 
percentages (for categorical variables) and n, mean, standard deviation, minimum, median and 
maximum (for continuous variables) using both the PK and safety analysis set.
Relevant medical history/current medical conditions will be coded using the version in force 
at DBL of the Medical Dictionary for Regulatory Activities (MedDRA) and summarised by 
system organ class (SOC) and preferred term (PT) using frequency and percentage of subjects. 
Virology results obtained at screening will be summarised using frequency and percentage of 
subjects presenting HBsAg, HCAb, HIV-1 and HIV-2.
Prior and concomitant medications, categorised according to the World Health Organization 
(WHO) Drug Reference List dictionary which employs the Anatomical Therapeutic Chemical 
(ATC) classification system, will be summarised as frequency and percentage of subjects 
reporting usage. Prior medications are defined as those which stopped before IP. Concomitant 
medications are defined as those which either started or continued after IP. 
Important protocol deviations will be defined at subject level prior to DBL and will be 
summarised and listed. The definitions of each category of important protocol deviation will 
be fully specified in the study Non-Compliance Handling Plan and will include (but may not 
be limited to): subjects who received IP without fulfilling key entry criteria; subjects who 
received prohibited or restricted concomitant medications during the study; subjects who 
received the incorrect IP dose.
In general, the last valid non-missing measurement taken on or prior to the date of treatment 
will serve as the baseline measurement. If there is no value on or prior to the date of treatment, 
then the baseline value will not be imputed and will be set to missing.

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
Teze pel u ma b - D 5 1 8 0 C 0 0 0 2 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y
6 3
A bs ol ute c ha n ge fr o m baseli ne is defi ne d as t he differe nce bet wee n t he rele va nt p ost -baseli ne 
val ue a n d t he baseli ne val ue. U nless s pecifie d ot her wise, “c ha n ge fr o m baseli ne ” is ass u me d 
t o be a bs ol ute c ha n ge fr o m baseli ne.
F urt her details re gar di n g basel i ne a n d/ or c ha n ge fr o m baseli ne defi niti ons will be pr o vi de d i n 
t he S A P.
9. 4. 2
Effic ac y 
9. 4. 2. 1
Pri m ar y E n d p oi nts
All P K a nal yses will be base d o n t he P K a nal ysis set. T eze pel u ma b ser u m c o nce ntrati o n data 
will be liste d b y  in di vi d ual  a nd s u m marise d b y n o mi nal t i me usi ng descri pt i ve statistics, 
i ncl u di n g N, ge o metric mea n, ge o metric C V %, arit h metic mea n, arit h met ic S D, me dia n, 
mi ni m u m a n d ma xi m u m. T he mea n a n d i n di vi d ual ser u m teze pel u ma b c o nce ntrati o ns will be 
pl otte d o ver ti me. Base d o n t he ser u m c o nce ntrati o n -ti me data of teze pelu ma b, t he f oll o wi n g 
P K para meters will be est i mate d usi n g n o nc om part me ntal a nal ysis met h o d as a p pr o priate: 
A U C 0- i nf, A U C0- last, Cma x, tma x , ter mi nal t1/ 2, C L/ F a n d Vss/ F. A d diti on al  P K para meters ma y be 
re p orte d if a p pr o priate. P K para meters will be liste d b y in di vi d ual  a n d s u m marise d usi n g 
descri pt i ve statistics. T he P K a nal ysis will be perf or me d usi n g Wi n N o nli n® versi o n 5. 1 or 
hi g her.
T he P K data o btai ne d i n t his st u d y  ma y be i ncl u de d i n a p o p ulati o n P K a nal ysis, as 
a p pr o priate, t o assess a n y P K  differe nces bet wee n c hil dre n a ge d ≥5 t o 1 1 years a n d 
a d ults/a d olesce nts, a n d g ui de d osi n g f or f ut ure st u dies of teze pel u ma b i n pae diatric s u bjects. 
If c o n d ucte d, t his a nal ysis will be re p orte d se paratel y fr om t he C S R.
9. 4. 2. 2
Sec o n d ar y E n d p oi nts
T he pre vale nce a n d i nci de nce o f A DA t o teze pelu ma b will be re p orte d usi n g t he safet y 
a nal ysis set. A nt i-dr u g a nt i b o dies data will be s u m marise d usi n g descri pti ve statistics b y visit. 
S a m ples c o nfi r me d p ositive f or A D A  will be arc hi ve d f or p ossi ble testi n g f or n A b. T he 
p ote nti al effects of A D A o n P K a n d safety will be e val uate d, if a p pr o priate.
9. 4. 2. 3
E x pl or at or y E n d p oi nts
 
 
 
 
C CI

Cli nical St u d y Pr ot oc ol – 4 . 0
Astra Ze neca
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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
9. 4. 3
S afet y
S af et y a nal yses will be perf or me d usi n g t he safet y  a nal ysis set. Safety data will be prese nte d 
usi n g descri pt i ve statistics u nless ot her wise s pecifie d.
Ve r bati m ter ms of A Es will be c o de d t o a sta n dar dise d P T usi n g t he Me d D R A versio n  in f orce 
at D B L. 
T he o verall n u m ber a n d perce nta ge of s u bjects wit h A Es a n d S A Es will be prese nte d. T he 
occ urre nce of A Es a n d S A Es will be descri be d als o b y  S O C, P T a n d se paratel y b y se verit y 
a n d b y r el atio ns hi p t o t he I P (as deter mi ne d b y t he I n vest i gat or). S h o ul d a s u bject re p ort t he 
sa me PT/ S O C wit hi n m ult i ple se verity or r el at i ons hi p cate g ories, t he s u bject ’s w orst 
occ urre nce ( m ost se vere/ m ost relate d) will be ta b ulate d. 
S eri o us A Es, A Es lea di n g t o deat h, A Es lea di n g t o wit h dra wal fr o m st u d y, c o m mo nl y  
occ urri n g A Es a n d A E SIs will be s u m ma rise d b y S O C a n d P T. 
La b orat or y  data, i ncl u di n g ser u m c he mistr y, hae mat olo g y  a n d uri nal ysis will be s u m marise d 
b y prese nt i n g s u m mar y statistics of o bser ve d a n d c ha n ge fr om baseli ne val ues at eac h 
sc he d ule d assess me nt visit. S hift ta bles usi n g n or mal ra n ges ( baseli ne t o m ost e xtre me 
p ost baseli ne val ue) will als o be prese nte d. T he i nci de nce of cli nicall y n ota ble la b orat or y 
a b n or malities will be s u m marise d. S hift ta bles will als o be pr o vi de d. 
N u m ber of s u bjects wit h ele vate d li ver f u nct i on tests t hat meet t h e H L defi niti on will be 
s u m marise d a n d e val uate d. 
Vit al si g ns data will be s u m marise d b y prese nti n g s u m mar y statistics of o bser ve d a n d c ha n ge 
fr om baseli ne val ues at eac h sc he d ule d assess me nt visit. T he i nci de nce o f cli nicall y n ota ble 
vit al si g ns a b n or malities will be s u m marise d.
A b n or m al E C Gs as per I n vesti gat or's o verall i nter pretati o n will be s u m marise d usi n g 
fre q ue nc y a nd perce nta ge of s u bjects.
A d dit i onal a nal yses assessi n g t he i m pact of C O VI D- 1 9 ma y be i ncl u de d i n t he S A P.
9. 4. 4
Ot her A n al yses 
T here are n o ot her a nal yses pla n ne d f or t his st u d y.
9. 5
I nteri m A n al yses 
T here are n o i nteri m a nal yses pla n ne d f or t his st u d y . 
C CI

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9.6
Data Monitoring Committee
The use of an Independent Data Monitoring Committee is not foreseen for this study.

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10
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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 5 1 8 0c 0 0 0 2 5-cs p- v 4
D oc u me nt Title:
D 5 1 8 0 C 0 0 0 2 5 Cli nical St u d y Pr ot oc ol versi o n 4
D oc u me nt I D:
Versi o n L a bel:
5. 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 4-Ja n- 2 0 2 2 0 8: 0 0 U T C
C o nte nt A p pr o val
1 4-Ja n- 2 0 2 2 1 0: 0 6 U T C
C o nte nt A p pr o val
1 4-Ja n- 2 0 2 2 1 2: 1 0 U T C
C o nte nt A p pr o val
1 3-Ja n- 2 0 2 2 2 2: 0 1 U T C
C o nte nt A p pr o val
P P D
P P D
P P D
P P D
C CI
C CI