Clinical trial NCT04643158
Conditions: Asthma
Keywords: AZD1402 placebo Anticalin® protein dry powder inhaler inhaled corticosteroids efficacy safety
Sponsor: AstraZeneca
Start date: 2021-03-12; Completion date: 2023-07-20
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to assess the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a Lead-in Cohort for each dose level to evaluate the safety and pharmacokinetics (PK) in a population with asthma controlled on medium dose inhaled corticosteroids (ICS)-long acting beta agonists (LABA) before progressing to dosing in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose ICS with LABA for Part 1 and participants receiving treatment with medium-to-high dose ICS with LABA for Part 2 (separate inhalers or combination product).

Part 2 will be initiated following evaluation of safety and PK at the relevant dose level in Part 1a. The entire study period for each participant in both Parts 1 and 2, is approximately 3.5 months; a 2-week Screening Period, a 4 week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of Follow-Up Period.

Detailed description:
Part 1 of the study will be randomised, double blind, placebo-controlled, and conducted in parallel for the 2 lower dose levels (Part 1a) followed by an unblinded safety review and escalation to the highest dose (Part 1b) dependent on the outcome of the safety review.

Part 1a will consist of 30 participants who will be randomised 1:1:1 to receive 1 of the 2 lower AZD1402 dry power inhaler (DPI) doses (Dose 1 or Dose 2) or placebo in parallel. Part 1b will consist of 15 participants who will be randomised 2:1 to receive the highest AZD1402 DPI dose (Dose 3) or placebo.

Part 1a Lead-in Cohort

* AZD1402 Dose 1
* AZD1402 Dose 2
* Placebo

Part 1b Lead-in Cohort

* AZD1402 Dose 3
* Placebo

Part 2 will be randomised, double blind, placebo controlled and will include approximately 165 participants randomised 2:1 (active to placebo) to evaluate 2 inhaled dose levels of AZD1402 versus placebo.

Part 2 will be started after the unblinded safety review for Part 1a. Part 2 will include:

* AZD1402 Dose 1
* AZD1402 Dose 2
* Placebo

Arms: arm 1: Randomised participants will receive oral inhalation of AZD1402 Dose 1 via DPI. arm 2: Randomised participants will receive oral inhalation of AZD1402 Dose 2 via DPI. arm 3: Randomised participants will receive oral inhalation of AZD1402 Dose 3 via DPI. arm 4: Randomised participants will receive oral inhalation of matching placebo via DPI.
Interventions: intervention 1: AZD1402 intervention 2: Placebo intervention 3: Short acting beta agonist (SABA) (rescue medication) intervention 4: Run-in medications (ICS-LABA combination)
Intervention descriptions: intervention 1: Randomised participants will receive oral inhalation of AZD1402, via DPI. intervention 2: Randomised participants will receive oral inhalation of matching placebo via DPI. intervention 3: In addition to study intervention, all participants will be provided with a SABA as rescue medication (eg, salbutamol/albuterol), to be used throughout the Run-in and Treatment Periods. All participants should refrain from taking a SABA as rescue medication 6 hours prior to pulmonary function tests.

Dosage levels: 100 μg per nominal dose 90 μg per nominal dose pro re nata (as required) (PRN) intervention 4: During the Run-in Period, the participants are required to maintain on their ICS-LABA dose. Controller medications (eg, ICS LABA) should remain at a stable dose and be taken after study intervention as applicable.

These drugs are used as standard of care.

Protocol documents:
Prot_000.pdf: 
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Clinical Study Protocol
Study Intervention
AZD1402
Study Code
D2912C00003
Version
8.0
Date
24 Mar 2023
A Two-part Phase IIa Randomised, Double-blind, 
Placebo-controlled, Dose-ranging, Multi-centre Study to Assess 
Efficacy and Safety of Inhaled AZD1402 Administered as a Dry 
Powder Twice Daily for Four Weeks in Adults with Asthma on 
Medium-to-High Dose Inhaled Corticosteroids
Sponsor Name: 
Legal Registered Address: AstraZeneca AB, SE-15185 Södertälje, Sweden
Regulatory Agency Identifier Number
EudraCT Number: 2020-002828-37
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.


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Protocol Number: D2912C00003
Amendment Number: 7
Study Intervention: AZD1402
Study Phase: IIa
Short Title: Efficacy and Safety of Inhaled AZD1402 administered Twice Daily for Four 
Weeks in Adults with Asthma on Medium-to-High Dose Inhaled Corticosteroids
Acronym: APATURA


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 7
24 Mar 2023
Amendment 6
03 Aug 2022
Amendment 5
04 Mar 2022
Amendment 4
13-Jan-2022
Amendment 3
09-Jun-2021
Amendment 2
10-Mar-2021
Amendment 1
23-Nov-2020
Original Protocol
20-Oct-2020
Amendment 7 (24 Mar 2023)
The Clinical Study Protocol (CSP) version 7.0, 03 Aug 2022 has been amended to optimize 
the selection of the participant population to be included in Part 2 of the study. The CSP 
changes included the update of period of required stable control by maintenance control 
medications, removal of inclusion criterion that participant should have had at least one severe 
asthma exacerbation in the 3 years prior to Visit 1, update of Part 2-specific inclusion and 
randomisation criteria to allow patients with FEV1 range from 40% to 85% (instead of patients 
with FEV1 range 50% to 85%) and C-reactive protein of < 10 mg/ml (instead of < 5 mg/ml) be 
included, update of Part 2-specific criterion related to minimum ePRO compliance 
(70% completion instead of 80%) to reduce impact of participant burden and align with 
asthma controller compliance requirements, update of exclusion criteria related to COVID-19 
and TB infections. Other CSP changes included the update of the number of participants
included in Part 2 (to 165 from 180), update of follow-up anti-drug antibody (ADA) sample 
collection, and amendment of the interim analysis text to allow flexibility on timing. 
Additional requirements for European Union Clinical Trial Regulation (EU-CTR) have been
included. Furthermore, some study procedures have been clarified and inconsistencies in the 
CSP text have been corrected.
Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 1.1 
Synopsis
Section 1.2 
Figure 1
Follow-up ADA sample 
collection timing updated 
to ‘approximately 2 years 
after randomisation’ from 
‘2 years after 
randomisation’
To account for logistical 
considerations in recall of 
participants and timing of 
sample collection
Non-substantial


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 1.3
Table 1
Section 1.1
Synopsis
Section 4.1.1
Figure 3
Section 4.1.2
Section 9.5
Main purpose of interim 
analysis changed to 
estimate the variability 
for a sample-size re-
estimation or perform 
futility analysis in Part 2. 
The timing of the interim 
analysis in Part 2 was 
corrected
Added flexibility on timing 
of interim analysis and
estimated variability enable 
an informative decision on
whether to revise the sample 
size in Part 2
Non-substantial
Section 1.1
Synopsis
Section 4.1.1 
Figure 3
Section 4.1.2
Section 9.2
Planned number of 
participants in Part 2 
updated to 165 from 180. 
Number of participants 
randomised into 
the
mg arm corrected 
to 5 from 20
To reflect number of 
participants randomised prior 
to stopping randomisation 
into the mg arm 
(reduced to 5 from 20)
Non-substantial
Section 1.1
Synopsis
Section 4.1.2
Section 5.1.2
Stability of ICS-LABA 
dose requirement prior to 
Visit 1 updated from 
3 months to 4 weeks
To take into account existing 
duration of screening and 
run-in period prior to 
randomisation
Substantial
Section 1.1
Synopsis
Section 4.1.2
Section 5.1.2
Stability of additional 
maintenance controller 
medications prior to 
Visit 1 updated from 
3 months to 4 weeks
To take into account existing 
duration of screening and 
run-in period prior to 
randomisation
Substantial
Section 1.3 
Table 2
Footnote clarified to 
include information about
serum pregnancy test in 
case of positive result of 
urine pregnancy test in 
Part 2
For verification of pregnancy 
status (leading to permanent 
discontinuation of study 
intervention in case of 
positive result)
Non-substantial
Section 4.1.2
Section 5.1.2
Removal of inclusion 
criterion that participant
should have at least one 
severe asthma 
exacerbation in the 
3 years prior to Visit 1
Amended to optimise 
selection of the participant 
population allowing
participants without severe 
asthma exacerbations to be 
included in Part 2
Substantial
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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 4.1.2 
Section 5.1.2 
Section 5.1.4
Part 2-specific inclusion
and randomisation
criteria updated to have
FEV1 range 
from 40% to 85%.
Amended throughout the 
protocol as applicable
Amended to optimise 
selection of the participant 
population using broader 
FEV1 range inclusion criteria
Substantial
Section 4.4
Clarified definition of the 
end of study according to 
European Union and 
Food and Drug 
Administration 
requirements.
For consistency and 
alignment in terms of posting 
study results
Non-substantial
Section 5.1.4
Part 2-specific 
randomisation criterion 
updated minimum 
compliance with ePRO 
completion to 70%
Amended to optimize 
selection of the participant 
population using less stricter 
compliance randomisation 
criteria
Substantial
Section 5.1.4
Part 2-specific 
randomisation criterion 
regarding level of 
C-reactive protein at 
Visit 2 updated to 
< 10 mg/L from < 5 mg/L
Amended to optimize 
selection of the participant 
population using broader 
range for C-reactive protein
Substantial
Section 5.2
Section 5.4
Update of exclusion 
criteria on participants 
with history of severe 
COVID-19 and further 
clarification of diagnosis 
of COVID-19 and 
removal of text related to 
rescreening participants 
diagnosed with 
SARS-COV-2
Amended to perform 
diagnostics as per local 
guidelines and as clinically 
indicated
Substantial
Section 5.2
Section 1.3
Table 2
Update of exclusion 
criteria on participants 
with active TB and 
footnote in Schedule of 
Activities for Part 2 
aligned
Amended to perform 
diagnostics as per local 
guidelines and as clinically 
indicated
Substantial
Section 5.3.4
Additional restriction 
added to exclude MART 
For clarification
Non-substantial


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
regime for the duration of 
the study
Section 6.4.2
Updated e-Diary 
compliance description
Updated to align with 
updated inclusion criteria
Substantial
Section 8.2.4
Clarified requirements for
results of Hepatitis C –
Virus Antibody and PCR
tests for participants that 
may be enrolled
For consistency and 
alignment with exclusion 
criterion 12
Non-substantial
Section 8.3.10.2
Updated information 
about paternal exposure
in line with inclusion 
criterion
To correct inconsistencies in 
the protocol
Non-substantial
Section 8.3.11
Added Drug Abuse and 
Drug Misuse definition
Update required due to 
‘CT-3’ Regulation and 
corporate safety CAPA
Non-substantial
Section 9.4.4.2
Presentation of 
immunogenicity AEs 
results changed from 
graphical to tabular
For clarification
Non-substantial
Appendix A1
Added sub-section
“Regulatory Reporting 
Requirements for Serious 
Breaches”
Update required to comply 
with regulatory requirement 
(eg, EU-CTR) and global 
company requirement
Non-substantial
Appendix A6
Updated information 
about dissemination of 
clinical study data
Update required to comply 
with EU-CTR
Non-substantial
Appendix A7
Updated information 
about retention timelines 
of records and documents 
to 25 years after study 
archiving
Update required to comply 
with EU-CTR and global 
company requirement
Non-substantial
Appendix B4
Updated to include latest 
template wording on 
Medication error, drug 
abuse, and drug misuse
Update required due to 
‘CT-3’ Regulation and 
corporate safety CAPA
Non-substantial
Appendix K
Changes from previous 
amendment moved to 
appendix
Update as per template 
requirements
Non substantial


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TABLE OF CONTENTS
TITLE PAGE........................................................................................................................ 1
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3
TABLE OF CONTENTS ...................................................................................................... 7
1
PROTOCOL SUMMARY ................................................................................ 12
1.1
Synopsis ........................................................................................................... 12
1.2
Schema............................................................................................................. 21
1.3
Schedule of Activities ....................................................................................... 23
2
INTRODUCTION............................................................................................ 36
2.1
Study Rationale ................................................................................................ 36
2.2
Background ...................................................................................................... 36
2.2.1
Asthma ............................................................................................................. 36
2.2.2
Current Therapies ............................................................................................. 36
2.2.3
AZD1402.......................................................................................................... 37
2.3
Benefit/Risk Assessment................................................................................... 38
2.3.1
Risk Assessment ............................................................................................... 38
2.3.1.1
Further Risk Mitigation Approaches.................................................................. 38
2.3.2
Benefit Assessment........................................................................................... 39
2.3.3
Overall Benefit: Risk Conclusion...................................................................... 39
3
OBJECTIVES AND ENDPOINTS................................................................... 40
4
STUDY DESIGN ............................................................................................. 42
4.1
Overall Design.................................................................................................. 42
4.1.1
Part 1................................................................................................................ 43
4.1.2
Part 2................................................................................................................ 47
4.1.3
Study Conduct Mitigation During Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis ................................................ 49
4.1.4
Study Conduct Mitigation During SARS-CoV-2 Pandemic ............................... 50
4.2
Scientific Rationale for Study Design ............................................................... 50
4.3
Justification for Dose........................................................................................ 51
4.4
End of Study Definition.................................................................................... 52
4.4.1
Premature Termination of the Study and Stopping Criteria................................ 52
5
STUDY POPULATION.................................................................................... 53
5.1
Inclusion Criteria .............................................................................................. 54
5.1.1
Part 1-specific Inclusion Criteria....................................................................... 56
5.1.2
Part 2-specific Inclusion Criteria....................................................................... 56
5.1.3
Part 1-specific Randomisation Criteria at Visit 3 ............................................... 57
5.1.4
Part 2-specific Randomisation Criteria at Visit 3 ............................................... 58
5.2
Exclusion Criteria ............................................................................................. 58
5.3
Lifestyle Considerations/Restrictions................................................................ 62
5.3.1
Meals................................................................................................................ 62


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5.3.2
Caffeine and Alcohol ........................................................................................ 62
5.3.3
Activity............................................................................................................. 62
5.3.4
Others............................................................................................................... 62
5.4
Screen Failures ................................................................................................. 63
6
STUDY INTERVENTION ............................................................................... 63
6.1
Study Intervention(s) Administered................................................................... 64
6.1.1
Investigational Products.................................................................................... 64
6.1.2
Medical Devices ............................................................................................... 65
6.1.3
Dose and Treatment Regimens.......................................................................... 65
6.1.3.1
Throughout the Study ....................................................................................... 65
6.1.3.2
Run-in Period ................................................................................................... 65
6.1.3.3
Treatment Period .............................................................................................. 65
6.2
Preparation/Handling/Storage/Accountability ................................................... 66
6.3
Measures to Minimise Bias: Randomisation and Blinding................................. 66
6.4
Study Intervention Compliance......................................................................... 67
6.4.1
Study Intervention Compliance......................................................................... 67
6.4.2
E-Diary Compliance ......................................................................................... 67
6.5
Concomitant Therapy........................................................................................ 67
6.5.1
Rescue Medication............................................................................................ 68
6.5.2
Required Medication......................................................................................... 68
6.5.3
Medication Withhold Periods............................................................................ 69
6.5.4
Restricted and Prohibited Medications.............................................................. 69
6.6
Intervention After the End of the Study............................................................. 71
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL........................................................... 71
7.1
Discontinuation of Study Intervention............................................................... 71
7.1.1
Permanent Discontinuation of Study Intervention for Individual Participants 
(Part 1 and Part 2)............................................................................................. 71
7.1.2
Temporary Interruption of Study Intervention for Individual Participants.......... 73
7.1.2.1
Dosing Suspension for Individual Participants (Part 1)...................................... 73
7.1.2.2
Dosing Suspension for Individual Participants (Part 1 and 2) ............................ 74
7.2
Participant Withdrawal from the Study.............................................................. 75
7.3
Lost to Follow-up ............................................................................................. 75
8
STUDY ASSESSMENTS AND PROCEDURES.............................................. 76
8.1
Efficacy Assessments........................................................................................ 76
8.1.1
Lung Function Test – Spirometry...................................................................... 76
8.1.2
Reversibility Testing ......................................................................................... 78
8.1.3
Fractional Exhaled Nitric Oxide........................................................................ 78
8.1.4
Electronic Diary................................................................................................ 78
8.1.5
Asthma Exacerbation........................................................................................ 79
8.1.6
Asthma Symptom Score.................................................................................... 81
8.1.7
Use of Rescue Medication ................................................................................ 81
8.1.8
..................................................................................... 82
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8.1.9
Background Medications .................................................................................. 82
8.1.10
Participant Reported Outcomes......................................................................... 82
8.1.11
Peak Expiratory Flow ....................................................................................... 83
8.1.12
................................................................................................ 84
8.2
Safety Assessments........................................................................................... 84
8.2.1
Physical Examinations...................................................................................... 84
8.2.2
Vital Signs ........................................................................................................ 85
8.2.3
Electrocardiograms........................................................................................... 85
8.2.4
Clinical Safety Laboratory Assessments............................................................ 86
8.2.5
Other Safety Assessments ................................................................................. 89
8.2.5.1
Safety Immuno-biomarkers............................................................................... 89
8.2.5.2
FEV1................................................................................................................. 89
8.2.5.3
FeNO................................................................................................................ 89
8.2.5.4
High-resolution Computed Tomography ........................................................... 89
8.3
Adverse Events and Serious Adverse Events..................................................... 89
8.3.1
Time Period and Frequency for Collecting AE and SAE Information................ 89
8.3.2
Follow-up of AEs and SAEs ............................................................................. 90
8.3.3
Causality Collection.......................................................................................... 90
8.3.4
Adverse Events Based on Signs and Symptoms ................................................ 91
8.3.5
Adverse Events of Special Interest.................................................................... 91
8.3.6
Adverse Events Based on Examinations and Tests ............................................ 92
8.3.7
Hy’s Law.......................................................................................................... 93
8.3.8
Disease Under Study......................................................................................... 93
8.3.9
Reporting of Serious Adverse Events ................................................................ 93
8.3.10
Pregnancy......................................................................................................... 94
8.3.10.1
Maternal Exposure............................................................................................ 94
8.3.10.2
Paternal Exposure............................................................................................. 94
8.3.11
Medication Error, Drug Abuse, and Drug Misuse.............................................. 95
8.3.11.1
Timelines.......................................................................................................... 95
8.3.11.2
Medication Error............................................................................................... 95
8.3.11.3
Drug Abuse....................................................................................................... 95
8.3.11.4
Drug Misuse ..................................................................................................... 95
8.3.12
Medical Device Deficiencies............................................................................. 96
8.4
Overdose .......................................................................................................... 96
8.5
Human Biological Samples............................................................................... 96
8.5.1
Pharmacokinetics.............................................................................................. 97
8.5.1.1
Part 1................................................................................................................ 97
8.5.1.2
Part 2................................................................................................................ 97
8.5.1.3
Determination of Drug Concentration ............................................................... 98
8.5.2
Immunogenicity Assessments ........................................................................... 98
8.5.3
Pharmacodynamics........................................................................................... 98
8.6
Human Biological Sample Biomarkers ............................................................. 99
8.6.1
Collection of Mandatory Samples for Biomarker Analysis ................................ 99
8.6.2
Collection of Optional Samples for Biomarker Analysis ................................... 99
8.7
Optional Genomics Initiative Sample................................................................ 99
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8.8
Health Economics........................................................................................... 100
9
STATISTICAL CONSIDERATIONS.............................................................. 100
9.1
Statistical Hypotheses..................................................................................... 100
9.2
Sample Size Determination............................................................................. 100
9.3
Populations for Analyses................................................................................. 101
9.4
Statistical Analyses ......................................................................................... 102
9.4.1
General Statistical Considerations................................................................... 102
9.4.2
Efficacy – Part 2 ............................................................................................. 103
9.4.2.1
Primary Endpoint............................................................................................ 103
9.4.2.2
Secondary Endpoints ...................................................................................... 103
9.4.2.3
Exploratory Endpoints .................................................................................... 104
9.4.3
Safety ............................................................................................................. 104
9.4.3.1
Adverse Events............................................................................................... 104
9.4.3.2
Deaths ............................................................................................................ 105
9.4.3.3
Exposure......................................................................................................... 105
9.4.3.4
Vital Signs ...................................................................................................... 105
9.4.3.5
Laboratory Parameters.................................................................................... 105
9.4.3.6
Immuno-biomarkers........................................................................................ 105
9.4.3.7
Electrocardiogram........................................................................................... 106
9.4.4
Other Analyses................................................................................................ 106
9.4.4.1
Pharmacokinetics............................................................................................ 106
9.4.4.2
Immunogenicity.............................................................................................. 108
9.5
Interim Analyses............................................................................................. 108
9.6
Data Monitoring Committees.......................................................................... 108
10
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ...................................................................................... 110
11
REFERENCES............................................................................................... 171
LIST OF FIGURES
Figure 1
Study Design Part 1 ................................................................................. 21
Figure 2
Study Design Part 2 ................................................................................. 22
Figure 3
Dose Staggering and Decision Points Part 1a/b and Part 2 ....................... 46
LIST OF TABLES
Table 1
Schedule of Activities Part 1.................................................................... 24
Table 2
Schedule of Activities Part 2.................................................................... 31
Table 3
Objectives and Endpoints (Part 1)............................................................ 40
Table 4
Objectives and Endpoints (Part 2)............................................................ 41


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Table 5
Investigational Products........................................................................... 64
Table 6
Laboratory Safety Variables..................................................................... 87
Table 7
Populations for Analysis ........................................................................ 101
LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations....................... 111
Appendix B
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ...................................................................... 118
Appendix C
Handling of Human Biological Samples ................................................ 124
Appendix D
Optional Genomics Initiative Sample..................................................... 126
Appendix E
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law......................................................................... 130
Appendix F
COVID-19 Specifics.............................................................................. 136
Appendix G
Changes Related to Mitigation of Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health ...................................... 140
Appendix H
Patient-reported Outcomes..................................................................... 142
Appendix I
Definitions, Management and Classifications of Hypersensitivity 
Reactions............................................................................................... 147
Appendix J
Abbreviations ........................................................................................ 148
Appendix K
Protocol Amendment History................................................................. 152


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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Two-part Phase IIa Randomised, Double-blind, Placebo-controlled, 
Dose-ranging, Multi-centre Study to Assess Efficacy and Safety of Inhaled AZD1402 
Administered as a Dry Powder Twice Daily for Four Weeks in Adults with Asthma on 
Medium-to-High Dose Inhaled Corticosteroids
Short Title: Efficacy and Safety of Inhaled AZD1402 administered Twice Daily for Four 
Weeks in Adults with Asthma on Medium-to-High Dose Inhaled Corticosteroids
Rationale:
Asthma is a chronic, complex, and heterogeneous respiratory disease characterised by a range 
of pathogenic features including pulmonary inflammation, mucus hypersecretion, variable 
airway obstruction, and airway remodelling. Symptoms and airway obstruction can resolve in 
response to therapy or spontaneously, but participants remain at risk of severe worsening of 
their asthma (exacerbations). These asthma exacerbations can be life-threatening, can 
significantly impact the participant’s quality of life, and result in significant healthcare costs.
International treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first 
line therapy. For individuals who are symptomatic on medium dose ICS monotherapy, step-up 
therapy with long-acting beta agonists (LABAs) is the recommended next treatment option 
followed by other controller therapies including leukotriene receptor antagonists, theophylline, 
and oral corticosteroids (OCS). ‘Biologic agents’ (eg, omalizumab and benralizumab) that 
inhibit specific molecular targets such as immunoglobulin E (IgE) or T helper cell type 2 
(Th2) cytokines and their respective receptors are reserved for those with severe uncontrolled 
asthma. For most asthma participants, a treatment regime of a controller and bronchodilator 
therapy provides adequate long-term control. Inhaled corticosteroids are considered the “gold 
standard” in controlling asthma symptoms and LABAs are the most effective bronchodilators 
currently available. These agents are often given in combination as research has demonstrated 
that combination therapy of an ICS with an inhaled LABA provides better asthma control than 
high doses of ICS alone. Although the majority of participants respond to therapy, it is 
estimated that 5% to 10% of the population with asthma has symptomatic disease despite 
maximum recommended treatment with combinations of anti-inflammatory and 
bronchodilator drugs. For those moderate/severe asthma participants that remain uncontrolled 
on currently approved inhaled or oral treatments there is a clear unmet need for new therapies
before introducing systemic biologic treatment. Inhalation as opposed to systemic and 
subcutaneous administration of biologics, could offer several potential advantages. Inhaled 
drugs are advantageous as the drug delivery is localised to the lung (target organ) which may 
allow for a lower dose than needed with systemic delivery. Inhalation is also non-invasive, 


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and thus offers advantages in terms of ease of use. Current research is focusing on the 
different pathological mechanisms or endotypes of severe asthma and it is anticipated that this 
will lead to the development of effective therapies for these subsets of asthma patients.
AZD1402 is derived from human tear lipocalin (Tlc) and is a potent and selective antagonist 
of interleukin (IL)-4Rα, which antagonises the pro-inflammatory actions of IL-4 and IL-13. 
AZD1402 is presented as an inhalation powder and belongs to a new class of therapeutics, 
Anticalin® proteins, which are modified lipocalins. AZD1402 is being developed as an inhaled 
IL-4Rα antagonist controller therapy for the treatment of moderate to severe persistent asthma 
in participants who are not adequately controlled on standard of care therapies. The current 
study aims to assess the efficacy and safety of inhaled AZD1402 administered via dry power 
inhaler (DPI)
for 4 weeks in adults with asthma on medium-to-high dose 
ICS in a 2-part randomised, double-blind, placebo-controlled, and multi-centre study.
Objectives and Endpoints
Part 1
Objectives
Outcome Measure
Primary
•
To evaluate the safety and tolerability of 
AZD1402 compared to placebo at different dose 
levels in adults with asthma controlled on 
medium dose ICS-LABA
Primary safety endpoint: 
•
Adverse events / AESIs / SAEs with a 
particular focus on infection, eosinophilia, and 
hypersensitivity-like events
•
Vital signs
•
Changes in clinical chemistry, haematology, 
and coagulation parameters
•
Immuno-biomarkers (including but not limited 
to cytokines, CRP, immunoglobulins including 
IgE)
•
ECGs
•
FEV1
•
FeNO (in-clinic)
Secondary
•
To investigate the PK profile and 
immunogenicity of AZD1402, and associated 
effects on safety
•
PK parameters (full profile in all participants)
•
ADAs
Exploratory
•
 
•
Change from baseline in FeNO at Day 28 and 
average over the Treatment Period
•
 
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Part 1
Objectives
Outcome Measure
•
To assess the effect of AZD1402 compared to 
placebo on cough by a VAS in adults with 
asthma controlled on medium dose ICS-LABA
•
Change from baseline average in cough VAS 
over the Treatment Period
•
 
•
 
•
 
•
 
•
•
 
•
 
 
•
•
 
Abbreviations: 
 ADAs = anti-drug antibodies; AESI = adverse event 
of special interest; CSR = clinical study report; CRP = C-reactive protein; ECG = electrocardiogram; 
FeNO = fractional exhaled nitric oxide; FEV1 = forced expiratory volume in 1 second; 
 
 ICS = inhaled corticosteroids; IgE = immunoglobulin E; LABA = long-acting beta agonist; 
 PK = pharmacokinetics; SAEs = serious adverse events; VAS = Visual Analogue 
Scale
Part 2
Objectives
Outcome Measure
Primary
•
To investigate the efficacy of inhaled AZD1402 
compared to placebo in adults with asthma who 
are uncontrolled on medium-to-high dose 
ICS-LABA
Primary efficacy endpoint: 
•
Change from baseline in pre-bronchodilator 
FEV1 at Week 4
Secondary
•
To further investigate the efficacy of AZD1402 
compared to placebo in adults with asthma who 
are uncontrolled on medium-to-high dose 
ICS-LABA
•
Change from baseline in pre-bronchodilator 
FEV1 average over the 4-week Treatment 
Period 
•
Change from baseline in ACQ-6 at Week 4 and 
average over the Treatment Period
•
Proportion of participants with a decrease in 
ACQ-6 score of ≥0.5 from baseline to Week 4
•
Change from baseline in average morning PEF 
over the Treatment Period
•
Change from baseline in average evening PEF 
over the Treatment Period
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Part 2
Objectives
Outcome Measure
•
Change from baseline in daily average asthma 
symptom score (AM/PM) over the Treatment 
Period
•
To investigate the effect of AZD1402 compared 
to placebo on airway inflammation in adults with 
asthma who are uncontrolled on medium-to-high 
dose ICS-LABA
•
Change from baseline in FeNO (in-clinic) at 
Week 4 and average over the Treatment Period
•
To investigate the PK profile and 
immunogenicity of AZD1402, and associated 
effects on safety
•
PK parameters (sparse in all, full profile in a 
subset of participants in each treatment arm)
•
ADAs
•
To evaluate the safety and tolerability of 
AZD1402 compared to placebo in adults with 
asthma who are uncontrolled on medium-to-high 
dose ICS-LABA
•
Adverse events / AESIs / SAEs with a 
particular focus on infection, eosinophilia, and 
hypersensitivity-like events
•
Vital signs
•
Changes in clinical chemistry, haematology, 
and coagulation parameters
•
Immuno-biomarkers (including but not limited 
to cytokines, CRP, immunoglobulins including 
IgE)
•
ECGs
•
FEV1 
•
FeNO (in-clinic)
Exploratory
•
 
 
 
•
 
•
•
•
 
•
 
•
 
•
Change from baseline in FeNO (in-clinic)
•
 
 
•
 
•
 
•
•
 
•
 
 
•
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Part 2
Objectives
Outcome Measure
 
 
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; AESIs = adverse events of special interest; 
ADAs = anti-drug antibodies; AM = before noon (antemeridiem); CRP = C-reactive protein; CSR = clinical 
study report; ECG = electrocardiogram; FeNO = fractional exhaled nitric oxide; FEV1 = forced expiratory 
volume in 1 second; 
; ICS = inhaled corticosteroids; IgE = immunoglobulin E; 
LABA = long-acting beta agonist; 
; PEF = peak expiratory flow; 
PK = pharmacokinetics; PM = after noon (post meridiem); SAEs = serious adverse events
Overall Design
This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to assess 
the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a Lead-in Cohort for 
each dose level to evaluate the safety and pharmacokinetics (PK) in a population with asthma 
controlled on medium dose ICS-LABA before progressing to at-home dosing in adults with 
asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. Part 2 will be 
initiated following evaluation of safety and PK in Part 1a. The study intervention in both parts 
of the study will be administered 
 using the 
 DPI for a period of 4
weeks.
A Lead-in Dose Progression and Escalation Cohort approach with 3 dose levels has been 
selected to confirm Phase I data dose-response observations and further evaluate safety and 
PK in adults with asthma controlled on medium dose ICS. The Part 1a safety cohort will be 
completed before progressing to at-home dosing in adults with asthma uncontrolled on 
medium-to-high dose ICS-LABA in Part 2.
This study will be conducted in approximately 8-10 countries. The entire study period for each 
participant in both Parts 1 and 2, is approximately 3.5 months; a 2-week Screening Period, a 
4-week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of Follow-up Period.
Part 1
Part 1 of the study will be randomised, double-blind, placebo-controlled, and conducted in 
parallel for the 2 
 dose levels (Part 1a) followed by an unblinded safety review and 
escalation to the 
 dose (Part 1b) dependent on the outcome of the safety review. Data 
evaluated in the safety review will be unblinded; however, blinding will be maintained for 
participants and Investigators. The total sample size for Part 1 is estimated to be 45 
participants.
The target population is adults with asthma (age 18 to 75 years, inclusive) who are adequately 
controlled on a stable medium dose ICS-LABA and additional rescue medication as needed, 
Asthma Control Questionnaire-6 (ACQ-6) score ≤1.0 and pre-bronchodilator forced 
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expiratory volume in one second (FEV1) ≥70%, and with no exacerbation requiring systemic 
treatment or hospitalisation/emergency department visit for asthma during the 12 months prior 
to study start.
Part 1a will consist of 30 participants who will be randomised 1:1:1 to receive 1 of the 2
 
AZD1402 DPI doses (
mg) or placebo in parallel. Part 1b will consist of 15 participants 
who will be randomised 2:1 to receive the 
 AZD1402 DPI dose (
mg) or placebo.
Due to logistical reasons, the randomisation in Part 1 will be stratified by site in Australia and 
Germany.
Part 1a Lead-in Cohort

AZD1402 inhalation
mg 

AZD1402 inhalation
mg 

Placebo inhalation 
Part 1b Lead-in Cohort

AZD1402 inhalation 
mg 

Placebo inhalation 
Part 2
Part 2 will be randomised, double-blind, placebo-controlled and will include approximately 
165 participants to evaluate 2 inhaled dose levels ( mg and mg) of AZD1402 against 
placebo. Approximately 5 participants will be randomised to mg and 80 participants per arm
will be randomised to mg and placebo, respectively. The number of subjects enrolled in the 
mg dose will depend on the enrolment rate and the randomisation ratio will change during 
the study. Patients will be randomised 2:1 (active to placebo) whilst the mg arm is ongoing. 
Once the mg has stopped recruiting and randomisation continues in the mg and placebo 
arms, the randomisation ratio will be 1:1 (active to placebo). Adult participants (age 18 to 75
years, inclusive) with physician-diagnosed uncontrolled asthma treated with medium-to-high
dose ICS (total daily dose > 400μg of budesonide dry powder formulation or equivalent) with
LABA, as maintenance treatment, for at least 6 months prior to Visit 1 will be included. 
ICS-LABA and any additional asthma maintenance controller medications (eg, leukotriene 
receptor inhibitors, theophylline, long-acting muscarinic antagonist [LAMA], and chromones) 
must be stable for at least 4 weeks prior to Visit 1.
Apart from the scheduled clinic visits, the 4 weeks of dosing in Part 2 of the study will be at 
home. Part 2 will be started after the unblinded safety review for Part 1a. Part 2 will include:

AZD1402 inhalation mg 
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
AZD1402 inhalation mg 

Placebo inhalation 
Participants in both parts of the study will receive a handheld e-Diary device which they are 
required to complete twice daily during the entire duration of the study.
Disclosure Statement: For Part 2 this is a parallel group treatment study with 3 arms that is 
participant, Investigator, and Sponsor blinded.
Number of Participants:
Approximately 45 participants will be randomised in Part 1 of the study and approximately 
165 participants will be randomised in Part 2 of the study.
Intervention Groups and Duration:
Both parts of the study will have a Screening Period of 14 days. The Run-in, Treatment
Period, and Follow-up Periods are 28 days each. In Part 1 only, participants with a positive 
ADA sample at the final Follow-up Visit, will also have an anti-drug antibody (ADA) sample 
taken up to approximately 2 years after randomisation.
Data Monitoring Committees:
An unblinded Safety Review Committee (SRC), including the Sponsor study team will review 
PK and unblinded safety data following the completion of Part 1a before progressing to 
Part 1b/2, and following completion of Part 1b. An unscheduled SRC meeting may also be 
held in the event of any safety or tolerability events requiring further review that may impact 
continuation of a cohort or the study, including unblinding data as required. 
A Data Safety Monitoring Board (DSMB) will oversee Part 2 of the study and review the 
unblinded interim outputs. In addition to a full DSMB periodic review of safety data, the 
committee can meet on an ad hoc basis.
A separate review committee of AstraZeneca representatives will review the unblinded interim 
outputs for the interim analysis if performed.
Details of the composition of the each of these committees, frequency of meetings, and remit
can be found in the respective charters.
Statistical Methods
No statistical hypotheses will be tested for in Part 1 (Lead-in Cohort) of this study.
The null hypotheses for the primary analysis in Part 2 (Main Cohort) are that there is no 
difference in the change from baseline at Week 4 in FEV1 in AZD1402 treated participants 
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compared to placebo-treated participants.
Sample Size:
In Part 1 (Lead-in Cohort), approximately 45 participants will be randomised. Part 1a will 
consist of 30 randomised participants and Part 1b will consist of 15 randomised participants. 
The sample size for Part 1 (Lead-in Cohort) is not based on any sample size calculation, but 
was chosen to obtain reasonable evidence of safety and tolerability without exposing undue 
number of participants to the study intervention.
In Part 2 (Main Cohort), 73 evaluable participants per treatment arm ( mg and placebo) will 
provide 
% power using a 1-sided test and % significance level to detect a difference of 
175 mL in FEV1 versus placebo. Assuming a dropout rate of 
%, approximately 
 evaluable 
participants per arm are needed. Due to the restricted recruitment into the mg dose arm the 
precision of inference in terms of statistical power will be less than 
% for the comparisons 
mg versus placebo. A participant will be considered evaluable if he/she has baseline and 
Week 4 FEV1 results available. Part 2 will include approximately 165 participants (5, 80 and 
80 in the
mg,
mg and placebo arms, respectively).
General Statistical Considerations:
Continuous data will be summarised using descriptive statistics. For log-transformed data 
geometric mean and geometric coefficient of variation will also be presented. For PK data, 
geometric ± standard deviation (SD) will also be presented in addition to geometric mean and 
geometric coefficient of variation. Frequencies and percentages will be used for summarising 
categorical (discrete) data.
Confidence intervals will generally be 2-sided with 95% confidence level, and p-values will 
be one-sided, unless otherwise indicated.
Unless otherwise stated, summaries will be presented by Part and treatment. The treatment 
comparisons of interest are the different doses of AZD1402 versus placebo. No formal 
comparisons between the different AZD1402 doses will be conducted.
The analysis of all efficacy variables (Part 2) will be performed on the full analysis set (FAS).
Mixed model repeated measures analysis (MMRM) will be used for primary efficacy 
endpoint, within-participant correlation will be modelled using the unstructured covariance 
matrix and Kenward-Roger approximation will be used to estimate the degrees of freedom.
Safety analysis will be performed using the safety set (SS). Safety data will be presented 
descriptively unless otherwise specified. Adverse events (AEs) will be presented separate for 
each Part by treatment, system organ class and/or preferred term covering number and 
percentage of participants reporting at least one event and number of events where 
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appropriate.
An interim analysis of the primary endpoint (FEV1) may be performed. The main objective of 
this analysis is to estimate the variability for a sample-size re-estimation or perform a futility 
analysis. The timing of the interim analysis is to be determined such that the estimated 
variability enables an informative decision on whether to revise the sample size. Decision 
criteria will be pre-specified in an interim analysis plan (charter).


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1.2
Schema
Figure 1
Study Design Part 1
 SRC = Safety review committee
Participants may also be required to attend a Visit up to approximately 2 years after randomisation for a follow-up ADA sample. 
Screening
Run-In (4wks)
AZD1402 
mg 
AZD1402 
mg, 
AZD1402 
mg, 
Placebo, 
Follow-Up (4wks)
Visit 1
Week -6
Screening
Visit 2
Week -4
Run-In
Visit 3
Day -1 to 14
Visit 4
Day 16
Visit 5
Day 20
Visit 6
Day 24
Visit 7
Day 28-29
Visit 10
Week 5/6
Follow-Up
Visit 11
Week 8
Follow-Up
Placebo, 
 
Part 1b - Triggered by Part 1a SRC decision
Part 1a 
Visit 8 & 9
Day 30&32
Residential
Optional Residential
Residential
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Figure 2
Study Design Part 2
 SRC = Safety review committee
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1.3
Schedule of Activities
Once informed consent has been obtained, e-Diary provision and training for site and home 
visits should occur first during Visit 1, followed by PRO assessments. The PRO assessments 
should be conducted first at all other visits. For all participants, in-clinic spirometry testing 
must be initiated between 6:00 AM and 11:00 AM during the Screening, Rescreening, and 
Run-in Period. 
Whenever ECGs, vital signs, and blood draws are scheduled for the same nominal time, the 
order should be as follows: ECGs, vital signs (vital signs can occur immediately after ECG 
using the same rest period), then blood draws. The timing of the first 2 assessments should be 
such that it allows the blood draw (eg, PK blood sample) to occur at the assigned nominal 
time.
FeNO and spirometry should follow above assessments. Whenever FeNO and spirometry are 
scheduled for the same nominal time, the order should be as follows: FeNO followed by 
spirometry.
Nasal/nasopharyngeal/oropharyngeal sampling should be performed last.
Safety urine samples may be collected at any time during the visit.
If required, the order of assessments may be modified in consultation with the Sponsor Study 
Physician.
Refer to Section 8 for details on the study assessments.


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Table 1
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in 
CSP Section 
or Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 
24 
28 d
– 2
29
30
32
39 
± 6
56 
± 4
Signed informed consent
X
5.1
Admission
X
X
4.1.1
Discharge
X e
X
4.1.1
Optional residential stay 
(throughout Treatment Period)
X
4.1.1
Inclusion and exclusion criteria
X
X
X
X
5.1, 5.2
Demography
X
5.1
Medical/surgical history
X
5.1
Smoking history including 
cotinine testing 
X
X
5.1
Asthma history
X
5.1
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
6.5
Height/weight f
X
X
X
8.2.1
Physical examination
X g
X h
X h
X g
X h
X g
8.2.1
Vital signs (blood pressure, pulse 
rate, temperature, respiratory 
rate) i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.2.2
Study drug inhalation training
X
X
X j
6.1.3
Home device dispensation (FeNO 
and spirometer)
X
6.1.2
Home device training (FeNO and 
spirometer)
X
X j
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Table 1
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in 
CSP Section 
or Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 
24 
28 d
– 2
29
30
32
39 
± 6
56 
± 4
Rescue medication (eg, 
salbutamol) k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
6.5.1
FeNO test (in-clinic) l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.3
FeNO at-home assessments (Niox 
Vero) l, m
X
X
X
X
X
X
X
8.1.3
Spirometry (FEV1 and FVC) n
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.1
12-lead ECG o
X 
X
X
(Day 7)
X
X
8.2.3
ACQ-6
X 
X 
X
X
(Day 7)
X
X
(Day 20)
X
X
8.1.10
FEV1/PEF (home device) p
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.1, 
8.1.11
Cough VAS
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.10
SPFQ (optional)
X
X
X
X
8.1.10
Assign e-Diary q
X
8.1.4
Dispense e-Diary r
X
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Table 1
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in 
CSP Section 
or Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 
24 
28 d
– 2
29
30
32
39 
± 6
56 
± 4
Check e-Diary compliance
X
X
X
X
X
X
X
X
X
X
X
X
6.4.2
Check compliance with 
background medication
X
X
X
X
X
X
X
X
X
X
X
X
6.5
Collect e-Diary
X
X
8.1.4
Asthma symptom score and 
rescue medication use
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.6, 8.1.7
Study drug dispensation
X
6.1
Study drug administration s
6.1.3
Drug accountability
X
X
6.2
Return unused medication and 
DPI
X
X
6.2
AEs t
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.3
Blood samples for biochemistry
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for haematology
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for clotting profile
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for CRP (local 
laboratory) w
X
X
X
X
X
X
X
X
X
X
X
X
8.2.4
Blood sample for hs-CRP
X
X
X u
X v
X
X
X
X
X
X
X
8.2.5.1
Blood samples for safety 
immuno-biomarkers
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples allergen-specific 
IgE x
X
8.6.1
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Table 1
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in 
CSP Section 
or Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 
24 
28 d
– 2
29
30
32
39 
± 6
56 
± 4
Blood samples for serum 
pregnancy test (all female
participants)
X
5.1, 8.2.4
Blood samples for Hepatitis B 
(HBsAg, anti-HBs, anti-HBc), 
and C; HIV-1 and HIV-2; QFT 
for TB y
X
5.1, 8.2.4
Blood samples for PK 
measurements z
X
X
X
X
X
X
X
X
X
X
X
8.5.1
Blood samples for ADA aa
X
X
X 
(Day 20,
24)
X
X
X
X
8.5.2
bb
X
8.6.2, 8.7
 
 
X 
(pre-
dose)
X
(pre-
dose)
X
X
8.6.2
Urinalysis
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for FSH (if needed 
to confirm postmenopausal status 
in female participants < 50 years 
and not on HRT)
X
5.1, 8.2.4
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Table 1
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in 
CSP Section 
or Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 
24 
28 d
– 2
29
30
32
39 
± 6
56 
± 4
Urine pregnancy test (females of 
childbearing potential) cc
X
X
X
X
5.1, 8.2.4
Urine drug screen
X
X
5.2, 8.2.4
SARS-CoV-2 PCR dd
X 
X
X ee
X
X
X
X
X
X
X
X
X
X
X
5.2, 8.2.4
SARS-CoV-2 serology dd
X
X
X
5.2, 8.2.4
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; 
 COVID-19 = Coronavirus disease-2019; CRP =C-reactive protein; CSP = clinical study protocol; DPI = dry powder inhaler; ECG = 
electrocardiogram; e-Diary = electronic diary; ETV = early termination visit; FEV1 = forced expiratory volume in 1 second; FeNO = fractional exhaled nitric 
oxide; FSH = follicle stimulating hormone; FVC = forced vital capacity; 
 HBsAg = hepatitis B surface antigen; HIV = human 
immunodeficiency virus; 
 HRT = hormone replacement therapy; hs-CRP = high sensitivity CRP; IgE = immunoglobulin E; 
IPD = Intervention Discontinuation Visit; 
 PCR = polymerase chain reaction; PEF = peak expiratory flow; PK = 
pharmacokinetics; QFT = QuantiFERON; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SPFQ = Study Participant Feedback Questionnaire; 
SoA = Schedule of Activities; TB = tuberculosis; VAS = Visual Analogue Scale
a
In-clinic outpatient visits during the Treatment Period will be scheduled so that they fall at the time of morning dose administration.
b
Time between Visit 1 and Visit 2 may be extended up to 28 days upon input from the Study Physician.
c
Visit 1 can be done on several/different days prior to Visit 2.
d
Participants may be admitted on Day 27. Day 28 should be performed on the scheduled calendar day as far as possible; the -2-day window may be utilised 
only if required. If the -2-day window is utilised, all subsequent visits will be adjusted to follow time window between visits as specified in the SoA.
e
Discharge on Day 14 after the morning post-dose procedures.
f
Height only at Visit 1.
g
A complete physical examination including an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including 
ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal and neurological systems will be performed.
h
A brief physical examination including an assessment of the general appearance, skin, abdomen, cardiovascular, and respiratory systems will be performed.
i
Vital signs to be performed BID whilst participants are in-clinic. Vital signs will be measured pre-dose at the scheduled morning dose in-clinic visits and 
additionally prior to the evening dose if participants receive the evening dose at the clinic (eg, due to optional overnight stay).
j
Refresher training as required.
k
Rescue medication to be as necessary. Check if participant has enough rescue medicine for use at-home use and refill if necessary.
l
FeNO will be measured pre-spirometry, pre-dose (as applicable), and pre-bronchodilation.
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m
FeNO assessments at home will only be performed (morning and evening) at non-clinic visit timepoints.
n
In-clinic spirometry on Days 1 to 14 and Day 28 will be performed pre-dose and 2 h post-dose (± 15 min) in the morning (prior to taking controller 
medication) and on Days 1 to 13 pre-dose and 4 h post-dose (-2 h) in the evening. Where possible, all post-randomisation morning pre-dose clinic 
spirometry assessments should be performed within ± 30 minutes of the time that the randomisation spirometry was performed during the residential 
period. The evening pre-dose spirometry should also be performed within a ± 30 minutes window relative to the evening assessment timepoint. If patients 
remain in the unit without discharge to stay overnight during Days 14 to 27, a pre-dose and 2 h post-dose spirometry assessment will be performed in the 
morning (prior to taking controller medication) and pre-dose and 4 h (-2h) post-dose spirometry assessment in the evening. If patients are discharged and 
re-admitted to the unit for overnight stay on Days 15 to 27, the morning and evening post-dose spirometry assessment will be 4 h (-2h) post-dose (controller 
medication timing will remain unchanged from home dosing and controller medication will be taken directly after study intervention). At clinic visits with 
no overnight stay, morning pre-bronchodilator and 2 h post spirometry will be performed. The timing of controller medication and clinic post-dose 
spirometry assessments may be adjusted by the Sponsor.
o
ECG will be measured before (within 75 min) and 1 hour (± 10 min) after administration of study intervention on visits as indicated.
p
Home device spirometry will be performed pre-dose twice daily, including on in-clinic assessment days. On in-clinic assessment days, home spirometry 
may be performed up to 2 hours prior to dosing.
q
At Visit 1 the e-Diary is set up, participants perform training and ACQ-6 and SNOT-22 is completed.
r
The e-Diary will be completed twice daily during the Run-in, Treatment, and Follow-up Period.
s
Study intervention will be administered 
 
 While at clinic, the study drug administration will be monitored by the site staff. Administration will be registered in the e-Diary by the 
participant.
t
AEs will be collected from the time of informed consent. Unscheduled safety sampling may be performed at the discretion of the Investigator in the event 
of AEs/AESIs, including but not limited nasal swabs to confirm infection.
u
Baseline safety sampling will be performed pre-dose on Day 1.
v
Sampling on Days 2, 6, 8, 10, and 12.
w
CRP must be done locally on Day -1 (may be performed on Day -2 for logistical reasons) to confirm eligibility as per inclusion criterion 26. It may be 
performed throughout the study in the event of AE/AESI as required to inform suspension/stopping criteria.
x
Blood samples will be analysed for IgE if potential drug related IgE response is observed in any participant; may be collected on Day -1 or Day 1 pre-dose.
y
PCR may be performed to confirm hepatitis B / hepatitis C status if required.
z
Blood samples for PK measurements will be collected for all participants. Timing of samples: Day 1 pre-dose (-60 min), 1, 2, 3 (± 10 min), 4, 6, 8
(± 20 min) and 12 h (up to 1h prior to the next dose, must be before the subsequent dose); Day 28 pre-dose (-60 min), 1, 2, 3 (± 10 min), 4, 6, 8 (± 20 min), 
and 12h (± 1 h; single dose of AZD1402 only on Day 28). Pre-dose on Days 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 (up to 1 h prior to the next dose, must be 
before the subsequent dose), 29 (24 h ± 2 h after Day 28 dose), 30 (48 h ± 2.5 h after Day 28 dose), 32 (96 h ± 2.5 h after Day 28 dose), 39 (± 6 days), and 
56 (± 4 days). Part Ib only: Day 20, 4 h post-morning dose (± 20 min). The PK sampling timepoints may be amended based on results from Part 1a/b. An 
unscheduled PK sample may be collected in the case of AEs and / or unscheduled safety blood sampling.
aa
ADA sampling, pre-dose Day 1, Day 14, Day 20, Day 24 (Part 1b only) and Day 28 and on Follow-up/unscheduled visits.
 
An unscheduled ADA sample may also be collected in case of AEs/AESIs and/or unscheduled safety blood sampling.
bb
Sample collection if consented only. If for any reason the sample is not drawn at Visit 3, it may be taken at any visit until the last study visit.
cc
All urine pregnancy tests will be done pre-dose.
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dd
SARS-CoV-2 serology at Screening, End of Trial and final Follow-up Visits; PCR is optional and may be performed centrally or at the local laboratory as
clinically indicated and as per local guidelines for the duration of the study. Ad hoc nasal and/or throat-swab specimen is to be collected for the 
identification of a suspected respiratory infection during any visit. This may be performed locally, or if required by central laboratory.
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Table 2
Schedule of Activities Part 2
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
Signed informed consent
X
5.1
Inclusion and exclusion criteria
X
X
X
5.1, 5.2
Demography
X
5.1
Medical/surgical history
X
5.1
Smoking history including cotinine testing
X
5.1
Asthma history
X
5.1
Concomitant medication
X
X
X
X
X
X
X
X
X
X
6.5
Height/weight d
X
X
8.2.1
Physical examination
X e
X f
X f
X f
X f
8.2.1
Vital signs (blood pressure, pulse rate, temperature, 
respiratory rate) g
X
X
X
X
X
X
X
X
X
X
8.2.2
Study drug inhalation training
X
X h
6.1.3
Home device (spirometer) dispensation
X
6.1.2
Home device training (spirometer)
X
X h
6.1.2
Rescue medication (eg, salbutamol) i
X
X
X
X
X
X
X
X
X
X
6.5.1
FeNO test (in-clinic) j
X
X
X
X
X
X
X
X
X
X
8.1.3
Spirometry (FEV1 and FVC) k
X
X
X
X
X
X
X
X
X
X
8.1.1
Reversibility test l
X
8.1.2
12-lead ECG m
X
X
X
X
8.2.3
ACQ-6
X
X
X
X
X
X
X
X
X
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Table 2
Schedule of Activities Part 2
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
SPFQ (optional)
X
X
X
X n
8.1.10
FEV1/PEF (home device) o
X
X
X
X
X
X
X
8.1.1, 8.1.11
Assign e-Diary p
X
8.1.4
Dispense e-Diary q
X
8.1.4
Check e-Diary compliance
X
X
X
X
X
X
X
X
X
6.4
Check compliance with background medication
X
X
X
X
X
X
X
X
X
8.1.4
Check compliance with study medication
X
X
X
X
X
X
Collect e-Diary
X
X
8.1.5
Asthma symptom score and rescue use
X
X
X
X
X
X
X
X
8.1.6, 8.1.7
Study drug dispensation
X
X
6.1
Study drug administration r
6.1
Drug accountability
X
X
X
6.2
Return unused medication and inhaler 
X
X
X
6.2
AE s
X
X
X
X
X
X
X
X
X
X
X
8.3
Blood samples for biochemistry
X
X t
X
X
X
X
X
X
8.2.4
Blood samples for haematology
X
X
X t
X
X
X
X
X
X
8.2.4
Blood samples for clotting profile
X
8.2.4
Blood sample for hs-CRP
X
X
X t
X
X
X
X
X
X
8.6.1
Blood samples for safety immuno-biomarkers
X
X t
X
X
X
X
X
X
8.2.5.1
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Table 2
Schedule of Activities Part 2
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
Blood samples allergen-specific IgE u
X u
8.2.4
Blood samples for CRP (local laboratory) v
X
X
X
X
X
X
X
X
X
8.2.4
Blood samples for serum pregnancy test (all female 
participants)
X
5.1, 8.2.4
Blood samples for Hepatitis B (HBsAg, anti-HBs, 
anti-HBc), and C; HIV-1 and HIV-2; QFT for TB w
X
5.1, 8.2.4
Blood samples for PK measurements x
X
X
X
X
X
X
X
8.5.1
Blood samples for ADA y
X
X
X
X
X
X
X
X
8.5.1
 
z
X
8.6.2, 8.7
X aa
X aa
X aa
X
X aa
8.6.1
X aa
X aa
X
X aa
8.6.1
X aa
Urinalysis
X
8.2.4
Blood samples for FSH (if needed to confirm 
postmenopausal status in female participants 
< 50 years and not on HRT)
X
5.1, 8.2.4
Urine pregnancy test (females of childbearing 
potential) bb
X
X
X
X
5.1, 8.2.4
Urine drug screen
X
5.2, 8.2.4
SARS-CoV-2 PCR cc
X
X
X
X
X
X
X
X
X
X
X
5.2, 8.2.4
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Table 2
Schedule of Activities Part 2
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
SARS-CoV-2 serology cc
X
5.2, 8.2.4
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; 
COVID-19 = Coronavirus disease-2019; CRP =C-reactive protein; CSP = clinical study protocol; ECG = electrocardiogram; e-Diary = 
electronic diary; ETV = early termination visit; FEV1 = forced expiratory volume in 1 second; FeNO = fractional exhaled nitric oxide; FSH = follicle stimulating 
hormone; FVC = forced vital capacity; 
 HBsAg = hepatitis B surface antigen; HIV = human immunodeficiency virus; 
 
 HRT = hormone replacement therapy; hs-CRP = high sensitivity CRP; IgE = immunoglobulin E; IPD = Intervention Discontinuation Visit;
 PCR = polymerase chain reaction; PEF = peak expiratory flow; PK = pharmacokinetics: RNA = ribonucleic acid; 
QFT = QuantiFERON; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SPFQ = Study Participant Feedback Questionnaire; TB = tuberculosis
a
In-clinic outpatient visits during the Treatment Period will be scheduled so that they fall at the time of morning dose administration.
b
Time between Visit 1 and Visit 2 may be extended up to 28 days upon input from the Study Physician.
c
Visit 1 can be done on several/different days prior to Visit 2.
d
Height at Visit 1 only.
e
A complete physical examination including an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including 
ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal and neurological systems will be performed.
f
A brief physical examination including an assessment of the general appearance, skin, abdomen, cardiovascular, and respiratory systems will be performed.
g
Vital signs will be measured pre-dose at the scheduled morning dosing in-clinic visits.
h
Refresher training if required.
i
Check if participant has enough rescue medicine for use at-home use and refill if necessary.
j
FeNO will be measured pre-spirometry, pre-dose (as applicable), and pre-bronchodilation.
k
Spirometry will be performed 45 minutes and 15 minutes prior to first dose of study intervention on Day 1 and pre-dose at all other visits. If possible, all 
post-randomisation pre-dose morning clinic device spirometry assessments should be performed within ± 1.5 hours of the time that the 15 min prior to 
randomisation spirometry was performed.
l
Reversibility testing will be performed 15 to 30 minutes after inhalation of 400 μg of salbutamol.
m
ECG will be measured before study drug administration on Day 1 (within 75 min), and 1 hour (± 20 min) after administration of study intervention on post 
randomisation visits as indicated.
n
SPFQ (optional) will not be completed at unscheduled visits.
o
At-home spirometry will be completed up to V8 and only to be completed at non-clinic visit timepoints. 
p
At Visit 1 the e-Diary is set up, participants perform training and ACQ-6 is completed.
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q
The e-Diary will be completed twice daily during the Run-in, Treatment, and Follow-up Period.
r
Study intervention will be administered 
 
28). Date and time of administration at home will be registered in the e-Diary by the participant. Study drug administration at the clinic will be under 
supervision. The Day 28 dosing window ± 2 days should only be used if needed, and where possible to keep within ± 1 day.
s
AEs will be collected from the time of informed consent. Unscheduled safety sampling may be performed at the discretion of the Investigator in the event of 
AEs/AESIs, including but not limited nasal swabs to confirm infection.
t
Baseline safety sampling will be performed pre-dose on Day 1.
u
Blood samples will be analysed for IgE if potential drug related IgE response is observed in any participant.
v
Local CRP may be performed from Visit 3 and throughout the study in the event of AE/AESI as required to inform suspension/stopping criteria.
w
PCR may be performed to confirm hepatitis B / hepatitis C status if required. Additional evaluation may be required in participants with any signs of active 
TB at the time of screening or positive interferon-gamma release assay (IGRA, QuantiFERON®-TB Gold) test according to the local standard of care.
x
Blood samples for PK measurements will be collected in all participants pre-dose at each visit, including unscheduled visits. Intense sampling may be 
performed in approximately 25% of participants per treatment arm (for example, 20 subjects in the mg treatment arm). Timing of intense samples: Day 1: 
1, 2, 3 (± 10 min), 6, and 8 h (± 20 min), Day 21 4 h post-morning dose (± 20 min) and Day 28 (last dose), 1, 2, 3 (± 10 min), 6, 8 (± 20 min), 24 (± 2 h), 48
(± 2.5 h), and 96 h (± 2.5 h; single dose of AZD1402 only on last day of dosing). PK sampling timepoints may be amended based on results from Part 1a/b. 
An unscheduled PK sample may be collected in the case of AEs and / or unscheduled safety blood sampling.
y
ADA sampling, pre-dose Day 1, Day 14, Day 21, Day 28, and at the Follow-up Visits. An unscheduled ADA sample may also be collected in the case of 
AEs/AESIs and/or unscheduled safety blood sampling.
z
Sample collection only if consented. If for any reason the sample is not drawn at Visit 3, it may be taken at any visit until the last study visit.
aa
Proposed samples and times: Serum: Pre-dose Day 1, pre-dose Week 2, Week 4 and at Follow-up.
 Pre-dose Day 1, and Week 4. 
: Pre-dose Day 1, Day 28, and Day 39. 
 Pre-dose Day 1.
bb
All urine pregnancy tests will be done pre-dose. In case of a positive result, a serum pregnancy test will be performed.
cc
SARS-CoV-2 serology at Screening; PCR is optional and may be performed centrally or at the local laboratory as clinically indicated and as per local 
guidelines for the duration of the study. Ad hoc nasal and/or throat-swab specimen is to be collected for the identification of a suspected respiratory infection 
during any visit. This may be performed locally, or if required by central laboratory.
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2
INTRODUCTION
AZD1402 is being developed as an inhaled therapy for patients with moderate to severe 
persistent asthma who are not controlled on standard of care therapies. This study will include 
adults with asthma on medium dose ICS-LABA with the aim to expand the population to 
include adults with more severe asthma in future studies.
2.1
Study Rationale
The current study aims to assess the efficacy and safety of inhaled AZD1402 administered as a 
dry powder 
for 4 weeks in adults with asthma on medium-to-high dose ICS-LABA in a 
2-part randomised, double-blind, placebo-controlled, and multi-centre study.
2.2
Background
2.2.1
Asthma
Asthma is a chronic, complex, and heterogeneous respiratory disease characterised by a range 
of pathogenic features including pulmonary inflammation, mucus hypersecretion, variable 
airway obstruction, and airway remodelling. It is defined by a history of respiratory symptoms 
that includes wheezing, shortness of breath, and cough, which vary over time and in severity. 
Both symptoms and airway obstruction can be triggered by a range of factors including 
exercise, exposure to inhaled irritants or allergens, or respiratory infections. Symptoms and 
airway obstruction can resolve in response to therapy or spontaneously, but participants 
remain at risk of severe worsening of their asthma (exacerbations). These asthma 
exacerbations can be life-threatening, can significantly impact the participant’s quality of life, 
and result in significant healthcare costs. It has been shown that asthma can be split into 
distinct clusters or phenotypes based on clinical and pathophysiological characteristics; these 
include allergic, non-allergic, eosinophilic, obese, late-onset, and severe systemic 
corticosteroid-dependent phenotypes. The treatment response of participants of different 
phenotypes varies, highlighting the need to develop new therapies for those participants who
are unresponsive to standard of care therapy (Ray, et al. 2016).
2.2.2
Current Therapies
Participants with asthma most often present with symptoms of wheezing, shortness of breath, 
cough, and chest tightness. The aim of asthma treatment is to achieve good symptom control, 
and minimise future risk of exacerbations as well as the potential side-effects of treatment 
International treatment guidelines for asthma recommend ICS as first line therapy
(GINA 2022). For individuals who are symptomatic on medium dose ICS monotherapy, 
step-up therapy with LABAs is the recommended next treatment option followed by other 
controller therapies including leukotriene receptor antagonists, theophylline, and OCS. 
‘Biologic agents’ (eg, omalizumab and benralizumab) that inhibit specific molecular targets 
such as IgE or Th2 cytokines and their respective receptors are reserved for those with severe 
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uncontrolled asthma. For most adults with asthma, a treatment regimen of a controller and 
bronchodilator therapy provides adequate long-term control. Inhaled corticosteroids are 
considered the “gold standard” in controlling asthma symptoms and LABAs are the most 
effective bronchodilators currently available. These agents are often given in combination as 
research has demonstrated that combination therapy of an ICS with an inhaled LABA provides 
better asthma control than high doses of ICS alone (Greening, et al, 1994; Woolcock, et al. 
1996). Inhaled corticosteroids/LABA combination therapies are the recommended therapy for 
participants who are not controlled on low doses of ICS alone.
Although the majority of adults with asthma respond to therapy, it is estimated that 5% to 10% 
of the population with asthma has symptomatic disease despite maximum recommended 
treatment with combinations of anti-inflammatory and bronchodilator drugs. This severe 
asthma population accounts for up to 50% of the total asthma health cost through hospital 
admissions, use of emergency services, and unscheduled physician visits (World Allergy 
Organisation 2013). Approved treatment options for severe asthma include tiotropium, a 
long-acting inhaled muscarinic antagonist bronchodilator; omalizumab, an anti-IgE 
monoclonal antibody; benralizumab, mepolizumab and reslizumab, which are monoclonal 
antibodies that target the eosinophil chemokine IL-5, and dupilumab, a monoclonal antibody 
blocker of IL-4Rα which blocks the downstream actions of IL-4 and IL-13. Oral
corticosteroids are associated with significant side effects and are therefore not prescribed 
over longer timeframes. For those adults with moderate/severe asthma who remain 
uncontrolled on currently approved inhaled or oral treatments, there is a clear unmet need for 
new therapies before introducing systemic biological treatment. Inhalation, as opposed to 
systemic and subcutaneous administration of biologics, could offer several potential 
advantages. In addition to much better convenience for participants, inhaled biologics might 
require a significantly lower dose, a reduced cost of goods, and hence an expanded participant
population. Lower systemic target engagement might also result in better tolerability (Rothe 
and Skerra, 2018). Inhaled drugs are advantageous as the drug delivery is localised to the lung 
(target organ) which may allow for a lower dose than needed with systemic delivery.
Inhalation is non-invasive, and thus advantageous in terms of ease of use. Current research is 
focusing on the different pathological mechanisms or endotypes of severe asthma and it is 
anticipated that this will lead to the development of effective therapies for these subsets of 
asthma patients.
2.2.3
AZD1402
AZD1402 is derived from human Tlc and is a potent and selective antagonist of IL-4Rα, 
which antagonises the pro-inflammatory actions of IL-4 and IL-13. AZD1402 is presented as 
an inhalation powder and belongs to a new class of therapeutics, Anticalin® proteins, which 
are modified lipocalins. Anticalin proteins are homologous with naturally occurring lipocalins 
(eg, Tlc and NGAL) and can be generated against a variety of targets using mutation and 
selection processes. AZD1402 is being developed as an inhaled IL-4Rα antagonist controller 


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therapy for the treatment of moderate to severe persistent asthma in participants who are not 
controlled on standard of care therapies.
A detailed description of the chemistry, pharmacology, efficacy, and safety of AZD1402 is 
provided in the IB.
2.3
Benefit/Risk Assessment
2.3.1
Risk Assessment
Safety observations from the AZD1402 PK bridging study identified hypersensitivity-like 
events following a double period of intermittent dosing as part of a cross over study design. 
During the multiple ascending dose study in untreated participants with mild asthma, several 
participants experienced respiratory signs and symptoms events such as shortness of breath, 
dyspnoea; these events could be observed concurrently with FEV1 decline. These events
tended to be associated with higher doses, including the 60 mg nebulised dose not being taken 
forward. These observations changed the known risk profile of AZD1402. Further 
characterisation of the safety profile of AZD1402 will be performed in the follow-on studies. 
The potential risks to participants will be mitigated via safety monitoring activities ongoing 
throughout the studies, as included in the study design and protocol to ensure the safety of the 
participants. The benefit or risk to participants is considered to be acceptable.
Detailed information about known and expected potential risks of AZD1402 can be found in 
the IB.
2.3.1.1
Further Risk Mitigation Approaches
The development of any AE, abnormality in laboratory variables, or any other safety variables 
will be closely monitored and evaluated on an ongoing basis during this clinical study. Data 
from all participants will include AEs, clinical chemistry, vital signs, ECG, spirometry (from a 
safety perspective), and PK.
In the event of respiratory AESIs, FEV1 decline, or clinically indicated AEs or findings, 
appropriate tests, including an HRCT scan, could be performed considered to evaluate the 
potential effect of the study intervention on the airways of participants. Note, ionising 
radiation carries an increased risk of developing cancer.
This study will include a placebo arm. However, all participants will remain on their current 
standard of care (or equivalent) and rescue medication as required. Participants will be treated 
for exacerbations of asthma if they occur and the e-Diary will trigger ‘worsening of asthma 
alerts’ for participants and research sites.
Participants enrolled in the study will be requested to take protocol-defined asthma 
medications only, which may include their usual asthma medication or equivalent. All 


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participants will be provided with a rescue medication (eg, SABA) to be used throughout the 
Run-in and Treatment Periods, when required. The Investigators will carefully monitor the 
participants throughout the study, and evidence of worsening of asthma (through study visits 
and e-Diary recordings of lung function, symptoms, and rescue inhaler use), will trigger an 
alert to the local clinician as well as the Study Physician. Participants who use daily rescue 
medication of SABA ≥8 puffs for ≥3 consecutive days at any time during Run-in Period and 
before randomisation will be excluded from the study. Participants are free to withdraw from 
participation in the study at any time. Upon completion of the study, participants’ choice of 
medical therapies are not restricted.
Risk mitigation will be applied as follows: Part 1 will include a safety review step prior to 
continuation into Part 2. A DSMB will be utilised for the ongoing evaluation of safety during 
Part 2.
The risks associated of participating this study in the scenario of COVID-19 and the 
mitigation approaches are detailed in Appendix F.
2.3.2
Benefit Assessment
The purpose of this Phase II, proof-of-concept clinical study is to evaluate the efficacy, safety 
and tolerability of AZD1402 in adult participants with asthma on medium-to-high dose 
ICS-LABA. For participants randomised to AZD1402, there is a potential benefit in terms of 
improvement of their asthma status as indicated by a reduction in the lung inflammation 
biomarker FeNO seen in Phase I studies. Participants may derive benefit from health 
assessments (eg, ECG, clinical laboratory safety measurements, and standard of care
adherence monitoring) performed as part of the study.
2.3.3
Overall Benefit: Risk Conclusion
Considering the measures taken to minimise risk to participants in this study, the potential 
risks identified in association with AZD1402 are justified by the anticipated benefits that may 
be afforded to patients with asthma.
Detailed information about the known and expected benefit, potential risks, and mitigation 
strategies of AZD1402 risks can be found in the IB.


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3
OBJECTIVES AND ENDPOINTS
Table 3
Objectives and Endpoints (Part 1)
Objectives
Outcome Measure
Primary
•
To evaluate the safety and tolerability of 
AZD1402 compared to placebo at different dose 
levels in adults with asthma controlled on 
medium dose ICS-LABA
Primary safety endpoint: 
•
Adverse events / AESIs / SAEs with a 
particular focus on infection, eosinophilia, and 
hypersensitivity-like events
•
Vital signs
•
Changes in clinical chemistry, haematology,
and coagulation parameters
•
Immuno-biomarkers (including but not limited 
to cytokines, CRP, immunoglobulins including 
IgE)
•
ECGs
•
FEV1
•
FeNO
Secondary
•
To investigate the PK profile and 
immunogenicity of AZD1402, and associated 
effects on safety
•
PK parameters (full profile in all participants)
•
ADAs
Exploratory
•
 
 
•
Change from baseline in FeNO at Day 28 and 
average over the Treatment Period
•
 
•
To assess the effect of AZD1402 compared to 
placebo on cough by a VAS in adults with 
asthma controlled on medium dose ICS-LABA
•
Change from baseline average in cough VAS 
over the Treatment Period
•
 
•
 
•
 
•
 
•
•
 
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Table 3
Objectives and Endpoints (Part 1)
Objectives
Outcome Measure
•
 
 
•
•
 
Abbreviations: 
 ADAs = anti-drug antibodies; AESI = adverse event 
of special interest; CSR = clinical study report; CRP = C-reactive protein; ECG = electrocardiogram; 
FeNO = fractional exhaled nitric oxide; FEV1 = forced expiratory volume in 1 second;
 
 ICS = inhaled corticosteroids; IgE = immunoglobulin E; LABA = long-acting beta agonist; 
 PK = pharmacokinetics; SAEs = serious adverse events; VAS = Visual Analogue 
Scale
Table 4
Objectives and Endpoints (Part 2)
Objectives
Outcome Measure
Primary
•
To investigate the efficacy of inhaled AZD1402 
compared to placebo in adults with asthma who 
are uncontrolled on medium-to-high dose 
ICS-LABA
Primary efficacy endpoint: 
•
Change from baseline in pre-bronchodilator 
FEV1 at Week 4
Secondary
•
To further investigate the efficacy of AZD1402 
compared to placebo in adults with asthma who 
are uncontrolled on medium-to-high dose 
ICS-LABA
•
Change from baseline in pre-bronchodilator 
FEV1 average over the 4-week Treatment 
Period 
•
Change from baseline in ACQ-6 at Week 4 and 
average over the Treatment Period
•
Proportion of participants with a decrease in 
ACQ-6 score of ≥0.5 from baseline to Week 4
•
Change from baseline in average morning PEF 
over the Treatment Period
•
Change from baseline in average evening PEF 
over the Treatment Period
•
Change from baseline in daily average asthma 
symptom score (AM/PM) over the Treatment 
Period
•
To investigate the effect of AZD1402 compared 
to placebo on airway inflammation in adults with
asthma who are uncontrolled on medium-to-high 
dose ICS-LABA
•
Change from baseline in FeNO (in-clinic) at 
Week 4 and average over the Treatment Period
•
To investigate the PK profile and 
immunogenicity of AZD1402, and associated 
effects on safety
•
PK parameters (sparse in all, full profile in a 
subset of participants in each treatment arm)
•
ADAs
•
To evaluate the safety and tolerability of 
AZD1402 compared to placebo in adults with 
asthma who are uncontrolled on medium-to-high 
dose ICS-LABA
•
Adverse events / AESIs / SAEs with a 
particular focus on infection, eosinophilia, and 
hypersensitivity-like events
•
Vital signs
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Table 4
Objectives and Endpoints (Part 2)
Objectives
Outcome Measure
•
Changes in clinical chemistry, haematology,
and coagulation parameters
•
Immuno-biomarkers (including but not limited 
to cytokines, CRP, immunoglobulins including 
IgE)
•
ECGs
•
FEV1 
•
FeNO
Exploratory
•
 
 
 
•
 
•
•
•
•
•
 
•
Change from baseline in FeNO
•
 
 
•
 
•
 
•
•
 
•
 
 
•
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; AESIs = adverse events of special interest; 
ADAs = anti-drug antibodies; AM = before noon (antemeridiem); CRP = C-reactive protein; CSR = clinical 
study report; ECG = electrocardiogram; FeNO = fractional exhaled nitric oxide; FEV1 = forced expiratory 
volume in 1 second; 
 ICS = inhaled corticosteroids; IgE = immunoglobulin E; 
LABA = long-acting beta agonist; 
; PEF = peak expiratory flow; 
PK = pharmacokinetics; PM = after noon (post meridiem); SAEs = serious adverse events;
4
STUDY DESIGN
4.1
Overall Design
This is a randomised, placebo-controlled, double-blind, multi-centre, study to assess the 
efficacy and safety of inhaled AZD1402. The study consists of two parts. Part 1 will be 
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performed in a Lead-in Cohort to evaluate the safety and PK in a population with asthma 
controlled on medium dose ICS-LABA before progressing to at-home dosing in adults with 
asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. Part 2 will be 
initiated for each dose level following evaluation of safety and PK at the relevant dose level in 
Part 1a. The study intervention in both parts of the study will be administered 
 using the 
 DPI for a period of 4 weeks.
This study will be conducted in approximately 8-10 countries. The date of first participant
screened is estimated to be in December 2020 and the date of last participant last visit is 
estimated to be in Q3 2023. The entire study period for each participant in both Parts 1 and 2, 
is approximately 3.5 months; a 2-week Screening Period, a 4-week Run-in Period, 4 weeks of 
Treatment Period, and 4 weeks of Follow-up Period.
Participants in both parts of the study will receive a handheld e-Diary device which they are 
required to complete twice daily during the entire duration of the study. Participants will be 
provided training on the use of the handheld device. Further details on e-Diary is provided in 
Section 8.1.4.
4.1.1
Part 1
Part 1 of the study will be randomised, double-blind, placebo-controlled, and conducted in 
parallel for the 2 
 dose levels (Part 1a) followed by an unblinded safety review and 
escalation to the 
 dose (Part 1b) dependent on the outcome of the safety review. An 
unscheduled safety review meeting may also be held in the event of any safety or tolerability 
events requiring further review that may impact continuation of a cohort or the study (see 
Appendix A 5.2). Data evaluated in the safety review will be unblinded; however, blinding 
will be maintained for participants and Investigators. Part 1 will be conducted at 
approximately 8 study centres.
Part 1a will consist of 30 participants who will be randomised 1:1:1 to receive 1 of the 2
 
AZD1402 DPI doses ( or mg) or placebo in parallel. Part 1b will consist of 15 participants 
who will be randomised 2:1 to receive the 
 AZD1402 DPI dose (
 mg) or placebo.
Due to logistical reasons, the randomisation in Part 1 will be stratified by site in Australia and 
Germany.
The target population is adults with asthma (age 18 to 75 years, inclusive) who are adequately 
controlled on a stable medium dose ICS-LABA (and additional rescue medication as needed), 
ACQ-6 score ≤1.0 and pre-bronchodilator FEV1 ≥70%, and with no exacerbation requiring 
systemic treatment or hospitalisation/emergency department visit for asthma during the 
12 months prior to study start.
The primary objective in Part 1 is to determine the safety and tolerability of AZD1402 in 
relation to placebo at 3 different dose levels in adults with asthma controlled on medium dose 
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ICS-LABA with 4 weeks of dosing and will include assessments of AEs, vital signs, safety 
blood samples, immuno-biomarkers, ECGs, FEV1, and FeNO. In addition to clinic spirometry 
assessments, participants will receive a home spirometry device to use in-clinic and at home 
as described in the SoAs (Table 1 and Table 2). The secondary objective is to investigate the 
PK profile and immunogenicity of AZD1402. A full PK and ADA profile will be taken in all 
participants as per the SoAs (Table 1 and Table 2). Part 1 is not powered for efficacy, but 
exploratory endpoints will include FeNO and 
 over the 4-week Treatment Period. 
Additionally cough and 
 The e-Diary will be 
used to record daily symptoms and questionnaire data.
Participants will sign informed consent prior to participating in any study specific procedures. 
Visit 1 may be completed over several days prior to Visit 2. If participants are eligible at 
Visit 1 and the FEV1 criterion of ≥70% predicted and ACQ-6 score of ≤ 1.0 is met, they will 
return for Visit 2, beginning the Run-in Period. During the Run-in Period, all participants will 
continue their own stable treatment regime, which will include medium dose ICS-LABA. 
Treatment must remain stable for the duration of the study, unless clinically indicated 
adjustments are required.
At Visit 3, Day -1, following the 4-week Run-in Period, participants will be admitted to the 
clinic. If they remain controlled on a stable dose of ICS-LABA, fulfill the entry criterion of 
FEV1 ≥70%, and have an ACQ-6 score of ≤1.0, the participants will be randomised on the 
following day as follows:
Part 1a Lead-in Cohort

AZD1402 inhalation mg 

AZD1402 inhalation mg 

Placebo inhalation 
Part 1b Lead-in Cohort

AZD1402 inhalation 
mg 

Placebo inhalation 
Following randomisation to the 4 weeks of dosing, participants will remain at the clinic for a 
mandatory residential period of at least 2 weeks followed by 3 outpatient visits (Day 16, 20 
and 24). The participants are re-admitted to the clinic on Day 28 and discharged the next day
(Day 29) followed by 2 outpatient visits (Day 30 and 32). Additionally, following the 
minimum 2-week residential period, participants may remain overnight in the clinic any time 
during Week 3 and Week 4 for any reason. Resuming of dosing following suspension for 
safety reasons will be performed at the clinic.
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Part 1 will contain a total of 11 visits. At Visit 7, participants will complete the Treatment 
Period. Two outpatient visits for safety and PK (Visit 8 and 9) are scheduled 1 and 3 days after 
discharge from the clinic. A Follow-up (Visit 10) will occur 1 to 2 weeks following Visit 7, 
and a second and final Follow-up (Visit 11), will occur 4 weeks after Visit 7.


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Figure 3
Dose Staggering and Decision Points Part 1a/b and Part 2
 DPI = dry powder inhaler; N = number of participants; SRC = Safety review committee
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4.1.2
Part 2
Part 2 will be randomised, double-blind, placebo-controlled and will include approximately 
165 participants randomised 2:1 (active to placebo) to evaluate 2 inhaled dose levels of 
AZD1402 versus placebo. Adult participants (age 18 to 75 years, inclusive) with 
physician-diagnosed uncontrolled asthma treated with medium-to-high dose ICS (total daily 
dose > 400 μg of budesonide dry powder formulation or equivalent) with LABA
(GINA 2022), as maintenance treatment for at least 6 months prior to Visit 1 will be included. 
ICS-LABA and any additional asthma maintenance controller medications (eg, leukotriene 
receptor inhibitors, theophylline, LAMA, and chromones) must be stable for at least 4 weeks
prior to Visit 1. Standard of care should not include systemic steroid or biologic therapy. 
Participants will be required to have a FEV1 of 40% to 85% (inclusive) predicted at Screening, 
start of Run-in and prior to randomisation (Visits 1, 2 and 3). Participants will also be required 
to have a blood eosinophil count ≥150 cells/μL at Screening, and FeNO ≥25 ppb and ACQ-6 
score ≥1.5 at Screening and randomisation together with documented compliance to 
ICS-LABA treatment during the 4-week Run-in.
Apart from the scheduled clinic visits, the 4 weeks of dosing in Part 2 of the study will be at 
home. Part 2 will be started after the unblinded safety review for Part 1a and will be 
conducted at approximately 68 study centres.
The primary objective in Part 2 of the study is to determine the efficacy of AZD1402 after
4 weeks of dosing as assessed by change from baseline in pre-bronchodilator FEV1 compared 
to placebo. The study will recruit participants receiving treatment with medium-to-high dose 
ICS-LABA at Screening and in order to ensure a balanced distribution across the treatment 
arms; the randomisation of participants will be stratified by country.
Participants will sign informed consent prior to participating in any study specific procedures. 
Visit 1 may be completed over several days prior to Visit 2. If participants are eligible at 
Visit 1 with a confirmed asthma diagnosis and FEV1 criteria (≥40% to ≤85% predicted) are 
met, they will return for Visit 2, beginning the Run-in Period. During the Run-in Period, all 
participants will continue their standard of care including ICS-LABA. The ICS-LABA dose 
must remain stable for the duration of the study, unless clinically indicated adjustments are 
required.
At Visit 3, following the 4-week ICS-LABA Run-in, participants who remain uncontrolled, as 
assessed by an ACQ-6 score of ≥1.5 (Visit 1 and Visit 3), pre-bronchodilator FEV1 of 40% to
85% (inclusive) at baseline (Visit 3), and FeNO ≥25 ppb (Visit 1 and Visit 3) will be 
randomised to 1 of 3 possible treatment arms. Eighty participants will be randomised to the 
mg dose and placebo, respectively. Approximately 5 participants will be randomised to mg 
dose arm:
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
AZD1402 inhalation mg 

AZD1402 inhalation mg 

Placebo inhalation 
The primary assessment of efficacy is measured by the change in pre-bronchodilator FEV1
from baseline (Visit 3), as compared to placebo in the 4-week Treatment Period (Visit 7). 
Secondary assessments of efficacy include FeNO, PEF, ACQ-6 and daily symptoms as 
recorded in the e-Diary.
 
 
 
 
 
 
 
Part 2 will contain a total of 9 visits. At Visit 7, participants will complete the Treatment 
Period. A Follow-up (Visit 8) will occur approximately 1 to 2 weeks following Visit 7, and a 
second and final Follow-up (Visit 9), will occur approximately 4 weeks after the end of 
treatment.
Pharmacokinetic sampling (sparse sampling in all, full profile in a subset of approximately
25% of participants per treatment arm) will be performed. In Part 2 an interim analysis may be 
performed which will be evaluated by the URC.
For both Parts 1 and 2, in addition to the PK, blood samples for ADA assessment will be 
collected in all participants. Blood samples and nasal/nasopharyngeal/oropharyngeal swabs
may be collected for diagnosis of COVID-19 and identification of SARS-CoV2 antibodies as 
indicated in the SoAs. Clinical monitoring of any suspected hypersensitivity events may 
prompt unscheduled assessments of safety parameters, including FEV1, FeNO, CRP, routine 
safety blood samples, ADA, immuno-biomarkers, and PK. 
 
 
 
 
 
 
Spirometry, FeNO measurement, ECG, and ACQ-6 will be performed at site visits as 
indicated in the SoAs (Table 1 and Table 2). Spirometry measurements will also be performed 
in-house and at home as well as daily e-Diary entries and rescue medication use. Home FeNO 
measurement and cough VAS will be performed in Part 1.
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Safety variables (including AEs, safety laboratory parameters, and lung function) will be 
continually evaluated.
If required for safety reasons/COVID-19 mitigation, home sampling and assessments may be 
conducted for any of the scheduled visits (Appendix F).
In order to provide an independent periodic review of safety throughout the study, in addition 
to the ongoing, blinded review provided by the Sponsor/Designee Medical Monitor for
detection of any potential safety signals, an unblinded DSMB will be utilised for Part 2 of the 
study. Set up of the DSMB, and frequency of data transfer will be described in the DSMB 
Charter. The DSMB will make any necessary recommendations regarding further conduct of 
the study based on their evaluation of emerging data in Part 2 of the study. Additionally, an 
unblinded SRC, including the Sponsor study team will review PK and unblinded safety data
following completion of Part 1a before progressing to Part 1b/2, and following completion of 
Part 1b.
Refer to Appendix A 5 for details on different committees involved in this study.
4.1.3
Study Conduct Mitigation During Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis
The guidance given below supersedes instructions provided elsewhere in this CSP and should 
be implemented only during cases of civil crisis, natural disaster, or public health crisis (eg, 
during quarantines and resulting site closures, regional travel restrictions, and considerations if 
site personnel or study participants become infected with SARSCoV-2 or similar pandemic 
infection) which would prevent the conduct of study-related activities at study sites, thereby 
compromising the study site staff or the participant’s ability to conduct the study. The 
Investigator or designee should contact the study Sponsor to discuss whether the mitigation 
plans below should be implemented.
To ensure continuity of the clinical study during a civil crisis, natural disaster, or public health 
crisis, changes may be implemented to ensure the safety of study participants, maintain 
compliance with GCP, and minimize risks to study integrity.
Where allowable by local health authorities, ethics committees, healthcare provider guidelines 
(eg, hospital policies) or local government, these changes may include the following options: 

Obtaining consent or reconsent for the mitigation procedures (note, in the case of verbal
consent or reconsent, the ICF should be signed at the participant’s next contact with the 
study site).

Rescreening: Additional rescreening for screen failure and to confirm eligibility to
participate in the clinical study can be performed once in previously screened participants


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once if there is reason to believe the reason for screen failure was temporary. It is only 
permitted to rescreen more than once for logistical reasons.

Home or Remote visit: Performed by a site qualified HCP or HCP provided by a TPV.

Telemedicine visit: Remote contact with the participants using telecommunications 
technology including phone calls, virtual or video visits, and mobile health devices.

At-home IMP administration.

At-home study procedure: Performed by a qualified HCP from the study site or TPV
service.

Additional information that cannot be obtained via a site visit can be obtained via 
telemedicine.

Centralised assessments may be performed locally.
For further details on study conduct during civil crisis, natural disaster, or public health crisis, 
refer to Appendix G.
4.1.4
Study Conduct Mitigation During SARS-CoV-2 Pandemic
In case of local or global SARS-CoV-2 outbreaks, appropriate risk assessments and mitigation 
measures will need to be taken into consideration to protect participants and health care 
professionals involved in the clinical trial and ensure data quality as per regulatory agencies 
and local guidelines. 
If, for reasons related to the COVID-19 pandemic (eg, local lockdown, self-isolation 
requirements), a participant is not able to attend their scheduled visit within the visit window, 
they can have their visit rescheduled as per agreement with the Sponsor Study Physician. 
Additionally, on-site visits may be replaced by a telemedicine visit if allowed by 
local/regional guidelines. Having a telemedicine contact with the participants will allow 
collection of data for AEs and ensure continuous medical care and oversight. The term 
telemedicine visit refers to remote contact with the participants using telecommunications 
technology including phone calls, virtual or video visits, and mobile health devices.
Applicable measures for source data verification, if on-site monitoring at the trial sites is not 
indicated due to the coronavirus pandemic should be implemented.
For further details on study conduct during SARS-CoV-2 or similar pandemic refer to 
Appendix F.
4.2
Scientific Rationale for Study Design
A placebo-controlled, double-blind design has been chosen to limit the occurrence of 
conscious and unconscious bias in the conduct and interpretation of the clinical study arising 
from the influence that the knowledge of treatment may have on the recruitment and 


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allocation of participants. The inclusion of a placebo arm is considered the most reliable 
method to minimise participant and Investigator bias and is also recommended by the EMA 
regulatory guidance in the design of dose-finding studies for moderate-severe asthma.
The efficacy endpoints chosen in this study are commonly measured endpoints in asthma 
studies. Spirometry is one of the fundamental outcome measures used in asthma studies. It 
provides an objective and highly reproducible measure of airflow limitation caused by smooth 
muscle contraction or structural changes. Forced expiratory volume in 1 s is recommended as 
the primary endpoint for studies of bronchodilator therapy by the ATS and the ERS in their 
official statement on asthma control and exacerbations (Reddel, et al. 2009). The ACQ is also 
widely regarded as a useful measure that includes some core asthma symptoms and symptom-
related clinical markers of asthma. Traditionally, PEF, occurrence of exacerbations, use of 
rescue medication, markers of airway inflammation as assessed by FeNO, and participant
reported symptoms scores are also among the different measures used to assess the efficacy of 
asthma interventions in clinical trials (GINA 2022).
 
 
4.3
Justification for Dose
The proposed inhaled doses of AZD1402 in this study are 
mg 
The doses in the relevant range were selected considering the following data from previous 
clinical studies:

 
 
 
 
 
 
 
 

 
 
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Safety and tolerability data from previous studies with AZD1402 support ongoing 
development with step-wise dose increase as described in the current study design.
4.4
End of Study Definition
For the purpose of CTT the definition of the end of the study differs under FDA and EU 
regulatory requirements:
European Union requirements define study completion as the last visit of the last subject for 
any protocol related activity.
Food and Drug Administration requirements defines two completion dates:
Primary Completion Date – the date that the final participant is examined or receives an 
intervention for the purposes of final collection of data for the primary outcome measure, 
whether the clinical study concluded according to the pre-specified protocol or was 
terminated. In the case of clinical studies with more than one primary outcome measure with 
different completion dates, this term refers to the date on which data collection is completed 
for all of the primary outcomes.
Study Completion Date – the date the final participant is examined or receives an intervention 
for purposes of final collection of data for the primary and secondary outcome measures and 
AEs (for example, last participant’s last visit), whether the clinical study concludes according 
to the pre-specified protocol or is terminated.
A participant is considered to have completed the study if he/she has completed all periods of 
the study including the last scheduled procedure shown in the SoAs (Table 1 and Table 2).
4.4.1
Premature Termination of the Study and Stopping Criteria
The Sponsor will suspend or terminate a dose level or the entire study (as applicable) 
following the review of all available safety data if any of the following occurs at the dose or 
study level:
Per dose level (Part 1)

Two participants experience a FEV1 drop ≥30% from baseline (in-clinic)* attributable to 
AZD1402.

One participant experiences a hypersensitivity-like SAE attributable to AZD1402.
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
Day 28 exposure in one participant in Part 1 exceeds or is predicted to exceed (for 
Part 1b) a peak concentration Cmax of 5420 ng/mL or exposure AUC(0-24 h) of 
68700 ng.h/mL.
*Baseline Part 1: Mean of Day -1 and Day 1.
Per dose level (Part 2)

Clinically significant FEV1 decline from baseline* attributable to AZD1402 comparing 
the number of participants reaching a FEV1 drop ≥ 30% in active versus placebo as 
assessed by the DSMB.

One participant experiences a hypersensitivity-like SAE attributable to AZD1402.
*Baseline Part 2: Mean of Day 1 (15 minutes and 45 minutes pre-dose).
Study level

Two participants experience a hypersensitivity-like SAE and/or severe hypersensitivity 
event attributable to AZD1402.

The overall safety and tolerability profile as determined by the DSMB does not justify 
continuation with dosing as per the current protocol.

Significant immunogenicity impacting safety and tolerability.

The Sponsor considers the applied doses of the study intervention to be no longer 
relevant.

The Sponsor decides to discontinue the study.

Data not known before, become available and raise concern about the safety of AZD1402 
so that continuation would pose potential risks to the participants.
5
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known 
as protocol waivers or exemptions, is not permitted.
Note: Visit 1 and Visit 2 assessments (Table 1 and Table 2) can be repeated once (within 
1 week of the original visit for Visit 2), but only if the Investigator believes that a repeat visit 
may allow the participant to become eligible to enter the study and the screening window is 
maintained. CRP may be repeated for the duration of the run-in period to inform V2 eligibility 
for randomisation. Run-in may be extended on a case-by-case basis at the discretion of the 
Sponsor in the event of logistical challenges.


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5.1
Inclusion Criteria
Participants will be enrolled into this study only if they meet all of the following inclusion 
criteria:
Age
1
Participants 18 to 75 years (inclusive) of age, at the time of signing the informed consent
at Visit 1.
Type of Participant and Disease Characteristics
2
Participants who have a documented clinical diagnosis of asthma for ≥12 months before 
Visit 1.
3
Participants who are able to perform acceptable pulmonary function testing for FEV1 
according to ATS/ERS acceptability criteria.
4
Participants who are able to demonstrate the ability to use the study inhalation device 
properly (at Visit 2).
Weight
5
Body mass index within the range 18 to 35 kg/m2 (both inclusive).
Sex
6
Male or female
Contraceptive use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
(a) Male participants must be surgically sterile or agree to use highly-effective 
contraceptives for the entire duration of the study (from the time they sign the 
informed consent), or for 3 weeks after the last dose of study intervention, whichever 
is longer. Non-sterilised male partners of a woman of childbearing potential must use 
a male condom plus spermicide (condom alone where spermicides are not approved)
from the time they sign the informed consent for the duration of the study or for 3 
weeks after the last dose of the study intervention, whichever is longer. It is strongly 
recommended for the female partner of a male participant to also use a highly-
effective method of contraception (described below) throughout this period.
(b) Female participants:

All female participants must have a negative serum pregnancy test at Screening. 
Female participants are considered to be of non-childbearing potential, if they are 
either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy) or postmenopausal. Women will be considered postmenopausal 


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if they have been amenorrhoeic for ≥12 months prior to the planned date of 
randomisation without an alternative medical cause. The following age-specific 
requirements apply:

Women < 50 years old would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of exogenous 
hormonal treatment and FSH levels in the postmenopausal range.

Women ≥50 years old would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of all 
exogenous hormonal treatment. Women who are considered to be 
postmenopausal without documentation of 12-month amenorrhea and 
receiving HRT, will have to use one of the non-hormonal highly-effective 
contraception methods in addition to HRT, or discontinue HRT and to use 
hormonal highly-effective method for at least 3 months prior to Visit 1, 
Screening Period.

Female participants of childbearing potential 

must have a negative urine pregnancy test before the administration of first 
dose of study intervention and

must agree to use a highly-effective method of birth control (confirmed by 
the Investigator) from randomisation throughout the study duration or for 3 
weeks after the last dose of study intervention, whichever is longer.
NOTE: Highly-effective methods of birth control (those that can achieve a failure rate of 
less than 1% per year when used consistently and correctly) include:

Combined (oestrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation- oral, intravaginal, or transdermal.

Progestogen-only hormonal contraception associated with inhibition of 
ovulation- oral, injectable, or implantable.

Intrauterine device.

Intrauterine hormone-releasing system.

Bilateral tubal occlusion.

Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the clinical 
study and the preferred and usual lifestyle of the participant).

Vasectomised sexual partner provided that partner is the sole sexual partner of 
the study participant and that the vasectomised partner has received medical 
assessment of the surgical success.


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Informed Consent
7
Capable of giving signed informed consent as described in Appendix A which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol.
8
Provision of signed and dated written Optional Genetic Research Information informed 
consent prior to collection of samples for optional genetic research that supports Genomic 
Initiative.
Others
9
Participant is a non-smoker or an ex-smoker (this includes marijuana, e-cigarettes or 
inhaled tobacco products and must have quit ≥3 months before Visit 1) with a total 
smoking history of less than 10 pack-years (not applicable for e-cigarettes).
10 Participant is willing and able to follow study procedures and restrictions.
In addition to the above, participants should meet all the specific inclusion and randomisation
criteria for respective parts of the study as listed below.
5.1.1
Part 1-specific Inclusion Criteria
11 Documented treatment with medium dose ICS with LABA for at least 6 months prior to 
Screening (Visit 1) (ICS equivalent of budesonide dry powder formulation > 400 to 
800 μg/day). 
12 ICS and LABA must be on a stable dose for at least 3 months prior to Visit 1, during 
Screening and Run-in Periods and may be contained in a combination product or separate 
inhalers.
13 No asthma exacerbations in last 12 months requiring oral or IV steroids or hospitalisation/ 
emergency room visit due to asthma.
14 Pre-bronchodilator FEV1 ≥70% predicted at Screening (Visit 1) and start of Run-in 
(Visit 2). Prior to spirometry, the following medication withhold periods should be 
observed:
(a) SABA for at least 6 hours.
(b) Twice daily LABA-containing therapies for at least 12 hours.
(c) Once daily LABA-containing therapies for at least 24 hours.
15 Asthma Control Questionnaire 6 score of ≤1.0 at Screening (Visit 1) and start of Run-in 
(Visit 2).
5.1.2
Part 2-specific Inclusion Criteria
16 Documented evidence of asthma as demonstrated by any of the following:


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(a) Post-BD reversibility of FEV1 ≥12% and ≥200 mL within 5 years prior to Visit 1, or 
at Visit 1, or
(b) PEF average daily variability > 10% over a 2-week period within 5 years prior to 
Visit 1, or
(c) Variability of FEV1 ≥12% and ≥200 mL between any two clinical visits within 
5 years prior to Visit 1, or
(d) Positive bronchial challenge test within 5 years prior to Visit 1. A positive test is 
defined as a fall in FEV1 from pre-challenge of ≥20% with standard doses of 
methacholine or histamine, or ≥15% with standardized hyperventilation, hypertonic 
saline or mannitol challenge, or
(e) Positive exercise test within 5 years prior to Visit 1. A positive test is defined as a fall 
in FEV1 of > 10% and > 200 mL from pre-challenge.
17 Documented treatment with medium-to-high dose ICS-LABA for at least 6 months prior 
to Screening (Visit 1) (ICS equivalent of budesonide dry powder formulation 
> 400 μg/day). ICS and LABA must be on a stable dose for at least 4 weeks prior to 
Visit 1, during Screening and Run-in Periods.
18 If on asthma maintenance controller medications in addition to ICS-LABA, the dose of 
the additional controller medications (eg, leukotriene receptor inhibitors, theophylline, 
LAMA, and chromones) must be stable for at least 4 weeks prior to Visit 1, during 
Screening and Run-in Periods.
19 Pre-bronchodilator FEV1 of 40% to 85% (inclusive) predicted at Screening (Visit 1) and 
start of Run-in (Visit 2).
20 Blood eosinophil count of ≥150 cells/μL and FeNO ≥25 ppb at Screening (Visit 1).
21 Asthma Control Questionnaire 6 score ≥1.5 at Screening (Visit 1).
5.1.3
Part 1-specific Randomisation Criteria at Visit 3
22 Pre-bronchodilator FEV1 ≥70% predicted.
Prior to spirometry, the following medication withhold periods should be observed:
(a) SABA for at least 6 hours.
(b) Twice daily LABA-containing therapies for at least 12 hours.
(c) Once daily LABA-containing therapies for at least 24 hours.
23 At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period 
(from Visit 2 to Visit 3) based on daily e-Diary.
24 Minimum 80% compliance with ePRO completion. 80% compliance is defined as 
completing daily e-Diary for any 8 mornings and any 8 evenings of the last 10 days of the 
Run-in Period.
25 Asthma Control Questionnaire 6 score of ≤ 1.0.


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26 C-reactive protein < 5 mg/L on Day -1.
5.1.4
Part 2-specific Randomisation Criteria at Visit 3
27 Pre-bronchodilator FEV1 of 40% to 85% (inclusive) predicted.
Prior to spirometry, the following medication withhold periods should be observed:
(a) SABA and SAMA for at least 6 hours.
(b) Twice daily LABA and/or LAMA-containing therapies for at least 12 hours.
(c) Once daily LABA and/or LAMA-containing therapies for at least 24 hours.
(d) LTRA for at least 24 hours.
(e) Twice daily theophyllines for at least 12 hours.
(f) Once daily theophyllines for at least 24 hours.
28 Asthma Control Questionnaire 6 score of ≥1.5.
29 At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period 
from (Visit 2 to Visit 3) based on daily e-Diary.
30 Minimum 70% compliance with ePRO completion. 70% compliance is defined as 
completing daily e-Diary for any 7 mornings and any 7 evenings of the last 10 days of the 
Run-in Period.
31 C-reactive protein < 10 mg/L at Visit 2.
32 A FeNO of ≥25 ppb.
5.2
Exclusion Criteria
Participants are excluded from inclusion in the study if any of the following criteria apply:
Medical Conditions
1
Women who are pregnant or breastfeeding, or who are planning to become pregnant 
during the study.
2
Known or suspected hypersensitivity including anaphylaxis/anaphylactoid reaction 
following any biologic therapy, or known history of drug hypersensitivity to any 
component of the study intervention formulation.
3
Evidence of any active clinically important pulmonary disease, other than asthma, within 
5 years at screening (eg, active lung infection, COPD, bronchiectasis, idiopathic 
pulmonary fibrosis, cystic fibrosis, lung cancer, alpha-1 antitrypsin deficiency, etc.).
4
History of pulmonary or systemic disease, other than asthma, that are associated with 
elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis, 
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5
History or clinical suspicion of any clinically relevant or active disease or disorder which, 
in the opinion of the Investigator, may either put the participant at risk because of 
participation in the study, or influence the results or the participant’s ability to participate 
in the study, or any other safety concerns in the opinion of the Investigator.
6
History of severe COVID-19 infection requiring hospitalisation within the last 12 months 
or clinical history compatible with long COVID (symptoms beyond 12 weeks of acute 
infection).
7
Confirmed symptomatic COVID-19 infection during Screening, Run-in or prior to 
randomisation. Participants can be rescreened once recovered if infection is not severe.
Participants who are asymptomatic with a positive COVID-19 test could continue in 
Screening if a repeat test done according to applicable local guidelines is negative within 
the screening window.
8
Current malignancy or history of malignancy, except for:
(a) Patients who have had basal cell carcinoma, localized squamous cell carcinoma of 
the skin or in situ carcinoma of the cervix are eligible provided that the patient is in 
remission and curative therapy was completed at least 12 months prior to the date of 
informed consent, and assent when applicable, was obtained.
(b) Patients who have had other malignancies are eligible provided that the patient is in 
remission and curative therapy was completed at least 5 years prior to the date of 
informed consent.
9
Significant history of recurrent or ongoing ‘dry eye’, which has been diagnosed and 
treated with medications prescribed by an Ophthalmologist.
10 Diagnosis of Sjögren’s syndrome.
11 High risk of infection suggesting abnormal immune function, including history of 
invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, 
pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, 
recurrent or prolonged infections, per Investigator’s judgment.
12 History of, or known significant infection or positivity at Visit 1, Screening Period, 
including hepatitis B or C, or HIV, that may put the participant at risk during participation 
in the study. Participants with positive anti-HBsAg test, a negative HBsAg test and a 
negative hepatitis B core total test at Screening may be included into the study if they 
have a positive hepatitis B vaccination history. Participants where the interpretation of the 
hepatitis B panel results is inconclusive, may be included following the confirmation of a
negative PCR test. Participants who test positive for anti-hepatitis C antibody may be 
enrolled if their hepatitis C virus RNA test result is negative in the absence of cirrhosis.
13 Evidence of active TB in the opinion of the Investigator. Participants with a recent first-
time (within 2 years) or newly positive interferon gamma release assay (IGRA, 
QuantiFERON®-TB Gold) test need to complete an appropriate course of treatment as 
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considered for inclusion. Evaluation may consist of history, physical examinations, 
imaging and/or TB tests as determined by local guidelines.
14 Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to 
Screening and during Run-in, as determined by the Investigator.
15 Clinically significant upper respiratory tract infection at Screening and during Run-in, as 
determined by the Investigator.
16 A helminth parasitic infection diagnosed within 24 weeks prior to the date informed 
consent is obtained, that has not been treated with, or has failed to respond to standard of 
care therapy.
17 Any clinically important ECG abnormalities obtained during the Screening/Run-in
Period, which in the opinion of the Investigator may put the participant at risk or interfere 
with study assessments.
18 Any clinically significant cardiac disease:
(a) Acute coronary syndrome (acute myocardial infarction, unstable angina), coronary 
intervention with percutaneous coronary intervention / coronary artery bypass 
surgery or stroke within 6 months.
(b) Heart failure NYHA II-IV.
(c) Untreated high degree atrioventricular-block (≥3:1 conduction rate / Grade III block) 
/ significant sinus node dysfunction / pause or therapy requiring tachyarrhythmia.
(d) Family history of long QT-syndrome.
(e) Hypertrophic cardiomyopathy or clinically significant valvular heart disease.
19 Uncontrolled hypertension with BP > 150/90 mmHg.
20 History of life-threatening asthma attack or asthma attack requiring ventilation.
21 Part 2 only: History of 3 or more severe asthma exacerbations (defined as a worsening of 
asthma requiring treatment with systemic corticosteroids for 3 days or more, or 
hospitalisation/emergency room visit due to asthma) in the 12 months prior to Visit 1.
22 Daily rescue use of SABA ≥8 puffs for ≥3 consecutive days at any time during Run-in
Period, before randomisation.
23 History of anaphylaxis that required the use of epinephrine or hospitalisation.
24 Any clinically significant abnormalities in haematology.
25 Alanine aminotransferase or AST level ≥3 times the ULN, confirmed by repeated testing 
during Screening Period. Transient increase of AST/ALT level that resolves by the time 
of randomisation is acceptable if in the Investigator’s opinion, the participant does not 
have an active liver disease and meets other eligibility criteria.
26 History of, or reason to believe a participant has a history of, drug or alcohol abuse within 
the past 2 years prior to Screening as judged by the Investigator which may include a 


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positive drugs of abuse test not consistent with the participant’s acute or chronic 
treatment.
27 Planned in-patient surgery, major dental procedure or hospitalisation during the study.
Prior/Concomitant Therapy
28 Systemic corticosteroid use within the 6 weeks before Visit 1, Screening Period and 
during Run-in.
29 Participants who have previously received AZD1402.
30 Treatment with marketed or investigational biologicals such as monoclonal antibodies or 
chimeric biomolecules, and within 6 months or 5 half-lives before Visit 1, Screening 
Period and during Run-in, which includes but is not limited to:
(a) Anti-IgE (eg, omalizumab).
(b) Anti-IL5 and anti-IL5R (eg, mepolizumab, reslizumab, benralizumab).
(c) Anti-IL4R (eg, dupilumab).
31 Any investigational nonbiologic drug within 60 days (or 5 half-lives, whichever is longer) 
prior to Visit 1 and during Run-in.
32 Any immunosuppressive therapy (other than systemic corticosteroids) within 3 months of 
Visit 1, Screening Period and during Run-in.
33 Live or attenuated vaccine within 4 weeks of Visit 1, Screening Period and during Run-in.
34 Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to 
randomisation.
35 Immunoglobulin or blood products within 4 weeks of Visit 1, Screening Period and 
during Run-in.
36 Any immunotherapy within 3 months of Visit 1, Screening Period and during Run-in, 
except for stable maintenance dose allergen-specific immunotherapy started, at least 
4 weeks prior to Visit 1 and expected to continue through to the end of the Follow-up 
Period.
37 Part 1 only: Additional asthma maintenance controller medications in addition to 
ICS-LABA (eg, leukotriene receptor inhibitors, theophylline, LAMA, chromones) within 
3 months of Visit 1, Screening Period and during Run-in.
Other Exclusions
38 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca 
staff and/or staff at the study site).
39 Judgment by the Investigator that the participant should not participate in the study if the 
participant is unlikely to comply with study procedures, restrictions, and requirements.


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40 Donation of blood (≥450 mL) within 3 months or donation of plasma within 14 days 
before Visit 1, Screening Period.
41 Previous participation or prior screen failure in the current study unless for reasons 
specified in the protocol, or participation in any other research study within 1 month prior 
to Visit 1.
42 Vulnerable persons (eg, persons kept in detention).
5.3
Lifestyle Considerations/Restrictions
5.3.1
Meals
1
Participants should avoid eating a large meal for at least 2 hours prior to all spirometry 
and FeNO assessments at the site.
2
Participants should not eat or drink 1 hour prior to having FeNO assessment.
5.3.2
Caffeine and Alcohol
1
For Part 1, participants should abstain from ingesting caffeine- or xanthine-containing 
products (eg, coffee, tea, cola drinks, and chocolate) for 4 hours prior to Screening, 
baseline, and morning in-clinic spirometry assessment. For Part 2, participants should 
abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, tea, cola 
drinks, and chocolate) during the Treatment Period, for 4 hours prior to in-clinic 
spirometry assessment.
2
During the residential Treatment Period, participants should abstain from alcohol for 
24 hours before admission until discharge.
5.3.3
Activity
1
Participants should avoid engaging in strenuous exercise at least 2 hours prior to all 
spirometry and FeNO assessments, both in-clinic and at home.
5.3.4
Others
1
Participants should abstain from donating blood and plasma from the time of informed 
consent until the final Follow-up Visit or 28 days of study intervention in the case of early 
termination.
2
It is recommended that participants’ pneumonia / influenza vaccinations are up to date as 
per local guidelines.
3
Maintenance and Reliever Therapy (MART) regime is not permitted for the duration of 
the study.


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5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once if there is reason to believe the reason for screen failure was temporary. The 
timing of the Rescreening should be determined by the Investigator, taking into account the 
initial reason for screen failure. Rescreened participants should be assigned the same 
participant number as for the initial Screening. It is only permitted to rescreen more than once 
for logistical reasons. In the case of more than one rescreening, a different participant number 
should be assigned.
Prior to Rescreening, participants must be reconsented.
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s) or 
placebo intended to be administered to or medical device(s) utilised by a study participant 
according to the study protocol.


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6.1
Study Intervention(s) Administered
6.1.1
Investigational Products
Table 5
Investigational Products
Intervention 
name
AZD1402
Placebo
SABA (rescue 
medication)
Run-in 
medications 
(ICS-LABA
combination) (if 
applicable)
Type 
Drug
Drug
Drug
Drug
Dose 
formulation
Inhalation powder 
 
Inhalation powder 
 
Inhalation aerosol 
by MDI
Inhalation powder
Unit dose 
strength(s)
mg, mg, and 
mg
NA
100 μg
Depends on 
particular 
medication
Dosage level(s)
mg, mg, and 
mg, all 
NA
100 μg per nominal 
dose
90 μg per nominal 
dose PRN
As required
Route of 
administration
Oral inhalation
Oral inhalation
Oral inhalation
Oral inhalation
Use
experimental
placebo
rescue medication
standard of care
IMP and NIMP
IMP
IMP
NIMP
NIMP
Sourcing
Provided centrally by 
the Sponsor
Provided centrally 
by the Sponsor
Provided locally by 
the study site
Provided locally by 
the study site
Packaging and 
labelling
Provided in labelled 
patient kits (1 
capsule in labelled 
 
placed in 
labelled 
container/box). 
Patient kits will be 
labelled in 
accordance with 
GMP Annex 13 and 
per country 
regulatory 
requirement
Provided in labelled 
patient kits (1 
capsule in labelled 
 
placed in 
labelled 
container/box). 
Patient kits will be 
labelled in 
accordance with 
GMP Annex 13 and 
per country 
regulatory
requirement
Provided in labelled 
kits in accordance 
with GMP Annex 13 
and per country 
regulatory 
requirement
Provided in 
labelled kits in 
accordance with 
GMP Annex 13 
and per country 
regulatory 
requirement
Abbreviations: 
 GMP = Good Manufacturing practice; 
 
 ICS = inhaled corticosteroids; IMP = Investigational Medicinal product; LABA = long-acting 
beta agonists; MDI = multiple dose inhaler; NA = Not applicable; NIMP = non-investigational medicinal 
product; PRN = pro re nata (as required); SABA = short-acting beta antagonist
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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6.1.2
Medical Devices
1
Medical devices (not manufactured by or for Sponsor) provided for use in this study are.

 DPI (Status, Approved/CE Marketed).

 (Status, Approved/CE Marketed).

Spirometer FEV1/PEF measuring device (Status, Approved/CE Marketed).
2
Instructions for medical device use are provided in the Investigator Manual.
3
All medical device deficiencies (including malfunction, use error and inadequate 
labelling) shall be documented and reported by the Investigator throughout the clinical 
investigation (see Section 8.3.12) and appropriately managed by the Sponsor.
6.1.3
Dose and Treatment Regimens
In Part 1 and in Part 2 at Visit 2 and Visit 3 (refresher training if appropriate), participants will 
receive training to use the DPI for AZD1402 or placebo using appropriate DPIs not containing 
AZD1402, for that purpose. Retraining on the DPIs as well as other medical devices will be 
provided to the participants on any of their visits to the clinic as and when required. 
Participants will be asked to record their intake of study intervention daily in their e-Diary.
6.1.3.1
Throughout the Study
In addition to study intervention, all participants will be provided with a SABA as rescue 
medication (eg, salbutamol/albuterol), to be used throughout the Run-in and Treatment 
Periods. All participants should refrain from taking a SABA as rescue medication 6 hours 
prior to pulmonary function tests.
6.1.3.2
Run-in Period
The Run-in Period will be 4 weeks long. During this period, the participants are required to 
maintain their ICS-LABA dose.
6.1.3.3
Treatment Period
The Treatment Period will be 4 weeks long with the study intervention administered
 
Controller medications (eg, ICS-LABA) should remain at a stable dose and be taken 
after the 
 study intervention as applicable.
In Part 1 on Days 1 to 14 and Day 28, controller medication will be taken 2 hours after study 
intervention
 If patients are not discharged on Day 14, but remain in the unit 
during Days 15 to 27, controller medication will continue to be taken 2 hours after study 
intervention
 
 At all other timepoints in Part 1, controller medication will be taken directly after 
study intervention, including 
 doses and on re-admission to the unit on Days 15 to 27 
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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post discharge (ie, controller medication timing will remain unchanged from home dosing). 
The timing of the controller medication in Part 1 may be adjusted by the Sponsor.
6.2
Preparation/Handling/Storage/Accountability
1
The Investigator or designee must confirm appropriate temperature conditions 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 participants enrolled in the study may receive study intervention and only authorised 
site staff may supply or 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).
4
Further guidance and information for the final disposition of unused study interventions
are provided in the Investigator’s Manual.
6.3
Measures to Minimise Bias: Randomisation and Blinding
All participants will be centrally assigned to randomised study intervention using an 
IRT/RTSM.
The IRT/RTSM will provide to the Investigators or pharmacists the kit identification number 
to be allocated to the participants at the dispensing visit.
Routines for this will be described in the IRT/RTSM user manual that will be provided to each 
site.
The randomisation code should not be broken except in medical emergencies when the 
appropriate management of the participant requires knowledge of the treatment randomisation. 
The IRT/RTSM will be programmed with blind-breaking instructions. In case of an 
emergency, in which the knowledge of the specific blinded study intervention will affect the 
immediate management of the participant’s condition (eg, antidote available), the Investigator 
has the sole responsibility for determining if unblinding of a participant’s study intervention
assignment is warranted. Participant safety must always be the first consideration in making 
such a determination. If a participant’s study intervention assignment is unblinded, the 
Sponsor must be notified within 24 hours after breaking the blind. The Investigator documents 
and reports the action to AstraZeneca, without revealing the treatment given to participant to 
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AstraZeneca retains the right to break the code for SAEs that are unexpected and are 
suspected to be causally related to a study intervention and that potentially require expedited 
reporting to regulatory authorities. Randomisation codes will not be broken for the planned 
analysis of data until all decisions on evaluability of the data from each individual participant
have been made and documented.
The laboratory vendor personnel performing the bioanalyses of the serum samples will have 
access to the randomisation list.
6.4
Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention under medical 
supervision and witnessing the study intervention administration. The date and time, 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 participant 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.
6.4.1
Study Intervention Compliance
When participants self-administer study intervention at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by checking the daily 
e-Diary and eCRF. Deviation(s) from the prescribed dosage regimen should be recorded in the 
eCRF. Compliance is expected to be ≥80% during the Treatment Period. Retraining is to be 
performed for those participants who demonstrate lower compliance.
6.4.2
E-Diary Compliance
The expected compliance with the e-Diary in both Run-in and Treatment Periods is at least 
80% of days in Part 1 and at least 70% of days in Part 2. Participants with < 80% e-Diary 
compliance during Run-in Period in Part 1 as well as participants with < 70% e-Diary 
compliance during Run-in Period in Part 2 will not be randomised.
Reminding or retraining of the participant on proper e-Diary documentation will be conducted 
if there is a discrepancy between the drug accountability data and e-Diary entries.
A record of the number of medication and inhalers dispensed to and taken by each participant
must be maintained and reconciled with study intervention and compliance records. 
Medication start and stop dates, including dates for medication delays and/or dose reductions 
will also be recorded in the eCRF. In the event that e-diary cannot be completed due to 
technical problems, the run-in may be prolonged, at Sponsor’s discretion.
6.5
Concomitant Therapy
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and/or herbal supplements [or other specific categories of interest)] that the participant 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
The Study Physician should be contacted if there are any questions regarding concomitant or 
prior therapy.
The study will recruit participants receiving treatment with medium dose ICS with LABA for 
Part 1 and participants receiving treatment with medium-to-high dose ICS with LABA for 
Part 2 (separate inhalers or combination product). During Run-in, all participants in Part 1 will 
continue on their own medication of medium dose ICS with LABA. This standard of care 
medication must remain stable for the duration of the study, including a 4-week Treatment 
Period and a 4-week Follow-up Period, unless clinically indicated adjustments are required.
Participants must be instructed to inform the Investigator of plans to take any new treatment 
during the participation in the study, including over-the-counter medicinal and herbal 
products.
6.5.1 Rescue Medication
The study site will provide the participants with rescue medication (SABA; salbutamol, 
100 μg per nominal dose and albuterol, 90 μg per nominal dose, US) starting from the 
Screening Visit.
The date and time of rescue medication administration as well as the name and dosage 
regimen of the rescue medication must be recorded.
6.5.2
Required Medication
Participants should continue to use the following controller medications at stable dose and 
regimen throughout the study as per their individual requirements, with the exception of 
medication withhold periods described in Section 6.5.3.

Medium dose ICS (Part 1), medium-to-high dose ICS (Part 2).

LABA.

Part 2 only: any additional asthma controller therapies in use at time of Screening, eg, 
LAMA, LTRA, theophylline, Chromones. Standard of care should not include systemic 
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6.5.3
Medication Withhold Periods
In Part 1 and following randomisation, participants should withhold the following 
medications for the specified times prior to scheduled spirometry and FeNO measurements at 
site:

SABAs and SAMAs for at least 6 hours, where possible.

Twice daily LABA-containing therapies should be taken after study intervention with the 
aim to have a withhold period of approximately 10 to 12 hours.

Once daily LABA-containing therapies should be taken after study intervention with the 
aim to have approximately 22 to 24 hours prior to the morning assessment.
Additionally, participants should withhold SABA for 6 hours prior to at-home spirometry 
assessments, where possible. Controller medication should be taken after study intervention as 
applicable 
Details of timing of controller medication are provided in 
Section 6.1.3.3. 
Note: Screening, start of Run-in, baseline, and Day 28 withhold period for pre-bronchodilator 
FEV1 should be at least 6, 12 or 24 hours for SABA, twice daily LABA, or once daily LABA 
respectively.
In Part 2, participants should withhold the following medications for the specified times prior 
to scheduled spirometry and FeNO measurements at the clinic scheduled visits.

SABAs and SAMA for at least 6 hours.

Twice daily LABA and/or LAMA-containing therapies for at least 12 hours.

Once daily LABA and/or LAMA-containing therapies for at least 24 hours.

LTRA for at least 24 hours.

Twice daily theophylline for at least 12 hours.

Once daily theophylline for at least 24 hours.
Additionally, participants should withhold SABA for 6 hours and all bronchodilator 
medications for 8 hours prior to at-home spirometry assessments, where possible. Controller 
medication should be taken directly after study intervention as applicable 
6.5.4
Restricted and Prohibited Medications
The following medications are restricted from Visit 1 (Screening) to the end of the Follow-up 
Period, unless clinically indicated, as determined by a physician:
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
Acute systemic (oral or injectable) corticosteroids within 6 weeks of Visit 1 until the end 
of the Follow-up Period, except for treatment of acute exacerbations of asthma during the 
course of the study.
The following medications are prohibited in Part 1: 

Leukotriene receptor inhibitors

Inhaled short- and long-acting anticholinergics

Combination of SABA and SAMA

Xanthines

Inhaled chromones

Oral and inhaled beta2 agonists (except salbutamol/albuterol used as rescue medication)
The following medications are prohibited in Part 1 and Part 2:

Marketed or investigational biologicals such as monoclonal antibodies or chimeric 
biomolecules, and within 6 months or 5 half-lives before Visit 1, whichever is longer, 
until the end of the Follow-up Period. These may include, but is not limited to:

Anti-IgE (eg, omalizumab)

Anti-IL5 and anti-IL5R (eg, mepolizumab, reslizumab, benralizumab)

Anti-IL4R (eg, dupilumab)

Any immunotherapy within 3 months of Visit 1 up to end of Follow-up, except for stable 
maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to 
Visit 1 and expected to continue through to the end of the Follow-up Period.

Any immunosuppressive therapy (other than systemic corticosteroids) within 3 months of 
Visit 1 and until the end of the Follow-up Period.

Any investigational nonbiologic drug within 60 days or 5 half-lives, whichever is longer,
prior to Visit 1 and until the end of the Follow-up Period.

Immunoglobulin or blood products within 4 weeks of Visit 1 until the end of the 
Follow-up Period.

Live or attenuated vaccine within 4 weeks of Visit 1 and until the end of the Follow-up 
Period.

If a participant is being considered for enrolment into the study and also being considered 
for COVID-19 vaccination, the participant must not be randomised until at least 30 days 
after the last dose of vaccine or booster.
Other than the permitted medications, use of concomitant medications or therapies from
Screening through to the ETV/end of study is discouraged. Medications or therapies that are 


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not prohibited and neither compromise participant safety nor affect study data, as judged by 
the Investigator, will be permitted.
6.6
Intervention After the End of the Study
There are no plans to provide the study intervention, Run-in medications, rescue medication 
after termination of the study. Participants can return to their usual standard of care medication 
for their asthma after completion of the study.
7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1
Discontinuation of Study Intervention
7.1.1
Permanent Discontinuation of Study Intervention for Individual 
Participants (Part 1 and Part 2)
If any participant meets with any of the following criteria, then he/she will be permanently 
discontinued from the study intervention.
Part 1

FEV1 decrease ≥30% from baseline* (as determined by pre first study intervention 
assessments) 

In-clinic assessment: Stop dosing and enter participant into Follow-up.

Home assessment: Stop dosing and confirm spirometry results in-clinic at earliest 
opportunity. Enter participant into Follow-up if decline in FEV1 confirmed (as 
described in the study reference manual).

Characterise potential reasons for the reduction in FEV1 and determine if consistent 
with a hypersensitivity-like event, infection, or asthma exacerbation.

Participant should be followed until resolution of the symptoms and recovery or 
stabilisation of FEV1.
Part 2

FEV1 decrease ≥30% from baseline*

In-clinic assessment: Stop dosing and enter participant into Follow-up:

Home assessment: If ≥30% decline is sustained over 2 consecutive assessments.
o
Assess associated symptoms and suspend dosing if clinically indicated.
o
Confirm spirometry results in-clinic at earliest opportunity. Enter participant into 
Follow-up if decline in FEV1 confirmed.


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
If dosing was suspended and if FEV1 decline is not confirmed, dosing may be 
resumed at the discretion of the Investigator.

Characterise potential reasons for the reduction in FEV1 and determine if consistent 
with a hypersensitivity-like event, infection, or asthma exacerbation.

Participant should be followed until resolution of the symptoms and recovery or 
stabilisation of FEV1.

Dosing may be suspended at any time for safety reasons at the discretion of the 
Investigator.

Once dosing has been interrupted and resumed, should dosing be suspended again 
due to safety concerns, the event should be characterised and the patient withdrawn 
from dosing.
Part 1 and 2

Withdrawal of consent to further treatment with study intervention.

Lost to Follow-up.

Acute severe hypersensitivity or hypersensitivity-like event/anaphylaxis.

Any TESAE that is considered related to the study intervention by the Investigator.

Pregnancy.

Any other AE that, in the opinion of the Investigator or the Sponsor, warrants 
discontinuation of further dosing of study intervention.

Haematologic toxicity defined as 1 or more of:

Confirmed leucocyte count < 2.0 × 109/L.

Confirmed neutrophil count < 1.0 × 109/L.

Confirmed platelet count < 75 × 109/L.

Confirmed lymphocyte count < 0.5 × 109/L.

Symptomatic bradycardia defined as heart rate < 45 bpm or asymptomatic bradycardia 
defined as resting supine pulse < 30 bpm while awake persisting for at least 10 minutes.

Hepatic toxicity defined as 1 or more of:

Confirmed ALT or AST increase to > 3 × the ULN.

Confirmed isolated TBL increase to > 2 × ULN.

Confirmed ALT or AST increase to > 2 × ULN concurrent with an increase in TBL 
to > 1.5 × ULN.

A severe asthma exacerbation as defined in Section 8.1.5.

Confirmed diagnosis of COVID-19 (Part 1 only).

COVID-19 vaccination** during the study (Part 1 only).


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*Baseline Part 1: Mean of Day -1 and Day 1; Baseline Part 2: Mean of Day 1 (15 minutes and 
45 minutes pre-dose).
** In Part 1, if the participant is vaccinated during the study, study intervention will be 
discontinued. The participant will be followed up and included as part of the safety 
population.
Participants in Part 1 of the study who are permanently discontinued from receiving the study 
intervention will be followed for protocol specified assessments and follow-up of any AEs as 
indicated clinically unless consent is withdrawn from further study participation or the 
participant is lost to Follow-up. Unscheduled assessments for safety may be performed if 
required. Where possible, participants in Part 1 should follow the PK sampling time frame 
associated with the last dose as per SoA (Table 1) for Days 28-32 or as directed by the Study 
Physician. An IPD Visit followed by both follow-up at visits (11 and 28 days after the last 
study drug intake) may be performed at the Investigator’s discretion if visits as per protocol 
SoA (Table 1) are not required for safety follow-up.
Participants in Part 2 of the study who are permanently discontinued from receiving the study 
intervention will be followed for any AEs as indicated clinically. This will include performing 
an IPD Visit as soon as possible after the last study drug intake followed by both follow-up at
visit (11 and 28 days) after the last study drug intake unless consent is withdrawn from further 
study participation or the participant is lost to Follow-up. Unscheduled assessments may be 
performed in between if required.
Note that discontinuation from study intervention is NOT the same thing as a withdrawal from 
the study.
7.1.2
Temporary Interruption of Study Intervention for Individual 
Participants
7.1.2.1
Dosing Suspension for Individual Participants (Part 1)

FEV1 decrease ≥20% relative to the prior pre-dose assessment and without recovery to at 
least 95% of the reference in-clinic assessment prior to the next dose of study intervention 
during the scheduled residential period

Suspend dosing in order to characterise potential reasons for the reduction in FEV1
and determine if consistent with a hypersensitivity-like event, infection, or asthma 
exacerbation.

Dosing may resume upon recovery of FEV1 to at least 95% of the reference
assessment value and the exclusion of a hypersensitivity-like event, ie, where an 
alternative explanation is clearly present such as a confirmed upper respiratory tract 
infection or CRP detection within the normal range.


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
Once the dosing has resumed, should a similar reduction in FEV1 reoccur, 
characterise the event and withdraw from dosing.

FEV1 decrease ≥20% from baseline* sustained until prior to the next dose of study 
intervention or associated with increased rescue medication use (defined as an increase in 
rescue medication use of 4 or more puffs on at least 2 consecutive days compared with 
the average use during baseline** or use of 12 puffs/day or more on any one day), or 
respiratory AESIs.

Suspend dosing in order to characterise potential reasons for the reduction in FEV1, 
confirm FEV1 in-clinic at the earliest opportunity and determine if consistent with a 
hypersensitivity-like event, infection or asthma exacerbation.

Dosing may resume upon resolution of symptoms, stabilisation of rescue medication 
use and/or recovery of FEV1 to at least 88% of the baseline value.

Once the dosing has resumed, should a similar reduction in FEV1 reoccur, 
characterise the event and withdraw from dosing.

CRP ≥10 mg/L plus a moderate AESI (Part 1 only)

Reasons for a significant CRP elevation must be investigated.

Suspend dosing if accompanied by a moderate AESI.

Dosing may resume should the AESI resolve and the reason for CRP elevation 
attributable to a cause other than AZD1402 eg, confirmed infection and it is 
considered safe to proceed and no more than 48 hours of the previous dose.

Should the CRP ≥10 mg/L elevation remain or increase, the new AESIs occur upon 
resumption of dosing the participant must be withdrawn into the Follow-up.
*Baseline Part 1: Mean Day -1 and Day 1.
**Baseline for rescue medication use defined as the last 7 days of the Run-in Period.
7.1.2.2
Dosing Suspension for Individual Participants (Part 1 and 2)

Any severe AE or AESI (See Section 8.3.5) with the potential for being classed as a 
hypersensitivity-like event and not rapidly diagnosed as an infection should result in the 
suspension of dosing

Suspend dosing and fully characterise the event(s).

Dosing may resume only in the event of a hypersensitivity-like event being excluded 
following a full evaluation, including a CRP < 10 mg/L and resolution of the AE(s).
Refer to Section 7.1.1 for further information on FEV1 30% decline home assessments to 
inform dosing suspension as per Investigator discretion.


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7.2
Participant Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioural,
compliance, or administrative reasons. This is expected to be uncommon.

A participant who considers withdrawing from the study must be informed by the 
Investigator about modified Follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records).

At the time of withdrawal from the study, if possible, an ETV should be conducted, as 
shown in the SoAs (Table 1 and Table 2). See SoAs for data to be collected at the time of 
study withdrawal and Follow-up and for any further evaluations that need to be 
completed.

The participant will discontinue the study intervention and be withdrawn from the 
study at that time.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.

If a participant withdraws from the study, it should be confirmed if he/she still agrees for 
existing samples to be used in line with the original consent. If he/she requests withdrawal 
of consent for use of samples, destruction of any samples taken and not tested should be 
carried out in line with what was stated in the informed consent 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.
7.3
Lost to Follow-up
A participant will be considered lost to Follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study.

Before a participant is deemed lost to Follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and,
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record.


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
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix A.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarised in the SoAs (Table 1 and Table 2).
Protocol waivers or exemptions are not allowed.

Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.

Adherence to the study design requirements, including those specified in the SoAs, is 
essential and required for study conduct.

All Screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a Screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
Screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilised for Screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoAs.

The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required will not exceed 500 mL.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples.
8.1
Efficacy Assessments
8.1.1
Lung Function Test – Spirometry
A centralised spirometry vendor will provide the spirometers and all necessary equipment 
(computer, calibration syringe, printer, paper, ink, etc.), a detailed study manual, and training 
to the technicians and Investigator (as needed) in charge of conducting the spirometry for this 
clinical study. The medications that should be withheld before any pulmonary function tests
are mentioned in Section 6.5.3.
Lung function parameters including, but not limited to, FEV1 and FVC, will be measured by 
spirometry using equipment provided by a central vendor. Spirometry will be performed by 
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The vendor providing central spirometry is responsible for assuring that the spirometer meets 
ATS/ERS recommendations and that the study site personnel who will be performing the 
testing are properly certified. Spirometry calibration will be detailed in a separate vendor
manual. Participants should follow the relevant medication and other restrictions beforehand 
(Sections 5.1.3 and 5.1.4) If any of the specified restrictions are not met, and the assessment
cannot be sufficiently delayed on the day, the assessment should be rescheduled within the 
allowed visit window.
Time of Day for Scheduled In-clinic Spirometry
Spirometry will be performed at specified timepoints in Part 1 and Part 2 as detailed in the 
SoAs (Table 1 and Table 2). For all participants, spirometry testing must be initiated between 
6:00 AM and 11:00 AM during the Screening, Rescreening, and Run-in Period prior to 
randomisation. For Part 1, if possible, all post-randomisation morning spirometry assessments 
should be performed within ± 30 minutes of the time that the randomisation spirometry was 
performed during the scheduled residential or unscheduled residential period. The evening 
spirometry should also be performed within a ± 30 minutes window relative to the evening 
assessment timepoint to ensure the timing of pre-and post-spirometry, study intervention, and 
controller medication are consistent throughout the residential period. In Part 1 outpatient 
visits (Day 16, 20, 24, 30 and 32) and visits in Part 2, if possible, all post-randomisation 
pre-dose morning clinic device spirometry assessments should be performed within 
± 1.5 hours of the time that the 15 min prior to randomisation spirometry was performed. For 
example, if the randomisation spirometry was started at 8:00 AM, then all subsequent 
spirometry testing needs to be initiated between 6:30 AM and 9:30 AM. 
Spirometry Technique
Detailed procedure for performing spirometry will be described in a separate spirometry 
procedures manual. Details regarding assessment of the quality of spirometry and the BTR 
(Best Test Report) process will also be detailed in the manual.
At-home Spirometry
During the study period, participants will be required to monitor lung function at home twice 
daily using an at-home spirometry device. Participants should follow the relevant medication 
and other restrictions beforehand (Sections 5.3 and 6.5.3). Further details will be provided in a 
separate instruction manual.
The at-home spirometry device should not be used for decision making purposes and is 
instead intended to identify declines in lung function that can then be further evaluated (ie,
in-clinic spirometry device measurement of lung function, evaluation of symptoms, 
assessment of key safety laboratory tests).


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8.1.2
Reversibility Testing
Airflow reversibility is not an outcome variable. Reversibility testing will be conducted at 
Visit 1 of Part 2. Participants will need to have a signed ICF prior to the reversibility testing. 
Participants should be on maintenance ICS-LABA at the time of enrolment (Visit 1), and 
adhere to medication withhold periods as follows:
(a) SABA and SAMA for at least 6 hours.
(b) Twice daily LABA and/or LAMA-containing therapies for at least 12 hours.
(c) Once daily LABA and/or LAMA-containing therapies for at least 24 hours.
(d) LTRA for at least 24 hours.
(e) Twice daily theophyllines for at least 12 hours.
(f) Once daily theophyllines for at least 24 hours.
For reversibility testing, participants will have a baseline spirometry and a repeat spirometry
15 to 30 minutes after inhalation of 400 µg of salbutamol.
Post-bronchodilator reversibility will be used to determine eligibility only if historical 
evidence of asthma as per inclusion criteria 16 are not met. 
8.1.3
Fractional Exhaled Nitric Oxide
To investigate the effect of AZD1402 on airway inflammation, the measurement of FeNO will 
be performed in accordance with ATS/ERS guidelines. Standardised conditions with regard to 
exhalation flow rate and duration of exhalation will be followed such that plateau definition 
can be evaluated over a minimum of 3 seconds. The concentration of FeNO will be measured 
in units of ppb. On days when spirometry and FeNO are to be performed on the same day, 
FeNO measurement should always be carried out prior to spirometry assessments.
Home FeNO will be performed in Part 1. In-clinic FeNO will be performed in Part 1 and 2.
8.1.4
Electronic Diary
At Visit 1 the e-Diary is set up, participants perform training and ACQ-6 is completed. At Visit 
2, the participants will receive a handheld e-Diary device to complete during the entire 
duration of the study. Participants will be provided training on the use of the handheld device.
During the study, all participants will be required to take their asthma controller therapy 
regularly and complete the e-Diary twice daily during the Run-in, Treatment, and Follow-up 
Period (as per SoA).
Daily assessments will include asthma symptom score (Section 8.1.5), use of rescue 
medication (Section 8.1.7), 
 (Section 8.1.8), FEV1 data (Section 8.1.1), 
PEF data (Section 8.1.11), background medication use, and 
 use of study intervention. 
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Participants will also be required to fill in the selected PROs (Section 8.1.10) in the e-Dairy at 
regular timepoints as indicated in SoAs.
8.1.5
Asthma Exacerbation
During the study, an asthma exacerbation will be defined as a change in the participant’s usual 
asthma symptoms that leads to any of the following:
1
A temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days to treat 
symptoms of asthma worsening; a single depo-injectable dose of corticosteroids will be 
considered equivalent to a 3-day bolus/burst of systemic corticosteroids.
2
An emergency room or urgent care visit (defined as evaluation and treatment for 
< 24 hours in an emergency department or urgent care centre) due to asthma that required 
systemic corticosteroids (as per the above).
3
An in-patient hospitalisation (defined as admission to an in-patient facility and/or
evaluation and treatment in a healthcare facility for ≥24 hours).
A hospitalised asthma exacerbation is defined as any worsening of asthma that leads to 
(3) above.
Note: For each exacerbation, the criterion/criteria met to confirm exacerbation status should 
be documented.
Assessment and Documentation of an Asthma Exacerbation
The list below defines what is acceptable documentation for historical exacerbations.

Discharge summaries from a hospital, emergency room, or an urgent care facility 
indicating that a participant was hospitalised/treated with systemic corticosteroids for an 
asthma exacerbation.

Signed and dated notes from a referring physician, including information regarding 
diagnosis and treatment of an exacerbation with systemic corticosteroids.

Evidence of prescriptions for systemic corticosteroids used during an exacerbation.

A documented conversation between the treating/referral physician or nurse/nurse 
practitioner certifying that a participant was treated for an exacerbation with 
corticosteroids at their clinic or under their supervision. The dates (month/year) of the 
exacerbations and verbal confirmation that appropriate prescriptions were provided is 
necessary. This option should be used only if reasonable attempts to procure participant 
records have been unsuccessful.
The guidance below defines assessment of asthma exacerbations. The start of an exacerbation 
is defined as the earliest of the following:

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
Date of emergency room or urgent care visits requiring systemic corticosteroids.

Date of hospital admission due to asthma.

The end date of an exacerbation is defined as the latest of the following.

Last date of systemic corticosteroid dose.

Date of discharge from emergency room or urgent care visit.

Date of hospital discharge.

If < 7 days have elapsed since the end date of an asthma exacerbation and the start date of 
a new asthma exacerbation, the second event will be considered a relapse of the prior 
asthma exacerbation in the statistical analysis.

All asthma exacerbations that occur during the Treatment Period and Follow-up, must be 
recorded as an AE in the eCRF. 
See Section 8.3.8 for additional information on recording asthma exacerbations as an AE/SAE 
during the study.
e-Diary Data and Exacerbations
Any sustained increase in asthma symptoms as reported via the e-Diary (or change in 
background medication that does not meet the definition of criteria of an asthma exacerbation) 
as defined in the protocol/study reference manual will be graded as a worsening of asthma and 
will include, but are not limited to:

An increase in rescue medication use of 4 or more puffs on at least 2 consecutive days 
compared with the average use during the Run-in baseline or use of 12 puffs/day on any 
one day. Systemic steroid use for < 3 days (without hospitalisation ≥ 24 hours). 
Worsening of asthma should be recorded as AEs in the EDC.
Additionally alerts to the study site to inform AESIs/study stopping/suspension criteria and 
potential exacerbation/worsening of asthma will also be triggered as defined in the 
protocol/study reference manual. These may include, but are not limited to:

FEV1 decrease ≥ 20% relative to the pre-dose assessment (Part 1 in-clinic assessment 
only), or 

FEV1 decrease ≥ 20% compared to baseline (Part 1 home assessment), or

FEV1 decrease ≥ 20% compared to baseline (in-clinic assessment), or

FEV1 decrease ≥ 30% on 2 consecutive scheduled time points compared to baseline 
(Part 2 home assessment), or

Respiratory AESIs* (may include wheeze, cough, shortness of breath), or


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
An increase in rescue medication use of 4 or more puffs on at least 2 consecutive days 
compared with the average use during the Run-in baseline or use of 12 puffs/day on any 
one day.
Participants will be required to keep a record of their asthma symptoms in the e-Diary as per
the SoAs (Table 1 and Table 2). The applicable data captured in the e-Diary will also be used 
to determine individuals 
(Section 8.1.12).
* Respiratory symptoms of wheeze, cough and dyspnoea will be reported as alerts in the 
e-Diary. AESI qualification for reporting purposes are described in Section 8.3.5.
8.1.6
Asthma Symptom Score
Severity scores for asthma symptoms will be recorded twice daily in the morning and evening 
and documented in the e-Diary during the Run-in, Treatment, and Follow-up Period as per 
SoAs.
Day-time is defined as the time period between the morning lung function assessment (upon 
rising in the morning) and the evening lung function assessment. Night-time is defined as the 
time period between the evening lung function assessment (at bedtime) and the morning lung 
function assessment.
Asthma symptom scores during night-time and day-time will be assessed by the participant
each morning and evening according to the following scoring system:
0: You have no asthma symptoms.
1: You are aware of your asthma symptoms but you can easily tolerate the symptoms.
2: Your asthma is causing you enough discomfort to cause problems with normal 
activities (or with sleep).
3: You are unable to do your normal activities (or to sleep) because of your asthma.
8.1.7
Use of Rescue Medication
Participants will be provided with a SABA as rescue medication, to be used as needed, starting 
from Visit 1. Participants will be asked to record their daily use of rescue medication in the 
e-Diary during the Run-in, Treatment, and Follow-up Period. The number of doses of rescue 
medication (1 dose unit = 1 puff on inhaler) taken will be recorded by the participant in the e-
Diary twice daily. The number of inhalations taken between the morning and evening lung 
function assessments will be recorded in the evening. The number of inhalations taken 
between the evening and morning lung function assessments will be recorded in the morning.
If possible, the rescue medication should be withheld at least 6 hours before any lung function 
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tests and FeNO measurement.
8.1.8
 
8.1.9
Background Medications
Background (ICS and LABA) medication use will be recorded once or twice daily as 
applicable in the daily e-Diary as “yes” or “no” response.
8.1.10
Participant Reported Outcomes
Participants will be asked to complete the PRO questionnaires on their e-Diary (Section 8.1.4)
supplied to the site according to the SoAs (Table 1 and Table 2). The PRO questionnaires to be
completed at the site visits must be completed prior to study intervention administration and 
ideally before any discussions of health status or other study procedures, such as collection of
laboratory samples to avoid biasing the participant’s responses to the questions. All
within-window PRO assessments for the morning and evening assessments at home should be
completed within this set time window programmed into the device and will notify the
participant when it is time to respond to the questions. A representation of each PRO is 
included in Appendix H.
Asthma Control Questionnaire-6
The ACQ (Juniper, et al. 1999) was developed to measure asthma control and has been fully
validated for use in adults and children 6 to 17 years of age. International guidelines for the
treatment of asthma have identified that the primary clinical goal of asthma management is to
optimise asthma control (minimisation of symptoms, activity limitation, bronchoconstriction,
and rescue bronchodilator use) and thus reduce the risk of life-threatening exacerbations and 
long-term morbidity. The ACQ was developed to meet these criteria by measuring both the 
adequacy of asthma control and change in asthma control, which occur either spontaneously 
or as a result of treatment.
In the ACQ-6, participants will be asked to recall how their asthma has been during the 
previous week by responding to one bronchodilation use question and 5 symptom questions as 
follows:

On average, during the past week, how often were you woken by your asthma during the 
night?

On average, during the past week, how bad were your asthma symptoms when you woke 
up in the morning?
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
In general, during the past week, how limited were you in your activities because of your 
asthma?

In general, during the past week, how much shortness of breath did you experience 
because of your asthma?

In general, during the past week, how much of the time did you wheeze?
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely 
uncontrolled). The mean ACQ-6 score is the mean of the responses. Mean scores of ≤0.75 
indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled 
asthma, and scores > 1.5 indicate not well-controlled asthma (Juniper, et al. 2006). Individual 
changes of at least 0.5 are considered clinically meaningful.
The questionnaire will be completed using the e-Diary in accordance with the SoAs
(Table 1and Table 2).
Cough VAS
In Part 1 participants will be asked to complete a cough severity VAS (100 mm linear scale 
marked with a horizontal line by the participant, with 0 mm representing ‘‘no cough’’ and 100 
mm representing “worst cough”) measuring subjective assessment by the participant for the 
prior 24 hours for severity of cough symptoms (Smith, et al 2006)
Study Participant Feedback Questionnaire
This study will include an option for participants to complete an anonymised questionnaire, 
‘Study Participant Feedback Questionnaire’ for participants to provide feedback on their 
clinical trial experience. Individual participant level responses will not be reviewed by 
Investigators. Responses would be used by the Sponsor to understand where improvements 
can be made in the clinical trial process. This questionnaire does not collect data about the 
participant’s disease, symptoms, treatment effect, or AEs and therefore would not be study 
data.
8.1.11
Peak Expiratory Flow
Peak expiratory flow will be measured by the participant at home after completing morning 
and evening e-Diary using a peak flow meter during the Run-in, Treatment Period, and 
Follow-up Period as per SoAs. Participants will be provided with a device at Visit 2 and 
receive training on peak flow monitoring at that time.
The morning PEF measurement must be done immediately upon waking up, after the 
participant has cleared out mucus and before inhaling the study intervention and any rescue 
medication. The evening measurement should be done just before taking the study
intervention. The measurements should be made while standing and the best of 3 attempts. 
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conclusion of the morning and evening e-Diary entry. Participants will have peak flow 
reviewed at study visits, and can be offered retraining if there are any concerns with the 
technique.
8.1.12
 
 
 
 
 
 
 



 
 
8.2
Safety Assessments
8.2.1
Physical Examinations

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, muscular-skeletal 
(including spine and extremities) and neurological systems.

A brief physical examination will include, at a minimum, assessments of the general 
appearance, skin, abdomen, cardiovascular, and respiratory systems.
Body weight and height will be measured at Visit 1 (Screening) for calculation of body mass 
index. Participants should be in light indoor clothes without shoes. Body weight will be 
measured again at Visit 7 and at the last Follow-up Visit.
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Physical examination will be performed at timepoints as specified in the SoAs (Table 1 and 
Table 2).
8.2.2
Vital Signs
Vital signs will be performed at timepoints as specified in the SoAs (Table 1 and Table 2).
The vital signs to be assessed (prior to study intervention administration) are BP (in mmHg) 
and pulse rate (in bpm), temperature (consistently either oral or tympanic), and respiratory rate
measurements.
Systolic and diastolic BP will be measured after at least 5 minutes resting, and before taking 
any blood sample and conducting any spirometry. Measurements will be carried out with the 
participant in a seated position and preferably always on the same arm. Data will be recorded 
on the eCRF.
If there is any suspicion of an unreliable measurement, BP will be measured again. The value 
obtained on the second measurement will be considered as definitive and will be the one 
recorded on the eCRF.
8.2.3
Electrocardiograms
An ECG will be performed at timepoints as specified in the SoAs (Table 1 and Table 2).
Standard digital ECG evaluations will be recorded after approximately 5 minutes resting in 
supine position and before any blood sampling and spirometry test. Digital ECGs will be 
recorded by appropriately trained personnel.
The vendor will provide the research sites with the equipment, supplies, specific training, and 
written instructions.
Following an acquisition of a quality ECG tracing, the Investigator or designee will 
electronically transfer the data to the vendor.
Individual ECG analysis will be performed by the Investigator at each site. Results will be 
available on the ECG report printed from the ECG equipment. The responsible Investigator 
will need to print, date and sign the printed ECG report.
The digital ECG will be recorded at 25 mm/sec and will consist of a recording of leads I, II, 
III, aVR, aVL, aVF and V1 to V6 and 10 seconds recording of lead II (rhythm strip). At least 
3 complete evaluable complexes per lead will be recorded. The following ECG parameters
will be determined:

Heart rate.


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
RR interval: Duration in milliseconds between 2 R peaks of 2 consecutive QRS 
complexes.

PR interval: Duration in milliseconds from the beginning of wave P to onset of 
ventricular depolarisation (Q and R).

QRS interval: Duration in milliseconds of the QRS complex.

QT interval: Duration in milliseconds from the beginning of Q wave to the end of the 
T-wave.

QTcB interval: QT interval corrected by HR, using Bazett’s formula (QT[msec]/ 
RR[sec]1/2).

QTcF interval: QT interval corrected using Fridericia’s formula (QT[msec]/RR[sec]1/3).
Individual ECG analysis will be performed by the Investigator at each site. Investigators will 
assess participants’ eligibility according to the ECG report of Visit 1 and Visit 3.
Any abnormal finding in the ECG tracing will be evaluated by the Investigator and will be 
specifically documented and registered in the eCRF.
In case of technical problems, the Investigator considers any result is clinically relevant or 
doubtful, additional digital ECGs may be performed, using the same equipment, within a 
reasonable time.
8.2.4
Clinical Safety Laboratory Assessments
Blood and urine samples for determination of clinical chemistry, haematology, coagulation,
and urinalysis will be taken at the visits indicated in the SoAs (Table 1 and Table 2). Blood 
samples should be collected after at least 8-hour fasting at Screening, baseline (prior to first 
dose of study intervention administration at Visit 3), and Day 28. The results of tests 
performed at Visit 3 will be regarded as baseline data. Fasting is not required at other 
timepoints.
Additional safety samples may be collected if clinically indicated at the discretion of the 
Investigator. The date, time of collection and results (values, units and reference ranges) will 
be recorded on the appropriate eCRF.
Clinical chemistry, haematology, coagulation, and urinalyses will be analysed centrally. A 
specific manual will be distributed by the central laboratory.
Local laboratory/on-site assessment of CRP, SARS-CoV-2 PCR, urine cotinine and urine 
pregnancy tests are described in the SoAs (Table 1 and Table 2).
The following laboratory variables will be measured.


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Table 6
Laboratory Safety Variables
Haematology/Haemostasis (whole blood)
Clinical Chemistry (serum or plasma)
B-Haemoglobin 
SARS-CoV-2 PCR
B-Haematocrit
S/P-Creatinine
B-Erythrocytes
eGFR
B-Reticulocytes (abs, %)
S/P-Bilirubin, total
B-Platelet count
S/P-Alkaline phosphatase 
B-Mean corpuscular volume
S/P-Aspartate transaminase 
B-Mean corpuscular haemoglobin
S/P-Alanine transaminase 
B-Mean corpuscular haemoglobin concentration
S/P-Albumin
B-Red cell distribution width
S/P-Glucose (fasting and non-fasting)
B-Red blood cell morphology
S/P-Cholesterol***
B-Leucocyte count
S/P-Triglycerides***
B-Leukocyte differential count 
S/P-C-reactive protein
B-Neutrophils (abs, %)
S/P-Potassium
B-Lymphocytes (abs, %)
S/P-Calcium, total
B-Eosinophils (abs, %)
S/P-Sodium
B-Monocytes (abs, %)
S/P-Creatine kinase 
B-Basophils (abs, %)
S/P-high sensitivity C-reactive protein
Urinalysis (dipstick)*
S/P-Direct Bilirubin
U-Haemoglobin/Erythrocytes/Blood 
S/P-Indirect Bilirubin (calculation)
U-Protein/Albumin 
S/P-Gamma glutamyl transferase
U-Glucose 
S/P-Lactate dehydrogenase
U-drug screen**
S/P-Urea nitrogen
U-Specific gravity
S/P-Uric acid
U-pH
S/P-Phosphorus
U-Protein
S/P-Total protein
U-Ketones
S/P-Globulin (calculation)
U-Bilirubin
S/P-Bicarbonate
U-Urobilinogen
S/P-Chloride
U-Nitrite
S/P-Magnesium
U-Leukocyte Esterase
Coagulation
Others
International normalised ratio
Hepatitis B Core Total
Activated partial thromboplastin time
Anti Hep B Surface AG2 Qual
Prothrombin time
Hepatitis B – Qual
Reproductive hormones (Females only)
Hepatitis B – PCR****
U-human chorionic gonadotropin hormone
Hepatitis C – Virus Antibody
S-human chorionic gonadotropin hormone
Hepatitis C – PCR****
S-Follicle stimulating hormone
HIV 1/2 Ag/Ab Screen
Safety-Immuno-biomarkers


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Table 6
Laboratory Safety Variables
HIV-1 Ab Supplemental, Geenius
C-reactive protein
HIV-2 Ab Supplemental, Geenius
Immunoglobulins
HIV Ab Interpretation, Geenius
Cytokines*****
HIV Confirmation
Tryptase
QuantiFERON®-TB Gold test
SARS-CoV-2-serology
SARS-CoV-2 PCR
*If clinically relevant abnormalities are detected (positive result in dipstick), the urine sample will be sent to the 
central laboratory for analysis of the sediment.
**Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates
***Cholesterol and triglycerides will be measured at Screening, baseline (Day 1 pre-dose), and Day 28
**** Participants with positive anti HBsAg test, negative HBsAg and negative hepatitis B core total at Screening 
may be included into the study if they have a positive vaccination history. Participants where the interpretation of 
the hepatitis B panel results is inconclusive, may be included following the confirmation of a negative virus PCR 
test. Participants with positive Hepatitis C – Virus Antibody test may be enrolled following the confirmation of a 
negative virus PCR test and the absence of liver cirrhosis. Assessments will preferably be done centrally but may 
be done locally
***** Cytokines may include, but are not limited to IFNγ, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8,
TNFα
Abbreviations: eGFR = estimated glomerular filtration rate; HIV = human immunodeficiency virus; 
PCR = polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; 
TB = tuberculosis
NB. In case a participant shows an AST or ALT ≥3 × ULN together with TBL ≥2 × ULN 
please refer to Appendix E. Actions required in cases of increases in liver biochemistry and 
evaluation of Hy’s Law, for further instructions.
The central laboratory will provide the centre with the necessary material and instructions for 
the sampling. Laboratory data generated will be transmitted to the company in charge of data 
management activities.
Urine sediment analysis will be performed centrally, only when a positive result in dipstick is 
obtained. The central laboratory will provide the centres with the necessary material and 
instructions for urine sampling collection in case sediment analysis is required. Data from the 
sediment analysis will also be transferred to the company in charge of data management 
activities.
In addition, details on the collection, processing, shipment of samples and reporting of the 
results by the central laboratory will be provided to Investigators in the Laboratory Manual.
Safety results will be communicated to the Investigators after each study visit. Investigators 
must review the lab reports upon receipt, write down the assessment for the abnormal 
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8.2.5
Other Safety Assessments
8.2.5.1
Safety Immuno-biomarkers
Blood samples will be collected for immuno-biomarker testing to assess the safety of 
AZD1402 and per the timepoints mentioned in the SoAs (Table 1 and Table 2) for analysis of 
immuno-biomarkers including, but not limited to:

Cytokines, CRP, hs-CRP, and immunoglobulins including IgE.
8.2.5.2
FEV1
For details on this assessment, refer to Section 8.1.1.
8.2.5.3
FeNO
For details on this assessment, refer to Section 8.1.3.
8.2.5.4
High-resolution Computed Tomography
In the event of respiratory AESIs, FEV1 decline, or clinically indicated AEs or findings, an 
HRCT scan of the chest on inspiration may be considered.
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 participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorised representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
Adverse events will be collected from time of signature of the ICF throughout the Treatment 
Period and including 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 study 
intervention that occurs after the end of the clinical study in a participant treated by him or 
her, the Investigator shall, without undue delay, report the SAE to the Sponsor.


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8.3.2
Follow-up of AEs and SAEs
Any AEs that are unresolved at the participant’s last AE assessment in the study are followed 
up by the Investigator for as long as medically indicated and/or agreed with Sponsor, but 
without further recording in the eCRF. AstraZeneca retains the right to request additional 
information for any participant with ongoing AE(s)/SAE(s) at the end of the study, if judged 
necessary.
Adverse Event Variables
The following variables will be collected for each AE;

AE (verbatim)

The date and time when the AE started and stopped

Maximum intensity

Whether the AE is serious or not

Investigator causality rating against the study intervention (yes or no)

Action taken with regard to study intervention

Adverse event caused participant’s withdrawal from study (yes or no)

Outcome
In addition, the following variables will be collected for SAEs:

Date AE met criteria for SAE

Date Investigator became aware of SAE

AE is serious due to (ie, seriousness criteria)

Date of hospitalisation

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 study intervention 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?’


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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 found in Appendix B to the CSP.
8.3.4 Adverse Events Based on Signs and Symptoms
All AEs spontaneously reported by the participant or reported in response to the open question 
from the study site staff: ‘Have you had any health problems since 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 of Special Interest
The following events (occurring after first dose) will be considered to qualify as an AESI for 
this study.

FEV1 ≥ 20% reduction from baseline as informed by in-clinic assessment (“forced 
expiratory volume decreased”)

FEV1 ≥30% reduction from baseline as informed by

in-clinic assessment

decline is sustained over 2 scheduled consecutive home assessments resulting in 
either dosing suspension or discontinuation (Part 2)

Confirmed fever (> 38°C for > 4 hours)

Wheeze*

Cough*

Dyspnoea/shortness of breath*

Infection 

respiratory tract infection, ideally supported by pathogen identification and 
confirmation

COVID-19 infection.

non-respiratory tract infection
* Part 1: All new events of wheeze, cough, dyspnoea/shortness of breath.
Part 2: All new worsening events of wheeze, cough, dyspnoea/shortness of breath compared to 
baseline / individual pre-existing disease characteristics as judged by the Investigator. 


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In the event of suspected respiratory infection, pathogen identification include: 

SARS-CoV-2 PCR.

Viral panel which may include, but are not limited to influenza (all types), parainfluenza, 
respiratory syncytial virus, human metapneumovirus, adenovirus and Bordetella pertussis.

Mycoplasma pneumonia and Chlamydophila pneumoniae (sometimes included in viral 
panel).

Bacterial swab to detect any growth which may include, but are not limited to 
Streptococcus, Klebsiella, Pneumoniae, Pseudomonas, Staphylococcus aureus, E.coli, 
Citrobacter, Acinetobacter and Haemophilus influenza.
The pathogen identification may be performed locally in the first instance, in which case 
the available tests may differ from those listed. In the event that local laboratory is not 
used, it may be performed centrally as per standard panel agreed with the Sponsor.
Additionally, CRP ≥10 mg/L should be used to support the evaluation and identification of 
the potential cause of an AESI and to guide further dosing. Unscheduled visit including blood 
samples collection (including but not limited by haematology, CRP, immuno-biomarkers), 
local CRP, spirometry, throat swab for pathogen identification, and any other relevant tests
which might be required for AE assessment may be requested and scheduled.
8.3.6 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, vital signs, 
immuno-biomarkers, and ECG should therefore only be reported as AEs if they fulfil any of 
the SAE criteria, are the reason for discontinuation of treatment with the study intervention or 
are considered to be clinically relevant as judged by the Investigator (which may include but 
not limited to consideration as to whether treatment or non-planned visits were required or 
other action was taken with the study intervention, eg, drug interruption).
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information eg, in the case of increased CRP with associated 
AESI. 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).
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pre-existing medical conditions (for example hypertriglyceridemia, elevated glucose, 
increased BMI) may be reported as medical history if applicable and should not be reported as 
AEs.
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.
8.3.7 Hy’s Law
Cases where a participant shows elevations 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 E for further instruction on cases of 
increases in liver biochemistry and evaluation of Hy’s Law.
8.3.8 Disease Under Study
The Investigator should report clinically significant worsening of asthma symptoms, including 
exacerbations, as an AE. Signs and symptoms consistent with a participant’s baseline asthma 
status will not be reported as an AE, unless identified as an AESI.
8.3.9
Reporting of Serious Adverse Events
All SAEs have to be reported, whether or not considered causally related to the study 
intervention, or to the study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, Investigators or other site personnel will inform 
the appropriate AstraZeneca representatives immediately (without undue delay), but no later 
than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative will work with the Investigator to ensure that all 
the necessary information is provided to the AstraZeneca Patient Safety data entry site within 
one calendar day of initial receipt for fatal and life-threatening events and within 5 calendar
days of initial receipt for all other SAEs.
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
immediately (without undue delay), 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 EDC system, an 
automated email alert is sent to the designated AstraZeneca representative.
If the EDC system is not available, then the Investigator or other study site staff reports a SAE 


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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 of the CSP.
The reference document for definition of expectedness/listedness is the IB.
8.3.10
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca except for:

If the pregnancy is discovered before the study participant has received any study 
intervention.
8.3.10.1
Maternal Exposure
If a participant becomes pregnant during the course of the study, AZD1402 should be 
discontinued immediately.
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study intervention
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 
participant 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 1 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 1 or 
5 calendar days for SAEs (see Section 8.3.9) 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.
8.3.10.2
Paternal Exposure 
Male participants should refrain from fathering a child or donating sperm during the study and 
for 3 weeks following the last dose of study intervention.


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Pregnancy of the participant’s partners is not considered to be an AE. However, the outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth or congenital abnormality), occurring from the date of the first dose until 3 weeks after 
the last dose of study intervention should, if possible, be followed up and documented in the 
Pregnancy Report Form. Consent from the partner must be obtained before the Pregnancy 
Report Form is completed.
8.3.11
Medication Error, Drug Abuse, and Drug Misuse
8.3.11.1
Timelines
If an event of medication error, drug abuse, or drug misuse occurs during the study, then the 
Investigator or other site personnel informs the appropriate AstraZeneca representatives within 
one calendar day, ie, immediately but no later than 24 hours of when they become 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 event of medication error, drug abuse, or misuse (see Section 8.3.9) 
and within 30 days for all other events.
8.3.11.2
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake 
in the treatment process for an IMP or AstraZeneca NIMP that either causes harm to the 
participant or has the potential to cause harm to the participant.
The full definition and examples of medication error can be found in Appendix B 4.
8.3.11.3
Drug Abuse
Drug abuse is the persistent or sporadic intentional, non-therapeutic excessive use of IMP or 
AstraZeneca NIMP for a perceived reward or desired non-therapeutic effect.
The full definition and examples of drug abuse can be found in Appendix B 4.
8.3.11.4
Drug Misuse
Drug misuse is the intentional and inappropriate use (by a study participant) of IMP or 
AstraZeneca NIMP for medicinal purposes outside of the authorised product information, or 
for unauthorised IMPs or AstraZeneca NIMPs, outside the intended use as specified in the 
protocol and includes deliberate administration of the product by the wrong route.
The full definition and examples of drug misuse can be found in Appendix B 4.


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8.3.12
Medical Device Deficiencies
In this study any deficiency observed with a third-party medical device will be collected and 
reported to the manufacturer.
A medical device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Medical device deficiencies include 
malfunctions, use errors, and information supplied by the manufacturer.
8.4
Overdose
For guidance refer to AstraZeneca standard operating procedures Reporting of Individual 
Safety Events in Clinical Studies. 
For this study, an overdose is defined as a participant receiving a dose of study intervention in 
excess of that specified in the IB, unless otherwise specified in this protocol.

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 intervention occurs in the course of the study, 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 8.3.9) 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. The 
results from future analysis will not be reported in the CSR.


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
Pharmacokinetic samples will be disposed of after the Bioanalytical Report finalisation or 
6 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, or individual 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.
8.5.1
Pharmacokinetics

Blood samples will be collected for measurement of serum concentrations of AZD1402 as 
specified in the SoAs (Table 1 and Table 2).

Samples may be collected at additional timepoints during the study if warranted and 
agreed upon between the Investigator and the Sponsor, eg, for safety reasons. The timing 
of sampling may be altered during the course of the study based on newly available data 
(eg, to obtain data closer to the time of peak or trough matrix concentrations) to ensure 
appropriate monitoring.

Serum samples will be used to analyse the PK of AZD1402. Samples collected for 
analyses of AZD1402 (serum) concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study.

Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory 
Manual.
8.5.1.1
Part 1
Blood samples for PK assessments will be collected from all the participants at timepoints 
mentioned in the SoA (Table 1).
8.5.1.2
Part 2
A sparse PK sampling will be carried out for all participants in Part 2 of the study at 
timepoints mentioned in the SoA (Table 2).
Intense sampling will be performed for a subset of approximately 25% of participants in each 
treatment arm at timepoints mentioned in the SoA (Table 2). The participants in these subsets 
may be asked to stay in the clinic overnight for logistical reasons depending on the sampling 
timepoints.


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8.5.1.3
Determination of Drug Concentration
Samples for determination of drug concentration in serum will be assayed by bioanalytical test 
sites operated by or on behalf of AstraZeneca, using an appropriately validated bioanalytical 
method. Full details of the analytical method used will be described in a separate Bioanalytical 
Report.
Placebo samples will not be analysed, unless there is a need to confirm that correct treatment 
has been given to study participants.
Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate Bioanalytical Report.
8.5.2
Immunogenicity Assessments
Blood samples for determination of ADA in serum will be assayed by bioanalytical test site 
operated by or on behalf of AstraZeneca, using an appropriately validated bioanalytical 
method. A tiered testing scheme will be employed, with the first step being screening. Samples 
found positive in the screening step will be tested in the confirmatory step. Samples confirmed 
positive for ADA in the confirmatory step will undergo endpoint titre determination. 
Remaining ADA aliquots will be banked and may be used for further characterisation of the 
ADA response. The results from these tests will be reported outside of the CSR and full details 
of the methods used will be described in a separate report. Blood samples for determination of 
ADA in serum will be collected as specified at timepoints mentioned in the SoAs (Table 1 and 
Table 2).
Additional samples may be collected during the study if warranted and agreed upon between 
the Investigator and the Sponsor, eg, for safety reasons.
At the last Follow-up Visit in Part 1 only, if a participant’s sample is confirmed ADA positive, 
the participant will be asked to return to provide another sample to evaluate whether or not 
ADAs persist.
Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory Manual.
8.5.3
Pharmacodynamics
Collection of Samples
 
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For storage, re-use and destruction of pharmacodynamic samples see Section 8.5 and 
Appendix C.
8.6
Human Biological Sample Biomarkers
8.6.1
Collection of Mandatory Samples for Biomarker Analysis
By consenting to participate in the study the participant consents to the mandatory research 
components of the study.

Samples for biomarker research are required and will be collected from all participants in 
this study as specified in the SoAs.

 
 

 

Blood samples for allergen-specific IgE will be collected for 
 and 
tested in the case of AEs that have characteristics of a type I hypersensitivity-like
response.
8.6.2
Collection of Optional Samples for Biomarker Analysis
Collection of optional samples for this part of biomarker analysis is part of this study as 
specified in the SoAs and is subject to agreement in the ICF addendum.
Blood samples will be collected from participants who have consented to participate in the 
part of biomarker component of the study. Participation is optional. Participants who do not 
wish to participate in the optional biomarker research may still participate in the study.

 

For storage, re-use and destruction of biomarker samples, see Section 8.5. 
8.7
Optional Genomics Initiative Sample
Collection of optional samples for Genomics Initiative research is also part of this study as 
specified in the SoAs and is subject to agreement in the ICF addendum.
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Blood sample for DNA isolation will be collected from participants who have consented to 
participate in the genetic analysis component of the study. Participation is optional. 
Participants who do not wish to participate in the genetic research may still participate in the 
study.
 
Details on processes for collection and shipment and destruction of these samples can be 
found either in the appendices or in the Laboratory Manual. 
For storage and destruction of genetic samples see Appendix D.
8.8
Health Economics
Not applicable.
9
STATISTICAL CONSIDERATIONS
9.1
Statistical Hypotheses
No statistical hypotheses will be tested for in Part 1 (Lead-in Cohort) of this study.
Part 2 (Main Cohort) of this study aims to demonstrate that AZD1402 improves FEV1
compared to placebo.
The null hypotheses for the primary analysis in Part 2 (Main Cohort) are that there is no 
difference in the change from baseline at Week 4 in FEV1 in AZD1402 treated participants 
compared to placebo-treated participants. The following comparisons will be performed:

AZD1402 inhalation mg 
 versus placebo inhalation 

AZD1402 inhalation mg 
 versus placebo inhalation 
No adjustments for multiple testing will be performed.
9.2
Sample Size Determination
In Part 1 (Lead-in Cohort), approximately 45 participants will be randomised. Part 1a will 
consist of 30 randomised participants and Part 1b will consist of 15 randomised participants. 
The sample size for Part 1 (Lead-in Cohort) is not based on any sample size calculation, but 
was chosen to obtain reasonable evidence of safety and tolerability without exposing undue 
number of participants to the study intervention. In Part 2 (Main Cohort), 73 evaluable 
participants per treatment arm will provide 
% power using a 1-sided test and % 
significance level to detect a difference of 175 mL in FEV1 versus placebo. This is based on a 
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SD of 
 mL, derived from an inter-participant SD of 
 mL in change from baseline to 
Week 4, adjusted for 4 repeated measurements and a correlation of 
 between weekly 
measurements. Assuming a dropout rate of 
%, approximately 80 evaluable participants per 
arm are needed. Due to the restricted recruitment into the mg dose arm the precision of 
inference in terms of statistical power will be less than 
% for the comparisons mg versus 
placebo. A participant will be considered evaluable if he/she has baseline and Week 4 FEV1
results available.
Part 2 will consist of approximately 165 participants.
9.3
Populations for Analyses
The following populations are defined:
Table 7
Populations for Analysis
Population/Analysis set
Description
Enrolled 
All participants who sign the informed consent form.
Full Analysis Set (FAS)
All participants who are randomised and received any study intervention.
Participants are evaluated according to the treatment assigned at 
randomisation. The FAS will be used for all analyses of demographic 
baseline characteristics and efficacy data.
Per Protocol Set (PPS)
A subset of the FAS consisting of all participants who do not violate the 
terms of the protocol in a way that may affect the primary efficacy 
endpoint significantly. All decisions to exclude participants from the PPS 
will be made and documented prior to the unblinding of the study.
Safety Set (SS)
All participants who are randomised and received any study intervention.
Participants are evaluated according to the actual treatment they received.
If a participant received a different treatment dose than randomised 
throughout the study, they will be analysed according to treated dose, not 
the randomised dose. If a participant received study intervention from the 
wrong kit for only part of the treatment duration, they will be analysed 
according to their randomised dose.
The SS will be used for all safety analyses.
Pharmacokinetic (PK) set
All participants in the SS who have detectable PK data and with no major 
protocol deviations considered to impact on the analysis of PK data.
The exclusion of any participants or timepoints from the calculation of 
the PK parameters will be documented by the PK scientist including the 
reason(s) for exclusion prior to the unblinding of the study. The available 
concentration data and PK parameter data for any participants excluded 
from the PK analysis set will be listed only, and presented in the 
individual figures of concentration-time plots.
The PK analysis set will be used for all PK analyses.
Immunogenicity set
All participants in the SS with at least one post-treatment ADA result
(positive or negative) with exception for any analysis of relationship of 
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Population/Analysis set
Description
ADA with PK where the immunogenicity set will instead include all 
participants in the PK set.
The immunogenicity analysis set will be used for all ADA analyses.
Abbreviations: ADA = anti-drug antibody; FAS = full analysis set; PPS = per protocol set; 
PK = pharmacokinetics; SS =safety set
Additional analysis sets may be defined in the Statistical Analysis Plan (SAP) for exploratory 
analyses.
9.4
Statistical Analyses
The SAP will be finalised prior to first participant in and will include a more technical and 
detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints including primary 
and key secondary endpoints.
9.4.1
General Statistical Considerations
Analyses will be performed by Parexel, except for the derivation of PK parameters, which will 
be performed by bioanalytical test sites operated on behalf of AstraZeneca Research and 
Development.
Continuous data will be summarised using descriptive statistics (number of observations, 
mean, SD, median, 25th and 75th percentiles [where appropriate], minimum and maximum). 
For log-transformed data (where appropriate) geometric mean and geometric coefficient of 
variation will also be presented. For PK data, geometric +SD and geometric -SD are also 
presented in addition to geometric mean and geometric coefficient of variation. Frequencies 
and percentages will be used for summarising categorical (discrete) data.
Confidence intervals will generally be 2-sided with 95% confidence level, and p-values will 
be one-sided, unless otherwise indicated.
Unless otherwise stated, summaries will be presented by Part and treatment. The treatment 
comparisons of interest are the different doses of AZD1402 versus placebo. No formal 
comparisons between the different AZD1402 doses will be conducted.
All statistical analyses will be conducted using SAS® version 9.4.
Deviations from the protocol will be assessed as “important” or “not-important”. Important 
deviations from the protocol may lead to the exclusion of participants from any of the study 
analysis set. Deviations will be defined before database hard lock. Important deviations will 
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
Violation of inclusion and/or exclusion criteria.

Administration of prohibited concomitant medications that are expected to influence the
measurement of the primary endpoint.

Receiving incorrect study intervention than randomised to.
All protocol deviations will be discussed at a data review meeting prior to database hard lock 
in order to define the analysis sets for the study. All important protocol deviations will be 
listed by participant. Further details will be provided in the SAP.
9.4.2
Efficacy – Part 2
The analysis of all efficacy variables will be performed on the FAS.
9.4.2.1
Primary Endpoint
The primary efficacy endpoint for Part 2 (Main Cohort) is the change from baseline in 
pre-bronchodilator FEV1 at Week 4 compared to placebo.
The change from baseline in FEV1 will be analysed using MMRM with treatment group, week 
(1 to 4), country, eosinophil count group (< 300, ≥300 cells/μL), baseline FEV1, and 
treatment-by-week interaction as fixed effects with participant as random effect. In this model, 
Week 1 to 4 corresponds to Visit 4 to 7. The within-participant correlation will be modelled 
using the unstructured covariance matrix. The Kenward-Roger approximation will be used to 
estimate the degrees of freedom.
Baseline for FEV1 will be defined as the mean of the 2 measured values before first study 
intervention administration (30 minutes apart, at -45 minutes and -15 minutes, before study 
intervention) on Day 1.
Besides the main analysis in the FAS, treatment effect in primary endpoint will be evaluated in 
subgroups defined by measurements of eosinophil count (< 300 and ≥300 cells/μL), and of 
FeNO (< 50 and ≥50 ppb) evaluated at Day 1 pre-dose.
9.4.2.2
Secondary Endpoints
Secondary efficacy endpoints for Part 2 (Main Cohort) will include:

Change from baseline in pre-bronchodilator FEV1 average over the 4-week Treatment 
Period

Change from baseline in ACQ-6 at Week 4 and average over the Time Period

Change from baseline in average morning PEF over the Treatment Period

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
Change from baseline in daily average asthma symptoms score (AM/PM) over the 
Treatment Period

Change from baseline in FeNO at Week 4 and average over the Treatment Period
(analysed on natural log scale and results back transformed to linear scale).
Similar MMRM as for the primary variable will be used for analysis of change from baseline 
in ACQ-6 and in FeNO. Analysis of covariance with treatment and country as fixed effects, 
and baseline as covariate will be used for the analysis of change from baseline in average PEF.
Further details on the models for secondary endpoints will be provided in the SAP.
9.4.2.3
Exploratory Endpoints
 
 
Analyses of exploratory endpoints for Part 2 (Main Cohort) will be specified in the SAP.
9.4.3
Safety
Safety analysis will be performed using the SS. Individual safety and tolerability data will be 
provided in data listings and summarised as appropriate by treatment and overall, separate for 
each part.
Further details on the analysis of safety data will be described in the SAP.
9.4.3.1
Adverse Events
Adverse events will be coded using the most recent version of the MedDRA.
Adverse events will be presented separate for each Part by treatment, SOC and/or PT 
presenting number and percentage of participants reporting at least one event. Number of 
events will be presented separately.
Only AEs occurring with an onset date, or worsening, on or after first dose of study 
intervention will be presented in summary tables. Adverse events occurring prior the first dose 
of study intervention will be included in data listings.
An overview of AEs will be presented for each Part and treatment. The presentation will 
include the number and percentage of participants with any AE, AEs with outcome of death, 
SAEs, AEs leading to discontinuation of study intervention, AEs leading to withdrawal from 
study, and AEs of special interest (including infection, eosinophilia, and hypersensitivity 
events) as well as the number of individual occurrences in those categories.
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An additional table will present the number and percentage of participants with most common 
AEs. Most common (eg, frequency of >5%) will be defined in the SAP.
In accordance with the requirements of the FDA, a separate table will present non-serious AEs 
occurring in more than 5% of participants in any treatment group.
Key participant information will be presented for participants with SAEs with outcome of 
death, SAEs, and AEs leading to discontinuation of study intervention.
An AE listing for the SS will cover details for each individual AE; an AE listing for 
participants who were not exposed to study intervention will be presented separately.
Full details of the AE analyses will be provided in the SAP.
9.4.3.2
Deaths
Details on deaths will be listed by participant.
9.4.3.3
Exposure
Details on study intervention administration will be provided in listings and will be 
summarised descriptively.
9.4.3.4
Vital Signs
Vital sign parameters will be presented separately for each Part by treatment using descriptive 
statistics.
For each scheduled post-baseline visit, descriptive statistics for all vital sign parameters will 
be presented for observed values and changes from baseline.
9.4.3.5
Laboratory Parameters
Laboratory parameters will be presented separately for each Part by treatment using 
descriptive statistics.
For each scheduled post-baseline visit, descriptive statistics for all clinical chemistry,
haematology, and coagulation parameters will be presented for observed values and changes 
from baseline.
Elevation in liver parameters for assessment of Hy’s Law will be done and reported 
appropriately if potential cases have been identified during the course of the study.
Shift tables will present the baseline assessment against the maximum on-treatment results.
9.4.3.6
Immuno-biomarkers
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presented descriptively by treatment, separately for each part.
9.4.3.7
Electrocardiogram
Descriptive statistics will be produced at each scheduled assessment timepoint for all 
quantitative ECG parameters for both absolute values and changes from baseline.
An analysis of potentially clinically significant ECG values on QT, QTcB, QTcF, QRS and PR 
interval and heart rate will be performed. The number of participants with potentially 
clinically significant ECG values will be tabulated across time and treatment. The criteria 
based on severity will be defined in the SAP.
Outlier with respect to QTcF will also be tabulated for the following categories:

Absolute value > 450 msec

Absolute value > 480 msec

Absolute value > 500 msec

Increase from baseline > 30 msec

Increase from baseline > 60 msec
9.4.4
Other Analyses
9.4.4.1
Pharmacokinetics
Pharmacokinetic analysis for AZD1402 will be performed by PK analysis vendor on behalf of 
AstraZeneca Research and Development. Pharmacokinetic parameters will be derived using 
standard non-compartmental methods using Phoenix® WinNonLin® version 8.1 or higher 
(Certara). All descriptive statistics will be performed using SAS® version 9.4.
The PK parameters will be calculated/estimated according to AstraZeneca standards.
Pharmacokinetics analysis will, where data allow, be carried out using actual elapsed times 
determined from the PK sampling and dosing times recorded in the database. If actual elapsed 
times are missing, nominal times may be used. Nominal sampling times may be used for any 
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Where data allow, the following PK parameters for AZD1402 will be derived from serum 
concentrations: 
Cmax
Maximum observed serum (peak) drug concentration
tmax 
Time to reach peak or maximum observed concentration or response following drug 
administration
Ctrough
Observed lowest drug concentration reached before the next dose is administered 
(pre-dose)
z 
Terminal rate constant, estimated by log-linear least squares regression of the 
terminal part of the concentration-time curve
t1/2λz
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time 
curve
AUClast 
Area under the serum concentration-curve from zero to the last quantifiable 
concentration
AUC
Area under serum concentration-time curve in the dosing interval 
CL/F 
Apparent total body clearance of drug from serum after extravascular administration
Vz/F
Volume of distribution (apparent) at steady state following extravascular 
administration (based on terminal phase)
Dose normalised 
AUC
Area under the serum concentration-time curve in the dosing interval divided by the 
dose administered
Dose normalised 
Cmax
Maximum observed serum (peak) drug concentration divided by the dose 
administered
Dose normalised 
AUClast
Area under the serum concentration-time curve from zero to the last quantifiable 
concentration divided by the dose delivered in mg
tlast
Time of last observed (quantifiable) serum concentration
Rac AUC
Accumulation ratio for AUC
Rac Cmax
Accumulation ratio for Cmax
The following diagnostic parameters for PK analysis will be provided:
λz lower
Lower (earlier) t used for λz determination
λz upper
Upper (later) t used for λz determination
λzN
Number of data points used for λz determination
Rsq
Statistical measure of fit for the regression used for λz determination
Rsq adj
Statistical measure of fit for the regression used for λz determination adjusted for the 
number of used data points (n obs)
z span ratio
Time period over which z was determined as a ration of t½z
Additional PK parameters may be determined where appropriate.
Serum concentrations will be listed and summarised by treatment and PK day using 
appropriate descriptive statistics. Where possible, the following descriptive statistics will be 
presented: n, geometric mean, geometric coefficient of variation, geometric mean +geometric 
standard deviation, geometric mean –geometric standard deviation, arithmetic mean, 
arithmetic SD, median, minimum and maximum based on the PK analysis set. Serum
concentrations that are BLQ will be handled as described in the SAP.


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Combined individual serum concentration per dose level and PK day (spaghetti plots) will be 
presented in linear and semi-logarithmic scale with separate plots for each dose level and PK 
day. Figures for the geometric mean concentration-time data will be presented for all doses 
overlaid on the same plot for a given PK day, in both a linear and semi-logarithmic scale.
Figures for the geometric mean concentration-time data will also be presented for PK Days 1 
and 28 overlaid on the same plot for a given dose level, in both a linear and semi-logarithmic 
scale.
Individual Ctrough values will be plotted versus study day, in linear and semi-logarithmic 
scale for each dose level and PK day. Figures for geometric mean Ctrough versus study day 
will be presented for all doses and study days overlaid on the same plot, in both linear and 
semi-logarithmic scales.
All serum PK parameters will be listed for each participant and summarised by treatment and 
PK day using similar descriptive statistics.
Further details regarding the calculation and descriptive statistics of the PK parameters will be 
detailed in the SAP.
9.4.4.2
Immunogenicity
Immunogenicity results will be presented descriptively, separately for each Part.
Participants will be classified as ADA positive or ADA negative. ADA-positive results will 
further be classified on whether positivity was observed during the 4-week Treatment Period
or after the 4-week Treatment Period. Pharmacokinetic and safety profiles will be presented 
graphically for ADA-positive participants with onset during the 4-week Treatment Period, 
ADA-positive participants with onset after the 4-week Treatment Period and ADA-negative
participants. Similarly, tabular presentation for AEs across the 3 ADA groups will also be 
presented. Further details will be provided in the SAP.
9.5
Interim Analyses
An interim analysis of the primary endpoint (FEV1) may be performed. The main objective of 
this analysis is to estimate the variability for a sample-size re-estimation or perform a futility 
analysis. The timing of the interim analysis is to be determined such that the estimated 
variability enables an informative decision on whether to revise the sample size. Decision 
criteria will be pre-specified in an interim analysis plan (charter). Depending on the outcome 
of the interim analysis, the sample size may be increased from 80 up to 107 per arm ( mg 
dose and placebo) in Part 2.
9.6
Data Monitoring Committees
The SRC including the Sponsor study team will review PK and unblinded safety data 
CCI


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following completion of Part 1a before progressing to Part 1b/2 and following completion of 
Part 1b. An unscheduled SRC meeting may also be held in the event of any safety or 
tolerability events requiring further review that may impact continuation of a cohort or the 
study, including unblinding data as required. 
A DSMB will oversee Part 2 of the study and review the unblinded interim outputs. In 
addition to a full DSMB periodic review of safety data, the committee can meet on an ad hoc 
basis, eg, in the event of any potential suspension or stopping criteria for dose level or study 
being met. Details of the composition of the DSMB, frequency of meetings and remit can be 
found in the DSMB Charter. 
A separate review committee of AstraZeneca representatives will review the unblinded interim 
outputs for the interim analysis if performed.
The finalized version of the charter will be submitted to regulatory and ethics authorities (as 
appropriate/per local requirements) once complete, once data from Part 1 are available and 
prior to inclusion of the first patient in Part 2 of the study.
For details on the SRC, DSMB, and URC, refer to Appendix A 5.


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10
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS


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Appendix A
Regulatory, Ethical, and Study Oversight Considerations
A 1
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines

Applicable ICH GCP Guidelines

Applicable laws and regulations

The protocol, protocol amendments, ICF, IB, and other relevant documents (eg,
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.

Any amendments to the protocol will require IRB/IEC and applicable Regulatory 
Authority approval before implementation of changes made to the study design, except 
for changes necessary to eliminate an immediate hazard to study participants.

AstraZeneca will be responsible for obtaining the required authorisations to conduct the 
study from the concerned Regulatory Authority. This responsibility may be delegated to a 
CRO, but the accountability remains with AstraZeneca.

The Investigator will be responsible for providing oversight of the conduct of the study at 
the site and adherence to requirements of 21 CFR, ICH guidelines, the IRB/IEC, 
European Regulation 536/2014 for clinical studies, European Medical Device Regulation 
2017/745 for clinical device research, and all other applicable local regulations.
Regulatory Reporting Requirements for SAEs

Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met.

The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/ IEC, and Investigators.

For all studies except those utilising medical devices, Investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions (SUSAR) according to local 
regulatory requirements and Sponsor policy and forwarded to Investigators as necessary.

Adherence to European Medical Device Regulation 2017/745 for clinical device research 
(if applicable), and all other applicable local regulations.


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
An Investigator who receives an Investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements.
Regulatory Reporting Requirements for Serious Breaches

Prompt notification by the Investigator to AstraZeneca of any (potential) serious breach 
of the protocol or regulations is essential so that legal and ethical obligations are met.

A ‘serious breach’ means a breach likely to affect to a significant degree the safety 
and rights of a participant or the reliability and robustness of the data generated in the 
clinical study.

If any (potential) serious breach occurs in the course of the study, Investigators or other 
site personnel will inform the appropriate AstraZeneca representatives immediately after 
he or she becomes aware of it.

In certain regions/countries, AstraZeneca has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about such breaches.

AstraZeneca will comply with country-specific regulatory requirements relating to 
serious breach reporting to the regulatory authority, IRB/IEC, and Investigators. If 
EU Clinical Trials Regulation 536/2014 applies, AstraZeneca is required to enter 
details of serious breaches into the European Medicines Agency (EMA) Clinical 
Trial Information System (CTIS). It is important to note that redacted versions of 
serious breach reports will be available to the public via CTIS.

The Investigator should have a process in place to ensure that:
o
The site staff or service providers delegated by the Investigator/institution are 
able to identify the occurrence of a (potential) serious breach

A (potential) serious breach is promptly reported to AstraZeneca or delegated party, 
through the contacts (email address or telephone number) provided by AstraZeneca.
A 2
Financial Disclosure
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.


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A 3
Informed Consent Process

The Investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorised representative and answer all questions regarding 
the study.

Participants must be informed that their participation is voluntary and they are free to 
refuse to participate and may withdraw their consent at any time and for any reason 
during the study. Participants will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the 
IRB/IEC or study centre.

The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorised person obtaining the informed consent must also sign the ICF.

Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study.

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorised representative.
Participants who are rescreened are required to sign a new ICF.
The ICF will contain a separate section that addresses and documents the collection and use of 
any mandatory and/or optional human biological samples. The Investigator or authorised 
designee will explain to each participant the objectives of the analysis to be done on the 
samples and any potential future use. Participants will be told that they are free to refuse to 
participate in any optional samples or the future use and may withdraw their consent at any 
time and for any reason during the retention period.
A 4
Data Protection

Participants will be assigned a unique identifier by the Sponsor. Any participant records 
or datasets that are transferred to the Sponsor will contain the identifier only; participant
names or any information which would make the participant identifiable will not be 
transferred.

The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure and use 
of their data must also be explained to the participant in the informed consent 

The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorised personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities.


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A 5
Committees Structure
A 5.1
Data Safety Monitoring Board
In order to provide a periodic review of safety throughout the study, in addition to the 
ongoing, blinded review provided by the Sponsor/Designee Medical Monitor for detection of 
any potential safety signals, an unblinded DSMB will be utilised. Set up of the DSMB, and 
frequency of data transfer will be described in the DSMB Charter. The DSMB will make any 
necessary recommendations regarding further conduct of the study based on their evaluation 
of emerging data.
A 5.2
Safety Review Committee
This study will convene an unblinded SRC whose membership and remit will be detailed in 
the SRC charter and may include the Sponsor study team and the Study Physician, to review 
unblinded safety and PK data at the following timepoints:

After completion of Part 1a treatment period, prior to starting Part 1b and Part 2.

Following completion of Part 1b treatment period.

An unscheduled SRC meeting (as detailed in the SRC Charter) in the event of any safety 
or tolerability events requiring further review that may impact continuation of a cohort or 
the study, including unblinding data as required.
A 5.3
Unblinded Review Committee
The URC is a committee internal to AstraZeneca and responsible for reviewing interim data 
from trials and accountable for ensuring each review is done in a way that maintains the 
scientific integrity of the trial.
Details regarding each of these committees will be made available in their respective charters.
A 6
Dissemination of Clinical Study Data
Any results both technical and lay summaries for this trial, will be submitted to EU Clinical 
Trials Information System within a year from global End of Trial Date in all participating 
countries, due to scientific reasons, as otherwise statistical analysis is not relevant.
A description of this clinical study will be available on http://astrazenecaclinicaltrials.com and 
http://www.clinicaltrials.gov as will the summary of the main study results when they are 
available. The clinical study and/or summary of main study results may also be available on 
other websites according to the regulations of the countries in which the main study is 
conducted.


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A 7
Data Quality Assurance

All participant data relating to the study will be recorded on eCRF unless transmitted to 
the Sponsor or designee electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by electronically 
signing the eCRF.

The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.

The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.

Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the study reference manual.

The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.

The Sponsor assumes accountability for actions delegated to other individuals (eg,
CROs).

Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorised site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements.

Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator for a minimum of 25 years after study archiving, 
according to the AstraZeneca Global retention and Disposal (GRAD) Schedule. No 
records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor.
A 8
Source Documents

Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s site.

Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The Investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.


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
Definition of what constitutes source data can be found in source data agreement and 
computerised data check list for electronic source data.
A 9
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The Sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed.
The Investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or Investigator may include but 
are not limited to:

Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the Investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any CROs used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. 
The Investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up.
A 10
Publication Policy

The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments.

The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multi-centre studies only in their entirety and not as individual site data. In 
this case, a Coordinating Investigator will be designated by mutual agreement.


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
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.


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Appendix B
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
B 1
Definition of Adverse Events
An AE is the development of any untoward medical occurrence in a participant or clinical 
study participant administered a medicinal product and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavourable and 
unintended sign (eg, an abnormal laboratory finding), symptom (for example nausea, chest 
pain), or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
The term AE is used to include both serious and non-serious AEs and can include a 
deterioration of a pre-existing medical occurrence. An AE may occur at any time, including 
Run-in or washout periods, even if no study intervention has been administered.
B 2
Definition of Serious Adverse Events
An SAE is an AE occurring during any study phase (ie, Run-in, Treatment, Follow-up), that 
fulfils one or more of the following criteria:

Results in death.

Is immediately life-threatening.

Requires in-participant hospitalisation or prolongation of existing hospitalisation.

Results in persistent or significant disability or incapacity. 

Is a congenital abnormality or birth defect.

Is an important medical event that may jeopardise the participant or may require medical 
treatment to prevent one of the outcomes listed above.
Adverse events for malignant tumours reported during a study should generally be assessed 
as Serious AEs. If no other seriousness criteria apply, the ‘Important Medical Event’ criterion 
should be used. In certain situations, however, medical judgement on an individual event basis 
should be applied to clarify that the malignant tumour event should be assessed and reported 
as a non-serious AE. For example, if the tumour is included as medical history and 
progression occurs during the study, but the progression does not change treatment and/or 
prognosis of the malignant tumour, the AE may not fulfil the attributes for being assessed as 
serious, although reporting of the progression of the malignant tumour as an AE is valid and 
should occur. Also, some types of malignant tumours, which do not spread remotely after a 
routine treatment that does not require hospitalisation, may be assessed as non-serious; 
examples in adults include Stage 1 basal cell carcinoma and Stage 1A1 cervical cancer 
removed via cone biopsy.


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Life-threatening
‘Life-threatening’ means that the participant was at immediate risk of death from the AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
participant’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (eg, hepatitis that resolved without hepatic failure).
Hospitalisation
Outparticipant treatment in an emergency room is not in itself an serious AE, although the 
reasons for it may be (eg, bronchospasm, laryngeal oedema). Hospital admissions and/or 
surgical operations planned before or during a study are not considered AEs if the illness or 
disease existed before the participant was enrolled in the study, provided that it did not 
deteriorate in an unexpected way during the study.
Important Medical Event or Medical Treatment
Medical and scientific judgement should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalisation, disability or incapacity but may jeopardise the participant or may 
require medical treatment to prevent one or more outcomes listed in the definition of serious. 
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgement must be used.

Angioedema not severe enough to require intubation but requiring iv hydrocortisone 
treatment

Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment with 
N-acetylcysteine

Intensive treatment in an emergency room or at home for allergic bronchospasm

Blood dyscrasias (eg, neutropenia or anaemia requiring blood transfusion, etc.) or 
convulsions that do not result in hospitalisation

Development of drug dependency or drug abuse
Intensity Rating Scale:

Mild (awareness of sign or symptom, but easily tolerated)

Moderate (discomfort sufficient to cause interference with normal activities)

Severe (incapacitating, with inability to perform normal activities)
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Appendix B 2. An AE of severe 


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intensity need not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not a SAE unless it meets the criteria 
shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be a SAE when it satisfies the criteria 
shown in Appendix B 2.
B 3
A Guide to Interpreting the Causality Question
When making an assessment of causality consider the following factors when deciding if there 
is a ‘reasonable possibility’ that an AE may have been caused by the drug.

Time Course. Exposure to suspect drug. Has the participant actually received the suspect
drug? Did the AE occur in a reasonable temporal relationship to the administration of the 
suspect drug?

Consistency with known drug profile. Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties?

De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose 
of the suspect drug?

No alternative cause. The AE cannot be reasonably explained by another aetiology such 
as the underlying disease, other drugs, other host or environmental factors.

Re-challenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? AstraZeneca would not normally recommend or support a 
re-challenge.

Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship.
In difficult cases, other factors could be considered such as:

Is this a recognised feature of overdose of the drug?

Is there a known mechanism?
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data including enough 
information to make an informed judgment. With no available facts or arguments to suggest a 


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causal relationship, the event(s) will be assessed as ‘not related’.
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility.
B 4
Medication Error, Drug Abuse, and Drug Misuse
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an IMP or AstraZeneca NIMP that either causes harm to the 
participant or has the potential to cause harm to the participant. 
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or participant.
Medication error includes situations where an error:

Occurred

Was identified and intercepted before participant received the drug

Did not occur, but circumstances were recognised that could have led to an error
Examples of events to be reported in clinical studies as medication errors:

Drug name confusion

Dispensing error, eg, medication prepared incorrectly, even if it was not actually given to 
the participant

Drug not administered as indicated, eg, wrong route or wrong site of administration

Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a 
solid tablet

Drug not stored as instructed, eg, kept in the refrigerator when it should be at room 
temperature

Wrong participant received the medication (excluding IRT/RTSM errors)

Wrong drug administered to participant (excluding IRT/RTSM errors)
Examples of events that do not require reporting as medication errors in clinical studies:

Errors related to or resulting from IRT/RTSM – including those which lead to one of the 
above listed events that would otherwise have been a medication error

Participant accidentally missed drug dose(s), eg, forgot to take medication

Accidental overdose (will be captured as an overdose)


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
Participant failed to return unused medication or empty packaging
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error.
Drug Abuse
For the purpose of this study, drug abuse is defined as the persistent or sporadic intentional, 
non-therapeutic excessive use of IMP or AstraZeneca NIMP for a perceived reward or desired 
non-therapeutic effect.
Any events of drug abuse, with or without associated AEs, are to be captured and forwarded to 
the Data Entry Site (DES) using the Drug Abuse Report Form. This form should be used both 
if the drug abuse happened in a study participant or if the drug abuse involves a person not 
enrolled in the study (such as a relative of the study participant).
Examples of drug abuse include but are not limited to:

The drug is used with the intent of getting a perceived reward (by the study participant or 
a person not enrolled in the study)

The drug in the form of a tablet is crushed and injected or snorted with the intent of 
getting high
Drug Misuse
Drug misuse is the intentional and inappropriate use (by a study participant) of IMP or 
AstraZeneca NIMP for medicinal purposes outside of the authorised product information, or 
for unauthorised IMPs or AstraZeneca NIMPs, outside the intended use as specified in the 
protocol and includes deliberate administration of the product by the wrong route.
Events of drug misuse, with or without associated AEs, are to be captured and forwarded to 
the DES using the Drug Misuse Report Form. This form should be used both if the drug 
misuse happened in a study participant or if the drug misuse regards a person not enrolled in 
the study (such as a relative of the study participant).
Examples of drug misuse include but are not limited to:

The drug is used with the intention to cause an effect in another person

The drug is sold to other people for recreational purposes 

The drug is used to facilitate assault in another person

The drug is deliberately administered by the wrong route

The drug is split in half because it is easier to swallow, when it is stated in the protocol 
that it must be swallowed whole


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
Only half the dose is taken because the study participant feels that he/she is feeling better 
when not taking the whole dose

Someone who is not enrolled in the study intentionally takes the drug


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Appendix C
Handling of Human Biological Samples
C 1
Chain of Custody
A full chain of custody is maintained for all samples throughout their lifecycle.
The Investigator at each centre keeps full traceability of collected biological samples from the 
participants while in storage at the centre until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples whilst at site.
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps record of receipt of arrival and onward 
shipment or disposal.
AstraZeneca or delegated representatives will keep oversight of the entire life cycle through 
internal procedures, monitoring of study sites, auditing or process checks, and contractual 
requirements of external laboratory providers
Samples retained for further use will be stored in the AstraZeneca-assigned biobanks or other 
sample archive facilities and will be tracked by the appropriate AstraZeneca Team for the 
remainder of the sample life cycle.
C 2
Withdrawal of Informed Consent for Donated Biological Samples 
If a participant withdraws consent to the use of donated biological samples, the samples will 
be disposed of/destroyed/repatriated, and the action documented. If samples are already 
analysed, AstraZeneca is not obliged to destroy the results of this research.
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent.
The Investigator:

Ensures the participant’s withdrawal of informed consent to the use of donated samples is 
highlighted immediately to AstraZeneca or delegate.

Ensures that relevant human biological samples from that participant, if stored at the 
study site, are immediately identified, disposed of as appropriate, and the action 
documented.

Ensures that the participant and AstraZeneca are informed about the sample disposal.
AstraZeneca ensures the organisation(s) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed of or repatriated as appropriate, 
and the action is documented and study site is notified.


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C 3
International Airline Transportation Association 6.2 Guidance 
Document
LABELLING AND SHIPMENT OF BIOHAZARD SAMPLES
International Airline Transportation Association (IATA) 
(https://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) classifies infectious 
substances into 3 categories: Category A, Category B or Exempt
Category A Infectious Substances are infectious substances in a form that, when exposure to 
it occurs, is capable of causing permanent disability, life-threatening or fatal disease in 
otherwise healthy humans or animals. 
Category A Pathogens are, eg, Ebola, Lassa fever virus. Infectious substances meeting these 
criteria which cause disease in humans or both in humans and animals must be assigned to 
UN 2814. Infectious substances which cause disease only in animals must be assigned to 
UN 2900.
Category B Infectious Substances are infectious Substances that do not meet the criteria for 
inclusion in Category A. Category B pathogens are, eg, Hepatitis A, C, D, and E viruses. They 
are assigned the following UN number and proper shipping name:

UN 3373 – Biological Substance, Category B

are to be packed in accordance with UN 3373 and IATA 650
Exempt – Substances which do not contain infectious substances or substances which are 
unlikely to cause disease in humans or animals are not subject to these regulations unless they 
meet the criteria for inclusion in another class.

Clinical study samples will fall into Category B or exempt under IATA regulations

Clinical study samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging 
(https://www.iata.org/whatwedo/cargo/dgr/Documents/DGR-60-EN-PI650.pdf)

Biological samples transported in dry ice require additional dangerous goods specification 
for the dry-ice content


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Appendix D
Optional Genomics Initiative Sample
D 1
Use/Analysis of DNA

AstraZeneca intends to collect and store DNA for genetic research to explore how genetic 
variations may affect clinical parameters, risk and prognosis of diseases, and the response 
to medications. This genetic research may lead to better understanding of diseases, better 
diagnosis of diseases or other improvements in health care and to the discovery of new 
diagnostics, treatments or medications. Therefore, where local regulations and IRB/IEC 
allow, a blood sample will be collected for DNA analysis from consenting participants.

This optional genetic research may consist of the analysis of the structure of the 
participant´s DNA, ie, the entire genome. 

The results of genetic analyses may be reported in a separate study summary.

The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.
D 2
Genetic Research Plan and Procedures
Selection of Genetic Research Population

All participants will be asked to participate in this genetic research. Participation is 
voluntary and if a participant declines to participate there will be no penalty or loss of 
benefit. The participant will not be excluded from any aspect of the main study.
Inclusion Criteria
For inclusion in this genetic research, participants must fulfil all of the inclusion criteria 
described in the main body of the CSP and: Provide informed consent for the Genomics 
Initiative sampling and analyses.
Exclusion Criteria

Exclusion from this genetic research may be for any of the exclusion criteria specified in 
the main study or any of the following:

Previous allogeneic bone marrow transplant

Non-leukocyte depleted whole blood transfusion in 120 days of genetic sample 
collection

Healthy Volunteers and paediatric participant samples will not be collected for the 
Genomics Initiative.


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Withdrawal of Consent for Genetic Research

Participants may withdraw from this genetic research at any time, independent of any 
decision concerning participation in other aspects of the main study. Voluntary 
withdrawal will not prejudice further treatment. Procedures for withdrawal are outlined in 
Section 7.2 of the main CSP.
Collection of Samples for Genetic Research

The blood sample for this genetic research will be obtained from the participants at 
Visit 3 after randomisation. Although DNA is stable, early sample collection is preferred 
to avoid introducing bias through excluding participants who may withdraw due to an 
AE. If for any reason the sample is not drawn at Visit 3, it may be taken at any visit until 
the last study visit. Only one sample should be collected per participant for genetics 
during the study.
Coding and Storage of DNA Samples

The recommended default storage time is 15 years; this may vary in different territories. 
In some circumstances, there may be a rationale for the storage of DNA samples until 
they are depleted. When defining the storage time local laws and regulations for the 
storage of genetic samples must be considered.

The processes adopted for the coding and storage of samples for genetic analysis are 
important to maintain participant confidentiality. Samples will be stored for a maximum 
of 15 years, from the date of last participant last visit, after which they will be destroyed. 
DNA is a finite resource that is used up during analyses. Samples will be stored and used 
until no further analyses are possible or the maximum storage time has been reached.

An additional second code will be assigned to the sample either before or at the time of 
DNA extraction replacing the information on the sample tube. Thereafter, the sample will 
be identifiable only by the second, unique number. This number is used to identify the 
sample and corresponding data at the AstraZeneca genetics laboratories, or at the 
designated organisation. No personal details identifying the individual will be available to 
any person (AstraZeneca employee or designated organisations working with the DNA).

The link between the participant enrolment/randomisation code and the second number 
will be maintained and stored in a secure environment, with restricted access at 
AstraZeneca or designated organisations. The link will be used to identify the relevant 
DNA samples for analysis, facilitate correlation of genotypic results with clinical data, 
allow regulatory audit, and permit tracing of samples for destruction in the case of 
withdrawal of consent.


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Ethical and Regulatory Requirements

The principles for ethical and regulatory requirements for the study, including this 
genetics research component, are outlined in Appendix A.
Informed Consent

The genetic component of this study is optional and the participant may participate in 
other components of the main study without participating in this genetic component. To 
participate in the genetic component of the study, the participant must sign and date both 
the consent form for the main study and the addendum for the Genomics Initiative 
component of the study. Copies of both signed and dated consent forms must be given to 
the participant and the original filed at the study centre. The Investigator is responsible for 
ensuring that consent is given freely and that the participant understands that they may 
freely withdrawal from the genetic aspect of the study at any time.
Participant Data Protection

AstraZeneca will not provide individual genotype results to participant, any insurance 
company, any employer, their family members, general physician unless required to do so 
by law.

Extra precautions are taken to preserve confidentiality and prevent genetic data being 
linked to the identity of the participant. In exceptional circumstances, however, certain 
individuals might see both the genetic data and the personal identifiers of a participant. 
For example, in the case of a medical emergency, an AstraZeneca Physician or an 
Investigator might know a participant’s identity and also have access to his or her genetic 
data. Regulatory authorities may require access to the relevant files, though the 
participant’s medical information and the genetic files would remain physically separate.
Data Management

Any genetic data generated in this study will be stored at a secure system at AstraZeneca 
and/or designated organisations to analyse the samples.

AstraZeneca and its designated organisations may share summary results (such as genetic 
differences from groups of individuals with a disease) from this genetic research with 
other researchers, such as hospitals, academic organisations or health insurance 
companies. This can be done by placing the results in scientific databases, where they can 
be combined with the results of similar studies to learn even more about health and 
disease. The researchers can only use this information for health-related research 
purposes. Researchers may see summary results but they will not be able to see individual 
participant data or any personal identifiers. 


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
Some or all of the clinical datasets from the main study may be merged with the genetic 
data in a suitable secure environment separate from the clinical database.


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Appendix E
Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of Hy’s Law
E 1
Introduction
This Appendix describes the process to be followed in order to identify and appropriately 
report PHL cases and HL cases. It is not intended to be a comprehensive guide to the 
management of elevated liver biochemistries. 
During the course of the study, the Investigator will remain vigilant for increases in liver 
biochemistry. The Investigator is responsible for determining whether a participant meets 
potential PHL criteria at any point during the study.
All sources of laboratory data are appropriate for the determination of PHL and HL events; 
this includes samples taken at scheduled study visits and other visits including central and all 
local laboratory evaluations even if collected outside of the study visits; for example, PHL 
criteria could be met by an elevated ALT from a central laboratory and/or elevated TBL from 
a local laboratory. 
The Investigator will also review AE data (for example, for AEs that may indicate elevations 
in liver biochemistry) for possible PHL events.
The Investigator participates, together with AstraZeneca clinical project representatives, in 
review and assessment of cases meeting PHL criteria to agree whether HL criteria are met. HL 
criteria are met if there is no alternative explanation for the elevations in liver biochemistry 
other than DILI caused by the study intervention. 
The Investigator is responsible for recording data pertaining to PHL/HL cases and for 
reporting SAEs and AEs according to the outcome of the review and assessment in line with 
standard safety reporting processes.
E 2
Definitions
Potential Hy’s Law
Aspartate Aminotransferase or ALT ≥3 × ULN together with TBL ≥2× ULN at any point 
during the study following the start of study intervention irrespective of an increase in alkaline 
phosphatase (ALP).
Hy’s Law
Aspartate Aminotransferase or ALT ≥3× ULN together with TBL ≥2× ULN, where no other 
reason, other than the study intervention, can be found to explain the combination of 
increases, eg, elevated ALP indicating cholestasis, viral hepatitis, another drug. 
For PHL and HL the elevation in transaminases must precede or be coincident with (ie, on the 


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same day) the elevation in TBL, but there is no specified timeframe within which the 
elevations in transaminases and TBL must occur.
E 3
Identification of Potential Hy’s Law Cases
In order to identify cases of PHL it is important to perform a comprehensive review of 
laboratory data for any participant who meets any of the following identification criteria in 
isolation or in combination:

ALT ≥3 × ULN

AST ≥3 × ULN

TBL ≥2 × ULN
Central Laboratories Being Used:
When a participant meets any of the PHL identification criteria, in isolation or in combination, 
the central laboratory will immediately send an alert to the Investigator (also sent to 
AstraZeneca representative). 
The Investigator will also remain vigilant for any local laboratory reports where the PHL 
identification criteria are met, where this is the case the Investigator will:

Notify the AstraZeneca representative

Request a repeat of the test (new blood draw) by the central laboratory without delay

Complete the appropriate unscheduled laboratory eCRF module(s) with the original local 
laboratory test result
When the identification criteria are met from central or local laboratory results the Investigator
will without delay:

Determine whether the participant meets PHL criteria (see Section E 2 for definition) by 
reviewing laboratory reports from all previous visits (including both central and local 
laboratory results)
E 4
Follow-up
E 4.1
Potential Hy’s Law Criteria Not Met
If the participant does not meet PHL criteria the Investigator will:

Inform the AstraZeneca representative that the participant has not met PHL criteria.


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
Perform follow-up on subsequent laboratory results according to the guidance provided in 
the CSP.
E 4.2
Potential Hy’s Law Criteria Met
If the participant does meet PHL criteria the Investigator will:

Determine whether PHL criteria were met at any study visit prior to starting study 
intervention

Notify the AstraZeneca representative who will then inform the central Study Team 

Within 1 day of PHL criteria being met, the Investigator will report the case as an SAE of 
Potential Hy’s Law; serious criteria ‘Important medical event’ and causality assessment 
‘yes/related’ according to CSP process for SAE reporting

For participants that met PHL criteria prior to starting study intervention, the Investigator 
is not required to submit a PHL SAE unless there is a significant change# in the 
participant’s condition

The Study Physician contacts the Investigator, to provide guidance, discuss and agree an 
approach for the study participant’s follow-up (including any further laboratory testing) 
and the continuous review of data

Subsequent to this contact the Investigator will:

Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated. Completes follow-up SAE Form as required.

Investigate the aetiology of the event and perform diagnostic investigations as 
discussed with the Study Physician. This includes deciding which the tests available
in the Hy’s Law lab kit should be used.

Complete the 3 Liver eCRF Modules as information becomes available.
#A ‘significant’ change in the participant’s condition refers to a clinically relevant change 
in any of the individual liver biochemistry parameters (ALT, AST or TBL) in isolation or in 
combination, or a clinically relevant change in associated symptoms. The determination of 
whether there has been a significant change will be at the discretion of the Investigator, this 
may be in consultation with the Study Physician if there is any uncertainty.
E 5
Review and Assessment of Potential Hy’s Law Cases
The instructions in this Section should be followed for all cases where PHL criteria are met.
As soon as possible after the biochemistry abnormality was initially detected, the Study 
Physician contacts the Investigator in order to review available data and agree on whether 


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there is an alternative explanation for meeting PHL criteria other than DILI caused by the 
study intervention, to ensure timely analysis and reporting to health authorities within 
15 calendar days from date PHL criteria was met. The AstraZeneca Global Clinical Lead or 
equivalent and Global Safety Physician will also be involved in this review together with 
other subject matter experts as appropriate. 
According to the outcome of the review and assessment, the Investigator will follow the 
instructions below.
Where there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for a SAE:

If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF

If the alternative explanation is an AE/SAE: update the previously submitted Potential 
Hy’s Law SAE and AE eCRFs accordingly with the new information (reassessing event 
term; causality and seriousness criteria) following the AstraZeneca standard processes.
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IMP:

Send updated SAE (report term ‘Hy’s Law’) according to AstraZeneca standard 
processes. 

The ‘Medically Important’ serious criterion should be used if no other serious 
criteria apply

As there is no alternative explanation for the HL case, a causality assessment of 
‘related’ should be assigned.
If, there is an unavoidable delay, of over 15 calendar days in obtaining the information 
necessary to assess whether or not the case meets the criteria for HL, then it is assumed that 
there is no alternative explanation until such time as an informed decision can be made:

Provides any further update to the previously submitted SAE of PHL, (report term now 
‘Hy’s Law case’) ensuring causality assessment is related to study intervention and 
seriousness criteria is medically important, according to CSP process for SAE reporting.

Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are still met. Update the previously submitted PHL SAE report 
following CSP process for SAE reporting, according to the outcome of the review and 


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amending the reported term if an alternative explanation for the liver biochemistry 
elevations is determined.
E 6
Laboratory Tests
Hy’s Law Lab Kit for Central Laboratories 
Additional standard chemistry and coagulation 
tests
GGT
LDH
Prothrombin time
INR
Viral hepatitis
IgM anti-HAV 
HBsAg
IgM and IgG anti-HBc
HBV DNA a
IgG anti-HCV
HCV RNA b
IgM anti-HEV
HEV RNA
Other viral infections
IgM and IgG anti-CMV
IgM and IgG anti-HSV
IgM and IgG anti-EBV
Alcoholic hepatitis
Carbohydrate deficient transferrin (CD-transferrin) c
Autoimmune hepatitis
Antinuclear antibody (ANA)
Anti-Liver/Kidney Microsomal Ab (Anti-LKM)
Anti-Smooth Muscle Ab (ASMA)
Metabolic diseases
alpha-1-antitrypsin
Ceruloplasmin
Iron
Ferritin
Transferrin c
Transferrin saturation
aHBV DNA is only recommended when IgG anti-HBc is positive
bHCV RNA is only recommended when IgG anti-HCV is positive or inconclusive 
cCD-transferrin and Transferrin are not available in China. Study teams should amend this list accordingly
E 7
References
Aithal et al, 2011
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, et al. 
Case definition and phenotype standardization in drug-induced liver injury.2011, Clinical 
Pharmacology and Therapeutics 2011, 89(6):806-815.
FDA Guidance for Industry, July 2009
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing 
clinical evaluation’. Available from; https://www.fda.gov/regulatory-information/search-fda-


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guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation


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Appendix F
COVID-19 Specifics
F 1
Background to COVID-19
There is currently an outbreak of respiratory disease (COVID-19) caused by a novel
SARS-CoV-2 that was first detected in Wuhan City, Hubei Province, China in 2019. This new
virus has rapidly spread across the globe causing the WHO to declare a pandemic situation on
12 March 2020. The countermeasures initiated by national and local governments worldwide
and the recommendations issued by the health authorities have impacted current and new
clinical studies. As the threat of pandemic burden including new outbreaks, locally or globally,
will impact the further conduct of clinical studies, appropriate risk assessments and mitigation
measures will need to be taken into consideration in all clinical studies to protect participants, 
site staff, and society as a whole.
Both EMA and FDA as well as national health authorities in Europe have issued new 
guidelines that aim to provide recommendations for actions for conduct of clinical studies of 
medical products during COVID-19 pandemic. Since the pandemic situation is evolving, 
guidelines, recommendations, national laws, and local restrictions may change at high pace. 
Given the circumstances of potentially relapsing pandemic or epidemic situation with regard 
to the spread of COVID-19 in future, special attention will be paid to protect participants 
participating in the study and site staff involved in the investigations against infection with 
SARS-CoV-2 as requested by the newly issued EMA guideline.
F 2
Risk Assessment for COVID-19 Pandemic
The study intervention and its mechanism of action is unlikely to impact on the course of
infection with SARS-CoV-2. AZD1402 administration results in blockade of IL-4α that could 
result in increased susceptibility to lung infections in general, but the risk of susceptibility to 
SARS-CoV-2 is unknown. The risk of exposure to infected people cannot be completely 
excluded as the participants may need to be in public areas (eg, commute to the site) and have 
additional human contact (eg, with site staff and other participants of the clinical study).
Measures to mitigate the additional risks caused by COVID-19 are:

Participant specific inclusion and exclusion criteria:

Exclusion of patients with active COVID-19 infection or significant respiratory 
disease (other than asthma)

Exclusion of participants with a diagnosis of / suspected COVID-19 infection with 
associated pneumonia / pneumonitis as described in Section 5.2.

This study is going to start enrolling only when the Sponsor and CRO in collaboration 
deem it is safe to start the study. In addition, the study will not start until the local 


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confinement measures or other safety restrictions linked to the COVID-19 pandemic 
imposed by the local authorities are compatible with safe conduct of the study.

Current national laws and local recommendations for prevention of pandemic will be 
strictly adhered to.

Participants will be closely monitored for any signs and symptoms of COVID-19, 
including fever, dry cough, dyspnoea, sore throat, and fatigue throughout the study during 
the pandemic. Once clinical signs of infection are reported by participants, the 
Investigator needs to determine whether samples can be collected, and safety data can be 
recorded on site. If not, AEs and concomitant medications will be obtained via phone 
calls. The decision to continue with dosing the participant with the study intervention in 
the event of him/her showing symptoms of COVID-19 infection will be per Investigator’s 
discretion.

The probability of virus transmission will be controlled as much as possible by:

Advice for participant to adhere to local requirements for reduction of the public 
exposure while ambulatory.

Confirmation of COVID-19 infection by optional laboratory assessment will be 
conducted based on availability (test capacity and turnaround time) of approved tests, 
logistical aspects of travel/test site, and on Investigator’s discretion.

Requesting all participants are contacted by phone 1 day prior to every visit for 
assessing COVID-19 symptoms and signs and are asked not to attend the site in case 
of suspected reports. In addition, participants are asked for any contact with a person 
who has tested positive for SARS-CoV-2. If applicable, participants will be referred 
to the local health care system for further follow-up and treatment.

Physical distancing and person-to-person contact restrictions will be applied during 
site visits.

Where physical distancing is not possible, personal protective equipment will be used 
by study participants (surgical face mask, gloves) and staff (for example but not 
limited to masks, gloves, protectors, medical suits) if deemed appropriate by the 
Investigators and site staff and guided by local requirements.

Logistical improvements of the site and structural measures of the study site building 
will be implemented to further improve physical distancing.

If, for reasons related to the COVID-19 pandemic (eg, local lockdown, self-isolation 
requirements), a participant is not able to attend their scheduled visit within the visit 
window, they can have their visit rescheduled as detailed in the study reference 
manual/as per agreement with the Sponsor study physician. Where visits cannot be 
rescheduled, participants should continue at the next scheduled visit. Additionally, 
on-site visits may be replaced by a telemedicine visit if allowed by local/regional 
guidelines. Having a telemedicine contact with the participants will allow collection 


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of data for AEs, concomitant medications, adherence to the e-Diary and PRO
measures to be reported and documented. The term telemedicine visit refers to 
remote contact with the participants using telecommunications technology including 
phone calls, virtual or video visits, and mobile health devices.

If site visits are not possible due to local restrictions, home nursing visits may be 
considered after discussion with and approval by the Sponsor according to local 
regulations. The Principal Investigator will be responsible to delegate any study 
procedure, however the Principal Investigator will retain responsibility for evaluation of 
the data collected. In all cases, informed consent should always be collected in writing.
F 3
Restrictions Related to COVID-19
During the COVID-19 pandemic, participants are advised to adhere to local requirements for 
reduction of the public SARS-CoV-2 exposure while ambulatory. If applicable, prior to 
Screening (Visit 1), potential participants should be called to confirm they are not 
experiencing any COVID-19 symptoms and signs and are asked not to attend the site in case 
of suspected infection. If appropriate, participants will be referred to the local health care 
system. Physical distancing and person-to-person contact restrictions will be applied and 
explained to participants while staying at the study site. Where physical distancing is not 
possible, study participants will be asked to use surgical face masks and/or gloves if deemed 
appropriate by the Investigator and site staff and guided by local requirements.
F 4
Data Quality Assurance Related to COVID-19
Monitoring visits at site will be limited to a minimum required as deemed appropriate during
COVID-19 pandemic, per local regulations.
In addition, where possible, other measures for carrying out protocol related activities, such as
but not limited to home nursing, may be employed as required.
F 5
References

Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) 
pandemic, EMA, Version 4 (04/02/2021). 
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf

Supplementary recommendations of BfArM and PEI to the European Guidance on the 
Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, version 4 
(2021.05.06). 
https://www.bfarm.de/EN/Drugs/licensing/clinicalTrials/news/CT_COVID19.html


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
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 
Public Health Emergency, March 2020, Updated on June 03, 2020 
https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/fda-
guidance-conduct-clinical-trials-medicalproducts-during-covid-19-public-health-
emergency.


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Appendix G
Changes Related to Mitigation of Study Disruptions Due to 
Cases of Civil Crisis, Natural Disaster, or Public Health
Note: Changes below should be implemented only during study disruptions due to any of or a 
combination of civil crisis, natural disaster, or public health crisis (eg, during quarantines and 
resulting site closures, regional travel restrictions and considerations if site personnel or study 
participants become infected with SARS-CoV-2 or similar pandemic infection) during which 
participants may not wish to or may be unable to visit the study site for study visits. These 
changes should only be implemented if allowable by local/regional guidelines and following 
agreement from the Sponsor.
G 1
Reconsent of Study Participants During Study Interruptions
During study interruptions, it may not be possible for the participants to complete study visits 
and assessments on site and alternative means for carrying out the visits and assessments may 
be necessary, eg, remote visits. Reconsent should be obtained where applicable, and where 
consent has not already been provided for the alternative means of carrying out visits and 
assessments. Local and regional regulations and/or guidelines regarding reconsent of study 
participants should be checked and followed. Reconsent may be verbal if allowed by local and 
regional guidelines (note, in the case of verbal reconsent the ICF should be signed at the 
participant’s next contact with the study site). Visiting the study sites for the sole purpose of 
obtaining reconsent should be avoided.
G 2
Rescreening of Participants to Reconfirm Study Eligibility
Additional rescreening for screen failure due to study disruption can be performed in 
previously screened participants. The Investigator should confirm this with the designated 
study physician.
In addition, during study disruption there may be a delay between confirming eligibility of a 
participant and either enrolment into the study or commencing of dosing with IMP. If this 
delay is outside the screening window specified in Table 1 and Table 2, the participant will 
need to be rescreened to reconfirm eligibility before commencing study procedures. This will 
provide another opportunity to re-screen a participant in addition to that detailed in Table 1
and Table 2. The procedures detailed in Section 5.1 and Section 5.2 must be undertaken to 
confirm eligibility using the same randomisation number as for the participant.
G 3
Home or Remote Visit to Replace On-site Visit (where applicable)
A qualified HCP from the study site or TPV service may visit the participants home/or other 
remote location as per local SOPs/local regulations, as applicable. Supplies will be provided 
for a safe and efficient visit. The qualified HCP will be expected to collect information per the 
CSP. Home visits may be combined with telemedicine visits.


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G 4
Telemedicine Visit to Replace On-site Visit (Where Applicable)
In this appendix, the term telemedicine visit refers to remote contact with the participants 
using telecommunications technology including phone calls, virtual or video visits, and 
mobile health devices.
During a civil crisis, natural disaster, or public health crisis, on-site visits may be replaced by 
a telemedicine visit if allowed by local/regional guidelines and where a home or remote visit 
is not possible. Having a telemedicine contact with the participants will allow collection of 
AEs, concomitant medication, adherence to the e-Diary and PRO measures to be reported and 
documented, and any information that may be possible to collect virtually.
G 5
At-home or Remote Location IMP Administration Instructions
If a site visit is not possible, at-home or remote location administration of IMP may be 
performed where this is not already specified in the protocol. The option of at-home or remote 
location IMP administration ensures participants safety in cases of a pandemic where 
participants may be at increased risk by traveling to the site/clinic. This will also minimize 
interruption of IMP administration during other study disruptions, eg, site closures due to 
natural disaster.
G 6
At-home or Remote Location IMP Administration by the 
Participant
Prior to at-home or remote location IMP administration outside the scope of the protocol, the 
Investigator must assess the participant or his/her caregiver to determine whether they are 
appropriate for continued at-home or remote location administration of IMP. All necessary 
supplies and instructions for administration and documentation of continued home IMP 
administration will be provided. More information related to the visit can be obtained via a 
telemedicine or home / remote visit.
G 7
Data Capture During Telemedicine or Home / Remote Visits
Data collected during telemedicine or home/remote visits will be captured by the qualified 
HCP from the study site or TPV service in the source documents, or by the participant 
themselves.


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Appendix H
Patient-reported Outcomes
H 1
Asthma Control Questionnaire-6


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H 2
Cough VAS


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H 3
SPFQ
There will be 3 optional questionnaires for participant completion at Run-in (Visit 2), during 
the Treatment Period (Visit 3 in Part 1 and Visit 5 in Part 2), and at end of the study
(Follow-up Visit 11 in Part 1 and Follow-up Visit 9 in Part 2, or ETV).
A. SPFQ at Run-in
Your experience before you started the study: to be completed within 28 days prior to 
randomisation


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B. SPFQ during the Treatment Period
Your experience during the study: to be completed during the Treatment Period


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C. SPFQ at the end of the study participation
Your experience at the end of the study: to be completed at last Follow-up Visit or ETV


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Appendix I
Definitions, Management and Classifications of 
Hypersensitivity Reactions
National Institute of Allergy and Infectious Diseases and Food Allergy and Anaphylaxis 
Network Guidance for Anaphylaxis Diagnosis 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson FN Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: Summary report –
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006;117(2):391-7. 
Dispenza MC. Classification of Hypersensitivity reactions. Allergy Asthma Proc 2019 
40:470-473. 


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Appendix J
Abbreviations
Abbreviation or special 
term
Explanation
ACQ-6
Asthma Control Questionnaire-6
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase/transaminase
AM
before noon (ante meridiem)
AST
aspartate aminotransferase/transaminase
ATS
American Thoracic Society
BID
twice daily
BP
blood pressure
bpm
beats per minute
CAPA
Corrective and Preventative Action
COPD
chronic pulmonary obstructive disease
COVID-19
Coronavirus disease-2019
CRP
C-reactive protein
CRO
Contract Research Organisation
CSP
Clinical Study Protocol
CSR
Clinical Study Report
DILI
drug induced liver injury
DNA
deoxyribonucleic acid 
DPI
dry powder inhaler
DSMB
Data and Safety Monitoring Board
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
eGFR
Estimated glomerular filtration rate
EMA
European Medicines Agency
ERS
European Respiratory Society
ETV
early termination visit
EU-CTR
European Union Clinical Trial Regulation
FAS
full analysis set
FDA
United States Food and Drug Administration


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Abbreviation or special 
term
Explanation
FeNO
fractional exhaled nitric oxide
FEV1
forced expiratory volume in one second
FSH
follicle stimulating hormone
FVC
Forced vital capacity
GCP
Good Clinical Practice
GINA
Global Initiative for Asthma
GMP
Good Manufacturing Practice
HBsAg
hepatitis B surface antigen
HCP
Health Care Professional 
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HL
Hy’s Law
hs-CRP
high-sensitivity CRP
HR
heart rate
HRCT
high-resolution computed tomography
HRT
hormone replacement therapy
IATA
International Airline Transportation Association
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
ICS
inhaled corticosteroids
IEC
Independent Ethics Committee
IPD
Intervention Discontinuation Visit
IgE
immunoglobulin E
IgG
immunoglobulin G
IgM
immunoglobulin M
IGRA
interferon gamma release assay
IL
interleukin
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
IRT
Interactive Response Technology
LABA
long-acting beta-adrenoceptor agonist
LAMA
long-acting muscarinic antagonist
CCI
CCI
CCI
CCI


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Abbreviation or special 
term
Explanation
LTRA
leukotriene receptor antagonists
MART
Maintenance and Reliever Therapy
MMRM
mixed model repeated measure
MedDRA
Medical Dictionary for Regulatory Activities
MDI
multiple dose inhaler
NIMP
Non-investigational medicinal product
NYHA
New York Heart Association Score
NGAL
neutrophil gelatinase-associated lipocalin
OCS
oral corticosteroids
PCR
polymerase chain reaction
PD
pharmacodynamics
PHL
potential Hy’s Law
PEF
peak expiratory flow
PM
after noon (post meridiem)
PPS
per protocol set
ppb
part per billion
PK
pharmacokinetic(s)
PRO
patient-reported outcomes
PT
preferred term
QT
QT interval
QTcF
QT interval corrected using Fridericia’s formula
QTcB
QT interval corrected using Bazett’s formula
QRS
QRS interval
RNA
ribonucleic acid
RR
RR interval
RTSM
Randomisation and Trial Supply Management
SABA
short-acting beta agonist
SAE
serious adverse event 
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SAMA
short-acting muscarinic antagonist
SAP
statistical analysis plan
SAS
statistical analysis system
SD
standard deviation
SoA
Schedule of Activities
CCI
CCI


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Abbreviation or special 
term
Explanation
SPFQ
Study Participant Feedback Questionnaire
SOC
system organ class
SOP
Standard Operating Procedures
SRC
Safety Review Committee
SS
safety set
TB
tuberculosis
TBL
total bilirubin
Th2
T helper cell type 2
Tlc
tear lipocalin
TPV
Third-party Vendor
ULN
upper limit of normal
URC
Unblinded Review Committee
VAS
Visual Analogue Scale


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Appendix K
Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 1: 23 November 2020
Overall Rationale for the Amendment
The original Clinical Study Protocol (CSP), Final 1.0, dated 20 October 2020, was updated to:

Clarify Safety Review Committee (SRC) requirements, stratification, sampling, and 
medical device deficiencies for clarity and completeness.

Add study mitigation language which will provide sites with measures that may be
implemented if a participant is not able to visit a study site to ensure that the clinical trial 
can continue whilst minimizing risk to the participant, maintaining compliance with Good 
Clinical Practice (GCP), and minimizing risks to the study integrity.

Clarify some study procedures. 

Make minor editorial updates throughout.
Section Number 
and Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Section 1.1 
Synopsis, 
Section 4.1.1 
Part 1
Additional description that data 
will be unblinded for SRC 
review, but study participants 
will remain blinded
Additional clarification on 
unblinding of data for SRC 
review
Non-substantial
Update of stratification for 
Part 1 of the study to 
stratification by site in Australia 
and New Zealand
Update made for logistical 
reasons
Substantial
Section 1.1 
Synopsis, 
Section 4.1.1 
Part 1, Section 9.6 
Data Monitoring 
Committees, 
Appendix A 5.2 
Safety Review 
Committee
Addition of unscheduled SRC 
meeting
To allow for an unscheduled SRC 
meeting in the event of any safety 
or tolerability events requiring 
further review that may impact 
continuation of a cohort or the 
study
Substantial
Section 1.3 
Schedule of 
Activities
 
 
 
 
Non-substantial
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Section Number 
and Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
 
Added for clarification
Non-substantial
Addition/revision of footnote to 
clarify timing of in-clinic 
outpatient visits and timing of 
vital sign measurements.
Added for clarification
Non-substantial
Section 4.1.3 
Study Conduct 
Mitigation During 
Study Disruptions 
Due to Cases of 
Civil Crisis, 
Natural Disaster, 
or Public Health 
Crisis
Appendix G 
Changes Related 
to Mitigation of 
Study Disruptions 
Due to Cases of 
Civil Crisis, 
Natural Disaster, 
or Public Health
New wording was added which 
would give guidance on how the 
study could continue in the 
event of a serious disruption 
with details of mitigation that
could be employed to ensure 
study continuity
The impact of COVID-19 has 
highlighted the risk to continuity 
of clinical trials during times of 
study disruption, whether by civil 
crisis, natural disaster or public 
health crisis. This section details 
the measures that may be 
implemented if a participant is not 
able to visit a study site to ensure 
that the clinical trial can continue 
whilst minimizing risk to the 
participant, maintaining 
compliance with GCP, and 
minimizing risks to study 
integrity.
These changes will only be 
initiated at a time of study 
disruption.
Substantial
Section 6.1.1 
Investigational 
Products
Update of dosage levels for 
placebo to “NA”
Updated to match the unit dose 
strength as there are no dose 
levels of placebo
Non-substantial
Section 8.3.2 
Follow-up of AEs 
and SAEs
Section 8.6.1 
Collection of 
Mandatory 
Samples for 
Biomarker 
Analysis 
Removal of blood samples for 
complement testing
Test will not clearly inform safety 
or scientific data
Substantial
Section 8.3.12 
Medical Device 
Deficiencies
Removal of the sentence “The 
manufacturers medical device 
complaint report will be used to 
collect the deficiency.”
Collection of deficiencies and 
reporting to third party is already 
stated, this level of detail is not 
required in the protocol
Non-substantial
Section 8.6.2 
Collection of 
Optional Samples 
Removal of genomics initiative 
sample from this section
To allow for two separate samples 
to simplify optional consent
Non-substantial
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Section Number 
and Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
for Biomarker 
Analysis
Appendix A 5.2 
Safety Review 
Committee
Removal of “independent” from 
and addition of PK data to the 
unblinded SRC review
To clarify protocol inconsistency 
in SRC data review description
Non-substantial
Amendment 2: 10 March 2021
Overall Rationale for the Amendment
The Clinical Study Protocol (CSP), Final 2.0, dated 23 November 2020, was updated to 
increase flexibility in assessments, increase clarity, and to account for COVID-19 vaccination. 
Numerous other minor editorial updates also made throughout.
Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Section 1.1 Synopsis
Section 4.1.2 Part 2
Randomisation strategy of 
2:1 (active to placebo) added 
for Part 2
For clarity on randomisation 
strategy
Non-substantial
Section 1.3 Schedule 
of Activities
Order and timings of home 
device versus clinical 
spirometry updated
For flexibility in assessments and 
to increase clarity
Non-substantial
Urine pregnancy test for 
Part 1 of the study moved to 
Day -1
To decrease the number of tests 
required on dosing day
Non-substantial
Collection windows for 
clinical spirometry and 
timing of clinical spirometry 
relative to randomisation 
spirometry specified
For flexibility in assessments and 
to increase clarity
Non-substantial
Statement added to allow 
order of assessments to be 
updated in consultation with 
the Sponsor study physician
For flexibility in assessments
Non-substantial
Vital sign collection times 
updated
For flexibility in assessments and 
to increase clarity
Non-substantial
Collection windows updated 
for electrocardiogram 
collection
For flexibility in assessments and 
to increase clarity
Non-substantial
Pharmacokinetic sampling 
windows updated
For flexibility in assessments and 
to increase clarity
Non-substantial


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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Blood sample collection 
timepoint for IgE updated to 
Day -1 or Day 1 pre-dose
For logistical reasons
Non-substantial
Collection timepoint for 
optional samples updated
For flexibility in assessments
Non-substantial
Additional urine pregnancy 
test collection timepoints 
added to Part 2
To cover duration of study 
participation
Non-substantial
Section 1.3 Schedule 
of Activities
Section 4.1.1 Part 1
Section 4.1.2 Part 2
Section 6.1.3.3 
Treatment Period
Dosing interval for study 
intervention/placebo updated 
to 
 
To clarify the required time 
windows
Non-substantial
Section 1.1 Synopsis
Section 4.1.1 Part 1
Stratification by site for 
randomization updated to 
replace New Zealand with 
Germany
To reflect updated country 
selection.
Non-substantial
Section 4.1.1 Part 1
Figure 3 updated to correct 
typo in Part 1a mg 
(DPI/DPI corrected to 
DPI/
)
To fix typo
Non-substantial
Section 4.4.1 
Premature 
Termination of the 
Study and Stopping 
Criteria
Update to pharmacokinetic 
stopping criteria
The Phase I peak concentration 
and exposure limits, which 
included a 3-fold safety factor, 
have been updated for Phase IIa 
to match the observed values 
achieved at the no-observed-
adverse-effect-level (total 
AZD1402 assay) in the 4-week 
humanised mouse toxicology 
study (matching the duration of 
the Phase IIa study).
Substantial
Section 5.1 Inclusion 
Criteria
Contraception requirements 
updated for male 
participants
To accommodate countries where 
spermicides are not available
Non-substantial
Section 5.2 Exclusion 
Criteria
Exclusion criterion added 
regarding receipt of 
COVID-19 vaccination
Criterion added to address any 
potential safety concerns and/or 
interpretation of data as a result of 
COVID-19 vaccination
Substantial
Section 6.5.4 
Restricted and 
Enrolment requirements for 
participants receiving 
Added to clarify prohibited 
medication in relation to 
COVID-19 vaccination in order to 
Substantial
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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Prohibited 
Medications
COVID-19 vaccination 
added
address any potential safety 
concerns and/or interpretation of 
data as a result of vaccination
Section 7.1.1 
Permanent 
Discontinuation of 
Study Intervention 
for Individual 
Participants (Part 1 
and Part 2)
Withdrawal criteria related 
to COVID-19 vaccination 
added
Criterion added to address any 
potential safety concerns and/or 
interpretation of data as a result of 
COVID-19 vaccination
Substantial
Section 8.1.1 Lung 
Function Test –
Spirometry
Specified that it is post-
randomisation clinical 
device spirometry that 
should be performed within 
± 1.5 hrs of the time that 
randomisation spirometry 
was performed
For clarity alignment with 
changes made to Section 1.3
Non-substantial
Section 8.1.4 
Electronic Diary
Section 8.1.6 Asthma 
Symptom Score
Section 8.1.7 Use of 
Rescue Medication
Section 8.1.8
Specified the periods 
wherein the eDiary needs to 
be completed
Clarification of inconsistency in 
the time period for eDiary 
completion
Non-substantial
Section 8.1.11 Peak 
Expiratory Flow
Timing of evening 
measurement updated from “ 
just before going to bed” to 
 
To clarify inconsistency and 
timing of PEF measurement 
timing in relation to study 
intervention
Non-substantial
Section 8.2.2 Vital 
Signs
Requirement for temperature 
measurement to be 
consistently oral or tympanic 
added
To ensure consistency of 
measurement method
Non-substantial
Section 8.2.3 
Electrocardiograms
Requirement for consistency 
in technicians for each 
participant updated to allow 
any appropriately trained 
personnel to perform the 
ECG
For logistical reasons
Non-substantial
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments
Estimated glomerular 
filtration rate added to the 
Additional laboratory safety 
assessment
Non-substantial
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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
list of laboratory safety 
variables in Table 6
Section 9.4.2.1 
Primary Endpoint
Site removed from statement 
of random effects.
Clarified that 'visit' in the 
model specification only 
refers to the weekly visits 
during treatment.
Clarified that subgroup 
analyses are additional (not 
primary) analyses.
Text modification to clarify 
evaluation of primary endpoint
Non-substantial
Amendment 3 (09 June 2021)
This amendment is considered to be non-substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union.
Overall Rationale for the Amendment
The Clinical Study Protocol (CSP), Final 3.0, dated 10 March 2021, was updated to clarify 
study stop criteria, procedure for written Informed Consent in case of SARS-CoV-2 pandemic 
situation, study conduct mitigation during study disruptions due to COVID-19 pandemic, SAE 
reporting, time and reason for DSMB meetings, home nursing, and to update COVID-19 
guidances. Numerous other minor editorial updates also made throughout.
Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Section 1.3, Table 1
Deletion of cross-reference 
for blood sample collection 
for 
 
To clarify that this cross-reference 
was previously added 
erroneously.
Non-substantial
Section 4.1.3, 
Section 4.1.4
Appendix G
Inclusion of references to 
applicable appendices
Clear reference for study conduct 
due to SARS-CoV-2 or similar 
pandemic has to be provided in 
addition to the general reference 
to cases of civil crisis, natural 
disaster, or public health crisis
Non-substantial
Section 4.4.1.
Change of wording to clarify 
that the study will be 
terminated prematurely in 
case specified stopping 
criteria are fulfilled. 
To provide clear instructions/ 
stopping criteria
Non-substantial
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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/ 
Non-substantial
Section 8.3.9
Change of wording to clarify 
the time requirements for 
SAEs reporting
To provide clear timeframes for 
the reporting of SAEs
Non-substantial
Section 9.6
Change of wording to clarify 
time and reason for DSMB 
meetings
To clarify when and how often 
the DSMB will meet
Non-substantial
Appendix F 2
Inclusion of clarifying text 
regarding home nursing 
visits 
Text has to be clarified regarding 
local regulations for home 
nursing.
Non-substantial
Appendix F 5
Inclusion of updated EMA 
and BfArM guidance
Reference to updated guidances 
has to be provided
Non-substantial
Amendment 4 (13 Jan 2022)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
The Clinical Study Protocol (CSP) Final 4.0, dated 09 Jun 2021, was amended to reduce the
sample size for Part 2b based on the expectation on effect size for the 
mg dose and by 
utilizing the total number of placebo participants from both Part 2a and Part 2b to achieve 
satisfactory power, to modify the PK and ADA sampling timepoints for Part 1b and Part 2a 
and 2b, to add clarification that women who are breastfeeding or planning to become pregnant 
are excluded from study participation and to update to the definition of the covariate 
eosinophil count group.
A number of additional clarifications and minor editorial changes have also been added.
Section Number and 
Name
Description of Change
Brief Rationale
Substantial/
Non-substantial
Section 1.1 Synopsis, 
Overall Design, 
Number of 
Participants, Sample 
Size; Section 4.1.1; 
Figure 3, Section 
4.1.2 Section 9.2
Total number of participants in 
Part 2 changed from 360 to 300 
by reducing the number of 
participants in Part 2b/
mg dry 
powder inhaler 
 from 
80 to 40 and in Part 2b/placebo 
from 40 to 20 and sample size 
considerations updated
Sample size for Part 2b 
was reduced based on the 
higher expectation on 
effect size for the 
mg 
dose (targeting 200 mL 
instead of 175 mL) and by 
utilizing the total of 100 
placebo participants (80 
from Part 2a and 20 from 
Part 2b) to achieve 
satisfactory power
Substantial
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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/
Non-substantial
Section 1.1 Synopsis, 
Objective and 
Endpoints;
Section 3, Table 4 
Removal of reference to at-home 
monitoring for FEV1
To clarify that home FEV1
measurements form part of 
the e-Diary alert process, 
in-clinic spirometry 
assessment will be used to 
assess the study safety 
objective and will 
primarily be used for 
decision making
Non-substantial
Sections 1.1 
Synopsis, General 
Statistical 
Consideration
Section 4.1.2
Section 9.5
Main purpose of interim analysis 
changed to futility analysis
A futility analysis may be 
needed to inform internal 
AZ portfolio decisions
Non-substantial
Section 1.3 Table 1
Addition of ‘2 hour post’ 
spirometry to clarify time point 
Added for clarification
Non-substantial
Section 1.3 Table 1 
and Table 2
Addition of ‘in-clinic’ to FeNO 
test
Added for clarification as 
at-home assessments are 
also performed 
Non-substantial
Section 1.3 Table 1 
and Table 2,
Section 5.1
Addition of language to clarify 
requirement for negative serum 
pregnancy test at Screening as per 
Schedule of Activities
Added for clarification
Non-substantial
Section 1.3 Table 1 
and Table 2,
Section 5.2, 
Section 8.2.4, Table 6
Addition of text to allow for 
inclusion of participants with 
previous vaccination history for 
hepatitis B and positive 
anti-hepatitis B surface Ag at 
Screening can be included into the 
study following providing 
negative PCR test
Addition of hepatis B PCR test to 
laboratory safety variables
Added for clarification
Non-substantial
Section 1.3 Table 1 
and Table 2,
Section 5.1.3
Addition of language to clarify 
CRP testing requirements 
Added for clarification
Non-substantial
Section 1.3 Table 1 
and Table 2
Addition of PK and ADA 
sampling timepoints
Addition of PK and ADA 
timepoints to further 
characterize the PK and 
ADA profile
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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/
Non-substantial
Section 1.3 Table 2, 
Section 4.1.2,
Section 8.5.1.2
Number of participants for PK 
intense sampling arm updated to 
‘approximately 20 participants per 
treatment arm’ 
Wording corrected
Non-substantial
Section 1.3 Table 2
Addition of weeks in the Schedule 
of Activities
Added for clarification as 
endpoints are listed in 
weeks
Non-substantial
Section 1.3 Table 2, 
Section 8.6.2
 
 
Updated as a result of 
logistics and feasibly of 
sampling 
Non-substantial
Section 1.1 Synopsis, 
Intervention Groups 
and Duration
Section 1.3 Table 2,
Section 8.5.2
Increased window (Part 1) and 
removal (Part 2) of final ADA 
assessment
Given the short half-life of 
AZD1402 and experience 
with other non-monoclonal 
antibody therapeutic 
biologicals, measurements 
up to Day 56 is considered 
adequate for ADA 
characterisation
Non-substantial
Section 3
Table 3
Replaced 'Week 4' with ‘Day 28’, 
in the definition of exploratory 
endpoints in Part 1 
Added for clarification as
weeks are not referenced 
in Schedule of Activates 
for Part 1
Non-substantial
Section 5.2
Addition of the exclusion 
criterion: ‘Women who are 
pregnant or breastfeeding, or who 
are planning to become pregnant 
during the study’
Additional clarification 
that women who are 
breastfeeding or planning 
to become pregnant are 
excluded from study 
participation
Substantial
Section 5.3.4
Update of time participants 
should abstain from donating 
blood and plasma from 
5 half-lives to 28 days
Added for consistency 
with Informed Consent 
Form language
Non-substantial
Section 6.3
Section 9.4.4.1
References to plasma for PK 
samples replaced with ‘serum’
Updated to remove 
erroneous inclusion 
previously
Non-substantial
Section 6.4
Definition for compliance added
Added for clarification
Non-substantial
Section 1.3 Table 1 
and Table 2,
Section 7.1.1
Addition of Intervention 
Discontinuation visit and text to 
clarify steps to be taken when a 
participant withdraws from study 
intervention
Added for clarification
Non-substantial
CCI


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Section Number and 
Name
Description of Change
Brief Rationale
Substantial/
Non-substantial
Section 7.1.2.1
Wording added to clarify FEV1
in-clinic assessment will be used 
Added for clarification
Non-substantial
Section 8.1.1
Wording added to clarify 
spirometry assessments should be 
performed pre-dose
Added for clarification
Non-substantial
Section 8.1.5
Section 8.3.5
Section 9.3, Table 7
Section 9.4.2.1
Section 9.4.3.1
Section 9.5
Minor text updates to align with 
the statistical analysis plan
Added for clarification
Non-substantial
Section 8.2.4
Section 9.4.1
Section 9.4.4
Vendor names replaced with 
generic wording 
Administrative change to 
align with AZ standards 
Non-substantial
Section 8.2.4, Table 6
Further information of cytokine 
assessments
Added for clarification 
Non-substantial
Section 9.4.2.1
Update of definition of covariate 
eosinophil count group from 
‘150 to 299, ≥ 300 cells/μL’ to 
‘< 300, ≥ 300 cells/μL’
To account for patients 
who may have eosinophil 
count lower than 150 
cells/μL on Day 1
Substantial
Appendix A 5
Wording added to clarify when 
decision making is made by the 
SRC 
Added for clarification
Non-substantial
Amendment 5 (04 Mar 2022)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
The Clinical Study Protocol (CSP) Final 5.0, dated 13 Jan 2022, was amended to redefine the 
stopping criteria and update the inclusion criteria for Part 2. The study stopping criteria have 
been adjusted to reflect the role of the Data Safety Monitoring Board (DSMB) in evaluating 
all clinical data, including spirometry, as applicable to the larger sample size and expected 
variability in the Part 2 participant population. Additionally, the individual suspension and 
stopping criteria have been amended to distinguish between criteria for Part 1 and Part 2 as 
applicable to different participant populations and variability in home assessment spirometry, 
in particular for Part 2 where there is no residential period. The inclusion criteria were updated 
to allow more flexibility in recruitment around ICS-LABA guidance and asthma 
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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 1.1, 
Section 1.2 
Figure 1, 
Section 1.3 
Table 1
Extension to period of 
collection of additional 
ADA samples from 
169 days ± 1 month to up 
to a year after 
randomisation.
To further characterise ADA 
profile and permit sampling 
following SRC unblinded 
data review
Non-substantial
Section 1.1 
Overall Design 
Part 2, 
Section 4.1.2
Updated text to state 
Part 2b 3 dose levels 
‘may’ run in parallel.
Clarification that the Part 2b 
decision to proceed is 
dependent on Part 1b 
completion with SRC review 
and may commence after the 
completion of Part 2a.
Non-substantial
Section 1.1, 
Section 9.5
Text added to interim 
analysis section to state it 
may be performed after 
Part 2a. 
An efficacy evaluation of the 
primary endpoint may be 
performed to inform internal 
AZ portfolio decisions
Non-substantial
Section 1.3 
Table 1 and 
Table 2, 
Section 8.1.4
Updates made to clarify 
subjects receive the 
e-Diary for completion at 
home from Visit 2, 
compliance checks will 
be done following this 
and e-diary completion is 
twice daily throughout 
study. 
Added for clarification
Non-substantial
Section 1.3 
Table 1 and 
Table 2
Timing of ECG before 
administration of study 
intervention clarified to 
be “within” 75 min.
Added for clarification
Non-substantial
Footnote added to clarify 
urinalysis samples taken
pre-dose on Day 1
Added for clarification
Non-substantial
Footnote added to clarify 
all urine pregnancy 
samples taken pre-dose.
Added for clarification
Non-substantial
Section 1.3 
Table 2
Footnote added to 
baseline samples to 
confirm they are taken 
pre-dose.
Added for clarification
Non-substantial
Section 1.3 
Table 1 and 
Table 2
Updated to clarify FeNO 
measurement is to be 
Added for clarification
Non-substantial


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Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
performed in the morning 
and evening.
Section 1.3 
Table 2
Removal of text in 
footnote u that duplicated 
central laboratory 
assessment. 
Removed for clarification
Non-substantial
Section 4.1.3
Bullet added to allow 
centralised assessments to 
be performed locally 
during study disruptions 
due to cases of civil 
crisis, natural disaster, or 
public health crisis.
Added for clarification
Non-substantial
Section 4.4.1, 
Section 7, 
Section 7.1.1, 
Section 7.1.2.1, 
Section 7.1.2.2, 
Section 8.1.5
Study stopping and 
suspension criteria 
redefined to distinguish 
between Part 1 and 
Part 2.
Study stopping criteria 
adjusted to reflect the role of 
the DSMB in evaluating all 
clinical data, including 
spirometry, as applicable to 
the larger sample size and 
expected variability in the 
Part 2 participant population. 
Individual suspension and 
stopping criteria amended to 
distinguish between criteria 
for Part 1 and Part 2 as 
applicable to different 
participant populations and 
variability in home 
assessment spirometry (no 
residential period in Part 2)
Substantial
Section 5.1
Updates added 
throughout criteria to 
clarify that reference to 
Visit 1 includes the 
Screening Period 
Added for clarification
Non-substantial
Section 5.1.2, 
Section 6.5
Additional guidance on 
dose stability and 
ICS-LABA device in 
inclusion criteria 18.
Added for clarification
Substantial
Section 5.1.2
Inclusion criteria 20 
amendment to extend the 
period of exacerbations 
from 12 months to 
Amended to optimize 
selection of the participant 
population in view of the 
Substantial


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
3 years prior to 
Screening.
SARS-CoV-2 pandemic 
restrictions
Section 6.1.3
Text updated to clarify 
participants in Part 2 
receive training at Visit 3 
only.
Updated for clarification
Non-substantial
Section 8.1.12
Clarification on the term 
‘severe exacerbation’. 
Added for clarification
Non-substantial
Section 8.1.5, 
Section 8.3.5
Clarification on AESI 
definition to distinguish 
respiratory infections 
from non-respiratory, to 
clarify AESI reporting 
based on Investigators' 
assessment.
Added for clarification
Non-substantial
Amendment 6 (03 Aug 2022)
The Clinical Study Protocol (CSP) version 6.0, 04 Mar 2022 has been amended to optimize 
recruitment into the mg dose arm which is expected to inform the primary endpoint. The 
CSP changes include the removal of the 
mg dose and stopping the
mg dose arm in Part 2. 
The 
mg dose level has been removed in Part 2 as data from earlier studies indicate that 
similar efficacy is expected at the 
mg dose. The rationale to stop randomisation to the 
mg dose arm in Part 2 is to optimize recruitment to reach the required number of evaluable 
participants for the primary endpoint comparison of efficacy between mg and placebo. The 
mg will be evaluated to inform the dose-response, safety profile and PK profile. The 
inclusion/exclusion criteria have been amended following the safety review committee 
outcome for Part 1 of the study, aligning with the intended target population of moderate to 
severe asthma patients and considering general medical treatment and practice. Furthermore, 
the Schedule of Activities has been modified to simplify the protocol, decrease the number of 
assessments and reduce patient and site burden.
Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 1.1
Section 1.3
Section 3
Section 4.1.2
Section 4.2
Change from baseline 
SGRQ score to Week 4 
has been removed as 
secondary endpoint
SGRQ removed as ACQ-6 is 
considered sufficient to 
inform Patient Reported 
Outcome scores over the 
4 week treatment period
Substantial
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 8.1.10
Section 9.4.2
Appendix J
References
Section 1.1
Section 3
 
 
 
 
 
 
Non-substantial
Section 1.1
Section 4.1
Updated number of 
countries participating in 
the study
Updated recruitment planning
Non-substantial
Section 1.1
Section 4.1.2
Section 9.2
Updated section based on 
amended study design in 
Part 2: Total number of 
participants amended 
from 300 to 
approximately 180 by 
removing the 
mg dose 
arm and stopping 
recruitment into the mg 
dose arm
Phase 1 study data indicate 
similar efficacy is expected at 
the 
mg dose, 
therefore evaluating the mg 
dose is sufficient to inform 
the primary endpoint. 
Stopping the mg dose arm 
will optimize recruitment to 
reach the required number of 
evaluable participants for the 
primary endpoint comparison 
of efficacy between mg and 
placebo. The mg will be 
evaluated to inform the 
dose-response, safety profile 
and PK profile.
Substantial
Section 1.1
Section 9.4.2.2
Table 4
Change from baseline in 
post-bronchodilator FEV1
average over the 4-week 
Treatment period
Correction as 
post-bronchodilator 
spirometry is not performed 
during the treatment period
Non-substantial
Section 1.2
Updated schema 
consistent with study 
design update
Updated to reflect removal of 
mg dose and adjusted 
recruitment into the mg 
dose arm in Part 2
Non-Substantial
Section 1.3
Updated study drug 
inhalation training to be 
added at Visit 2 (run-in) 
for both Part 1 and Part 2
To correct inconsistencies in 
the protocol
Non-substantial
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 1.3
Mandatory SARS-CoV-2 
PCR to be removed from 
screening visit
Amended to permit 
Investigators to perform 
SARS-CoV-2 PCR tests as 
per local guidelines and as 
clinically indicated
Non-substantial
Section 1.3
Part 2 Schedule of 
assessments updated to 
reflect updated endpoints, 
removal of 
 
 timepoints, 
laboratory sampling and 
footnote amendments 
made in spirometry 
footnote k, ECG footnote 
m, PK measurements-
footnote x and Proposed 
samples and time 
footnote aa
Assessments aligned with 
updated endpoints. Removal 
of blood sampling and/or 
assessments at run-in, Day 7 
and Day 56 not required to 
inform primary or secondary 
endpoints. Reduction in 
overall number of procedures 
to reduce protocol 
complexity, site and patient 
burden.
Non-substantial
Section 1.3
Part 1 Schedule of 
Assessments updated
For clarification
Non-substantial
Section 1.3
Section 8.1.1
Clarification on 
post-randomisation 
spirometry assessment 
time window
For clarification
Non-substantial
Section 2.3.1.1
Further risk mitigation 
section updated
Section reworded and aligned 
with exclusion criteria update
Substantial
Section 4
Updated Figure 3 based 
on updated study design
To update study design and 
number of countries 
participating in the study
Non-Substantial
Section 4.1.2
Section 5.1.2
Section 5.1.4
Part 2 randomisation 
criterion updated FEV1
range inclusion criteria to 
50% to 85%.
Amended throughout the 
protocol as applicable 
Amended following positive 
outcome of Part 1a SRC and 
to align with intended target 
population
Substantial
Section 5
Updated text to clarify 
CRP retest at Visit 2 may 
be repeated during the 
run-in period
For clarification
Non-substantial
CCI


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 5.1
Updated on female and 
male contraception 
requirements after last 
study dose
Updated to reflect AZD1402 
short half-life and time 
required for epididymal 
maturation and production of 
seminal fluid in an 
environment which is 
investigational drug free
Substantial
Section 5.1
Section 5.3.4
Removal of inclusion 
criterion that a 
participant’s 
influenza/pneumonia 
vaccination should be up 
to date as per local 
guidelines, and added as 
a recommendation
To reflect real world 
treatment history of target 
population
Substantial
Section 5.1.2
Part 2 inclusion criterion 
updated to include 
historically documented 
evidence of asthma 
within the 5 years prior to 
Visit 1
Updated to permit historical 
evidence of an asthma 
diagnosis 
Substantial
Section 5.1.2
Part 2 updated to include 
patients on 
medium-to-high dose ICS 
for at least 6 months prior 
to screening 
Amended throughout the 
protocol as applicable
Updated to include target 
population of uncontrolled 
moderate to severe asthma 
patients
Substantial
Section 5.2
Separation of exclusion 
criteria and time frame 
added on evidence of any 
active clinically 
important pulmonary 
disease, other than 
asthma, within 5 years at 
screening, and history of 
pulmonary or systemic 
disease, other than 
asthma, that are 
associated with elevated 
peripheral eosinophil 
counts 
For clarification
Substantial


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 5.2
Removal of exclusion 
criteria on participants 
with a positive diagnostic 
assess SARS-CoV-2 
nucleic acid test (PCR), 
and further clarification 
of diagnosis of 
COVID-19
Amended to perform 
diagnostics as per local 
guidelines and as clinically 
indicated 
Substantial
Section 5.2
Criteria for evidence of 
active or untreated latent 
TB infection (LTBI) 
updated
For clarification
Substantial
Section 5.2
Exclusion criteria related 
to current or history of 
malignancy updated
Adjusted as per product 
safety specification 
requirements
Substantial
Section 5.2
Removal of exclusion 
criteria of 
Pre-bronchodilator FEV1
decrease or increase in 
Part 2
Removed as per protocol 
population include 
uncontrolled moderate to 
severe asthma patients
Substantial
Section 5.2
Exclusion criteria 
updated to permit 
inclusion of participants 
with a positive 
anti-hepatitis C antibody 
test and negative PCR 
test 
For clarification
Substantial
Section 5.4
Clarification regarding 
re-screening in 
participants with positive 
SARS-CoV-2
Adjusted to permit 
re-screening within 2 weeks 
where infection has resolved
Non-substantial
Section 6.1.3
Included inhaler training 
at visit 2 for both Part 1 
and Part 2 based on 
schedule of activities
To correct inconsistencies in 
the protocol
Non-substantial
Updated to add flexibility 
to prolong run-in at 
Sponsor’s discretion, in 
the event of technical 
problems and e-diary 
cannot be completed 
For clarification 
Non-substantial


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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 6.5.2
Updated text to align with 
revised inclusion criteria
For clarification 
Non-substantial
Section 6.5.2
Updated medium dose 
ICS for Part 1 and 
medium-to-high dose ICS 
for Part 2
Updated to align with 
updated inclusion criteria
Substantial
Section 8.1.2
Updated text to align with 
inclusion criterium; 
medication withhold 
periods before 
reversibility testing added
For clarification 
Non-substantial
Section 8.1.3
Section 4.1.2
Home FeNO assessment 
removed in Part 2.
Clarification that Home 
FeNO measurements will 
only be performed in 
Part 1
Safety and Secondary FeNO 
endpoints will be informed 
by in-clinic assessments
Non-substantial
Section 1.1
Section 1.3
Section 3
Section 4.1.2
Section 4.2
Section 8.1.10
Section 9.4.2
Appendix H2
Appendix J
References
Change from baseline 
SGRQ score to Week 4 
has been removed as 
secondary endpoint
SGRQ removed as ACQ-6 
considered sufficient to 
inform Patient Reported 
Outcome scores over the 
4 week treatment period
Non-substantial
Section 1.1
Section 1.3
Section 3
Section 4.1.2
Section 8.1.10
Appendix H2
Appendix J
References
 
 
 
Exploratory endpoint 
removed to reduce patient 
burden
Non-substantial
Section 1.1
Section 1.3
Section 3
Section 4.1.2
Section 8.1.4
 
 
Exploratory endpoint 
removed to reduce patient 
burden
Non-substantial
CCI
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Section 
Number and 
Name
Description of Change
Brief Rationale
Substantial/Non-substantial
Section 8.1.10
Appendix H5
Appendix J
References
Section 1.1
Section 1.3
Section 3
Section 4.1.2
Section 8.1.10
References
Change from baseline 
Cough VAS over the 
treatment period has been 
removed as an 
exploratory endpoint in 
Part 2
Clarification that Cough 
VAS will only be 
performed in Part 1
Exploratory endpoint 
removed to reduce patient 
burden
Non-substantial
Section 9.4.4.1
Update on PK parameters
Addition of Dose 
normalised AUClast
To update on PK parameters 
derivations
Non-substantial
Section 9.4.3
Section 9.4.3.1
SAS to be replaced by SS
For clarification
Non-substantial
Section 9.5
Removed option to 
perform interim analysis 
after Part 2a and removed 
reference to Part 2b
Updated based on removal of 
Part 2b
Non-substantial
Section 9.6
Appendix A5.2
Updated SRC data review 
description in line with 
removal of Part 2b
For clarification
Non-substantial


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11
REFERENCES
Fuhlbrigge, et al. 2017
Fuhlbrigge AL, Bengtsson T, Peterson S, Jauhiainen A, Eriksson G, et al. A novel endpoint for 
exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised 
controlled trials. The Lancet. Resp. Med. 2017: 5(7), 577-590.
GINA 2022
Available at https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-
FINAL-22-07-01-WMS.pdf (accessed 02 Aug 2022)
Greening, et al, 1994
Greening AP, Ind PW, Northfield M, Shaw G. Added salmeterol versus higher-dose 
corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Lancet 
1994;344:219–224.
Hopkins, et al 2009
Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item 
Sinonasal Outcome Test. Clin. Oto. 2009;34:447–454.
Jones, et al. 1991
Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Resp. 
Med. 1991; 85: 25-31.
Juniper, et al. 1999
Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a 
questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-907.
Juniper, et al. 2006
Juniper EF, Bousquet J, Abetz L, Bateman ED. Identifying ‘well-controlled’ and ‘not well-
controlled’ asthma using the Asthma Control Questionnaire. Resp. Med. 2006 Apr; 100 
(4):616-621.
Miller, et al. 2005
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation 
of spirometry. Eur Respir J. 2005;26(2):319-38.
Ray, et al. 2016
Ray A, Raundhal M, Oriss TB, Ray P, Wenzel SE. Current concepts of severe asthma. J. Clin. 
Invest. 2016;126:2394–2403.
Reddel, et al. 2009
Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official 
American Thoracic Society/European Respiratory Society statement: asthma control and 


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exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J 
Respir Crit Care Med. 2009;180(1):59–99.
Rothe and Skerra, 2018
Rothe C, Skerra A. Anticalin® proteins as therapeutic agents in human diseases. BioDrugs 
2018;32(3):233-43.
Woolcock, et al. 1996
Woolcock A, Lundback B, Ringdal N, and Jacques LA. Comparison of addition of salmeterol 
to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit. Care Med 
1996;153:1481–88.
World Allergy Organisation 2013
WAO White Book on Allergy | World Allergy Organization (World Allergy Organization). 
Available from: URL: http://www.worldallergy.org/UserFiles/file/WhiteBook2-2013-v8.pdf


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Document Name: d2912c00003-csp-v8
Document Title:
D2912C00003 Clinical Study Protocol version 8
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SAP_001.pdf: 
Parexel International
AstraZeneca
D2912C00003
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 1 of 64
Parexel International
AstraZeneca
D2912C00003
A Two-part Phase IIa Randomised, Double-blind, Placebo-controlled, Dose-ranging, Multi-centre 
Study to Assess Efficacy and Safety of Inhaled AZD1402 Administered as a Dry Powder Twice 
Daily for Four Weeks in Adults with Asthma on Medium-to-High Dose Inhaled Corticosteroids
Statistical Analysis Plan
Version: 5.0
Parexel Project Number: 248066


Parexel International
AstraZeneca
D2912C00003
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 2 of 64
SPONSOR SIGNATURE PAGE
Approved by:
_________________________
_______________
           Date
AstraZeneca
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Parexel International
AstraZeneca
D2912C00003
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
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TABLE OF CONTENTS
1
INTRODUCTION.............................................................................................................. 11
2
STUDY OBJECTIVES...................................................................................................... 12
2.1
Part 1 Objectives.................................................................................................................. 12
2.1.1
Primary Objective ......................................................................................................... 12
2.1.2
Secondary Objective...................................................................................................... 12
2.1.3
Exploratory Objectives ................................................................................................. 12
2.2
Part 2 Objectives.................................................................................................................. 12
2.2.1
Primary Objective ......................................................................................................... 12
2.2.2
Secondary Objective...................................................................................................... 12
2.2.3
Exploratory Objectives ................................................................................................. 13
3
INVESTIGATIONAL PLAN ............................................................................................ 13
3.1
Overall Study Design and Plan............................................................................................. 13
3.1.1
Part 1.............................................................................................................................. 13
3.1.2
Part 2.............................................................................................................................. 14
3.2
Endpoints and Associated Variables..................................................................................... 16
3.2.1
Efficacy Endpoints and Associated Variables (Part 2) ................................................ 16
3.2.2
Safety Endpoints and Associated Variables ................................................................. 17
3.2.3
Pharmacokinetic Endpoints and Associated Variables................................................ 22
3.2.4
Immunogenicity Endpoints and Associated Variables................................................. 23
3.2.5
Exploratory Endpoints and Associated Variables ....................................................... 23
4
STATISTICAL METHODS.............................................................................................. 24
4.1
Data Quality Assurance ....................................................................................................... 24
4.2
General Presentation Considerations.................................................................................... 24
4.3
Software .............................................................................................................................. 26
4.4
Study Subjects ..................................................................................................................... 26
4.4.1
Disposition of Subjects .................................................................................................. 26
4.4.2
Protocol Deviations........................................................................................................ 27
4.5
Analysis Sets ....................................................................................................................... 28
4.5.1
Safety Set ....................................................................................................................... 28
4.5.2
Full Analysis set............................................................................................................. 28
4.5.3
Pharmacokinetic Set...................................................................................................... 28
4.5.4
Immunogenicity Set....................................................................................................... 29
4.6
Demographics and Baseline Characteristics ......................................................................... 29
4.6.1
Baseline, Change from Baseline and Percentage Change from Baseline Definitions . 31
4.7
Medical History and Concomitant Illnesses.......................................................................... 32
4.8
Prior and Concomitant Medications ..................................................................................... 32
4.9
Treatment Exposure/Compliance ......................................................................................... 33
4.9.1
Treatment Exposure...................................................................................................... 33
4.9.2
Treatment Compliance.................................................................................................. 33
4.10 Efficacy Evaluation.............................................................................................................. 33
4.10.1
Analysis and Data Conventions .................................................................................... 34
4.10.2
No formal comparisons between the different AZD1402 doses will be conducted. 
Adjustments for Covariates .......................................................................................... 34
4.10.3
Handling of Dropouts or Missing Data......................................................................... 34


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4.10.4
Multiple Comparisons/Multiplicity .............................................................................. 34
4.11 Primary Efficacy Variable (Part 2)....................................................................................... 34
4.12 Secondary Efficacy Variables (Part 2).................................................................................. 35
4.12.1
Forced Expiratory Volume in One Second................................................................... 35
4.12.2
Asthma Control Questionnaire-6.................................................................................. 35
4.12.3
PEF and Asthma Symptoms Score ............................................................................... 35
4.12.4
Fractional Exhaled Nitric Oxide................................................................................... 36
4.13 Exploratory 
 Variables (Part 1)................................................................................ 36
4.13.1
.................................................................................. 36
4.13.2
Fractional Exhaled Nitric Oxide................................................................................... 37
4.13.3
Cough VAS .................................................................................................................... 37
4.14 Exploratory 
 Variables (Part 2)................................................................................ 37
4.14.1
................................................................................................. 38
4.14.2
 
.................................................... 38
4.15 Pharmacokinetics................................................................................................................. 38
4.15.1
Pharmacokinetic Concentrations.................................................................................. 38
4.15.2
Handling of Values Below the Limit of Quantification for Summarising and 
Presentation of Concentration Data ............................................................................. 39
4.15.3
Pharmacokinetic Parameters........................................................................................ 40
4.16 Immunogenicity Evaluation................................................................................................. 41
4.17 Safety Evaluation................................................................................................................. 42
4.17.1
Adverse Events/Serious Adverse Events....................................................................... 42
4.17.2
Clinical Laboratory Evaluation.................................................................................... 45
4.17.3
Vital Signs...................................................................................................................... 47
4.17.4
Electrocardiogram......................................................................................................... 47
4.17.5
Spirometry..................................................................................................................... 48
4.17.6
Fractional Exhaled Nitric Oxide................................................................................... 49
4.18 Data Monitoring Committees............................................................................................... 49
4.19 Determination of Sample Size.............................................................................................. 49
4.20 Change in the Conduct of the Study or Planned Analysis ..................................................... 50
4.21 References........................................................................................................................... 50
5
APPENDICES.................................................................................................................... 51
5.1
Schedule of Assessments ..................................................................................................... 51
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LIST OF TABLES
Table 1
Laboratory Safety Variables................................................................................... 19
Table 2
Schedule of Activities Part 1.................................................................................. 52
Table 3
Schedule of Activities Part 2.................................................................................. 58
LIST OF FIGURES
Figure 1
Study Design Part 1 ............................................................................................... 15
Figure 2
Study Design Part 2 ............................................................................................... 15


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REVISION HISTORY
Version No.
Effective Date
Summary of Change(s)
Draft 0.1
03 Dec 2020
New document
Draft 0.2
29 March 2021
Updated with AstraZeneca (AZ) comments
Draft 0.3
20 April 2021
Updated after Comment Resolution meeting (CRM)
Final 1.0
26 April 2021
Updated after AZ final review
Final 2.0
25 November 2021
Statistical Analysis Plan (SAP) approved and finalised
before the Safety Review Committee (SRC) n. 1: Updated 
to align with the new AZ standards and for the programming 
requirements of the SRC.
Final 3.0
05 July 2022
SAP updated to align with Version 5.0 and 6.0 of the 
Protocol, updating the new standards and some baseline 
definitions. Two endpoints had been removed:

Change from baseline in post-bronchodilator FEV1
average over the 4-week Treatment Period (Visit 3-
Visit 7)

Change from baseline in post-bronchodilator FEV1 at 
Week 2 (Visit 5)
Final 4.0
Last Signature
SAP updated to align with Protocol version 7.0.
Final 5.0
Last Signature
SAP updated for anticipated closure to remove some of the
exploratory endpoints, the Per Protocol analysis and 
subgroup analysis. In addition the AE tables were presented 
for all the AEs after IP and by ADA status. The table 
including the number and percentage of subjects with a 
change from baseline in hsCRP higher then 5 and 10 mg/dL 
by ADA category and the Figure for hsCRP by week by 
ADA status and by treatment group will be also presented.


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LIST OF ABBREVIATIONS
Abbreviation/Acronym
Definition/Expansion
ACQ-6
Asthma Control Questionnaire-6
ADA
Anti-drug antibody
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase/transaminase
ANCOVA
Analysis of covariance
AST
Aspartate aminotransferase/transaminase
ATC
Anatomical therapeutic chemical
AUClast
Area under the serum concentration-curve from zero to the last 
quantifiable concentration
AUCτ
Area under serum concentration-time curve in the dosing interval 
BDRM
Blind data review meeting
BID
Bis in die (twice daily)
BLQ
Below the lower limit of quantification
BMI
Body Mass Index
BP
Blood pressure
CI
Confidence interval
CL/F
Apparent total body clearance of drug from serum after 
extravascular administration
CRF
Case Report Form
CRP
C-reactive protein
CSP
Clinical study protocol
CSR
Clinical study report
Cmax
Maximum observed (peak) serum concentration
CS
Clinically significant
Ctrough
Concentration immediately prior to dosing
CV
Coefficient of variation
DBP
Diastolic blood pressure


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Abbreviation/Acronym
Definition/Expansion
DPI
Dry powder inhaler
DRM
Data Review Meeting
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
eCRF
electronic Case Report Form
EN
Enrolled analysis set
FAS
Full analysis set
FDA
Food and Drug Administration
FeNO
Fractional exhaled nitric oxide
FEV1
Forced expiratory volume in 1 second
FSH
Follicle stimulating hormone
FVC
Forced vital capacity
GeoCV
Geometric coefficient of variation
GeoLSMeans
Geometric LS means
gSD
Geometric SD
HR
Heart rate
ICF
Informed consent form
ICH
International Council for Harmonisation
ICS
Inhaled corticosteroids
IgE 
Immunoglobulin E
IL
Interleuken
IP
Investigational Product
IPD
Important protocol deviations
IS
Immunogenicity set
LABA
Long-acting beta-adrenoceptor agonists
LLOQ
Lower limit of quantification
LOCF
Last observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
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Abbreviation/Acronym
Definition/Expansion
MMRM
Mixed model repeated measure
NA
Not applicable
NCS
Not clinically significant
ND
Not determined
NR
Not reportable
NS
No sample
PCR
Polymerase chain reaction
PD
Pharmacodynamic
PDF
Portable document format
PEF
Peak expiratory flow
PK
Pharmacokinetic
PPS
Per protocol set
PRO
Patient Reported Outcomes
QT
The QT interval is measured from the beginning of the QRS 
complex to the end of the T-wave
QTcB interval
QT corrected using Bazett’s formula
QTcF
QT corrected using Fridericia’s formula
Rac
Drug accumulation ratio
RS
Randomised set
SABA
Short-acting beta agonist
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SBP
Systolic blood pressure
SD
Standard deviation
SE
Standard error of the mean
SoA
Schedule of Assessments
SOC
System Organ Class
SPFQ
Study Participant Feedback Questionnaire
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Abbreviation/Acronym
Definition/Expansion
SRC
Safety Review Committee
SS
Safety set
t
Time of last observed (quantifiable) concentration
t1/2λz
Half-life associated with terminal slope (λz) of a semi-logarithmic 
concentration-time curve
TB
Tuberculosis
TFLs
Tables, Figures, and Listings
tmax
Time to reach peak or maximum observed concentration
ULN
Upper limit of normal
ULOQ
Upper limit of quantification
URC
Unblinded Review Committee
VAS
Visual Analogue Scale
Vz/F
Volume of distribution (apparent) at steady state following 
extravascular administration (based on terminal phase)
WHO-DD
World Health Organization Drug Dictionary
WNL
WinNonlin
λz
Terminal elimination rate constant


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1
INTRODUCTION
Inhaled corticosteroids are considered the “gold standard” in controlling asthma symptoms and 
long-acting beta agonists (LABAs) are the most effective bronchodilators currently available. These 
agents are often given in combination as research has demonstrated that combination therapy of an 
inhaled corticosteroid (ICS) with an inhaled LABA provides better asthma control than high doses of 
ICS alone. It is estimated that 5% to 10% of the population with asthma has symptomatic disease 
despite maximum recommended treatment with combinations of anti-inflammatory and 
bronchodilator drugs. For those moderate/severe asthma participants that remain uncontrolled on 
currently approved inhaled or oral treatments there is a clear unmet need for new therapies before 
introducing systemic biologic treatment. Inhaled drugs are advantageous as the drug delivery is 
localised to the lung (target organ) which may allow for a lower dose than needed with systemic 
delivery. Inhalation is also non-invasive, and thus offers advantages in terms of ease of use. Current 
research is focusing on the different pathological mechanisms or endotypes of severe asthma and it 
is anticipated that this will lead to the development of effective therapies for these subsets of asthma 
patients. AZD1402 is being developed as an inhaled interleukin (IL-)4Rα antagonist controller 
therapy for the treatment of moderate to severe persistent asthma in participants who are not 
adequately controlled on standard of care therapies. The current study aims to assess the efficacy and 
safety of inhaled AZD1402 administered via dry powder inhaler (DPI) 
 
 for 4 weeks in adults with asthma on medium-to-high dose ICS in a 2-part 
randomised, double-blind, placebo-controlled, and multi-centre study.
This Statistical Analysis Plan (SAP) details the statistical methodology to be used for analysing the 
study data and outlines the statistical programming specifications for the tables, figures, and listings 
(TFLs). It describes the variables and analysis sets, anticipated data transformations and 
manipulations and other details of the analyses not provided in the Clinical Study Protocol (CSP).
The SAP describes the statistical analysis as it is foreseen when the study is being planned. If 
circumstances should arise during the study rendering this analysis inappropriate, or if in the 
meantime improved methods of analysis should come to light, different analyses may be performed. 
Any deviations after database lock, reasons for such deviations and all alternative or additional 
statistical analyses that may be performed, will be described in a SAP addendum and discussed in the 
Clinical Study Report (CSR). Any changes to this SAP prior to database lock will be described in a 
new version of the SAP.
The following endpoints will be reported outside of the CSR and are therefore outside of the scope 
of this SAP:

 


The analyses described in this SAP are based upon the following study documents:

Study Protocol, Version 8.0 (24 March 2023).

Annotated Case Report Form 1.0 (21 January 2021).

Annotated Case Report Form updates 7.0 (16 February 2023)
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2
STUDY OBJECTIVES
2.1
Part 1 Objectives
2.1.1
Primary Objective
The primary objective in Part 1 of the study is to evaluate the safety and tolerability of AZD1402 
compared to placebo at different dose levels in adults with asthma controlled on medium-to-high dose 
ICS-LABA.
2.1.2
Secondary Objective
The secondary objective in Part 1 of the study is to investigate the pharmacokinetic (PK) profile and 
immunogenicity of AZD1402, and associated effects on safety.
2.1.3
Exploratory Objectives
The exploratory objectives in Part 1 are:
i)
 
ii)
To assess the effect of AZD1402 compared to placebo on cough by a Visual Analogue 
Scale (VAS) in adults with asthma controlled on medium dose ICS-LABA.
iii)
iv)
 
v)
 
 
Note that, the exploratory objectives iii), iv), and v) described above will not be presented as part of 
the final CSR, therefore, they are not part of this SAP.
2.2
Part 2 Objectives
2.2.1
Primary Objective
The primary objective in Part 2 of the study is to investigate the efficacy of inhaled AZD1402 
compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-
LABA.
2.2.2
Secondary Objective
The secondary objectives in Part 2 are:
i)
To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma 
who are uncontrolled on medium-to-high dose ICS-LABA.
ii)
To investigate the effect of AZD1402 compared to placebo on airway inflammation in 
adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA.
iii)
To investigate the PK profile and immunogenicity of AZD1402, and associated effects on 
safety.
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iv)
To evaluate the safety and tolerability of AZD1402 compared to placebo in adults with 
asthma who are uncontrolled on medium-to-high dose ICS-LABA.
2.2.3
Exploratory Objectives
The exploratory objectives in Part 2 are:
i)
 
ii)
 
iii)
iv)
 
 
Note that, the exploratory objectives ii), iii), and iv) described above will not be presented as part of 
the final CSR, therefore, they are not part of this SAP.
3
INVESTIGATIONAL PLAN
3.1
Overall Study Design and Plan
This is a 2-part Phase IIa, randomised, double-blind, placebo-controlled, multi-centre study to assess 
the efficacy and safety of AZD1402 administered via DPI,
 for 4 weeks in adults with asthma on 
medium-to-highdose ICS.
3.1.1
Part 1
Part 1 of the study will be randomised, double-blind, placebo-controlled, and conducted in parallel 
for the 2 
 dose levels (Part 1a) followed by an unblinded safety review and escalation to the 
 dose (Part 1b) dependent on the outcome of the safety review. Part 1a will consist of 
30 participants who will be randomised 1:1:1 to receive 1 of the 2 
 AZD1402 DPI doses (1 or 
mg) or placebo in parallel. Part 1b will consist of 15 participants who will be randomised 2:1 to
receive the 
 AZD1402 DPI dose (
mg) or placebo. Due to logistical reasons, the 
randomisation in Part 1 will be stratified by site in Australia and Germany.
The target population is adults with asthma (age 18 to 75, inclusive) who are adequately controlled 
on a stable medium dose ICS-LABA (and additional rescue medication as needed), Asthma Control 
Questionnaire-6 (ACQ-6) score ≤1.0, and pre-bronchodilator forced expiratory volume in 1 second 
(FEV1) ≥70%, and with no exacerbation requiring systemic treatment or hospitalisation/emergency 
department visit for asthma during the 12 months prior to study start.
At Visit 3, following the 4-week Run-in Period, participants who remain controlled on a stable dose 
of ICS-LABA, and fulfil the entry criterion of FEV1 ≥70% and have an ACQ-6 score of ≤1.0, will 
be randomised as follows:
Part 1a Lead-in Cohort

AZD1402 inhalation mg 
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
AZD1402 inhalation mg 

Placebo inhalation 
Part 1b Lead-in Cohort

AZD1402 inhalation 
mg 

Placebo inhalation 
Following randomisation to the 4 weeks of dosing, participants will remain at the clinic for a 
mandatory residential period of at least 2 weeks followed by 3 outpatient visits (Day 16, 20, and 24).
The participants are re-admitted to the clinic on Day 28 and discharged the next day (Day 29) 
followed by 2 outpatient visits (Day 30 and 32). Additionally, following the minimum 2-week 
residential period, participants may remain overnight in the clinic any time during Week 3 and 
Week 4 for any reason.
Part 1 will contain a total of 11 visits, and at Visit 7 participants will complete the Treatment Period. 
Two outpatient visits for safety and PK (Visit 8 and 9) are scheduled 1 and 3 days after discharge 
from the clinic. A follow-up (Visit 10) will occur 1 to 2 weeks following Visit 7, and a second and 
final follow-up (Visit 11), will occur 4 weeks after Visit 7.
3.1.2
Part 2
Part 2 will be randomised, double-blind, placebo-controlled and will include approximately 165
participants to evaluate 2 inhaled dose levels ( mg and 
mg) of AZD1402 against placebo. 
Approximately 5 participants will be randomized to mg and 80 participants will be randomized to 
mg and placebo, respectively. The number of subjects enrolled in the mg dose will depend on the 
enrolment rate and the randomisation ratio will change during the study. Patients will be randomised 
2:1 (active to placebo) whilst the 
mg arm is ongoing. Once the
mg has stopped recruiting and 
randomisation continues in the mg and placebo arms, the randomisation ratio will be 1:1 (active to 
placebo).
Part 2, will be started after the unblinded safety review for Part 1a
Part 2 will include:

AZD1402 inhalation mg 

AZD1402 inhalation mg 

Placebo inhalation 
Part 2 will contain a total of 9 visits, and at Visit 7 participants will complete the Treatment Period. 
A follow-up (Visit 8) will occur approximately 1 to 2 weeks following Visit 7, and a second and final 
follow-up (Visit 9), will occur approximately 4 weeks after the end of treatment.
The entire study period for each participant in both Parts 1 and 2, is approximately 3.5 months; a 
2-week Screening Period, a 4-week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of 
Follow-up Period.
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Figure 1
Study Design Part 1
; SRC = Safety Review Committee; wks = weeks.
Participants may also be required to attend a Visit up to 2 years after randomisation for a follow-up ADA sample. 
Figure 2
Study Design Part 2
 SRC = Safety review committee
The Schedule of Assessments (SoA) for the Part 1 and Part 2 are provided in Table 2 and Table 3of 
Appendix 5.1. Further details regarding the study design are provided in Section 4 of the CSP.
A Safety Review Committee (SRC) will review unblinded safety data following completion of Part 1a 
before progressing to Part 1b and Part 2 and following completion of Part 1b treatment period.
A Data Safety Monitoring Board (DSMB) will oversee Part 2 of the study and review the unblinded 
interim outputs. Details of the composition of the DSMB, frequency of meetings and remit can be 
found in the DSMB Charter.
Screening
Run-In (4wks)
AZD1402
mg 
AZD1402 
mg, 
AZD1402 
mg, 
Placebo, 
Follow-Up (4wks)
Visit 1
Week -6
Screening
Visit 2
Week -4
Run-In
Visit 3
Day -1 to 14
Visit 4
Day 16
Visit 5
Day 20
Visit 6
Day 24
Visit 7
Day 28-29
Visit 10
Week 5/6
Follow-Up
Visit 11
Week 8
Follow-Up
Placebo, 
 
Part 1b - Triggered by Part 1a SRC decision
Part 1a 
Visit 8 & 9
Day 30&32
Residential
Optional Residential
Residential
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A separate review committee of AstraZeneca representatives will review the unblinded interim 
outputs for the interim analysis if performed.
3.2
Endpoints and Associated Variables
3.2.1
Efficacy Endpoints and Associated Variables (Part 2)
The primary efficacy variable to assess the primary objective for the Part 2 is the change from baseline 
in pre-bronchodilator FEV1 at Week 4.
The secondary efficacy endpoints to investigate the efficacy of AZD1402 compared to placebo in 
adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA are:

Change from baseline in pre-bronchodilator FEV1 average over the 4-week Treatment Period 
(Visit 3 to Visit 7).

Change from baseline in ACQ-6 at Week 4 and average over the Treatment Period (Visit 3 to 
Visit 7).

Proportion of participants with a decrease in ACQ-6 score of ≥0.5 from baseline to Week 4 
(Visit 7).

Change from baseline in average morning peak expiratory flow (PEF) over the Treatment 
Period (Visit 3 to Visit 7).

Change from baseline in average evening PEF over the Treatment Period (Visit 3 to Visit 7).

Change from baseline in daily average asthma symptom score (AM/PM) over the Treatment 
Period (Visit 3 to Visit 7).
The secondary efficacy variable to investigate the effect of AZD1402 compared to placebo on airway 
inflammation in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA, is the 
change from baseline in fractional exhaled nitric oxide (in-clinic FeNO) at Week 4 (Visit 7) and 
average over the Treatment Period (Visit 3 to Visit 7).
3.2.1.1
Peak Expiratory Flow
Peak expiratory flow will be measured by the participant at-home after completing morning and 
evening e-Diary using a peak flow metre during the Run-in, Treatment Period, and Follow-up Period. 
Participants will be provided with a device at Visit 2 and receive training on PEF monitoring at that 
time. The PEF measurement must be done immediately upon waking up, after the participant has 
cleared out mucus 
 and any rescue medication. The evening 
measurement should be done 
. The measurements should be 
made while standing and the best of 3 attempts recorded/reported.
3.2.1.2
Patient Reported Outcomes
Participants will be asked to complete the Patient Reported Outcomes (PRO) questionnaires on their 
e-Diary device supplied to the site according to the SoA (Table 2 and Table 3). During the study, all 
participants will be required to complete the e-Diary twice daily during the Run-in, Treatment, and 
Follow-up Period.
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3.2.1.2.1 Asthma Control Questionnaire-6
The ACQ-6 was developed to measure asthma control and will be administered to participants as 
indicated in the SoA, Appendix 5.1. In the ACQ-6, participants will be asked to recall how their 
asthma has been during the previous week by responding to one bronchodilation use question and 
5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 
6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. Mean scores of ≤0.75 
indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and 
scores > 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered 
clinically meaningful. More details on the ACQ-6 are included in Appendix H of the CSP.
3.2.1.3
Spirometry
Spirometry measurements (in-clinic spirometry), FEV1 (L) and forced vital capacity (FVC; L), will 
be performed at the timepoints outlined in the SoA, (Table 2 and Table 3). For all participants, 
spirometry testing must be initiated between 6:00 AM and 11:00 AM during the screening or re-
screening period. If possible, all post-randomisation morning spirometry assessments should be 
performed within ± 1.5 hours of the time that the randomisation spirometry was performed. For 
example, if the randomisation spirometry was started at 8:00 AM, then all subsequent spirometry 
testing needs to be initiated between 6:30 AM and 9:30 AM. The evening spirometry should also be 
performed within a 2 hours window relative to the evening assessment time point.
3.2.1.4
Fractional Exhaled Nitric Oxide
FeNO test and FeNO at-home assessments will be measured at the timepoints outlined in the SoA, 
(Table 2 and Table 3). On days when spirometry and FeNO are to be performed on the same day, 
measurement should always be carried out prior to spirometry assessments.
3.2.1.5
Asthma Symptom Score
Severity scores for asthma symptoms will be recorded BID in the morning and evening and 
documented in the e-Diary during the Run-in, Treatment Period, and Follow-up Period. Daytime is 
defined as the time period between the morning lung function assessment (upon rising in the morning) 
and the evening lung function assessment. Night-time is defined as the time period between the 
evening lung function assessment (at bedtime) and the morning lung function assessment.
Asthma symptom scores during night-time and daytime will be assessed by the participant each 
morning and evening according to the following scoring system:
0: You have no asthma symptoms.
1: You are aware of your asthma symptoms, but you can easily tolerate the symptoms.
2: Your asthma is causing you enough discomfort to cause problems with normal activities (or 
with sleep).
3: You are unable to do your normal activities (or to sleep) because of your asthma.
3.2.2
Safety Endpoints and Associated Variables
Vital signs, laboratory abnormalities, and electrocardiograms (ECGs) collected at the Screening visit
and associated with pre-existing medical conditions (for example hypertriglyceridemia, elevated 


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glucose, increased body mass index [BMI]) may be reported as medical history if applicable and 
should not be reported as adverse events (AEs).
3.2.2.1
Adverse Events/Serious Adverse Events
Adverse events, including serious AEs (SAEs) will be collected from the time the subject signs the
Informed Consent Form (ICF), throughout the Run-in, Treatment Period, and Follow-up Period for 
any study phase. All AEs will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA).
The following variables will be collected for each AE:

AE diagnosis/description (verbatim)

The date and time when the AE started and stopped

Maximum intensity

Whether the AE is serious or not

Investigator causality rating against the study intervention (yes or no)

Action taken with regard to investigational product (IP)

AE caused participant’s withdrawal from the study (yes or no)

Outcome
Additional variables will be collected for all SAEs including treatment given for the event:

Date AE met criteria for SAE

Date investigator became aware of SAE

AE is serious due to (ie, seriousness criteria)

Probable cause of death

Date of death

Required in-patient hospitalisation or prolongation of existing hospitalisation

Date of hospitalisation/discharge

Autopsy performed

SAE caused by other medication or study procedure
The following intensity ratings will be used:
1. mild (awareness of sign or symptom, but easily tolerated)
2. moderate (discomfort sufficient to cause interference with normal activities)
3. severe (incapacitating, with inability to perform normal activities)
Some AEs are considered of special interest (AESI).
Additionally, C-reactive protein (CRP) ≥10 mg/L should be used to support the evaluation and 
identification of the potential cause of an AESI and to guide further dosing.
3.2.2.2
Laboratory Assessments
Laboratory assessments (haematology, coagulation, clinical chemistry, urinalysis, QuantiFERON®
Tuberculosis [TB] Gold test, assessments of CRP, severe acute respiratory syndrome coronavirus 2


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[SARS-CoV-2] serology, SARS-CoV-2 polymerase chain reaction [PCR] and urine pregnancy test)
will be performed at the timepoints specified in the SoA, Section 5.1.
Clinical chemistry, haematology, coagulation, and urinalyses will be analysed centrally.
Assessment of CRP, SARS-CoV-2 PCR, urine cotinine, and urine pregnancy tests will be analysed
locally/on site.
Blood samples will be collected for immuno-biomarker testing to assess the safety of AZD1402 and 
per the timepoints mentioned in the SoA (Table 2 and Table 3) for analysis of immuno-biomarkers 
including, but not limited to:
Cytokines, local CRP, high sensitivity (hs)-CRP, and immunoglobulins including immunoglobulin E
(IgE).
The following parameters will be assessed:
Table 1
Laboratory Safety Variables
Haematology/Haemostasis (whole blood)
Clinical Chemistry (serum or plasma)
B-Haemoglobin 
SARS-CoV-2 PCR
B-Haematocrit
S/P-Creatinine
B-Erythrocytes
eGFR
B-Reticulocytes (abs, %)
S/P-Bilirubin, total
B-Platelet count
S/P-Alkaline phosphatase 
B-Mean corpuscular volume
S/P-Aspartate transaminase 
B-Mean corpuscular haemoglobin
S/P-Alanine transaminase 
B-Mean corpuscular haemoglobin concentration
S/P-Albumin
B-Red cell distribution width
S/P-Glucose (fasting and non-fasting)
B-Red blood cell morphology
S/P-Cholesterol***
B-Leucocyte count
S/P-Triglycerides***
B-Leukocyte differential count 
S/P-C-reactive protein
B-Neutrophils (abs, %)
S/P-Potassium
B-Lymphocytes (abs, %)
S/P-Calcium, total
B-Eosinophils (abs, %)
S/P-Sodium
B-Monocytes (abs, %)
S/P-Creatine kinase 
B-Basophils (abs, %)
S/P-high sensitivity C-reactive protein
Urinalysis (dipstick)*
S/P-Direct Bilirubin
U-Haemoglobin/Erythrocytes/Blood 
S/P-Indirect Bilirubin (calculation)
U-Protein/Albumin 
S/P-Gamma glutamyl transferase
U-Glucose 
S/P-Lactate dehydrogenase
U-drug screen**
S/P-Urea nitrogen
U-Specific gravity
S/P-Uric acid
U-pH
S/P-Phosphorus
U-Protein
S/P-Total protein
U-Ketones
S/P-Globulin (calculation)
U-Bilirubin
S/P-Bicarbonate
U-Urobilinogen
S/P-Chloride


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Table 1
Laboratory Safety Variables
U-Nitrite
S/P-Magnesium
U-Leukocyte Esterase
Coagulation
Others
International normalised ratio
Hepatitis B Core Total
Activated partial thromboplastin time
Anti Hep B Surface AG2 Qual
Prothrombin time
Hepatitis B - Qual
Reproductive hormones (Females only)
Hepatitis B - PCR****
U-human chorionic gonadotropin hormone
Hepatitis C - Virus Antibody
S-human chorionic gonadotropin hormone
Hepatitis C - PCR****
S-Follicle stimulating hormone
HIV 1/2 Ag/Ab Screen
Safety-Immuno-biomarkers
HIV-1 Ab Supplemental, Geenius
C-reactive protein
HIV-2 Ab Supplemental, Geenius
Immunoglobulins
HIV Ab Interpretation, Geenius
Cytokines*****
HIV Confirmation
Tryptase
QuantiFERON-TB Gold test
SARS-CoV-2-serology
SARS-CoV-2 PCR
*If clinically relevant abnormalities are detected (positive result in dipstick), the urine sample will be sent to the central 
laboratory for analysis of the sediment.
**Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates
***Cholesterol and triglycerides will be measured at Screening, baseline (Day 1 pre-dose), and Day 28
**** Participants with positive anti HBsAg test, negative HBsAg and negative hepatitis B core total at Screening may 
be included into the study if they have a positive vaccination history. Participants where the interpretation of the 
hepatitis B panel results is inconclusive, may be included following the confirmation of a negative PCR test. 
Assessments will preferably be done centrally but may be done locally 
***** Cytokines may include, but are not limited to IFNγ, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4,IL-6, IL-8,TNFα
Abbreviations: eGFR = estimated glomerular filtration rate; HIV = human immunodeficiency virus; PCR = polymerase 
chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TB = tuberculosis
3.2.2.3
Vital Signs
The vital signs assessments will be performed at the timepoints specified in the SoA, Section 5.1.
The following variables will be collected:

Systolic blood pressure (SBP) (mmHg)

Diastolic BP (DBP) (mmHg)

Pulse rate (beats per minute [bpm])

Oral or tympanic body temperature (°C)

Respiratory rate (breaths per minute)
The vital signs to be assessed (prior to study intervention) are blood pressure (BP; in mmHg) and 
pulse rate (in bpm), temperature (oral or tympanic, in °C), and respiratory rate measurements (breaths 
per minute).
Systolic BP and DBP will be measured after at least 5 minutes resting, and before taking any blood 
sample and conducting any spirometry.


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Measurements will be carried out with the participant in a seated position and preferably always on 
the same arm.
If there is any suspicion of an unreliable measurement, BP will be measured again. The value obtained 
on the second measurement will be considered as definitive and will be recorded on the electronic 
Case Report Form (eCRF).
3.2.2.4
12-lead Safety Electrocardiogram
At the timepoints specified in the SoA, Section 5.1, 12-lead ECGs will be obtained after the subject 
rested in the supine position for at least 5 minutes and should be measured before any blood sampling 
and spirometry assessments are completed. The ECG machine used should automatically calculate 
the heart rate and measures RR, PR, QRS, QT, and QTcF intervals.
The following ECG parameters will be determined:

Heart rate.

RR-interval: Duration in milliseconds between 2 R peaks of 2 consecutive QRS complexes.

PR-interval: Duration in milliseconds from the beginning of wave P to onset of ventricular 
depolarisation (Q and R).

QRS interval: Duration in milliseconds of the QRS complex.

QT interval: Duration in milliseconds from the beginning of Q wave to the end of the T-wave.

QTcB-interval: QT interval corrected using Bazett’s formula (QT[msec]/ RR[sec]1/2).

QTcF interval: QT interval corrected using Fridericia’s formula (QT[msec]/RR[sec]1/3).
The investigator will judge the overall interpretation as normal, abnormal, or borderline and/or 
clinically significant.
3.2.2.5
Physical Examinations
The full and brief physical examinations will be performed at the timepoints outlined in the SoA, 
Section 5.1.
The results of the physical examination at screening will be documented in medical history for each 
subject.
Any new or aggravated clinically relevant abnormal medical physical examination finding compared 
to the baseline assessment will be reported as an AE.
Full
The complete physical examinations will include an assessment of the 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.
Brief (Abbreviated)
The brief physical examinations will include an assessment of the general appearance, skin, abdomen, 
cardiovascular, and respiratory system.


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3.2.2.6
In-clinic and At-home Spirometry
For details on the in-clinic spirometry, refer to Section 3.2.1.3.
During the study period, participants will be required to monitor lung function at-home BID using an 
at-home spirometry device. Participants should follow the relevant medication and other restrictions 
beforehand.
3.2.2.7
Fractional Exhaled Nitric Oxide
For details on this assessment, refer to Section 3.2.1.4
3.2.3
Pharmacokinetic Endpoints and Associated Variables
Blood samples for PK assessments will be collected from all the participants at timepoints mentioned 
in the SoA (Table 2 and Table 3).
Intense sampling will be performed in Part 2 of the study in a subset of approximately 20 participants 
per treatment arm at timepoints mentioned in the SoA (Table 2 and Table 3).. The participants in 
these subsets may be asked to stay in the clinic overnight for logistical reasons depending on the 
sampling timepoints.
Pharmacokinetic analysis for AZD1402 from intense sampling profiles will be performed by 
bioanalytical test sites operated on behalf of AstraZeneca Research and Development.
Where data allow, the following PK parameters for AZD1402 will be derived from serum 
concentrations:
Cmax
Maximum observed serum (peak) drug concentration
tmax 
Time to reach peak or maximum observed concentration or response following drug 
administration
Ctrough
Observed lowest drug concentration reached before the next dose is administered (pre-dose)
z 
Terminal rate constant, estimated by log linear least squares regression of the terminal part 
of the concentration-time curve
t½λz
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve 
AUClast 
Area under the serum concentration-curve from zero to the last quantifiable concentration
AUC
Area under serum concentration-time curve in the dosing interval 
CL/F 
Apparent total body clearance of drug from serum after extravascular administration 
Vz/F
Volume of distribution (apparent) at steady state following extravascular administration 
(based on terminal phase)
Dose normalised AUC
Area under the serum concentration-time curve in the dosing interval divided by the dose 
administered in mg
Dose normalised Cmax
Maximum observed serum (peak) drug concentration divided by the dose delivered in mg
Dose normalised 
AUClast
Area under the serum concentration-curve from zero to the last quantifiable concentration
divided by the dose delivered in mg
tlast
Time of last observed (quantifiable) serum concentration
Rac AUC
Accumulation ratio for AUC
Rac Cmax
Accumulation ratio for Cmax


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The following diagnostic parameters for PK analysis will be provided:
Additional PK parameters may be determined where appropriate.
3.2.4
Immunogenicity Endpoints and Associated Variables
Blood samples for determination of ADA in serum will be collected as specified at timepoints 
mentioned in the SoA (Table 2 and Table 3).
Immunogenicity parameters are:

ADA

Immunogenicity titre
These parameters are tested in an external laboratory. A validated screening assay will be used to 
determine ADA positive samples. Any positive samples will be tested in a confirmatory assay 
whereby the specificity of the ADA response will be confirmed as either positive or negative with 
respect to AZD1402. Titre evaluations are performed on samples that are confirmed positive for 
ADA.
Anti-drug antibodies will be defined as positive when titre measurements reported as ≥10 (minimum 
required dilution).
All these parameters are assigned to the analysis visits and to the analysis phases as described in 
Figure 1 and Figure 2 of Section 3.1.2. Measurements with missing or partial missing dates are not 
assigned to any analysis visit.
The study day of ADA measurement is calculated as the date of the ADA sample collection – the date 
of first IP +1 for ADA sample collected on or after the day of first IP and as the date of the ADA 
sample collection – the date of first IP for ADA sample collected before the day of first IP.
3.2.5
Exploratory Endpoints and Associated Variables
Part 1:
The exploratory endpoints for Part 1 are:

Change from baseline in FeNO at Day 28 and average over the Treatment Period.


Change from baseline average in cough VAS over the Treatment Period.
λz lower
Lower (earlier) t used for λz determination
λz upper
Upper (later) t used for λz determination
λzN
Number of data points used for λz determination
Rsq
Statistical measure of fit for the regression used for λz determination
Rsq adj
Statistical measure of fit for the regression used for λz determination adjusted for the 
number of used data points (n obs)
λz span ratio
Time period over which λz was determined as a ration of t½λz
CCI


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For details on these assessments except cough VAS, refer to Section 3.1.2.
Part 2:
The exploratory endpoints for Part 2 are:

Change from baseline in FeNO (in-clinic).
3.2.5.1
Cough VAS
In Part 1 participants will be asked to complete a cough severity VAS (100 mm linear scale marked 
with a horizontal line by the participant, with 0 mm representing “no cough” and 100 mm representing 
“worst cough”) measuring subjective assessment by the participant for the prior 24 hours for severity 
of cough symptoms. More details on the Cough VAS are included in the Appendix H of CSP.
3.2.5.2
 
3.2.5.3
 
 
 
 
 
 
3.2.5.4
3.2.5.5
Fractional Exhaled Nitric Oxide
For details on this assessment, refer to Section 3.2.1.4.
3.2.5.6
Cough VAS
For details on this assessment, refer to Section 3.2.1.2.
4
STATISTICAL METHODS
4.1
Data Quality Assurance
All tables, figures, and data listings to be included in the report will be independently checked for 
consistency, integrity and in accordance with standard Parexel procedures.
4.2
General Presentation Considerations
‘Baseline’ (unless stated otherwise) is defined as the last available pre-treatment assessment. ‘End of 
Study’ is defined as the last available post-treatment assessment. ‘Treatment Day’ will be calculated 
CCI
CCI
CCI
CCI
CCI
CCI


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relative to the date of randomisation, ie, Treatment Day = Assessment Date - Randomisation Date 
+ 1.
All variables, if not otherwise specified, will be summarised by each Part (Part 1 and Part 2) and study 
treatment group (dose level of AZD1402 or placebo) and AZD1402 overall (when required), using 
descriptive statistics, tables and/or figures, as applicable.
Continuous data will in general be summarised in terms of the mean, standard deviation (SD), median, 
minimum, maximum, and number of observations. Continuous data that are expected to be skewed 
will be presented in terms of the maximum, upper quartile (Q3), median, lower quartile (Q1), 
minimum and number of observations. 
The same level of precision should be used for means, SD, SE, and CIs. The minimum and maximum 
values would normally be reported to the same number of decimal places as the individual values, 
unless a decision has been made to report the summary statistics to a lesser number of decimal places 
than the original data. Medians may be presented to 1 more decimal place than the recorded values 
to account for ties.
In general, the maximum number of decimal places reported shall be 4 for any summary statistic. 
These summaries will be provided by timepoint of assessment as appropriate. If at a given timepoint, 
n < 3, then only n, minimum and maximum will be presented. If n = 3, then only n, mean, median, 
minimum, and maximum will be presented. The other descriptive statistics will be left blank.
A missing category shall be included only for categorical variables where no data is available. The 
missing category will be omitted if there were no missing values for that variable. Categorical data 
will be summarised in terms of the number of subjects providing data at the relevant time point (n), 
frequency counts and percentages.
Percentages will be presented to 1 decimal place. Percentages will not be presented for zero counts. 
Percentages will be calculated using n as the denominator. If sample sizes are small, the data displays 
will show the percentages, but any textual report will describe frequencies only.
Changes from baseline in categorical data will be summarised using shift tables where appropriate.
All confidence intervals (CIs) will be 2-sided 95% CIs, unless stated otherwise, and presented to one 
more decimal place than the raw data recorded in the database. If a model is used to estimate the 
treatment difference, the corresponding CI according to the model will be presented. Otherwise, the 
unadjusted CI will be used. Nominal p-values may also be presented. Care should be taken when 
interpreting CIs and p-values since no correction for multiple testing is done for the endpoints.
P-values greater than or equal to 0.001, in general, will be presented to 3 decimal places. P-values 
less than 0.001 will be presented as “<0.001”.
Descriptive statistics for calculated PK parameters and FeNO will include: n, mean, SD, geometric 
mean, geometric coefficient of variation (GeoCV%), median, minimum and maximum values.
The GeoCV% will be calculated as SQRT(es²-1)*100 where s is the SD of the log-transformed values.
Daylight saving dates will be considered in the calculation of the absolute scheduled and actual times 
and in the duration when this is based on times. Therefore, if any daylight saving change occurs 
during the study development, this will impact the description of the blood sample collections, the 
calculation of the PK parameters and any AE duration in case the time is included in the calculation 
of the duration.


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All other requirements and specifications for programming and presentation of TFLs will be specified 
in the TFL shells document.
The following rules will be applied for any repeated safety assessments:

For repeated assessments at any timepoint before first IP administration (including screening 
values and baseline): the latest assessment obtained per timepoint will be used in the 
calculation of descriptive statistics.

For repeated assessments at any timepoint after first IP (including Follow-up visit): the first 
(non-missing) value after dosing will be used in the calculation descriptive statistics.
The AM and PM assessments will be combined into a daily assessment according to the following 
formula:
Let assessment (Day i) = (PM assessment (Day i) + AM assessment Day (i+1)) / 2
4.3
Software
All report outputs will be produced using SAS® version 9.4 in a secure and validated environment.
PK parameters will be calculated using Phoenix® WinNonlin (WNL) version 8.1 or a later version 
in a secure and validated environment.
All TFLs will be presented in individual files (.rtf or.docx) and also in one portable document format 
(PDF and.docx) book-marked document containing all Tables and Figures (14.x outputs) combined 
and distinct PDF book-marked files for each of the 16.2.x subsections, ie, one for all 16.2.1.x outputs, 
one for all 16.2.2.x outputs, etc.
4.4
Study Subjects
4.4.1
Disposition of Subjects
A clear accounting of the disposition of all subjects who enter the study will be provided for each 
study part, from screening to study completion.
Subject disposition will be summarised for screening failures (in the screening phase), subject 
discontinuation during Run-in phase, randomised subjects separately for each study part. Screening 
failures data will be summarised based on the subjects enrolled in the study.
The following information will be provided:

Number of subjects screened.

Number of screening failures including the reason of failing.
Disposition summaries of randomised subjects will be presented for each study Part by treatment 
group (each dose level of AZD1402, placebo, and pooled AZD1402), and overall and include the 
following information:

Number of subjects randomised.

Number of subjects randomised, not treated, including the reason.

Number and percentage of subjects who started treatment.

Number and percentage of subjects who completed treatment.


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
Number and percentage of subjects who discontinued treatment, including the reason.

Number and percentage of subjects who completed study part.

Number and percentage of subjects who withdrawn from study part, including the reason.

Number and percentage of subjects who discontinued treatment due to global/country 
situation

Number and percentage of subjects who withdraw due to global/country situation.
Percentage will be based on number of subjects started the treatment.
A disposition figure will be also presented for each treatment and study part.
The global country situation study disruption will be summarised. 
A subject who completed the study Part is defined as a subject who completed all scheduled visits 
including the Follow-up visit.
A subject who completed the treatment is defined as a subject who completed the treatment period.
Subjects’ discontinuations will be listed including the date of study discontinuation, treatment 
duration exposure (in days) as well as reason for discontinuation for each study part.
Subject affected by the global/country situation will also be presented in listings.
The number of subjects recruited per country/site will be also summarised by analysis population and 
treatment group.
4.4.2
Protocol Deviations
Important protocol deviations (IPD) are defined as those deviations from the protocol likely to have 
an impact on the perceived efficacy and/or safety of study treatments. The impact of IPD on the 
efficacy and/or safety results will be investigated by assessing the robustness of the study results and 
conclusions to the choice of analysis set, both including and excluding data potentially affected by 
IPD.
This evaluation will be performed on a Blind Data Review Meeting (BDRM) shortly before database 
lock/unblinding. Results and population assignments will be summarised in a BDRM report which 
will be signed off by all relevant scientific experts.
Important protocol deviations and any action to be taken regarding the exclusion of subjects or 
affected data from specific analyses are defined in the project-specific Protocol Deviation 
Specification. The IPD will be summarised for each study part by treatment group (each dose level
of AZD1402, placebo, and pooled AZD1402), and overall.
The IPD include the following:

Inclusion/exclusion criteria deviations.

Treatment deviations.

Visit out of window.

Subjects receiving prohibited concomitant medications.

Procedures not performed or out of window.


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By-participant listings of IPD will be provided.
4.5
Analysis Sets
A summary of the number and percentage of subjects included and excluded from each analysis 
population will be presented by treatment group and overall, for each part of the study.
A by subject listing of analysis set details should be provided. This listing should be presented by 
treatment group and should include subject identifier, exclusion flag for each population, and reason 
for exclusion from each analysis set. All subjects randomised should appear in this listing.
A BDRM will be held before opening randomisation codes in order to assign the subjects to the 
different analysis populations according to the specified definitions. The precise reasons for excluding 
subjects from the study populations will be fully defined and documented in the BDRM Report.
4.5.1
Safety Set
The Safety set (SS) will include all participants who are randomised and received any study 
intervention.
Participants are evaluated according to the actual treatment they received.
If a participant received a different treatment dose than randomised throughout the study, they will 
be analysed according to treated dose, not the randomised dose. If a participant received study 
intervention from the wrong kit for only part of the treatment duration, they will be analysed
according to their randomised dose.
The SS will be used for all safety analyses.
4.5.2
Full Analysis set
The Full analysis set (FAS) will include all participants who are randomised and received any study 
intervention.
Participants are evaluated according to the treatment assigned at randomisation.
The FAS will be used for all analyses of demographic baseline characteristics and efficacy data.
4.5.3
Pharmacokinetic Set
The Pharmacokinetic set (PKS) set will include all participants in the SS who have detectable PK
data, and with no major protocol deviations considered to impact on the analysis of PK data.
The exclusion of any participants or timepoints from the calculation of the PK parameters or statistical 
analysis will be documented by the PK scientist including the reason(s) for exclusion prior to the 
unblinding of the study. The available concentration data and PK parameter data for any participants 
excluded from the PK analysis set will be listed only and presented in the individual figures of 
concentration-time plots.
The PK analysis set will be used for all PK analyses. For the SRCs at completion of Part 1a before 
progressing to Part 1b/2a and from Part 1b before progressing to Part 2b the protocol deviations for 
the PK set will not be evaluated.


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4.5.4
Immunogenicity Set
The Immunogenicity set (IS) will include all participants in the SS with at least 1 post-treatment ADA 
result (positive or negative), with exception for any analysis of relationship of ADA with PK where 
will instead include all participants in the PK set.
The immunogenicity analysis set will be used for all ADA analyses.
All the immunogenicity parameters and listings will be based on the IS and presented for each 
treatment group.
4.6
Demographics and Baseline Characteristics
Analyses of demographic and baseline characteristics will be performed on the FAS.
Demographic characteristics to be assessed are age (years), sex, race, ethnic group and country. Age 
groups 18 to 64, 65 to 75 will also be presented (for EudraCT reporting).
For demography, height/weight baseline is defined as the assessment on screening
Participant baseline characteristics to be assessed are height (cm), weight (kg), BMI (kg/m2), CRP
(mg/L) and Eosinophils count (10^9 /L), and smoking history.
Asthma characteristics at baseline will include: time since asthma diagnosis, time since last 
exacerbation, number of exacerbations and most recent exacerbation type in the 12-month period 
preceding the subject enrolment in the study.

Time since asthma diagnosis (years) is calculated as follows:
(Asthma diagnosis date-Screening date/Re-screening date) /365.25

Time since last exacerbation (days) is calculated as follows: 
(Last exacerbation date- Screening date/Re-screening date) + 1
For missing day and/or month the following strategy will be followed:

Initial asthma diagnosis date/last exacerbation date with valid year and month but missing 
day:
Such a date will be assumed at the 15th of the month in the Year.

Initial asthma diagnosis date with valid year but missing month and day:
Such a date will be assumed at the 15th of June in the Year,
Baseline lung function data to be assessed for Part 1 include:

In-clinic pre-bronchodilator FEV1 and FVC in absolute value (L) and percent of predicted 
values (% PN).

In-clinic pre-bronchodilator ratio FEV1/FVC (%).

Home assessment pre-bronchodilator spirometry absolute values of FEV1 (L).

In-clinic FeNO (part per billion [ppb]) (geometric mean and geometric coefficient of variation 
[GeoCV (%)] will be presented instead of mean and SD for this variable).

FeNO at home assessment (ppb) (geometric mean and GeoCV [%] will be presented instead 
of mean and SD for this variable).


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Lung function and reversibility data at screening to be assessed for Part 2 include:

In-clinic pre-bronchodilator FEV1 and FVC in absolute value (L) and percent of predicted 
values (% PN).

In-clinic pre-bronchodilator ratio FEV1/FVC (%).

Home assessment pre-bronchodilator spirometry absolute values of FEV1 (L).

In-clinic post-bronchodilator FEV1 and FVC in absolute value (L) and percent of predicted 
values (% PN).

In-clinic post-bronchodilator ratio FEV1/FVC (%).
Baseline lung function data to be assessed for Part 2 include:

In-clinic FEV1 in absolute value (L) 

In-clinic FeNO (part per billion [ppb]) (geometric mean and geometric coefficient of variation 
[GeoCV (%)] will be presented instead of mean and SD for this variable).
Baseline diary data to be assessed for 
 Part 2 include:

ACQ-6 score
Baseline diary data to be assessed for Part 1 include:

Cough VAS (mm)
Baseline diary data to be assessed for Part 2 include:

Morning PEF (L/min).

Evening PEF (L/min).

Daily asthma symptom score.
The daily values of rescue medication use and of asthma symptom scores are calculated as the mean 
of the evening measurement for day n and the morning measurement for day n + 1.
Additional baseline assessments to be assessed for Part 1 and Part 2 include:

Eosinophils count (109/L).

hsCRP (mg/L).
Additional baseline assessments to be assessed for Part 2 include:

Eosinophils count group (cells/μL): < 300, ≥300.
The baseline assessments detailed above will be summarised by treatment group (each dose level of 
AZD1402, placebo, and pooled AZD1402) and overall.
By-participant listings of demographics, participants characteristics, asthma history will be provided 
for the randomised subjects. For weight, height and BMI, and asthma exacerbation the listings will 
be presented for the safety set. All listings will be presented for each study Part.
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4.6.1
Baseline, Change from Baseline and Percentage Change from Baseline Definitions
In general, the baseline which will be used in calculation of change from baseline will be the last 
value obtained before first study intervention.
Exceptions to the general definition of baseline (for calculation of change from baseline) are the 
following:

In-clinic FeNO test: baseline is defined as the mean of measurements at Day -1 and at Day 1
morning pre-dose at Visit 3 in Part 1 and as Day 1 morning pre-dose at Visit 3 in Part 2.

FeNO at home assessments: baseline is defined as the mean of all available measurements 
during the 7 days period prior to Day 1 in Part 1.

In-clinic pre-bronchodilator FEV1, FVC and FEV1/FVC in absolute values and in percent of 
predicted values: baseline for Part 1 is the mean of measurements at Day -1 and at Day 1
morning pre-dose at Visit 3; for Part 2 is the pre-bronchodilator assessment at Visit 1.

In-clinic FEV1 is the mean of Day -1 and Day 1 morning pre-dose at Visit 3 for Part 1 and is 
the mean of measurements at Day 1 pre-dose timepoints (15 and 45 minutes pre-dose) for 
Part 2.

In-clinic post-bronchodilator FEV1, FVC and FEV1/FVC in absolute values and in percent of 
predicted values: baseline is the measurement at Visit 1 (1 measurement) within performed 
15 to 30 minutes after inhalation of 400 μg of salbutamol.

FEV1 home spirometry: baseline is defined as the mean of all available measurements during 
the 7 days period prior to Day 1 in both Part 1 and Part 2. i.e. The baseline for the morning 
assessments will be: the mean of all available morning measurements in the 7 days period 
prior to Day 1. Same approach will be used for the baseline for the evening assessments.

e-Diary variables (cough VAS, 
, evening PEF, daily asthma symptom 
score): baseline is average over measurements on the 7 days prior to randomisation. For the 
morning assessments of PEF, daily use of rescue medication and asthma symptoms the 
baseline is average over morning assessments from Day -6 to Day -1 and the Day 1 pre-dose 
assessment.
For e-Diary any study day will be derived relative to randomisation.
In case of missing values among the measurements defining the baseline of the e-Diary variables, the 
baseline will be defined as the mean of all available measurements in the 7 days period. In all other 
cases of missing values in measurements defining a baseline, the baseline value will be defined as the 
last non-missing value prior to Day 1.
Change from baseline will be defined as the value post-dosing minus the baseline defined, for each 
timepoint.
Percent change from baseline will be calculated as:

Percent change from baseline = ((visit value – baseline value)/baseline value) ×100%
The average change from baseline over the treatment period will be calculated from the subjects’ 
average measurements of all assessments performed while subjects are on-treatment, minus the 
baseline value.
If either a visit value or the baseline visit value is missing, the absolute change from baseline value 
and the percent change from baseline will also be set to missing.
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4.7
Medical History and Concomitant Illnesses
Medical and surgical history (presented together) and concomitant illness will be listed by subject 
including treatment, description of the disease/procedure, MedDRA System Organ Class (SOC), 
MedDRA preferred term, start date and stop date (or ongoing if applicable) based on the FAS.
A summary of the number and percentage of subjects with any relevant medical history, surgical 
history and concomitant illness will be summarised based on the FAS for each study Part by each 
dose level of AZD1402, placebo and pooled AZD1402 and overall, by SOC and preferred term.
4.8
Prior and Concomitant Medications
Prior medication stopped prior to the first dose of IP (exclusive), as well as all concomitant 
medications taken during the conduct of the study will be described.
Prior and concomitant medication will be coded according to the World Health Organization Drug 
Dictionary (WHO-DD), version March 2020 or later.
Medication start and stop dates will be compared to the date of first dose of study medication to allow 
medications to be classified as either prior only, both prior and concomitant, or concomitant only. 
Medications starting after the completion + 4 days/discontinuation of the treatment/will be listed but 
will not be classified or summarised.
Medications that started and stopped prior to the first dose of IP (exclusive) will be considered as 
prior medications. Any medication or vaccine (including over the counter or prescription medicines, 
vitamins, and/or herbal supplements or other specific categories of interest) that starts after first dose 
of IP will be recorded as concomitant.
If a medication starts prior to the first dose of IP and continued on or and stops after first dose of IP
then the medication will be classified as both prior and concomitant. Medications will be classified 
as concomitant only if they have a start date on or after first dose of IP and during the study conduct 
(including Follow-up Period).
If medication start and/or stop dates are missing or partial, the dates will be compared as far as 
possible with the date of the first dose of IP. Medications will be assumed to be concomitant only, 
unless there is clear evidence (through comparison of partial dates) to suggest that the medication 
started prior to the first dose of IP. If there is clear evidence to suggest that the medication started 
prior to the first dose of IP, the medication will be assumed to be both prior and concomitant, unless 
there is clear evidence to suggest that the medication stopped prior to the first dose of IP. If there is 
clear evidence to suggest that the medication stopped prior to the first dose of IP, the medication will 
be assumed to be prior only.
Prior and concomitant medications will be listed by subject, treatment group, and study part and will 
include the following information: reported name of drug, medications or therapy, anatomical 
therapeutic chemical (ATC) and generic drug name, the route of administration, dose, frequency, 
study day of start of medication and duration, and indication.
A summary of prior medications received and concomitant medications, preferably by ATC level 4 
category when possible or the highest ATC level when level 4 is not available and generic drug name,
and by treatment part will be reported. 
The duration will be calculated as:


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
Duration (in hours) = end date/time – start date/time, in case date and time is available.

Duration (in days) = (end date – start date) + 1, in case only date is provided.
The duration may be presented in hours or days in the listing depending on the applicability to the 
emerging data. For medications with partial or completely missing start date/times and/or end 
date/times, the duration will not be calculated.
For summary tables, multiple records for a subject in the same ATC level 4 category when possible 
or the highest ATC level when level 4 is not available and generic drug name will be counted only 
once.
4.9
Treatment Exposure/Compliance
4.9.1
Treatment Exposure
In the assessment of the treatment exposure, interruptions will be considered.
When there is no interruption treatment exposure duration (in days) will be calculated as follows:
Treatment exposure duration (in days) = min (date of last dose received, date of death, data of data 
cut-off) - date of first dose received) + 1.
When there is any interruption treatment exposure duration will be calculated as follows:

for each interruption the duration of interruption will be calculated as follows:
(date of first dose received after the interruption - date of first day of interruption).

the treatment exposure duration (in days) will be calculated as follows:
Treatment duration (in days) = (date of last dose received, date of death, data of data cut-off -
date of first dose received) + 1 – (sum of interruptions).
Treatment duration of exposure (days) will be summarised per each Part by treatment for the SS, 
using descriptive statistics.
A by subject listing of drug administration data will be provided.
4.9.2
Treatment Compliance
Compliance will be assessed by checking the daily e-Diary and eCRF.
For all treatments, treatment compliance will be calculated as:
Treatment compliance (%) =
    ! "!# ! $"
   $%!! (&' (∗) "!# ! $" × 100.
*The number of doses planned is 55 since there is only 1 dose in the morning of Day 28.
Compliance is expected to be ≥80% during the Treatment Period.
4.10 Efficacy Evaluation
All the efficacy analysis will be based on FAS.


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4.10.1 Analysis and Data Conventions
No statistical hypotheses will be tested in Part 1 (Lead-in Cohort) of this study. Part 2 (Main cohort) 
of this study aims to demonstrate that AZD1402 improves FEV1 compared to placebo.
The null hypotheses for the primary analysis in Part 2 is that there is no difference in the change from 
baseline at Week 4 (Visit 7) in pre-bronchodilator in-clinic FEV1 in AZD1402 treated participants 
compared to placebo-treated participants.
The following comparisons will be performed:

AZD1402 inhalation mg 
 versus placebo inhalation 
.

AZD1402 inhalation mg 
 versus placebo inhalation 
4.10.2 No formal comparisons between the different AZD1402 doses will be conducted.
Adjustments for Covariates
The primary efficacy analysis for Part 2 will be adjusted for the following baseline covariates:
1.
Country (stratification variable)
2.
Baseline FEV1
4.10.3 Handling of Dropouts or Missing Data
With exception of some dates for the AEs calculation, missing data will not be imputed.
In case the end date of the treatment is known but the time is missing, then end time will be imputed 
with a time of 00:00. 
The analysis based on mixed model for repeated measure (MMRM) will be performed using only the 
observed measurements without imputation of missing values.
4.10.4 Multiple Comparisons/Multiplicity
No adjustments for multiple testing will be performed.
4.11 Primary Efficacy Variable (Part 2)
The primary variable for the assessment of efficacy for Part 2 is the change from baseline 
pre-bronchodilator in-clinic FEV1 at Week 4.
The change from baseline in pre-bronchodilator FEV1 will be analysed using MMRM with treatment 
group, week (1 to 4), country, baseline FEV1, and treatment-by-week interaction as fixed effects and 
with participant as random effect. In this model, Week 1 to Week 4 corresponds to Visit 4 to Visit 7.
The within participant correlation will be modelled using the unstructured covariance matrix. The 
Kenward-Roger approximation will be used to estimate the degrees of freedom. The REML method 
will be applied.
If the estimating algorithms will not converge, the following steps will be taken to simplify the model 
until convergence is achieved:
1. As a first step, try in order these 3 covariance structures: Toeplitz, the first-order 
autoregressive, and compound symmetry. Stop as soon as convergence is achieved.
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2. If step 1 does not work, the treatment-by-week interaction will be removed from the last model 
in step 1, ie, from the model with compound symmetry.
3. In case non-convergence persists, the analysis will be changed to use the analysis of 
covariance (ANCOVA) instead of mixed-effects model for repeated measures.
Each treatment effect and treatment comparisons (all active treatments to placebo) will be estimated 
by the Least Square means (LS means) and the difference in LS means at the corresponding week
(Week 1, Week 2, Week 3, Week 4) on the treatment-by-week interaction, along with their standard 
errors (SE) and 95% CIs, and the p-value corresponding to the between-treatment group difference.
A plot showing the LS mean change (+/- SE) from baseline in FEV1 over time within each treatment 
group will be provided.
Missing values will not be imputed. In this analysis it is thus assumed that any missing FEV1 values 
are missing at random.
A listing of the primary efficacy data will be provided based on the FAS.
4.12 Secondary Efficacy Variables (Part 2)
4.12.1 Forced Expiratory Volume in One Second
The analysis of change from baseline in pre-bronchodilator in-clinic FEV1 average over the treatment 
period will be conducted as part of the analysis for the primary endpoint as described in Section 4.11.
The overall treatment effect and treatment difference over the 4-week treatment period will be 
estimated by the LS means and the difference in LS means on the treatment factor, along with the
SEs, and 95% CIs and the p-value corresponding to the between-treatment group difference.
4.12.2 Asthma Control Questionnaire-6
A summary by treatment group (different doses of AZD1402, pooled AZD1402 and placebo) in terms 
of absolute values at baseline and average over the treatment period, as well as change from baseline 
and its average over the treatment period, will be presented for ACQ-6. Information from ACQ-6 
assessments will also be listed. The average over the treatment period will be calculated from the 
subjects’ average measurements of all assessments performed while subjects are on-treatment. Also, 
the number and percentage of participants with a decrease in ACQ-6 score of ≥ 0.5 (responders) over 
the treatment period for each treatment group will be described.
4.12.3 PEF and Asthma Symptoms Score
A summary by treatment group (different doses of AZD1402, pooled AZD1402 and placebo) in terms 
of absolute values at baseline and average over the treatment period, as well as change from baseline 
and its average over the treatment period, will be presented for average morning PEF, average evening 
PEF and in daily average asthma symptom score (AM/PM).
The average morning PEF will be calculated as:
(sum of morning PEF values in treatment period) / (number of morning e-Diary sessions 
completed during period).
The average evening PEF will be calculated analogously.


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Daily asthma symptom score for day n will be the average of the evening score recorded for day n 
and the morning score for day n+1.
The average daily asthma symptom score will be calculated as:
(sum of daily values in treatment period) / (number of calculated daily values during period).
4.12.4 Fractional Exhaled Nitric Oxide
The analysis of change from baseline in log transformed FeNO will be performed as described for 
the primary endpoint in Section 4.11. These analyses will be done on the natural log scale and the 
results will be back-transformed to linear scale. Hence treatment effects will be presented in terms of 
Geometric LS means (GeoLSMeans) and treatment differences and associated CIs will be presented 
in terms of GeoLSMeans ratios. Due to the log-transformation, the GeoLSMeans represent a relative 
change from baseline rather than an absolute change from baseline.
Percentage change from baseline in FeNO at each week and average over the treatment period will 
be summarised by treatment group and the following summary statistics will be presented: n, 
geometric mean, GeoCV (%), median, minimum, and maximum.
For repeated follow-up post-baseline measurements that are taken on the same day and time as a 
scheduled visit and time point, the average response value of the morning assessments will be used.
The average over the treatment period will be calculated from the subjects’ average measurements of 
all assessments performed whilst subjects are on-treatment between Visit 3 and Visit 7. 
All the efficacy variables will be presented in listings.
The following figures will be presented:

In-clinic FeNO, individual subject data over time.

Mean FeNO in-clinic absolute values (ppb) by week

Mean FeNO in-clinic percentage change from baseline by week

GeoLSMeans of the ratio (post/baseline) (+/- SE) in FeNO over time within each treatment 
group will be provided.
4.13 Exploratory 
 Variables (Part 1)
All the exploratory analysis will be presented based on FAS. The exploratory efficacy variables will 
be evaluated with descriptive statistics. All the efficacy variables will be presented in listings
4.13.1
 
 
 
 
 
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4.13.2 Fractional Exhaled Nitric Oxide
A summary by treatment group (different doses of AZD1402, pooled AZD1402 and placebo) in terms 
of absolute values (ppb) at baseline (Visit 3) and at each day during treatment as well as the average 
over the treatment period, will be presented. Moreover, change from baseline at each visit during 
treatment and over the treatment period will be calculated as % change from baseline.
The average over the treatment will be calculated from the subjects’ average measurements of all 
assessments performed whilst subjects are on-treatment.
Fractional exhaled nitric oxide (ppb) assessments will also be listed.
For FeNO at home assessments, the same summary described above for FeNO test (in-clinic 
assessments) will be presented. The average over the treatment will be calculated as the average of 
all assessments measurements for a given subject during the treatment period.
For repeated post-baseline FeNO test measurements that are taken on the same day and time as a 
scheduled visit and time point, the average response value of the morning pre-dose will be used.
For repeated post-baseline FeNO at home measurements that are taken on the same day and time, the 
highest results of the morning pre-dose will be used.
The following figures will be presented:

In-clinic FeNO, individual subject data over time.

Mean FeNO in-clinic absolute values (ppb) by day

Mean FeNO in-clinic percentage change from baseline by day
4.13.3 Cough VAS
A summary by treatment group (different doses of AZD1402, pooled AZD1402 and placebo) in terms 
of absolute values at baseline, average over the treatment period, and change from baseline average 
over the treatment period, will be presented for cough VAS. Information from the VAS assessments 
will also be listed.
For cough VAS the average is defined as:
(sum of values in treatment period)/(number of e-Diary sessions completed during period)
The average over the treatment will be calculated as the average of all assessments measurements for 
a given subject during the treatment period.
All the efficacy variables will be presented in listings.
4.14 Exploratory 
 Variables (Part 2)
All the exploratory analysis will be presented based on FAS.
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4.14.1
4.14.2
 
 
4.15 Pharmacokinetics
4.15.1 Pharmacokinetic Concentrations
The PK parameters will be summarised and plotted separately for Part 1 and for Part 2 by dose level, 
nominal timepoints (PK Day) and for ADA status. Pharmacokinetic serum concentration data for 
AZD1402, will be listed by dose level (treatment) and subject. Listings will include actual sampling 
times relative to dose administration. Serum concentrations below the lower limit of quantification 
(LLOQ) will be presented as BLQ in the listings. Serum concentrations for AZD1402 will be 
summarised by dose level, and nominal timepoint (PK Day).
Summary statistics for the PK serum concentrations will be presented separately for Part 1 and for 
Part 2 by dose level, nominal timepoints (PK Day) and for ADA status and will include number of 
observations, number of observations below the LLOQ, geometric mean, Geometric CV% (calculated 
as: GeoCV% =SQRT(es²-1)*100; where s is the SD of the log transformed values), geometric mean, 
arithmetic mean, arithmetic SD, median, minimum, and maximum. Any values that are not reportable 
or where no sample is available will be excluded from the summary tables. Three observations > 
LLOQ are required as a minimum for a serum concentration to be summarised. Where there are only
2 observations > LLOQ, these are presented as minimum and maximum and the other summary 
statistics are not calculated.
The following rules will be followed with regards to the number of decimal places and presentation 
of data in the tables and listings of concentration data:

Source data shall be used in all derived PK concentrations without prior rounding.

The mean, SD, geometric mean and median will be tabulated to 1 more significant digit 
compared to the source data, but with a maximum of 4 significant digits.

Minimum and maximum values will be tabulated to the same precision as the source data, but 
with a maximum of 4 significant digits.
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
Geometric CV% will be presented to 1 decimal place.
To visualise the comparison between dose levels the following descriptive PK graphs will be 
generated for each part:

Geometric Mean (± gSD) AZD1402 serum concentration versus time by dose (linear scale 
and semi-log linear scale) presented for all doses overlaid on the same plot for a given PK 
Day (Day 1, Day 28). A different graph will be created for each ADA status.

Geometric Mean (± gSD) AZD1402 serum concentration-time data (linear scale and semi-log 
linear scale) presented for PK Days 1 and 28 overlaid on the same plot for a given dose level.
A different graph will be created for each ADA status.

Individual Ctrough of AZD1402 will be plotted versus study day (linear scale and semi-log 
linear scale) for each dose level and all PK days (Day 1 to Day 56 for Part 1 and Day 1 to Day 
39 for Part 2). A different graph will be created for each ADA status.

Geometric mean (±gSD) AZD1402 Ctrough versus study day (linear scale and semi-log linear 
scale) will be presented for all study days (Day 1 to Day 56 for Part 1 and Day 1 to Day 39 
for Part 2) and by dose overlaid on the same plot. A different graph will be created for each 
ADA status.

Individual serum concentrations of AZD1402 versus actual time by dose will be plotted for 
each subject in linear and semi-log linear scale separately for Day 1 and Day 28.

Individual serum concentrations of AZD1402 versus actual time by dose will be plotted for 
each Subject in linear and semi-log linear scale overlaid on the same figure for Day 1 and Day 
28 (dose levels will be displayed separately).

Box plot of Ctrough over time by ADA category.
4.15.2 Handling of Values Below the Limit of Quantification for Summarising and 
Presentation of Concentration Data
Individual concentrations below the LLOQ of the bioanalytical assay will be reported as BLQ in the 
listings with the LLOQ defined in the footnotes of the relevant TFLs. Individual serum concentrations 
that are Not Reportable will be reported as NR and those that are missing will be reported as NS (No 
Sample) in the listings.
Serum concentrations that are BLQ, NR, or NS will be handled as follows for the provision of 
descriptive statistics:

Any values report as NR or NS will be excluded from the summary tables and figures.

At a time point where less than or equal to 50% of the values are BLQ, all BLQ values will 
be set to the LLOQ, and all descriptive statistics will be calculated accordingly.

At a time point where more than half (but not all) of the values are BLQ, the geometric mean, 
Geometric mean/gD, Geometric mean * gSD and GeoCV% will be set to Not Determined 
(ND). The maximum value will be reported from the individual data, and the minimum and 
median will be set to BLQ.

If all values are BLQ at a time point, no descriptive statistics will be calculated for that time 
point. The arithmetic mean, geometric mean, minimum, median, and maximum will be 


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reported as BLQ and the SD, GeoCV% and geometric mean / gSD and geometric mean * gSD 
as Not Applicable (NA).

The number of BLQ values (n below LLOQ) will be reported for each time point.
Three observations > LLOQ are required as a minimum for a serum concentration to be summarised.
If there are only 2 observations > LLOQ they are presented as minimum and maximum and the other 
summary statistics presented as NA.
Pharmacokinetic concentration and parameter data for subjects excluded from the PK set will be 
included in the data listings, but not in the descriptive or inferential statistics or in mean figures or 
combined individual figures.
4.15.3 Pharmacokinetic Parameters
Pharmacokinetic parameters will be calculated by non-compartmental analysis methods from the 
concentration-time data using Phoenix® WinNonlin® (Version 8.1) or higher following these 
guidelines:

Concentration data will be used as supplied by the analytical laboratory for PK analysis. The 
units of concentration and resulting PK parameters, with the amount and concentration units, 
will be presented as they are received from the analytical laboratory.

Cmax and tmax will be derived directly from the serum concentration-time profiles. For 
multiples peaks the highest post-dose concentration will be reported as Cmax. In the case that 
the multiple peaks are of equal magnitude, the earliest tmax will be reported.

Serum concentrations which are BLQ from the time of pre-dose sampling (t = 0) up to the 
time of first quantifiable concentration will be set to a value of zero. After the first quantifiable 
concentration, any BLQ serum concentrations will be set to missing for all concentration 
profiles.

Where 2 or more consecutive concentrations are BLQ at the end of a profile, the profile will 
be deemed to have terminated and therefore any further quantifiable concentrations will be 
set to missing for the calculation of the PK parameters unless there is a scientific rational not 
to do so, which will be documented in the CSR.

Any embedded BLQ value (between 2 quantifiable concentrations) will be set to missing for 
the purposes of PK analysis.

If an entire concentration-time profile is BLQ, the profile will be excluded from the PK 
analysis.

Terminal elimination half-life, calculated as (ln2)/λz, will be estimated by log-linear LS 
regression of the terminal part of the concentration-time curve. The start of the terminal 
elimination phase for each subject will be defined by visual inspection and will be the first 
point at which there is no systematic deviation from the log-linear decline in serum 
concentrations. A minimum of 3 data points following Cmax and including the last 
measurable concentration will be used in calculating λz. The duration of time over which λz 
should, where possible, span 3 half-lives. The adjusted correlation coefficient (Rsq adj) 
should be ≥0.8.

AUCs (including AUClast and AUC) will be calculated using the linear trapezoidal method 
when concentrations are increasing and the logarithmic trapezoidal method when 
concentrations are decreasing (linear up log down). The minimum requirement for the 


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calculation of AUC will be the inclusion of at least 3 consecutive serum concentrations above 
the LLOQ.

If the concentration at the time of dosing is missing, then this will be set to 0.

Data exclusions from analysis should be avoided. However, in clear cases of technical issues, 
such as documented sample mix up, bioanalytical error or mis-dosing, individual or subject 
level data may be excluded from summaries or summarised separately. Data exclusions will 
be agreed with the AstraZeneca Clinical Pharmacology Scientist and discussed in the CSR.

Pharmacokinetic parameters associated with positive pre-dose value(s) of greater than 5% 
Cmax for the first dose may be excluded from the summary statistics of PK tables and 
statistical analysis at the discretion of the pharmacokineticist.
Pharmacokinetic parameters will be listed by subject and summarised by AZD1402 dose and study 
Part. Descriptive statistics for calculated PK parameters will include: n, mean, SD, geometric mean, 
GeoCV%, median, minimum and maximum values. For tmax, only median, minimum, and maximum 
values will be presented. No descriptive statistics will be determined when fewer than 3 individual 
PK parameters are available.
The following rules will be followed with regards to the number of decimal places and presentation 
of data in the tables and listings for PK parameters:

Individual PK parameters will be presented to 4 significant digits, with the exception of tmax, 
which will be presented to 2 decimal places.

Parameters derived directly from source data (eg, Cmax,) shall be reported with the same 
precision as the source data (if this is not 4 significant digits).

The mean, geometric mean, median, and SD values will be reported to 4 significant digits, all 
other descriptive statistics will be reported to 3 significant digits.

For tmax, the minimum and maximum will be presented to 2 decimal places and all other 
descriptive statistics will be presented to 3 decimal places.

Estimates and CIs in the form of percentages will be presented to 2 decimal places.
4.16 Immunogenicity Evaluation
Anti-drug antibodies will be summarised as categorical variables with the number and percentages 
with a positive result at the specific visit. Immunogenicity titre will be summarised descriptively as a 
continuous variable, only for ADA positive tests, with median, interquartile range, minimum, and 
maximum, at each analysis visit.
ADA will also be summarised based on the IS including the following:

ADA positive at baseline and/or post-baseline (ADA prevalence).

Treatment emergent (TE)-ADA positive (ADA incidence): defined as the sum of treatment-
induced ADA positive and treatment-boosted ADA positive.

Treatment-induced ADA positive: defined as ADA negative at baseline and post-baseline 
ADA positive.

Treatment-boosted ADA positive: defined as ADA positive at baseline and boosted the 
pre-existing titre post-baseline (≥4-fold increase).


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
TE-ADA negative: defined as ADA positive but not fulfilling the definition of TE-ADA 
positive.

Both baseline and post-baseline positive.

Only baseline positive.

ADA persistently positive: defined as either ADA negative at baseline and ADA positive at 
≥2 post-baseline assessments, or ADA positive at last post-baseline assessment.

ADA transiently positive: defined as ADA negative at baseline, having at least one post-
baseline ADA positive assessment and not fulfilling the conditions of ADA persistently 
positive.

TE-ADA positive with maximum titre > median of maximum titres.
Post-baseline includes on-treatment and follow-up phases.
The median of maximum titres is calculated based on the maximum titre for each ADA positive 
subject within each treatment group (including both baseline and post-baseline measurements).
All immunogenicity parameters will also be reported in listing. Days from previous dose of IP will 
be calculated as the ADA date minus date of previous dose. Days from previous dose of IP for ADA 
measured during pre-treatment period will be set to missing. Listings of all subjects excluded from 
the ADA analysis set will also be provided. Listing will be based on SS.
4.17 Safety Evaluation
All safety summaries and analyses will be based upon the SS as defined in Section 4.5.1 and will be 
presented by dose level of AZD1402, pooled AZD1402, and placebo and by study part.
In general, there will be no imputation of missing data for the safety analyses. All safety data 
(scheduled and unscheduled) will be presented in the data listings.
Baseline for safety evaluations will be the last value obtained before first study intervention.
4.17.1 Adverse Events/Serious Adverse Events
Adverse events will be coded using MedDRA latest available version.
All reported AEs will be listed along with the date of onset, date of resolution (if AE is resolved), 
investigator’s assessment of intensity, outcome, action taken with IP, and possible relationship to 
study drug (assessed by investigator). A by subject listing of all AE (including AEs before first dose 
of study medication) will be provided. This listing will include the following information: study 
period, verbatim term, MedDRA SOC, and preferred term, start date/time, end date/time, time from 
last dose, intensity, causality, action taken, whether the AE was classified as serious, the outcome of 
the AE and the concomitant or additional treatment given, if any. Any AE occurring before the first 
dose of IP and/or the AE assessments that are unresolved at the participant’s last assessment in the 
study will be included in the data listings but will not be included in the summary tables of AEs.
Multiple occurrences of an AE in the same subject will only be counted once overall considering start 
date as the first day of first occurrence and stop date the last day of the last occurrence and the AE 
will assigned to the treatment of the first occurrence period study drug. Multiple occurrences of an
AE in the same subject for the same treatment will only be counted once for that treatment.


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The number of subjects will be tabulated also by SOC, preferred term, and treatment.
In the case that, during the study, a subject has more than 1 episode of the same preferred term with 
different levels of intensity, action taken, outcome causality or seriousness, then the maximum 
intensity level, action taken (ie, withdrawn) and outcome (ie, fatal), causality level (ie, related), or 
seriousness level (ie, serious), respectively will be used.
The following ordering will be used to define maximum intensity level, action taken, outcome 
causality level, or seriousness level:

Intensity: Mild < Moderate < Severe

Causality: No < Yes

Seriousness: No < Yes

Action taken: Unknown < Not applicable < Dose not changed < Drug interrupted < Drug 
withdrawn

Outcome: Unknown < Recovered/resolved < Recovered/resolved with sequelae 
< Recovering/ resolving < Not recovered/not resolved < Fatal
A general summary of all AEs will show the number and percentage of subjects with:

Any AE

Any SAE

Any SAE with outcome death

Any AE leading to discontinuation of IP

Any AE leading to withdrawal from study
An overview summary of AEs together with a presentation of AEs (event count) by preferred terms
and sorted by decreasing frequency on preferred term will be also produced. In addition, an overview 
summary of the number and percentage of subjects with AEs and by SOC, preferred term, and 
treatment will be also presented by ADA status.
Additional tables will present the number and percentage of subjects with any AESI occurring after 
first dose (including infection, eosinophilia, and hypersensitivity events) and the in-clinic alerts with
the individual occurrences in those categories.
The AESI presented in the table will be (for in-clinic assessments):

FEV1 drop ≥20% reduction from baseline as informed by in-clinic assessment: information 
extracted from the AE page on the eCRF.

FEV1 drop ≥30% reduction from baseline as informed by:
-
in-clinic assessment.
-
decline is sustained over 2 scheduled consecutive home assessments resulting in either dosing 
suspension or discontinuation (Part 2).

Confirmed fever (> 38°C for > 4 hours)

Wheeze*

Cough*

Dyspnoea/shortness of breath*


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
Infection
-
respiratory tract infection, ideally supported by pathogen identification and confirmation.
-
COVID-19 infection.
-
non-respiratory tract infection.
*Part 1: All new events of wheeze, cough, dyspnoea/shortness of breath.
Part 2: All new worsening events of wheeze, cough, dyspnoea/shortness of breath compared to 
baseline / individual pre-existing disease characteristics as judged by the Investigator.
In the event of suspected respiratory infection, pathogen identification include:

SARS-CoV-2 PCR.

Viral panel which may include but are not limited to influenza (all types), parainfluenza, 
respiratory syncytial virus, human metapneumovirus, adenovirus, and Bordetella pertussis.

Mycoplasma pneumonia and Chlamydophila pneumoniae (sometimes included in viral panel).

Bacterial swab to detect any growth which may include, but are not limited to Streptococcus, 
Klebsiella, Pneumoniae, Pseudomonas, Staphylococcus aureus, E.Escherichia coli, 
Citrobacter, Acinetobacter and Haemophilus influenza.
The number and percentage of subjects who experience one or more AEs will be tabulated by each 
study part, treatment group (dose level of AZD1402, pooled AZD1402, and placebo) and by:

SOC and preferred term.

SOC, preferred term, and maximum intensity.

SOC, preferred term, and relationship to study intervention judged by investigator.
Adverse event summaries will be ordered in terms of decreasing frequency for SOC, and preferred 
term within SOC.
The tables of AE will include all the AEs with an onset date and time on or after the date and time of 
first dose of IP up to the end of treatment + 96 hours. Additional tables including all the AEs 
experienced after the IP until last follow-up (Day 56) and for ADA status will be reported for both 
Part 1 and Part 2.
Adverse events sorted by decreasing frequency and AEs leading to discontinuation of investigational 
product by SOC and preferred term will be summarised.
The number and percentage of subjects who experience 1 or more SAEs will be tabulated by treatment 
group (AZD1402 and placebo) and by SOC and preferred term and by SOC and preferred term and
with outcome of death.
For each subject and each AE, the worst severity recorded will be attributed and used in the 
by-severity summaries. Similarly, the worst causality (most related to treatment) will be attributed 
and used in the by-causality summaries. If severity or causality is missing, a conservative approach 
for AE assessment (taking into account the worst case) will be followed.
Key subject information for participants experiencing SAE with outcome death, SAEs, and AEs 
leading to discontinuation of IP will be presented in a listing. All the AE will be included in the data 
listings.


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For AEs with partial dates/times, worst case is always assumed; if possibly on-treatment, then on-
treatment is assumed, on-treatment AEs will be considered to have the longest possible duration and 
off-treatment AEs will be considered to have the shortest possible duration. In accordance with this 
principle, any AEs with incomplete start and end dates/times will be treated as follows:

AEs with unknown start times, but with start date known, will be imputed with a time of 
00:00, unless the start date corresponds to any given dosing date. In this case the start time 
will be imputed with the time of dosing. If this results in a start date/time after end date/time 
of the AE, then the time will also be imputed with 00:00.

AEs with completely unknown start dates will be imputed with the date and time of dosing, 
unless the end date is known and prior to dosing; in that case the start date will be imputed as 
the date of Screening and a time of 00:00.

AEs with partially known start dates/times will be treated as follows:
-
If only the day is missing, then the day will be imputed with the first day of the month, unless 
the month and year in which the AE started is a month and year in which IP was administered, 
then the day will be imputed with the first day on which IP was administered in that month. 
If this results in a start date after the end date, then the day will be imputed with the first day 
of the month.
-
If only the month is missing and the year is a year in which IP was administered, then the 
month will be imputed with the first month in which IP was administered. If this results in a 
start date after the end date of the AE, then the month will be imputed with JAN. If the known 
year part is not a year in which IP was administered, then the month will also be imputed with 
JAN.
-
If both the day and month is missing and the year is a year in which IP was administered, then 
the day and month will be imputed with the day and month of dosing. If this results in a start 
date after end date, then the day and month will be imputed with 01JAN. If the year is not a 
year in which IP was administered, then the day and month will also be imputed with 01JAN.
-
If only the year is missing, then the year will be imputed with the year of dosing.
4.17.2 Clinical Laboratory Evaluation
Refer to Section 3.2.2.2 for the list of clinical safety laboratory tests to be performed and the SoA 
(Table 2 and Table 3), for timing and frequency.
Laboratory values and immune biomarkers measurements including IFNg, IL-10, IL-12p70, IL-13, 
IL-1b, IL-2, IL-4, IL-6, IL-8, TNFa, CRP, and IgE will be listed by subject and study time point 
including when possible changes from baseline.In case the units and the normal reference ranges are 
not the same for all subjects and assessments, units will be standardised to the same units and 
normalised to the same reference ranges.
The reference ranges and the values outside the clinical reference ranges will be presented and flagged 
in the data listings. The abnormal values will be flagged with ‘L’ for values below the lower limit of 
the clinical reference range and ‘H’ for values above the upper limit of the clinical reference range 
and included in the listings. The Investigator will assess whether the values outside the clinical 
reference range are clinically significant. Clinically significant laboratory values will be recorded by 
the investigator as AEs.


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Descriptive statistics (for clinical chemistry, haematology coagulation parameters and immune
biomarkers) will be presented separately for each part by treatment and time for both absolute values 
(N, mean, SD, median, minimum, maximum) and changes from baseline.
The following figures will be produced:

Subject profile of haematology laboratory data (absolute values) for Part 1 and mean plots for 
Part 2.

Subject profile of clinical chemistry laboratory data (absolute values) for Part 1 and mean 
plots for Part 2.

Subject profile of immune biomarkers (absolute values) for Part 1 and Part 2 

Subject profile of CRP, absolute values and mean plots for Part 1 and Part 2.

Mean immune biomarkers parameters by day, absolute values for Part 1 and Part 2.
Values of the form “< x” (ie, below the LLOQ) or “> x” (ie, above the upper limit of quantification 
[ULOQ]) will be imputed as “x” in the calculation of summary statistics but displayed as “< x” or “> 
x” in the listings.
Shift from baseline to maximum and to minimum on-treatment tables will be presented for laboratory 
parameters (chemistry, haematology and coagulation, urinalysis and immune biomarkers) including
all blood white cells. The number of subjects with treatment emergent haematology abnormalities
will be summarised.
The criteria for the haematology treatment emergent abnormalities (respect to baseline) are: 

Confirmed leucocyte count < 2.0 × 109/L

Confirmed neutrophil count < 1.0 × 109/L

Confirmed platelet count < 75 × 109/L

Confirmed lymphocyte count < 0.5 × 109/L
Shift tables for the immune biomarkers IFNg, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8,
TNFa, CRP, and IgE, will be presented by treatment and separately for each part.
Individual subject data where alanine aminotransferase/transaminase (ALT) and/or aspartate 
aminotransferase/transaminase (AST) and total bilirubin are elevated at any time will be listed 
(ie, ALT and/or AST ≥3 × the upper limit of normal [ULN] and total bilirubin ≥2 × ULN, at any 
time) to evaluate potential Hy’s Law cases.
A figure for both ALT and AST versus total bilirubin expressed as multiple of ULN will be presented. 
Plot will be produced on the log scale, and reference lines will be included at 2xULN for total bilirubin 
and at 3 × ULN for ALT/AST.
Clinical laboratory data will be reported in the units provided by the clinical laboratory for the SRC 
meeting (if applicable), and in System International units in the CSR.
The number and percentage of subjects with a change from baseline in hsCRP higher then 5 and 10 
mg/dL will be also reported by specified ADA status.
Figure for hsCRP over time by ADA status and by treatment group will be presented.


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On-treatment and treatment emergent definition refer all the assessments with an onset date and time 
on or after the date and time of first dose of IP up to the end of treatment + 96 hours.
4.17.3 Vital Signs
Vital signs data will be listed by subject and visit including the planned time point, and reference 
ranges based on SS. Flag for a clinically significant assessment will be provided in the listing.
For each scheduled post-baseline visit, descriptive statistics for all vital sign parameters will be 
presented for absolute values and changes from baseline by treatment group (AZD1402 and placebo) 
and overall, per each study part. Vital sign shift tables from baseline to maximum on-treatment will 
be reported. The number of subjects with treatment emergent vital signs abnormalities will 
summarised considering the following table:
Vital sign
Observed value
Notable change from baseline
Systolic BP (mmHg)
High
≥140
Increase of ≥20
Low
< 90
Decrease of ≥20
Diastolic BP (mmHg)
High
≥90
Increase of ≥10
Low
< 60
Decrease of ≥10
Pulse Rate (bpm)
High
≥110
Increase of ≥20
Respiratory Rate (breaths per minute)
Temperature (°C)
Low
High
Low
High
Low
< 50
> 20/min
< 12/min
> 37.5
< 35
Decrease of ≥20
Abbreviations: BP = blood pressure; bpm = beats per minute.
On-treatment and treatment emergent definition refer all the assessments with an onset date and time 
on or after the date and time of first dose of IP up to the end of treatment + 96 hours.
4.17.4 Electrocardiogram
Standard safety 12-lead ECGs will be performed as shown in the SoA.
The following ECG parameters will be recorded:

QRS interval (msec)

RR-interval (msec)

PR-interval (msec)

QT interval (msec)

QT-interval corrected using the Bazett correction formula (QTcB) (msec)

QT-interval corrected using the Fridericia correction formula (QTcF) (msec)

Heart rate (HR) (bpm)


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The ECG will be evaluated by the investigator as ‘Normal’, ‘Abnormal’ or ‘Borderline’ and will be 
tabulated at baseline versus last value on-treatment by each dose and each part.
All ECG parameters will be listed by subject for each dose cohort and time point and each part. The 
baseline for the ECG measurements will be obtained pre-dose on Day 1.
Descriptive statistics (n, mean, SD, median, minimum, maximum) over time for absolute values and 
changes from baseline will be presented by each dose cohort and each Part. Categorical QT and QTc 
analyses will also be performed.
Shift tables will report the shift from baseline to the maximum value on-treatment: the number and 
percentage of subjects with QT/QTc intervals exceeding some predefined upper limits (eg,
> 450 msec, > 480 msec, > 500 msec for absolute values as well as > 30 msec, > 60 msec for increase 
from baseline) of ECG parameters.
Abnormalities in electrocardiogram data will be listed based on SS.
On-treatment definition refer all the assessments with an onset date and time on or after the date and 
time of first dose of IP up to the end of treatment + 96 hours.
4.17.5 Spirometry
In-clinic and home spirometry values (FEV1 and FVC) will be listed by subject and timepoint 
including absolute values, change from baseline, and percentage change from baseline.
Change from baseline will be calculated and presented by timepoint in each study part. Summary 
tabulations for absolute values, change from baseline and percentage change from baseline will be 
presented by treatment group (AZD1402, pooled AZD1402, and placebo) and overall, and by 
timepoint for in-clinic and e-Diary spirometry FEV1. For in-clinic FVC similar tables will be 
presented.
For repeated post-baseline in-clinic spirometry morning measurements that are taken on the same day 
and time as a schedule visit and timepoint, the best response value of the morning pre-dose will be 
used.
For repeated post-baseline home spirometry measurements that are taken on the same day and time
as a scheduled visit and time point, the highest results of the morning pre-dose will be used.
For repeated follow-up post-baseline in-clinic spirometry morning measurements that are taken on 
the same day and time as a scheduled visit and time point, the best response value of the morning 
assessments will be used.
For repeated follow-up post-baseline home spirometry measurements that are taken on the same day 
and time as a scheduled visit and time point, the highest results of the morning assessments will be 
used.
For Part 1, tables and figures presenting FEV1 by study day will be based on the morning pre-dose 
values in case not differently indicated.
For Part 1 and/or Part 2 the following figures will be presented:

In-clinic FEV1 absolute values (L), individual subject by study day/week.


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
In-clinic FEV1 percentage change from baseline, individual subject data by study day/week.

FEV1 home spirometry absolute values (L), individual subject data by study day.

FEV1 home spirometry percentage change from baseline, individual subject data by study day.

In-clinic FEV1 mean absolute values (L) by study day/week and treatment group.

In-clinic FEV1 mean percentage change from baseline by study day/week and treatment 
group.

FEV1 home spirometry mean absolute values (L) by study day and treatment group.

FEV1 home spirometry mean percentage change from baseline by study day and treatment 
group.
The summary statistics for FEV1 in-clinic spirometry and e-Diary spirometry will be presented 
separately.
For in-clinic FEV1 for Part 1, the morning and evening post-dose percentage change from pre-dose 
by day, will also be summarised.
4.17.6 Fractional Exhaled Nitric Oxide
Fractional exhaled nitric oxide will be listed by subject and timepoint including the date/time of the 
assessment, percentage changes from baseline and repeat/unscheduled measurements.
Descriptive statistics (n, mean, SD, median, minimum, maximum) for absolute values and percentage 
changes from baseline will be presented by treatment group (AZD1402 and placebo) and by pooled 
AZD1402 groups.
4.18 Data Monitoring Committees
The SRC including the Sponsor study team will review PK and unblinded safety data following 
completion of Part 1a before progressing to Part 1b/2 and following completion of Part 1b. An 
unscheduled SRC meeting may also be held in the event of any safety or tolerability events requiring 
further review that may impact continuation of a cohort or the study, including unblinding data as 
required. All details on how the safety reviews are conducted are described in the SRC charter. A 
DSMB will oversee Part 2 of the study and review the unblinded interim outputs. In addition to a full 
DSMB periodic review of safety data, the committee can meet on an ad hoc basis. Details of the 
composition of the DSMB, frequency of meetings and remit can be found in the DSMB Charter. A 
separate review committee of AstraZeneca representatives will review the unblinded interim outputs 
for the interim analysis if performed.
4.19 Determination of Sample Size
In Part 1 (lead-in cohort), approximately 45 participants will be randomised. Part 1a will consist of 
30 randomised participants and Part 1b will consist of 15 randomised participants. The sample size 
for Part 1 (lead-in cohort) is not based on any sample size calculation but was chosen to obtain 
reasonable evidence of safety and tolerability without exposing undue number of participants to the 
study intervention. In Part 2 (main cohort), 73 evaluable participants per treatment arm ( mg and 
placebo) will provide 
% power using a 1-sided test and 5% significance level to detect a difference 
of 175 mL in FEV1 between AZD1402 versus placebo. This is based on a SD of 
 mL, derived 
from an inter-participant SD of 
 mL in change from baseline to Week 4, adjusted for 4 repeated 
measurements and a correlation of 
between weekly measurements. Assuming a dropout rate of 
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%, approximately 80 evaluable participants per arm are needed. Due to the restricted recruitment 
into the mg dose arm the precision of inference in terms of statistical power will be less than 
% 
for the comparisons mg versus placebo. A participant will be considered evaluable if he/she has a 
baseline and Week 4 FEV1 results available. Part 2 will consist of approximately 165 participants.
4.20 Change in the Conduct of the Study or Planned Analysis
SAP updated for anticipated closure to remove some of the exploratory endpoints, the Per Protocol 
analysis and subgroup analysis.  
4.21 References
Fuhlbrigge, et al. 2017
Fuhlbrigge AL, Bengtsson T, Peterson S, Jauhiainen A, Eriksson G, et al. A novel endpoint for 
exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised 
controlled trials. The Lancet. Resp. Med. 2017: 5(7), 577-590.
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5
APPENDICES
5.1
Schedule of Assessments
Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Signed informed consent
X
5.1
Admission
X
X
4.1.1
Discharge
X e
X
4.1.1
Optional residential stay (throughout 
Treatment Period)
X
4.1.1
Inclusion and exclusion criteria
X
X
X
X
5.1, 5.2
Demography
X
5.1
Medical/surgical history
X
5.1
Smoking history including cotinine 
testing 
X
X
5.1
Asthma history
X
5.1
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
6.5
Height/weight f
X
X
X
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Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Physical examination
X g
X h
X h
X g
X h
X g
8.2.1
Vital signs (blood pressure, pulse rate, 
temperature, respiratory rate) i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.2.2
Study drug inhalation training
X
X
X j
6.1.3
Home device dispensation (FeNO and 
spirometer)
X
6.1.2
Home device training (FeNO and 
spirometer)
X
X j
6.1.2
Rescue medication (eg, salbutamol) k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
6.5.1
FeNO test (in-clinic) l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.3
FeNO at-home assessments (Niox 
Vero) l, m
X
X
X
X
X
X
X
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Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Spirometry (FEV1 and FVC) n
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.1
12-lead ECG o
X 
X
X
(Day 7)
X
X
8.2.3
ACQ-6
X 
X 
X
X
(Day 7)
X
X(Day 20)
X
X
8.1.10
FEV1/PEF (home device) p
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.1, 8.1.11
Cough VAS
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.10
SPFQ (optional)
X
X
X
X
8.1.10
Assign e-Diary q
X
8.1.4
Dispense e-Diary r
X
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Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Check e-Diary compliance
X
X
X
X
X
X
X
X
X
X
X
X
6.4.2
Check compliance with background 
medication
X
X
X
X
X
X
X
X
X
X
X
X
6.5
Collect e-Diary
X
X
8.1.4
Asthma symptom score and rescue 
medication use
X
X
X
X
X
X
X
X
X
X
X
X
X
8.1.6, 8.1.7
Study drug dispensation
X
6.1 
Study drug administration s
6.1.3
Drug accountability
X
X
6.2
Return unused medication and DPI
X
X
6.2
AEs t
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.3
Blood samples for biochemistry
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for haematology
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for clotting profile
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples for CRP (local 
laboratory) w
X
X
X
X
X
X
X
X
X
X
X
X
8.2.4
Blood sample for hs-CRP
X
X
X u
X v
X
X
X
X
X
X
X
8.2.5.1
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Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Blood samples for safety immuno-
biomarkers
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
Blood samples allergen-specific IgE x
X
8.6.1
Blood samples for serum pregnancy 
test (all female participants)
X
5.1, 8.2.4
Blood samples for Hepatitis B 
(HBsAg, anti-HBs, anti-HBc), and C; 
HIV-1 and HIV-2; QFT for TB y
X
5.1, 8.2.4
Blood samples for PK measurements z
X
X
X
X
X
X
X
X
X
X
X
8.5.1
Blood samples for ADA aa
X
X
X (Day 20, 
24)
X
X
X
X
8.5.2
 
 
bb
X
8.6.2, 8.7
 
X 
(pre-
dose)
X (pre-
dose)
X
X
8.6.2
Urinalysis
X
X
X u
X v
X
X
X
X
X
X
X
8.2.4
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Table 2
Schedule of Activities Part 1
Procedure
Screening
Run-
in
Treatment Period a
ETV/ 
IPD
Follow-up
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4,5,6
7
8
9
10
11
Day
(up to 14 days 
before V2) b,c
-28 
± 2
-1
1
2 to 13
14
16, 20, 24 
28 d - 2
29
30
32
39 
± 6
56 
± 4
Blood samples for FSH (if needed to 
confirm postmenopausal status in 
female participants < 50 years and not 
on HRT)
X
5.1, 8.2.4
Urine pregnancy test (females of 
childbearing potential) cc
X
X
X
X
5.1, 8.2.4
Urine drug screen
X
X
5.2, 8.2.4
SARS-CoV-2 PCR dd
X 
X
X ee
X
X
X
X
X
X
X
X
X
X
X
5.2, 8.2.4
SARS-CoV-2 serology dd
X
X
X
5.2, 8.2.4
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; 
 COVID-19 = Coronavirus 
disease-2019; CRP =C-reactive protein; CSP = clinical study protocol; DPI = dry powder inhaler; ECG = electrocardiogram; e-Diary = electronic diary; ETV = early termination visit; FEV1 = forced 
expiratory volume in 1 second; FeNO = fractional exhaled nitric oxide; FSH = follicle stimulating hormone; FVC = forced vital capacity; 
 HBsAg = hepatitis B surface antigen; 
HIV = human immunodeficiency virus; 
 HRT = hormone replacement therapy; hs-CRP = high sensitivity CRP; IgE = immunoglobulin E; IPD = Intervention 
Discontinuation Visit; 
 PCR = polymerase chain reaction; PEF = peak expiratory flow; PK = pharmacokinetics; QFT = QuantiFERON; 
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SPFQ = Study Participant Feedback Questionnaire; SoA = Schedule of Activities; TB = tuberculosis; VAS = Visual Analogue Scale
a
In-clinic outpatient visits during the Treatment Period will be scheduled so that they fall at the time of morning dose administration.
b
Time between Visit 1 and Visit 2 may be extended up to 28 days upon input from the Study Physician.
c
Visit 1 can be done on several/different days prior to Visit 2.
d
Participants may be admitted on Day 27. Day 28 should be performed on the scheduled calendar day as far as possible; the -2-day window may be utilised only if required. If the -2-day window is 
utilised, all subsequent visits will be adjusted to follow time window between visits as specified in the SoA.
e
Discharge on Day 14 after the morning post-dose procedures.
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f
Height only at Visit 1.
g
A complete physical examination including an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose and throat), lymph 
nodes, thyroid, musculoskeletal and neurological systems will be performed.
h
A brief physical examination including an assessment of the general appearance, skin, abdomen, cardiovascular, and respiratory systems will be performed.
i
Vital signs to be performed BID whilst participants are in-clinic. Vital signs will be measured pre-dose at the scheduled morning dose in-clinic visits and additionally prior to the evening dose if 
participants receive the evening dose at the clinic (eg, due to optional overnight stay).
j
Refresher training as required.
k
Rescue medication to be as necessary. Check if participant has enough rescue medicine for use at-home use and refill if necessary.
l
FeNO will be measured pre-spirometry, pre-dose (as applicable), and pre-bronchodilation.
m
FeNO assessments at home will only be performed (morning and evening) at non-clinic visit timepoints.
n
In-clinic spirometry on Days 1 to 14 and Day 28 will be performed pre-dose and 2 h post-dose (± 15 min) in the morning (prior to taking controller medication) and on Days 1 to 13 pre-dose and 4 
h post-dose (-2 h) in the evening. Where possible, all post-randomisation morning pre-dose clinic spirometry assessments should be performed within ± 30 minutes of the time that the 
randomisation spirometry was performed during the residential period. The evening pre-dose spirometry should also be performed within a ± 30 minutes window relative to the evening 
assessment timepoint. If patients remain in the unit without discharge to stay overnight during Days 14 to 27, a pre-dose and 2 h post-dose spirometry assessment will be performed in the morning 
(prior to taking controller medication) and pre-dose and 4 h (-2h) post-dose spirometry assessment in the evening. If patients are discharged and re-admitted to the unit for overnight stay on 
Days 15 to 27, the morning and evening post-dose spirometry assessment will be 4 h (-2h) post-dose (controller medication timing will remain unchanged from home dosing and controller 
medication will be taken directly after study intervention). At clinic visits with no overnight stay, morning pre-bronchodilator and 2 h post spirometry will be performed. The timing of controller 
medication and clinic post-dose spirometry assessments may be adjusted by the Sponsor.
o
ECG will be measured before (within 75 min) and 1 hour (± 10 min) after administration of study intervention on visits as indicated.
p
Home device spirometry will be performed pre-dose twice daily, including on in-clinic assessment days. On in-clinic assessment days, home spirometry may be performed up to 2 hours prior to 
dosing.
q
At Visit 1 the e-Diary is set up, participants perform training and ACQ-6 and SNOT-22 is completed.
r
The e-Diary will be completed twice daily during the Run-in, Treatment, and Follow-up Period.
s
Study intervention will be administered 
 While at clinic, the study drug 
administration will be monitored by the site staff. Administration will be registered in the e-Diary by the participant.
t
AEs will be collected from the time of informed consent. Unscheduled safety sampling may be performed at the discretion of the Investigator in the event of AEs/AESIs, including but not limited 
nasal swabs to confirm infection.
u
Baseline safety sampling will be performed pre-dose on Day 1.
v
Sampling on Days 2, 6, 8, 10, and 12.
w
CRP must be done locally on Day -1 (may be performed on Day -2 for logistical reasons) to confirm eligibility as per inclusion criterion. It may be performed throughout the study in the event of 
AE/AESI as required to inform suspension/stopping criteria.
x
Blood samples will be analysed for IgE if potential drug related IgE response is observed in any participant; may be collected on Day -1 or Day 1 pre-dose.
y
PCR may be performed to confirm hepatitis B / hepatitis C status if required.
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z
Blood samples for PK measurements will be collected for all participants. Timing of samples: Day 1 pre-dose (-60 min), 1, 2, 3 (± 10 min), 4, 6, 8 (± 20 min) and 12 h (up to 1h prior to the next 
dose, must be before the subsequent dose); Day 28 pre-dose (-60 min), 1, 2, 3 (± 10 min), 4, 6, 8 (± 20 min), and 12h (± 1 h; single dose of AZD1402 only on Day 28). Pre-dose on Days 2, 4, 6, 8, 
10, 12, 14, 16, 20, 24 (up to 1 h prior to the next dose, must be before the subsequent dose), 29 (24 h ± 2 h after Day 28 dose), 30 (48 h ± 2.5 h after Day 28 dose), 32 (96 h ± 2.5 h after Day 
28 dose), 39 (± 6 days), and 56 (± 4 days). Part Ib only: Day 20, 4 h post-morning dose (± 20 min). The PK sampling timepoints may be amended based on results from Part 1a/b. An unscheduled 
PK sample may be collected in the case of AEs and / or unscheduled safety blood sampling.
aa
ADA sampling, pre-dose Day 1, Day 14, Day 20, Day 24 (Part 1b only) and Day 28 and on Follow-up/unscheduled visits. Participants
 
 An unscheduled ADA sample may also be collected in case of AEs/AESIs and/or 
unscheduled safety blood sampling.
bb
Sample collection if consented only. If for any reason the sample is not drawn at Visit 3, it may be taken at any visit until the last study visit.
cc
All urine pregnancy tests will be done pre-dose.
dd
SARS-CoV-2 serology at Screening, End of Trial and final Follow-up Visits; PCR is optional and may be performed centrally or at the local laboratory as clinically indicated and as per local 
guidelines for the duration of the study. Ad hoc nasal and/or throat-swab specimen is to be collected for the identification of a suspected respiratory infection during any visit. This may be 
performed locally, or if required by central laboratory. 
ee
May be performed on Day -2 for logistical reasons.
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Table 3 Schedule of Activities Part 2
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
Signed informed consent
X
5.1
Inclusion and exclusion criteria
X
X
X
5.1, 5.2
Demography
X
5.1
Medical/surgical history
X
5.1
Smoking history including cotinine testing
X
5.1
Asthma history
X
5.1
Concomitant medication
X
X
X
X
X
X
X
X
X
X
6.5
Height/weight d
X
X
8.2.1
Physical examination
X e
X f
X f
X f
X f
8.2.1
Vital signs (blood pressure, pulse rate, temperature, 
respiratory rate) g
X
X
X
X
X
X
X
X
X
X
8.2.2
Study drug inhalation training
X
X h
6.1.3
Home device (spirometer) dispensation
X
6.1.2
Home device training (spirometer)
X
X h
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Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
Rescue medication (eg, salbutamol) i
X
X
X
X
X
X
X
X
X
X
6.5.1
FeNO test (in-clinic) j
X
X
X
X
X
X
X
X
X
X
8.1.3
Spirometry (FEV1 and FVC) k
X
X
X
X
X
X
X
X
X
X
8.1.1
Reversibility test l
X
8.1.2
12-lead ECG m
X
X
X
8.2.3
ACQ-6
X
X
X
X
X
X
X
X
X
8.1.10
SPFQ (optional)
X
X
X
X n
8.1.10
FEV1/PEF (home device) o
X
X
X
X
X
X
X
8.1.1, 8.1.11
Assign e-Diary p
X
8.1.4
Dispense e-Diary q
X
8.1.4
Check e-Diary compliance
X
X
X
X
X
X
X
X
X
6.4
Check compliance with background medication
X
X
X
X
X
X
X
X
X
8.1.4
Check compliance with study medication
X
X
X
X
X
X
Collect e-Diary
X
X
8.1.5
Asthma symptom score and rescue use
X
X
X
X
X
X
X
X
8.1.6, 8.1.7
Study drug dispensation
X
X
6.1


Parexel International
AstraZeneca
AstraZeneca
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 61 of 64
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
Study drug administration r
6.1
Drug accountability
X
X
X
6.2
Return unused medication and inhaler 
X
X
X
6.2
AE s
X
X
X
X
X
X
X
X
X
X
X
8.3
Blood samples for biochemistry
X
X t
X
X
X
X
X
X
8.2.4
Blood samples for haematology
X
X
X t
X
X
X
X
X
X
8.2.4
Blood samples for clotting profile
X
8.2.4
Blood sample for hs-CRP
X
X
X t
X
X
X
X
X
X
8.6.1
Blood samples for safety immuno-biomarkers
X
X t
X
X
X
X
X
X
8.2.5.1
Blood samples allergen-specific IgE u
X u
8.2.4
Blood samples for CRP (local laboratory) v
X
X
X
X
X
X
X
X
X
8.2.4
Blood samples for serum pregnancy test (all female 
participants)
X
5.1, 8.2.4
Blood samples for Hepatitis B (HBsAg, anti-HBs, 
anti-HBc), and C; HIV-1 and HIV-2; QFT for TB w
X
5.1, 8.2.4
Blood samples for PK measurements x
X
X
X
X
X
X
X
8.5.1
Blood samples for ADA y
X
X
X
X
X
X
X
X
8.5.1
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Parexel International
AstraZeneca
AstraZeneca
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 62 of 64
Procedure
Screening
Run-in
Treatment Period a
ETV/ 
IPD
Follow-up
Unscheduled 
Visit
Details in CSP 
Section or 
Appendix
Visit 
1
2
3
4
5
6
7
8
9 
Day
(up to 14 days 
before V2) b,c
-28 ± 2
1
7 
± 2
14 
± 2
21 
± 2
28 
± 2
39 
± 6
56 ± 
4
Week
-6
-4
0
1
2
3
4
5/6
8
 
z
X
8.6.2, 8.7
X aa
X aa
X aa
X
X aa
8.6.1
X aa
X aa
X
X aa
8.6.1
X aa
Urinalysis
X
8.2.4
Blood samples for FSH (if needed to confirm 
postmenopausal status in female participants 
< 50 years and not on HRT)
X
5.1, 8.2.4
Urine pregnancy test (females of childbearing 
potential) bb
X
X
X
X
5.1, 8.2.4
Urine drug screen
X
5.2, 8.2.4
SARS-CoV-2 PCR cc
X
X
X
X
X
X
X
X
X
X
X
5.2, 8.2.4
SARS-CoV-2 serology cc
X
5.2, 8.2.4
Abbreviations: ACQ-6 = Asthma Control Questionnaire-6; ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; 
 COVID-19 = Coronavirus 
disease-2019; CRP =C-reactive protein; CSP = clinical study protocol; ECG = electrocardiogram; e-Diary = electronic diary; ETV = early termination visit; FEV1 = forced expiratory volume in 1 
second; FeNO = fractional exhaled nitric oxide; FSH = follicle stimulating hormone; FVC = forced vital capacity; 
 HBsAg = hepatitis B surface antigen; HIV = human 
immunodeficiency virus; 
 HRT = hormone replacement therapy; hs-CRP = high sensitivity CRP; IgE = immunoglobulin E; IPD = Intervention Discontinuation Visit; 
 PCR = polymerase chain reaction; PEF = peak expiratory flow; PK = pharmacokinetics: RNA = ribonucleic acid; QFT = QuantiFERON; SARS-CoV-2 = 
severe acute respiratory syndrome coronavirus 2; SPFQ = Study Participant Feedback Questionnaire; TB = tuberculosis
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Parexel International
AstraZeneca
AstraZeneca
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 63 of 64
ff
In-clinic outpatient visits during the Treatment Period will be scheduled so that they fall at the time of morning dose administration.
gg
Time between Visit 1 and Visit 2 may be extended up to 28 days upon input from the Study Physician.
hh
Visit 1 can be done on several/different days prior to Visit 2.
ii
Height at Visit 1 only.
jj
A complete physical examination including an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, 
thyroid, musculoskeletal and neurological systems will be performed.
kk
A brief physical examination including an assessment of the general appearance, skin, abdomen, cardiovascular, and respiratory systems will be performed.
ll
Vital signs will be measured pre-dose at the scheduled morning dosing in-clinic visits.
mm
Refresher training if required.
nn
Check if participant has enough rescue medicine for use at-home use and refill if necessary.
oo
FeNO will be measured pre-spirometry, pre-dose (as applicable), and pre-bronchodilation.
pp
Spirometry will be performed 45 minutes and 15 minutes prior to first dose of study intervention on Day 1 and pre-dose at all other visits. If possible, all post-randomisation pre-dose morning clinic 
device spirometry assessments should be performed within ± 1.5 hours of the time that the 15 min prior to randomisation spirometry was performed.
qq
Reversibility testing will be performed 15 to 30 minutes after inhalation of 400 μg of salbutamol.
rr
ECG will be measured before study drug administration on Day 1 and Day 28 (within 75 min) and 1 hour (± 20 min) after administration of study intervention on Day 1 and Day 28.
ss
SPFQ (optional) will not be completed at unscheduled visits.
tt
At-home spirometry will be completed up to V8 and only to be completed at non-clinic visit timepoints. 
uu
At Visit 1 the e-Diary is set up, participants perform training and ACQ-6 is completed.
vv
The e-Diary will be completed twice daily during the Run-in, Treatment, and Follow-up Period.
ww
Study intervention will be administered 
 Date and time of administration at 
home will be registered in the e-Diary by the participant. Study drug administration at the clinic will be under supervision. The Day 28 dosing window ± 2 days should only be used if needed, and 
where possible to keep within ± 1 day. 
xx
SAEs will be collected from the time of informed consent. Non-serious AEs will be collected from the time of randomization. Unscheduled safety sampling may be performed at the discretion of 
the Investigator in the event of AEs/AESIs, including but not limited nasal swabs to confirm infection.
yy
Baseline safety sampling will be performed pre-dose on Day 1.
zz
Blood samples will be analysed for IgE if potential drug related IgE response is observed in any participant.
aaa
Local CRP may be performed from Visit 3 and throughout the study in the event of AE/AESI as required to inform suspension/stopping criteria.
bbb
PCR may be performed to confirm hepatitis B / hepatitis C status if required.
ccc
Blood samples for PK measurements will be collected in all participants pre-dose at each visit, including unscheduled visits. Intense sampling may be performed in approximately 25% of 
participants per treatment arm (for example, 20 subjects in the mg treatment arm). Timing of intense samples: Day 1: 1, 2, 3 (± 10 min), 6, and 8 h (± 20 min), Day 21 4 h post-morning dose (± 20 
min) and Day 28 (last dose), 1, 2, 3 (± 10 min), 6, 8 (± 20 min), 24 (± 2 h), 48 (± 2.5 h), and 96 h (± 2.5 h; single dose of AZD1402 only on last day of dosing). PK sampling timepoints may be 
amended based on results from Part 1a/b. An unscheduled PK sample may be collected in the case of AEs and / or unscheduled safety blood sampling.
ddd
ADA sampling, pre-dose Day 1, Day 14, Day 21, Day 28, and at the Follow-up Visits. An unscheduled ADA sample may also be collected in the case of AEs/AESIs and/or unscheduled safety 
blood sampling.
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Parexel International
AstraZeneca
AstraZeneca
Statistical Analysis Plan
TP-GDO-WW-133-02
CONFIDENTIAL
Project Document Version No. 5.0
Effective Date:  26 Nov 19
Project Document Effective Date: <Date of last signature>
Related to:  SOP-GDO-WW-019
Page 64 of 64
eee
Sample collection only if consented. If for any reason the sample is not drawn at Visit 3, it may be taken at any visit until the last study visit.
fff
Proposed samples and times: Serum: Pre-dose Day 1, pre-dose Week 2, Week 4 and at Follow-up. 
 Pre-dose Day 1, and Week 4. 
 
Pre-dose Day 1, Day 28, and Day 39. 
 Pre-dose Day 1.
ggg
All urine pregnancy tests will be done pre-dose. In case of a positive result, a serum pregnancy test will be performed.
hhh
SARS-CoV-2 serology at Screening; PCR is optional and may be performed centrally or at the local laboratory as clinically indicated and as per local guidelines for the duration of the study. Ad 
hoc nasal and/or throat-swab specimen is to be collected for the identification of a suspected respiratory infection during any visit. This may be performed locally, or if required by central 
laboratory.
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SIGNATURE PAGE
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic signature
Document Name: d2912c00003-sap-ed-5
Document Title:
Statistical Analysis Plan Edition 5
Document ID:
Doc ID-004568748
Version Label:
5.0 CURRENT LATEST APPROVED
Server Date
(dd-MMM-yyyy HH:mm ‘UTC’Z)
Signed by
Meaning of Signature
09-Aug-2023 06:41 UTC
Content Approval
Notes: (1) Document details as stored in ANGEL, an AstraZeneca document management system.
PPD