An Open-label, Long-term Extension Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (INTREPID OLE)
Phase: PHASE3
Conditions: Crohn's Disease, IBD
Sponsor: AstraZeneca

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Clinical Study Protocol 
Study Intervention
Brazikumab
Study Code
D5271C00002 (Legacy #3150-303-008)
Version
Amendment 4 v5.0
Date
04 April 2022
An Open-label, Long-term Extension Study of Brazikumab in 
Participants With Moderately to Severely Active Crohn’s Disease
(INTREPID OLE)
Sponsor Name: 
AstraZeneca AB
Legal Registered Address:
151 85 Södertälje, Sweden
Regulatory Agency Identifier Number(s)
IND: 111,773
EudraCT: 2019-001866-14
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
Standard procedures. The Clinical Study Protocol is publicly registered and the results are 
disclosed and/or published according to the AstraZeneca Global Policy on Bioethics and in 
compliance with prevailing laws and regulations.
Redacted
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Long
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Protocol Number: D5271C00002 (Legacy #3150-303-008)
Amendment Number: 4
Study Intervention: Brazikumab
Study Phase: 3
Short Title: Open-label Extension Study of Brazikumab in Crohn’s Disease
Acronym: INTREPID OLE
Sponsor Study Physician/designee and Contact Information will be provided separately
Feinstein IBD Clinical Center
17 East 102nd St, 5th Floor
New York, NY 10029
PPD
PPD

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
AstraZeneca Protocol D5271C00002 (Legacy #3150-303-008)
DOCUMENT HISTORY
Document
Date
Amendment 4
April 2022
Amendment 3
March 2021
Amendment 2
August 2020
Amendment 1
June 2019
Original Protocol
March 2019
Amendment 4 (04-April-2022)
This amendment is considered non-substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical/mental integrity of participants 
nor the scientific value of the study.
Overall Rationale for the Amendment:
This amendment removes unnecessary assessments related to study entry, collection of 
assessments throughout the study, and provides further clarity on protocol text. Previously 
omitted exploratory objectives and endpoints are also included.

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All changes have been classified as non-substantial. The granular summary of changes in the 
tabular format is included below.
Section # and name
Description of change
Brief rationale
Throughout
Minor editorial and document 
formatting revisions.
Minor corrections were made to improve 
interpretation.
Section 1.1 Synopsis, 
Section 3 Objectives and 
Endpoints
Added an omitted primary 
endpoint to include physical 
exams.
Correction to ensure physical exam was 
included as an endpoint for the primary 
safety objective.
Section 1.1 Synopsis, 
Section 1.2 Schema, 
Section 4.1 Overall Design, 
Section 6 Study 
Intervention
Revised text to clarify that 
participants with suboptimal 
response at Week 52 of lead-in 
study will roll over to 
 
Clarification to enable non-responders at 
Week 52 of the lead-in study to potentially 
benefit from re-induction with 
 regimen.
Section 1.1 Synopsis, 
Section 9.3 Populations for 
Analyses, Section 9.4.2
Efficacy
Changed name of ITT 
Population to FAS.
To be consistent with AZ procedures and 
protocols.
Section 1.3 SoA, Table 1, 
Section 8.2.2 Vital Signs
Removed collection of height 
measurement at Visit 1.
Height is collected in the lead in study, and 
safety assessments are not impacted by 
measurement of height.
Section 1.3 SoA, Table 1, 
Section 5.2 Exclusion 
Criterion #7, #8, #16, 
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments, Table 12
Removed hepatitis B and C 
and HIV testing at all 
timepoints (including study 
entry).
Hepatitis B and C and HIV testing occur 
upon study entry in the lead-in study, and the 
brazikumab mechanism of action is not 
associated with an increased risk of infection. 
Investigators will assess and manage the risk 
of hepatitis B and C and HIV, as per local 
standard of care.
Section 1.3 SoA, Table 1, 
Table 2, Section 5.1
Inclusion Criterion #2, 
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments, Table 12, 
Previous Appendix E
Procedure for Tuberculosis 
Testing
Removed chest x-ray, 
QFT-TB, and TB testing at all 
timepoints (including study 
entry)
TB testing occurs upon study entry in the 
lead-in study, and the brazikumab mechanism 
of action is not associated with an increased 
risk of infection. Investigators will assess and 
manage the risk of TB, as per local standard 
of care.
Section 1.3 SoA, Table 1
Updated physical exam 
description.
Revisions were made for clarity to 
distinguish general physical exams for safety 
from those for exploratory efficacy 
assessments.
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Section # and name
Description of change
Brief rationale
Section 1.3 SoA Table 1, 
Table 2, Section 5.2
Exclusion Criterion #16g, 
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments, Table 12
Removed testing of stool for 
C. difficile at all timepoints 
(including study entry).
C. difficile testing occurs upon study entry in 
the lead-in study, and the brazikumab 
mechanism of action is not associated with an 
increased risk of infection. Investigators will 
assess and manage the risk of C. difficile, as 
per local standard of care.
Section 1.3 SoA Table 1
Added PK sampling at 
Week 12 for participants who 
have 
. 
To align PK and PD timepoints to facilitate 
PK/PD modelling.
Section 1.3 SoA Table 1
Removed biomarker sampling 
(exploratory biomarkers, stool 
for lactoferrin and FCP, and 
PAXgene RNA) at Week 24.
Decreased exploratory assessments to reduce 
site and participant burden.
Section 1.3 SoA Table 1
Moved biomarker sampling 
(exploratory biomarkers, 
PAXgene RNA) from Week 0 
to Screening. Samples will 
only be collected from 
participants if not collected at 
the lead-in study end-of-study 
visit.
Biomarker assessments from the last visit in 
the lead-in study will be used as baseline.
Section 1.3 SoA Table 1
Clarified PAXgene RNA 
collection notes that it should 
not be collected if whole blood 
transfusion within 120 days.
Added clarification to align with lead-in CSP 
and to ensure necessary sample quality.
Section 1.3 SoA Table 1
and Table 3
Removed exploratory efficacy 
assessments (CDAI and 
PROs) at Weeks 24 and 36 
and indicated Week 12 only 
for participants who have 
 
.
Decreased exploratory assessments to reduce 
site and participant burden.
Section 1.3 SoA Table 1, 
Table 3, Section 8.1.2
Crohn’s Disease Activity 
Index, Section 8.1.3 Patient-
Reported Outcomes-
Evening Diary
Clarified that PRO paper diary 
will be collected for 7 days 
before visit or prior to bowel 
prep if endoscopy is planned 
for the visit.
To provide clear guidance for PRO data 
collection for sites and maintain data quality.
Section 1.3 SoA Table 1
Added a column and footnote 
to the SoA for unscheduled 
visits.
Added to provide guidance to the investigator 
on assessments to be performed at an 
unscheduled visit.
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Section # and name
Description of change
Brief rationale
Section 1.3 SoA Table 1, 
Section 8 Study 
Assessments and 
Procedures
Added text to footnote ‘b’ to 
indicate that a repeat 
ileocolonoscopy is not 
required for participants that 
discontinued from the lead-in 
study between Weeks 12 to 
16.
The Week 12 ileocolonoscopy acquired in the 
lead-in study will be used for the screening 
assessment in this OLE study to reduce 
participant burden.
Section 1.3 SoA Table 1, 
Section 8 Study 
Assessments and 
Procedures, Appendix G
Added text (Notes column and 
footnote ‘c’) to clarify window 
for Week 0 dose 
administration from the last 
dose in the lead-in study.
Added to maintain participant safety by 
keeping at least a 14-day gap between doses 
and to minimize potential delay in dosing of 
participants.
Section 1.3 SoA Table 2
Added follow-up visit 
window.
Added flexibility to visit window for site and 
participant benefit.
Section 1.3 SoA Table 2
Removed duplicate FCP row.
Revisions were made for clarity.
Section 1.3 SoA Table 2
Added PK blood sample at ET 
and follow-up visits.
Aligned PK and ADA assessments as PK 
information is essential for the interpretation 
of ADA sampling.
Section 1.3 SoA Table 2
Removed biomarker sampling 
(exploratory biomarkers, stool 
for lactoferrin and FCP, and 
PAXgene RNA) at follow-up 
visit 2.
Decreased exploratory assessments to reduce 
site and participant burden.
Section 1.3 SoA, Table 3
Indicated evening diary to be 
collected at ET.
Revisions were made to maintain data 
integrity by aligning ET PRO data collection 
at Week 52 visit.
Section 2.3 Benefit/Risk 
Assessment
The important potential risks 
of brazikumab were modified 
to incorporate the correct 
terminology of ‘severe 
hypersensitivity’.
Corrections were made to align the potential 
risks with terminology used in the 
Brazikumab IB.
Section 3 Objectives and 
Endpoints, Table 4
Added an exploratory 
objective for evaluating the 
PK and immunogenicity of 
brazikumab.
PK and immunogenicity sampling is 
mandatory per the SoA, and planned sample 
analysis is well defined (Section 8.5). This 
addition is to ensure intended use is 
appropriately reflected in study objectives.
Section 3 Objectives and 
Endpoints, Table 4
Added an additional 
exploratory objective needed 
to cover any/all biomarker 
analyses to be completed.
Biomarker sampling is mandatory per the 
SoA, and planned sample analysis is well 
defined (Section 8.5). This additional 
objective is to ensure intended use is 
appropriately reflected in the study 
objectives.

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Section # and name
Description of change
Brief rationale
Section 5.1 Inclusion 
Criterion #1b
Removed language regarding 
worsening of disease.
Removed for clarity as rescue criteria are 
clearly defined in the lead-in study CSP and 
include worsening of disease.
Section 6.1 Study 
Interventions Administered
Revised the language 
describing the IP.
Modified to clearly describe the IP 
formulation.
Section 6.1.2 Subcutaneous 
Administration, Figure 2, 
Section 6.2
Preparation/Handling/
Storage/Accountability
Additional injection sites for 
 were added.
Additional injection sites were added to 
reduce the risk of AEs when the same site is 
repeatedly used, and to collect safety and 
tolerability information for different 
 
Section 6.2
Preparation/Handling/
Storage/Accountability
Revised the language for the 
equilibration time and 
temperature of the 
 
 Included a standard 
clause regarding storing the 
prefilled syringe in the inner 
carton during temperature 
equilibration.
Further investigation has determined that an 
equilibration time of at least 40 minutes at 
room temperature is required for 
 
Section 6.3 Measures to 
Minimize Bias: 
Randomization and 
Blinding
A sentence was added to 
explain that treatment 
assignment from the lead-in 
study not be unblinded, and 
this OLE study is not 
randomized.
Explanation that while this study is open-
label, it is still critical that the lead-in study is 
not unblinded. Blinded endoscopy review 
will not be performed.
Section 6.5.2 Corticosteroid 
Study Guidelines
Reduced specifications in 
regards to corticosteroid doses 
in this study.
To enable investigators to manage 
corticosteroid dose to maintain safety of 
participants.
Section 6.5.4 Prohibited 
Interventions During the 
Study
Removed language regarding 
exemptions to live attenuated 
vaccine usage.
To maintain participant safety during the 
study and clarity for sites.
Section 8.1.1.2 Biopsy
Revised the language to state 
that histological indices for 
biopsies will be detailed in a 
separate, exploratory analysis 
plan.
Correction made to describe the approach for 
histological analysis.
Section 8.1.2 Crohn’s 
Disease Activity Index
Amended the rating and range 
of the total general well-being 
score.
Correction of error in previous protocol 
version.
Section 8.1.3 Patient-
Reported Outcomes-
Evening Diary
Urgency and blood in stool 
added to the description of the 
diary. Clarified when diary 
should be completed and the 
appropriate scale for the 
assessment.
Modified text for accuracy and clarity.
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Section # and name
Description of change
Brief rationale
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments, Table 12
Removed coagulation group 
assessment from the 
hematology panel for the 
clinical laboratory 
assessments.
Coagulopathy is adequately assessed by the 
remaining Hy’s Law kit.
Section 8.2.4 Clinical 
Safety Laboratory 
Assessments, Table 12
Added FCP and fecal 
lactoferrin to fecal tests.
Specific analyses added to ensure accuracy 
and transparency with intended use in the 
study.
Section 8.3 Adverse Events 
and Serious Adverse Events
Revised the language for 
collecting and reporting AE 
information.
Revisions were made to align with current 
AZ standard safety reporting.
Section 8.3.1 Time Period 
and Frequency for 
Collecting AE and SAE 
Information
Revised the language for 
collecting AE information 
before the start of study 
intervention.
Revisions were made to align with current 
AZ standard safety reporting.
Section 8.3.8 Reporting of 
Serious Adverse Events
Revised the language of safety 
reporting via EDC.
Revision was made to align with migration 
from legacy EDC to AZ EDC and standard 
safety reporting
Section 8.3.9.1 Maternal 
Exposure
Revised the language of 
pregnancy reporting.
Revision was made to align with migration 
from legacy EDC to AZ EDC and standard 
safety reporting
Section 8.8 Medical 
Resource Utilization and 
Health Economics
Removed Medical Resource 
Utilization and Health 
Economics data from the 
assessments.
These parameters were included in error and 
are not to be collected in this study. 
Section 9.3 Populations for 
Analyses
Added Screened Analysis Set.
To facilitate reporting of disposition.
Appendix F 1 and F 2
Removed electronic device 
text.
Correction made as all PROs will be 
administered on paper.
ADA = anti-drug antibody; AE = adverse event; AZ = AstraZeneca; C. difficile = Clostridium difficile; 
CSP = clinical study protocol; EDC = electronic data capture; ET = Early Termination Visit; FAS = Full 
Analysis Set; FCP = fecal calprotectin; HIV = human immunodeficiency virus; IB = Investigator’s Brochure; 
IP = investigational product; ITT = intent-to-treat; 
 OLE = open-label extension; 
PD = pharmacodynamic(s); PK = pharmacokinetic(s); PRO = patient-reported outcomes; 
QFT-TB = QuantiFERON-TB test; RNA = ribonucleic acid; SAE = serious adverse event; 
 
SoA = schedule of activities; TB = tuberculosis.
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TABLE OF CONTENTS
TITLE PAGE........................................................................................................................ 1
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3
TABLE OF CONTENTS ...................................................................................................... 9
1
PROTOCOL SUMMARY ................................................................................ 14
1.1
Synopsis ........................................................................................................... 14
1.2
Schema............................................................................................................. 17
1.3
Schedule of Activities ....................................................................................... 18
2
INTRODUCTION............................................................................................ 29
2.1
Study Rationale ................................................................................................ 30
2.2
Background ...................................................................................................... 30
2.3
Benefit/Risk Assessment................................................................................... 34
2.3.1
Overall Benefit: Risk Conclusion...................................................................... 35
3
OBJECTIVES AND ENDPOINTS................................................................... 36
4
STUDY DESIGN ............................................................................................. 37
4.1
Overall Design.................................................................................................. 37
4.1.1
Study Conduct Mitigation During Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis ................................................ 38
4.2
Scientific Rationale for Study Design ............................................................... 38
4.3
Justification for Dose........................................................................................ 39
4.4
End of Study Definition.................................................................................... 39
5
STUDY POPULATION.................................................................................... 41
5.1
Inclusion Criteria .............................................................................................. 41
5.2
Exclusion Criteria ............................................................................................. 44
5.3
Lifestyle Considerations ................................................................................... 46
5.3.1
Meals and Dietary Restrictions ......................................................................... 46
5.3.2
Caffeine, Alcohol, and Tobacco......................................................................... 46
5.4
Screen Failures ................................................................................................. 47
6
STUDY INTERVENTION ............................................................................... 48
6.1
Study Interventions Administered ..................................................................... 48
6.1.1
............................................................................................. 49
6.1.2
............................................................................................ 50
6.1.3
Study Intervention Administration Rescheduling .............................................. 51
6.1.4
Study Supplies.................................................................................................. 52
6.2
Preparation/Handling/Storage/Accountability ................................................... 52
6.3
Measures to Minimize Bias: Randomization and Blinding ................................ 53
6.4
Study Intervention Compliance......................................................................... 54
6.5
Concomitant Therapy........................................................................................ 54
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6.5.1
Permitted Interventions..................................................................................... 54
6.5.2
Corticosteroid Study Guidelines........................................................................ 56
6.5.3
Rescue Treatment ............................................................................................. 57
6.5.4
Prohibited Interventions During the Study ........................................................ 57
6.6
Dose Modification ............................................................................................ 58
6.7
Intervention After the End of the Study............................................................. 59
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL........................................................... 60
7.1
Discontinuation of Study Intervention............................................................... 60
7.2
Participant Withdrawal from the Study.............................................................. 62
7.3
Lost to Follow-up ............................................................................................. 62
8
STUDY ASSESSMENTS AND PROCEDURES.............................................. 64
8.1
Efficacy Assessments........................................................................................ 64
8.1.1
Ileocolonoscopy................................................................................................ 64
8.1.1.1
Simple Endoscopic Score for Crohn’s Disease.................................................. 65
8.1.1.2
Biopsy .............................................................................................................. 66
8.1.2
Crohn’s Disease Activity Index......................................................................... 66
8.1.3
Patient-reported Outcomes - Evening Diary...................................................... 68
8.1.4
Patient-reported Outcomes – Site Visits ............................................................ 69
8.2
Safety Assessments........................................................................................... 69
8.2.1
Physical Examinations...................................................................................... 69
8.2.2
Vital Signs ........................................................................................................ 70
8.2.3
Electrocardiograms........................................................................................... 70
8.2.4
Clinical Safety Laboratory Assessments............................................................ 70
8.3
AEs and SAEs .................................................................................................. 72
8.3.1
Time Period and Frequency for Collecting AE and SAE Information................ 72
8.3.2
Follow-up of AEs and SAEs ............................................................................. 73
8.3.3
Causality Collection.......................................................................................... 74
8.3.4
AEs Based on Signs and Symptoms.................................................................. 74
8.3.5
AEs Based on Examinations and Tests.............................................................. 74
8.3.6
Hy’s Law.......................................................................................................... 75
8.3.7
Disease Under Study......................................................................................... 75
8.3.8
Reporting of SAEs............................................................................................ 75
8.3.9
Pregnancy......................................................................................................... 76
8.3.9.1
Maternal Exposure............................................................................................ 76
8.3.9.2
Paternal Exposure............................................................................................. 76
8.3.10
AEs of Special Interest...................................................................................... 77
8.3.10.1
Infusion-related Reactions and Injection Site Reactions .................................... 77
8.3.10.2
Malignancies .................................................................................................... 77
8.3.10.3
Hypersensitivity Reactions (Anaphylaxis)......................................................... 78
8.3.10.4
Infections.......................................................................................................... 78
8.3.11
Medication Error............................................................................................... 78
8.4
Overdose .......................................................................................................... 79

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8.5
Human Biological Samples............................................................................... 79
8.5.1
Pharmacokinetics.............................................................................................. 80
8.5.1.1
Determination of Drug Concentration ............................................................... 80
8.5.2
Immunogenicity Assessments ........................................................................... 80
8.5.3
Pharmacodynamics........................................................................................... 81
8.6
Human Biological Sample Biomarkers ............................................................. 81
8.6.1
Collection of Mandatory Samples for Biomarker Analysis ................................ 81
8.7
Genomics Initiative Sample .............................................................................. 81
8.8
Medical Resource Utilization and Health Economics ........................................ 82
9
STATISTICAL CONSIDERATIONS................................................................ 83
9.1
Statistical Hypotheses....................................................................................... 83
9.2
Sample Size Determination............................................................................... 83
9.3
Populations for Analyses................................................................................... 83
9.4
Statistical Analyses ........................................................................................... 83
9.4.1
General Considerations..................................................................................... 83
9.4.2
Efficacy ............................................................................................................ 84
9.4.2.1
Exploratory Endpoints ...................................................................................... 84
9.4.3
Safety ............................................................................................................... 84
9.4.3.1
AEs................................................................................................................... 85
9.4.3.2
Clinical Laboratory Assessments....................................................................... 85
9.4.3.3
Vital Signs ........................................................................................................ 86
9.4.3.4
ECGs................................................................................................................ 86
9.4.4
Exploratory BM Analyses................................................................................. 86
9.5
Interim Analyses............................................................................................... 86
9.6
Data Monitoring Committee ............................................................................. 86
10
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ........................................................................................ 87
11
REFERENCES............................................................................................... 147

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LIST OF FIGURES
Figure 1
Study Design ........................................................................................... 17
Figure 2
.................................... 50
LIST OF TABLES
Table 1
Schedule of Activities.............................................................................. 18
Table 2
Schedule of Activities: Early Termination Visit and Safety Follow-up 
Period...................................................................................................... 27
Table 3
Schedule of Activities – PRO Assessments.............................................. 28
Table 4
Objectives and Endpoints......................................................................... 36
Table 5
Exposure Margins Supporting Planned Doses.......................................... 39
Table 6
Rescue Criteria from Study D5271C00001 (Legacy #3150-301-008)....... 42
Table 7
Study Interventions.................................................................................. 48
Table 8
Permitted Concomitant Treatments.......................................................... 56
Table 9
Corticosteroid Tapering Guidelines.......................................................... 56
Table 10
Simple Endoscopic Score for Crohn’s Disease Values ............................. 66
Table 11
Items Included in CDAI and Their Weights ............................................. 68
Table 12
Protocol-required Safety Laboratory Assessments.................................... 71
Table 13
Populations for Analysis .......................................................................... 83
LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations......................... 88
Appendix B
AEs: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting .......................................................................................... 93
Appendix C
Handling of Human Biological Samples .................................................. 99
Appendix D
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law......................................................................... 101
Appendix E
Sample Corticosteroid Tapering............................................................. 107
Appendix F
Patient-reported Outcomes Questionnaires, Descriptions, and 
Instructions............................................................................................ 108
Appendix G
Changes Related to Mitigation of Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis ............................ 128
Appendix H
Abbreviations ........................................................................................ 131
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Appendix I
Protocol Amendment History................................................................. 134

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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: An Open-label, Long-term Extension Study of Brazikumab in 
Participants with Moderately to Severely Active Crohn’s Disease (INTREPID OLE)
Short Title: Open-label Extension Study of Brazikumab in Crohn’s Disease
Rationale:
Brazikumab, a human immunoglobulin that selectively binds to human IL-23 with high 
affinity and prevents IL-23 from interacting with the IL-23 receptor, is being studied for the 
treatment of CD in Study D5271C00001 (Legacy #3150-301-008).
The purpose of Study D5271C00002 (Legacy #3150-303-008) is to collect long-term safety 
data from participants in Study D5271C00001 (Legacy #3150-301-008) who receive 
open-label brazikumab in Study D5271C00002 (Legacy #3150-303-008).
Objectives and Endpoints
The objectives and endpoints are presented below:
Objectives
Endpoints
Primary
!
To assess the safety of long-term treatment 
with brazikumab in CD participants who 
previously completed Study D5271C00001 
(Legacy #3150-301-008) or discontinued 
from Study D5271C00001 (Legacy #3150-
301-008) at or after Week 12 due to lack of 
efficacy.
!
AEs
!
Clinical laboratory values
!
Vital signs
!
Physical exams
!
ECGs
For exploratory objectives and endpoints, see Section 3 of the protocol.
Overall Design
This is a global, multicenter, open-label extension study of brazikumab limited to participants 
previously enrolled in Study D5271C00001 (Legacy #3150-301-008) (hereinafter referred to 
as the lead-in study). Participants in the lead-in study are eligible to enroll in 
Study D5271C00002 (Legacy #3150-303-008) provided they continue to meet eligibility 
criteria and have not had adverse experiences considered to be related to study medication that 
resulted in discontinuation of the initial lead-in study intervention, or that in the judgement of 
the investigator, would disqualify them from participating. Participants will be eligible for 
inclusion into this study if they have completed the lead-in study, or have completed 12 weeks 

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of treatment, but were subsequently discontinued due to lack of efficacy. Eligible participants 
do not need to complete the 18-week safety follow-up period of the lead-in study, if they 
roll-over into this study after they complete the Week 52 visit of the lead-in study.
Disclosure Statement: 
This is a parallel group treatment study with 2 arms that is open-label.
Number of Participants:
This study is an extension study and the sample size is determined by the number of 
participants in the lead-in study who are eligible and choose to participate in this study. No 
separate sample size calculation was performed. Up to a maximum of 240 participants may 
enter this study, based on the expected number of participants in the lead-in study.
Intervention Groups and Duration:
The 240 mg SC dose of brazikumab will be administered every 4 weeks to all who completed 
requirements through Week 52 and met CDAI response (CDAI score of < 150 points or CDAI 
reduction from Baseline of ≥ 100 points) without ongoing rescue treatment at Week 52 in the 
lead-in study. Participants who met criteria for early termination due to lack of efficacy 
(rescue treatment criteria) or who did not meet CDAI response at Week 52 in the lead-in study 
are considered inadequate/non responders, and will receive 
 dosing with 
 
 followed by maintenance dosing of 
brazikumab 
.
There will be an 18-week post-last dose safety follow-up period during which there will be no 
intervention administered for participants in the safety follow-up.
Study Duration:
The study will consist of a 52-week open-label treatment period and an 18-week safety 
follow-up period, for a total of up to 70 weeks.
Data Monitoring Committee: 
Not applicable.
Statistical Methods
All safety and efficacy analyses for this study will be summarized descriptively by the visit 
and the treatment sequences and overall, unless stated otherwise. For participants who were 
previously enrolled in the lead-in study, the baseline from the lead-in study will be used for 
the analyses. Continuous variables will be summarized by the number of participants and 
mean, SD, median, Q1, Q3, minimum, and maximum values. Categorical variables will be 
summarized by number and percentage of participants. 
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The FAS population will comprise all participants who are assigned to an 
 
brazikumab study intervention in the study. The Safety Population will comprise all 
participants who receive 
 administration of study intervention in this extension study. The 
efficacy analyses will be based on the FAS population using the observed-cases approach. The 
safety analysis will be performed using the Safety Population and will include AEs, clinical 
laboratory parameters, vital signs, and ECG parameters.
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1.2
Schema
Figure 1
Study Design
The safety follow-up periods are based on the last investigational dose at Week 52 (Visit 14). Participants 
discontinued at any time during the study will be required to proceed to the untreated safety follow-up period.
CDAI = Crohn’s Disease Activity Index; 
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1.3
Schedule of Activities
Separate SoAs are presented for the Screening and Treatment Period (Table 1), Early Termination/Safety Follow-up Period (Table 2), 
and for the PROs (Table 3).
Table 1
Schedule of Activities
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Eligibility 
criteria 
assessment
Written ICF 
and 
participant 
identification 
assignment in 
IWRS
X
5.1
Inclusion and 
exclusion 
criteria
X
X
5.1 and 
5.2
Demographics
X
Medical, 
surgical, and 
CD history
X

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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Prior and 
concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
6.5
Vital signs 
and weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.2.2
Safety 
assessments
AE/SAE 
assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.3
Physical exam
X
X
X
X
X
X
X
Including 
abdominal 
exam, EIM 
assessment 
for CDAI 
score, fistula 
exam (as 
applicable) at 
W0, W12e, 
W52
8.2.1
12-lead ECG
X
X
X
8.2.3
Assessment of 
injection-site 
reactions
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Laboratory 
assessments
Serum 
chemistry, 
hematology, 
and CRP
X
X
X
X
X
X
8.2.4
Stool for fecal 
calprotectin, 
fecal 
lactoferrin, 
and 
exploratory 
biomarkers
X
Xe
X
X
All stool tests 
should be 
collected prior 
to start of 
bowel prep 
for visits 
where ileo-
colonoscopy 
is needed
8.6
Urinalysis
X
X
X
8.2.4
Urine
pregnancy test 
performed 
locally
(WOCBP 
only)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
5

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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Biomarkers
sampling
Predose PK 
blood sample
X
Xe
X
X
Note the exact 
time and date 
for sampling
8.5.1
Serum for 
ADA 
(pre-dose)
X
X
X
6.1
Blood for 
exploratory 
biomarkers
X
Xe
X
8.6.1
PAXgene 
RNA
X
X
X
Do not collect 
if whole blood 
transfusion 
within 
120 days
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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Efficacy 
assessments
Ileo-
colonoscopy 
including 
terminal ileum 
and colon 
mucosal 
biopsies
X
X
X
Daily PRO 
data collected 
7 days prior to 
bowel prep 
will be used 
to calculate 
CDAI
8.1.1.1
SES-CD 
assessment
X
X
X
SES-CD will 
be assessed by 
a central 
reader 
8.1.1.1
CDAI
X
Xe
X
X
Week 0 CDAI 
to be 
calculated 
using the 
screening 
hematocrit
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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Provide PRO 
paper diary
X
Xe
X
X
Provide the 
paper diary to 
the participant 
and instruct 
them to 
collect the 
data 1 week 
prior to the 
next visit or 
1 week prior 
to bowel prep 
if endoscopy 
is planned for 
that visit; W0 
paper diary to 
be provided at 
the last visit 
in lead-in 
Study 
D5271C0000
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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
PRO 
assessments 
(paper)
X
Xe
X
X
Evening diary 
will be 
collected 
every evening 
for 1 week 
prior to the 
indicated 
scheduled 
visits or 
1 week prior 
to bowel prep 
if endoscopy 
is planned for 
that visit
Table 3
and 8.1.3
Site visit 
PROs
X
Xe
X
X
Will be 
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site visit

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Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
UNSa
Notes
Details in 
CSP 
Section 
or 
Appendix
Visit name
Scrb
W0c
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Study dayd
1
29
57
85
113
141
169
197
225
253
281
309
337
365
Visit window 
(days)
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Study 
intervention 
administration
First dose 
should be 
administered 
no earlier than 
14 days and 
no later than 
56 days from 
last dose in 
Study 
D5271C0000
1 (Legacy 
#3150-301-
008) 
4.1 and 6
a
Not all assessments indicated for the UNS need to be performed. The assessments are to be performed at the discretion of the investigator, as clinically 
indicated.
b
All assessments made at the final visit of Study D5271C00001 (Legacy #3150-301-008) will be utilized as screening assessments for this study, unless 
Week 0 for this study occurs greater than 28 days from the final assessment(s) of the lead-in study, in which case the participant will need to complete all 
required screening assessments, except the ileocolonoscopy and CDAI. A repeat ileocolonoscopy is not required for participants who discontinue from the 
lead-in study after Week 12 and prior to Week 16.
c
Week 0 dose administration must occur no earlier than 14 days and no later than 56 days from the last dose administration in Study D5271C00001 (Legacy 
#3150-301-008).
d
The visit schedule will always be calculated from Week 0 date.
e
Collect Week 12 samples and data from participants who have 
 only.
f
Participants who receive 
 dosing will be administered brazikumab 
 at 4-week intervals starting Week 12 through Week 52.
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ADA = anti-drug antibody; AE = adverse event; CD = Crohn’s disease; CDAI = Crohn’s Disease Activity Index; CRP = C-reactive protein; CSP = clinical study 
protocol; ECG = electrocardiogram; EIM = extraintestinal manifestation; ICF = informed consent form; 
 IWRS = interactive web-response 
system; PK = pharmacokinetic; PRO = patient-reported outcome; RNA = ribonucleic acid; SAE = serious adverse event; 
 Scr = screening; 
SES-CD = Simple Endoscopic Score for Crohn’s Disease; UNS = unscheduled visit; W = week; WOCBP = women of childbearing potential.
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Table 2
Schedule of Activities: Early Termination Visit and Safety Follow-up 
Period
Study period
Open-label
18-week follow-upa
Visit name
Early Termination Visit
Follow-up 1
(Week 60)
Follow-up 2
(Week 70)
Visit timing (and window)
At study withdrawal or 
premature discontinuation of 
study intervention
8 weeks post 
last dose 
(± 7 days)
18 weeks post 
last dose 
(± 7 days)
AE/SAE assessment
X
X
X
Concomitant medications
X
X
X
Physical examination, vital signs, and 
weightb
X
X
X
ECG
X
Serum chemistry, hematology, CRP, 
and urinalysis
X
X
X
Urine pregnancy test
X
X
X
PK blood sample
X
X
X
Serum brazikumab, ADA 
immunogenicity
X
X
X
Blood for exploratory biomarker 
analysis
X
PAXgene RNA
X
Stool for calprotectin, lactoferrin, and 
exploratory biomarkers
X
Ileocolonoscopy including terminal 
ileum and colon mucosal biopsies
X
SES-CD assessment
X
CDAI and PROs
X
Assessment of injection-site reactions
X
a
Study intervention will not be administered during the 18-week safety follow-up period.
b
Including abdominal exam, EIM assessments for CDAI score, fistula exam (as applicable) to be performed 
only at ET.
ADA = anti-drug antibody; AE = adverse event; CDAI = Crohn’s Disease Activity Index; CRP = C-reactive 
protein; ECG = electrocardiogram; EIM = extraintestinal manifestation; ET = Early Termination Visit; 
PK = pharmacokinetic; PRO = patient-reported outcome; RNA = ribonucleic acid; SAE = serious adverse event; 
SES-CD = Simple Endoscopic Score for Crohn’s Disease.

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Table 3
Schedule of Activities – PRO Assessments
PRO assessment
Frequency of administration
Notes
Evening Diarya 
(CDAI, PRO items, 
and NRS)
Paper diaries will be provided to 
participants at site visits prior to 
collection visits. Participants will 
be prompted to begin recording 
PRO data 1 week prior to the site 
visit or bowel prep if endoscopy 
is planned for the visit. The night 
before the site visit or bowel prep 
should be day 7.
IBDQ
Collected at the site
SF-36v2
Collected at the site
EQ-5D-5L
Collected at the site
a
Evening is defined as 18:00 to 23:59 and participants should be instructed to complete the paper diaries 
during this time interval each evening.
b
Week 12 assessments for participants who have 
CDAI = Crohn’s Disease Activity Index; ET = Early Termination Visit; EQ-5D-5L = European Quality of Life-5 
Dimensions; IBDQ = Inflammatory Bowel Disease Questionnaire; 
 NRS = Numerical Rating 
Scale; PRO = patient-reported outcome; SF-36v2 = 36-item Health Survey Version 2.
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2
INTRODUCTION
This study is an open-label continued access study for participants with CD who have been 
enrolled in Study D5271C00001 (Legacy #3150-301-008). The nature of CD and the rationale 
for studying brazikumab in this disorder has been discussed previously in the protocol for 
Study D5271C00001 (Legacy #3150-301-008) and in the current Brazikumab IB 
(Brazikumab/MEDI2070).
Crohn’s disease is a chronic transmural inflammatory disease that most commonly affects the 
distal ileum and colon and may occur in any part of the gastrointestinal tract (Crohn’s and 
Colitis Foundation of America, Burger et al, 2011, Rutgeerts et al, 2003). Patients with CD 
have uncontrolled inflammation that causes direct damage to the intestinal mucosa. This 
inflammation is believed to result either from persistence of inflammatory stimulus, due to 
impaired gut barrier function, or from a dysregulated inflammatory response. Crohn’s disease 
occurs most commonly between 15 to 30 and 60 to 80 years of age; although, persons of any 
age may be affected. Commonly used medical therapies include aminosalicylates 
(eg, sulfasalazine and mesalamine), systemic CS, immunosuppressive agents (eg, azathioprine 
and methotrexate), antibacterial agents, and biologic agents (eg, adalimumab [Humira®, 
Abbvie, Inc, North Chicago, IL], infliximab [Remicade®, Janssen Biotech, Inc, USA], 
certolizumab [Cimzia®, UCB, Inc, Smyrna, GA], vedolizumab [Entyvio®, Takeda 
Pharmaceuticals America Inc, Deerfield, IL], and natalizumab [Tysabri®, Biogen Idec Inc, 
Cambridge, MA]). Despite treatment with these agents, the residual morbidity, and the 
complications of CD (eg, intestinal obstruction and/or perforation, fistula formation, 
malnutrition) represent a burden of disease sufficient to warrant new therapies.
Brazikumab is a human immunoglobulin that selectively binds to human IL-23 with high 
affinity and prevents IL-23 from interacting with the IL-23 receptor. The roles of IL-23 are 
believed to be important for the recruitment and activation of a range of inflammatory cells 
involved in IBD (CD and UC). In preclinical models and studies in participants, anti-
IL-12/23p40 antibodies (eg, ustekinumab and briakinumab) have been shown to induce 
clinical responses in a variety of inflammatory diseases. Phase 2 data in participants with CD 
have demonstrated clinical efficacy of brazikumab comparable with that of antibodies 
targeting IL-12/23, suggesting that IL-23 activity may play an important, if not dominant, role 
in the inflammatory conditions under study. Thus, IL-23 blockade represents a novel 
mechanism to inhibit the inflammation and clinical symptoms associated with CD; 
specifically, targeting IL-23 by brazikumab may offer a better benefit-risk profile compared 
with the IL-12/23 antibodies.
Targeting CD with brazikumab is supported by robust genetic and nonclinical data and by the 
demonstrated clinical efficacy of anti-IL-12/23p40 antibodies (ustekinumab and briakinumab) 
and anti-IL-23p19 antibodies in CD (Mannon et al, 2004, Sandborn et al, 2012, Feagan et al, 

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2016, Feagan et al, 2017) and UC (Sandborn et al, 2020). Mice deficient in IL-23p19 are 
protected against experimental colitis, while mice deficient in IL 12p35 are not (Hue et al, 
2006, Yen et al, 2006). Preclinical studies in several different animal models of IBD have 
demonstrated strong efficacy with IL-23-specific antagonism (Kullberg et al, 2006, Uhlig et 
al, 2006, Ahern et al, 2008, IB Section 4.1).
2.1
Study Rationale
Brazikumab, a human immunoglobulin that selectively binds to human IL-23 with high 
affinity and prevents IL-23 from interacting with the IL-23 receptor, is being studied for the 
treatment of CD in Study D5271C00001 (Legacy #3150-301-008).
The purpose of Study D5271C00002 (Legacy #3150-303-008) is to permit participants in 
D5271C00001 (Legacy #3150-301-008) to receive open-label brazikumab in Study 
D5271C00002 (Legacy #3150-303-008). This will permit long-term observation of safety in 
these participants and further characterize the efficacy of brazikumab. There are no formal 
hypotheses to be tested. Safety data will be included in regulatory product submissions as 
appropriate.
2.2
Background
Interleukin-23, a member of the IL-12 family of cytokines, is a heterodimeric cytokine 
consisting of 2 subunits: p40 and p19. The p40 subunit is shared by IL-12 and IL-23 as a 
common subunit and is targeted by inhibitors of IL-12/23 (eg, ustekinumab and briakinumab). 
The main known effects of IL-23 are to drive the differentiation of T helper 17 cells, as well as 
macrophages, natural killer cells, dendritic cells, and innate lymphoid cells leading to up 
regulation of IL-17, IL-22, TNFα, granulocyte-macrophage colony-stimulating factor, and 
IFNγ, and down regulation of IL-10 (Bettelli et al, 2007).
Studies in participants have demonstrated that IL-23 is upregulated in cells and target tissues 
of CD and UC, while IL-12 is not (Schmidt et al, 2005). Similar observations have been 
reported in psoriatic skin lesions (Lee et al, 2004), dendritic cells from participants with 
multiple sclerosis (Vaknin-Dembinsky et al, 2006), and active lesions from participants with 
multiple sclerosis (Li et al, 2007). Genome wide association studies in CD and psoriasis 
participants showed significant association between polymorphisms in the unique IL-23 
receptor component and disease (Cargill et al, 2007, Duerr et al, 2006). Furthermore, allelic 
variants of IL-23 receptor have shown significant correlation with the frequency of UC 
(Cargill et al, 2007), rheumatoid arthritis (Farago et al, 2008), ankylosing spondylitis (Burton 
et al, 2007), and multiple sclerosis (Illes et al, 2008).
In the clinic, anti-IL-12/23p40 antibodies (eg, ustekinumab and briakinumab) and
anti-IL-23p19 antibodies have been shown to induce clinical responses in CD (Sandborn et al, 
2012, Mannon et al, 2004, Feagan et al, 2017), UC (Sandborn et al, 2020), and psoriasis 

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(Phase 2 and Phase 3 studies; Gordon et al, 2012, Kimball et al, 2012, Langley et al, 2012, 
Gottlieb et al, 2011, Reich et al, 2011, Strober et al, 2011, Leonardi et al, 2008, Papp et al, 
2008). Phase 1 and Phase 2 clinical studies with anti-IL-23p19 antibodies brazikumab (Amgen 
Study 20080767) and CNTO 1959 (Sofen et al, 2011) in participants with psoriasis have 
demonstrated clinical efficacy comparable with antibodies targeting both IL-12 and IL-23, 
indicating that therapeutic effects of the anti-IL-12/23p40 antibodies may be due to 
neutralization of IL-23 alone.
Brazikumab, previously known as MEDI2070 and AMG 139, is briefly described below. 
Refer to the current Brazikumab IB (Brazikumab/MEDI2070) for details.
Brazikumab is a human, Chinese hamster ovary cell-derived, IgG2 monoclonal antibody 
consisting of 2 heavy chains of the IgG2 subclass and 2 light chains of the lambda subclass, 
which are covalently linked through disulfide bonds.
The nonclinical safety of brazikumab was evaluated in several studies with cynomolgus 
monkeys as the pharmacologically relevant species. In a safety pharmacology study, no 
brazikumab related effects were noted on evaluated cardiovascular, respiratory, or 
neurobehavioral parameters after single 
 In studies of 
2 weeks, 3 months, and 6 months duration in cynomolgus monkeys, brazikumab was 
generally well tolerated when 
 Brazikumab administration at doses up 
to and including 300 mg/kg had no effect on in-life observations, peripheral blood 
immunophenotyping, or clinical and anatomic pathology, and no sex-related differences in 
exposure. In the 6-month toxicology study, administration of brazikumab to cynomolgus 
monkeys by 
 at 
 once weekly for 26 weeks had no 
toxicologically significant effects on study parameters. Approximately 14% (4 of 28) of the 
brazikumab-treated animals developed binding ADAs during the dosing period and 25% (1 of 
4) of animals at 300 mg/kg developed binding ADAs in the recovery period. No NABs were 
detected in animals that tested positive for binding ADAs, and binding ADAs did not decrease 
brazikumab exposure. The no observed adverse effect level following 
 
brazikumab was 
 the maximum dose tested, corresponding to a Cmax of 
 and an AUC of 
Four clinical studies with brazikumab have been completed: Phase 1a Study 20080767, 
Phase 1b Study 20090519, Phase 2a Study D5170C00001, and Phase 1 Study 3150-101-008.
The first study with brazikumab was Study 20080767 (conducted by Amgen), a 2-part, single 
dose study in healthy participants (Part A) and participants with moderate to severe psoriasis 
(Part B). A total of 73 participants were administered brazikumab as a 
 
 or placebo. Overall, brazikumab 
demonstrated an acceptable safety profile that supported further clinical development. In 
participants with psoriasis, 
 and an 
 
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brazikumab, also showed evidence of clinical efficacy as demonstrated by improvements in 
the Psoriasis Area Severity Index score.
The Phase 1b Study, Study 20090519, was a randomized, double-blind, placebo-controlled, 
ascending multiple-dose study to evaluate safety, tolerability, PK, and pharmacodynamic of 
brazikumab in healthy participants (Part A) and these same parameters, plus efficacy, in 
participants with mild to severe CD (Part B). A total of 40 participants were randomized and 
received at least one dose of study intervention (brazikumab or placebo) in Part A and an 
additional 8 participants with CD were randomized into Part B of the study and received study 
intervention (brazikumab or placebo). No TESAEs or deaths were reported, and no 
participants withdrew from the study because of a TEAE.
Study D5170C00001 was a 2-part, Phase 2a study comprising a 12-week, double-blind, 
placebo-controlled period followed by a 100-week, open-label period to evaluate the 
short-term efficacy and the short- and long-term safety of brazikumab in participants with 
moderate to severe, active CD who failed, or were intolerant to, anti-TNFα therapy. During 
the double-blind period of the study, participants received a 
 of brazikumab 
(
 or placebo at Weeks 0 and 4. At the completion of the double-blind, 
placebo-controlled period (Week 12), all participants had the option to enter a 100-week, 
open-label period where they received open-label brazikumab (
 every 4 weeks; 
Week 12 through Week 112). Of 119 participants who received study intervention during the 
double-blind period of the study, 112 participants had completed study participation through 
Week 8 (primary efficacy time point) and 104 participants had completed the double-blind 
period to Week 12 and entered the open-label period of the study. All 104 participants received 
at least 1
 brazikumab in the open-label period; 93 participants (89.4%) 
completed their Week 24 Visit; and 57 participants (54.8%) completed the 100-week 
open-label period.
The primary efficacy endpoint of Study D5170C00001, CDAI response at Week 8 (defined by 
either a CDAI score of < 150 or a reduction from baseline of at least 100 points) was met. The 
proportion of participants that achieved a CDAI response at Week 8 was statistically 
significantly higher in the brazikumab group than in the placebo group (49.2% vs 26.7%, 
respectively, p = 0.010). The secondary efficacy endpoints generally supported the findings of 
the primary efficacy analysis. The proportion of participants that achieved a CDAI 100-point 
improvement at Week 8 was statistically significantly higher in the brazikumab group than in 
the placebo group (45.8% vs 25.0%, respectively, p = 0.017). A marginal treatment group 
difference compared with placebo was also observed for CDAI remission at Week 8 (27.1% vs 
15.0%) that was not statistically significant.
Post hoc analysis of Study D5170C00001 revealed a statistically significant treatment by-
baseline interaction (p = 0.04) for the IL-22 serum interaction term in the logistic regression 
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model used in the analysis of clinical response at Week 8, which suggested that the treatment 
effect at Week 8 differed by-baseline IL-22 serum concentration (Sands et al, 2017). In 
addition, it was observed that the group of participants receiving brazikumab had a substantial 
reduction in IL-22 serum concentration (81% reduction at Week 8 compared with baseline), in 
contrast to the slight increase observed for the group of participants receiving placebo (6% 
increase, data on file). The median IL-22 serum concentration at baseline for the entire study 
population was 
 In the analyses of CDAI clinical response and CDAI remission 
stratified by the median baseline IL-22 serum concentration for the population (ie, 
<15.6 pg/mL and ≥15.6 pg/mL), it was observed that among participants with baseline IL-22 
serum concentrations of ≥ 15.6 pg/mL, the brazikumab-treated participants had an increased 
likelihood of clinical response and clinical remission at Week 8. In the subgroup of 
participants meeting this threshold, the placebo-adjusted CDAI clinical response rate was 
41.6% (p = 0.0009 for brazikumab versus placebo) and the placebo-adjusted CDAI clinical 
remission rate was 29.2% (p = 0.0116 for brazikumab versus placebo). In contrast, among 
participants with baseline IL-22 serum concentrations of < 15.6 pg/mL, brazikumab-treated 
participants had CDAI clinical response and remission rates similar to participants receiving 
placebo; the placebo-adjusted rates were 3.0 and -3.9, respectively (p = 0.8026 and 
p = 0.6681, respectively), for brazikumab compared with placebo.
The safety data from Study D5170C00001 for 
 and 
 
 showed an acceptable safety profile that is consistent with 
previous studies and supports clinical development. AEs reported in this study were generally 
mild or moderate in intensity. There were no deaths reported.
Study 3150-101-008 was a randomized, double-blind, placebo-controlled, ascending-dose 
study to evaluate the PK and dose proportionality of brazikumab in healthy White and 
Japanese male and female participants aged 18 to 50 years. The objectives of the study were: 
(1) to evaluate the PK and dose proportionality of brazikumab in healthy Japanese and White 
participants; (2) to evaluate safety and tolerability of brazikumab in healthy Japanese and 
White participants; (3) to explore the differences in the PK and safety of brazikumab in 
healthy Japanese versus White participants; and (4) to evaluate the impact of infusion rate on 
the PK, safety, and tolerability of brazikumab in White participants. 
 
 and 
 and 
 
 followed by an 
 brazikumab or 
placebo were administered to 3 groups of 16 male and female study participants (8 Japanese 
and 8 White). A single 
 of brazikumab in a 
 was also 
administered to 8 White male and female participants. All dose strengths were well tolerated.
In Study D5271C00001 (Legacy #3150-301-008), the brazikumab and brazikumab placebo 
 will be administered in a 
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A detailed description of the chemistry, pharmacology, efficacy, and safety of brazikumab is 
provided in the IB (Brazikumab/MEDI2070).
2.3
Benefit/Risk Assessment
Medical therapy of IBD remains complex with the need to individualize treatment based on 
various clinical factors including concomitant medical conditions and medications, prior 
treatment response to therapy, and consideration of potential short- and long-term toxicity 
associated with treatment based on individual risks. The overall goal of treatment in IBD is 
diminishing inflammation and improving signs and symptoms of IBD. Presently available 
treatments for IBD act to reduce inflammation by different actions including inhibition of 
cyclooxygenase and prostaglandin production and inflammatory cytokines 
(eg, aminosalicylates, steroids), immunomodulatory effects, inhibition α4β7 integrin 
(eg, vedolizumab), or blockade of TNFα (eg, infliximab). There are limited options for 
patients who fail biological treatment with the aforementioned therapies and continue to have 
evidence of active IBD. Brazikumab is being developed to meet this unmet need.
Interleukin-23 blockade represents a novel mechanism to inhibit the inflammation and clinical 
symptoms associated with autoimmune diseases such as CD, UC, and psoriasis. Therapeutic 
agents have previously targeted the IL-12/23p40 subunit, including the monoclonal antibodies 
ustekinumab and briakinumab. Because the IL-12/23p40 subunit is common to IL-12 and 
IL-23, these agents inhibit the actions of both cytokines. In contrast, brazikumab is a 
monoclonal antibody that specifically targets the IL-23p19 subunit preventing IL-23 from 
interacting with the IL-23R subunit of the IL-23 receptor complex so as to inhibit the actions 
of IL-23 but not those of IL-12.
In a Phase 2a study of brazikumab (comprising a 12-week, double-blind, placebo-controlled, 
treatment period followed by a 100-week, open-label period, in participants with moderate to 
severe active CD who have failed or are intolerant to anti-TNFα therapy) the primary endpoint 
of the study, CDAI response at Week 8 (defined by either a CDAI score of < 150 or a CDAI 
score reduction from baseline of at least 100 points), was met. In the modified intent-to-treat 
Population, the proportion of participants that achieved a CDAI response at Week 8 was 
statistically significantly higher in the brazikumab group than in the placebo group. 
Brazikumab, at doses of 
 4 weeks apart or 
 was well tolerated and 
showed an acceptable short- and long-term safety profile. During the entire study period, 
21/111 (18.9%) of participants experienced a Grade 3 TEAE and there were no Grade 4 
(life-threatening) or Grade 5 (fatal) TEAEs. Crohn’s disease was the most frequently reported 
SAE. No malignancies were reported and no MACE occurred. Clinically significant infections 
were mostly urinary tract infection, vulvovaginal mycotic infection, sinusitis, bronchitis, and 
upper respiratory tract infection. No clinically significant trends were observed in the clinical 
laboratory evaluations, vital sign measurements, ECGs, or physical findings.
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The safety profile of brazikumab, as determined at this stage of clinical development does not 
include any important identified risks. The important potential risks remain hypothetical, 
based on the mechanism of action and class effect. The following have been defined as 
important potential risks based on the mechanism of action and class-effect, to be closely 
monitored in the clinical development program:
!
Serious and medically significant infections
!
Malignancies
!
Vaccine complications
!
Infusion-related reactions and injection-site reactions
!
Severe hypersensitivity (including anaphylaxis)
!
Immune complex disease
However, it is to be noted that, due to the fact that brazikumab is a selective IL-23 inhibitor, 
but not IL-12 inhibitor, its safety profile is expected to be free of IL-12 inhibitory side effects.
2.3.1
Overall Benefit: Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with brazikumab are justified by the 
anticipated benefits that may be afforded to participants with CD.

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3
OBJECTIVES AND ENDPOINTS
The objectives and endpoints of the study are shown in Table 4.
Table 4
Objectives and Endpoints
Objectives
Endpoints
Primary
!
To assess the safety of long-term 
treatment with brazikumab in 
participants who previously completed 
Study D5271C00001 (Legacy #3150-
301-008) or discontinued from the study 
at or after Week 12 due to lack of 
efficacy.
!
AEs
!
Clinical laboratory values
!
Vital signs
!
Physical exams
!
ECGs
Exploratory
!
To assess efficacy of long-term 
treatment with brazikumab in 
participants who previously completed 
Study D5271C00001 (Legacy #3150-
301-008) or discontinued from the study 
at or after Week 12 due to lack of 
efficacy.
!
SES-CD
!
CDAI
!
PRO
!
To evaluate the PK and immunogenicity 
of brazikumab.
!
Serum concentration of brazikumab
!
Serum ADAs
!
To explore transcriptional, histological, 
protein, microbiome and clinical 
biomarkers in participants who 
previously completed Study 
D5271C00001 (Legacy #3150-301-008) 
or discontinued from the study at or 
after Week 12 due to lack of efficacy, 
and the effect of long-term brazikumab 
treatment on these biomarkers.
!
Serum, plasma, fecal, or gut tissue 
proteins; whole blood or gut 
transcriptional changes; histological, 
microbiome, and clinical lab 
assessments
ADA = anti-drug antibody; AE = adverse event; CDAI = Crohn’s Disease Activity Index; 
ECG = electrocardiogram; PK = pharmacokinetic(s); PRO = patient-reported outcome; SES-CD = Simple 
Endoscopic Score for Crohn’s Disease.

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4
STUDY DESIGN
4.1
Overall Design
The study is a global, multicenter, open-label extension study of brazikumab limited to 
participants previously enrolled in Study D5271C00001 (Legacy #3150-301-008) (hereinafter 
referred to as the “lead-in study”). Participants in the lead-in study are eligible to enroll in 
Study D5271C00002 (Legacy #3150-303-008) provided they continue to meet eligibility 
criteria and have not had adverse experiences considered to be related to study medication that 
resulted in discontinuation of the initial lead-in study intervention, or that in the judgment of 
the investigator, would disqualify them from participating. Participants will be eligible for 
inclusion into this study if they have completed the lead-in study, or have completed 12 weeks 
of treatment in the lead-in study, but were subsequently discontinued due to lack of efficacy. 
Eligible participants do not need to complete the 18-week safety follow-up period of the 
lead-in study if they rollover into this study after they complete the Week 52 visit of the 
lead-in study.
It is anticipated that the enrolled population will consist of participants who have had varying 
endoscopic and clinical symptom responses during the lead-in study, ranging from complete 
endoscopic and clinical remission to no response or worsening of their signs and symptoms of 
CD. Participants who roll over to this open-label extension study (Study D5271C00002 
[Legacy #3150-303-008]) within 28 days of completing their final visit (Week 52 or Early 
Termination Visit) assessments in the lead-in study may use the assessments from the final 
visit of the lead-in study as screening assessments for this study.
A study schematic is presented in Section 1.2.
Intervention and Study Duration
Intervention:
 of brazikumab will be administered every 4 weeks to all who completed 
requirements through Week 52 and met CDAI response without ongoing rescue treatment at 
Week 52 in the lead-in study. Participants who met criteria for early termination due to lack of 
efficacy (rescue treatment criteria) or who did not meet CDAI response at Week 52 in the 
lead-in study are considered inadequate/non-responders, and will receive 
 dosing 
with 
 of brazikumab at Week 0, Week 4, and Week 8 followed by maintenance dosing 
of brazikumab 
There will be an 18-week post-last dose safety follow-up period during which there will be no 
intervention administered for participants in the safety follow-up.
Study Duration:
The study will consist of a maximum 52-week open-label treatment period and an 18-week 
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safety follow-up period, for a total of up to 70 weeks.
For studies conducted at US (IND) sites and non-US (non-IND) sites, data from IND and 
non-IND study sites will be pooled together for analysis.
4.1.1
Study Conduct Mitigation During Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis
The guidance given below supersedes instructions provided elsewhere in this CSP and should 
be implemented only during cases of civil crisis, natural disaster, or public health crisis 
(eg, during quarantines and resulting site closures, regional travel restrictions, and 
considerations if site personnel or study participants become infected with SARS-CoV-2 or 
similar pandemic infection) which would prevent the conduct of study-related activities at 
study sites, thereby compromising the study-site staff or the participant’s ability to conduct the 
study. The investigator or designee should contact the study sponsor to discuss whether the 
mitigation plans below should be implemented.
To ensure continuity of the clinical study during a civil crisis, natural disaster, or public health 
crisis, changes may be implemented to ensure the safety of study participants, maintain 
compliance with GCP, and minimize risks to study integrity.
Where allowable by local health authorities, ethics committees, healthcare provider guidelines 
(eg, hospital policies) or local government, these changes may include the following options:
!
Obtaining consent/reconsent for the mitigation procedures (note, in the case of verbal 
consent/reconsent, the ICF should be signed at the participant’s next contact with the 
study site).
!
Rescreening: Additional rescreening for screen failure and to confirm eligibility to 
participate in the clinical study can be performed in previously screened participants. The 
investigator should confirm this with the designated Sponsor Study Physician/designee.
!
Home or Remote visit: Performed by a site qualified HCP or HCP provided by a TPV.
!
Telemedicine visit: Remote contact with the participants using telecommunications 
technology including phone calls, virtual or video visits, and mobile health devices.
!
At-home IP administration: Performed by a site qualified HCP, HCP provided by a TPV, 
if possible. Additional information related to the visit can be obtained via telemedicine.
For further details on study conduct during civil crisis, natural disaster, or public health crisis, 
refer to Appendix G.
4.2
Scientific Rationale for Study Design
The sponsor proposes to conduct an open-label study to obtain safety and efficacy experience 

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with long-term administration of brazikumab and to provide an opportunity, for participants 
who agree, to continue treatment with brazikumab for up to 1 year (52 weeks).
4.3
Justification for Dose
The no adverse effect level of 
 for brazikumab was established in cynomolgus 
monkeys in 3 studies in which brazikumab was 
 
 At this dose, no toxicologically significant effects were 
observed. 
In the Phase 1 Study 3150-101-008, conducted in healthy Japanese and White participants to 
evaluate the PK, dose proportionality, safety, and tolerability of brazikumab, a 
 
of 
 brazikumab in a 
 has been well tolerated by healthy White 
male study participants; there were no treatment-related AEs or clinically significant 
abnormalities in vital signs, clinical laboratory values, or ECG assessments. This 
 
 brazikumab represents approximately comparable brazikumab exposure 
(AUC0-28 days) to a third 
 dose administered by 
 The administered 
 
 as part of the induction treatment and the 
 dose as part 
of the maintenance treatment in this study are therefore also expected to be well tolerated. 
Furthermore, in Study 3150-101-008, 
 brazikumab infused over a 
 and 
 period was well tolerated. The
 brazikumab study 
interventions in this study will be administered in a 
Table 5 presents the margins of exposure calculated for the doses proposed in this study, based 
on Cmax and AUC values following 
 in the 14-week toxicology study, the 
clinical Phase 1b Study 20090519, and the clinical Phase 1 Study 3150-101-008.
Table 5
Exposure Margins Supporting Planned Doses
Phase 1b Study 20090519.
b
Estimated values based on exposure in Phase 1b Study 20090519.
c
Phase 1 Study 3150-101-008.
AUC0-28days = area under the concentration-time curve from zero to 28 days; Cmax = maximum serum drug 
concentration; 
4.4
End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study or 
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last scheduled procedure shown in the SoA for the last participant in the study globally.
A participant is considered to have completed the study if he/she has not been terminated early 
and has completed all phases of the study including the last visit or the last scheduled 
procedure shown in the SoA (Section 1.3).

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5
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
Participants must have participated in Study D5271C00001 (Legacy #3150-301-008). The 
inclusion and exclusion criteria are meant to create a population of participants that is well 
characterized as having CD with symptoms that require chronic treatment.
5.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Type of Participant and Disease Characteristics
1
Male or female participants with successful completion or early termination due to lack of 
efficacy from Study D5271C00001 (Legacy #3150-301-008).
Meets 1 of the following criteria for successful completion or early termination due to 
lack of efficacy from Study D5271C00001 (Legacy #3150-301-008):
(a) A participant is considered to have completed the D5271C00001 (Legacy #3150-
301-008) study if they have received scheduled study interventions, completed 
scheduled visits, and completed Week 52 assessments.
(b) A participant in Study D5271C00001 (Legacy #3150-301-008) who discontinued 
from the study due to lack of efficacy after a minimum of 12 weeks of double-blind 
treatment and met criteria for the use of rescue treatment (Table 6) in the lead-in 
protocol.
Note: Any suboptimal ileocolonoscopy result that cannot be fully assessed by the 
central reader and/or any missed doses/assessments in the lead-in study must be 
discussed with the Sponsor Study Physician/designee for determination of eligibility 
into this study.

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Table 6
Rescue Criteria from Study D5271C00001 (Legacy #3150-301-008)
Week of Assessment
Criteria for use of rescue treatment
Week 12-16
•
No improvement in CDAI by at least 70 points from Baseline CDAI for 
2 consecutive visits starting at Week 12
AND
•
No improvement in the SES-CD score by at least 1 point from Baseline 
relative to Week 12 endoscopy
After Week 16 (disease 
worsening after 
induction)
•
CDAI has increased by at least 70 points from Week 12 CDAI for 
2 consecutive visits
AND
•
No improvement in the SES-CD score by at least 25% from Baseline
Note: Must obtain 2 CDAI scores prior to proceeding with endoscopy after 
Week 16
CDAI = Crohn’s Disease Activity Index; SES-CD = Simple Endoscopic Score for Crohn’s Disease.
2
Criterion deleted as part of Amendment 4.
3
Each participant must have had the ileocolonoscopic procedure at the final visit 
(Week 52, Week 12, or early termination after Week 12 [endoscopy used for assessment 
of rescue criteria may be utilized for Early Termination Visit]) of the lead-in Study 
D5271C00001 (Legacy #3150-301-008).
Reproduction
Contraceptive use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
4
Female participants of childbearing potential must have a negative urine pregnancy test 
prior to administration of study intervention and must agree to use a highly effective 
method of birth control (confirmed by the investigator) from signing the ICF throughout
the study duration and for at least18 weeks after last dose of study intervention; cessation 
or continuation of contraception after this point is to be discussed with a responsible 
physician in accordance with local regulations and guidelines. Highly effective methods 
(those that can achieve a failure rate of less than 1% per year when used consistently and 
correctly) include:
∀
Combined (estrogen and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, or transdermal)
∀
Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, or implantable)
∀
Intrauterine device 
∀
Intrauterine hormone-releasing system

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5
Women not of childbearing potential are defined as women who are either permanently 
sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are 
postmenopausal. Women will be considered postmenopausal if they have been 
amenorrhoeic for 12 months prior to signing the ICF without an alternative medical 
cause. The following age-specific requirements apply:
∀
Women < 50 years old would be considered postmenopausal if they have been 
amenorrhoeic for 12 months or more following cessation of exogenous hormonal 
treatment and FSH levels in the postmenopausal range. Until FSH is documented to 
be within menopausal range, treat the participant as having childbearing potential.
∀
Women ≥ 50 years old would be considered postmenopausal if they have been 
amenorrhoeic for 12 months or more following cessation of all exogenous hormonal 
treatment.
If these criteria are not met, the participant should be regarded as having childbearing 
potential.
6
Nonsterilized males who are sexually active with a female partner of childbearing 
potential should use condoms during treatment and until the end of relevant systemic 
exposure in the male participant, plus a further 18 weeks. For a female partner of 
childbearing potential, contraception recommendations should also be considered (as 
described in Inclusion Criterion 4).
Informed Consent
7
Capable of giving signed informed consent as described in Appendix A which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol
8
Written informed consent from the participant has been obtained prior to any study-
related procedures.
9
Legally authorized representative consent has been obtained (if applicable).
10 Written documentation has been obtained in accordance with the relevant country and 
local privacy requirements, where applicable (eg, Written Authorization for Use and 
Release of Health and Research Study Information [US sites] and written Data Protection 
consent [European Union sites]).
Other
11 Demonstration of adequate compliance with the study procedures in Study D5271C00001 
(Legacy #3150 301-008) in the opinion of the investigator and/or sponsor.
12 Willingness and ability to attend all study visits, comply with the study procedures, read 
and write in order to complete questionnaires, and be able to complete the study.

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5.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1
Any participant with an unresolved AE from the lead-in study that, in the investigator’s 
opinion, would limit the participant’s ability to participate in or complete this study (see 
also Section 5.1 and Section 8.3). Any unresolved AE related to an infection will require 
further discussion with the Study Physician/designee prior to enrollment.
2
Current diagnosis of ischemic colitis, colonic mucosal dysplasia, or primary sclerosing 
cholangitis. Bile acid malabsorption and other conditions that may potentially confound 
assessments must be treated prior to baseline (Week 0).
3
Organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell 
transplantation) with the exception of corneal transplant.
4
Any other condition or finding that, in the investigator’s or sponsor’s opinion, would 
either confound proper interpretation of the study or expose a participant to unacceptable 
risk, including, but not limited to, clinically significant findings on physical examination, 
clinical laboratory test, ECG (including QTc prolongation), or clinically significant renal, 
hepatic, cardiopulmonary disease, or any demyelinating condition.
5
History of cancer with the following exceptions:
(a) A history of basal cell carcinoma and/or squamous cell carcinoma of the skin, with 
apparent successful curative therapy > 12 months prior to screening would not be 
exclusionary.
(b) Carcinoma in situ of the cervix, with apparent successful curative therapy, is 
exclusionary within 12 months prior to Week 0.
If there is evidence of intestinal epithelial dysplasia on endoscopy, and confirmed on 
biopsy, the participant must be excluded.
6
Participant meets criteria for discontinuation of study intervention during prior lead-in 
study (excluding lack of efficacy).
7
Criterion deleted as part of Amendment 4.
8
Known history of primary immunodeficiency, splenectomy, or any underlying condition 
that predisposes the subject to infection, including HIV infection.
9
Prolonged QTcF interval (QTc >450 msec or QTC >480 for participants with bundle 
branch block; determined by central ECG), or conditions leading to additional risk for QT 
prolongation (eg, congenital long-QT syndrome). Participants with electrolyte 
abnormalities such as hypokalemia and hypomagnesemia that would increase the risk of 
QT prolongation are to be corrected prior to enrollment; the ECG for these participants 
may be repeated after electrolyte correction for determination of eligibility if needed.
10 Clinically significant kidney disease including but not limited to:

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(a) Chronic kidney disease with an estimated glomerular filtration rate of less than 
30 ml/min calculated by MDRD equation, as applicable, by the central laboratory at 
screening are excluded.
Prior/Concomitant Therapy
11 Participant requires additional immunosuppressive therapy (aside from permitted 
concomitant medication), biological treatment, or prohibited treatment (see 
Section 6.5.4).
12 Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 
(Visit 1) or any other live vaccine < 4 weeks prior to Week 0 (Visit 1) or is planning to 
receive any such vaccine over the course of the study.
13 Participant received a prohibited medication during participation in the lead-in study or 
during screening for this study (see Section 6.5.4).
Prior/Concurrent Clinical Study Experience
14 Participant is planning to receive an investigational drug (other than study intervention) or 
investigational device at any time during Study D5271C00002 (Legacy #3150-303-008) 
with the exception of “registry” or “cohort” trials, which may include periodic biological 
sampling and/or participant questionnaires but in which no other unlicensed IP is 
administered.
15 Participants with a known hypersensitivity to brazikumab or any of the excipients of the 
product.
Diagnostic Assessments
16 Abnormal laboratory results at screening (screening window may be extended to obtain 
screening test results after discussion with the Study Physician/designee):
(a) Liver tests: either AST, ALT, or ALP > 2.0 × ULN or TBL > 1.5 × ULN (except for 
subjects with Gilbert Syndrome, pathological evidence of conjugated [direct] 
hyperbilirubinemia per investigator and/or sponsor discretion is exclusionary)
(b) Neutrophil count < 1 × 103/μL (or < 1.0 × 109/L)
(c) Hemoglobin < 8 g/dL
(d) Platelet count < 100 × 103/μL (or < 100 × 109/L)
(e) Criterion deleted as part of Amendment 4.
(f) Criterion deleted as part of Amendment 4.
(g) Criterion deleted as part of Amendment 4.
(h) Participant has any other abnormal laboratory results at screening, which, in the 
opinion of the investigator, will prevent the participant from completing the study or 
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Other Exclusions
17 Females who are pregnant, nursing, or planning a pregnancy during the study OR females 
who are of childbearing potential and do not agree to use a highly effective method of 
contraception consistently and correctly
18 Participant is directly or indirectly involved in the conduct and administration of this 
study as an investigator, subinvestigator, study coordinator, other study staff member, or 
employee of AstraZeneca, or the participant is a first-degree family member, significant 
other, or relative residing with one of the above persons involved directly or indirectly in 
the study; or the participant is enrolled in this study at another clinical study site.
19 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca 
staff and/or staff at the study site).
20 Judgment by the investigator that the participant should not participate in the study if the 
participant is unlikely to comply with study procedures, restrictions, and requirements.
21 Previous participation in the present study.
5.3
Lifestyle Considerations
The following restrictions apply while the participant is receiving study intervention and for 
the specified times before and after:
1
Women of childbearing potential must use highly effective contraceptive methods from 
enrollment throughout the study and for at least 18 weeks after last administration of the 
study intervention, as stated in Inclusion Criterion 4, Section 5.1. Cessation or 
continuation of contraception after this point is to be discussed with a responsible 
physician in accordance with local regulations and guidelines.
2
Participants should not donate blood or blood components while participating in this 
study and through 18 weeks after the last dose of study intervention.
5.3.1
Meals and Dietary Restrictions
There are no meal, dietary, or activity restrictions in this study.
5.3.2
Caffeine, Alcohol, and Tobacco
1
Due to the influence of such lifestyle factors on the severity of CD symptoms, participants 
should keep their habits broadly constant throughout the study. Use of nicotine 
replacement therapy should be recorded as concomitant medication.
2
Participants who use tobacco products will be instructed that use of nicotine-containing 
products (including nicotine patches) will not be permitted during study intervention 
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3
Participants are to be encouraged to avoid caffeine intake for a minimum of 1 hour prior 
to their clinic visit.
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
subsequently do not receive open-label study intervention. Participants entering from the 
lead-in study who are defined as screen failures and discontinued under this protocol must 
participate in the 18-week safety follow-up period for the lead-in study. 
A minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants to meet the Consolidated Standards of Reporting Trials publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes indicating screen failure as reason for ending the study, demography, screen failure 
details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failures) may 
not be rescreened, except for participants who are awaiting resolution of an AE or those who 
cannot reach the site due to the COVID-19 pandemic (see Appendix G) who may be 
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6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s) or 
placebo intended to be administered to or medical device(s) utilized by a study participant 
according to the study protocol.
This is an open-label study in which the only study intervention planned is the administration 
of brazikumab once every 4 weeks to all participants enrolled. Administration is to be 
 
dosing and 
IV Induction Dosing
Intravenous induction dosing 
 brazikumab at 
 will 
be administered to participants who met criteria for early termination due to lack of efficacy 
(rescue treatment criteria) or who did not meet CDAI response at Week 52 in Study 
D5271C00001 and therefore, considered inadequate/non-responders.
Maintenance Dosing
Participants who completed requirements through Week 52 and met CDAI response without 
ongoing rescue treatment at Week 52 of the lead-in study will receive 
 
6.1
Study Interventions Administered
Participants will receive all study intervention administrations at the investigational site. 
Table 7 presents details regarding study interventions and administration.
Table 7
Study Interventions
Study intervention name
Brazikumab
Brazikumab
Dosage form
Route of administration
Dose (mg)
Dosing instructions
Packaging and labeling
 
Each 
 will be labeled as 
required per country requirement.
 
. Each 
 will be labeled as 
required per country requirement.
Provider
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a
For 
, contents of 
will be added to an 
 bag of 
 to a 
 of 
 then administered by 
 
Brazikumab for 
Brazikumab for
administration will be supplied as a 
 
 brazikumab, 
 
 The 
 volume is 
Brazikumab for 
 is a sterile,
 
Brazikumab for 
Brazikumab for 
 will be supplied as a 
 
. The label-claim volume is 
Brazikumab for 
 is a sterile, 
 
All Formulations
 
 
6.1.1
If criteria for induction dosing are met, participants will receive brazikumab 
 
 An experienced and qualified 
staff member will place the 
 The total volume administered will be recorded in the 
eCRF.
Vital signs (BP, temperature, pulse rate, and respiration rate) will be obtained before 
 
intervention administration at all treatment visits. In addition, participants will be monitored 
for changes in vital signs and/or new symptoms approximately every 15 minutes during 
 
administration, immediately after completion of infusion, 
 
 The first 
and last vital signs are to be recorded on the eCRF. Participants will be discharged from the 
site when they are deemed clinically stable by the investigator, 
 
 for the 
 The 
 
 the discretion of the investigator. 
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Infusion-related reactions have been reported with the administration of 
 
. As with any antibody, allergic reactions to dose administration are possible. 
Appropriate drugs, such as epinephrine, antihistamines, CS, and medical equipment to treat 
anaphylactic reactions must be immediately available at study sites, and/or emergency 
procedures must be in place, and study personnel must be trained to recognize and treat 
anaphylaxis according to local guidelines. Any infusion-related reaction and/or 
hypersensitivity reaction is to be reported as an AESI (see Section 8.3.7).
6.1.2
Administration
Brazikumab will be administered to all participants by 
 at the visits specified in 
Table 1 (Section 1.3). Each 
dose will be administered by an experienced and qualified staff 
member. Each 
 will be no more than 
 in volume 
 
Each open-label brazikumab intervention will be administered via 
 
 Injections will be over 
 for all 
 and at a distance of 
. 
It is advised that the site of study intervention injection be rotated such that the participant 
receives study intervention at a different anatomical site at each treatment visit. 
 
 (Figure 2). The 
 must be 
documented in the source at each treatment visit and recorded in the eCRF. The date and time 
of all study intervention administrations, as well as any missed doses, should be recorded in 
the appropriate section of the eCRF.
 the reason 
for this must be documented in the source.
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Vital signs (BP, temperature, pulse rate, and respiration rate) will be obtained before and 
immediately after 
 administration during treatment visits outlined in the 
SoA (Section 1.3). The first and last vital signs (pre- and post-dose) are to be recorded on the 
eCRF. For Visits 1 and 2, study participants will be discharged from the testing facility a 
minimum of 20 minutes post dosing or until stable as determined by the investigator or 
designee, whichever is longer. For subsequent visits, discharge from the site will be 
determined at the discretion of the investigator or designee. 
 
 is to be reported as an AE if considered more severe than expected 
(eg, excessive redness, swelling, tenderness, bruising) or the expected time for resolution is 
delayed.
6.1.3
Study Intervention Administration Rescheduling
Every effort should be taken to keep study intervention administration within the scheduled 
window. If a participant presents with a condition that contraindicates dosing, IP will be 
withheld and administered as soon as possible after the contraindicating condition resolves.
Study intervention should not be administered, and the dosing is to be rescheduled, in the 
presence of any clinically significant infection, illness, SAE, or laboratory abnormality that, in 
the opinion of investigator, contraindicates dosing.
It is recommended that the Sponsor Study Physician/designee be contacted in case of any 
questions.
When study intervention dosing needs to be postponed, it is recommended that all scheduled 
treatment visit procedures (except for study intervention administration) are still performed 
within the visit window. Rescheduled study intervention dose can then be administered at an 
unscheduled visit. All required minimum procedures are to be performed at this visit. It may 
also include remaining visit procedures (not performed at the scheduled visit) and additional 
assessments as deemed necessary by the investigator.
If the visit procedures cannot be conducted within the window (eg, the participant is unable to 
attend the study site), then the entire visit will be rescheduled along with study intervention 
dose.
If a dose is significantly delayed, it is recommended to keep at least a 2-week interval before 
the next dose. If a postponed dose overlaps with the next treatment visit window, the 
postponed dose will be skipped, and the next dose of study intervention given at the regularly 
scheduled visit.
The visit schedule will always be calculated from Week 0 date.
If a participant misses more than 1 dose of study intervention during the treatment period, it is 
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recommended that a conversation between the investigator and Sponsor Study 
Physician/designee takes place to review the participant’s adherence to treatment and decide 
on the participant’s further disposition.
6.1.4
Study Supplies
AstraZeneca will supply the following study interventions manufactured by a third party for 
the study:
1
Brazikumab 
 for 
 of 
deliverable volume at a concentration of 
 brazikumab.
2
Brazikumab
 for 
 consisting of 
 of deliverable volume at a 
concentration of 
 brazikumab.
Additional instructions for brazikumab use are provided in the Pharmacy Manual. All defects 
in study intervention (including malfunction, use error, and inadequate labeling) shall be 
reported by the investigator as described in the Pharmacy Manual.
6.2
Preparation/Handling/Storage/Accountability
1
Brazikumab must be 
 and 
 
Brazikumab must be 
 
. The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention.
2
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. 
3
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized site staff.
4
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).
5
All unused study intervention must be stored securely. Unused study intervention should 
be destroyed locally at site wherever possible, once expired or at the termination of the 
study, after accounted for by the site. Where local destruction is not possible, then return 
to supplying depot can be arranged.
Brazikumab Preparation for 
The dose of brazikumab for 
 must be prepared by the investigator’s or site’s 
designated IP manager using aseptic technique. Prepared study intervention must be 
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administered 
 will be administered 
 
 
Brazikumab 
Brazikumab infusions are to be administered through an 
 set with a 
 
 filter; acceptable configurations include
 
The brazikumab 
 however, if there are interruptions, the total allowed 
time must 
The 
 according to local practices to ensure the 
 is administered. 
If either preparation time or
 time exceeds the time limits a new dose must be 
prepared from new 
 Brazikumab 
, and any unused portion 
must be discarded.
Brazikumab for 
 are required for
 
. The dose of brazikumab for 
 must be administered at room 
temperature within 6 hours after removal of 
Brazikumab 
For 
 the person administering the dose will wipe the skin surface of the 
injection site with alcohol and allow the skin to air dry. The skin will be pinched to isolate the 
 from the
Avoiding the belly button, ribs, hip bones, scars, or moles, the 
needle will be inserted at a 
approximately halfway into the 
 Brazikumab 
will be 
 into the 
 using 
gentle pressure. The area is not to be massaged after injection.
 
and noted in the source documents only. The total volume of dose administered will be 
recorded in the eCRF.
6.3
Measures to Minimize Bias: Randomization and Blinding
Precautions will be taken so that activities conducted during the open-label Study 
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D5271C00002 (Legacy #3150-303-008) do not unblind treatment allocation in 
Study D5271C00001 (Legacy #3150-301-008). It is critical that the treatment assignment(s) 
from the lead-in study not be unblinded.
No randomization will be performed for the present study.
6.4
Study Intervention Compliance
Participants will receive all doses under the direct supervision of study center personnel. 
Study intervention compliance will be assumed to be 100% when dosing has been recorded in 
the eCRF.
The study center will keep an accurate drug disposition record that specifies the amount of 
study intervention administered to each participant and the date of administration.
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second member of the study-site staff (refer to the Pharmacy 
Manual).
A record of the number of brazikumab doses dispensed to and taken by each participant must 
be maintained and reconciled with study intervention and compliance records. Intervention 
start and stop dates, including dates for intervention delays and/or dose reductions will also be 
recorded in the eCRF. Deviation(s) from the prescribed dosage regimen should be recorded in 
the eCRF.
The IP Storage Manager is responsible for managing the study intervention from receipt by 
the study site until the destruction or return of all unused study intervention. Concomitant 
Therapy
Any medication or vaccine (including over-the-counter, prescription medicines, vitamins, 
herbal supplements, and/or cannabis or other specific categories of interest) that the 
participant is receiving at the time of enrollment or receives during the study must be recorded 
along with:
!
Indication
!
Dates of administration, including start and end dates
!
Dosage information, including dose and frequency
The Sponsor Study Physician/designee should be contacted if there are any questions 
regarding concomitant or prior therapy.
6.5.1 Permitted Interventions
Investigators may prescribe concomitant medications or treatments deemed necessary to 

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provide adequate supportive care except for those medications identified as “prohibited” as 
listed in Section 6.5.4. Specifically, participants are to receive full supportive care during the 
study, including transfusions of blood and blood products, and treatment with antibiotics, 
anti-emetics, antidiarrheals, and analgesics, and other care as deemed appropriate, and in 
accordance with institutional guidelines or local site practice.
The following concomitant medications for CD are permitted during the study:
!
Oral antibiotics for CD
!
Probiotics (eg, Culturelle® and Saccharomyces boulardii)
!
Antidiarrheals (eg, loperamide and diphenoxylate with atropine) for control of chronic 
diarrhea, as needed 
!
Immunomodulators (azathioprine, 6-mercaptopurine, methotrexate)
!
5-ASA
!
CS therapy (oral prednisone and oral budesonide)
Permitted concomitant medications used for the treatment of CD during the lead-in study 
should be continued at stable doses, except for cases of toxicity where the dose may be 
lowered or discontinued and should not be restarted during the study. 
Concomitant CD medications (eg, CSs) are not regarded as study intervention and will not be 
provided by the sponsor.
The use of NSAIDs is generally discouraged for IBD patients due to risk of flares. Use of 
NSAIDs is to be limited to occasional short courses for less than 7 days.
Therapy considered necessary for the participant’s welfare may be given at the discretion of 
the investigator. If the permissibility of a specific medication/treatment is in question, please 
contact the sponsor or designee.
The following concomitant treatments/interventions used in the care of IBD participants are 
permitted during the study, with adherence to the details described in Table 8.

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Table 8
Permitted Concomitant Treatments
Treatment
Details
Oral antibiotics for CD (except for the 
treatment of acute illness)
Permitted only if being taken at Screening for the treatment for 
CD. If participant is taken off an oral antibiotic for CD treatment, 
the antibiotic is not to be restarted for the purpose of treating CD 
during the treatment period. Antibiotics used for the treatment of 
acute illness are permitted as needed and are to be recorded in 
association with an AE.
Probiotics (eg, Culturelle and 
Saccharomyces boulardii)
Permitted only if being taken at Week 0 (study Day 1).
Antidiarrheals (eg, loperamide and 
diphenoxylate with atropine) for control 
of chronic diarrhea
Permitted as needed and recorded as part of the CDAI score (as 
applicable).
NSAIDs
Limited to occasional short courses for less than 7 days. The use 
of NSAIDs is generally discouraged for IBD patients due to the 
risk of flares. Chronic NSAID use is exclusionary.
Inactivated/killed vaccination (eg,
inactive influenza
Not allowed within the 7 days before or within 7 days after any 
IP dosing study visit.
AE = adverse event; CD = Crohn’s disease; CDAI = Crohn’s disease activity index; IBD = inflammatory bowel 
disease; IP = investigational product; NSAID = non-steroidal anti-inflammatory drugs.
6.5.2 Corticosteroid Study Guidelines
Participants may continue treatment with CS during the study.
Participants receiving oral CS should initiate tapering as per local standard of care and as 
recommended per guidelines in Table 9. Additional details are provided in Appendix E.
Table 9
Corticosteroid Tapering Guidelines
Initial corticosteroid dose
Dose reduction
 
(or equivalent)
 
(or equivalent)
Oral beclomethasone 
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General tapering guidelines:
!
If there are worsening symptoms of CD attributed to the steroid tapering per the 
investigator’s judgment, the participant may be instructed to return to the previous oral 
CS dose. These situations would not represent the use of rescue medication. The increase 
in steroid dose is to be recorded in the appropriate eCRF along with the indication for 
increase.
!
If an oral steroid dose is temporarily increased back to the previous dose due to worsening 
CD symptoms, tapering is to be attempted again within 2 weeks after symptoms have 
improved and remain stable.
6.5.3 Rescue Treatment
For study purposes, any new concomitant medication, any increase in dose of a baseline 
medication required to treat new or unresolved CD symptoms (except for antidiarrheal 
medications) will be considered rescue treatment. Other IPs are not permitted to be used as 
rescue treatment. An increase in 
 that does not exceed the Week 0 dose level for 
participants undergoing CS tapering within the guidelines in Section 6.5.2 is not considered 
rescue treatment.
The new initiation of medications or interventions listed below will be considered as rescue 
treatment and will not require stopping study intervention:
!
5-ASA
!
Parenteral, oral, or rectal CS
!
Oral steroid doses above initial (Day 1) dose
!
Immunomodulators (azathioprine, 6-mercaptopurine, methotrexate)
!
Administration of rescue treatment constitutes treatment failure. Rescue treatments are not to 
be withheld if, in the opinion of the investigator, failure to prescribe them would compromise 
participant safety. If rescue treatment is needed, investigators should consider study 
discontinuation for lack of efficacy. The use of specific rescue treatment (eg, prohibited 
interventions) in the lead-in study will be exclusionary for this study (Study D5271C00002/
Legacy #3150-303-008) and may preclude participants from enrolling.
6.5.4
Prohibited Interventions During the Study
Participants must be instructed to not take any medications, including over-the-counter 
products, without first consulting with the investigator.
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The following medications or interventions are considered exclusionary and are not permitted 
during the study. The sponsor must be notified if a participant receives any of these during the 
study, and study intervention must simultaneously be discontinued:
!
Natalizumab
!
Anti-TNFα agents
!
Vedolizumab
!
Ustekinumab
!
Any commercially available or experimental biologic agent (eg, risankizumab, 
guselkumab)
!
Calcineurin inhibitors (eg, cyclosporine and tacrolimus)
!
Mycophenolate mofetil
!
Sirolimus (rapamycin)
!
Thalidomide
!
Live attenuated vaccine
!
Intra-abdominal surgery
!
Fecal microbial transplantation
!
Any experimental product or device as specified in Section 5.2.
!
The use of alternative or complementary treatments must be discussed with the Study 
Physician/designee. Treatments such as Chinese herbal therapies are considered 
prohibited interventions.
Note: The use of other immunosuppressant therapies not listed above will require discussion 
with the Study Physician/designee to determine whether study intervention must be 
discontinued.
The decision to administer a prohibited medication/intervention during the study period is 
done with the safety of the study participant as the primary consideration. When possible, the 
sponsor is to be notified before the prohibited medication/intervention is administered. If the 
study intervention is discontinued, the participant is to be encouraged to continue with 
assessments and visit schedule for the safety follow-up period.
6.6
Dose Modification
There is no provision for brazikumab dose reduction or increase. There will be a 
recommended 
 for the duration of the study, but the decision to 
discontinue the participant from the study will be determined as stated in Section 7 or by the 
investigator.
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If a delay in dosing is expected within the dosing window, then all study assessments will be 
delayed until the day of dosing.
See Section 6.1.3 for details on dose delays.
6.7
Intervention After the End of the Study
No interventions will be dispensed after the end of the study.

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7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
A premature discontinuation will occur if a participant who signs the ICF and receives study 
intervention ceases participation in the study, regardless of circumstances, before the 
completion of the protocol-defined study procedures.
Notification of early participant discontinuation from the study and the reason for 
discontinuation will be made to the sponsor and will be clearly documented on the CRF.
Reasons for discontinuation from the study intervention and/or the study may include the 
following commonly used or other acceptable terms:
!
AE
!
Death
!
Lack of efficacy
!
Lost to follow-up
!
Noncompliance with study intervention 
!
Other
!
Physician decision
!
Pregnancy
!
Protocol deviation
!
Screen failure
!
Site terminated by sponsor
!
Study terminated by sponsor
!
Withdrawal by participant
7.1
Discontinuation of Study Intervention
Note that discontinuation from study intervention is NOT the same thing as a withdrawal from 
the study.
It is the right and the duty of the investigator or subinvestigator to stop treatment in any case 
in which emerging effects are of unacceptable risk to the individual participant. In addition, 
the investigator or subinvestigator is to stop treatment of any participant with unmanageable 
factors that may interfere significantly with the trial procedures and/or the interpretation of 
results.

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A participant must be discontinued from study intervention for any of the following reasons: 
1
Participant requires intra-abdominal surgery during study participation
2
Participant receives any live vaccine during study participation
3
Mycobacterial infections, systemic fungal infections, or viral infections requiring 
hospitalization or parenteral antimicrobial therapy
4
Sepsis (CTCAE Grade 3 or higher)
5
Any worsening of an infection (beyond CTCAE Grade 2)
6
New diagnosis of malignancy with the exception of non-melanocytic, non-metastatic skin 
cancer at the investigator’s discretion with sponsor agreement
7
Participant receives prohibited intervention listed in Section 6.5.4
8
Participant becomes pregnant
Discontinuation of study intervention for abnormal liver function is to be considered by the 
investigator when a participant meets 1 of the conditions outlined below, or if the investigator 
believes that it is in best interest of the participant.
Discontinuation of study intervention for abnormal liver function is to be considered by the 
investigator when a participant meets criteria for HL (See Section 8.3.6 and Appendix D 2), 
1 of the conditions outlined below, or if the investigator believes that it is in best interest of the 
participant.
Abnormal liver function, defined as meeting 1 of the conditions outlined below, and 
confirmed by repeat testing within 48 to 72 hours of awareness or if the investigator believes 
that it is in best interest of the participant:
!
ALT or AST > 8 × ULN
!
ALT or AST > 5 × ULN for more than 2 weeks
!
ALT or AST > 3 × ULN and TBL > 2 × ULN or INR > 1.5
!
ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
Potential Hy’s Law cases are to be reported as AEs up to 18 weeks post-last dose as outlined 
in Section 8.3.6.
If a clinically significant finding is identified (including, but not limited to changes from 
screening in QTc after enrollment), the investigator or qualified designee will determine if the 
participant can continue in the study and if any change in participant management is needed. 

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This review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding is to be reported as an AE.
Discontinuation of a participant from study intervention is to be considered if there is a 
marked prolongation of the QT/QTc interval during treatment, especially if the measurement 
is obtained from more than 1 ECG. Increases in QT/QTc to > 500 msec or of > 60 msec over 
baseline require study drug discontinuation.
If the study intervention is discontinued, the participant is required to complete the visit and 
assessments for the Early Termination Visit and safety follow-up period. See the SoA 
(Section 1.3) for a listing of the data to be collected at the time of treatment discontinuation 
and follow-up and for any further evaluations that need to be completed.
7.2
Participant Withdrawal from the Study
!
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons.
!
A participant who considers withdrawing from the study must be informed by the 
investigator about modified follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records).
!
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
!
If a participant withdraws from the study, it should be confirmed if he/she still agrees for 
existing samples to be used in line with the original ICF. If he/she requests withdrawal of 
consent for use of samples, destruction of any samples taken and not tested should be 
carried out in line with what was stated in the ICF and local regulation. The investigator 
must document the decision on use of existing samples in the site study records and 
inform the Global Study Team.
!
See the SoA (Section 1.3) for data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed.
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
!
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 

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schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study.
!
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record.
!
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix A.

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8
STUDY ASSESSMENTS AND PROCEDURES
!
Study procedures and their timing are summarized in the SoA (Section 1.3). 
!
Protocol waivers or exemptions are not allowed.
!
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.
!
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.
!
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
!
All assessments made at the final visit of Study D5271C00001 (Legacy #3150-301-008) 
will be utilized as screening assessments for this study, unless Week 0 for this study 
occurs greater than 28 days from the final assessment(s) of the lead-in study, in which 
case the participant will need to complete all required screening assessments, except the 
ileocolonoscopy and CDAI. A repeat ileocolonoscopy is not required for participants who 
discontinue from the lead-in study after Week 12 and prior to Week 16.
!
Week 0 dose administration must occur no earlier than 14 days and no later than 56 days 
from the last dose administration in Study D5271C00001 (Legacy #3150-301-008).
!
Paper PRO collection must be initiated 7 days prior to Week 0.
!
The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will not exceed 300 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples.
8.1
Efficacy Assessments
The SES-CD, CDAI, and PROs will be used for efficacy assessments.
8.1.1
Ileocolonoscopy
An ileocolonoscopy will be performed at screening and at the end of the study (Week 52 
[Visit 14]) or at an Early Termination or Unscheduled Visit. In all cases, video recordings are 
to be performed for the duration of the ileocolonoscopy procedure, including collection of 
biopsy specimens. Technical instructions for making the video recording will be provided 
separately (these instructions will include how to capture the depth of insertion and how to 
mark bowel segments during the recording).

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Ileocolonoscopic procedures will be recorded using a video capture kit as supplied by the 
central reading facility. All video recordings will be labeled with segment names by the local 
reader vendor to produce a complete ileocolonoscopy video visualized up to the terminal 
ileum. A complete endoscopic video may not include the terminal ileum if it cannot be 
visualized. The video clips will be read centrally for mucosal lesions and endoscopic severity 
based on the SES-CD score by independent gastroenterologists experienced in IBD. The worst 
affected area of each segment is to be assessed for the SES-CD score calculation. 
The risks for endoscopy procedures may include perforation, bleeding after collection of 
biopsy samples, and complications related to sedation when administered. Individual risks and 
benefits of the endoscopy procedure should be further discussed with participants and consent 
for the procedure should be obtained per local guidelines.
The central reader is to promptly notify both the Sponsor Study Physician/designee and the 
investigator of the detection of any clinically significant findings (eg, bowel lesions) that are 
not manifestations of CD.
To ensure quality data and standardization, the same endoscopist for a participant is to be used 
at each study site throughout the study whenever possible.
If the participant cannot complete a full ileocolonoscopy due to technical failure in obtaining 
evaluable video recording for SES-CD scoring and/or biopsy or participant-related reason 
(other than non-compliance), a potential repeat of the procedure can be scheduled. The 
ileocolonoscopy can be repeated within a reasonable timeframe from the originally scheduled 
time, under the discretion of the investigator after consultation with the Study 
Physician/designee.
8.1.1.1
Simple Endoscopic Score for Crohn’s Disease
The SES-CD is a validated endoscopic activity score used to assess the status and change of 
mucosal lesions in participants with CD (Daperno et al, 2004). The SES-CD for each of the 
5 segments will be assessed during ileocolonoscopy. The score assesses 4 variables in up to 
5 segments to yield its result (Table 10).
The 5 segments assessed are:
!
Rectum, defined as that portion distal to the rectosigmoid junction
!
Left colon including the sigmoid colon
!
Transverse colon defined as the segment between the hepatic and the splenic flexures
!
Right colon including the ileocecal valve, cecum, and ascending colon to the hepatic 
flexure
!
Ileum

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Table 10
Simple Endoscopic Score for Crohn’s Disease Values
Variable
0
1
2
3
Size of ulcers
None
Aphthous ulcers
Large ulcers
Very large 
ulcers
Ulcerated surface
None
< 10%
10-30%
> 30%
Affected surface
Unaffected segment
< 50%
50-75%
> 75%
Presence of narrowings
None
Single, can be passed
Multiple, can be 
passed
Cannot be 
passed
8.1.1.2
Biopsy
Mucosal biopsies will be collected for each study ileocolonoscopic procedure performed. At 
least 4 biopsies per segment (total of 5 segments) are to be obtained, focusing on the areas of 
greatest inflammation or areas of ulceration within each segment. If no inflammation or 
ulceration is present, then random biopsies of the segment are to be obtained. The biopsies 
will be used to support assessments of changes in inflammation or BMs over time. 
Histological indices that will be used for evaluation of the biopsies will be detailed in a 
separate, exploratory analysis plan.
Detailed instructions for biopsy collection, kits for processing, handling, and shipping will be 
provided to the sites, to support the centralized testing for each of the various exploratory 
objectives. A central laboratory will be used to process, stain, and analyze BMs from the 
biopsy specimens.
8.1.2
Crohn’s Disease Activity Index
The CDAI is a composite index with weighted domains that quantifies the global disease 
severity in a single numerical score in a range from 0-600. The CDAI measures the severity of 
active disease using symptom scores that are monitored over the previous week and includes 
participant-reported symptoms, physician-assessed signs, and laboratory markers (Best et al, 
1976, Sands and Ooi, 2005). The CDAI is calculated by summing weighted scores for 
subjective items (number of liquid or very soft stools, AP, and general well-being) recorded by 
a diary during a 1-week period, and objective items (associated symptoms, taking 
antidiarrheal such as loperamide/opiates, abdominal mass, hematocrit, daily morning 
temperature, and body weight). The CDAI scores range from 0 to 600, with higher scores 
indicating greater disease activity. Subjects with scores of < 150, 150 to 219, and 220 to 450 
represent remission, mild disease, and moderate to severe disease, respectively; whereas 
subjects with scores of > 450 have very severe disease (Buxton et al, 2007).
The components of the CDAI score (Table 11) are collected as follows:
!
Abdominal mass, EIM: physical examination (Section 8.2.1)

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!
Antidiarrheal medications (Section 6.5.1)
!
Hematocrit: laboratory assessment (Section 8.2.4)
!
Weight (calculated as percent change from standard; Best et al, 1976) assessed with vital 
signs (Section 8.2.2)
!
Temperature: paper diary (Section 8.1.3)
!
Patient-reported components (LSF [Appendix F 1], AP, and general well-being): paper 
Diary (Section 8.1.3). Daily PRO data collected 7 days prior to the scheduled visit or 
prior to bowel prep if endoscopy is planned for that visit, will be used to calculate CDAI.
Participants will be provided a paper diary at the visit prior to the reporting visit described in 
the SoA (Section 1.3). The daily diary will contain the following participant-reported 
components of the CDAI: temperature, LSF, AP, and general well-being. These 4 assessments 
will be recorded by the participant for the 7 days prior to the scheduled visit or prior to bowel 
prep if endoscopy is planned for the visit for which CDAI will be assessed. The study 
participant will be prompted 7 days prior to the scheduled visit or bowel prep to begin 
recording temperature, LSF, AP, and general well-being.

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Table 11
Items Included in CDAI and Their Weights
Item
Weight
Total
Total number of liquid or very soft stools over past week
×2
X1
Total abdominal pain score (rating: 0-3) over past week (range: 0-
21)
×5
X2
Total general well-being score (rating: 0-4) over past week (range: 
0-28)
×7
X3
Sum of presence of following clinical signs over past week: 
1.
Arthritis/arthralgia (1 = yes, 0 = no)
2.
Iritis/uveitis (1 = yes, 0 = no)
3.
Erythema nodosum/pyoderma gangrenosum/aphthous 
stomatitis (1 = yes, 0 = no)
4.
Anal fissure, fistula or abscess (1 = yes, 0 = no)
5.
Other fistula (1 = yes, 0 = no)
6.
Fever >37.8 ºC during past week (1 = yes, 0 = no)
×20
X4
Antidiarrheal use (eg, diphenoxylate hydrochloride) 
(0 = none, 1 = yes)
×30
X5
Abdominal mass (none = 0, equivocal = 2, present = 5)
×10
X6
Deviation of hematocrit levels (minimum value = 0)
47 - hematocrit (males) 
42 - hematocrit (females)
×6
X7
(if value < 0, 
enter 0)
Weight ratio
100 × (1-[Current body weight / standard weight])
Minimum = -10 for overweight subject
Maximum = 10 for underweight subject
×1
X8
(if value < -10, 
enter -10,
if value > 10, 
enter 10)
CDAI score
Sum total of all 
weighted scores
CDAI = Crohn’s Disease Activity Index.
8.1.3
Patient-reported Outcomes - Evening Diary
The Evening Diary will be collected 1 week before each visit where CDAI is calculated, and if 
endoscopy is planned for the visit, the 1 week prior to bowel prep. The Evening Diary will 
include the CDAI items of AP, LSF, well-being, and temperature. The diary will also include 
items to capture urgency and blood in stool, as well as NRS symptom items including AP, 
fatigue, tiredness, weakness, lack of energy, and joint pain. The NRS measures the severity of 
symptoms in the past 24 hours using an 11-point scale (0 to 10). A paper Evening Diary will 
be provided to each participant at the visit prior to the reporting visit. Participants will be 

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instructed to complete the diaries every day in the evening for the 7 days prior to the visit (or 
prior to bowel prep, if endoscopy is scheduled for that visit), with the last daily diary of the 
7-day period completed the evening prior to the study visit or bowel prep. Participants will 
bring the diaries to the site at the appropriate visit. Participants will be prompted as to when to 
begin recording these assessments.
8.1.4
Patient-reported Outcomes – Site Visits
The HRQoL measures IBDQ, SF-36v2, and EQ-5D-5L, will be administered via paper at 
select site visits.
The IBDQ is a disease-specific PRO instrument that measures HRQoL in patients with IBD 
(Guyatt et al, 1989). The IBDQ covers the following dimensions: bowel symptoms (10 items), 
systemic symptoms (5 items), emotional function (12 items), and social function (5 items). 
Items are scored on a 7-point Likert scale, yielding a global score in the range 32 to 224 (with 
higher scores indicating better quality of life). The IBDQ has been frequently used in drug 
approval applications to assess treatment efficacy in IBD. The IBDQ has been designed to be 
self-administered and completed in 5 minutes.
The EQ-5D-5L is a standardized instrument used to measure self-reports of health status and 
functioning, consisting of 5 elements: mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. Empirically derived weights can be applied to an individual’s responses to 
the EQ-5D-5L descriptive system to generate an index measuring the value to society of his or 
her current health. In addition, the EQ-5D-5L includes a VAS that allows respondents to rate 
their own current health on a 101-point scale ranging from “best imaginable” to “worst 
imaginable” health.
The SF-36v2 is a standardized instrument used to measure self-reports of health status and 
functional well-being, consisting of 8 domains: physical functioning, role physical, bodily 
pain, general health, vitality, social functioning, role emotional, and mental health. 
Empirically derived weights can be applied to an individual’s responses to the SF-36v2 
descriptive system to generate an index measuring the value to society of his or her current 
health.
8.2
Safety Assessments
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3).
8.2.1
Physical Examinations
Physical examination will be performed at timepoints as specified in the SoA (Section 1.3). 
!
A complete physical examination will include assessments of the following; general 
appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, 

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eyes, nose, and throat), lymph nodes, thyroid, muscular-skeletal (including spine and 
extremities), and neurological systems.
!
Abdominal mass and EIM will be assessed during the physical examination and will be 
used to calculate CDAI.
!
Any new findings or aggravated existing abnormalities, judged as clinically significant by 
the investigator, will be reported as an AE as described in Section 8.3.5.
!
For participants who present with a fistula (eg, perianal fistula), a fistula exam should 
include the following assessments: number of openings, location of openings, and 
whether the openings drain with gentle compression.
8.2.2
Vital Signs
Vital signs will be performed at timelines as specified in the SoA (Section 1.3).
!
Pulse rate, respiratory rate, temperature, and BP will be assessed.
!
Blood pressure and pulse measurements will be assessed in the sitting position with a 
completely automated device. Manual techniques will be used only if an automated 
device is not available.
!
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest 
for the participant in a quiet setting without distractions (eg, television, cell phones).
!
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse 
and 1 BP measurement and will be recorded on the eCRF.
!
Weight will be recorded in kilograms as part of CDAI.
!
Procedure for monitoring vital signs before, during, and 
 
 are further detailed in Sections 6.1.1 and 6.1.2.
8.2.3
Electrocardiograms
!
Single 12-lead ECGs will be obtained as outlined in the SoA (Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. Refer to Section 7.1 for QTc withdrawal criteria and additional QTc readings 
that may be necessary.
8.2.4
Clinical Safety Laboratory Assessments
!
See Table 12 for the list of clinical laboratory tests to be performed and the SoA 
(Section 1.3) for the timing and frequency.
!
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
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abnormal laboratory findings are those that are not associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the participant’s 
condition.
!
All laboratory tests with values considered clinically significant during participation in 
the study or within 18 weeks after the last dose of study intervention should be repeated 
until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or Sponsor Study Physician/designee.
∀
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified.
∀
All protocol-required laboratory assessments, as defined in Table 12, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3).
∀
If laboratory values from non-protocol-specified laboratory assessments performed at 
the institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results will be recorded in the eCRF.
The clinical chemistry, hematology, and urinalysis will be performed by the central laboratory. 
The following laboratory variables will be measured.
Table 12
Protocol-required Safety Laboratory Assessments
Laboratory 
assessments
Parameters
Hematology
Platelet count
RBC indices:
MCV
MCH
%Reticulocytes
WBC count with differential 
(absolute):
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC count
Hemoglobin
Hematocrit
Clinical 
Chemistrya
BUN
C-reactive protein
Potassium
Sodium
AST
Total and direct 
bilirubin
Creatinine
ALT
Total protein
eGFR
Glucose 
(nonfasting)
Magnesium
Uric acid
Calcium
Chloride
Alkaline 
phosphatase
Albumin
Bicarbonate
Phosphate
Fecal Tests
Fecal calprotectin
Fecal lactoferrin

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Laboratory 
assessments
Parameters
Routine 
Urinalysis
•
Specific gravity
•
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick
•
Microscopic examination (reflexively as needed)
Other Screening 
Tests
•
FSH (as needed in women of non-childbearing potential only)b
•
Urine hCG is to be performed locally at each visit prior to administering study 
intervention and as outlined in the SoA.
•
All study-required laboratory assessments will be performed by a central laboratory 
unless indicated (eg, local urine hCG testing).
a
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver 
stopping or monitoring event are given in Section 7.1 and Appendix D.
b
FSH does not need to be repeated at Week 52 if it was in the post-menopausal range at screening. If not, 
and the female participant becomes amenorrhoeic during the course of the study, FSH should be assessed at 
Week 52.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
eGFR = estimated glomerular filtration rate; FSH = follicle-stimulating hormone; hCG = human chorionic 
gonadotropin; MCH = mean corpuscular hemoglobin; MCV = mean corpuscular volume; RBC = red blood cell; 
SoA = Schedule of Activities; WBC = white blood cell.
8.3
AEs and SAEs
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). The investigator or designee 
will determine whether these meet the criteria for an AE.
The PI is responsible for ensuring that all staff involved in the study are familiar with the 
content of this section.
The definitions of an AE or SAE can be found in Appendix B.
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
All AEs and SAE from the signing of the ICF and until 18 weeks after the last dose of study 
intervention will be collected at the timepoints specified in the SoA (Section 1.3), and as 
observed or reported spontaneously by study participants.
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix B. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available.
If the investigator becomes aware of an SAE with a suspected causal relationship to the IP that 

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occurs after the end of the clinical study in a participant treated by him or her, the investigator 
shall, without undue delay, report the SAE to the sponsor.
8.3.2
Follow-up of AEs and SAEs
Any AEs that are unresolved at the participant’s last AE assessment in the study are followed 
up by the investigator for as long as medically indicated, but without further recording in the 
eCRF. AstraZeneca retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary.
New or updated information will be recorded in the originally completed eCRF.
AE Variables
The following variables will be collected for each AE:
!
AE (verbatim)
!
The date when the AE started and stopped
!
Maximum intensity 
!
Whether the AE is serious or not
!
Investigator causality rating against the IP(s) (yes or no)
!
Action taken with regard to IP(s)
!
AE caused participant’s withdrawal from study (yes or no)
!
Outcome
In addition, the following variables will be collected for SAEs:
!
Date AE met criteria for SAE
!
Date investigator became aware of SAE
!
AE is serious due to
!
Date of hospitalization
!
Date of discharge
!
Probable cause of death
!
Date of death
!
Autopsy performed
!
Causality assessment in relation to study procedure(s)
!
Causality assessment to other medication

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8.3.3 Causality Collection
The investigator should assess causal relationship between IP and each AE, and answer yes or 
no to the question ‘Do you consider that there is a reasonable possibility that the event may 
have been caused by the IP?’
For SAEs, causal relationship should also be assessed for other medication and study 
procedures. Note that for SAEs that could be associated with any study procedure the causal 
relationship is implied as yes.
A guide to the interpretation of the causality question is found in Appendix B to the CSP.
8.3.4 AEs Based on Signs and Symptoms
All AEs spontaneously reported by the participant or care provider, reported in response to the 
open question from the study-site staff: ‘Have you had any health problems since the previous 
visit/you were last asked?’, or revealed by observation will be collected and recorded in the 
eCRF. When collecting AEs, the recording of diagnoses is preferred (when possible) to 
recording a list of signs and symptoms. However, if a diagnosis is known and there are other 
signs or symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom will be recorded separately.
8.3.5 AEs Based on Examinations and Tests
The results from the CSP-mandated laboratory tests and vital signs will be summarized in the 
CSR. 
Deterioration as compared to baseline in protocol-mandated laboratory values and vital signs 
should therefore only be reported as AEs if they fulfill any of the SAE criteria, are the reason 
for discontinuation of treatment with the IP, or are considered to be clinically relevant as 
judged by the investigator (which may include but not limited to consideration as to whether 
treatment or non-planned visits were required or other action was taken with the study 
intervention, eg, dose adjustment or drug interruption).
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible the reporting investigator 
uses the clinical, rather than the laboratory term (eg, anaemia versus low hemoglobin value). 
In the absence of clinical signs or symptoms, clinically relevant deteriorations in non-
mandated parameters should be reported as AE(s).
Deterioration of a laboratory value, which is unequivocally due to disease progression, should 
not be reported as an AE/SAE.

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Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE unless unequivocally 
related to the disease under study.
8.3.6 Hy’s Law
Cases where a participant shows elevations in liver biochemistry may require further 
evaluation and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may 
need to be reported as SAEs. Please refer to Appendix D for further instruction on cases of 
increases in liver biochemistry and evaluation of HL.
8.3.7
Disease Under Study
Symptoms of disease under study are those which might be expected to occur as a direct result 
of CD (eg, AP and diarrhea). Events which are unequivocally due to disease under study 
should not be reported as an AE during the study unless they meet SAE criteria or lead to 
discontinuation of the IP.
8.3.8
Reporting of SAEs
All SAEs have to be reported, whether or not considered causally related to the IP, or to the 
study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, investigators or other site personnel will inform 
the appropriate AstraZeneca representatives within 1 calendar day ie, immediately but no 
later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative will work with the investigator to ensure that all 
the necessary information is provided to the AstraZeneca Patient Safety data entry site within 
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. Investigators or other site personnel will inform 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
within one calendar day, ie, immediately but no later than 24 hours of when he or she 
becomes aware of it.
Once the investigators or other site personnel indicate an AE is serious in the EDC system, an 
automated email alert is sent to the designated AstraZeneca representative.
If the EDC system is not available, then the investigator or other study site staff reports an 
SAE to the appropriate AstraZeneca representative by telephone. The AstraZeneca 
representative will advise the investigator/study staff how to proceed.

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For further guidance on the definition of a SAE, see Appendix B of the CSP.
The reference document for definition of expectedness/listedness is the IB for the AstraZeneca 
drug.
8.3.9
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca except for:
!
If the pregnancy is discovered before the study participant has received any study 
intervention
8.3.9.1
Maternal Exposure
If a participant becomes pregnant during the course of the study, IP should be discontinued 
immediately.
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IP under study
may have interfered with the effectiveness of a contraceptive medication. Congenital 
anomalies/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. The outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth or congenital anomaly) should be followed up and documented even if the participant 
was discontinued from the study.
If any pregnancy occurs in the course of the study, then the investigator or other site personnel 
informs the appropriate AstraZeneca representatives within 1 calendar day, ie, immediately
but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for SAEs (see Section 8.3.8) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available. The pregnancy report 
(PREGREP) module in the eCRF is used to report the pregnancy, and the paper-based 
pregnancy outcome report (PREGOUT) module is used to report the outcome of the 
pregnancy.
8.3.9.2
Paternal Exposure 
Male participants should refrain from fathering a child or donating sperm during the study and 
for 18 weeks following the last dose.
Pregnancy of the participant’s partner is not considered to be an AE. However, the outcome of 
all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 

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birth, or congenital anomaly), occurring from the date of the first dose until 18 weeks 
following the last dose should, if possible, be followed up and documented in the Pregnancy 
Report Form. Consent from the partner must be obtained before the Pregnancy Report Form is 
completed.
8.3.10
AEs of Special Interest
8.3.10.1
 
 
 
 
 
 
 
 
8.3.10.2
Malignancies
Emerging data from clinical trials with briakinumab and ustekinumab suggest a possible 
association between dual inhibition of IL-12 and IL-23 and the development of certain 
malignancies; however, it remains uncertain whether inhibition of IL-23 alone would have 
similar effects.
Nonclinical studies evaluating the genotoxic, mutagenic, and carcinogenic potential of 
brazikumab have not been conducted because brazikumab is a large protein molecule that is 
not expected to cross the nuclear or mitochondrial membranes and interact directly with DNA 
or other chromosomal materials. In preclinical toxicology studies, no effects related to tumor 
formation were observed in cynomolgus monkeys treated with brazikumab for 6 months that 
resulted in exposures greater than those used in humans. Furthermore, results from preclinical 
studies in mice suggest that blockade of the IL-23 pathway or deficiencies in the IL-23 or 
IL-23 receptor genes result in decreased tumor formation, tumor volume, and metastases; and 
faster elimination of injected tumor cells.
Participants in this study will be monitored for the development of any malignancies by 
routine laboratory physical examination and TEAE assessments. In addition, participants will 
be advised of the potential risk of malignancy during the informed consenting process. If a 
malignancy is diagnosed during the study, investigators must obtain and report biopsy results 
and other relevant BMs and/or genetic test results.
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8.3.10.3
Hypersensitivity Reactions (Anaphylaxis)
Unlike infusion-related reactions, anaphylaxis is a rare event, usually occurring after 
subsequent exposure to an antigen, and it is most commonly accompanied by severe systemic 
skin and/or mucosal reactions.
8.3.10.4
Infections
The use of immunomodulatory drugs, including biological therapies, may increase 
susceptibility to infections. Participants should be counselled on infection risk, and a 
benefit/risk assessment should be considered prior to initiating treatment. Appropriate 
precautions should be considered, including vaccine administration for prevention prior to 
study enrollment, according to local guidelines.
The immunoregulatory role of IL-23 in humans is not completely understood. Nonclinical 
studies have suggested that IL-23 may play a role in host defense against certain extracellular 
and intracellular pathogens. Participants administered brazikumab may be at risk of 
developing, or have difficulty overcoming, certain types of infections.
Occurrence of infections will be monitored during studies by routine hematology, physical 
examination, and TEAE assessments.
8.3.10.4.1
Non-opportunistic Infections
A serious non-opportunistic infection is any non-opportunistic infection that meets the SAE 
criteria in Appendix B 3. Any relevant culture results and diagnostic and/or therapeutic 
procedure results for a participant with a serious non-opportunistic infection must be provided 
as an SAE update. Nonserious non-opportunistic infections will not be reported as AESIs.
8.3.10.4.2
Opportunistic Infections
An opportunistic infection is an infection caused by microorganisms that are normally 
non-pathogenic or rarely pathogenic or result in a more severe infection not experienced in 
individuals with normal immune function. Examples of opportunistic infections may include 
Pneumocystis jiroveci pneumonia, Salmonella septicemia, and certain Cytomegalovirus 
infections such as encephalitis or retinitis. 
Opportunistic infections are considered serious and must be reported as an SAE. Any relevant 
culture results and diagnostic and/or therapeutic procedure results for a participant with an 
opportunistic infection must be provided as an SAE update. 
8.3.11
Medication Error
If a medication error occurs in the course of the study, then the investigator or other site 
personnel informs the appropriate AstraZeneca representatives within 1 day, ie, immediately 
but no later than 24 hours of when he or she becomes aware of it.

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The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is completed within 1 (initial fatal/life-threatening or follow-up fatal/life-
threatening) or 5 (other serious initial and follow-up) calendar days if there is an SAE 
associated with the medication error (see Section 8.3.8) and within 30 days for all other 
medication errors.
The definition of a medication error can be found in Appendix B 5.
8.4
Overdose
For this study, any dose of brazikumab greater than 
 or 
per 
administration will be considered an overdose.
!
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.
!
An overdose without associated symptoms is only reported on the Overdose eCRF 
module.
If an overdose on an AstraZeneca study intervention occurs in the course of the study, the 
investigator or other site personnel informs appropriate AstraZeneca representatives 
immediately, but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for overdoses associated with an SAE (see Section 8.3.8) and within 30 days
for all other overdoses.
8.5
Human Biological Samples
Instructions for the collection and handling of biological samples will be provided in the study 
specific laboratory manual. Samples should be stored in a secure storage space with adequate 
measures to protect confidentiality. For further details on Handling of Human Biological 
Samples see Appendix C.
!
Samples will be stored for a maximum of 15 years from the date of the issue of the CSR 
in line with consent and local requirements, after which they will be 
destroyed/repatriated. 
∀
Pharmacokinetic samples will be disposed of after the Bioanalytical Report 
finalization or 6 months after issuance of the draft Bioanalytical Report (whichever is 
earlier), unless consented for future analyses. 
∀
Pharmacokinetic samples may be disposed of or anonymised by pooling. Additional 
analyses may be conducted on the anonymised, pooled PK samples to further 
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evaluate and validate the analytical method. Any results from such analyses may be 
reported separately from the CSR.
!
Remaining ADA sample aliquots will be retained at AstraZeneca or its designee for a 
maximum of 15 years following issue of the CSR. Additional use includes but is not 
limited to further characterization of any ADAs, confirmation, and/or requalification of 
the assay as well as additional assay development work. The results from future analysis 
will not be reported in the CSR.
8.5.1
Pharmacokinetics
!
Venous blood samples will be collected for measurement of serum brazikumab 
concentrations prior to study intervention administration as specified in the SoA 
(Section 1.3). The exact time and date of the samples should be noted.
!
Samples may be collected at additional time points during the study if warranted and 
agreed upon between the investigator and the sponsor, for example, for safety reasons. 
The timing of sampling may be altered during the course of the study based on newly 
available data (eg, to obtain data closer to the time of peak or trough matrix 
concentrations) to ensure appropriate monitoring. 
!
Serum samples will be used to analyze the PK of brazikumab. Samples collected for 
analyses of brazikumab serum concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study.
8.5.1.1
Determination of Drug Concentration
Samples for determination of drug concentration in serum will be assayed by bioanalytical test 
sites operated by or on behalf of AstraZeneca, using an appropriately validated bioanalytical 
method. Full details of the analytical method used will be described in a separate bioanalytical 
report.
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate bioanalytical report.
8.5.2
Immunogenicity Assessments
Serum samples to measure the presence of ADAs against brazikumab (binding antibodies and 
NABs) will be collected according to the SoA and will remain blinded. Instructions for sample 
collection, processing, storage, and shipment can be found in a separate laboratory manual 
provided to the sites.
Blood samples for ADAs and NABs will be analyzed using a validated immunoassay and a 
validated cell-based assay. Full details of the methods used will be described in a separate 

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report.
Anti-drug antibody samples may also be further tested for characterization of the ADA 
response.
Samples will be collected, labeled, stored, and shipped as detailed in the laboratory manual.
8.5.3
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.6
Human Biological Sample Biomarkers
8.6.1
Collection of Mandatory Samples for Biomarker Analysis
By consenting to participate in the study, the participant consents to the mandatory research 
components of the study.
Blood, stool, and biopsy samples will be collected and analyzed to evaluate protein, nucleic 
acid, metabolic and cellular BMs according to the SoA in Section 1.3. All samples should be 
collected predose and will be analyzed centrally at contracted third-party labs.
Biomarkers that may be analyzed include, but are not limited to, whole blood gene expression, 
gut biopsy tissue gene expression, stool microbiome composition, serum/plasma/stool proteins 
including, but not limited to cytokines, chemokines, and inflammatory mediators associated 
with IBD, immunological function, and the pharmacology of brazikumab. The intended 
purpose is to evaluate the association of these BMs with observed clinical responses over the 
entire treatment duration of the clinical study and to enhance knowledge and understanding of 
CD pathogenesis.
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. Specific procedures for sample collection, processing, storage, and shipment can be 
found in a separate laboratory manual provided to the sites. 
An additional whole blood sample will be collected for isolation of RNA and stored for future 
analyses. Ribonucleic acid may be used for the analyses of transcript expression using next-
generation sequencing, microarray, or other suitable techniques. 
All BM analyses are exploratory and will be described in a separate report. 
8.7
Genomics Initiative Sample
Optional Genomics Initiative research is not applicable in this study.

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8.8
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics parameters are not evaluated in this 
study.

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9
STATISTICAL CONSIDERATIONS
9.1
Statistical Hypotheses
Not applicable.
9.2
Sample Size Determination
This study is an extension study and the sample size is determined by the number of 
participants in the lead-in study who are eligible and choose to participate in this study. No 
separate sample size calculation was performed. Up to a maximum of 240 participants may 
enter this study, based on the expected number of participants in the lead-in study.
9.3
Populations for Analyses
The following populations are defined in Table 13:
Table 13
Populations for Analysis
Population/analysis set
Description
Screened Analysis Set
All participants who are screened for the study.
FAS
All participants who are assigned to an 
 brazikumab study 
intervention in the study.
Safety
All participants who receive ≥ 1 administration of study intervention in this 
extension study.
FAS = Full Analysis Set; 
9.4
Statistical Analyses
The SAP will be finalized prior to the lead-in study data base lock and it will include a more 
technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints 
including primary and exploratory endpoints.
9.4.1
General Considerations
The treatment sequences in this open-label extension study will be presented as 
Brazikumab/Brazikumab for participants who received brazikumab study intervention in the 
double-blind, lead-in study, and Placebo/Brazikumab for participants who received placebo 
study intervention in the double-blind, lead-in study. In addition, brazikumab patients in this 
extension study will be further classified and separated by those that needed induction and 
those that received maintenance dose directly. All safety and efficacy analyses for this study 
will be summarized descriptively by the visit and the treatment sequences and overall, unless 
stated otherwise. Continuous variables will be summarized by the number of participants and 
mean, SD, median, Q1, Q3, minimum, and maximum values. Categorical variables will be 
summarized by number and percentage of participants. Visit time window for safety 
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parameters will be defined in the SAP.
9.4.2
Efficacy
The efficacy analyses will be based on the FAS population using the observed-cases approach. 
Descriptive statistics for each efficacy endpoint, PK, and ADA will be presented overall. 
Pharmacokinetic data may be pooled and analyzed with data from other studies, and reported 
outside of the CSR.
Efficacy endpoints are exploratory in this extension study.
9.4.2.1
Exploratory Endpoints
The efficacy analyses include, but are not limited to, the following endpoints:
!
Endoscopic response
∀
Minimum of 50% decrease from baseline in SES-CD total score
!
Endoscopic remission
∀
Enhanced endoscopic remission with definition as SES-CD score of 0-2
∀
SES-CD total score of 0-2 OR
∀
SES-CD total score of ≤ 4 and at least 2-point reduction from baseline with no 
subscore > 1
!
CDAI response
∀
CDAI score < 150 or reduction from baseline CDAI score of ≥ 100 points
!
CDAI remission
∀
CDAI score < 150
!
PRO remission
∀
Average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND
∀
Average daily AP subscore of ≤ 1 as assessed on the CDAI AP item
!
CS-free (for the last 12 weeks before the assessment at Week 52) endoscopic response at 
Week 52
!
CS-free endoscopic remission at Week 52
!
CS-free CDAI response at Week 52
!
CS-free CDAI remission at Week 52
!
CS-free PRO remission at Week 52
9.4.3
Safety
The safety analysis will be performed using the Safety Population and will be fully defined in 

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the SAP. The safety parameters will include AEs, clinical laboratory parameters, vital signs, 
and ECG parameters. If Visit 1 for this study is the last visit from the lead-in study, the safety 
value at Visit 1 will not be included in the PCS evaluation as it had been evaluated in the 
lead-in study, but it will be included in the change-from-baseline summary analysis.
Safety endpoints are primary in this extension study.
9.4.3.1
AEs
An AE will be considered a TEAE if the AE began or worsened (increased in severity or 
became serious) on or after the date (and time, if known) of the first dose of study intervention 
in this study.
An AE that occurs more than 18 weeks after the last dose of study intervention in this study 
will not be counted as a TEAE.
An AE will be considered a TESAE if it is a TEAE that additionally meets any SAE criterion.
The number and percentage of participants with TEAEs during the study will be tabulated by 
system organ class and preferred term and by system organ class, preferred term, and severity.
The number and percentage of participants with treatment-related TEAEs during the study 
will be tabulated by system organ class and preferred term.
If more than 1 AE is coded to the same preferred term for the same participant, the participant 
will be counted only once for that preferred term using the most severe occurrence for the 
summarizations by severity.
Summary tables will be provided for participants with TESAEs and participants with TEAEs 
leading to discontinuation if these occurred in 5% or more participants. Listings of all AEs, 
SAEs, and AEs leading to discontinuation by participant will be presented.
In addition, AESIs as defined in Section 8.3.7 will also be summarized.
The definitions of an AE and SAE can be found in Appendix B.
9.4.3.2
Clinical Laboratory Assessments
Descriptive statistics for clinical laboratory values (in conventional and SI units) at baseline, 
postbaseline, and changes from baseline at each postbaseline timepoint will be presented for 
each clinical laboratory assessment.
The criteria for PCS laboratory values will be detailed in the SAP. The number and percentage 
of participants who have PCS postbaseline clinical laboratory values will be tabulated. The 
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non-PCS baseline values and at least 1 postbaseline assessment. The numerator will be the 
total number of participants with at least 1 PCS postbaseline value. A supportive listing of 
participants with PCS postbaseline values will be provided for the Safety Population.
9.4.3.3
Vital Signs
Descriptive statistics for vital signs (systolic and diastolic BP, pulse rate, weight, respiration 
rate, and temperature) at baseline, postbaseline, and changes from baseline at each 
postbaseline timepoint will be presented.
Vital signs values will be considered to be PCS if they meet both the observed-value criteria 
and the change-from-baseline-value criteria that will be detailed in the SAP. The number and 
percentage of participants who have PCS postbaseline vital signs values will be tabulated. The 
percentages will be calculated relative to the number of participants who have available non-
PCS baseline values and at least 1 postbaseline assessment. The numerator will be the total 
number of participants with at least 1 PCS postbaseline value. A supportive listing of 
participants with PCS postbaseline values will be provided for the Safety Population.
9.4.3.4
ECGs
Descriptive statistics for ECG parameters (heart rate, PR interval, QRS interval, QT interval, 
and QTc) at baseline, postbaseline, and changes from baseline at each postbaseline timepoint 
will be presented.
The criteria for PCS ECG values will be detailed in the SAP. The number and percentage of 
participants who have PCS postbaseline ECG values will be tabulated. The percentages will 
be calculated relative to the number of participants who have available non-PCS baseline 
values and at least 1 postbaseline assessment. The numerator will be the total number of 
participants with at least 1 PCS postbaseline value. A supportive listing of participants with 
PCS postbaseline values will be provided for the Safety Population.
9.4.4
Exploratory BM Analyses
Exploratory BM analyses may be defined and presented outside of the SAP and CSR.
9.5
Interim Analyses
No interim analysis is planned for this study.
9.6
Data Monitoring Committee
Not applicable.

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10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS

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

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!
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/IEC, if appropriate according to 
local requirements.
A 2
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
A 3
Informed Consent Process
!
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding 
the study.
!
Participants must be informed that their participation is voluntary and they are free to 
refuse to participate and may withdraw their consent at any time and for any reason 
during the study. Participants or their legally authorized representative will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/IEC or 
study center.
!
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF.
!
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study.
!
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.
Participants who are rescreened are required to sign a new ICF.
The ICF will contain a separate section that addresses and documents the collection and use of 
any mandatory and/or optional human biological samples. The investigator or authorized 
designee will explain to each participant the objectives of the analysis to be done on the 
samples and any potential future use. Participants will be told that they are free to refuse to 
participate in any optional samples or the future use and may withdraw their consent at any 
time and for any reason during the retention period.

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A 4
Data Protection
!
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.
!
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure and use 
of their data must also be explained to the participant in the informed consent.
!
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities.
A 5
Dissemination of Clinical Study Data
A description of this clinical study will be available on 
http://astrazenecagrouptrials.pharmacm.com and http://www.clinicaltrials.gov as will the 
summary of the study results when they are available. The clinical study and/or summary of 
study results may also be available on other websites according to the regulations of the 
countries in which the study is conducted.
A 6
Data Quality Assurance
!
All participant data relating to the study will be recorded on eCRF unless transmitted to 
the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by electronically 
signing the eCRF.
!
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.
!
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
!
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan.
!
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
!
The sponsor assumes accountability for actions delegated to other individuals (eg, CROs).

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!
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH, GCP, and all applicable regulatory requirements.
!
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 15 years after study completion unless local 
regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. No 
records may be transferred to another location or party without written notification to the 
sponsor.
A 7
Source Documents
!
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site.
!
Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.
!
Definition of what constitutes source data can be found in the Monitoring Plan.
A 8
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first site open and will be the study start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

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!
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines
!
Inadequate recruitment of participants by the investigator
!
Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Participants from terminated sites will have the opportunity to be transferred to another site to 
continue the study.
A 9
Publication Policy
!
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments.
!
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement.
!
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.

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

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

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intensity need not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not a SAE unless it meets the criteria 
shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be a SAE when it satisfies the criteria 
shown in Appendix B 2.
B 3
Definition of AESIs
An AESI (serious or nonserious) is one of scientific and medical concern specific to the 
sponsor’s study drug/device or program, which warrants ongoing monitoring and rapid 
communication by the investigator to the sponsor. Such an event might warrant further 
investigation in order to characterize and understand it. 
The following AESI(s) have been identified for the study intervention(s) in this protocol:
!
Infusion-related reactions and injection-site reactions
!
Malignancies
!
Hypersensitivity reactions (anaphylaxis)
!
Infections
∀Serious non-opportunistic infections
∀Opportunistic infections
Nonserious AESIs are to be recorded in eCRF within 72 hours, and serious AESIs are to be 
reported to the sponsor within 24 hours.
B 4
A Guide to Interpreting the Causality Question
When making an assessment of causality consider the following factors when deciding if there 
is a reasonable possibility that an AE may have been caused by the drug.
!
Time Course. Exposure to suspect drug. Has the participant actually received the suspect 
drug? Did the AE occur in a reasonable temporal relationship to the administration of the 
suspect drug?
!
Consistency with known drug profile. Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties?
!
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 another etiology such as 
the underlying disease, other drugs, or other host or environmental factors.

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!
Rechallenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? AstraZeneca would not normally recommend or support a 
rechallenge.
!
Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship.
In difficult cases, other factors could be considered such as:
!
Is this a recognized feature of overdose of the drug?
!
Is there a known mechanism?
Causality of related is made if following a review of the relevant data, there is evidence for a 
reasonable possibility of a causal relationship for the individual case. The expression 
reasonable possibility of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data including enough 
information to make an informed judgment. With no available facts or arguments to suggest a 
causal relationship, the event(s) will be assessed as not related.
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility.
B 5
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an AstraZeneca study intervention that either causes harm to the 
participant or has the potential to cause harm to the participant. 
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study-site staff or participant.
Medication error includes situations where an error. 
!
Occurred
!
Was identified and intercepted before the participant received the drug
!
Did not occur, but circumstances were recognized that could have led to an error
Examples of events to be reported in clinical studies as medication errors:
!
Drug name confusion

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!
Dispensing error (eg, medication prepared incorrectly, even if it was not actually given to 
the participant)
!
Drug not administered as indicated (eg, wrong route or wrong site of administration)
!
Drug not taken as indicated (eg, tablet dissolved in water when it should be taken as a 
solid tablet)
!
Drug not stored as instructed (eg, kept in the refrigerator when it should be at room 
temperature)
!
Wrong participant received the medication (excluding IRT/RTSM errors)
!
Wrong drug administered to participant (excluding IRT/RTSM errors)
Examples of events that do not require reporting as medication errors in clinical studies:
!
Errors related to or resulting from IRT/RTSM, including those which lead to one of the 
above listed events that would otherwise have been a medication error 
!
Participant accidentally missed drug dose(s) (eg, forgot to take medication)
!
Accidental overdose (will be captured as an overdose)
!
Participant failed to return unused medication or empty packaging
!
Errors related to background and rescue medication, or standard of care medication in 
open-label studies, even if an AstraZeneca product 
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error.
B 6
AE and SAE Recording
!
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.
!
The investigator will then record all relevant AE/SAE information in the eCRF within 
3 days.
!
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records in lieu of completion of the AE/SAE eCRF page.
!
There may be instances when copies of medical records for certain cases are requested by 
the sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to 
sponsor

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!
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.

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

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

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

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

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!
Perform follow-up on subsequent laboratory results according to the guidance provided in 
the CSP.
D 4.2
Potential Hy’s Law Criteria Met
If the participant does meet PHL criteria the investigator will:
!
Notify the AstraZeneca representative who will then inform the central Study Team 
!
Within 1 day of PHL criteria being met, the investigator will report the case as an SAE of 
PHL; serious criteria of Important Medical Event and causality assessment yes/related
according to CSP process for SAE reporting.
!
For participants that met PHL criteria prior to starting IP, the investigator is not required 
to submit a PHL SAE unless there is a significant change# in the participant’s condition.
!
The Sponsor Study Physician/designee contacts the investigator, to provide guidance, 
discuss and agree on an approach for the study participant’s follow-up (including any 
further laboratory testing) and the continuous review of data
!
Subsequent to this contact the investigator will:
∀
Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated. Complete follow-up SAE Form as required
∀
Investigate the aetiology of the event and perform diagnostic investigations as 
discussed with the Sponsor Study Physician/designee 
#A significant change in the participant’s condition refers to a clinically relevant change in 
any of the individual liver biochemistry parameters (ALT, AST, or TBL) in isolation or in 
combination, or a clinically relevant change in associated symptoms. The determination of 
whether there has been a significant change will be at the discretion of the investigator, this 
may be in consultation with the Sponsor Study Physician/designee if there is any uncertainty.
D 5
Review and Assessment of Potential Hy’s Law Cases
The instructions in this section should be followed for all cases where PHL criteria are met.
As soon as possible after the biochemistry abnormality is initially detected, the Sponsor Study 
Physician/designee contacts the investigator in order to review available data, agree on 
whether there is an alternative explanation for meeting PHL criteria other than DILI caused by 
the IP, and ensure timely analysis and reporting to health authorities within 15 calendar days 
from date PHL criteria was met. The AstraZeneca Global Clinical Lead or equivalent and 
Global Safety Physician will also be involved in this review together with other subject matter 
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According to the outcome of the review and assessment, the investigator will follow the 
instructions below.
Where there is an agreed alternative explanation for the ALT, AST, or 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 as detailed below:
!
If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF.
!
If the alternative explanation is an AE/SAE: update the previous PHL SAE and AE 
eCRFs accordingly with the new information (reassessing event term, causality, and 
seriousness criteria) following the AstraZeneca standard processes.
If it is agreed that there is no explanation for the ALT or AST and TBL elevations other than 
the IP:
!
Update the SAE page (report term Hy’s Law) according to AstraZeneca standard 
processes. 
∀
The Medically Important serious criterion should be used if no other serious 
criteria apply.
∀
As there is no alternative explanation for the HL case, a causality assessment of 
related should be assigned.
If there is an unavoidable delay of over 15 calendar days in obtaining the information 
necessary to assess whether or not the case meets the criteria for HL, then it is assumed that 
there is no alternative explanation until such time as an informed decision can be made:
!
Provides any further update to the previously entered SAE of PHL, (report term now Hy’s 
Law case) ensuring causality assessment is related to IMP and seriousness criteria is 
medically important, according to CSP process for SAE reporting.
!
Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are still met. Update the previously entered PHL SAE page following 
CSP process for SAE reporting, according to the outcome of the review and amending the 
reported term if an alternative explanation for the liver biochemistry elevations is 
determined.

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D 6
Laboratory Tests
Hy’s Law Lab Kit for Central Laboratories 
Additional standard chemistry and coagulation 
tests
GGT
LDH
Prothrombin time
INR
Viral hepatitis
IgM anti-HAV 
HBsAg
IgM and IgG anti-HBc
HBV DNA a
IgG anti-HCV
HCV RNA b
IgM anti-HEV
HEV RNA
Other viral infections
IgM & IgG anti-CMV
IgM & IgG anti-HSV
IgM & IgG anti-EBV
Alcoholic hepatitis
Carbohydrate deficient transferrin c
Autoimmune hepatitis
ANA
Anti-LKM
ASMA
Metabolic diseases
alpha-1-antitrypsin
Ceruloplasmin
Iron
Ferritin
Transferrin c
Transferrin saturation
a
HBV DNA is only recommended when IgG anti-HBc is positive
b
HCV RNA is only recommended when IgG anti-HCV is positive or inconclusive 
c
Carbohydrate deficient-transferrin and Transferrin are not available in China. Study teams should amend 
this list accordingly.
ANA = antinuclear antibody; Anti-LKM = Anti-Liver/Kidney Microsomal Ab; ASMA = anti-smooth muscle 
antibody; CMV = cytomegalovirus; DNA = deoxyribonucleic acid; EBV = Epstein-Barr virus; 
GGT = gamma-glutamyl transferase, HAV = hepatitis A virus; HBsAg = hepatitis B surface antigen; 
HBc = hepatitis B core; HBV = hepatitis B virus; HCV = hepatitis C virus; HEV = hepatitis E virus; 
HSV = herpes simplex virus; IgG = immunoglobulin G; IgM = immunoglobulin M; INR = international 
normalized ratio; LDH = lactate dehydrogenase; RNA = ribonucleic acid.
D 7
References
Aithal et al, 2011
Aithal et al 2011, Clinical Pharmacology and Therapeutics 89(6):806-815.
FDA Guidance for Industry, July 2009
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing 

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clinical evaluation.’ Available from; https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation

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Appendix E
Sample Corticosteroid Tapering
Corticosteroid Tapering for Prednisone/Budesonide in mg/day
Week 
11
Week 
12
Week 
13
Week 
14
Week 
15
Week 
16
Week 
17
Week 
18
Week 
19
Note: The rate of CS tapering will be at the investigator’s discretion and may depend on the 
participant’s medical history and clinical, laboratory, and endoscopic findings.
Examples of Approximate Equivalent Doses of Oral Prednisone
 
Equivalents
Equivalent Dose
CCI
CCI
CCI

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Appendix F
Patient-reported Outcomes Questionnaires, Descriptions, and 
Instructions
F 1
Evening Diary
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F 2
Site Visit Instruments
Note: The questionnaires presented below are is an approximation of the planned final 
documents. The order of some questions may change.
Patient Reported Outcomes Questionnaire: Evening Diary was removed due to copyrights.

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F 2.1
Inflammatory Bowel Disease Questionnaire (Sample Version)
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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: IBDQ was removed due to copyrights.

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F 2.2
EQ-5D-5L (US English Sample Version)
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Patient Reported Outcomes Questionnaire: EQ-5D-5L was removed due to copyrights.

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F 2.3
SF-36v2® Health Survey
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Patient Reported Outcomes Questionnaire: SF-36v2 was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: SF-36v2 was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: SF-36v2 was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: SF-36v2 was removed due to copyrights.

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Patient Reported Outcomes Questionnaire: SF-36v2 was removed due to copyrights.

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Appendix G
Changes Related to Mitigation of Study Disruptions Due to 
Cases of Civil Crisis, Natural Disaster, or Public Health 
Crisis
Note: Changes below should be implemented only during study disruptions due to any of or a 
combination of civil crisis, natural disaster, or public health crisis (eg, during quarantines and 
resulting site closures, regional travel restrictions and considerations if site personnel or study 
participants become infected with SARS-CoV-2 or similar pandemic infection) during which 
participants may not wish to or may be unable to visit the study site for study visits. These 
changes should only be implemented if allowable by local/regional guidelines and following 
agreement from the sponsor and instructions on how to perform these procedures will be 
provided at the time of implementation. If participant testing is performed as a result of the 
public health crisis, results may be documented for this study.
Please note that during civil crisis, natural disaster, or public health crisis, some study 
assessment and procedures may not be conducted due to international or local policies or 
guidelines, hospital or clinic restrictions, and other measures implemented to ensure patient’s 
safety. In case of doubts please contact the AstraZeneca Sponsor Study Physician/designee. If 
patient testing is performed as a result of the public health crisis, results may be documented 
for this study.
Reconsent of Study Participants During Study Interruptions
During study interruptions, it may not be possible for the participants to complete study visits 
and assessments on site and alternative means for carrying out the visits and assessments may 
be necessary (eg, remote visits). Reconsent should be obtained for the alternative means of 
carrying out visits and assessments and should be obtained prior to performing the procedures 
described in Section 8. Local and regional regulations and/or guidelines regarding reconsent 
of study participants should be checked and followed. Reconsent may be verbal if allowed by 
local and regional guidelines (note, in the case of verbal reconsent the ICF should be signed at 
the participant’s next contact with the study site). Visiting the study sites for the sole purpose 
of obtaining reconsent should be avoided.
Rescreening of Participants to Reconfirm Study Eligibility
Additional rescreening for screen failure due to study disruption can be performed in 
previously screened participants, as long as there have not been greater than 56 days from the 
last dose administration in the lead-in study and the first dose in this OLE study. The 
investigator should confirm this with the designated Sponsor Study Physician/designee. 
In addition, during study disruption there may be a delay between confirming eligibility of a 
participant and either enrollment into the study or commencing of dosing with IP. If this delay 
is outside the screening window specified in Table 1 of CSP the participant will need to be 

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rescreened to reconfirm eligibility before commencing study procedures. This will provide 
another opportunity to rescreen a participant in addition to that detailed in Section 5.4. The 
procedures detailed in Table 1 must be undertaken to confirm eligibility using the same 
identification number for the participant.
Home or Remote Visit to Replace On-site Visit (Where Applicable)
A qualified HCP from the study site or TPV service may visit the participants home or other 
remote location as per local SOPs, as applicable. Supplies will be provided for a safe and 
efficient visit. The qualified HCP will be expected to collect information per the CSP.
Telemedicine Visit to Replace On-site Visit (Where Applicable)
In this appendix and the associated Study Instruction Manual for Mitigation Due to Civil 
Crisis, Natural Disaster, or Public Health Crisis, the term telemedicine visit refers to remote 
contact with the participants using telecommunications technology including phone calls, 
virtual or video visits, and mobile health devices.
During a civil crisis, natural disaster, or public health crisis, onsite visits may be replaced by a 
telemedicine visit if allowed by local/regional guidelines. Having a telemedicine contact with 
the participants will allow AEs, concomitant medications, etc to be documented and reported 
according to study requirements.
At-home or Remote Location IP Administration Instructions
If a site visit is not possible, at-home or remote location administration of IP may be 
performed by a qualified site HCP, provided this is acceptable within local 
regulation/guidance. The option of at-home or remote location IP administration ensures 
participants safety in cases of a pandemic where participants may be at increased risk by 
traveling to the site/clinic. This will also minimize interruption of IP administration during 
other study disruptions (eg, site closures due to natural disaster).
At-home or Remote Location IP Administration by a Qualified HCP or TPV Service
A qualified HCP from the study site or TPV service may administer the IP at the participant’s 
home or other remote location according to the CSP and the Study Instruction Manual for 
Mitigation Due to Civil Crisis, Natural Disaster, or Public Health Crisis, and if allowed by 
local SOPs, as applicable. All necessary supplies and instructions for administration and 
documentation of IP administration will be provided. 
Additional information related to the visit can be obtained via a telemedicine or home visit. 
Refer to the Study Instruction Manual for Mitigation Due to Civil Crisis, Natural Disaster, or 
Public Health Crisis for step-by-step guidance including drug accountability and 
reconciliation requirements.

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Data Capture During Telemedicine or Home/Remote Visits
Data collected during telemedicine or home/remote visits will be captured by the qualified 
HCP from the study site or TPV service in the source documents. 

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Appendix H
Abbreviations
Abbreviation or special 
term
Explanation
5-ASA
5-aminosalicylates
ADA
anti-drug antibody
ADE
adverse device effect
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase/transaminase
AP 
abdominal pain
AST
aspartate aminotransferase/transaminase
AUC 
area under the serum concentration time-curve
AUC0-28
area under the curve from time 0 to 28 days
BM
biomarker
BP
blood pressure
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CFR
Code of Federal Regulations
Cmax
maximum serum concentration 
COVID-19
Coronavirus Disease 2019
CRO
Contract Research Organisation
CRP
C-reactive protein
CS
corticosteroids 
CSP
clinical study protocol
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
DILI
drug induced liver injury
DNA
deoxyribonucleic acid 
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
EIM
extraintestinal manifestation
EQ-5D-5L
5-level European Quality of Life - 5 Dimensions
FAS
Full Analysis Set
FCP
fecal calprotectin

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Abbreviation or special 
term
Explanation
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
hCG
human chorionic gonadotropin
HCP
Health Care Professional
HIPAA
Health Insurance Portability and Accountability Act
HL
Hy’s Law
HIV
human immunodeficiency virus
HRQoL
health related quality of life
IATA
International Airline Transportation Associations
IB
investigator’s brochure
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IL
interleukin
IMP
investigational medicinal product
IND
Investigational new drug
INR
international normalized ratio
IP
Investigational Product
IRB
institutional review board
IRT
Interactive Response Technology
LSF
loose stool frequency
MACE
major adverse cardiac events
MDRD
modification of diet in renal disease
NABs
neutralizing antibodies
NRS
Numerical Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
OLE
open-label extension
PCR
polymerase chain reaction
PCS
potentially clinically significant
PFS
pre-filled syringe
CCI
CCI

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Abbreviation or special 
term
Explanation
PHL
potential Hy’s law
PI
principal investigator 
PK
pharmacokinetic(s)
PRO
patient reported outcome
QTc
corrected QT interval
RBC
red blood cell
RNA
ribonucleic acid
RTSM
Randomisation and Trial Supply Management
SAE
serious adverse event 
SAP
statistical analysis plan
SES-CD
Simple Endoscopic Score for Crohn’s Disease
SF-36v2
Short-Form 36 Health Survey Version 2
SoA
schedule of activities
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reactions
TBL
total bilirubin
TEAE
treatment-emergent adverse event
TESAE
treatment-emergent serious adverse event
TNFα
tumor necrosis factor-alpha
TPV
third-party vendor
UC
ulcerative colitis
ULN
upper limit of normal
US
United States 
VAS
visual analog scale
W
week
w/v
weight/volume
CCI
CCI

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Appendix I
Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 3 (March 2021)
Overall Rationale for the Amendment:
In 2020, AstraZeneca resumed full ownership of brazikumab clinical development. 
AstraZeneca has re-evaluated the development plan and the CSP D5271C00002 (Legacy 
#3150-303-008) has consequently been reviewed and amended.
The granular summary of changes in the tabular format is included below. 
Section # and name
Description of change
Brief rationale
Throughout
The protocol was transferred to the 
AstraZeneca protocol template.
The sponsor of the study has changed to 
AstraZeneca. The protocol was transferred 
to the AstraZeneca template to align the 
study with AstraZeneca processes and 
approved language.
Throughout
Removed reference to Study 
D5170C00002 (previously terminated 
Ph2b study).
Participants from this terminated study 
were not enrolled in this protocol and 
therefore would no longer be applicable 
for this amendment. 
Throughout
Changed optional induction dosing to 
mandatory induction dosing for 
nonresponder/inadequate responders.
Maintain consistency in study population 
that receives induction dosing.
Synopsis
Revised to align with changes to the 
protocol and the AstraZeneca 
template.
The sponsor of the study has changed to 
AstraZeneca. The protocol was transferred 
to the AstraZeneca template to align the 
study with AstraZeneca processes and 
approved language.
SoA
Added screening visit. 
To make it clear what assessments are for 
eligibility requirements and separate these 
from the baseline visit (Week 0). For most 
participants, these assessments will be the 
same as their last visit in the lead-in study.
SoA
Added footnote regarding visit 
schedule calculation.
Revised for clarity.
SoA
Removed serum adalimumab 
immunogenicity test.
Removed Humira arm in Stage 1 of the 
lead-in study.
SoA
Moved assessments that are used for 
screening/eligibility from baseline 
(Week 0) to screening column.
A screening visit was added to the protocol 
to separate assessment needed for 
eligibility and to ensure all screening 

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Section # and name
Description of change
Brief rationale
assessments are performed prior to the 
Week 0 visit.
SoA
FSH should be carried forward from 
screening visit from lead-in study.
Menopausal status based on entry into 
lead-in study should not change and may 
be carried forward to reduce participant 
burden.
SoA
Removed HbA1c.
Not included in lead-in study and does not 
impact eligibility into OLE study.
SoA
Added FCP sampling at Week 12
Evaluate effect of reinduction on FCP as 
inflammatory marker.
SoA
Added PAXgene RNA sampling 
Revised to allow for RNA biomarker 
(IL-23 signature) analysis at late clinical 
endpoint.
SoA, Table 2
Added blood sample for exploratory 
biomarker analysis; PAXgene RNA; 
and stool for calprotectin, lactoferrin 
and exploratory biomarkers at ET and 
Week 70 follow-up. 
Biomarker assessment at ET is needed to 
compare changes in clinical efficacy to 
changes in BM profiles to enhance better 
understanding of brazikumab’s mechanism 
of action.
SoA, Table 2
Removed hepatitis B virus DNA test
Hepatitis B eligibility criteria modified to 
include PCR testing as applicable, and 
therefore, DNA testing removed.
SoA
Added PRO table
Added for clarity.
Section 2.2
Text was revised to update 
information from the recently 
completed Study 3150-101-008
Updated to include most recent data.
Section 2.3
Benefit/risk text from the Germany-
specific protocol amendment was 
added in place of the prior cross-
reference to the IB.
Text was added to provide more 
information on the benefits and potential 
risks of brazikumab administration, in 
alignment with the AstraZeneca template 
and SOPs and the Germany-specific 
amendment.
Section 4.1
Revised text regarding 
responders/completers and non-
responders
Text revised to reflect Humira arm 
removal in the lead-in study. More 
granular description of participants 
subgroups eligibility for OLE study added 
for clarity.
Section 4.1.1 and 
Appendix H 
New section on study conduct 
mitigation is added that would give 
guidance on how the study could 
continue in the event of a serious 
disruption with details of mitigation 
that could be employed to ensure 
study continuity.
The impact of COVID-19 has highlighted 
the risk to continuity of clinical trials 
during times of study disruption, whether 
by civil crisis, natural disaster or public 
health crisis. This section details the 
measures that may be implemented if a 
participant is not able to visit a study site 

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Section # and name
Description of change
Brief rationale
to ensure that the clinical trial can continue 
whilst minimizing risk to the participant, 
maintaining compliance with GCP, and 
minimizing risks to study integrity. These 
changes will only be initiated at a time of 
study disruption.
Section 4.3
Revised section on justification for 
dose
Edited for clarity.
5.1 Inclusion Criterion 
1(b) 
Revised criterion to include rescue 
criteria. Added text regarding 
participants who demonstrate 
evidence of endoscopic improvement.
Clarification of eligibility in the context of 
rescue criteria.
5.1 Inclusion Criterion 
#2(c), Appendix D
Excluded participants with newly-
identified latent TB.
Revised in consideration for participant 
safety in countries with high burden of TB.
5.1Inclusion Criteria 
#4-6
Revised the criteria for reproduction 
and contraception use
Criteria are consistent with prior 
requirements but provide additional 
specificity and clarity regarding acceptable 
contraception; revised wording aligns with 
standard AstraZeneca template.
5.2 Exclusion Criterion 
#5(a) 
Removed the exception for 
participants with a history of basal or 
squamous cell carcinoma > 3 months 
if the participant has no prior history 
of, or current, thiopurine use.
Revised for clarity and safety.
5.2 Exclusion Criterion 
#9
Defined a prolonged QTcF interval
Added for clarification.
5.2 Exclusion Criterion 
#16(a)
Aligned Gilbert syndrome wording 
with UK amendment 
Provided alignment between the global and 
the UK protocol amendments.
Section 5.3
Added restrictions regarding 
contraception and donation of blood
Added to align with standard AstraZeneca 
template wording.
Section 5.3.2
Added text as clarification that use of 
nicotine replacement therapy should 
be recorded as a concomitant 
medication.
Clarification for recording nicotine 
replacement therapy as concomitant 
treatment to support appropriate collection 
and review of applicable data.
Section 5.4
Added text regarding screen failures 
and rescreening.
Added for clarification.
Sections 6 and 6.1
Revised study intervention table and 
text.
Aligned with study design change from the 
main body of the protocol.
Section 6.1.1
Revised description of 
 
administration.
Aligned with study design changes and 
operational changes.
Section 6.1.3
Added section on Study Intervention 
Administration Re-Scheduling.
Section added to clarify guidance for 
rescheduling study drug administration if 
required.
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Section # and name
Description of change
Brief rationale
Section 6.1.4
Revised description of study supplies.
Revised for clarity and to align with 
available supplies.
Section 6.2
Revised text regarding study 
intervention handling.
Revised to align with AstraZeneca 
template and to provide clarification of 
existing text.
Section 6.5
Text added to describe study 
intervention compliance.
Revised to align with AstraZeneca 
template.
Section 6.5.1
Specified information to be collected 
on concomitant medications.
Added for clarification.
Section 6.5.2 and 
Appendix F
Revised corticosteroid study 
guidelines text; included an example 
steroid tapering schedule table
Revised to align and conform steroid 
tapering during maintenance. Steroid 
tapering aligns broadly with clinical 
guidelines.
Section 6.5.3
5-aminosalicylates and oral steroid 
doses above initial randomization 
(Day 1) dose added to the new 
initiation of medications or 
interventions specified as rescue 
treatment. 
Added for clarity.
Section 6.5.4
Added fecal microbial transplantation 
to list of prohibited interventions 
during the study.
Avoid confounding safety or efficacy 
assessments.
Section 7.1
Revised criteria for participant 
discontinuation.
Revised to align with lead-in study 
protocol.
Legacy Section 7.1.1
Removed Temporary Discontinuation 
section.
Revised for consistency of discontinuation 
criteria with lead-in study. Relevant text 
moved to Section 6.1.3.
Section 7.2
Added template text regarding 
participant withdrawal.
Additional text from the AstraZeneca 
template provides details on participant 
follow-up after discontinuation and 
guidance regarding the use of participant 
samples.
Section 8
Added information on data recording 
and blood volume collection.
Added to provide operational details and 
for participant safety.
Section 8.1.2
Crohn’s Disease 
Activity Index
Provided details on the calculation of 
the CDAI.
Added for clarification.
Section 8.1.3
Revised text describing the PRO 
Evening Diary.
Revised for clarification.
Section 8.1.4
New sections added to describe PRO 
Site Visits.
Study design changes.

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Section # and name
Description of change
Brief rationale
Section 8.2.1
Physical Examinations
Provided a list of assessments that 
constitute a full physical examination; 
added the requirement to assess 
abdominal mass, EIM, and fistula 
exam (as applicable).
To provide clarity for the investigator and 
to support the assessment of CDAI.
Section 8.2.2
Vital Signs
Revised text for vital signs; added text 
on recording weight.
For clarification and for study design 
changes.
Section 8.2.4
Revised the description of clinical 
laboratory assessments.
Revised to align with AstraZeneca 
template.
Sections 8.3 and 8.3.1
New text added to describe collection 
of AEs and SAEs.
Added to align with AstraZeneca template.
Sections 8.3.2
Removed prior Section 8.3.2 Method 
of Detecting AEs and SAEs.
Replaced prior text regarding follow-
up of AEs and SAEs with standard 
AstraZeneca template text.
Prior section 8.3.2 text is not needed per 
AstraZeneca template and SOPs
New text regarding follow-up of AEs and 
SAEs is consistent with prior information 
and includes more details. Provides 
alignment with AstraZeneca template and 
SOPs.
Section 8.3.3
New section on assessment of AE 
causality.
Revised to align with AstraZeneca 
template and SOPs; consistent with text 
that was in the prior Appendix 10.4.
Section 8.3.4
New section added to inform the sites 
of how to handle AEs based on signs 
and symptoms.
New information; added to align with 
AstraZeneca template and SOPs.
Section 8.3.5
New section added to inform the sites 
of how to handle AEs that were 
identified through examinations and 
tests.
New information; added to align with 
AstraZeneca template and SOPs.
Section 8.3.6 and 
Appendix D
Text on Hy’s Law replaces prior 
Section 8.3.9.1 and Appendix 9.
AstraZeneca standard template text was 
added to align with AstraZeneca template 
and SOPs. The new content is consistent 
with the prior text.
Section 8.3.7
New section was added to inform the 
sites how to handle AEs due to the 
disease under study.
New information; added to align with 
AstraZeneca template and SOPs.
Section 8.3.8
Text was added to inform the sites 
how to report SAEs; this information 
was previously provided in Appendix 
10.3.
Added to align with AstraZeneca template 
and SOPs; content is similar to the 
information that was removed from 
Appendix 10.3.

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Section # and name
Description of change
Brief rationale
Section 8.3.9
Replaced previous Section 8.3.5 with 
standard AstraZeneca template text on 
the handling of pregnancies
Removed the requirement to report 
elective abortions without 
complications as AEs or SAEs.
Added to align with AstraZeneca template 
and SOPs; except as noted, the content is 
similar to the information that was 
removed from previous Section 8.3.5.
Legacy Section 8.3.9
Section on Medical Device Incidents 
was removed.
The medical devices section was removed 
as irrelevant because the prefilled syringes 
are not medical devices but are 
combination products.
Section 8.3.10
Removed the AESI of Hy's Law in 
Section 8.3.10. Hy's Law is now 
included in Section 8.3.6.
Section 8.3.6 Hy's Law aligns with 
AstraZeneca Protocol Template. No need 
to duplicate as an AESI because it is not a 
specific risk for brazikumab.
Section 8.4
New text replaces prior Section 8.4 
with AstraZeneca standard template 
text on overdose.
Added details on overdose of 
 
brazikumab.
Removed standard Allergan text on 
the handling of overdose and replaced 
with standard AstraZeneca text.
Details on overdose of 
brazikumab 
were added to provide more information to 
the sites. Remaining changes were for 
alignment with AstraZeneca template and 
SOPs.
Section 8.5
Text was added to describe standard 
AstraZeneca process regarding the 
handling of biological samples.
Added to align with AstraZeneca template 
and SOPs.
Section 8.5.1
Revised PK collection details; added 
template text.
Study design change and alignment with 
AstraZeneca template.
Section 8.5.1.1
New section added to provide details 
on the determination of drug 
concentrations.
Added to align with AstraZeneca template.
Section 8.5.2
Template text was added to existing 
text.
Added to align with AstraZeneca template.
Sections 8.6 and 8.6.1
Added text to support new samples 
(stool samples and biopsies).
Study design change, additional BM 
assessment to enhance understanding of 
MOA and to provide rationale for IL-22 as 
BM for IL-23-driven inflammation in gut 
for CDx regulatory approval.
Section 8.8
Text added to support new medical 
resource utilization and health 
economics assessments.
Revised to align with lead-in study design 
change, and for clarification.
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Section # and name
Description of change
Brief rationale
Section 9.4.1
Deleted all references to Humira.
Added details regarding analyses of 
patients (induction versus 
maintenance directly). 
Revised to align with lead-in study design 
change, and for clarification.
Section 9.4.2 and 
9.4.2.1
Clarified that efficacy endpoints are 
exploratory.
Section structure alignment with 
AstraZeneca study protocol and 
clarification of efficacy endpoints 
categorisation.
Section 9.4.2.1
Added bullet for analyses of 
endoscopic remission.
Added definition of endoscopic remission / 
alignment with lead-in study protocol.
Section 9.4.3
Clarified that safety endpoints are 
primary endpoints for this study.
Section structure alignment with 
AstraZeneca study protocol and 
clarification of safety endpoints 
categorisation.
Section 9.4.4
Added section to state that 
exploratory biomarker analyses may 
be defined and presented outside of 
SAP and CSR.
Section structure alignment with 
AstraZeneca study protocol and 
clarification of safety endpoints 
categorisation 
Appendix A
Replaced legacy Appendix 10.1.1.
Alignment with AstraZeneca template.
Appendix B
Replaced legacy Appendix 10.3.
Alignment with AstraZeneca template.
Appendix C
New appendix.
Alignment with AstraZeneca template.
Appendix G
Updated PRO Appendix 10.11.
Revised to align with prior sections of the 
protocol.
Appendix G2.1
IBDQ sample version replaced with 
approved version.
Alignment with AstraZeneca licensed 
version.
Appendix D
Replaced legacy Appendix 10.9.
Alignment with AstraZeneca template.
Legacy 10.8 
Removed legacy Appendix 8 Medical 
Device Incidents.
Study design change.
Appendix I and 
Appendix K
Updated the list of abbreviations and 
list of references.
Revised to align with prior sections of the 
protocol.
Amendment 2: (August 2020)
Overall Rationale for the Amendment:
The protocol was updated to change the sponsor from Allergan to AstraZeneca. This included 
changes to the sponsor name, the study number, and SAE reporting information.

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Section # and name
Description of change
Brief rationale
Throughout
Change sponsor to AstraZeneca and 
change study number to AstraZeneca 
study number
The sponsor of the study is changing to 
AstraZeneca and an AstraZeneca study 
code will be used moving forward
Throughout 
Removed study 3150-302-008 from the 
text
Study 3150-302-008 will not be 
initiated. 
Throughout
Changed study number of lead-in study 
3150-301-008 to D5271C00001 
(Legacy #3150-301-008)
The sponsor of the lead in study is 
changing to AstraZeneca and an 
AstraZeneca study code will be used 
moving forward
Throughout
Change Medical Safety Physician 
(MSP) to study physician. 
This changed is being made to align 
with AstraZeneca terminology. 
Title Page
Change in Sponsor Name and Legal 
Registered Address
The Sponsor name and address were 
changed to AstraZeneca AB
Title Page
Emergency Telephone number 
removed
The Allergan emergency number was 
removed from the title page. This will 
be provided directly to investigators 
Title Page
SAE Reporting Fax Number/email 
removed
The Allergan SAE reporting Fax 
number/email were removed. Safety 
reporting information will be provided 
directly to investigators. 
Title Page
Sponsor signatory was removed
The Allergan sponsor signatory was 
removed 
Section 6.3, Study 
Intervention(s) 
Administered
AstraZeneca will be providing study 
interventions. 
With the sponsor change, AstraZeneca 
will be providing study interventions. 
Section 6.3.3, Study 
Supplies
Allergan was changed to AstraZeneca
AstraZeneca will supply the test 
articles for the study. 
Section 8.3.1, Time 
Period and Frequency for 
Collecting AE and SAE 
information
Section 8.3.3, Follow up 
of AEs and SAEs
Section 8.3.8.1 Potential 
Hy’s Law Cases
The Allergan specific AE reporting 
information was removed.  
AstraZeneca will provide safety 
reporting information directly to 
investigators. 
Section 10.3, Appendix 3 
Adverse Events: 
Definitions and 
Procedures for 
Recording, Evaluating, 
Follow-up, and 
Reporting
The Allergan specific AE reporting 
information was removed. AstraZeneca 
protocol language was added. 
AstraZeneca language was added due 
to change in Sponsor. AstraZeneca will 
provide safety reporting information 
directly to investigators. 

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Section # and name
Description of change
Brief rationale
Section 10.9, Appendix 
9: Liver Safety: 
Suggested Actions and 
Follow-up Assessments
The Allergan specific AE reporting 
information was removed.
AstraZeneca will provide safety 
reporting information directly to 
investigators.
Amendment 1: (June 2019)
The protocol was updated to change the sponsor from Allergan to AstraZeneca. This included 
changes to the sponsor name, the study number and SAE reporting information.
Overall Rationale for the Amendment
This protocol amendment includes updates to correct editorial errors, make clarifications to 
the protocol, and make updates to laboratory testing procedures, including the addition of 
adalimumab serum ADA sampling and hepatitis B virus DNA testing.
Formatting and grammatical edits are not listed below.
Section # and name
Description of change
Brief rationale
Title page
Added EudraCT #
No longer TBD
Header throughout
Updated to correct protocol number
Correction to protocol
1.1 Synopsis
Added exploratory efficacy to 
objectives and endpoints table
Clarification to protocol
1.1 Synopsis
Added that participants do not need to 
complete the 18-week follow-up period 
of the lead-in study
Clarification to protocol
1.1 Synopsis
Updated language for sample size 
calculation
Clarification to protocol
1.1 Synopsis
Added that information on non-
responder qualification is found in 
Section 6.1
Clarification to protocol
1.2 Schema
Updated figure to add “optional” for 
induction dose
Clarification to protocol
1.2 Schema
Removed sentence about continuing 
the study until brazikumab is 
commercially available or study 
discontinued
Updated to align with planned studies 
for the program
1.3 Schedule of 
Activities
Added HbA1c at Week 24
Update to the protocol
1.3 Schedule of 
Activities
Added line and footnote n for hepatitis 
B virus DNA testing for participants 
with positive hepatitis B core antibody 
Updated procedure for participant 
safety

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Section # and name
Description of change
Brief rationale
1.3 Schedule of 
Activities
Removed “pre-dose” for adalimumab
Correction to the protocol
1.3 Schedule of 
Activities
Added adalimumab serum ADA 
immunogenicity testing and updated 
footnote i
Updated procedures for efficacy 
assessment
1.3 Schedule of 
Activities
Footnote k modified to add reference to 
Appendix 11
Appendix 11 added with PRO diary 
information
Table 1-2
Added QFT-TB and hepatitis B virus 
DNA testing to early termination visit 
and added footnote b
As above and correction to protocol
2.2 Background
Corrected dose for 3150-101-008 
protocol from 
Correction to protocol
2.2 Background
Update to results of 3150-101-008
Updated based on new information 
from study
3 Objectives and 
Endpoints
Added exploratory efficacy to 
objectives and endpoints table
Clarification to protocol
4.1 Overall Design
Added that participants do not need to 
complete the 18-week follow-up period 
of the lead-in study and that the final 
visit is at Week 52 for Study 3150-301-
008
Clarification to protocol
4.1 Overall Design
Added that information on non-
responder qualification is found in 
Section 6.1
Clarification to protocol
5.1 Inclusion Criteria
Criterion 1.01 updated to correct study 
number for roll-over study
Correction to protocol
5.1 Inclusion Criteria
Updated criterion 3.02 to align with 
SoA and Appendix 7
Correction to protocol
5.2 Exclusion Criteria
Added other conditions that may 
potentially confound assessments to 
criterion 1.02
Clarification to protocol
5.2 Exclusion Criteria
Updated criterion 1.04 to add sponsors 
opinion
Clarification to protocol
5.2 Exclusion Criteria
Added criterion 1.05, cancer exclusions
To align with other studies in the 
program
5.2 Exclusion Criteria
Added additional exclusions with 
respect to hepatitis B to criterion 4.01
Updated based on new hepatitis B virus 
DNA laboratory testing added to 
protocol
6 Study Intervention
Added subheadings 6.1 and 6.2 to 
clarify IV induction versus 
maintenance dosing
Clarification to the protocol
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Section # and name
Description of change
Brief rationale
Clarified dose is 
 brazikumab 
and that 
 dosing is at the 
discretion of the investigator
Clarification to the protocol
Set minimum time for monitoring to
 
 and added an option for
emergency procedures to be in place to 
treat anaphylaxis
To align with other studies in the 
program and clarification to the 
protocol
6.4 Preparation/ 
Handling/ Storage/ 
Accountability
Added that additional guidance is 
found in the Pharmacy Manual
To align with other studies in the 
program
6.7.1 Permitted 
Interventions
Added more detail to CS therapy and 
tapering; added that oral 5-
aminosalicylate treatments should be 
continued at stable doses as tolerated; 
added use of NSAIDS is discouraged
To align with other studies in the 
program
6.7.4
Prohibited 
Interventions During the 
Study
Added an exception for live attenuated 
vaccine and directed to see Section 
7.1.1. Added that use of alternative and 
complementary treatments must be 
discussed and that Chinese herbal 
therapies are prohibited
Clarification to the protocol and to 
align with other studies in the program
7 Discontinuation 
Moved this sentence from 7.3, “That 
discontinuation of specific sites or of 
the study as a whole are handled as part 
of Appendix 1.
Clarification to the protocol
8.1.1 Ileocolonoscopy
Added that video will be taken for 
duration of the procedure and that 
central reader should also notify the 
investigator of any findings
Clarification to the protocol and to 
align with other studies in the program
8.1.1.1 Simple 
Endoscopic Score for 
Crohn’s Disease
Added, “SES-CD for each of the 5 
segments will be assessed during 
ileocolonoscopy”
To align with other studies in the 
program
8.1.3 Patient Reported 
Outcomes-Evening Diary
Added evening diary to the header, 
added abdominal pain to list of NRS 
items, reworded to make it clear the 
diary is to be completed in the evening
Correction and clarification to the 
protocol
8.2.1 Physical 
Examinations
Added neurological systems would be 
assessed
Alignment with other studies in the 
program
8.2.4 Clinical Safety 
Laboratory Assessments
Removed laboratory manual as 
redundant in sentence
Correction to the protocol
8.2.5 Immunogenicity 
Assessments
Added adalimumab and that sample 
collection will remain blinded
Added to explore the effect of 
adalimumab ADA on efficacy and a 
clarification to the protocol
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Section # and name
Description of change
Brief rationale
8.3.3
Follow-up of 
AEs and SAEs
Added “if autopsy is performed”
To align with other studies in the 
program
8.3 Adverse Events
Added subsections 8.3.6 and 8.3.7
To align with other studies in the 
program
8.3.8.4 Hypersensitivity 
Reactions 
Added examples of appropriate drugs 
and that emergency procedures are to 
be in place for anaphylaxis treatment 
Clarification to the protocol
8.4 Treatment of 
Overdose
Added that MSP information is in 
Study Contact Information tab and that 
it is at least 18 weeks for brazikumab to 
be eliminated from the body
To align with other studies in the 
program
9 Statistical 
Considerations
Added that participants who were 
previously enrolled in the lead-in 
studies of 3150-301-008 and 3150-302-
008, the baseline from the lead-in 
studies will be used for the analyses. 
For participants who were previously 
enrolled in Study D5170C00002, the 
last assessment before the first dose of 
the study intervention in this study will 
be used as the baseline for the analyses.
Clarification to the protocol
9.2 Sample Size 
Determination
Updated the description of how the 
sample size was calculated
Clarification to the protocol
9.3 Populations for 
Analyses
Updated wording for the populations
Clarification to the protocol
9.4.1.1 Efficacy 
Endpoints
Added more detail to the endpoints
Clarification to the protocol and to 
align with other studies in the program
9.4.1.2 Analyses for 
Efficacy Endpoints
Added that will also be presented by 
biomarker group and updated header
Clarification to the protocol
9.4.2 Safety Analyses
Added if Visit 1 for this study is the 
last visit from the lead-in study, the 
safety value at Visit 1 will not be 
included in the PCS evaluation, but will 
be included in the change-from-
baseline summary analysis.
Clarification to the protocol
9.4.2.1 Adverse Events
Removed reference related to study 
intervention
Correction to the protocol
9.4.2.2 Clinical 
Laboratory Assessments
Changed Visit 1 to baseline
Clarification to the protocol
10.1.3 Informed Consent 
Process
Added option for legally authorized 
representative
To align with other studies in the 
program
Table 10-1
Updated wording for microscopic 
examination of urinalysis
To align with other studies in the 
program

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Section # and name
Description of change
Brief rationale
10.3 Appendix 3
Deleted redundant sentence
Correction to the protocol
10.4 Appendix 4
Added FCP to abbreviations
Correction to the protocol
10.11 Appendix 11
This appendix was added and includes 
an example of the evening diary and 
the Bristol stool formation scale
To provide additional clarification on 
what is tested as part of PRO, and to 
better define liquid or soft stools.
10.12.1 Baseline
Added virology-related and ADA 
immunogenicity
As above
10.12.2 Open-label 
Treatment Period 
Added HbA1C at Week 24 and 
hepatitis B virus DNA
As above
10.12.3 Early 
Termination
Added hepatitis B virus DNA and 
QFT-TB
As above

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11
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Document Name: d5271c00002-csp-v5-amendment-4
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D5271C00002 Clinical Study Protocol Version 5 Amendment
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