A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 Pharmacokinetic Comparability Study of Benralizumab Administrated Using Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers.
Phase: PHASE1
Conditions: Asthma, Chronic Obstructive Pulmonary Disease
Sponsor: AstraZeneca

Protocol: D3250C00030 
 
 
 Protocol number: D3250C00030 
 Document title: Multicenter, Randomized, Open-Label, Parallel Group Phase I 
Pharmacokinetic Comparability Study of Benralizumab Administrated using 
Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers. 
 Version number: 1.0, Amendment 1 
 Date of the document: 07 July 2017 
 NCT number: NCT02968914 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 1 of 75 
07 July 2017 
 
Clinical Study Protocol 
A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab 
Administrated using Accessorized Pre-Filled Syringe (APFS) or 
Autoinjector (AI) in Healthy Volunteers 
PAREXEL Study No.: 
230172 
Sponsor Study Code: 
D3250C00030 
IND No./Eudra CT No: 
2016-002955-52 
Study Type: 
Clinical Pharmacology, Pharmacokinetic Comparability Study 
Test Product: 
Benralizumab administered via Autoinjector (AI) 
Reference Product: 
Benralizumab administered via accessorized pre-filled syringe (APFS) 
Therapeutic Indication: 
Asthma and Chronic Obstructive Pulmonary Disease (COPD) 
Pharmacological Class: 
Anti-eosinophil monoclonal antibody 
Development Phase: 
Clinical pharmacology 
Sponsor: 
AstraZeneca AB 
151 85 Södertälje 
Sweden 
Study Centers: 
PAREXEL Early Phase Clinical Unit Berlin 
On the premises of Klinikum Westend, Haus 31 
Spandauer Damm 130 
14050 Berlin 
Germany 
 
PAREXEL Early Phase Clinical Unit London 
Level 7, Northwick Park Hospital 
Watford Road, Harrow 
Middlesex HA1 3UJ 
United Kingdom 
Date of Original Protocol: 
Final 1.0, 19 October 2016 
Amendment No. 1 
Final 1.0, 07 July 2017 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki (Version 1996) and are consistent with International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and the AstraZeneca policy on Bioethics 
and Human Biological Samples. 
Confidentiality Statement 
This confidential document is the property of AstraZeneca.  No unpublished information 
contained herein may be disclosed without prior written approval from AstraZeneca.  Access 
to this document must be restricted to relevant parties. 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 2 of 75 
07 July 2017 
 
PROTOCOL AMENDMENT 
Clinical Study Protocol Amendment No. 1, Final 1.0, Dated 07 July 2017 
The following changes were made to the original clinical study protocol, Final 1.0, dated 
19 October 2016, to replace MedImmune Clinical Pharmacology with PAREXEL 
Quantitative Clinical Development (QCD) as the pharmacokinetic (PK) analyses vendor for 
this clinical study. 
1. The Sponsor’s (Lead) Clinical Pharmacologist was changed to 
, see 
Section 4. 
2. The Clinical Pharmacokineticist was changed to 
, see Section 4. 
3.  The physical examination text was updated to clarify that any new or aggravated 
clinically relevant abnormal medical physical examination finding compared to the 
baseline assessment will be reported as an AE see Section 9.3.4. 
4. The protocol text was updated to indicate that the non-compartmental pharmacokinetic 
analyses of the serum concentration data for benralizumab will be performed by 
PAREXEL QCD using Phoenix WinNonlin (version 6.3 or higher) in accordance to 
PAREXEL SOPs and the following sentence was deleted “Figures will be created using 
SigmaPlot for Windows (12.5, or higher, Systat Software Inc., Chicago, IL)” see 
Section 11.9.2. 
5. The protocol text was updated to indicate that serum concentration data associated with 
positive anti-drug antibody (ADA) status may be excluded from the non-compartmental 
analyses (NCA), see Section 11.9.2. 
6. The protocol text was updated to indicate that serum concentration data associated with 
positive ADA status will be flagged in the PK concentration listings and may be excluded 
from the summary statistics and/or mean profiles, see Section 11.9.3. 
7. The protocol text was updated to indicate that abnormal baseline/screening results of 
physical examination will be documented in medical history for each subject see 
Section 11.10.4. 
8. Added 
 (Lead Clinical Pharmacologist) in the signature Section 16.3. 
PPD
PPD
PPD

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 3 of 75 
07 July 2017 
 
PROTOCOL SYNOPSIS 
Title of the Study 
A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 Pharmacokinetic Comparability Study of 
Benralizumab Administrated using Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy 
Volunteers 
 
Principal Investigators (PIs) 
 and 
 
 
Study Centers 
PAREXEL Early Phase Clinical Unit Berlin, 
On the premises of Klinikum Westend, Haus 31, 
Spandauer Damm 130, 
14050 Berlin, 
Germany 
 
PAREXEL Early Phase Clinical Unit London,  
Level 7, Northwick Park Hospital,  
Watford Road, Harrow,  
Middlesex HA1 3UJ, 
United Kingdom 
 
Study Rationale 
Benralizumab is a humanized anti-eosinophil monoclonal antibody (mAb) and depletes eosinophils via a 
mechanism of enhanced antibody-dependent cell-mediated cytotoxicity (ADCC).  Benralizumab’s unique 
mechanism of action induces direct, rapid and nearly complete depletion of eosinophils in the lung tissue, 
sputum, blood and bone marrow.  Benralizumab has demonstrated pharmacodynamic (PD) activity and clinical 
efficacy in asthma control in Phase 1, 2 and 3 studies.  
In global pivotal trials, benralizumab has been administered by health care providers using accessorized 
pre-filled syringe (APFS) device.  The APFS combination product is a single-use, disposable system that is 
designed to administer the labeled dose into the subcutaneous (SC) space as 1 injection and automatically 
provides a safety mechanism to reduce the occurrence of accidental needle-sticks during disposal of the system.  
The functionality and reliability of APFS for home administration were evaluated in another study 
(GREGALE).  The Autoinjector (AI) combination product is an automated, single-use, disposable system that is 
designed to administer the labeled dose into the SC space as 1 injection in a two-step operation and has a 
locking needle shield to reduce the occurrence of accidental needle-sticks during disposal of the system. 
An open-label, single dose pharmacokinetic (PK) comparability study is required to demonstrate comparable 
drug exposure (AUC and Cmax) following SC benralizumab administration by using APFS or AI devices.  As for 
other therapeutic immunoglobulin G (IgG) monoclonal antibodies, body weight was previously identified as a 
relevant PK covariate for benralizumab.  In addition, the use of different anatomical regions for SC injections 
may influence the absorption of protein drugs.  In this study, descriptive comparison of benralizumab PK by 
weight and injection site will be provided. 
 
Number of Subjects Planned 
A total of 180 healthy subjects will be randomized to ensure at least 162 evaluable subjects at the end of the 
treatment period. 
 
Study Period 
Estimated date of first subject enrolled: 
November 2016 (signing of informed consent) 
Estimated date of last subject completed: 
June 2017 
PPD
PPD

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 4 of 75 
07 July 2017 
 
Study Objectives 
Primary Objective: 
• 
To compare the PK exposure following single SC administration of benralizumab by using APFS or AI 
devices 
Secondary Objectives: 
• 
To evaluate the PK of benralizumab administered to various anatomical injection sites and in subjects with 
different body weight ranges 
• 
To evaluate the safety and tolerability of benralizumab 
• 
To evaluate the immunogenicity of benralizumab 
 
Study Design 
This study will be a multicenter, randomized, open-label, parallel group Phase 1 study designed to compare 
benralizumab PK exposure in healthy subjects following single SC administration of fixed 30 mg dose of 
benralizumab by using APFS and single-use AI.  Eligible subjects will be healthy subjects aged 18 to 55 years, 
with a body weight of 55 to 100 kg and a body mass index of 18 to 29.9 kg/m2.  A total of 180 subjects will be 
randomized.  Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg), 
and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of 
treatment (APFS or AI) with injection site (upper arm, abdomen or thigh), presented in Table 1.  This study will 
be performed at 2 study centers. 
Table 1 Design of a Pharmacokinetic Comparability Study in Healthy Subjects for Benralizumab 
Accessorized Pre-Filled Syringe and Autoinjector Devices  
Number of Subjects 
APFS 
AI 
Total 
Upper Arm 
Abdomen 
Thigh 
Upper Arm 
Abdomen 
Thigh 
Body Weight 
55.0 to 69.9 kg 
10 
10 
10 
10 
10 
10 
60 
70.0 to 84.9 kg 
10 
10 
10 
10 
10 
10 
60 
85.0 to 100.0 kg 
10 
10 
10 
10 
10 
10 
60 
Total 
90 
90 
180 
AI: Autoinjector; APFS: Accessorized pre-filled syringe device 
The study will comprise of: 
• 
A screening period of maximum of 28 days, 
• 
One treatment period during which subjects will be resident from the day before dosing (Day -1), until 2 
hours after dosing on Day 1.  The subjects will then return to the center for ambulant visits on Days 2, 4, 5, 
6, 8, 15, 29 and 43, and 
• 
An End-of-Treatment visit on Day 57 (Week 8). 
After a screening period of up to 28 days, eligible subjects will be admitted to the unit on Day -1 (1 day before 
dosing) to reassess their eligibility.  Subjects who meet eligibility criteria will be randomized on Day 1 to 
receive a single dose of 30 mg benralizumab by either APFS or AI device.  The study will be completed after 
the End-of-Treatment visit on Day 57 (Week 8). 
 
Expected Duration of the Study 
Each subject will be involved in the study for 12 to 13 weeks (8 to 9 weeks active participation) and 28 days 
screening period. 
 
Targeted Study Population 
This study will be conducted in healthy male and/or female subjects (of non-child-bearing potential), 18 to 
55 years (inclusive) of age.  
 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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07 July 2017 
 
Identity of the Investigational Medicinal Product (Accessorized Pre-Filled Syringe) 
IMP: 
Benralizumab 
Formulation: 
30 mg/mL solution for injection in accessorized pre-filled syringe 
Strength/concentration: 
30 mg/mL 
Dose: 
30 mg 
Route of administration: 
SC 
Specific device for drug 
administration, if applicable: 
Accessorized pre-filled syringe 
Regimen: 
Single Dose 
Special handling requirements: 
Store between 2-8°C (36- 46°F), protected from the light 
Availability of the IMP: 
01 Nov 2016 
 
Identity of the Investigational Medicinal Product (Autoinjector) 
IMP: 
Benralizumab 
Formulation: 
30 mg/mL solution for injection in Autoinjector 
Strength/concentration: 
30 mg/mL 
Dose: 
30 mg 
Route of administration: 
SC 
Specific device for drug 
administration, if applicable: 
Autoinjector 
Regimen: 
Single Dose 
Special handling requirements: 
Store between 2-8°C (36- 46°F), protected from the light 
Availability of the IMP: 
01 Nov 2016 
 
Outcome Endpoints 
Pharmacokinetic Endpoints: 
Where possible, the following PK parameters will be assessed for benralizumab on serum concentrations. 
• 
Primary PK parameters: AUC, Cmax 
• 
Secondary PK parameters: Tmax, t½, CL/F, Vz/F 
Additional PK parameters may be determined where appropriate. 
Safety and Tolerability Endpoints: 
• 
Safety and tolerability variables will include 
• 
Adverse events (AEs) 
• 
Vital signs (systolic and diastolic blood pressure [BP], pulse rate and body temperature) 
• 
Electrocardiograms (ECGs) 
• 
Physical examination 
• 
Laboratory assessments (hematology, clinical chemistry and urinalysis). 
Viral serology and drugs of abuse and alcohol will be assessed for eligibility.  Follicle-stimulating hormone 
(females only), pregnancy testing (females only) and use of concomitant medication will also be assessed and 
reported. 
 
Statistical Methods 
Presentation and Analysis of Pharmacokinetic Data: 
A listing of PK blood sample collection times, as well as derived sampling time deviations will be provided. 
Serum concentrations and PK parameters will be summarized separately by treatment (device) only and by 
treatment (device), body weight and injection site, using appropriate descriptive statistics.   
The analysis of variance (ANOVA) model will be employed on the log-transformed Cmax and AUC separately, 
with fixed effects of treatment (device), body weight group and injection site in order to provide a descriptive 
comparison of the PK exposure between the 2 devices.  The estimated treatment (device) differences and the 
90% confidence interval (CI) (2-sided) on the log scale will be back-transformed to obtain the geometric mean 
ratios of AI to APFS and its corresponding 90% CI.    
 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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Presentation and Analysis of Safety and Eligibility Data: 
Adverse Events will be summarized by means of counts summaries by study period (pre-treatment and 
treatment period).  Adverse Events will be listed for each subject and summarized by System Organ Class and 
Preferred Term assigned to the event by Medical Dictionary for Regulatory Activities (MedDRA).  Laboratory 
safety variables will be summarized using standard summary statistics as appropriate. 
Other safety variables will be summarized as appropriate.   
Presentation and Analysis of Immunogenicity Data 
For the analysis of immunogenicity data, anti-drug antibodies (ADAs) to benralizumab will be summarized 
using descriptive statistics at each visit by treatment group.  Anti-drug antibody titers-time profiles of 
benralizumab by treatment group will be generated.  The impact of ADA on PK and eosinophil level will be 
assessed.  The potential association of ADA with safety will be evaluated.  The hypersensitivity reported during 
the on-study period will be evaluated for ADA status. 
 
Determination of Sample Size 
While this study is not a formal bioequivalence study, a total of 162 subjects (81 subjects per treatment group) 
are required for this study to achieve with 80% power and a 90% 2-sided CI for geometric mean ratios of AUC 
and Cmax being within a limit of 0.8 to 1.25 inclusive.  The calculation is based on two one-sided tests (TOST) at 
5% alpha level under an assumption of maximum 50% CV PK variability for primary endpoints of 
benralizumab AUC and Cmax.  Assuming 10% dropout rate, 180 subjects will be enrolled to provide adequate 
numbers of subjects to assess the primary and secondary objectives of the study. 
 
 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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07 July 2017 
 
1. 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ................................................................................................... 2 
PROTOCOL SYNOPSIS .......................................................................................................... 3 
1. 
TABLE OF CONTENTS ................................................................................................... 7 
1.1. 
List of Tables ............................................................................................................. 12 
2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ..................................... 13 
3. 
ETHICAL AND REGULATORY REQUIREMENTS ................................................... 16 
3.1. 
Ethical Conduct of the Study .................................................................................... 16 
3.2. 
Subject Data Protection ............................................................................................. 16 
3.3. 
Ethics and Regulatory Review .................................................................................. 16 
3.4. 
Insurance ................................................................................................................... 17 
3.5. 
Informed Consent ...................................................................................................... 17 
3.6. 
Changes to the Protocol and Informed Consent Document ...................................... 17 
4. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ....................... 18 
5. 
INTRODUCTION ............................................................................................................ 22 
5.1. 
Background Information ........................................................................................... 22 
5.2. 
Study Rationale ......................................................................................................... 23 
5.3. 
Dose Rationale .......................................................................................................... 23 
5.4. 
Adverse Events .......................................................................................................... 24 
5.5. 
Risk-benefit and Ethical Assessment ........................................................................ 24 
6. 
STUDY OBJECTIVES .................................................................................................... 26 
6.1. 
Primary Objective ..................................................................................................... 26 
6.2. 
Secondary Objectives ................................................................................................ 26 
7. 
OVERALL DESIGN AND PLAN OF THE STUDY...................................................... 27 
7.1. 
Overall Study Design ................................................................................................ 27 
7.1.1. 
End of Study ...................................................................................................... 27 
7.1.2. 
Interim Analyses ................................................................................................ 28 
7.1.3. 
Expected Duration of the Study ......................................................................... 28 
7.2. 
Schedule of Assessments .......................................................................................... 28 
7.3. 
Order of Assessments ................................................................................................ 29 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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7.4. 
Restrictions During the Study ................................................................................... 29 
7.4.1. 
Reproductive Restrictions .................................................................................. 30 
7.4.1.1. 
Women of Non-Child-Bearing Potential .................................................... 30 
7.4.1.2. 
Male Subjects ............................................................................................. 30 
7.5. 
Selection of Study Population ................................................................................... 32 
7.5.1. 
Inclusion Criteria ............................................................................................... 32 
7.5.2. 
Exclusion Criteria .............................................................................................. 33 
7.5.3. 
Discontinuation Individual Stopping Criteria and Withdrawal from the Study 35 
7.5.4. 
Premature Termination of the Study and Stopping Criteria .............................. 35 
7.5.5. 
Total Blood Volume .......................................................................................... 36 
8. 
TREATMENTS ................................................................................................................ 37 
8.1. 
Identity of the Investigational Medicinal Product ..................................................... 37 
8.2. 
Supply of Investigational Medicinal Product ............................................................ 37 
8.3. 
Storage and Handling Procedures ............................................................................. 38 
8.4. 
Labeling ..................................................................................................................... 38 
8.5. 
Drug Accountability, Dispensing and Destruction ................................................... 38 
8.6. 
Dose and Treatment Regimens ................................................................................. 38 
8.7. 
Concomitant and Post-study Treatment(s) ................................................................ 39 
8.8. 
Treatment Compliance .............................................................................................. 39 
8.9. 
Randomization .......................................................................................................... 39 
8.9.1. 
Subject Enrolment and Randomization ............................................................. 39 
8.9.2. 
Procedures for Randomization ........................................................................... 40 
8.9.3. 
Procedures for Handling Incorrectly Randomized Subjects .............................. 40 
8.10. Blinding ..................................................................................................................... 40 
9. 
MEASUREMENTS AND METHODS OF ASSESSMENTS ......................................... 41 
9.1. 
Appropriateness of Measurements ............................................................................ 41 
9.2. 
Pharmacokinetics ...................................................................................................... 41 
9.2.1. 
Sample Collection and Handling ....................................................................... 41 
9.2.2. 
Pharmacokinetic Drug Assays ........................................................................... 41 
9.2.3. 
Disposal of Pharmacokinetic Samples ............................................................... 41 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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07 July 2017 
 
9.3. 
Safety and Eligibility Measurements ........................................................................ 42 
9.3.1. 
Adverse Events .................................................................................................. 42 
9.3.2. 
Vital Signs .......................................................................................................... 42 
9.3.3. 
Resting 12-lead Electrocardiogram.................................................................... 42 
9.3.4. 
Physical Examination......................................................................................... 43 
9.3.5. 
Laboratory Assessments .................................................................................... 43 
9.3.5.1. 
Hematology ................................................................................................ 43 
9.3.5.2. 
Serum Clinical Chemistry .......................................................................... 43 
9.3.5.3. 
Urinalysis .................................................................................................... 44 
9.3.5.4. 
Pregnancy Testing (Female Subjects Only) ............................................... 44 
9.3.5.5. 
Viral Serology............................................................................................. 44 
9.3.5.6. 
Drugs of Abuse and Alcohol ...................................................................... 44 
9.3.6. 
Concomitant Medication .................................................................................... 44 
9.4. 
Immunogenicity ........................................................................................................ 44 
9.4.1. 
Sample Collection and Handling ....................................................................... 44 
9.4.2. 
Immunogenicity Assays ..................................................................................... 44 
9.4.3. 
Disposal of Immunogenicity Samples ............................................................... 45 
9.5. 
Procedures for Handling of Biological Samples ....................................................... 45 
9.5.1. 
Storage And Destruction of Biological Samples ............................................... 45 
9.5.1.1. 
Pharmacokinetic and Immunogenicity Samples......................................... 45 
9.5.2. 
Labeling and Shipment of Biohazard Samples .................................................. 45 
9.5.3. 
Chain of Custody Of Biological Samples .......................................................... 45 
9.5.4. 
Withdrawal of Informed Consent for Donated Biological Samples .................. 46 
10. DATA QUALITY ASSURANCE AND DATA MANAGEMENT ................................ 47 
10.1. Quality Control and Source Data Verification .......................................................... 47 
10.2. Audit/Inspections ...................................................................................................... 47 
10.3. Study Monitoring ...................................................................................................... 47 
10.4. Data Collection .......................................................................................................... 47 
10.4.1. Case Report Forms and Source Documents....................................................... 48 
10.4.2. Access to Source Documents ............................................................................. 48 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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10.5. Data Management ..................................................................................................... 48 
11. STATISTICAL METHODS............................................................................................. 50 
11.1. Overview ................................................................................................................... 50 
11.2. General Statistical Methodology ............................................................................... 50 
11.3. Study Populations ...................................................................................................... 50 
11.3.1. Safety Analysis Set ............................................................................................ 50 
11.3.2. Pharmacokinetic Analysis Set............................................................................ 50 
11.4. Determination of Sample Size................................................................................... 50 
11.5. Protocol Deviations ................................................................................................... 51 
11.6. Subject Disposition ................................................................................................... 51 
11.7. Demographic and Baseline Data ............................................................................... 51 
11.8. Prior and Concomitant Medication and Drug Administration .................................. 51 
11.9. Pharmacokinetic Analysis ......................................................................................... 51 
11.9.1. Pharmacokinetic Parameters .............................................................................. 51 
11.9.2. Derivation of Pharmacokinetic Parameters ....................................................... 52 
11.9.3. Presentation of Pharmacokinetic Data ............................................................... 52 
11.9.4. Statistical Analysis of Pharmacokinetic Data .................................................... 52 
11.9.4.1. 
Primary PK Analysis Method ..................................................................... 52 
11.9.4.2. 
Secondary PK Analysis Method ................................................................. 53 
11.10. Analysis of Safety Data ............................................................................................. 53 
11.10.1. Adverse Events .................................................................................................. 53 
11.10.2. Vital Signs .......................................................................................................... 53 
11.10.3. Resting 12-Lead Electrocardiogram .................................................................. 53 
11.10.4. Physical Examination......................................................................................... 53 
11.10.5. Laboratory Assessments .................................................................................... 53 
11.11. Analysis of Immunogenicity Data............................................................................. 54 
12. ADVERSE EVENTS ....................................................................................................... 55 
12.1. Definitions ................................................................................................................. 55 
12.1.1. Definition of Adverse Events............................................................................. 55 
12.1.2. Definitions of Serious Adverse Event................................................................ 55 

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Clinical Study Protocol 
Study Code: D3250C00030 
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Drug substance: Benralizumab (MEDI-563) 
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12.1.3. Other Significant Adverse Events ...................................................................... 55 
12.2. Recording of Adverse Events .................................................................................... 56 
12.2.1. Time Period for Collection of Adverse Events .................................................. 56 
12.2.2. Follow-up of Unresolved Adverse Events ......................................................... 56 
12.2.3. Variables ............................................................................................................ 56 
12.2.4. Causality Collection ........................................................................................... 57 
12.2.5. Adverse Events Based on Symptoms and Signs ................................................ 57 
12.2.6. Adverse Events Based on Examinations and Tests ........................................... 57 
12.2.7. Hy's Law ............................................................................................................ 58 
12.3. Reporting of Serious Adverse Events ....................................................................... 58 
13. LEGAL AND ADMINISTRATIVE ASPECTS .............................................................. 59 
13.1. Archiving of Study Documents ................................................................................. 59 
13.2. Publication of Study Results ..................................................................................... 59 
13.3. Clinical Study Report ................................................................................................ 59 
14. REFERENCE LIST .......................................................................................................... 60 
15. APPENDICES .................................................................................................................. 63 
15.1. Additional Safety Information .................................................................................. 63 
15.2. International Airline Transportation Association 6.2 Guidance Document .............. 65 
15.3. Actions Required in Cases of Combined Increase of Aminotransferase and Total 
Bilirubin - Hy’s Law ................................................................................................. 67 
16. SIGNATURES ................................................................................................................. 70 
16.1. Declaration of Sponsor or Responsible Medical Expert (Physician) ........................ 70 
16.2. Declaration of Sponsor or Responsible Medical Expert (Global Statistician) .......... 71 
16.3. Declaration of Sponsor or Responsible Medical Expert (Lead Clinical 
Pharmacologist) ....................................................................................................... 72 
16.4. Declaration of the Principal Investigator .................................................................. 73 
16.5. Declaration of the Principal Investigator .................................................................. 74 
16.6. Declaration of the Deputy Principal Investigator ...................................................... 75 
 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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07 July 2017 
 
1.1. 
List of Tables 
Table 1 
Design of a Pharmacokinetic Comparability Study in Healthy Subjects for 
Benralizumab Accessorized Pre-Filled Syringe and Autoinjector Devices ...... 27 
Table 2 
Schedule of Assessments ................................................................................... 28 
Table 3 
Total Blood Volume .......................................................................................... 36 
Table 4 
Identity of the Investigational Medicinal Product (Accessorized Pre-Filled 
Syringe) .............................................................................................................. 37 
Table 5 
Identity of the Investigational Medicinal Product (Autoinjector)...................... 37 
 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or 
special term 
Explanation 
ADA 
Anti-drug antibody 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
AE 
Adverse event (see definition in Section 12.1.1) 
AI 
Autoinjector 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANOVA 
Analysis of variance 
APFS 
Accessorized pre-filled syringe device 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve  
AZRand 
AstraZeneca randomization system 
beta-hCG 
Beta human chorionic gonadotropin 
BLQ 
Below the limit of quantification 
BMI 
Body mass index 
BP 
Blood pressure 
bpm 
Beats per minute 
CI 
Confidence interval  
CL/F 
Apparent extravascular clearance 
ClinBaseTM 
PAREXEL's electronic source data capturing and information 
management system 
Cmax 
Maximum observed concentration 
CRF 
Case report form 
CRO 
Contract research organization 
CRP 
C-reactive protein 
CSR 
Clinical study report  
CV 
Coefficient of variation 
DCF 
Data clarification form 
DGR 
Dangerous Goods Regulation 
DILI 
Drug-Induced Liver Injury 
DMP 
Data management plan 
DVS 
Data validation specification 
ECG 
Electrocardiogram 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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07 July 2017 
 
Abbreviation or 
special term 
Explanation 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transpeptidase (transferase) 
GINA 
Global Initiative for Asthma 
GMP 
Good Manufacturing Practice 
Hb 
Hemoglobin 
HBsAg 
Hepatitis B surface antigen 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
HL 
Hy’s Law 
IATA 
International Airline Transportation Association 
ICD 
Informed Consent Document 
ICH 
International Council for Harmonisation 
ICS 
Inhaled corticosteroids 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IL-5 
Interleukin-5  
IL-5R 
Interleukin 5 receptor 
IMP 
Investigational medicinal product 
IV 
Intravenous 
IUD 
Intrauterine device 
LABA 
Long-acting β2-agonists 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
n 
Number of subjects 
NCA 
Non-compartmental analysis 
OAE 
Other significant adverse events 
OTC 
Over-the-counter 
PD 
Pharmacodynamic (s) 
PDS 
Protocol deviation specification (document) 
PHL 
Potential Hy’s Law 
PI 
Principal Investigator 
PK 
Pharmacokinetic (s) 
Q4W 
Every 4 weeks 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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Abbreviation or 
special term 
Explanation 
Q8W 
Every 8 weeks 
QCD 
Quantitative Clinical Development 
R&D 
Research and Development 
RA 
Regulatory Authority 
RBC 
Red blood cell 
SAE 
Serious adverse event (see definition in Section 12.1.2). 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard deviation 
SOC 
System Organ Class 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
t½   
Terminal half-life 
TCA 
Tricyclic anti-depressant 
TCS 
Tata Consultancy Services – an AstraZeneca partner who conduct 
data entry onto Sapphire 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time when the maximum concentration is observed 
TOST 
Two one-sided test 
TSH 
Thyroid-stimulating hormone 
UK 
United Kingdom 
ULN 
Upper limit of normal 
USA 
United States of America 
Vz/F 
Apparent volume of distribution based on the terminal phase 
WBC 
White blood cell 
 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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3. 
ETHICAL AND REGULATORY REQUIREMENTS 
3.1. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki (version 1996) and are consistent with International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and the AstraZeneca policy on Bioethics 
and Human Biological Samples. 
3.2. 
Subject Data Protection 
The Informed Consent Document (ICD) will incorporate wording that complies with relevant 
data protection and privacy legislation. 
All clinical study findings and documents will be regarded as confidential.  The Investigator 
and members of his research team must not disclose such information without prior written 
approval from the Sponsor. 
The anonymity of participating subjects must be maintained.  Subjects will be specified in 
PAREXEL’s ClinBase™ system and other documents by their subject number, not by name.  
Documents that identify the subject (e.g., signed ICD) will be maintained in confidence by 
the Investigator. 
Study data will be stored in accordance with local and global data protection laws. 
3.3. 
Ethics and Regulatory Review 
The study will be submitted to the national regulatory agency for review and approval, by 
PAREXEL in accordance with local regulatory procedures. 
The study will be submitted to the Independent Ethics Committee (IEC) for ethical review 
and approval, by PAREXEL in accordance with local procedures. 
PAREXEL will provide the Ethics Committee and Principal Investigator (PI) with safety 
updates/reports according to local requirements, including Suspected Unexpected Adverse 
Reactions (SUSARs), where relevant. 
AstraZeneca will provide the Regulatory Authority (RA) with safety updates/reports 
according to local requirements, including SUSARs, where relevant.  
Compensation will be reasonable and related to the nature and degree of inconvenience and 
discomfort as a result of participation in the study.  Information on how participants will be 
compensated is contained in the ICD. 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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3.4. 
Insurance 
The Sponsor has covered this clinical study by means of an insurance of the clinical study 
according to national requirements.  The name and address of the relevant insurance 
company, the certificate of insurance, the policy number and the sum insured are provided in 
the Investigator's Site File. 
3.5. 
Informed Consent 
The subjects shall be informed of the nature, significance, implications and risks of the trial, 
and informed consent will be freely given and evidenced in writing, dated and signed, or 
otherwise marked, by the subject as evidence to indicate his free informed consent, prior to 
the start of the study. 
In conformance with the law, the nature of the informed consent will comply with the 
Declaration 
of 
Helsinki 
(version 
1996), 
the 
current 
requirements 
of 
GCP 
(CPMP/ICH/135/95) and local regulation, which ever affords the greater subject protection. 
3.6. 
Changes to the Protocol and Informed Consent Document 
Study procedures will not be changed without the mutual agreement of the Investigator and 
AstraZeneca. 
If there are any substantial changes to the study protocol, then these changes will be 
documented in a study protocol amendment and where required in a new version of the study 
protocol.  The amendment should be approved by the IEC and the national RA, before 
implementation, as appropriate.  Local requirements should be followed for revised protocols. 
If a protocol amendment requires a change to the ICD, the IEC should approve the revised 
ICD before the revised form is used. 
If local regulations require, any administrative change will be communicated to or approved 
by the IEC. 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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4. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
Sponsor: 
AstraZeneca AB 
151 85 Södertälje 
Sweden 
 
Sponsor’s Lead Physician: 
 
AstraZeneca R&D Gothenburg 
Pepparedsleden 1 
431 83 Mölndal 
Sweden 
Tel: 
 
 
Mobile: 
 
E-mail: 
 
 
Sponsor’s (Lead) Clinical 
Pharmacologist 
 
MedImmune LLC 
One MedImmune Way 
Gaithersburg, MD  20878 
United States 
Tel: 
 
 
E-mail: 
 
 
Clinical Pharmacokineticist 
 
Quantitative Clinical Development 
PAREXEL International 
The Quays, 101-105 Oxford Road 
Uxbridge, Middlesex, UB8 1LZ, 
United Kingdom 
Tel: 
 
 
E-mail: 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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Sponsor’s Biostatistician: 
 
AstraZeneca LP 
One MedImmune Way 
Gaithersburg, Maryland  20878 
United States 
Tel: 
 
 
E-mail: 
 
 
 
AstraZeneca LP 
One MedImmune Way 
Gaithersburg, Maryland  20878 
United States 
Tel: 
 
 
E-mail:  
 
 
Principal Investigators: 
 
PAREXEL Early Phase Clinical Unit Berlin 
Spandauer Damm 130 
14050 Berlin 
Germany 
Tel: 
 
 
E-mail: 
 
 
 
 
Senior Clinical Research Physician 
PAREXEL Early Phase Clinical Unit London 
Level 7, Northwick Park Hospital 
Watford Road, Harrow 
Middlesex HA1 3UJ 
United Kingdom 
Tel: 
 
 
E-mail: 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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07 July 2017 
 
Deputy Principal Investigator: 
 
PAREXEL Early Phase Clinical Unit Berlin 
Spandauer Damm 130 
14050 Berlin 
Germany 
Tel: 
 
 
E-mail: 
 
 
Contract Research 
Organization: 
PAREXEL Early Phase Clinical Unit Berlin 
On the premises of Klinikum Westend, Haus 31 
Spandauer Damm 130 
14050 Berlin 
Germany 
 
 
PAREXEL Early Phase Clinical Unit London 
Level 7, Northwick Park Hospital 
Watford Road, Harrow 
Middlesex HA1 3UJ 
United Kingdom 
 
Clinical Laboratory: 
Synlab Clinical Trial GmbH 
Turmstr. 21 (House M) 
10559 Berlin 
Germany 
Contact: 
 
E mail: 
  
Tel: 
 
 
Fax:  
 
 
 
The Doctors Laboratory (TDL) 
60 Whitfield Street 
London W1T 4EU 
United Kingdom 
Tel: 
 
 
Fax:  
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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07 July 2017 
 
Analytical Laboratory: 
(Pharmacokinetic Sample 
Analysis) 
PPD Bioanalytical Lab  
2244 Dabney Road  
Richmond, VA 23230-3323  
United States  
Contact: 
 
E-mail: 
 
Tel: 
 
 
 
Adverse Event Reporting: 
AstraZeneca Patient Safety Data Entry Site 
Tata Consultancy Services 
Fax:   
 
E-mail: AEMailboxClinicalTrialTCS@astrazeneca.com 
 
A list and contact details of Investigators and other key study team members are provided in 
the Project Plan in the electronic Investigator’s Site File.  A list of all participating 
Investigators will be provided in the clinical study report (CSR). 
PPD
PPD
PPD
PPD

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
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5. 
INTRODUCTION 
5.1. 
Background Information 
Asthma is a syndrome characterized by airway inflammation, reversible airway obstruction 
and airway hyper-responsiveness.  Patients present clinically with recurrent wheezing, 
shortness of breath, cough and chest tightness.  Asthma is a leading cause of morbidity with a 
global prevalence of approximately 300 million; it is estimated that the number of people 
with asthma may increase to 400 to 450 million people worldwide by 2025 [14]. 
The current approach to anti-inflammatory controller therapy in asthma is based on a 
stepwise intensification of a daily maintenance regimen centered around inhaled 
corticosteroids (ICS) and leukotriene receptor antagonists (LTRA), with the addition of 
long-acting β2 agonists (LABA) in patients with more severe asthma [10, 16].  Despite 
treatment per management guidelines, up to 50% of patients have asthma that is not well 
controlled [1; 2].  This results in considerable impact on quality of life, disproportionate use 
of healthcare resources, and adverse reactions from regular systemic steroid use.  Therefore, 
there remains an unmet medical need for patients whose asthma is not controlled by existing 
therapies. 
The observed variability in clinical response to currently available asthma therapies appears 
to be related, in part, to distinctive inflammatory phenotypes [21].  In particular, asthma 
associated with eosinophilic inflammation in the airway (often referred to as eosinophilic 
asthma) is common (approximately 40% to 60% of asthmatics) with the degree of 
eosinophilia associated with clinical severity including the risk of asthma exacerbations [4, 
13, 7, 17, 22, 18].  Interleukin-5 (IL-5) is a key cytokine essential for eosinophil trafficking 
and survival [15].  
Benralizumab (MEDI-563) is a humanized, afucosylated, monoclonal antibody (mAb) that 
binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.  The 
IL-5 receptor (IL-5R) is expressed almost exclusively on the surface of eosinophils and 
basophils [19, 20].  Afucosylation confers enhanced antibody-dependent cellular cytotoxicity 
(ADCC) which results in highly efficient eosinophil depletion by apoptosis [11].  Single and 
repeated doses of benralizumab in mild to severe asthma patients have resulted in depletion 
of blood and airway eosinophils [5, 15, 12].  A dose-finding trial in severe asthma proved 
benralizumab to have benefit across a range of asthma outcomes including reductions in 
asthma exacerbations, improvements in lung function, and reduction in symptoms [6].   
The efficacy and safety of benralizumab has been confirmed in 2 large Phase 3 trials, in 
severe asthmatics with a history of exacerbations and still symptomatic despite using 
medium-to-high dose ICS/LABAs with or without oral corticosteroids or additional controller 

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
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07 July 2017 
 
medications [3, 9].  The dose studied in these trials was 30 mg, a dose derived from 
pharmacokinetic/pharmacodynamic (PK/PD) modeling of the Phase 2 dose-finding study, 
administered in 2 dosing regimens – either 30 mg every 4 weeks (Q4W) or 30 mg Q4W for 
the first 3 doses followed by dosing every 8 weeks (Q8W) thereafter.  The primary endpoint 
in each study was the annual rate of asthma-related exacerbations with key secondary 
endpoints being FEV1 and asthma symptoms as defined by a daily patient diary.  
5.2. 
Study Rationale 
Benralizumab is a humanized anti-eosinophil mAb and depletes eosinophils via a mechanism 
of enhanced ADCC.  Benralizumab’s unique mechanism of action induces direct, rapid and 
nearly complete depletion of eosinophils in the lung tissue, sputum, blood and bone marrow.  
Benralizumab has demonstrated pharmacodynamic activity and clinical efficacy in asthma 
control in Phase 1, 2 and 3 studies.  
In global pivotal trials, benralizumab has been administered by health care providers using 
accessorized pre-filled syringe (APFS) device.  The APFS combination product is a 
single-use, disposable system that is designed to administer the labeled dose into the 
subcutaneous (SC) space as 1 injection and automatically provides a safety mechanism to 
reduce the occurrence of accidental needle-sticks during disposal of the system.  The 
functionality and reliability of APFS for home administration were evaluated in another study 
(GREGALE).  The Autoinjector (AI) combination product is an automated, single-use, 
disposable system that is designed to administer the labeled dose into the SC space as 
1 injection in a two-step operation and has a locking needle shield to reduce the occurrence of 
accidental needle-sticks during disposal of the system. 
An open-label, single dose PK comparability study is required to demonstrate comparable 
drug exposure (AUC and Cmax) following SC benralizumab administration by using APFS or 
AI devices.  As for other therapeutic immunoglobulin G (IgG) monoclonal antibodies, body 
weight was previously identified as a relevant PK covariate for benralizumab.  In addition, 
the use of different anatomical regions for SC injections may influence the absorption of 
protein drugs.  In this study, descriptive comparison of benralizumab PK by weight and 
injection site will be provided. 
5.3. 
Dose Rationale 
The efficacy and safety of a fixed 30 mg SC dose of benralizumab has been evaluated in 
2 large Phase 3 studies in severe asthma patients with an eosinophilic phenotype [3, 9].   

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Clinical Study Protocol 
Study Code: D3250C00030 
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Drug substance: Benralizumab (MEDI-563) 
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5.4. 
Adverse Events 
Possible Risks (Potential Risks) 
• Serious infections (defined as infections that are life-threatening, requiring intravenous 
(IV) antibiotics or hospitalization) 
• Helminth parasitic infections 
• Hypersensitivity/allergic reactions 
• Immune complex disease (type III hypersensitivity reactions) 
• Malignancies 
Adverse Events (Observed) 
In the recent Phase 3 SIROCCO study [3], the most common (observed in > 3% of the 
patients) adverse events (AEs) were asthma, nasopharyngitis, upper respiratory tract 
infection, headache, bronchitis, sinusitis, influenza, acute sinusitis, back pain, cough, 
hypertension, pyrexia, nausea, rhinitis, pharyngitis, arthralgia, rhinitis allergic, viral infection, 
pain in extremity, dyspnea, gastro esophageal reflux disease, asthenia, dizziness and 
gastroenteritis. 
In the recent Phase 3 CALIMA study [9], the most common (observed in > 3% of the 
patients) AEs were nasopharyngitis, asthma, upper respiratory tract infection, bronchitis, 
headache, sinusitis, hypertension, influenza, rhinitis, rhinitis allergic, nasal congestion, 
diarrhea, arthralgia, back pain, gastroenteritis, contusion, cough, pharyngitis, pyrexia, 
oropharyngeal pain, oral candidiasis, pneumonia bacterial and viral upper respiratory tract 
infection. 
In both studies, the AEs showed a largely similar distribution between treatment and placebo 
arms. 
5.5. 
Risk-benefit and Ethical Assessment 
Benralizumab is primarily being studied in severe asthma where there are few treatment 
options for patients whose asthma remains uncontrolled on high dose ICS/LABA and oral 
corticosteroids [10].  In adult patients whose asthma was poorly controlled on 
medium-to-high dose ICS/LABA therapy, benralizumab at doses of ≥ 20 mg produced 
improvements in multiple metrics of asthma control including the annual rate of asthma 
exacerbations, lung function, ACQ-6 scores, and symptoms [6].  These findings have 
subsequently been confirmed in 2 large Phase 3 studies [3, 9] where a fixed dose of 30 mg 
was given either Q4W or Q8W. 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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Development of anti-drug antibodies (ADA) to benralizumab has been documented.  
Theoretical risks of developing ADA include decreased drug efficacy and hypersensitivity 
reactions (e.g., anaphylaxis or immune complex disease).  Eosinophils are a prominent 
feature of the inflammatory response to helminthic parasitic infections and the presence of 
infiltrating eosinophils has been circumstantially associated with a positive prognosis in 
certain solid tumors.  Therefore, there is a theoretical risk that prolonged eosinophil depletion 
may diminish the ability to defend against helminthic parasites, or negatively impact the 
natural history of certain malignant tumors.  Risk minimization measures herein include 
exclusion of subjects with untreated parasitic infection and active or recent malignancy, in 
conjunction with the performance of routine pharmacovigilance activities. 
The efficacy and safety data obtained to date support the continued clinical development of 
benralizumab in patients with asthma.  
A detailed assessment of the overall risk/benefit of benralizumab is provided in the 
Investigator’s Brochure. 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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6. 
STUDY OBJECTIVES 
6.1. 
Primary Objective 
• To compare the PK exposure following single SC administration of benralizumab by 
using APFS or AI devices 
6.2. 
Secondary Objectives 
• To evaluate the PK of benralizumab administered to various anatomical injection sites 
and in subjects with different body weight ranges 
• To evaluate the safety and tolerability of benralizumab 
• To evaluate the immunogenicity of benralizumab 
Refer to Section 11.9.1 for PK parameters, Section 9.3 for safety variables and Section 9.4 for 
immunogenicity assessments. 

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
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7. 
OVERALL DESIGN AND PLAN OF THE STUDY 
7.1. 
Overall Study Design 
This study will be a multicenter, randomized, open-label, parallel group Phase 1 study 
designed to compare benralizumab PK exposure in healthy subjects following single SC 
administration of fixed 30 mg dose of benralizumab by using APFS and single-use AI.  
Eligible subjects will be healthy subjects aged 18 to 55 years, with a body weight of 55 to 
100 kg and a body mass index (BMI) of 18 to 29.9 kg/m2.  A total of 180 subjects will be 
randomized.  Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg 
and 85 to 100 kg), and within each of the 3 weight groups, subjects will be randomized 
1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS or AI) with injection site (upper 
arm, abdomen or thigh), presented in Table 1.  This study will be performed at 2 study 
centers. 
Table 1 
Design of a Pharmacokinetic Comparability Study in Healthy Subjects for 
Benralizumab Accessorized Pre-Filled Syringe and Autoinjector Devices  
Number of Subjects 
APFS 
AI 
Total 
Upper Arm 
Abdomen 
Thigh 
Upper Arm 
Abdomen 
Thigh 
Body 
Weight 
55.0 to 69.9 kg 
10 
10 
10 
10 
10 
10 
60 
70.0 to 84.9 kg 
10 
10 
10 
10 
10 
10 
60 
85.0 to 100.0 kg 
10 
10 
10 
10 
10 
10 
60 
Total 
90 
90 
180 
AI: Autoinjector; APFS: Accessorized pre-filled syringe device 
The study will comprise of: 
• A screening period of maximum of 28 days, 
• One treatment period during which subjects will be resident from the day before dosing 
(Day -1) until 2 hours after dosing on Day 1.  The subjects will then return to the center 
for ambulant visits on Days 2, 4, 5, 6, 8, 15, 29 and 43, and 
• An End-of-Treatment visit on Day 57 (Week 8). 
After a screening period of up to 28 days, eligible subjects will be admitted to the unit on 
Day -1 (1 day before dosing) to reassess their eligibility.  Subjects who meet eligibility 
criteria will be randomized on Day 1 to receive a single dose of 30 mg benralizumab by 
either APFS or AI device.  The study will be completed after the End-of-treatment visit on 
Day 57 (Week 8). 
7.1.1. 
End of Study 
The end of study is defined as the last subject’s last visit to the clinical unit. 

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7.1.2. 
Interim Analyses 
No interim analyses will be performed in this study. 
7.1.3. 
Expected Duration of the Study 
Each subject will be involved in the study for 12 to 13 weeks (8 to 9 weeks active 
participation) and 28 days screening period. 
7.2. 
Schedule of Assessments 
The schedule of assessments displaying assessments/tasks and time points is presented in 
Table 2. 
Table 2 
Schedule of Assessments 
 
Screening 
Day -28 to -2 
Day -1 
Days 1 to 57 
Informed consent 
X 
 
 
Inclusion/exclusion criteria 
X 
X 
 
Height 
X 
 
 
Weight 
X 
X 
 
Other demographic data 
X 
 
 
Medical history 
X 
 
 
Urinary drug and alcohol screen  
X 
X 
 
Serum pregnancy and FSH test  
X 
 
 
Urine pregnancy test (dipstick) 
 
X 
Day 57 
Serology 
X 
 
 
Randomization 
 
Day 1 
Study residency: 
 
 
 
Check-in 
 
X 
Check-out 
 
 
Day 1 (2 h post-dose) 
Non-residential visit 
X 
 
Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 
IMP (Benralizumab) 
administration: 
 
 
Day 1 (0 h) 
Safety and tolerability: 
 
 
 
Adverse event questioning 
 
 
Pre-dose and 2 h post-dose (Day 1), Days 2, 4, 
5, 6, 8, 15, 29, 43 and 57 
Vital signs 
X 
X 
Pre-dose and 2 h post-dose (Day 1), Days 2, 4, 
5, 6, 8, 15, 29, 43 and 57 
12-lead electrocardiogram 
X 
 
Days 1, 29 and 57 
Clinical laboratory evaluations 
X 
X 
Days 8, 29 and 57 
Physical examination 
X 
X(brief) 
Days 8, 29 and 57 
(2 h post dose (brief)) 
Pharmacokinetics 
 
 
 
Serum benralizumab 
concentrationa 
 
 
Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 
and 57 
Immunogenicity 
 
 
 
ADA 
 
 
Pre-dose (Day 1), Days 29 and 57 
ADA: anti-drug antibody; FSH: follicle-stimulating hormone; IMP: investigational medicinal product 
a 
Samples to determine serum Benralizumab concentrations will be collected at consistent times across the 
different study days. 

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7.3. 
Order of Assessments 
It is important that PK sampling occurs as close as possible to the scheduled time.  In order to 
achieve this, other assessments scheduled at the same time may be initiated prior to the time 
point. 
The sequence at a particular time point is: 
1. Electrocardiograms (ECGs), if applicable 
2. Vital signs (systolic and diastolic blood pressure [BP], pulse rate and oral temperature) 
3. Pharmacokinetic blood sampling (will be drawn at the specified time points) 
4. Anti-drug antibody and safety laboratory blood sampling. 
7.4. 
Restrictions During the Study 
The following restrictions apply for the specified times during the study period: 
1. On Day 1 of the treatment period, subjects will be fasted (except for water) for 10 hours 
prior to dosing until 2 hours after dosing.  Subjects will receive a meal before they are 
discharged from the clinical unit. 
2. Subjects should abstain from alcohol for 72 hours prior to check-in on Day -1, until after 
their Day 15 PK sampling visit. 
3. Subjects should abstain from caffeine-containing foods and beverages for 24 hour prior to 
check-in on Day -1, until discharge from the clinical unit. 
4. During admission period, subjects will receive a standard diet, which excludes 
alcohol-containing products.  No additional food or beverages must be consumed while in 
the clinical unit. 
5. During the subjects’ outpatient periods, subjects should abstain from consuming 
high-energy drinks (e.g., red bull), food containing poppy seeds and any over-the-counter 
(OTC) medication or herbal preparations until after their End-of-Treatment Visit has been 
completed.  Subjects should also limit their caffeine intake to equivalent of 3 cups of 
coffee per day (1 cup = 250 mL soda, 180 mL coffee or 240 mL tea).  Subjects should 
consume no more than 2 units of alcohol per day (1 unit = 10 mL or 8 g of pure alcohol) 
and completely abstain from 72 hours prior next visit. 
6. Subjects will be required to abstain from blood or plasma donation until 3 months after 
the final medical examination at the study End-of-Treatment visit. 
7. Medication restrictions.  Refer to Section 8.7. 

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7.4.1. 
Reproductive Restrictions 
7.4.1.1. 
Women of Non-Child-Bearing Potential 
Women of non-child-bearing potential are defined as female subjects who are permanently 
surgically sterilized or post-menopausal. 
Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral 
salpingectomy but excludes bilateral tubal ligation. 
Females are considered post-menopausal if they have had amenorrhea for at least 12 months 
or more following cessation of all exogenous hormonal treatments and follicle-stimulating 
hormone (FSH) levels are in the post-menopausal range. 
Pregnancy Testing 
Women of non-child-bearing potential can be included only after a negative highly sensitive 
serum pregnancy test.  Additionally urine pregnancy testing will be done as per the schedule 
of assessments. 
7.4.1.2. 
Male Subjects 
Restrictions for Male Subjects 
There is no information about effects that benralizumab could have on the development of the 
fetus in humans.  Therefore, it is important that women of child-bearing potential, who are 
the partners of male subjects, do not become pregnant during the study and for a total period 
of 16 weeks after the male subject has attended the study End-of-Treatment visit. 
As a precaution, all male subjects should avoid fathering a child by either true abstinence* or 
use together, with their female partner/spouse, a highly effective contraception form of birth 
control in combination with a barrier method, starting from the time of investigational 
medicinal product (IMP) administration until 16 weeks after the study End-of-Treatment 
visit.  
* True abstinence: When this is in line with the preferred and usual lifestyle of the subject. 
(Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], 
declaration of abstinence for the duration of a trial and withdrawal are not acceptable 
methods of contraception). 

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Highly effective contraception is defined as having a low failure rate, i.e., less than 1% per 
year when used consistently and correctly.  Highly effective contraception forms of birth 
control include: 
• Hormonal contraception, i.e., oral, injectable or implantable hormonal contraceptives for 
the female partner/spouse (Note: Not all oral contraception methods have a low failure 
rate.); 
• Hormonal or non-hormonal intrauterine device, established intrauterine device (IUD, 
loop) or intrauterine system for the female partner/spouse; 
• The subject has undergone effective surgical sterilization before he entered the clinical 
study; 
• The subject’s female partner/spouse that has undergone effective surgical sterilization 
before the subject entered the clinical study and she is the sole sexual partner of the 
subject during the clinical study. 
Barrier methods of contraception include: 
• Condom (without spermicidal foam/gel/film/cream/suppository or fat- or oil-containing 
lubricants); 
• Occlusive 
cap 
(diaphragm 
or 
cervical/vault 
caps) 
with 
spermicidal 
foam/gel/film/cream/suppository for the female partner/spouse 
Male subjects who have been sterilized are required to use one barrier method of 
contraception (condom) from the time of IMP administration until after the End-of-Treatment 
visit.  
Sperm Donation 
Male subjects should not donate sperm for the duration of the study and for at least 16 weeks 
after the study End-of-Treatment visit. 
Pregnancy 
Subjects will be instructed that if their partner becomes pregnant during the study this should 
be reported to the Investigator.  The Investigator should also be notified of pregnancy 
occurring during the study but confirmed after completion of the study.  In the event that a 
subject’s partner is subsequently found to be pregnant after the subject is included in the 
study, then consent will be sought from the partner and if granted any pregnancy will be 
followed and the status of mother and/or child will be reported to the Sponsor after delivery. 
A pregnancy notification form and follow-up will be completed. 

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7.5. 
Selection of Study Population 
The Investigator should keep a subject-screening log of all potential subjects who consented 
and were subjected to screening procedures. 
Subjects who fail to meet the inclusion criteria or meet any exclusion criterion should not, 
under any circumstances, be randomized into the study.  There can be no exceptions to this 
rule. 
This study will be conducted in male and female subjects.  The study may not necessarily be 
balanced regarding gender.  The study was not formally powered to detect differences 
between genders for the primary endpoint.  It is not planned to perform sub-analyses on 
gender. 
7.5.1. 
Inclusion Criteria 
For inclusion in the study, subjects should fulfill the following criteria: 
1. Provision of signed and dated, written informed consent prior to any study specific 
procedures. 
2. Healthy male and/or female subjects of non-child-bearing potential aged 18 to 55 years 
(inclusive) with suitable veins for cannulation or repeated venipuncture. 
3. Females must have a negative pregnancy test at screening and on admission to the unit, 
must not be lactating and must be of non-child-bearing potential, confirmed at screening 
by fulfilling one of the following criteria: 
3.1. Post-menopausal defined as amenorrhea for at least 12 months or more following 
cessation of all exogenous hormonal treatments and FSH levels in the 
post-menopausal range. 
3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral 
oophorectomy or bilateral salpingectomy but not tubal ligation. 
4.  All male subjects who are sexually active must agree to use a highly effective 
contraception form of birth control in combination with a barrier method from the first 
dose of IMP until 16 weeks after the study End-of-Treatment visit. 
5. Have a BMI between 18 and 29.9 kg/m2 inclusive and weigh at least 55 kg and no more 
than 100 kg inclusive. 
6. Only applicable to the PAREXEL Early Phase Clinical Unit Berlin: Able to understand, 
read and speak the German language. 

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7.5.2. 
Exclusion Criteria 
Subjects will not enter the study if any of the following exclusion criteria are fulfilled: 
1. History of any clinically significant disease or disorder which, in the opinion of the 
Investigator, may either put the subject at risk because of participation in the study, or 
influence the results or the subject’s ability to participate in the study. 
2. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged 
by the Investigator or known history of allergy or reaction to any component of the 
investigational product formulation. 
3. History of anaphylaxis to any biologic therapy. 
4. 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. 
5. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication 
within 30 days prior to the date informed consent is obtained or during the screening 
period. 
6. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, 
neurological, 
musculoskeletal, 
infectious, 
endocrine, 
metabolic, 
hematological, 
psychiatric, or major physical impairment that is not stable in the opinion of the 
Investigator and could: 
6.1. Affect the safety of the subject throughout the study. 
6.2. Influence the findings of the studies or their interpretations. 
6.3. Impede the subject’s ability to complete the entire duration of study. 
7. Any clinically significant abnormal findings in physical examination, vital signs, 
hematology, clinical chemistry, or urinalysis during screening, which in the opinion of the 
Investigator, may put the subject at risk because of his/her participation in the study, or 
may influence the results of the study, or the subject’s ability to complete entire duration 
of the study. 
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 1.5 times 
the upper limit of normal (ULN) confirmed during screening period. 
9. White blood cell count and neutrophils < lower limit of normal. 
10. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of 
the first administration of IMP. 

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11. Any positive result on screening for serum hepatitis B surface antigen or anti-HBc 
antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.  
Subjects with a history of hepatitis B vaccination without history of hepatitis B are 
allowed to enroll. 
12. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as 
judged by the Investigator. 
13. Has received another new chemical entity (defined as a compound which has not been 
approved for marketing) within 3 months of the first administration of  investigational 
product in this study.  The period of exclusion begins 3 months after the final dose or 
1 month after the last visit whichever is the longest.   
 
Note: subjects consented and screened, but not randomized in this study or a previous 
Phase I study, are not excluded. 
14. Plasma donation within 1 month of screening or any blood donation/loss more than 
500 mL during the 3 months prior to screening. 
15. Receipt of immunoglobulin or blood products within 30 days prior to the date informed 
consent is obtained. 
16. Receipt of any marketed (e.g., omalizumab, mepolizumab etc.) or investigational biologic 
within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever 
is longer. 
17. Receipt of live attenuated vaccines 30 days prior to randomization on Day 1. 
18. History of Guillain-Barré syndrome. 
19. Current smokers or those who have smoked or used nicotine products including 
e-cigarettes within the 3 months prior to screening, as judge by the Investigator.  
20. Current malignancy, or history of malignancy except for: 
o Subjects 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 subject is in 
remission and curative therapy was completed at least 12 months prior to the date 
informed consent was obtained. 
o Subjects who have had other malignancies are eligible provided that the subject is in 
remission and curative therapy was completed at least 5 years prior to the date 
informed consent was obtained. 
21. Positive screen for drugs of abuse, of alcohol at screening or on admission to the study 
unit. 
22. Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks 
prior to the first administration of IMP. 

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23. Use of any prescribed or non-prescribed medication including antacids, analgesics (other 
than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (intake of 20 to 
600 times the recommended daily dose) and minerals during the 2 weeks prior to the first 
administration of IMP or longer if the medication has a long half-life  
Note: Hormonal replacement therapy is not allowed for females. 
24. Involvement of any AstraZeneca, PAREXEL or study site employee or their close 
relatives. 
25. Subjects who have previously received benralizumab. 
26. Judgment by the Investigator that the subject should not participate in the study if they 
have any ongoing or recent (i.e., during the screening period) minor medical complaints 
that may interfere with the interpretation of study data or are considered unlikely to 
comply with study procedures, restrictions, and requirements. 
27. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, 
trusteeship, or committed to an institution by governmental or juridical order. 
7.5.3. 
Discontinuation Individual Stopping Criteria and Withdrawal from the 
Study 
Subjects will be discontinued from the study in the following situations: 
• Healthy subject decision.  The healthy subject is at any time free to discontinue treatment, 
without prejudice to further treatment. 
• Severe noncompliance to study protocol. 
• Any significant and clinically relevant changes in the safety parameters (e.g., ECG, BP, 
pulse rate, laboratory assessments and AEs). 
• Study specific withdrawal criteria: If a subject reports symptoms, which are considered 
unacceptable by the subject or the Investigator, he/she will be withdrawn from the study.  
In particular: 
o Any other severe or serious adverse event (SAE) that is judged as possibly related to 
the IMP by the Investigator 
o Any case of Potential Hy’s Law (PHL) according to Appendix 15.3 
The appropriate AE form in the case report form (CRF) is to be completed. 
7.5.4. 
Premature Termination of the Study and Stopping Criteria 
The study may be terminated prematurely if: 
• The PI and the Sponsor assess that the number and/or severity of AEs justify 
discontinuation of the study.  For instance, when there is at least 1 case of 1 SAE 
considered related to the IMP by the PI and the Sponsor. 
• The Sponsor considers the applied doses of the study drug to be no longer relevant. 

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• The Sponsor decides to discontinue the study. 
• Data not known before become available and raise concern about the safety of IMP so 
that continuation would pose potential risks to the subjects. 
Premature termination of the study must be mutually agreed upon by the PI and the Sponsor 
and must be documented.  However, study results will be reported according to the 
requirements outlined in this clinical study protocol as far as applicable. 
7.5.5. 
Total Blood Volume 
The approximate total amount of blood to be collected from each subject in this study, 
excluding repeat samples, is summarized in Table 3. 
Table 3 
Total Blood Volume 
Test 
Sample volume 
(mL) 
Number of samples 
Total blood volume 
(mL) 
Hematology 
2.7 
5 
13.5 
Clinical chemistry 
7.5 
5 
37.5 
Pharmacokinetics 
3.5 
10 
35 
Immunogenicity 
3.5 
3 
10.5 
Total 
 
 
96.5 
Repeat blood samples may be collected for safety reasons.  The maximum volume to be 
drawn from each subject must not exceed 500 mL. 

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8. 
TREATMENTS 
8.1. 
Identity of the Investigational Medicinal Product 
Details on the identity of the IMP are presented in Table 4 and Table 5. 
Table 4 
Identity of the Investigational Medicinal Product (Accessorized Pre-Filled 
Syringe) 
IMP: 
Benralizumab 
Formulation: 
30 mg/mL solution for injection in accessorized pre-filled syringe 
Strength/concentration: 
30 mg/mL 
Dose: 
30 mg 
Route of administration: 
SC 
Specific device for drug 
administration, if applicable: 
Accessorized pre-filled syringe 
Regimen: 
Single Dose 
Special handling requirements: 
Store between 2-8°C (36- 46°F), protected from the light 
Availability of the IMP: 
01 Nov 2016 
 
Table 5 
Identity of the Investigational Medicinal Product (Autoinjector) 
IMP: 
Benralizumab 
Formulation: 
30 mg/mL solution for injection in Autoinjector 
Strength/concentration: 
30 mg/mL 
Dose: 
30 mg 
Route of administration: 
SC 
Specific device for drug 
administration, if applicable: 
Autoinjector 
Regimen: 
Single Dose 
Special handling requirements: 
Store between 2-8°C (36- 46°F), protected from the light 
Availability of the IMP: 
01 Nov 2016 
AstraZeneca will provide detailed preparation, storage and handling instructions for each 
product and treatment.  Details of the batch numbers will be included in the Trial Master File 
and the final CSR, as applicable. 
8.2. 
Supply of Investigational Medicinal Product 
The IMP will be manufactured in accordance with Good Manufacturing Practice (GMP) and 
will be supplied by AstraZeneca. 
A technical agreement between PAREXEL and AstraZeneca will be in place to cover all 
pharmacy related activities, detailing roles and responsibilities prior to receipt of the IMP at 
the clinical unit. 

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8.3. 
Storage and Handling Procedures 
The IMP will be stored in a secure facility under appropriate storage conditions.  Details of 
storage conditions will be provided on the label of the IMP. 
AstraZeneca will be permitted, upon request, to audit the supplies, storage, dispensing 
procedures and records. 
8.4. 
Labeling 
Labels will be prepared in accordance with GMP and local regulatory guidelines.  The labels 
will fulfill GMP Annex 13 requirements and Annex 1 of medical device directive for 
labeling. 
8.5. 
Drug Accountability, Dispensing and Destruction 
The IMP provided for this clinical study will be used only as directed in the clinical study 
protocol. 
In accordance with GCP, the clinical unit will account for all supplies of the IMP.  Details of 
receipt, storage, assembly/dispensing and return will be recorded. 
All used and unused supplies of the IMP will be destroyed by PAREXEL at the end of the 
study.  The certificate of delivery and destruction must be signed, in accordance with 
instruction by AstraZeneca.  Destruction must not take place unless the responsible person at 
AstraZeneca has approved it. 
In the case of a malfunctioning APFS or AI, the center should contact the study monitor to 
initiate a product complaint process according to applicable guidelines. 
8.6. 
Dose and Treatment Regimens 
Subjects will be randomized to receive a single SC dose of 30 mg benralizumab by either 
APFS or AI device under fasted conditions.  Within each SC injection group, subjects will be 
stratified to 3 weight categories: 55 to 69.9 kg, 70 to 84.9 kg or 85 to 100 kg.  Within each 
weight category, subjects will be randomized 1:1:1:1:1:1 to receive the injection (APFS or AI 
device) at 1 of 3 anatomical sites: Upper arm, Abdomen and Thigh. 
Other restrictions are described in Section 7.4.  Data of subjects may be excluded from the 
PK analysis set as described in Section 11.3.2. 

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8.7. 
Concomitant and Post-study Treatment(s) 
Apart from paracetamol/acetaminophen (up to 2000 mg per day), no concomitant medication 
or therapy will be allowed. 
The subjects should be instructed that no other medication will be allowed, including herbal 
remedies, vitamin supplements and over-the-counter products, without the consent of the PI. 
Medication, which is considered necessary for the subject’s safety and well-being, may be 
given at the discretion of the PI during the residential period. 
When any medication is required, it should be prescribed by the PI or General Practitioner 
(GP) in case of a medical emergency.  Following consultation with AstraZeneca Lead 
Physician, the PI should determine whether or not the subject should continue in the study.  
Administration of concomitant medications that may influence the measurement of the PK 
endpoints may be documented as a protocol deviation after consultation of the PI with 
AstraZeneca Lead Physician. 
8.8. 
Treatment Compliance 
Dosing will take place at the PAREXEL Early Phase Clinical Units (Berlin and London).  
Compliance will be assured by direct supervision and witnessing of study drug 
administration.   
Administration of IMP will be recorded in ClinBase™. 
8.9. 
Randomization 
8.9.1. 
Subject Enrolment and Randomization 
The PI will ensure: 
• Signed informed consent is obtained from each potential subject before any study specific 
procedures are performed. 
• Each potential subject is assigned a unique enrolment number at screening upon signing 
the Informed Consent. 
• The eligibility of each subject is in accordance with the inclusion and exclusion criteria. 
• Each eligible subject is assigned a unique randomization code. 
Randomization will done prior to dosing on the day of dosing. 
Randomization codes will be assigned as subjects become eligible for randomization at the 
2 geographical sites (codes to be used without leading zero(s)). 

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When using unique enrolment number, the specific format must be followed (i.e., reduced 
enrolment number “01001” in ClinBase™ and on labels, full enrolment number “E0001001” 
for outputs). 
If a subject withdraws his/her participation in the study, then his/her enrolment/randomization 
code cannot be reused. 
8.9.2. 
Procedures for Randomization 
Upon completion of the randomization requirements specifications form, the randomization 
will be produced by PAREXEL according to the AZRand process. 
A total of 180 subjects will be randomized.  Subjects will be stratified by body weight 
category (55 to 69.9 kg/70 to 84.9 kg/85 to 100 kg).  Within each of the 3 weight groups, 
subjects will be randomized 1:1:1:1:1:1 to one of the 6 combinations of treatment (APFS or 
AI) with injection site (upper arm, abdomen or thigh).  As a result, 10 subjects will be 
allocated to each of the 18 randomization combinations for 2 device groups (Table 1).  
Randomization list will be prepared for each study site separately.  Randomization number 
will be assigned to subjects sequentially within each weight category at each site.  To keep 
the balance, each site must ensure they randomize subjects in complete blocks. 
Once a randomization number has been allocated to a subject, it should not be assigned to 
another subject.   
8.9.3. 
Procedures for Handling Incorrectly Randomized Subjects 
Subjects who fail to meet the inclusion criteria or meet any exclusion criterion should not, 
under any circumstances, be randomized into the study.  There can be no exceptions to this 
rule. 
Where a subject, who does not meet the selection criteria, is randomized in error and this is 
identified before dosing, the subject should be withdrawn from the study. 
If a subject, who does not meet the selection criteria, has been dosed before the error is 
identified, the subject should be advised to continue safety assessments to ensure their safety. 
8.10. Blinding 
This is an open-label study. 

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9. 
MEASUREMENTS AND METHODS OF ASSESSMENTS 
9.1. 
Appropriateness of Measurements 
Standard measures to assess PK, safety and tolerability apply during the study.  For the single 
doses of benralizumab planned to be given during this study, no safety issues are expected. 
For timing of assessments, refer to Table 2. 
9.2. 
Pharmacokinetics 
9.2.1. 
Sample Collection and Handling 
Blood samples for the determination of serum concentrations of benralizumab will be 
collected for the treatment period as specified in the schedule of assessments (Table 2). 
For the PK analysis, it is important that the date and time of each SC injection is recorded for 
each subject.  
Samples will be collected, handled, labeled, stored and shipped as detailed in the Laboratory 
Manual.  Serum samples will be analyzed for benralizumab using a validated assay. 
9.2.2. 
Pharmacokinetic Drug Assays 
Blood samples for determination of benralizumab concentrations in serum will be analyzed 
by PPD on behalf of AstraZeneca Research and Development (R&D), using a validated 
assay.  Additional analyses may be conducted on the biological samples to further investigate 
the presence and/or identity of drug metabolites. 
Full details of the analytical method and analyses performed used will be described in a 
separate bioanalytical report. 
9.2.3. 
Disposal of Pharmacokinetic Samples 
Pharmacokinetic samples will be retained at AstraZeneca or designee for a maximum of 
3 years following publication of the CSR to properly address potential questions from RAs. 
A summary of PK analysis results will be reported in the CSR. 
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples.  The results from the evaluation will not be reported in the CSR but 
separately in a bioanalytical report. 

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9.3. 
Safety and Eligibility Measurements 
Safety and tolerability variables will include: 
• Adverse events 
• Vital signs (systolic and diastolic BP, pulse rate and body temperature) 
• Electrocardiograms 
• Physical examination 
• Laboratory assessments (hematology, clinical chemistry and urinalysis). 
Viral serology and drugs of abuse and alcohol will be assessed for eligibility.  
Follicle-stimulating hormone (females only), pregnancy testing (females only) and use of 
concomitant medication will also be assessed and reported. 
9.3.1. 
Adverse Events 
Refer to Section 12.2.3. 
9.3.2. 
Vital Signs 
The following variables will be collected after the subject has rested in the supine position for 
at least 5 minutes: 
• Systolic BP (mmHg) 
• Diastolic BP (mmHg) 
• Pulse rate (beats per minute [bpm]) 
• Oral body temperature (degrees Celsius) 
The measurement of vital signs will be carried out according to the relevant PAREXEL 
standard operating procedures (SOPs). 
9.3.3. 
Resting 12-lead Electrocardiogram 
A 12-lead ECG will be obtained after the subject has rested in the supine position for at least 
10 minutes at each of the time points specified in the schedule of assessments (Table 2) using 
the sites own ECG machines. 
At each time point, the PI or study physician will judge the overall ECG as normal or 
abnormal and this evaluation will be reported in ClinBase.  If abnormal, it will be further 
documented as to whether or not the abnormality is clinically significant by the PI.  For all 
abnormalities (regardless of clinical significance), the specific type and nature of the 
abnormality will be documented in ClinBase.  Clinically significant findings should also be 
documented on the AE page of the CRF if applicable. 

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The PI or study physician may add extra 12-lead resting ECG safety assessments if there are 
any abnormal findings or if the PI considers it is required for any other safety reason.  These 
assessments should be entered as an unscheduled assessment. 
All ECG readings will be digitally stored as source documents. 
9.3.4. 
Physical Examination 
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 and neurological systems. 
Brief (Abbreviated) 
The brief physical examinations will include an assessment of the general appearance, skin, 
abdomen, cardiovascular and respiratory systems. 
Any new or aggravated clinically relevant abnormal medical physical examination finding 
compared to the baseline assessment will be reported as an AE. 
9.3.5. 
Laboratory Assessments 
9.3.5.1. 
Hematology 
White blood cell (WBC) count 
Lymphocytes absolute count  
Hemoglobin (Hb) 
Monocytes absolute count  
Platelets 
Eosinophils absolute count  
Neutrophils absolute count 
Basophils absolute count  
9.3.5.2. 
Serum Clinical Chemistry 
Sodium 
Alkaline phosphatase (ALP) 
Potassium 
Alanine aminotransferase (ALT)* 
Urea 
Aspartate aminotransferase (AST)* 
Creatinine 
Gamma glutamyl transpeptidase (GGT) 
Albumin 
Total bilirubin* 
Calcium 
 
Glucose(fasting) 
 
C-reactive protein (CRP) 
 
T4 (screening only) 
 
Thyroid-stimulating hormone (TSH) (screening only) 
Follicle-stimulating hormone (FSH) (post-menopausal 
women only) 
* In case a subject shows an AST or ALT ≥  3 x upper limit of normal (ULN) or total bilirubin ≥ 2 x ULN 
please refer to Appendix 15.3 ‘Actions required in cases of combined increase of Aminotransferase and Total 
Bilirubin – Hy’s Law’, for further instructions. 

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9.3.5.3. 
Urinalysis 
Glucose 
 
Protein 
 
Blood 
 
Microscopy (if positive for protein or blood): RBC, WBC, Casts (Cellular, Granular, Hyaline) 
9.3.5.4. 
Pregnancy Testing (Female Subjects Only) 
Beta human chorionic gonadotropin (beta-hCG) (at screening) 
Human chorionic gonadotropin (hCG) urine test (dipstick) (at admission and Day 57) 
9.3.5.5. 
Viral Serology 
Human immunodeficiency virus (HIV) I and II 
Hepatitis B core antibody 
Hepatitis B surface antigen (HBsAg) 
Hepatitis C virus antibody 
9.3.5.6. 
Drugs of Abuse and Alcohol  
Testing for the following drugs of abuse and alcohol will be conducted to determine 
eligibility at screening and prior to dosing (Table 2). 
Amphetamine 
Benzodiazepines 
Alcohol 
Methadone 
Tetrahydrocannabinol (THC) 
Barbiturates 
Cocaine 
Phencyclidine 
Opiates  
Urine creatinine 
Tricyclic anti-depressants (TCA) 
 
9.3.6. 
Concomitant Medication 
Refer to Section 8.7. 
9.4. 
Immunogenicity 
9.4.1. 
Sample Collection and Handling 
Serum samples for immunogenicity assessments (ADA) will be collected according to the 
schedule of study procedures (see Table 2). 
Instructions for immunogenicity (ADA) sample collection, processing, storage, and shipment 
can be found in the separate Laboratory Manual. 
9.4.2. 
Immunogenicity Assays 
Blood samples for the determination of serum concentrations of ADA will be analyzed by 
PPD on behalf of AstraZeneca R&D, using a validated assay. 
A summary of the analysis will be presented in the CSR.  Details of the analytical method 
used will be described in a bioanalytical report. 

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9.4.3. 
Disposal of Immunogenicity Samples 
The immunogenicity samples will be retained at AstraZeneca or designee for a maximum of 
3 years following publication of the CSR to properly address potential questions from RAs. 
9.5. 
Procedures for Handling of Biological Samples 
9.5.1. 
Storage And Destruction of Biological Samples 
The PK and immunogenicity samples will be retained at AstraZeneca or designee for a 
maximum of 3 years following publication of the CSR to properly address potential questions 
from RAs. 
9.5.1.1. 
Pharmacokinetic and Immunogenicity Samples 
For disposal of PK samples, see Section 9.2.3.  For disposal of immunogenicity samples, 
please see Section 9.4.3. 
9.5.2. 
Labeling and Shipment of Biohazard Samples 
Samples will be labeled and shipped in accordance with the Laboratory Manual and the 
Biological Substance, Category B regulations (materials containing or suspected to contain 
infectious substances that do not meet Category A criteria) (for International Airline 
Transportation Association [IATA] guidance, see Appendix 15.2 of this clinical study 
protocol). 
Any samples identified as Infectious Category A materials will not be shipped and no further 
samples will be taken from the subject unless agreed with AstraZeneca and appropriate 
labeling, shipment and containment provisions are approved. 
9.5.3. 
Chain of Custody Of Biological Samples 
A full chain of custody will be maintained for all samples throughout their life cycle. 
The PI will ensure full traceability of collected biological samples from the subjects while in 
storage at the clinical unit until shipment and will keep documentation of receipt of arrival. 
The sample receiver will keep full traceability of samples while in storage and during use, 
until used, disposed of, or until further shipment or disposal (where appropriate) and will 
keep documentation of receipt of arrival. 
Samples retained for further use will be registered in the AstraZeneca bio-bank system during 
the entire life cycle. 

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9.5.4. 
Withdrawal of Informed Consent for Donated Biological Samples 
If a subject withdraws consent to the use of donated biological samples, the samples will be 
disposed if not already analyzed and the action documented.  As collection of donated 
biological samples is an integral part of the study, consent withdrawal implies that the subject 
is withdrawn from further study participation. 
AstraZeneca ensures the laboratory holding the samples is informed about the withdrawn 
consent immediately and that samples are disposed of or destroyed, the action documented 
and the signed document returned to the clinical unit. 

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10. 
DATA QUALITY ASSURANCE AND DATA MANAGEMENT 
10.1. Quality Control and Source Data Verification 
Source data verification will be conducted with due regard to subject confidentiality. 
The clinical unit will allow the study monitor and Sponsor representative direct access to all 
study documents, medical files and source documents to enable verification of the study data, 
while maintaining the anonymity of the subject and confidentiality of the data. 
Internal quality control will be performed at all stages of the study by the clinical unit. 
10.2. Audit/Inspections 
The clinical unit facilities and all study data/documentation may be audited/inspected by 
independent auditor/inspector/any representatives of RAs.  The PI must allow the applicable 
persons access to all relevant facilities and data/documents.  The PI must be available to 
discuss any findings/issues. 
If an audit was performed, the audit certificate will be included in the CSR. 
10.3. Study Monitoring 
The conduct of the study will be monitored by an independent PAREXEL monitor or a 
subcontracted monitor to ensure compliance with applicable regulatory requirements and 
GCP.  The summary of the documentation of the monitoring visits will form part of the study 
documentation and will be archived as such. 
10.4. Data Collection 
The ClinBase system is an electronic source data capturing and information management 
system.  The system combines all aspects of source data capturing with process control and 
clinical study management.  All clinical and laboratory data, except those which are 
paper-based or provided by external vendor, will be collected in ClinBase.  Only paper-based 
data will be subject to data entry.  For electronic source data, no data entry will be performed. 
The responsible study monitor will check data at the monitoring visits to the clinical unit.  
The PI will ensure that the data collected are accurate, complete and legible.  Data will be 
monitored within ClinBase by the study monitor before being exported.  Any changes made 
during monitoring will be documented with a full audit trail within ClinBase. 

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10.4.1. 
Case Report Forms and Source Documents 
All data obtained using paper collection methods during the clinical study will be recorded in 
ClinBase.  All source documents from which ClinBase entries are derived should be placed in 
the subject’s personal records. 
The original ClinBase entries for each subject will be checked against source documents by 
the study monitor.  Instances of missing or uninterpretable data will be discussed with the PI 
for resolution. 
10.4.2. 
Access to Source Documents 
During the course of the clinical study, a study monitor will make clinical unit visits to 
review protocol compliance, compare ClinBase entries and individual subject’s personal 
records, assess IMP accountability and ensure that the clinical study is being conducted 
according to pertinent regulatory requirements.  ClinBase entries will be verified against 
source documents.  The review of medical records will be handled confidentially to ensure 
subject anonymity. 
Checking of the ClinBase entries for completeness and clarity and verifying with source 
documents, will be required to monitor the clinical study for compliance with GCP and other 
regulations.  Moreover, RAs of certain countries, IECs may wish to carry out source data 
inspections on-site, and the Sponsor’s clinical quality assurance group may wish to carry out 
audits.  Direct access to source data will be required for these inspections and audits; they 
will be carried out giving due consideration to data protection and subject confidentiality.  
The PI assures the Sponsor of the necessary support at all times. 
10.5. Data Management 
PAREXEL will utilize standardized and validated procedures and systems to collect, process 
and file the clinical data of this study.  Any system used will be compliant with Food and 
Drug Administration (FDA) 21 CFR Part 11 requirements. 
A data management plan (DMP) will be prepared to describe the processes and data-flow 
within the clinical study.  Timelines, versions for the computer systems and the coding will 
be defined in the DMP, and if applicable, Sponsor specific requests will also be documented 
within.  The DMP will be finalized before first dose where possible but before database lock. 
A data validation specification (DVS) will be created to outline the validation checks to be 
performed during the study.  The DVS must be finalized before data validation. 
After the data has been monitored by the responsible study monitor all data received will be 
reviewed, logged and filed. 

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The raw data intended for further processing will be checked by standard routines or 
according to the DVS and queries will be generated and sent to the PI for review and 
resolution.  Corrections resulting from these queries will be confirmed on the data 
clarification forms (DCFs).  This process will be repeated until no further discrepancies are 
found.  The data will then be declared as clean.  Applicable documentation will be stored in 
the study files. 
Only trained study staff will have access to the clinical database and every change in data will 
have a full audit trail. 

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11. 
STATISTICAL METHODS 
11.1. Overview 
The statistical methodology below describes the high-level statistical analysis principles as it 
is foreseen when the study is being planned. 
The statistical analysis plan (SAP) will be prepared prior to first subject enter treatment 
period and any subsequent amendments will be documented, with final amendments 
completed prior to database lock.  
11.2. General Statistical Methodology 
The analysis of all endpoints will include all data captured during the study, unless the 
subject withdraws consent from study participation, regardless of whether study treatment is 
prematurely discontinued or delayed, and/or irrespective of protocol adherence. 
Summary data will be presented in tabular format by treatment groups.  Categorical data will 
be summarized by the number and percentage of subjects in each category.  Continuous 
variables for parametric data will be summarized by descriptive statistics including n, mean, 
standard deviation, median, minimum value and maximum value (unless stated otherwise) for 
non-PK data.  For PK data, in addition, geometric mean and coefficient of variation (CV%) 
based on log-transformed data will be presented.  
11.3. Study Populations 
11.3.1. 
Safety Analysis Set 
The safety analysis set will include all subjects who received benralizumab. 
Unless otherwise stated the safety analysis set will be used for the presentation of all data 
except for PK data.  
11.3.2. 
Pharmacokinetic Analysis Set 
All subjects who received benralizumab and from whom PK blood samples are assumed not 
to be affected by factors such as protocol violations (e.g., disallowed medications) and who 
had at least one quantifiable serum PK observation post first dose will be included in the PK 
analysis dataset. 
11.4. Determination of Sample Size 
While this study is not a formal bioequivalence study, a total of 162 subjects (81 subjects per 
treatment group) are required for this study to achieve with 80% power and a 90% two-sided 
confidence interval (CI) for geometric mean ratios of AUC and Cmax being within a limit of 

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0.8 to 1.25 inclusive.  The calculation is based on two one-sided tests (TOST) at 5% alpha 
level under an assumption of maximum 50% CV PK variability for primary endpoints of 
benralizumab AUC and Cmax.  Assuming 10% dropout rate, 180 subjects will be enrolled to 
provide adequate numbers of subjects to assess the primary and secondary objectives of the 
study. 
11.5. Protocol Deviations 
Protocol deviations are considered any deviation from the clinical study protocol relating to a 
subject.  All protocol deviations will be discussed at the data review meeting prior to database 
hard lock in order to define the analysis sets for the study and all important protocol 
deviations will be listed by subject. 
11.6. Subject Disposition 
Subjects and/or data excluded from the PK analysis set will be listed including the reason for 
exclusion.  Summary tabulation of subject disposition will be provided.  A listing of informed 
consent response and a randomization listing will also be presented. 
11.7. Demographic and Baseline Data 
Demographic variables (age, gender, race, ethnicity, height, weight and BMI) will be listed 
by subject and summarized.  Listing of medical history will also be provided. 
11.8. Prior and Concomitant Medication and Drug Administration 
Prior and concomitant medication will be listed and drug administration dates and times will 
be listed for each subject. 
11.9. Pharmacokinetic Analysis 
11.9.1. 
Pharmacokinetic Parameters 
Where possible, the following PK parameters will be assessed for benralizumab on serum 
concentrations. 
Primary Pharmacokinetic Parameters 
AUC 
Area under the concentration-time curve 
Cmax 
Maximum observed concentration 

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Secondary Pharmacokinetic Parameters 
Tmax 
Time when the maximum concentration is observed 
t½ 
Terminal half-life 
CL/F 
Apparent extravascular clearance 
Vz/F  
Apparent volume of distribution based on the terminal phase 
Additional PK parameters may be determined where appropriate. 
11.9.2. 
Derivation of Pharmacokinetic Parameters 
The non-compartmental analysis (NCA) of the serum concentration data for benralizumab 
will be performed by PAREXEL Quantitative Clinical Development (QCD) using Phoenix 
WinNonlin (version 6.3 or higher) in accordance to PAREXEL SOPs. 
Pharmacokinetic analysis will, where possible, be carried out using actual times recorded in 
the raw data.  If actual times are missing, nominal times will be used.  Serum concentration 
data associated with positive ADA status may be excluded from the NCA.  
11.9.3. 
Presentation of Pharmacokinetic Data 
A listing of PK blood sample collection times, as well as derived sampling time deviations 
will be provided.  Serum concentrations and PK parameters will be summarized using 
appropriate descriptive statistics.  Figures showing individual and mean of PK 
concentration-time profiles will be produced on both semi-log and linear scales.  Serum 
concentration data associated with positive ADA status will be flagged in the PK 
concentration listings and may be excluded from the summary statistics and/or mean profiles. 
11.9.4. 
Statistical Analysis of Pharmacokinetic Data 
11.9.4.1. Primary PK Analysis Method 
The study primary objective is to compare AUC and Cmax between APFS and AI devices 
following a single SC administration of benralizumab.   
The analysis of variance (ANOVA) model will be employed on the log-transformed Cmax and 
AUC separately, with fixed effects of treatment (device), body weight group and injection 
site in order to provide a descriptive comparison of the PK exposure between the 2 devices.  
The estimated treatment (device) differences and the 90% CI (2-sided) on the log scale will 
be back-transformed to obtain the geometric mean ratios of AI to APFS and its corresponding 
90% CI.   

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11.9.4.2. Secondary PK Analysis Method 
For Tmax, a nonparametric analysis may be performed.  Secondary PK parameters will be 
summarized.  
To evaluate the PK of benralizumab administered to various anatomical injection sites, the 
PK parameters will be summarized by injection sites, body weight ranges and treatment 
(device).  Furthermore, a similar ANOVA model for primary analysis may be used to include 
the interaction of treatment (device)-by-injection site.  
11.10. Analysis of Safety Data 
11.10.1. 
Adverse Events 
Adverse events will be summarized by means of counts summaries by study period 
(pre-treatment and treatment period).  Adverse events will be listed for each subject and 
summarized by System Organ Class (SOC) and Preferred Term assigned to the event by 
Medical Dictionary for Regulatory Activities (MedDRA). 
Other safety variables will be summarized as appropriate.  Further details will be provided in 
the SAP. 
11.10.2. 
Vital Signs 
The results of the vital signs measurements will be listed and summarized. 
11.10.3. 
Resting 12-Lead Electrocardiogram 
Twelve-Lead ECG results will be listed for each subject.   
11.10.4. 
Physical Examination 
Abnormal baseline/screening results of the physical examination will be documented in 
medical history for each subject. 
11.10.5. 
Laboratory Assessments 
Laboratory safety variables (hematology and clinical chemistry) and change from baseline 
will be summarized using standard summary statistics as appropriate.  Shift tables using 
normal ranges (baseline to most extreme post-baseline value) will also be presented.  Change 
from baseline of eosinophils count will be summarized.  The results of viral serology and the 
drugs of abuse and alcohol screen will not be listed in the CSR. 

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11.11. Analysis of Immunogenicity Data 
For the analysis of immunogenicity data, ADA to benralizumab will be summarized using 
descriptive statistics at each visit.  Anti-drug antibody titers-time profiles of benralizumab by 
treatment group will be generated.  The impact of ADA on PK and eosinophil level will be 
assessed.  The potential association of ADA with safety will be evaluated.  The 
hypersensitivity reported during the on-study period will be evaluated for ADA status. 

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12. 
ADVERSE EVENTS 
12.1. Definitions 
12.1.1. 
Definition of Adverse Events 
An AE is the development of an undesirable medical condition or the deterioration of a 
pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product. 
An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., 
tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory 
findings, ECG). 
In clinical studies, an AE can include an undesirable medical condition occurring at any time 
after the subject has signed informed consent, including run-in or washout periods, even if no 
specific treatment has been administered. 
The term AE is used generally to include any AE whether serious or non-serious. 
12.1.2. 
Definitions of Serious Adverse Event 
A SAE is an AE occurring during any study phase (i.e., run-in, treatment, washout, 
follow-up), that fulfills one or more of the following criteria: 
• Results in death 
• Is immediately life-threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity or substantial disruption of the 
ability to conduct normal life functions 
• Is a congenital abnormality or birth defect 
• Is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. 
For further guidance on the definition of a SAE, see Appendix 15.1 of this clinical study 
protocol. 
12.1.3. 
Other Significant Adverse Events 
During the evaluation of the AE data, an AstraZeneca medically qualified expert will review 
the list of AEs that were not reported as SAEs.  Based on the expert’s judgment, significant 
AEs of particular clinical importance may, after consultation with the Global Safety 
Physician, be considered other significant adverse events (OAEs) and reported as such in the 

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CSR.  A similar review of other data from laboratory tests, vital signs, ECGs and other safety 
assessments will be performed for identification of OAEs. 
Examples of these are marked hematological and other laboratory abnormalities, and certain 
events that lead to intervention (other than those already classified as serious), dose reduction 
or significant additional treatment. 
12.2. Recording of Adverse Events 
12.2.1. 
Time Period for Collection of Adverse Events 
Adverse Events will be collected from randomization throughout the treatment period up to 
and including the End-of-Treatment visit. 
SAEs will be recorded from the time of informed consent. 
12.2.2. 
Follow-up of Unresolved Adverse Events 
Any AEs that are unresolved at the subject’s last visit in the study are followed up by the PI 
or study physician for as long as medically indicated, but without further recording in 
ClinBase. 
AstraZeneca retains the right to request additional information for any subject with ongoing 
AE(s)/SAE(s) at the end of the study, if judged necessary. 
12.2.3. 
Variables 
The following variables will be collected for each AE: 
• AE diagnosis/description 
• The date and time when the AE started and stopped 
• Intensity 
• Whether the AE is serious or not 
• Principle Investigator causality rating against the investigational product (yes or no) 
• Action taken with regard to investigational product 
• AE caused subject’s withdrawal from study (yes or no) 
• Outcome. 
Additional variables will be collected for all SAEs including treatment given for the event. 
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) 

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3.  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 Section 12.1.2. 
An AE of severe intensity need not necessarily be considered serious.  For example, nausea 
that persists for several hours may be considered severe nausea, but not a SAE.  On the other 
hand, a stroke that results in only a limited degree of disability may be considered a mild 
stroke but would be an SAE. 
12.2.4. 
Causality Collection 
The PI or study physician will assess causal relationship between investigational product and 
each AE, and answer “yes” or “no” to the question “Do you consider that there is a 
reasonable possibility that the event may have been caused by the investigational product?” 
For SAEs, causal relationship will also be assessed for other medication, any additional drug 
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 15.1 of this 
clinical study protocol. 
12.2.5. 
Adverse Events Based on Symptoms and Signs 
All AEs spontaneously reported by the subject or reported in response to the open question 
from the study personnel: “Have you had any health problems since you were last asked?”, 
or revealed by observation will be collected and recorded in ClinBase. 
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. 
12.2.6. 
Adverse Events Based on Examinations and Tests 
The results from protocol mandated laboratory tests, vital signs, ECGs and other safety 
assessments will be summarized in the CSR. 
Deterioration as compared to baseline in protocol mandated laboratory values, vital signs, 
ECGs and other safety assessments should therefore only be reported as AEs if they fulfill 
any of the SAE criteria. 

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If deterioration in a laboratory value or vital sign is associated with clinical signs and 
symptoms, the sign or symptom will be reported as an AE and the associated laboratory result 
or vital sign will be considered as additional information. 
Wherever possible the reporting PI or study physician should use the clinical, rather than the 
laboratory term (e.g., anemia versus low hemoglobin value). 
In the absence of clinical signs or symptoms, clinically relevant deteriorations in 
non-mandated parameters should be reported as AE(s). 
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. 
12.2.7. 
Hy's Law 
Cases where a subject shows elevations in liver biochemistry may require further evaluation 
and occurrences of AST or ALT ≥ 3 x ULN together with total bilirubin ≥ 2 x ULN may need 
to be reported as SAEs.  Please refer to Appendix 15.3 for further instruction on cases of 
increases in liver biochemistry and evaluation of Hy’s Law. 
12.3. Reporting of Serious Adverse Events 
All SAEs have to be reported, whether or not considered causally related to the 
investigational product, or to the study procedure(s).  All SAEs will be recorded in ClinBase. 
If any SAE occurs in the course of the study, then the PI, study physician or other site 
personnel will inform appropriate AstraZeneca representatives immediately, or no later than 
24 hours of when he or she becomes aware of it. 
The designated AstraZeneca representative will work with the PI to ensure that all the 
necessary information is provided to the AstraZeneca patient safety data entry site within 1 
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. 
Principle Investigators, study physicians or other site personnel will inform AstraZeneca 
representatives of any follow-up information on a previously reported SAE immediately, or 
no later than 24 hours of when he or she becomes aware of it. 
The reference document for definition of expectedness/listedness is the Investigator’s 
Brochure for the AstraZeneca drug 

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13. 
LEGAL AND ADMINISTRATIVE ASPECTS 
13.1. Archiving of Study Documents 
All source documents generated in connection with the study will be retained in the limited 
access file storage area, respecting the privacy and confidentiality of all records that could 
identify the subjects.  Direct access is allowed only for authorized people for monitoring and 
auditing purposes.  Source documents will be handled, stored and archived according to in 
house procedures. 
Investigator specific essential documents will be retained until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the IMP.  These documents could be 
retained for a longer period however, if required by the regulatory requirements or by an 
agreement with AstraZeneca.  It is the responsibility of AstraZeneca to inform the 
Investigator as to when these documents no longer need to be retained. 
Study documentation will be archived by the contract research organization (CRO) for 
15 years. 
13.2. Publication of Study Results 
All of the study information and data collected during the study are confidential and the 
property of AstraZeneca.  After completion of the study, the Investigator may prepare a joint 
publication with AstraZeneca.  The Investigator must undertake not to submit any part of the 
individual data from this clinical study protocol for publication without prior consent of 
AstraZeneca at a mutually agreed time. 
13.3. Clinical Study Report 
An integrated CSR will be prepared in accordance with the standards of the ICH guideline for 
structure and content of clinical study reports (ICH E3).  Copies of the CSR will be provided 
to the IEC and the national RA in accordance with regulatory requirements and PAREXEL 
SOPs.  In the event of premature termination of the study or other conditions specified in 
ICH E3, an abbreviated CSR may be prepared. 

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14. 
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Busse WW, Barker P, Sproule S, Gilmartin G, Werkström V, Aurivillius M, Goldman M, 
on behalf of the CALIMA study investigators, Benralizumab, an anti–interleukin-5 
receptor α monoclonal antibody, as add-on treatment for patients with severe, 

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uncontrolled, 
eosinophilic 
asthma 
(CALIMA): 
a 
randomised, 
double-blind, 
placebo-controlled phase 3 trial, Lancet Respir Med. 2016 Sept 05 (online) 
10. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma 
(GINA) Updated 2016. Available from: URL: http://ginasthma.org. Accessed May 2016. 
11. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, et al. 
MEDI-563, a humanized anti–IL-5 receptor a mAb with enhanced antibody-dependent 
cell-mediated cytotoxicity function. J Allergy Clin Immuno. 2010, Jun;125(6):1344-53. 
12. Laviolette, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, 
Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA, Effects of benralizumab on airway 
eosinophils in asthma with sputum eosinophilia. J Allergy Clin Immunol. 2013 Nov; 
132(5): 1086–1096.e5. 
13. Louis R, Lau LC, Bron AO, Roldaan AC, Radermerker M, Djukanovic R. The 
relationship between airways inflammation and asthma severity. Am J Respir Crit Care 
Med. 2000 Jan; 161(1):9-16. 
14. Masoli M, Holt S, Weatherall M, Beasley R. The dose-response relationship of inhaled 
corticosteroids in asthma. Curr Allergy Asthma Rep. 2004 Mar;4(2):144-8. 
15. Molfino NA, Gossage D, Kolbeck R, Parker JM, Geba GP. Molecular and clinical 
rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 
2011;42;712-37. 
16. NAEPP 2007, National Asthma Education Prevention Program. Expert Panel Report 
3:Guidelines 
for 
the 
Diagnosis 
and 
Management 
of 
Asthma. 
Available: 
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. 
17. Scott KA, Wardlaw AJ. Eosinophilic airway disorders. Semin Respir Crit Care Med. 
2006;27(2):128-133. 
18. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma and 
identification using induced sputum. Respirology. 2006 Jan; 11(1):54-61. 
19. Takatsu K, Takaki S, Hitoshi Y. Interleukin-5 and its receptor system: implications in the 
immune system and inflammation. Adv Immunol. 1994;57:145-90. 
20. Toba K, Koike T, Shibata A, Hashimoto S, Takahashi M, Masuko M, et al. Novel 
technique for the direct flow cytofluorometric analysis of human basophils in unseparated 
blood and bone marrow, and the characterization of phenotype and peroxidase of human 
basophils. Cytometry. 1999;35(3):249-259. 
21. Wenzel S E. Asthma phenotypes: the evolution from clinical to molecular approaches. 
2012 May 4;18(5):716-25. 

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22. Saito, Yuji W, Kawai H, Nakanishi T Ascending Single Intravenous And Subcutaneous 
Dose Studies Of Benralizumab In Japanese Healthy Male Volunteers: Safety, 
Tolerability, Pharmacokinetics And Pharmacodynamics. C36. ASTHMA THERAPY II. 
May 1, 2015, A4270-A4270 

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15. 
APPENDICES 
15.1. Additional Safety Information 
FURTHER GUIDANCE ON THE DEFINITION OF A SERIOUS ADVERSE EVENT 
Life-threatening 
‘Life-threatening’ means that the subject 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 
subject’s death.  ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (e.g., hepatitis that resolved without hepatic failure). 
Hospitalization 
Outpatient treatment in an emergency room is not in itself a SAE, although the reasons for it 
may be (e.g., bronchospasm, laryngeal edema).  Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study. 
Important Medical Event or Medical Intervention 
Medical and scientific judgment 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, hospitalization, disability or incapacity but may jeopardize the subject or may 
require medical intervention to prevent 1 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 judgment must be used. 
Examples of such events are: 
• Angioedema not severe enough to require intubation but requiring intravenous 
hydrocortisone treatment. 
• Hepatotoxicity caused by paracetamol/acetaminophen overdose requiring treatment with 
N-acetyl cysteine. 
• Intensive treatment in an emergency room or at home for allergic bronchospasm. 
• Blood dyscrasias (e.g., neutropenia or anemia requiring blood transfusion) or convulsions 
that do not result in hospitalization. 
• Development of drug dependency or drug abuse. 

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A GUIDE TO INTERPRETING THE CAUSALITY QUESTION 
The following factors should be considered when deciding if there is a “reasonable 
possibility” that an AE may have been caused by the IMP. 
• Time Course/Exposure to suspect drug 
• Has the subject 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? 
• Dechallenge 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 other etiology such as the underlying disease, 
other drugs, other host or environmental factors. 
• Rechallenge experience  
Did the AE reoccur if the suspected drug was reintroduced after having been stopped? 
Note: AstraZeneca would not normally recommend or support a rechallenge. 
• Laboratory tests  
A specific laboratory investigation (if performed) has confirmed the relationship? 
A “reasonable possibility” could be considered to exist for an AE where 1 or more of these 
factors exist. 
In contrast, there would not be a “reasonable possibility” of causality if none of the above 
criteria apply or where there is evidence of exposure and a reasonable time course but any 
dechallenge (if performed) is negative or ambiguous or there is another more likely cause of 
the AE. 
In difficult cases, other factors could be considered such as: 
o Is this a recognized feature of overdose of the drug? 
o Is there a known mechanism? 
Ambiguous cases should be considered as being a “reasonable possibility” of a causal 
relationship, unless further evidence becomes available to refute this.  Causal relationship in 
cases where the disease under study has deteriorated due to lack of effect should be classified 
as no reasonable possibility. 
 
 

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15.2. International Airline Transportation Association 6.2 Guidance Document 
LABELING AND SHIPMENT OF BIOHAZARD SAMPLES 
International Airline Transportation Association classifies bio hazardous agents into 
3 categories 
(http://www.iata.org/whatwedo/cargo/dangerous_goods/infectious_substances.htm). 
 
For 
transport purposes the classification of infectious substances according to risk groups was 
removed from the Dangerous Goods Regulations (DGR) in the 46th edition (2005).  
Infectious substances are now classified either as Category A, Category B or Exempt.  There 
is no direct relationship between Risk Groups and Categories A and B. 
CATEGORY A 
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 for example, Ebola and 
Lassa Fever viruses.  Category A pathogens: 
• Are to be packed and shipped in accordance with IATA Instruction 602. 
CATEGORY B 
Category B Infectious Substances are infectious substances that do not meet the criteria for 
inclusion in Category A.  Category B pathogens are for example, hepatitis A, B, C, D and E 
viruses, and HIV types 1 and 2.  They are assigned the following UN number and proper 
shipping name: 
• UN 3373 – Biological Substance, Category B 
Category B pathogens: 
• Are to be packed in accordance with UN3373 and IATA Instruction 650. 
EXEMPT 
Exempt refers to all other materials with minimal risk of containing pathogens. 
• Clinical trial samples will fall into Category B or Exempt under IATA regulations. 
• Clinical trial samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging.  
(http://www.iata.org/whatwedo/cargo/dangerous_goods/infectious_substances.htm) 
• Biological samples transported in dry ice require additional dangerous goods specification 
for the dry ice content. 
• IATA compliant courier and packaging materials should be used for packing and 
transportation.  Packing should be done by an IATA certified person, as applicable. 

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• Samples routinely transported by road or rail are subject to local regulations which 
require that they are also packed and transported in a safe and appropriate way to contain 
any risk of infection or contamination by using approved couriers and packaging / 
containment materials at all times.  The IATA 650 biological sample containment 
standards are encouraged wherever possible when road or rail transport is used. 
 
 

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15.3. Actions Required in Cases of Combined Increase of Aminotransferase and Total 
Bilirubin - Hy’s Law 
Guidance used: FDA Guidance for Industry ‘Drug-induced liver injury: Premarketing clinical 
evaluation’. July 2009 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
s/UCM174090.pdf 
Introduction 
During the course of the study, the PI will remain vigilant for increases in liver clinical 
chemistry.  The PI is responsible for determining whether a subject meets PHL criteria at any 
point during the study. 
The PI participates, together with AstraZeneca clinical project representatives, in review and 
assessment of cases meeting PHL criteria to agree whether Hy’s Law (HL) criteria are met.  
The HL criteria are met if there is no alternative explanation for the elevations in liver clinical 
chemistry other than Drug-Induced Liver Injury (DILI) caused by the IMP.  
The PI is responsible for recording data pertaining to PHL/HL cases and for reporting AE and 
SAE according to the outcome of the review and assessment in line with standard safety 
reporting processes. 
Definitions 
Potential Hy’s Law 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x ULN and 
total bilirubin (TBL) ≥ 2 x ULN at any point during the study irrespective of an increase 
in alkaline phosphatase (ALP). 
• The elevations do not have to occur at the same time or within a specified time frame. 
Hy’s Law (HL) 
• AST or ALT ≥ 3 x ULN and TBL ≥ 2 x ULN, where no other reason, other than the IMP, 
can be found to explain the combination of increases, e.g., elevated ALP indicating 
cholestasis, viral hepatitis, another drug. 
• The elevations do not have to occur at the same time or within a specified time frame. 
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 subject who meets any of the following identification criteria in 
isolation or in combination: 
• ALT ≥ 3 x ULN 

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• AST ≥ 3 x ULN 
• TBL ≥ 2 x ULN 
The PI will review without delay each new laboratory report and if the identification criteria 
are met will: 
• Notify the AstraZeneca representative 
• Determine whether the subject meets PHL criteria (see definition above) by reviewing 
laboratory reports from all previous visits 
• Promptly enter the laboratory data into the laboratory CRF 
Follow-Up 
Potential Hy’s Law Criteria not met 
If the subject does not meet PHL criteria the PI will: 
• Inform the AstraZeneca representative that the subject has not met PHL criteria. 
• Perform follow-up on subsequent laboratory results according to the guidance provided in 
the clinical study protocol. 
Potential Hy’s Law Criteria met 
If the subject does meet PHL criteria the PI will: 
• Notify the AstraZeneca representative who will then inform the central study team. 
The study physician contacts the PI, to provide guidance, discuss and agree an approach for 
the study subjects’ follow-up and the continuous review of data. 
Subsequent to this contact, the PI will: 
• Monitor the subject until liver clinical chemistry variables and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically indicated. 
• Investigate the etiology of the event and perform diagnostic investigations as discussed 
with the study physician. 
• Complete the 3 Liver CRF Modules as information becomes available. 
If at any time (in consultation with the study physician) the PHL case meets serious criteria, 
report it as an SAE using standard reporting procedures. 
Review and Assessment of Potential Hy’s Law Cases 
The instructions in this section should be followed for all cases where PHL criteria were met. 
No later than 3 weeks after the clinical chemistry abnormality was initially detected, the 
study physician contacts the PI in order to review available data and agree on whether there is 
an alternative explanation for meeting PHL criteria other than DILI caused by the IMP.  The 

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AstraZeneca Medical Science Director 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 PI will follow the instructions 
below. 
If 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 CRF. 
• If the alternative explanation is an AE/SAE, record the AE /SAE in the CRF accordingly 
and follow the AZ standard processes. 
If it is agreed that there is no explanation that would clarify the ALT or AST and TBL 
elevations other than IMP causality: 
• Report an SAE (report term ‘Hy’s Law’) according to AstraZeneca standard processes.  
o The ‘Medically Important’ serious criterion should be used if no other serious criteria 
apply. 
o 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 3 weeks, 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: 
• Report an SAE (report term ‘Potential Hy’s Law’) applying serious criteria and causality 
assessment as per above. 
• 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 met.  Update the SAE report according to the outcome of the 
review. 
 

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16. 
SIGNATURES 
16.1. Declaration of Sponsor or Responsible Medical Expert (Physician) 
 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Sponsor Signatory/Responsible Medical Expert 
 
 
Signature 
 
Date of signature 
 
 
 
AstraZeneca 
 
 
 
 
 
 
PPD

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Study Code: D3250C00030 
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Drug substance: Benralizumab (MEDI-563) 
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Final 1.0 
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16.2. Declaration of Sponsor or Responsible Medical Expert (Global Statistician) 
 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Sponsor Signatory/Global Statistician 
 
 
Signature 
 
Date of signature 
 
 
 
AstraZeneca 
 
 
 
PPD

AstraZeneca 
Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 72 of 75 
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16.3. Declaration of Sponsor or Responsible Medical Expert (Lead Clinical 
Pharmacologist) 
 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Sponsor Signatory/Global Statistician 
 
 
Signature 
 
Date of signature 
 
 
 
MedImmune 
 
 
 
 
 
PPD

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Study Code: D3250C00030 
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Drug substance: Benralizumab (MEDI-563) 
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16.4. Declaration of the Principal Investigator 
 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Principal/Coordinating Investigator 
 
 
Signature 
 
Date of signature 
 
 
 
PAREXEL Early Phase Clinical Unit London 
 
 
 
 
 
PPD

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Drug substance: Benralizumab (MEDI-563) 
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16.5. Declaration of the Principal Investigator 
 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Principal/Coordinating Investigator 
 
 
Signature 
 
Date of signature 
 
 
 
PAREXEL Early Phase Clinical Unit Berlin 
 
 
 
 
 
PPD

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Clinical Study Protocol 
Study Code: D3250C00030 
Revised according to Protocol Amendment No. 1 
Drug substance: Benralizumab (MEDI-563) 
CONFIDENTIAL 
 
Final 1.0 
Page 75 of 75 
07 July 2017 
 
16.6. Declaration of the Deputy Principal Investigator 
Protocol Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 
Pharmacokinetic Comparability Study of Benralizumab Administrated using Accessorized 
Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers 
This clinical study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the IMP, as well as with the 
ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on GCP applicable to this clinical study. 
Deputy Principal/Coordinating Investigator 
 
 
Signature 
 
Date of signature 
 
 
 
PAREXEL Early Phase Clinical Unit Berlin 
 
 
 
 
PPD