A Multicenter, Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Ankylosing Spondylitis
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Sponsor: UCB Biopharma S.P.R.L.

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 1 of 143
PROTOCOL AS0008 AMENDMENT 2
A MULTICENTER, PHASE 2B, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP, DOSE-RANGING STUDY TO EVALUATE 
THE EFFICACY AND SAFETY OF BIMEKIZUMAB IN 
SUBJECTS WITH ACTIVE ANKYLOSING SPONDYLITIS
PHASE 2B
EudraCT Number: 2016-001102-42
IND Number: 128708
UCB BIOPHARMA SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
29 Jul 2016
Not applicable
Protocol Amendment 1
15 Mar 2017
Nonsubstantial
Protocol Amendment 2
09 Mar 2018
Substantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
REDACTED COPY 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 2 of 143
STUDY CONTACT INFORMATION
Sponsor
UCB BIOPHARMA SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
, MD, MSc, PhD
Address:
UCB Pharma Ltd.
208 Bath Road
Slough, SL1 3WE
UNITED KINGDOM
Phone:
Clinical Project Manager
Name:
, PharmD, PhD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str.10
40789 Monheim am Rhein
GERMANY
Phone:
Clinical Trial Biostatistician
Name:
, MS
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 3 of 143
Clinical Monitoring Contract Research Organization
Name:
PRA Health Sciences
Address:
4130 Park Lake Avenue, Suite 400
Raleigh, NC 27612
UNITED STATES
Phone:
Fax:
REDACTED COPY 
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v
thereof. 

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 4 of 143
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com
REDACTED COPY 
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or variations 
v
thereof. 

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 5 of 143
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................16
2
INTRODUCTION ...........................................................................................................18
2.1 Axial spondyloarthritis.....................................................................................................18
2.1.1
Clinical studies.....................................................................................................19
2.1.2
Nonclinical studies...............................................................................................21
3
STUDY OBJECTIVES....................................................................................................21
3.1 Primary objective.............................................................................................................21
3.2 Secondary objectives .......................................................................................................22
3.3 Other objectives ...............................................................................................................22
4
STUDY VARIABLES.....................................................................................................22
4.1 Primary variable(s)...........................................................................................................22
4.1.1
Primary efficacy variable.....................................................................................22
4.2 Secondary variables .........................................................................................................22
4.2.1
Secondary efficacy variables ...............................................................................22
4.2.2
Secondary safety variables ..................................................................................23
4.3 Other variables.................................................................................................................23
4.3.1
Other efficacy variables.......................................................................................23
4.3.2
Other safety variables ..........................................................................................24
4.3.3
Other PK and PD variables..................................................................................24
4.3.4
Other immunological variables............................................................................24
4.3.5
Other pharmacogenomic, proteomic, and metabolite variables ..........................24
5
STUDY DESIGN.............................................................................................................25
5.1 Study description .............................................................................................................25
5.1.1
Screening Period/Baseline...................................................................................25
5.1.2
Double-Blind Period............................................................................................26
5.1.3
Dose-Blind Period ...............................................................................................26
5.1.4
Rescue therapy.....................................................................................................27
5.1.5
Safety Follow-Up Visit........................................................................................27
5.1.6
Safety monitoring strategy...................................................................................27
5.1.7
Imaging evaluation ..............................................................................................28
5.1.8
Study duration per subject ...................................................................................28
5.1.9
Planned number of subjects and site(s) ...............................................................28
5.1.10
Anticipated regions and countries .......................................................................28
5.2 Schedule of study assessments.........................................................................................28
5.3 Schematic diagram...........................................................................................................34
5.4 Rationale for study design and selection of dose.............................................................35
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 6 of 143
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................35
6.1 Inclusion criteria ..............................................................................................................35
6.2 Exclusion criteria .............................................................................................................37
6.3 Withdrawal criteria ..........................................................................................................41
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................43
7
STUDY TREATMENTS.................................................................................................43
7.1 Description of investigational medicinal products ..........................................................43
7.2 Treatments to be administered.........................................................................................44
7.3 Packaging.........................................................................................................................44
7.4 Labeling ...........................................................................................................................44
7.5 Handling and storage requirements..................................................................................44
7.6 Drug accountability..........................................................................................................45
7.7 Procedures for monitoring subject compliance................................................................45
7.8 Concomitant medication(s)/treatment(s)..........................................................................45
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................46
7.8.2
Prohibited concomitant treatments (medications and therapies).........................46
7.9 Blinding............................................................................................................................47
7.9.1
Procedures for maintaining and breaking the treatment blind.............................48
7.9.1.1
Maintenance of study treatment blind.......................................................48
7.9.1.2
Breaking the treatment blind in an emergency situation...........................48
7.10 Randomization and numbering of subjects......................................................................49
8
STUDY PROCEDURES BY VISIT ...............................................................................49
8.1 Screening (Visit 1) ...........................................................................................................49
8.2 Baseline (Day 1, first dose of IMP) (Visit 2)...................................................................51
8.3 Double-Blind Period (Week 1 to Week 12).....................................................................52
8.3.1
Week 1 (+/-3 days) (Visit 3)................................................................................52
8.3.2
Week 2 (+/-3 days) (Visit 4)................................................................................53
8.3.3
Week 4 (+/-3 days) (Visit 5)................................................................................53
8.3.4
Week 8 (+/-3 days) (Visit 6)................................................................................54
8.3.5
Week 12 (+/-3 days) (Visit 7)..............................................................................55
8.4 Dose-Blind Period (Week 16 to Week 48) ......................................................................56
8.4.1
Week 16 (+/-4 days) (Visit 8)..............................................................................56
8.4.2
Week 20 (+/-4 days) (Visit 9)..............................................................................57
8.4.3
Week 24 (+/-4 days) (Visit 10)............................................................................57
8.4.4
Week 28 (+/-4 days) (Visit 11)............................................................................59
8.4.5
Week 32 (+/-4 days) (Visit 12)............................................................................59
8.4.6
Week 36 (+/-4 days) (Visit 13)............................................................................60
8.4.7
Week 40 (+/-4 days) (Visit 14)............................................................................60
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 7 of 143
8.4.8
Week 44 (+/-4 days) (Visit 15)............................................................................61
8.4.9
Week 48 (+/-4 days) (Visit 16)............................................................................61
8.5 Early Termination Visit ...................................................................................................62
8.6 Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final dose)......................64
8.7 Unscheduled Visit............................................................................................................65
9
ASSESSMENT OF EFFICACY......................................................................................65
9.1 ASAS20, 40, ASAS 5/6 response, and ASAS partial remission .....................................65
9.2 Patient global assessment.................................................................................................66
9.3 Total and nocturnal spinal pain........................................................................................66
9.4 Function – BASFI............................................................................................................66
9.5 Inflammation – BASDAI (mean of questions 5 and 6) ...................................................66
9.6 CRP 66
9.7 ASDAS-CRP....................................................................................................................67
9.8 BASDAI...........................................................................................................................67
9.9 BASMI.............................................................................................................................67
9.10 MASES ............................................................................................................................68
9.11 PhGADA..........................................................................................................................68
9.12 SF-3668
9.13 MOS-12............................................................................................................................68
9.14 ASQoL.............................................................................................................................69
9.15 MRI Assessment (SPARCC and ASspiMRI)..................................................................69
9.16 Hospital Anxiety and Depression Scale...........................................................................70
10
ASSESSMENT OF PHARMACOKINETIC, PHARMACODYNAMIC, 
PHARMACOGENOMIC, AND PROTEOMIC VARIABLES......................................70
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................70
12
ASSESSMENT OF SAFETY..........................................................................................71
12.1 Adverse events.................................................................................................................71
12.1.1
Definition of adverse event..................................................................................71
12.1.2
Adverse events of special interest........................................................................71
12.1.3
Adverse events for special monitoring ................................................................71
12.1.4
Procedures for reporting and recording adverse events.......................................72
12.1.5
Description of adverse events..............................................................................72
12.1.6
Follow-up of adverse events................................................................................72
12.1.7
Rule for repetition of an adverse event................................................................73
12.1.8
Pregnancy ............................................................................................................73
12.1.9
Suspected transmission of an infectious agent via a medicinal product..............74
12.1.10
Overdose of investigational medicinal product ...................................................74
12.1.11
Safety signal detection.........................................................................................74
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 8 of 143
12.2 Serious adverse events .....................................................................................................75
12.2.1
Definition of serious adverse event .....................................................................75
12.2.2
Procedures for reporting serious adverse events .................................................75
12.2.3
Follow-up of serious adverse events....................................................................76
12.3 Immediate reporting of adverse events............................................................................76
12.4 Anticipated serious adverse events ..................................................................................76
12.5 Laboratory measurements................................................................................................77
12.5.1
Evaluation of PDILI ............................................................................................78
12.5.1.1
Consultation with Medical Monitor and local hepatologist ......................82
12.5.1.2
Immediate action: determination of IMP discontinuation.........................82
12.5.1.3
IMP restart/rechallenge .............................................................................82
12.5.1.4
Testing: identification/exclusion of alternative etiology...........................82
12.5.1.5
Follow-up evaluation.................................................................................84
12.6 Other safety measurements..............................................................................................84
12.6.1
Vital signs ............................................................................................................84
12.6.2
Body weight and height.......................................................................................85
12.6.3
Physical examination...........................................................................................85
12.6.4
12-lead electrocardiogram ...................................................................................85
12.6.5
Tuberculosis and TB risk factor assessment and management ...........................85
12.6.5.1
Tuberculosis assessment by IGRA............................................................87
12.6.5.2
Chest x-ray for tuberculosis ......................................................................87
12.6.5.3
Tuberculosis questionnaire........................................................................88
12.6.5.4
Tuberculosis management.........................................................................88
12.6.6
Pregnancy testing.................................................................................................89
12.6.7
Assessment of suicidal ideation and behavior.....................................................89
13
OTHER STUDY MEASUREMENTS ............................................................................89
13.1 Demography.....................................................................................................................89
13.2 Medical history ................................................................................................................89
13.3 Ankylosing spondylitis history ........................................................................................90
13.4 Prior and concomitant medications..................................................................................90
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................90
14.1 Adherence to protocol......................................................................................................90
14.2 Monitoring .......................................................................................................................90
14.2.1
Definition of source data .....................................................................................90
14.2.2
Source data verification .......................................................................................91
14.3 Data handling...................................................................................................................91
14.3.1
Case Report Form completion.............................................................................91
14.3.2
Database entry and reconciliation........................................................................91
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 9 of 143
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............92
14.4 Termination of the study..................................................................................................92
14.5 Archiving and data retention............................................................................................92
14.6 Audit and inspection ........................................................................................................92
14.7 Good Clinical Practice .....................................................................................................93
15
STATISTICS ...................................................................................................................93
15.1 Definition of analysis sets................................................................................................93
15.2 General statistical considerations.....................................................................................94
15.3 Planned efficacy analyses ................................................................................................94
15.3.1
Analysis of the primary efficacy variable............................................................94
15.3.1.1
Supportive analyses...................................................................................95
15.3.2
Other efficacy analyses........................................................................................95
15.3.2.1
Analysis of the secondary efficacy variables ............................................95
15.3.2.2
Analysis of the other efficacy variables ....................................................96
15.4 Subgroup analyses ...........................................................................................................96
15.5 Planned safety and other analyses....................................................................................96
15.5.1
Safety analyses.....................................................................................................96
15.5.2
Other analyses......................................................................................................97
15.6 Handling of protocol deviations.......................................................................................97
15.7 Handling of dropouts or missing data..............................................................................97
15.8 Planned interim analysis and data monitoring.................................................................99
15.9 Determination of sample size...........................................................................................99
16
ETHICS AND REGULATORY REQUIREMENTS....................................................100
16.1 Informed consent ...........................................................................................................100
16.2 Subject identification cards............................................................................................100
16.3 Institutional Review Boards and Independent Ethics Committees................................100
16.4 Subject privacy...............................................................................................................101
16.5 Protocol amendments.....................................................................................................101
17
FINANCE, INSURANCE, AND PUBLICATION.......................................................102
18
REFERENCES ..............................................................................................................102
19
APPENDICES ...............................................................................................................106
19.1 Modified New York (mNY) Classification Criteria for AS ..........................................106
19.2 Markedly abnormal laboratory values ...........................................................................107
19.3 Protocol Amendment 1 ..................................................................................................108
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................142
21
SPONSOR DECLARATION ........................................................................................143
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 10 of 143
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................29
Table 7‒1:
Prohibited or restricted medications and required wash-out periods prior 
to Baseline........................................................................................................46
Table 7‒2:
Preparation of placebo and bimekizumab injections .......................................48
Table 12‒1:
Anticipated serious adverse events for the population of subjects with 
ankylosing spondylitis .....................................................................................77
Table 12‒2:
Laboratory measurements................................................................................78
Table 12‒3:
Required investigations and follow-up for PDILI ...........................................80
Table 12‒4:
PDILI laboratory measurements......................................................................83
Table 12‒5:
PDILI information to be collected...................................................................84
Table 19‒1:
Modified New York (mNY) Classification Criteria for AS ..........................106
Table 19‒2:
Definitions of markedly abnormal hematology values..................................107
Table 19‒3:
Definitions of markedly abnormal biochemistry values................................107
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................34
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 11 of 143
LIST OF ABBREVIATIONS
AE
adverse event
AESI
adverse event of special interest
AESM
adverse event for special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AS
ankylosing spondylitis
ASAS
Assessment of SpondyloArthritis International Society
ASAS20, 40, 5/6
Assessment in SpondyloArthritis International Society 20%, 40%, 5 out
of 6 response criteria
ASDAS-CRP
Ankylosing Spondylitis Disease Activity Score-C-reactive protein
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score major improvement
ASspiMRI-a
Ankylosing Spondylitis spine Magnetic Resonance Imagine-activity
ASQoL
Ankylosing Spondylitis Quality of Life
AST
aspartate aminotransferase
axSpA
axial spondyloarthritis
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BASMI
Bath Ankylosing Spondylitis Metrology Index
BSA
body surface area
CDC 
Centers for Disease Control 
CDMS
clinical data management system
CHO
Chinese Hamster Ovarian
CL/F
total body clearance
COX-2 inhibitor
cyclooxygenase 2 inhibitor
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
CRP
C-reactive protein
C-SSRS/eC-SSRS
Columbia-Suicide Severity Rating Scale/electronic C-SSRS
CZP
certolizumab pegol
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 12 of 143
DBRS
Dose-Blind Responder Set
DBS
Dose-Blind Set
DMARD
disease-modifying antirheumatic drug
DMC
Data Monitoring Committee
DVU
disco-vertebral unit
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
ES
Enrolled Set
ESS
Escape Subject Set
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GI
gastrointestinal
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale—Anxiety 
HADS-D
Hospital Anxiety and Depression Scale—Depression 
HbcAg
hepatitis B core antibody
HbsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
HRQoL
health-related quality of life
hs-CRP
high sensitivity C-reactive protein
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
ICH
International Council for Harmonisation
ICF
Informed Consent Form
IEC
Independent Ethics Committee
IGRA
Interferon-Gamma Release Assay
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application and any extensions or variations thereof. 

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 13 of 143
IIV
interindividual variability
IL
interleukin
im
intramuscular
IMP
investigational medicinal product
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
iv
intravenous
IXRS
interactive voice or web response system 
LTB
latent tuberculosis
LTBI
latent tuberculosis infection 
MAR
missing at random
MASES
Maastricht Ankylosing Spondylitis Enthesitis Index
MCID
minimal clinically important difference
MCP-Mod
multiple comparison procedure – modeling
MCS
mental component summary
MedDRA®
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MMR
measles-mumps-rubella
mNY
Modified New York (criteria)
MOS
Medical Outcomes Study
MRI
magnetic resonance imaging
MTB
mycobacterium tuberculosis 
MTX
methotrexate
nr-axSpA
nonradiographic-axial spondyloarthritis
NRI
nonresponder imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
NTMB
nontuberculous mycobacteria
NYHA
New York Heart Association
OMERACT
Outcome Measures in Rheumatology Clinical Trials
OPV
oral polio vaccine
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 14 of 143
PCS
physical component summary
PD
pharmacodynamics
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamics Per-Protocol Set
PGADA
Patient’s Global Assessment of Disease Activity
PhGADA
Physician’s Global Assessment of Disease Activity
PK
pharmacokinetics
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per-Protocol Set
PS
Patient Safety
PsA
psoriatic arthritis
Q4W
every 4 weeks (monthly)
QTcB
QT interval corrected for heart rate using Bazett’s formula 
QTcF
QT interval corrected for heart rate using Fridericia’s formula 
RA
rheumatoid arthritis
RIF
mycobacterium tuberculosis rifampicin
RS
Randomized Set
RCTC
Rheumatology Common Toxicity Criteria
RUV
residual unexplained variability
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous(ly)
SD
standard deviation
SF-36
Short-Form 36-item Health Survey
SFU
Safety Follow-up
SI
sacroiliac
SpA
spondyloarthritis
SPARCC
Spondyloarthritis Research Consortium of Canada
SOP
standard operating procedure
SS
Safety Set
SSZ
sulfasalazine
STIR
short-tau-inversion recovery
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 15 of 143
t½
half-life
TB
tuberculosis
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
TNFα
tumor necrosis factor alpha
ULN
upper limit of normal
VAS
visual analog scale
V/F
volume of distribution
VU
vertebral unit
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 16 of 143
1
SUMMARY
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to investigate the efficacy, safety, pharmacokinetics (PK), and 
pharmacodynamics (PD) of bimekizumab (also known as UCB4940) compared with placebo in 
adult subjects with active ankylosing spondylitis (AS) in order to guide the selection of doses 
and clinical indices in the Phase 3 development program.
Eligible subjects will have active AS, determined by documented radiologic evidence (X-ray) 
fulfilling the Modified New York criteria for AS (1984), including symptoms for ≥3 months and 
age of onset <45. Furthermore, subjects will have moderate to severe active disease (Bath 
Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥4 and spinal pain ≥4 [BASDAI 
Question 2]). Subjects must have at least 1 of the following: 1) inadequate response to 
nonsteroidal anti-inflammatory drug (NSAID) therapy, 2) intolerance to administration of at least 
1 NSAID, or 3) contraindication(s) to NSAID therapy. Inadequate response to an NSAID is 
defined as lack of response for at least 4 weeks of continuous NSAID therapy at the highest 
tolerated dose of the administered NSAID or the lack of response to treatment with at least 
2 NSAIDs at the maximum tolerated dose for at least 4 weeks total duration. Subjects may be 
TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects who have been on a 
TNF inhibitor previously must have: 
•
experienced an inadequate response to previous treatment given for at least 3 months 
•
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
•
lost access to TNF inhibitor for other reasons 
The primary objective is to assess the dose-response based on the efficacy of bimekizumab
administered subcutaneously (sc) Q4W for 12 weeks in the treatment of subjects with active AS. 
The primary efficacy variable is the Assessment in Axial SpondyloArthritis International Society
40% response criteria (ASAS40) response at Week 12. An ASAS40 response is defined as an 
improvement of ≥40% and ≥2 units in at least 3 out of the following 4 domains on a scale of 
0 to 10 and no worsening at all in the remaining domain and includes the following assessments:
•
Patient global assessment: numeric rating scale (NRS) (global disease activity last week)
•
Pain assessment: NRS (last week/spine/at night due to AS) 
•
Function: Bath Ankylosing Spondylitis Functional Index (BASFI) 
•
Inflammation: mean of BASDAI Questions 5 and 6
The secondary objectives of the study are to assess the efficacy of the individual dose regimens 
of bimekizumab compared to placebo, safety and tolerability, PK, PD, immunogenicity, and the 
exposure:response relationship of bimekizumab as it relates to efficacy and safety. The 
secondary efficacy variables include: Change from Baseline in Ankylosing Spondylitis Disease 
Activity Score- C-reactive protein (ASDAS-CRP), Assessment in Axial SpondyloArthritis 
International Society 20% response criteria (ASAS20) response, Assessment in Axial 
SpondyloArthritis International Society 5 out of 6 response criteria (ASAS5/6) response, Change 
from Baseline in BASDAI, and Change from Baseline in BASFI, all at Week 12. Safety 
variables include incidence of adverse events (AEs), serious adverse events (SAEs), and 
withdrawal due to AEs as secondary safety variables and change from Baseline in vital signs, 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 17 of 143
body weight, physical examination, ECG, and clinical laboratory variables as other safety 
variables. 
Other objectives are to assess the impact on patient-reported quality of life (fatigue, sleep, and 
pain), the impact of administration of bimekizumab on biological pathways relating to disease 
biology and response to therapy via candidate biomarker analysis, and to enable genomic and 
proteomic analysis of subject samples and evaluation of the potential for subject stratification 
approaches, and to assess the impact of bimekizumab on inflammatory changes in the spine and 
sacroiliac (SI) joint using magnetic resonance imaging (MRI) in a subset of subjects. 
An estimated 100 sites in Europe and North America will randomize 285 subjects (57 subjects 
per treatment arm). The enrollment of TNF inhibitor-experienced subjects will be limited to 30% 
of the total study population.
The study consists of a Screening Period (up to 28 days), Double-Blind Period (12 weeks), 
Dose-Blind Period (36 weeks) and Safety Follow-up (SFU) Period (20 weeks; only for subjects 
who do not enter the extension study). Therefore, the maximum duration of the study is 
68 weeks. 
Screening Period/Baseline
The Screening Period will be up to 28 days. During the Screening Period, the Investigator will 
assess the eligibility of subjects according to the inclusion and exclusion criteria. The Screening 
Period will also enable washout of any medications not permitted for use during the study and 
allow initiation of latent TB treatment where necessary and appropriate. 
Double-Blind Period
At Baseline/Day 1 subjects will be randomized in a 1:1:1:1:1 ratio (stratified by region and prior 
TNF inhibitor exposure) to receive the following blinded study treatment regimens during the 
Double-Blind Period:
•
Placebo
•
Bimekizumab 16mg administered sc every 4 weeks (Q4W)
•
Bimekizumab 64mg administered sc Q4W
•
Bimekizumab 160mg administered sc Q4W
•
Bimekizumab 320mg administered sc Q4W
The investigational medicinal product (IMP) will be administered sc in the clinic at Baseline, 
Week 4, Week 8, and Week 12. Additional study visits in the Double-Blind Period (without 
dosing) will occur at Week 1 and Week 2. At Week 12, subjects will transition from the 
Double-Blind Period into the 36-week Dose-Blind Period. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 18 of 143
Dose-Blind Period
The Dose-Blind Period lasts from Week 12 to Week 48. Subjects randomized to bimekizumab 
160mg Q4W or bimekizumab 320mg Q4W will remain on their randomized dose and subjects 
randomized to placebo, bimekizumab 16mg Q4W, and bimekizumab 64mg Q4W, will be 
rerandomized in a 1:1 fashion to bimekizumab 160mg Q4W or bimekizumab 320mg Q4W. The 
total duration of treatment is 48 weeks.
During the 36-week Dose-Blind Period, subjects will be evaluated for eligibility to rescue
treatment at defined time points. Subjects who do not show an improvement in both PGADA and 
spinal pain compared to Baseline will be eligible to receive rescue therapy as defined in
Section 5.1.4.
Safety Follow-Up (SFU) Visit/Extension study
At the completion of the Dose-Blind Period, subjects will be given the opportunity to enter an 
extension study at Week 48. All subjects who complete the study and do not enter the extension
study or who discontinue early, including those withdrawn from study treatment, will have a 
SFU Visit at 20 weeks after their last dose of IMP. 
2
INTRODUCTION
2.1
Axial spondyloarthritis
Spondyloarthritis (SpA) is an umbrella term applied to a family of rheumatic diseases (including 
axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], reactive arthritis, the arthritis of 
inflammatory bowel disease [IBD], and undifferentiated spondyloarthritis) that have features in 
common with each other and distinct from other inflammatory arthritides, particularly 
rheumatoid arthritis (RA). 
Axial SpA is a chronic inflammatory disease that impacts a substantial proportion of the 
population. Limited evidence exists regarding the exact prevalence of axSpA; however, recent 
data suggest that the prevalence is similar to that of RA in the US (axSpA: 0.7% to 1.4%; 
RA: 0.5% to 1.0%) (Reveille et al, 2012; Myasoedova et al, 2010; Helmick et al, 2008).  
The ASAS working group established classification criteria to distinguish 2 broad categories of 
SpA: peripheral SpA and axSpA (Rudwaleit et al, 2011; Rudwaleit, 2010; Rudwaleit et al, 
2009b). This division is based on the body part predominantly involved in the inflammatory 
process. Therefore, peripheral SpA includes diseases affecting mainly peripheral joints, such as 
reactive arthritis and PsA, whereas axSpA comprises those diseases with mainly axial 
involvement (SI joints and spine), including AS diagnosed with radiographic involvement and 
nonradiographic axSpA (nr-axSpA). 
Patients with axSpA have inflammatory back pain. The disease typically originates in the 
sacroiliac joints, then progresses to the spine. In the sacroiliac joints and the spine, active 
inflammation results in erosions, sclerosis, and fatty lesions seen on MRI. However, the most 
characteristic feature is new bone formation leading to ankylosis of the SI joints and 
syndesmophytes attached to the vertebral bodies. As a result of extended syndesmophyte 
formation, over time the spine may become fused. Objective signs of inflammation (such as 
enthesitis, dactylitis, peripheral arthritis, or uveitis), genetic features (such as the presence of 
human leukocyte antigen [HLA] B27), and laboratory parameters (such as elevated C-reactive 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 19 of 143
protein [CRP]) may also be present (Braun, 2012; Rudwaleit et al, 2009a; Braun and Sieper, 
2007). Disability in axSpA is related to both the degree of inflammatory activity, causing pain, 
stiffness, fatigue, and poor quality of sleep, and to the degree of bony ankylosis, causing loss of 
spinal mobility. Patients with AS show radiographic progression of disease with X-ray identified 
sacroiliitis, while "Bamboo spine" may develop when the outer fibers of the fibrous ring of the 
intervertebral discs ossify, which results in the formation of marginal syndesmophytes between 
adjoining vertebrae.
Nonsteroidal anti-inflammatory drugs are often rapidly effective for the symptoms (pain and 
stiffness) of axSpA (Poddubnyy, 2013; Poddubnyy et al, 2012), but many patients lose or never 
have clinically meaningful response and structural damage often progresses despite their use. 
Conventional disease-modifying antirheumatic drugs (DMARDs,eg, methotrexate [MTX] and 
sulfasalazine [SSZ]) have no proven efficacy in axial disease, but may benefit patients with 
peripheral joint disease (Haibel et al, 2007; Braun et al, 2006; Haibel et al, 2005). Therefore, 
DMARDs are recommended only in patients with predominantly peripheral manifestations 
(Braun et al, 2011). Patients who are intolerant of or have inadequately responded to NSAIDs, or 
those in whom NSAIDs are contraindicated, have approved treatment options such as 
TNF inhibitors.
Recently, the interleukin (IL)-17 cytokine family has been identified as a therapeutic target in 
axSpA and secukinumab, an IL-17A monoclonal antibody, has recently been approved as a 
treatment option in active AS. 
Bimekizumab (UCB4940) is an engineered, humanized full-length monoclonal antibody of IgG1 
subclass of approximately 150,000 Dalton, which is expressed in a genetically engineered 
Chinese Hamster Ovarian (CHO) cell line. Bimekizumab has high affinity for human IL-17A 
and human IL-17F and selectively and potently inhibits the activity of both isoforms in vitro. 
Interleukin-17A and IL-17F are key proinflammatory cytokines believed to play important roles 
in autoimmune and inflammatory diseases. Therefore, bimekizumab permits an evaluation of the 
potential for additional efficacy, which may be conferred by dual inhibition of both cytokines, in 
patients suffering from diseases in which both cytokines are active. Bimekizumab is being 
developed for the treatment of patients with inflammatory diseases such as PsA, PsO, and 
AxSpA. 
As a consequence, a Phase 2b dose-ranging study (AS0008) was designed to investigate the 
efficacy and safety of various bimekizumab dose regimens in subjects with active AS. 
2.1.1
Clinical studies
Four clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, PA0007 in 53 subjects with PsA, 
and UP0031 in 12 healthy volunteers. 
UP0008 was a Phase 1, single ascending dose study in adults with mild to moderate psoriasis 
affecting ≤5% body surface area (BSA). In this blinded study, single doses of bimekizumab up to 
640mg (approximately 8mg/kg in an 80kg adult) were evaluated. There were no clinically 
relevant safety findings identified at any dose and all doses were well tolerated. The prespecified 
exploratory assessment of disease activity showed clinically relevant and statistically significant 
improvements at the higher doses studied.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 20 of 143
RA0124 was a Phase 1, open-label, parallel-group, single-dose study in healthy subjects. The 
primary objective of this study was to determine the absolute bioavailability of single sc doses of 
bimekizumab (80mg and 160mg). The secondary objectives were to evaluate the dose 
proportionality of bimekizumab 80mg and 160mg sc, and to evaluate the safety and tolerability 
of these sc doses and 160mg given by intravenous (iv) infusion. In RA0124, the absolute 
bioavailability was similar for the 2 doses tested (0.656 and 0.631 for the bimekizumab 80mg 
and 160mg sc doses, respectively). The median half-life (t½) following sc administration was 
similar to that following iv administration (27.81 days and 28.25 days for bimekizumab 160mg 
sc and bimekizumab 160mg iv, respectively).
Bimekizumab has also been investigated in a Phase 1b, proof of concept, randomized, 
placebo-controlled, multiple-dose study (PA0007). The primary objective of PA0007 was to 
assess the safety and PK of multiple dose administration of iv bimekizumab in subjects with 
PsA. Four active doses and a placebo were tested. Drug was administered as a loading dose of 
bimekizumab 80mg, 160mg, 240mg, or 560mg at Week 1, and 2 additional doses of 
bimekizumab 40mg, 80mg, 160mg, or 320mg at Week 4 and Week 7. In each treatment group, 
subjects received a total of 3 doses of bimekizumab, administered every 3 weeks. There were no 
unexpected clinically relevant safety findings and all doses were well tolerated. The PK was 
linear across the tested dose range and no change in PK was observed following multiple doses. 
Observed changes in inflammatory biomarkers were consistent with expectations based on the 
IL-17A and IL-17F mechanism of action. The exploratory analysis showed clinically relevant 
improvement in activity of PsA and in skin involvement in those subjects with concomitant 
active psoriatic lesions. Data from the top 3 bimekizumab dose groups pooled showed that by 
Week 9 80% [95% CI: 62.7, 90.5] of subjects achieved an ACR20 response (vs 16.7% [95% CI: 
4.7, 44.8] in the placebo group) and 100% [95% CI: 79.6, 100.0] of subjects with active psoriatic 
lesions had achieved a PASI75 response (vs 0% [95% CI: 0.0, 43.4] in the placebo group).
Infections (mostly nasopharyngitis) were the most commonly reported events in both the active
(36.8% of subjects) treatment and the placebo group (35.7% of subjects). None of the infections 
were considered serious or required treatment with antibiotics. Two subjects in the active 
treatment group experienced 1 local candida infection each (oropharyngitis and vulvovaginitis, 
respectively) that were nonserious and resolved with topical therapy. There was a reduction in 
mean neutrophil count in the active treatment group, although this drop was not clinically 
relevant and a clear relationship with dose or time was not evident. IL-17 plays a significant role 
in regulating neutrophil recruitment and granulopoiesis and thus, receipt of an anti-IL-17 
antibody may be associated with effects on neutrophil count. Previous clinical experience with 
administration of anti-IL-17 antibodies in humans indicates that this potential risk is low and 
reversible. Some increases in liver function tests were reported, but none had a convincing 
relationship to exposure to IMP. 
In the bimekizumab clinical studies to date, the most commonly reported GI AEs were 
abdominal distension, abdominal pain, diarrhea, flatulence, nausea, and vomiting. All of these 
events, except 1 event of vomiting, were mild or moderate in intensity. T helper-17 and other 
IL-17-producing cell types are present in a high frequency in the physiologic, healthy state of the 
intestinal mucosa. Interleukin-17 is recognized as an important player in the pathophysiology of 
infectious and immune-mediated GI diseases, and has been shown to contribute to the gut barrier 
function (Ivanov et al, 2008). Clinical data with secukinumab suggest that the drug may worsen 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 21 of 143
symptoms of co-existing Crohn’s disease in patients with psoriasis and ankylosing spondylitis 
(Baeten et al 2015). 
UP0031 was a Phase 1, open-label, parallel-group, randomized, single-dose study to evaluate the 
BA, PK, and tolerability of 2 different formulations of bimekizumab in healthy subjects. There 
were no treatment-emergent adverse events (TEAEs) leading to discontinuation, and no SAEs or 
fatalities were reported. 
One additional study of bimekizumab is ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
(CZP; Cimzia®) therapy in subjects with moderate to severe RA.
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
2.1.2
Nonclinical studies
Parallel inhibition of IL-17A and IL-17F has shown potent effects in a variety of animal models 
of inflammatory disease. Intravenously administered bimekizumab was well tolerated in repeat 
dose toxicology studies in Cynomolgus monkeys with a no adverse effect level of 
200mg/kg/week. The findings of note in toxicity studies were diarrhea related to infectious 
enteritis (observed in the single dose study) and asymptomatic mild colonic ulceration in a 
proportion of animals (in the repeat-dose study); this latter finding was not associated with 
hematology abnormalities. Data suggest that bimekizumab has induced primary lesions to the 
mucosa-associated lymphoid tissue via a pharmacologically-related mechanism. In a second 
repeat-dose study, none of the minor apoptosis/necrosis findings observed in gut associated 
lymph nodes were seen. In animals given the highest dose of bimekizumab in the study 
(20mg/kg/week), a slightly higher number of protozoa (Balantidium coli) was observed in the 
cecum and colon as compared to the control animals and low dose animals. Therefore, the 
gut-associated lymph node lesions observed in the first study are considered to be accidental 
and/or linked to exaggerated pharmacology and proliferation of Balantidium coli and are 
considered to be the result of a change in local mucosal immunity. 
Additional information on the nonclinical data for bimekizumab is available in the current 
version of the IB.
3
STUDY OBJECTIVES
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group 
dose-ranging study to evaluate the efficacy and safety of bimekizumab in subjects with active 
AS. 
3.1
Primary objective
The primary objective is to assess the dose-response based on the efficacy of bimekizumab
administered sc Q4W for 12 weeks in the treatment of subjects with active AS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 22 of 143
3.2
Secondary objectives
The secondary objectives of the study are as follows:
•
To assess the efficacy of the individual dose regimens of bimekizumab compared to placebo 
•
To assess the safety and tolerability of bimekizumab
•
To assess the PK of bimekizumab
•
To assess the PD of bimekizumab
•
To assess the immunogenicity of bimekizumab
•
To assess the exposure:response relationship of bimekizumab as it relates to efficacy and 
safety
3.3
Other objectives
•
To assess disease activity
•
To assess the impact on patient-reported quality of life (function, fatigue, sleep, and pain)
•
To assess the impact on enthesitis
•
To assess the impact of administration of bimekizumab on biological pathways relating to 
disease biology, progression, and response to therapy via biomarker analysis, and to enable 
genomic and related approaches for analysis of subject samples and evaluation of the 
potential for subject stratification approaches
•
To assess the impact of bimekizumab on inflammatory changes in the spine and SI joint 
using MRI in a subset of subjects
4
STUDY VARIABLES
4.1
Primary variable(s)
4.1.1
Primary efficacy variable
The primary efficacy variable for this study is as follows:
•
ASAS40 response at Week 12 
4.2
Secondary variables
4.2.1
Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Change from Baseline in ASDAS-CRP at Week 12
•
ASAS20 response at Week 12
•
ASAS5/6 response at Week 12
•
Change from Baseline in BASDAI at Week 12 
•
Change from Baseline in BASFI at Week 12
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 23 of 143
4.2.2
Secondary safety variables
Assessment time points for safety variables are specified in Table 5‒1. Variables are as follows: 
•
Incidence of AEs and SAEs
•
Withdrawal due to AEs
4.3
Other variables
4.3.1
Other efficacy variables
Assessment time points for the other efficacy variables are specified in Table 5‒1 (analyses at all 
time points not specified in Section 4.1.1 or Section 4.2.1 are exploratory). Variables are as 
follows:
•
ASAS40 response
•
Time to ASAS40 response
•
Change from Baseline in ASDAS-CRP
•
ASDAS status (eg, inactive disease, moderate, high and very high disease activity)
•
ASAS20 response 
•
Time to ASAS20 response
•
ASAS5/6 response
•
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) 
•
ASAS partial remission 
•
Change from Baseline in BASDAI 
•
Change from Baseline in BASFI 
•
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
•
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
•
Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Change from Baseline in total and nocturnal spinal pain (NRS)
•
Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
•
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey) 
•
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
•
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 24 of 143
•
Change from Baseline in:
−
Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index for Assessment 
of Spinal Inflammation in AS, and
−
Ankylosing Spondylitis spine MRI- activity (ASspiMRI-a) in the Berlin modification 
score 
•
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores 
•
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.3.2
Other safety variables
Assessment time points for other safety variables are specified in Table 5‒1. Variables are as 
follows: 
•
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight 
•
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas [QTcB and QTcF]), 
including changes from Baseline Electrocardiogram (ECG) variables 
•
Change from Baseline in clinical laboratory variables (hematology, biochemistry, and 
urinalysis)
4.3.3
Other PK and PD variables
•
The PK variables are plasma concentrations of bimekizumab.
•
The PD variables are concentrations of cytokines of relevance to the IL-17A/F signaling 
pathway and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-6, and 
TNFα. 
4.3.4
Other immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers. 
•
Anti-bimekizumab antibody detection prior to and following study treatment
•
Serum complement concentrations.
•
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
CD19, CD4, CD8, and CD69 (using fluorescence activated cell sorting). 
•
Cytokines and other exploratory markers  
4.3.5
Other pharmacogenomic, proteomic, and metabolite variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 25 of 143
5
STUDY DESIGN
5.1
Study description
This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to evaluate the efficacy and safety of bimekizumab in subjects with active 
AS. To be eligible to participate in this study, subjects must meet the following key inclusion 
criteria: 
•
Subject has active AS, determined by documented radiologic evidence (X-ray) fulfilling the 
Modified New York criteria for AS (1984) (see Table 19‒1), including symptoms for 
≥3 months and age of onset <45 years. 
•
Subject has moderate to severe active disease as defined by each of the following:
−
BASDAI score ≥4
−
Spinal pain ≥4 on a 0 to 10 NRS (from BASDAI item 2)
•
Subjects must have at least 1 of the following: 
−
inadequate response to NSAID therapy
−
intolerance to administration of at least 1 NSAID 
−
contraindication(s) to NSAID therapy
Inadequate response to an NSAID is defined as lack of response for at least 4 weeks of 
continuous NSAID therapy at the highest tolerated dose of the administered NSAID or the 
lack of response to treatment with at least 2 NSAIDs at the maximum tolerated dose for at 
least 4 weeks total duration.
•
Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have:
−
experienced an inadequate response to previous treatment given for at least 3 months 
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation)
−
lost access to TNF inhibitor for other reasons
Approximately 285 eligible subjects will be randomized to 1 of 5 treatment arms to receive 
treatment according to their randomized placebo or bimekizumab dose regimen (Section 5.1.2) 
until Week 12. Thereafter, subjects randomized to bimekizumab 160mg Q4W or bimekizumab
320mg Q4W will remain on their randomized dose and subjects randomized to placebo, 
bimekizumab 16mg Q4W, and bimekizumab 64mg Q4W, will be rerandomized in a 1:1 fashion 
to bimekizumab 160mg Q4W or bimekizumab 320mg Q4W. The total duration of treatment is 
48 weeks.
5.1.1
Screening Period/Baseline
Assessments of eligibility as described in Section 6 will be initiated during the 28-day Screening 
Period. The Screening Period will also enable the washout of medications not permitted for use 
during the study and allow initiation of latent TB treatment where necessary. 
The assessments at the Screening Period Visit are presented in Table 5‒1.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 26 of 143
5.1.2
Double-Blind Period
At Baseline/Day 1, subjects will be randomized 1:1:1:1:1 (stratified by region and prior 
TNF inhibitor exposure) to receive the following blinded IMP treatment regimens at the clinical 
site. The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% 
of the total study population.
•
Placebo
•
Bimekizumab 16mg administered sc Q4W
•
Bimekizumab 64mg administered sc Q4W
•
Bimekizumab 160mg administered sc Q4W
•
Bimekizumab 320mg administered sc Q4W
The IMP will be administered sc in the clinic at Baseline and Q4W thereafter up to Week 12. 
Additional study visits (without dosing) are scheduled at Week 1 and Week 2. At 12 weeks, 
subjects will transition from the Double-Blind Period into the 36-week Dose-Blind Period, as 
discussed in Section 5.1.3
Subjects withdrawing early from the study will undergo the Early Termination Visit assessments 
and will enter the SFU Period.
The assessments during the Treatment Period are presented in Table 5‒1.
5.1.3
Dose-Blind Period
After the 12-week Double-Blind Period, subjects will enter the 36-week Dose-Blind Period. At 
the Week 12 Visit, subjects will be allocated to bimekizumab treatment regimens as follows:
•
Subjects in the placebo group, bimekizumab 16mg Q4W, or bimekizumab 64mg Q4W will 
be rerandomized in a 1:1 fashion to bimekizumab 160mg or bimekizumab 320mg Q4W.
•
Subjects in the bimekizumab 160mg dose group will continue to receive bimekizumab 
160mg Q4W.
•
Subjects in the bimekizumab 320mg dose group will continue to receive bimekizumab 
320mg Q4W.
At the completion of the Dose-Blind Period, Investigators should discuss treatment options with 
the subject. Subjects will be given the opportunity to enter an extension study at Week 48.
The assessments during the Dose-Blind Period are presented in Table 5‒1.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 27 of 143
5.1.4
Rescue therapy
At Weeks 16, 24, and 36 of the Dose-Blind Period, subjects will be evaluated for their response 
to treatment to determine eligibility for rescue therapy. 
Subjects with <10% improvement from Baseline in both PGADA and total and nocturnal spinal 
pain (ASAS domain response criteria) are eligible for rescue treatment. Rescue therapy will be at 
the Investigator’s discretion, with the following options:
•
NSAIDS and/or joint injections as outlined below. Subjects may receive these add-on rescue 
therapies while continuing to receive their randomized dose of bimekizumab.
For subjects taking NSAID/COX-2 inhibitors at Baseline or at Weeks 16, 24, or 36, a change 
can be made to a different NSAID/COX-2 inhibitor. Changes from an NSAID to a COX-2 
inhibitor or from a COX-2 inhibitor to an NSAID are permitted up to the maximum approved 
or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 inhibitor may be taken at a 
given time.
−
For subjects not taking NSAID/COX-2 inhibitors at Baseline, Weeks 16, 24, or 36, either 
NSAIDs, or COX-2 inhibitors can be initiated, up to the maximum approved or tolerated 
dose, whichever is lower. Only 1 NSAID/COX-2 inhibitor may be taken at a given time.
−
After the NSAID/COX-2 regimen has been optimized, SI joint injection is permitted, 
either unilaterally or bilaterally, performed by a qualified physician. 
•
If the subject does not achieve sufficient response to the above options and/or the 
Investigator feels that a biologic other than bimekizumab is warranted, the subject must 
discontinue from study treatment (bimekizumab) and follow the withdrawal criteria and 
follow up as outlined in Section 6.3.
A decrease in dose or dosing frequency of any agent for the treatment of AS is permitted for 
reasons of intolerance/AEs/side effects at any time. 
Rescue therapy will be determined by the Investigator taking into account the half-life of 
bimekizumab (27.8 days).
Subjects may be withdrawn from the study or from study medication at any time and continue 
treatment per the Investigator’s discretion, as described in the Withdrawal Section (Section 6.3).
5.1.5
Safety Follow-Up Visit
All subjects who complete the study and do not enter the extension study or who discontinue 
from the study early, including those withdrawn from IMP treatment, will have a SFU Visit at 
20 weeks after their final dose of IMP. 
The assessments at the SFU Visit are presented in Table 5‒1.
5.1.6
Safety monitoring strategy
An independent Data Monitoring Committee (DMC) will review study safety data on an ongoing 
basis. Details will be available in the DMC charter. A cardiovascular adjudication committee 
will review cardiovascular events. Further details are provided in Section 12.1.11.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 28 of 143
5.1.7
Imaging evaluation
In a subpopulation of AS0008, MRIs of the spine and SI joints will be performed in 
approximately 20 subjects per treatment arm at Baseline. Magnetic resonance imaging at
Week 12 and Week 48 will be performed only for subjects who are MRI-positive at Baseline
based on an ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) 
assessment. The Baseline MRI should be performed after confirmation of eligibility for the study 
based on screening assessments and before the first bimekizumab injection. Magnetic resonance 
imaging at Week 12 and Week 48 should be performed as close to the Week 12/Week 48 Visit as 
possible. Further details are provided in Section 9.15. Analyses will be exploratory in nature and 
will be performed at selected sites.
5.1.8
Study duration per subject
For each subject, the study will last a maximum of up to 68 weeks, as follows:
•
Screening Period: up to 28 days
•
Double-Blind Period: 12 weeks
•
Dose-Blind Period: 36 weeks
•
A SFU Visit: 20 weeks after the final dose of IMP for subjects not entering the extension
study or discontinuing from the study early, including those withdrawn from study treatment.
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.9
Planned number of subjects and site(s)
The planned number of randomized subjects is 285; there will be 57 subjects per treatment arm. 
The planned number of study sites is approximately 100. The enrollment of 
TNF inhibitor-experienced subjects will be limited to 30% of the total study population. 
5.1.10
Anticipated regions and countries
The study sites will be located in Europe and North America.
5.2
Schedule of study assessments
The schedule of study assessments is presented in Table 5‒1.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 29 of 143
Table 5‒1:
Schedule of study assessments
Screening 
(Visit 1) (up to 
28 days)
Baseline 
(Day 1, Visit 2) 
(first dose)
Double-Blind Period 
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
Visita
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Weeka
1
2
4
8
12
16
20
24
28
32
36
40
44
48
Protocol activity
Written informed consent
X
Demographic data
X
AS history
X
Significant past medical history and 
concomitant diseases
X
Xc
Inclusion/exclusion criteria
X
X
Prior medication 
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
eC-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HADS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AsQoL
X
X
X
X
X
X
X
X
X
X
BASDAI
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
MOS Short Sleep Scale (12 items)
X
X
X
X
X
X
X
X
X
PGADA
X
X
X
X
X
X
X
X
X
X
X
X
Total and nocturnal spinal pain (NRS)
X
X
X
X
X
X
X
X
X
X
X
X
Tuberculosis questionnaire
X
X
X
X
X
X
X
X
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 30 of 143
Table 5‒1:
Schedule of study assessments
Screening 
(Visit 1) (up to 
28 days)
Baseline 
(Day 1, Visit 2) 
(first dose)
Double-Blind Period 
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
Visita
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Weeka
1
2
4
8
12
16
20
24
28
32
36
40
44
48
Height
X
Vital signs (BP, pulse, temperature)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
X
X
X
X
X
X
Physical examinatione
X
X
X
X
X
X
MASES
X
X
X
X
X
BASMI
X
X
X
X
X
X
X
X
X
X
PhGADA
X
X
X
X
X
X
X
X
X
X
ECGf
X
X
X
X
X
Hematology/biochemistry/urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood sample for CRPg
X
X
X
X
X
X
X
Blood sample for hs-CRPg
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testingh
X
X
X
X
X
Hepatitis B and C testing
X
HIV testing
X
Collect blood sample for determination of 
HLA-B27 status
X
Blood sample for bimekizumab plasma 
concentrationsg
X
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab antibody detectiong
X
X
X
X
X
X
X
X
X
X
X
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 31 of 143
Table 5‒1:
Schedule of study assessments
Screening 
(Visit 1) (up to 
28 days)
Baseline 
(Day 1, Visit 2) 
(first dose)
Double-Blind Period 
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
Visita
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Weeka
1
2
4
8
12
16
20
24
28
32
36
40
44
48
Blood samples for cytokines, complement, 
and biomarker analysisg
X
X
X
X
X
X
X
Blood sample for genomic, 
proteomic/metabolomic analysesg, i
X
X
X
X
X
X
X
Blood samples for genetic/epigenetic 
analysisg,i
X
X
X
X
For participating centers: 
Blood samples for flow cytometryg,
X
X
X
X
X
X
X
IGRA tuberculosis testj
X
X
X
X
Evaluation for rescue therapyk
X
X
X
Chest x-rayl
X
Sacroiliac joint x-ray
Xm
Spine and sacroiliac MRIn
X
X
X
Enter IXRSo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab or placebo administrationp, q
X
X
X
X
X
X
X
X
X
X
X
X
AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis International Society; AsQoL=Ankylosing Spondylitis Quality of Life; BASDAI=Bath 
Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology 
Index;BP=blood pressure; CRP=C-reactive protein; eC-SSRS=electronic Columbia Suicide Severity Rating Scale; ECG=electrocardiogram; ET=Early 
Termination; HADS=Hospital Anxiety and Depression Scale; HIV=human immunodeficiency virus; hs-CRP=high sensitivity C-reactive protein; 
IGRA=interferon gamma release assay; IMP=investigational medicinal product; IMS=International Menopause Society; IXRS= interactive voice or web 
response system; MASES=Maastricht Ankylosing Spondylitis Enthesitis Index; MOS=Medical outcomes study; MRI=magnetic resonance imaging; 
NRS=numeric rating scale; PGADA=Patient’s Global Assessment of Disease Activity; PhGADA=Physician’s Global Assessment of Disease, Activity; SF-
36=Short Form-36; SFU=Safety Follow-Up; TB=tuberculosis
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 32 of 143
Table 5‒1:
Schedule of study assessments
Screening 
(Visit 1) (up to 
28 days)
Baseline 
(Day 1, Visit 2) 
(first dose)
Double-Blind Period 
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
Visita
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Weeka
1
2
4
8
12
16
20
24
28
32
36
40
44
48
a Visit windows of +/-3 days from the first dose at all visits through Week 12 and +/- 4 days for all visits after Week 12 except SFU. The SFU Visit window 
is -3 and +7 days from last dose.
b Safety Follow-Up Visit occurs 20 weeks after the last dose for all subjects who complete the study and do not enter the extension study or who discontinue 
early, including those withdrawn from study treatment.
c Ensure there are no significant changes in medical history that would exclude the subject based on the exclusion criteria.
d At Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 30 minutes and 1 hour after dosing. At all other visits collect 
pulse and BP prior to drug administration and once after dosing. All other procedures are done prior to dosing. 
e Includes evaluation of signs and symptoms of active TB, risk for exposure to TB.
f ECGs will be performed at the study site and read locally.
g At dosing visits, all blood samples are taken prior to dosing. Blood samples for bimekizumab and anti-bimekizumab antibody detection will be processed as 
per instructions in the laboratory manual. Both CRP and hs-CRP will be tested. After Screening, both hs-CRP and CRP data will not be sent to the 
Investigator to protect the blinded nature of the treatment assignments.
h A serum pregnancy test will be performed at Screening for all women of childbearing potential. This recommendation also applies to women of childbearing 
potential with infrequent or irregular menstrual cycles and women during menopause. Natural menopause is recognized to have occurred after 12 consecutive 
months of amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause Society [IMS], 2015). A urine 
pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A urine pregnancy test will also be performed at any study visit where there 
has been a delay in menses. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. Pregnancy 
test results must be negative prior to administering IMP. 
i A separate Informed Consent Form will be required for subjects who provide samples for genetic testing. The Informed Consent Form must be signed prior to 
collecting samples.
j It is recommended that Quantiferon TB GOLD test be performed.
k At Weeks 16, 24, and 36 of the Dose-Blind Period, subjects will be evaluated for their response to treatment to determine eligibility for rescue therapy. 
Subjects with <10% improvement from Baseline in both PGADA and total and nocturnal spinal pain (ASAS domain response criteria) are eligible for rescue 
treatment. Rescue therapy will be at the Investigator’s discretion as outlined in Section 5.1.4.
l If a subject has had a recent radiograph of the chest within 3 months prior to the Screening Visit, it may be used as the Screening chest x-ray. 
m If subjects have a previous x-ray documenting AS meeting eligibility criteria, they are eligible for study entry after reconfirming their eligibility by central 
reading. If no x-ray is available one must be performed at Screening. If the previous x-ray is more than 1 year old, and central read criteria for randomization 
are not met, another x-ray may be performed if permitted by local guidelines.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 33 of 143
Table 5‒1:
Schedule of study assessments
Screening 
(Visit 1) (up to 
28 days)
Baseline 
(Day 1, Visit 2) 
(first dose)
Double-Blind Period 
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
Visita
3
4
5
6
7
8
9
10
11
12
13
14
15
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Weeka
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2
4
8
12
16
20
24
28
32
36
40
44
48
n An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 20 subjects per treatment arm at Baseline. A central reader will 
assess Baseline MRIs to identify MRI-positive subjects as per the ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria. An MRI 
at Week 12 and Week 48 will be performed for those subjects who were MRI-positive at Baseline. The Baseline MRI should be performed after confirmation 
of eligibility based on screening assessments for the study and before the first bimekizumab injection. Magnetic resonance imaging at Week 12 and Week 48 
should be performed as close to the Week12/Week 48 Visit as possible. For logistical reasons, it may not be possible to schedule the MRIs at the actual visit 
date and an additional visit for the MRI may be required.
o IXRS is used to register the Subject at Screening, randomize the Subject at Baseline/Day 1, rerandomize the Subject at Week 12 (Subject in the placebo, 
bimekizumab 16mg, and bimekizumab 64mg treatment groups), and to register all visits. 
p The minimum time between doses during the Double-Blind Period should be no less than 25 days and no more than 31 days and during the Dose-Blind Period 
should be no less than 24 days and no more than 32 days.
q At Week 12, the Dose-Blind Period dosing will start, as detailed in Section 5.1.3.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 34 of 143
5.3
Schematic diagram
The study schematic diagram for AS0008 is presented in Figure 5‒1.
Figure 5‒1: Schematic diagram
ASAS=Assessment of SpondyloArthritis International Society; DMARD=disease-modifying antirheumatic drug; 
NSAID=nonsteroidal anti-inflammatory drug; PGADA=Patient’s Global Assessment of Disease Activity; 
Q4W=every 4 weeks; SFU=Safety Follow-Up
a After 12 weeks of double-blind treatment, subjects randomized to placebo, bimekizumab 16mg Q4W, or 
bimekizumab 64mg Q4W doses will be rerandomized 1:1 to receive either bimekizumab 160mg Q4W or 
bimekizumab 320mg Q4W. Subjects randomized to bimekizumab 160mg Q4W or 320mg Q4W will continue to 
receive their originally randomized dose (Section 5.1.3).
b At Weeks 16, 24, and 36 of the Dose-Blind Period, subjects will be evaluated for their response to treatment to 
determine eligibility for rescue therapy. 
Subjects with <10% improvement from Baseline in both PGADA and total and nocturnal spinal pain (ASAS domain 
response criteria) are eligible for rescue treatment. Rescue therapy will be at the Investigator’s discretion as outlined 
in Section 5.1.4.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 35 of 143
5.4
Rationale for study design and selection of dose
The following doses of bimekizumab are proposed in the Phase 2b study: 16mg, 64mg, 160mg, 
and 320mg administered sc Q4W. The proposed dose range has been selected based on a dose 
response model developed using literature data of other biologics, such as secukinumab, in this 
disease and bimekizumab data in PsA (Diderichsen and Cox, 2016). 
Doses greater than 320mg have been previously studied in the development of bimekizumab. In 
the single ascending dose study UP0008, a single dose of bimekizumab 640mg was tested. In the 
multiple dose study PA0007, a bimekizumab 560mg loading dose followed by 2 subsequent 
320mg doses every 3 weeks was tested. At exposure levels achieved at these doses, the 
compound had no significant safety concerns. In the previous clinical studies, bimekizumab was 
administered iv and the current study proposes to administer the compound sc. Due to lower 
bioavailability, bimekizumab exposure is expected to be lower with sc administration compared 
to after iv administration , therefore, the dose regimens are expected to be safe. 
Simulations were performed using the developed model to predict the dose response of ASAS40 
at Week 12, which indicated that increasing doses above bimekizumab 320mg may not provide 
additional benefit in terms of efficacy. Therefore, bimekizumab 320mg has been selected as the 
maximum dose in the current study. Three dose levels below bimekizumab 320mg were selected 
to characterize the dose-exposure response curve at the end of current study. The lowest dose 
level of bimekizumab 16mg Q4W was selected because this dose is expected to provide an 
ASAS40 response rate close to placebo, while still delivering some benefit to patients. The 
bimekizumab 64mg and 160mg Q4W doses were selected in order to precisely characterize the 
dose-exposure response curves. The proposed doses will provide adequate information to study 
the dose-exposure response of bimekizumab in AS. This information will be used to determine 
the right dose and dosage regimen for future studies of bimekizumab in this indication.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent Form is signed and dated by the subject or legal representative. 
2. Subject or legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete diaries), visit schedule, or medication intake according 
to the judgment of the Investigator.
3. Subject is male or female and at least 18 years of age.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 36 of 143
4. Female subjects must be postmenopausal (at least 1 year; to be confirmed hormonally as part 
of the screening process, if less than 2 years since last menstrual period), permanently 
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing 
potential (and engaged in sexual activity that could result in procreation), must be willing to 
use a highly effective method of contraception up till 20 weeks after last administration of 
IMP, and have a negative pregnancy test at Visit 1 (Screening) and immediately prior to first 
dose. The following methods are considered highly effective when used consistently and 
correctly.
−
combined (estrogen and progestogen) hormonal contraception associated with inhibition 
of ovulation (oral, intravaginal or transdermal) 
−
progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable)
−
intrauterine device (IUD)
−
intrauterine hormone-releasing system (IUS)
−
bilateral tubal occlusion
−
vasectomized partner
−
sexual abstinence if it is in accordance with a subject’s preferred and common lifestyle. 
Subjects who use abstinence as a form of birth control must agree to abstain from 
heterosexual intercourse until 20 weeks after the last dose of IMP. Study personnel must 
confirm the continued use of abstinence is still in accordance with the subject’s lifestyle 
at regular intervals during the study.
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up till 20 weeks after the last administration of IMP (anticipated 5 half-lives).
5. Subject has active AS, determined by documented radiologic evidence (X-ray) fulfilling the 
Modified New York criteria for AS (1984) (see Table 19‒1), including symptoms for 
≥3 months and age of onset <45 years. 
6. Subject has moderate to severe active disease as defined by each of the following:
−
BASDAI score ≥4
−
Spinal pain ≥4 on a 0 to 10 NRS (from BASDAI item 2)
7. Subjects must have at least 1 of the following: 
−
inadequate response to NSAID therapy
−
intolerance to administration of at least 1 NSAID 
−
contraindication(s) to NSAID therapy
Inadequate response to an NSAID is defined as lack of response for at least 4 weeks of 
continuous NSAID therapy at the highest tolerated dose of the administered NSAID or the 
lack of response to treatment with at least 2 NSAIDs at the maximum tolerated dose for at 
least 4 weeks total duration.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 37 of 143
8. Subjects who are regularly taking NSAIDs/COX-2 inhibitors as part of their AS therapy are 
required to be on a stable dose for at least 14 days before Baseline and should remain on a 
stable dose up to Week 16.
9. Subjects taking corticosteroids must be on an average daily dose of ≤10mg/day prednisone or 
equivalent for at least 14 days before Baseline and should remain on a stable dose up to 
Week 16.
10. Subjects taking MTX (≤25mg/week) are allowed to continue their medication if started at 
least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization. 
Dose, dosing schedule, and route of administration (oral or subcutaneous) should remain 
stable up to Week 16. It is strongly recommended that subjects taking MTX are also taking 
folic acid supplementation.
11. Subjects taking sulfasalazine (up to 3g/day) or hydroxychloroquine (up to 400mg per day 
total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, 
with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule 
should remain stable up to Week 16.  
12. Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have: 
−
experienced an inadequate response to previous treatment given for at least 12 weeks 
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
−
lost access to TNF inhibitor for other reasons
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria are met:
1. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 20 weeks following last dose of IMP. Male subjects who are planning a 
partner pregnancy during the study or within 20 weeks following the last dose.
2. Subjects previously participating in a bimekizumab clinical study and receiving at least 
1 dose of IMP.
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 12 weeks or at least 5 half-lives whichever is greater. 
4. Subjects with a known hypersensitivity to any excipients of bimekizumab.
5. Subjects with a total ankylosis of the spine, or a diagnosis of any other inflammatory arthritis 
eg, RA, sarcoidosis, systemic lupus erythematosus, or reactive arthritis. 
6. Subjects with use of any medication listed in Table 7‒1 meeting the exclusionary criteria for 
the specific medication(s) including wash-out described in the table. 
7. Subject has any current sign or symptom that may indicate an active infection (except for the 
common cold) or has had an infection requiring systemic antibiotics within 2 weeks of 
Baseline.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 38 of 143
8. Subjects with a history of chronic or recurrent infections, or a serious or life-threatening 
infection within the 6 months prior to the Baseline Visit (including herpes zoster). Subjects 
with a high risk of infection in the Investigator’s opinion (eg, subjects with leg ulcers, 
indwelling urinary catheter, persistent or recurrent chest infections, subjects who are 
permanently bedridden or wheelchair assisted, prior prosthetic joint infection at any time, 
etc).
9.
Subjects with concurrent acute or chronic viral hepatitis B or C or human immunodeficiency 
virus (HIV) infection. Subjects who have evidence of, or tested positive for hepatitis B or 
hepatitis C are excluded. 
A positive test for the hepatitis B virus (HBV) is defined as: 
•
positive for hepatitis B surface antigen (HbsAg+); or, 
•
positive for anti-hepatitis B core antibody (HbcAb+) 
A positive test for the hepatitis C virus (HCV) is defined as: 
•
positive for hepatitis C antibody (anti-HCV Ab), and 
•
positive via a confirmatory test for HCV (for example, HCV polymerase chain reaction)
10. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), 
Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
11. Subjects receiving any live (includes attenuated) vaccination within the 8 weeks prior to 
Baseline (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal 
influenza vaccination is not permitted). Live vaccines are not allowed during the study or for 
20 weeks after the last dose of IMP.
Live vaccines include, but are not limited to the following: 
−
Anthrax vaccine
−
Intranasal influenza vaccine
−
Measles-mumps-rubella (MMR) vaccine
−
Polio live oral vaccine (OPV)
−
Smallpox vaccine
−
Tuberculosis BCG vaccine
−
Typhoid live oral vaccine
−
Varicella vaccine
−
Yellow fever vaccine
12. Subjects receiving Bacillus Calmette-Guerin (BCG) vaccinations within 1 year prior to IMP
administration.
13. Subjects with a history of a lymphoproliferative disorder including lymphoma or current 
signs and symptoms suggestive of lymphoproliferative disease.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 39 of 143
14. Subjects with primary immunosuppressive conditions, including subjects who are taking 
immunosuppressive therapy following organ transplants.
15. Subjects with known TB infection, at high risk of acquiring TB infection, with latent TB 
infection (LTBI)* or current or history of NTMB infection (refer to Section 12.6.5 for details 
on determining full TB exclusion criteria).
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire 
regimen.
16. Subjects who have had a splenectomy.
17. Subjects with concurrent malignancy or a history of malignancy (including surgically 
resected uterine/cervical carcinoma-in-situ) during the past 5 years will be excluded, with the 
following exceptions that may be included: 
a) ≤3 excised or ablated basal cell carcinomas of the skin
b) One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or 
ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of 
recurrence or metastases for more than 2 years prior to Screening 
c) Actinic keratosis (-es)
d) Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 
6 months prior to Screening
18. Subjects having had major surgery (including joint surgery) within the 6 months prior to 
Screening, or planned surgery within 6 months after entering the study.
19. Subjects with a current or recent history, as determined by the Investigator, of severe, 
progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac 
(eg, congestive heart failure New York Heart Association [NYHA] Grade 3 and 4), 
gastrointestinal (GI) (note: subjects with active peptic ulcer disease are excluded; subjects 
with a history of peptic ulcer disease are allowed), or neurological disease.
20. Subjects with a history of uncompensated heart failure, fluid overload, or myocardial 
infarction, or evidence of new-onset ischemic heart disease or in the opinion of the 
Investigator other serious cardiac disease, within 12 weeks prior to Baseline.
21. Subjects with clinically significant laboratory abnormalities (eg, glomerular filtration rate 
[GFR] <60 mL/min/1.73m2, neutropenia <1.5x109/L, hemoglobin <8.5g/dL, lymphocytes 
<1.0 x109/L, platelets <100x109/L). Individual screening tests, for which the results are in 
error, borderline, or indeterminate for inclusion in the study, can be repeated once for 
confirmation during the Screening Period if they are within 25% of the exclusion limit. Upon 
retesting, subjects whose results remain outside this threshold should not be randomized.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 40 of 143
22. Subject has >2x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase* (ALP), or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If subject has 
elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to 
identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
*An isolated elevation between 2xULN and <3xULN of ALP is acceptable in the absence of 
an identified exclusionary medical condition.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation during the Screening Period. Upon retesting, subjects whose ALT, 
AST, or ALP remain above the thresholds defined above, should not be randomized.
For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, 
a baseline diagnosis and/or the cause of any clinically meaningful elevation must be 
understood and recorded in the electronic Case Report Form (eCRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening, 
repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically 
relevant increase. In case of a clinically relevant increase, inclusion of the subject must be 
discussed with the Medical Monitor.
23. Subjects with any other condition which, in the Investigator's judgment, would make the 
subject unsuitable for inclusion in the study.
24. Subjects with erythrodermic, guttate, pustular form of PSO or drug-induced PSO.
25. Subjects with a diagnosis of inflammatory conditions other than AS, including but not 
limited to rheumatoid arthritis or systemic lupus erythematosus. Subjects with a diagnosis of 
Crohn’s disease or ulcerative colitis (whether primary or as an extra-articular manifestation 
of AS) are allowed provided they have no active and/or symptomatic disease at Screening 
and Baseline.
26. Subjects with fibromyalgia or osteoarthritis symptoms that in the Investigator’s judgement 
would have potential to interfere with efficacy assessments
27. Subject has a history of chronic alcohol or drug abuse within the previous year.
28. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review by the Investigator or designee. 
29. Subject has presence of significant uncontrolled neuropsychiatric disorder, active suicidal 
ideation, or positive suicide behavior using the “Baseline” version of the electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS) and the Hospital Anxiety and 
Depression Scale (HADS) with either of the following criteria: 
−
Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted 
attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by 
a positive response (“Yes”) to either Question 4 or Question 5 of the 
“Screening/Baseline” version of the eC-SSRS at screening. 
−
Any subject who develops a HADS-D Depression Score >10 or Anxiety (HADS-A)
score ≥15.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 41 of 143
30. Subject is Investigator site personnel directly affiliated with this study and/or immediate 
families of Investigator site personnel. Immediate family is defined as a spouse, parent, child, 
or sibling, whether biological or legally adopted.
31. Subject is a UCB employee or is an employee of a third-party organization involved in the 
study.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care. 
Subjects should be withdrawn from the study if any of the following events occur:
1. Subject withdraws his/her consent.
2. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
3. The Sponsor or a regulatory agency requests withdrawal of the subject.
Subjects withdrawn from study treatment: 
Subjects should be withdrawn from all study treatment if any of the following events occur: 
4. Subject develops an illness that would interfere with his/her continued participation. 
5. Subject considered as having either a suspected new LTBI or who develops active TB or 
NTMB infection during the study (including but not limited to, conversion demonstrated by 
interferon-gamma release assay [IGRA] or other diagnostic means) must be immediately 
discontinued from IMP, and an unscheduled visit must be conducted as soon as possible, but 
not later than the next regular visit.
The subject must be permanently withdrawn if further examinations result in a diagnosis of 
active TB, or if the subject is diagnosed with LTBI with no initiation of prophylactic 
treatment, prematurely discontinues prophylactic treatment, or, in the opinion of the 
Investigator or Sponsor, is noncompliant with prophylactic TB therapy. 
Confirmed active TB is a serious adverse event (SAE) and must be captured on an SAE 
Report Form and provided to the Sponsor in accordance with SAE reporting requirements. 
As with all SAEs, periodic follow-up reports should be completed as per protocol 
requirements until such time as the TB infection resolves. Additional information on TB 
policies are provided in Section 12.6.5.
6. Subject is noncompliant with the study procedures or medications which may present a risk 
to the safety of the subject in the opinion of the Investigator.
7. Subject uses prohibited concomitant medications as defined in this protocol (Section 7.8.2), 
that may present a risk to the safety of the subject in the opinion of the Investigator and the 
Medical Monitor. This includes subjects who start a biologic other than bimekizumab as 
described in Section 5.1.4.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 42 of 143
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 6.3.1; neutropenia <0.5x109/L; lymphopenia <0.5x109/L. Any 
laboratory value or change judged to be clinically significant by the Investigator should
prompt consideration of whether the subject should continue on IMP. For clarification, 
laboratory values that are markedly abnormal as per Table 19‒2 and Table 19‒3 will be 
flagged to the Investigator and to the medical monitor but do not trigger mandatory 
withdrawal unless listed above (Refer to Section 6.3.1 for withdrawal criteria in relation to 
potential drug-induced liver injury [PDILI].)
9. Subject has active suicidal ideation as indicated by a positive response (“Yes”) to 
Questions 4 or 5 or to the suicidal behavior questions of the “Since Last Visit” version of the 
self-rated eC-SSRS. The subject should be referred immediately to a Mental Healthcare 
Professional and must be withdrawn from the study.
10. Subjects with a HADS-D score ≥15 must be withdrawn. Any subject who develops a 
HADS-D score of >10 during the study should be referred immediately to a Mental 
Healthcare Professional for further evaluation and potential withdrawal by the Investigator.
11. Subjects with newly diagnosed IBD or with IBD flares during the study must:
−
Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist
−
Discontinue IMP and be followed-up until resolution of active IBD symptoms
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact the 
Medical Monitor and UCB study physician to confirm the subject's suitability for continued 
participation in the study.
In an attempt to prevent missing data during the study, efforts will be made to collect data from 
subjects that withdraw early from the study (NRC, 2010). If a subject withdraws from study 
treatment for any of the above criteria (#4 through #10) prior to Week 12, they will be asked to 
return for the study assessments 12 weeks after the first dose (ie, Week 12 Visit) and for the 
SFU Visit (20 weeks after last dose administration). These data will be used in a sensitivity 
analysis which is described in Section 15.7. If any of these criteria occur after Week 12, subjects 
will complete an Early Termination (ET) Visit and the SFU Visit. All subjects who withdraw 
from the study due to an AE must be followed until resolution of the event or until the event is 
considered stable. All subjects who withdraw from the study due to development of a laboratory 
abnormality specified in Criterion #8 must be closely monitored, with additional monitoring of 
hepatic markers every week or every 2 weeks until resolution of the event, the event is 
considered stable, or they have reached the end of the SFU Period for those who at any time have 
an ALT and/or AST >5X but <8X ULN.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow-up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The eCRF must document the primary reason for withdrawal or discontinuation.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 44 of 143
Further details of the IMPs and their specifications are provided in the Investigational Medicinal 
Product Handling Manual.
7.2
Treatments to be administered
The IMP is to be administered in the clinic by study site staff as 2 sc injections. Suitable areas for 
sc injections are the lateral abdominal wall and upper outer thigh. During each dosing visit, each 
of the 2 injections should be administered at a separate injection site. Injection sites should be 
rotated and injections should not be given into areas where the skin is tender, bruised, red or 
hard. 
The IMP (bimekizumab and placebo) will be administered at the times indicated in Table 5‒1. 
The minimum time between doses during the Double-Blind Period should be no less than 
25 days and no more than 31 days and during the Dose-Blind Period should be no less than 
24 days and no more than 32 days. 
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing.
7.3
Packaging
Bimekizumab and placebo will be manufactured, packaged and labeled according to Good 
Manufacturing Practice (GMP) guidelines and applicable laws or regulations. They will be 
suitably packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in the IMP 
Handling Manual.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good Manufacturing 
Practice and will include any locally required statements. If necessary, labels will be translated 
into the local language.
7.5
Handling and storage requirements
Investigational Medicinal Product must be stored under refrigerated conditions (2ºC to 8ºC) 
protected from light. The IMP must not be frozen. 
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access.
Appropriate storage conditions must be ensured either by controlled room temperature or by 
completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a week), showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately communicated to the 
Clinical Project Manager (CPM) (or designee) before further use of the IMP.
Investigational Medicinal Product will be shipped to the study sites in temperature controlled 
containers. Out-of-range shipping or storage conditions must be brought to the attention of the 
Sponsor or designee, immediately. Authorization to use any out-of-range IMP must be 
documented and received prior to dispensing or administering the IMP at the study site. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 45 of 143
7.6
Drug accountability
A Drug Accountability Form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost (due to breakage or wastage), not used, disposed of at the study site, or returned to 
the Sponsor or designee must also be recorded on the appropriate forms. All supplies and 
pharmacy documentation must be made available throughout the study for UCB (or designee) to 
review.
In order to maintain the blind, all IMP documentation (eg, shipping receipts, drug accountability 
logs, and interactive voice or web response system [IXRS] randomization materials) must be 
maintained and accessed by unblinded, trained site personnel only. Designated, unblinded site 
personnel must be appropriately trained and licensed (per country guidelines) to administer 
injections. 
The packaging identifies each kit by a unique number that does not correlate to the contents and 
therefore, does not unblind study site staff. Unblinded study staff will be responsible for 
preparation (breaking tamper proof sticker on kit, etc) of the clinical trial material, including 
recording the administration information on source document.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee.
The Investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers) and unused IMP containers must be reconciled and returned to UCB (or designee), 
preferably in their original package. Onsite destruction of used kits only may be allowed with 
prior approval from the Sponsor or designee after reconciliation. Investigational medicinal 
product intended for the study cannot be used for any other purpose than that described in this 
protocol.
7.7
Procedures for monitoring subject compliance
During the Double-Blind and Dose-Blind Periods, IMP will be administered in the clinic and 
compliance will be determined at the visit by study personnel. Drug accountability must be 
recorded on the Drug Accountability Form.
7.8
Concomitant medication(s)/treatment(s)
All concomitant medications, including over-the-counter products, herbal, traditional remedies, 
vitamin/mineral supplements, other dietary supplements, “nutraceuticals,” and hormones must be 
recorded in the subject’s source documentation (eg, clinical chart) and on the eCRF. This record 
should include the name of the drug, the dose, the route and date(s) of administration, and the 
indication for use.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 46 of 143
7.8.1
Permitted concomitant treatments (medications and therapies)
The following AS medications/treatments are allowed during this study from Baseline onward, 
with the following restrictions (if any):
Nonsteroidal anti-inflammatory drugs and/or joint injections as outlined below. For subjects 
taking NSAID/COX-2 inhibitors at Baseline or at Weeks 16, 24, or 36, a change can be made to 
a different NSAID/COX-2 inhibitor. Changes from an NSAID to a COX-2 inhibitor or from a 
COX-2 inhibitor to an NSAID are permitted up to the maximum approved or tolerated dose 
whichever is lower. Only 1 NSAID/COX-2 inhibitor may be taken at a given time.
•
For subjects not taking NSAID/COX-2 inhibitors at Baseline, Weeks 16, 24, or 36, either can 
be initiated, up to the maximum approved or tolerated dose, whichever is lower. Only 
1 NSAID/COX-2 inhibitor may be taken at a given time.
•
After the NSAID/COX-2 regimen has been optimized, SI joint injection is permitted, either 
unilaterally or bilaterally, performed by a qualified physician. 
•
If the subject does not achieve sufficient response to the above options and/or the 
Investigator feels that a biologic other than bimekizumab is warranted, the subject must 
discontinue from study treatment (bimekizumab) and follow the withdrawal criteria and 
follow up as outlined in Section 6.3.
A decrease in dose or dosing frequency of any agent is permitted for reasons of 
intolerance/AEs/side effects at any time. 
Subjects may be withdrawn from the study or from study medication at any time and continue 
treatment per the Investigator’s discretion, as described in the Withdrawal Section 6.3.
7.8.2
Prohibited concomitant treatments (medications and therapies)
Medications listed in Table 7‒1 are prohibited or restricted as follows:
Table 7‒1:
Prohibited or restricted medications and required wash-out periods 
prior to Baseline
Drug class
Dose
Exclusion criteria
Analgesics, including opioid analgesics
(acetaminophen/paracetamol, etc)
Any dose 
Any ad hoc use in the 24 hours prior to any
study visit. 
Stable doses of analgesics permitted.
NSAIDs/COX-2 inhibitors
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Oral corticosteroids
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Intramuscular (im)/intravenous (iv)/
intra-articular (ia) corticosteroids/bursal 
corticosteroids
Any dose 
Use in the 28 days prior to the Baseline 
Visit. 
Intra-articular hyaluronic acid 
Any dose 
Any use in the 6 months prior to the 
Baseline Visit. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 47 of 143
Table 7‒1:
Prohibited or restricted medications and required wash-out periods 
prior to Baseline
Drug class
Dose
Exclusion criteria
DMARDs:
-azathioprine
-cyclosporine,
-cyclophosphamide,
-mycophenolic acid,
-mycophenylate mofetil
-any other small molecule DMARDs 
(eg tofacitinib, apremilast)
Any dose
Use within 12 weeks prior to the Baseline 
Visit.
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #10 is met
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
DMARDs:
-leflunomide 
Any dose 
Use in the 6 months prior to the Baseline 
Visit unless a cholestyramine washout has 
been performed; in which case, use up to 
28 days prior to the Baseline Visit is 
acceptable. 
TNF inhibitors
-infliximab (IFX)
-adalimumab (ADA)
-etanercept (ETN)
-golimumab (GOL)
-certolizumab pegol (CZP)
Any dose
For IFX, ADA, GOL, and CZP, any use 
within the 12 weeks prior to the Baseline 
Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
This applies to biosimilar versions of any 
TNF inhibitors.
Any non-TNF biologic medications
Any dose
Any exposure history.
ADA=adalimumab; COX-2=cyclooxygenase 2; CZP=certolizumab pegol; DMARD=disease modifying 
antirheumatic drug; ETN=etanercept; GOL=golimumab; HCQ=hydroxychloroquine; IFX=infliximab; 
ia=intra-articular; im=intramuscular; iv=intravenous; MTX=methotrexate; NSAID=nonsteroidal 
anti-inflammatory drug; sc=subcutaneous; SSZ=sulfasalazine; TNF=tumor necrosis factor 
Subjects who are receiving an established anti-depressant regimen should be on a stable dose of 
anti-depressant for 12 weeks prior to Baseline.
7.9
Blinding
Due to differences in presentation of the IMPs (bimekizumab and placebo), special precautions 
will be taken to ensure study blinding and study sites will have blinded and unblinded personnel.
Bimekizumab and placebo injections will be prepared and administered at the investigational 
sites by unblinded, dedicated study personnel according to Table 7‒2. The unblinded personnel 
will not be involved in the study in any way other than assuring the medication is taken from the 
correct kit and prepared according to the pharmacy manual instructions, and administering the 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 48 of 143
drug to the subjects. Preparation will be made from either vials (bimekizumab) or Ampoule 
(placebo) and will be in identical syringe and needle for all arms of the study. Provisions will be 
made to ensure that volume of injection is not revealed to the subject. The number of injections 
will be kept identical for all patients by adding placebo injection when the bimekizumab dose 
requires only 1 injection. 
Table 7‒2:
Preparation of placebo and bimekizumab injections
Treatment Arm
Number/volume Placebo injections
Number/volume bimekizumab
injections
Placebo
2 x 1.0mL
0
Bimekizumab 16mg
1 x 0.1mL
1 x 0.1mL
Bimekizumab 64mg
1 x 0.4mL
1 x 0.4mL
Bimekizumab 160mg
1 x 1.0mL
1 x 1.0mL
Bimekizumab 320mg
0
2 x 1.0mL
Study sites will be required to have a written blinding plan in place, signed by the Principal 
Investigator, which will detail the site’s steps for ensuring that the double-blind nature of the 
study is maintained. 
During the study the Sponsor will provide blinded and unblinded site monitors for the purposes 
of verifying safety, efficacy, and drug administration and documentation records. Blinded study 
monitors and study site personnel, blinded to treatment assignment, will not discuss or have 
access to any drug-related information.
Bioanalytical staff analyzing blood samples for bimekizumab and anti-bimekizumab antibody 
detection will be unblinded. 
Further details are provided in the study manuals and site blinding plan.
7.9.1
Procedures for maintaining and breaking the treatment blind
7.9.1.1
Maintenance of study treatment blind
All subject treatment details (bimekizumab or placebo) will be allocated and maintained by the 
IXRS.
7.9.1.2
Breaking the treatment blind in an emergency situation
The integrity of this clinical study must be maintained by observing the treatment blind. In the 
event of an emergency for which the appropriate treatment for a subject cannot be made without 
knowing the treatment assignment, it will be possible to determine to which treatment arm and 
dose the subject has been allocated by contacting the IXRS. All sites will be provided with 
details of how to contact the system for code breaking at the start of the study. The Medical 
Monitor or equivalent should be consulted prior to unblinding, whenever possible.
The CPM will be informed immediately via the IXRS when a code is broken, but will remain 
blinded to specific treatment information. Any unblinding of the IMP performed by the 
Investigator must be recorded in the source documents and on the Study Termination eCRF 
page.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 49 of 143
7.10
Randomization and numbering of subjects
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by the Sponsor. 
The randomization schedule will be produced by an independent biostatistician with the Contract 
Research Organization (CRO) who is otherwise not involved in this study. Subject treatment 
assignment will be stratified by region and prior TNF inhibitor exposure (yes/no). The IXRS will 
generate individual assignments for subject kits of IMP, as appropriate, according to the visit 
schedule. Enrollment of TNF inhibitor experienced subjects will be limited to 30% of the total 
study population.
At Screening, each subject will be assigned a 5-digit number that serves as the subject identifier 
throughout the study. The subject number will be required in all communication between the 
Investigator or designee and the IXRS regarding a particular subject. 
At the Baseline Visit (Day 1), a subject will be randomized into the study. The Investigator or 
designee will use the IXRS for randomization. The IXRS will automatically inform the 
Investigator or designee of the subject’s ID number. The IXRS will allocate kit numbers to the 
subject based on the subject number during the course of the study.
Subject numbers and kit numbers will be tracked via the IXRS.
8
STUDY PROCEDURES BY VISIT 
The Schedule of Study Assessments (Table 5‒1) provides a general overview of study 
assessments. A list of procedures to be completed at each visit is described below.
Visit windows are +/-3 days from Baseline (Day1, first dose of IMP) at all visits through the 
Week 12 Visit and +/-4 days for all visits after Week 12 except the SFU Visit. For the SFU Visit 
(20 weeks after the last dose), the visit should occur no more than 3 days prior to the scheduled 
visit date and within 7 days after the scheduled visit date (-3 days/+7 days). The minimum of 
time between doses should be no less than 24 days and no more than 32 days. Changes to the 
dosing schedule outside of the allowed windows must be discussed with the Medical Monitor 
and may result in subject withdrawal.
8.1
Screening (Visit 1)
The Screening Period will last up to 28 days. 
Prior to any study specific activities, subjects will be asked to read, sign, and date an Informed 
Consent Form (ICF) that has been approved by the Sponsor and an IEC/IRB, and that complies 
with regulatory requirements. Subjects will be given adequate time to consider any information 
concerning the study given to them by the Investigator or designee. As part of the informed 
consent procedure, subjects will be given the opportunity to ask the Investigator any questions 
regarding potential risks and benefits of participation in the study.
Subjects will also be given the option to participate in the genomic, genetic/epigenetic, and 
proteomic substudy. Subjects who decide to participate in the substudy will need to complete a 
separate ICF following the same procedure and given the same considerations as the main ICF. 
Their willingness to participate in the substudy will be independent from their consent to 
participate in the main study.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 50 of 143
Subjects who initially fail to meet selected eligibility criteria (including but not limited to 
documented completion of LTBI prophylactic therapy) or for whom eligibility assessments could 
not be completed as planned may be rescreened once after discussion with the Medical Monitor.
The following procedures or assessments will be performed at the Screening Visit: 
•
Obtain written informed consent for main study. 
•
Collect demographic data.
•
Collect AS history. 
•
Collect significant past medical history and concomitant diseases.
•
Assess inclusion and no exclusion criteria. 
•
Record prior medications. 
•
Record concomitant medications.
•
eC-SSRS
•
HADS
•
Administer the tuberculosis questionnaire.
•
Measure height. 
•
Measure temperature, pulse, and blood pressure. 
•
Measure weight. 
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB. 
•
Perform an ECG. 
•
Collect samples for hematology/biochemistry/urinalysis. 
•
Perform a serum pregnancy test if the subject is a woman of childbearing potential. This 
requirement also applies to women of childbearing potential with infrequent or irregular 
menstrual cycles and women during menopause. Natural menopause is recognized to have 
occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015). 
•
Collect samples for Hepatitis B and C tests. 
•
Collect samples for an HIV test.
•
Perform an IGRA tuberculosis test.
•
Obtain a chest radiograph, unless one has been obtained 3 months prior to the Screening 
Visit.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 51 of 143
•
Obtain a radiograph of the SI joint. Note: If subject has a previous x-ray documenting AS 
meeting eligibility criteria, he/she is eligible for study entry after reconfirming his/her 
eligibility by central reading. If no x-ray is available one must be performed at Screening. If 
the previous x-ray is more than 1 year old, and central read criteria for randomization are not 
met, another x-ray may be performed if permitted by local guidelines.
•
Register the subject using the interactive voice or web response system (IXRS). 
The MRI (done at selected sites) can be performed prior to the Baseline (Day 1, first dose of 
IMP, Visit 2) if eligibility is confirmed based on screening assessments, and before the first dose 
of IMP. 
8.2
Baseline (Day 1, first dose of IMP) (Visit 2)
The following procedures of assessments will be completed prior to administration of IMP:
•
Review significant past medical history and concomitant diseases to ensure there are no 
significant changes in medical history that would exclude the subject based on the exclusion 
criteria. 
•
Confirm that the subject meets all inclusion and no exclusion criteria. 
•
Record concomitant medications.
•
Record AEs.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Determine the MASES.
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis. 
•
Collect blood sample for CRP. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 52 of 143
•
Collect blood sample for hs-CRP. 
•
Perform a urine pregnancy test if the subject is a woman of childbearing. This requirement 
also applies to women of childbearing potential with infrequent or irregular menstrual cycles 
and women during menopause. Natural menopause is recognized to have occurred after 12 
consecutive months of amenorrhea, for which there is no other obvious pathological or 
physiological cause (International Menopause Society [IMS], 2015).  
•
Collect blood sample for determination of HLA-B27 status.
•
Collect blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
If subject provides consent (separate from the consent for the main study): 
−
Collect blood samples for genomic and proteomic/metabolomic analyses
−
Collect blood samples for genetic/epigenetic analysis
•
For participating centers, collect blood sample for flow cytometry.
•
Obtain MRI of spine and the SI joint if the subject is participating in the MRI substudy. The 
Baseline MRI should be performed after confirmation of eligibility based on screening 
assessments for the study and before the first bimekizumab injection. 
•
Randomize the subject using the IXRS.
•
Administer IMP (bimekizumab or placebo). 
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP 30 minutes and 1 hour after dosing.
8.3
Double-Blind Period (Week 1 to Week 12)
8.3.1
Week 1 (+/-3 days) (Visit 3)
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Measure temperature, pulse, and BP.
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 53 of 143
•
Collect blood sample for bimekizumab plasma concentrations.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects:
−
Collect blood samples for genomic, proteomic/metabolomic analyses.
−
Collect blood sample for genetic/epigenetic analysis.
•
For participating centers, collect blood sample for flow cytometry.
•
Record visit in the IXRS.
8.3.2
Week 2 (+/-3 days) (Visit 4)
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect blood sample for bimekizumab plasma concentrations.
•
Record visit in the IXRS.
8.3.3
Week 4 (+/-3 days) (Visit 5)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 54 of 143
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Measure temperature, pulse, and BP. 
•
Determine the MASES.
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects, collect blood samples for genomic, and proteomic/metabolomic 
analyses.
•
For participating centers, collect blood sample for flow cytometry.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab or placebo). 
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.3.4
Week 8 (+/-3 days) (Visit 6)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
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•
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 55 of 143
•
Measure temperature, pulse, and BP. 
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab or placebo). 
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.3.5
Week 12 (+/-3 days) (Visit 7)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB.
•
Determine the MASES.
•
Determine the BASMI.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 56 of 143
•
Administer the PhGADA. 
•
Perform an ECG. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP. 
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects: 
−
Collect blood samples for genomic and proteomic/metabolomics analyses.
−
Collect blood sample for genetic/epigenetic analysis.
•
For participating centers, collect blood sample for flow cytometry.
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 12 should be 
performed as close to the Week 12 Visit as possible.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab). 
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing (pulse and BP to be collected 30 minutes and 1 hour 
after dosing).
8.4
Dose-Blind Period (Week 16 to Week 48)
8.4.1
Week 16 (+/-4 days) (Visit 8)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 57 of 143
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Measure temperature, pulse, and BP. 
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Evaluation for rescue treatment eligibility (Section 5.1.4).
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.2
Week 20 (+/-4 days) (Visit 9)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.3
Week 24 (+/-4 days) (Visit 10)
The following procedures of assessments will be completed prior to administration of IMP:
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 58 of 143
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB.
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP. 
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects: 
−
Collect blood samples for genomic and proteomic/metabolomic analyses.
−
Collect blood sample for genetic/epigenetic analysis.
•
For participating centers, collect blood sample for flow cytometry.
•
Evaluation for rescue treatment eligibility (Section 5.1.4).
•
Record visit in the IXRS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 59 of 143
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.4
Week 28 (+/-4 days) (Visit 11)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.5
Week 32 (+/-4 days) (Visit 12)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 60 of 143
8.4.6
Week 36 (+/-4 days) (Visit 13)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect blood sample for hs-CRP. 
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Evaluation for rescue treatment eligibility (Section 5.1.4).
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.7
Week 40 (+/-4 days) (Visit 14)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 61 of 143
•
eC-SSRS
•
HADS
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab).
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.8
Week 44 (+/-4 days) (Visit 15)
The following procedures of assessments will be completed prior to administration of IMP:
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Measure temperature, pulse, and BP. 
•
Collect samples for hematology/biochemistry/urinalysis.
•
If there has been a delay in menses, perform a urine pregnancy test.
•
Perform the IGRA tuberculosis test. 
•
Record visit in the IXRS.
•
Administer IMP (bimekizumab). This is the last dose of IMP. 
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing.
8.4.9
Week 48 (+/-4 days) (Visit 16)
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 62 of 143
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight. 
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB.
•
Determine the MASES.
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Perform an ECG.
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP. 
•
Collect blood sample for hs-CRP. 
•
Perform a urine pregnancy test if the subject is a woman of childbearing potential. This 
requirement also applies to women of childbearing potential with infrequent or irregular 
menstrual cycles and women during menopause. Natural menopause is recognized to have 
occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015).  
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects, collect blood samples for genomic and proteomic/metabolomic 
analyses.
•
For participating centers, collect blood sample for flow cytometry.
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 48 should be 
performed as close to the Week 48 Visit as possible.
•
Record visit in the IXRS.
8.5
Early Termination Visit
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 63 of 143
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB.
•
Determine the MASES.
•
Determine the BASMI.
•
Administer the PhGADA
•
Perform an ECG.
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP. 
•
Collect blood sample for hs-CRP. 
•
Perform a urine pregnancy test if the subject is a woman of childbearing potential. This 
requirement also applies to women of childbearing potential with infrequent or irregular 
menstrual cycles and women during menopause. Natural menopause is recognized to have 
occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015).  
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Collect blood samples for cytokines, complement, and biomarker analyses.
•
For consenting subjects, collect blood samples for genomic and proteomic/metabolomic 
analyses.
•
For participating centers, collect blood sample for flow cytometry.
•
Perform an IGRA tuberculosis test.
•
Record visit in the IXRS. 
•
If subject is a PDILI case that results in immediate, permanent IMP discontinuation, conduct 
a thorough evaluation as described in Section 12.5.1.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 64 of 143
8.6
Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final 
dose)
•
Record concomitant medications.
•
Record adverse events.
•
eC-SSRS
•
HADS
•
Administer the AsQoL.
•
Determine the BASDAI. 
•
Determine the BASFI.
•
Administer the SF-36.
•
Administer the MOS Short Sleep Scale.
•
Perform the PGADA.
•
Administer the total and nocturnal spinal pain NRS.
•
Administer the tuberculosis questionnaire.
•
Measure temperature, pulse, and BP. 
•
Measure weight.
•
Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB. 
•
Determine the BASMI.
•
Administer the PhGADA. 
•
Perform an ECG.
•
Collect samples for hematology/biochemistry/urinalysis.
•
Collect a blood sample for CRP. 
•
Collect blood sample for hs-CRP. 
•
Perform a urine pregnancy test if the subject is a woman of childbearing potential. This 
requirement also applies to women of childbearing potential with infrequent or irregular 
menstrual cycles and women during menopause. Natural menopause is recognized to have 
occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015).  
•
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
•
Perform an IGRA tuberculosis test.
•
Record visit in the IXRS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 65 of 143
8.7
Unscheduled Visit
At the Investigator’s discretion, an Unscheduled Visit may be completed at any time during the 
study but prior to the SFU Visit, if deemed necessary for the subject’s safety and well-being. 
If an Unscheduled Visit is conducted due to safety or efficacy reasons, an eC-SSRS assessment 
will be performed with the subject during the visit. If an Unscheduled Visit is conducted for 
reasons other than safety or efficacy concerns (eg, replacement of lost medication, repeated 
collection of a laboratory specimen due to collection or analysis issues) an eC-SSRS will not be 
required at these visits.
At this visit, any of the following assessments may be performed, depending on the reason for 
the visit:
•
Record concomitant medication
•
Record AEs
•
eC-SSRS
•
Vital signs 
•
Physical examination
•
Record 12-lead ECG 
•
If medically indicated, obtain blood sample(s) for:
−
Standard safety laboratory tests (hematology, serum chemistry) 
−
The blood sample may also be used for PK/PD assessments, if needed.
•
Obtain urine sample for standard safety laboratory tests (including urine pregnancy test)
9
ASSESSMENT OF EFFICACY
The timing for all assessments described below is specified in the Schedule of Assessments, 
Table 5‒1. 
9.1
ASAS20, 40, ASAS 5/6 response, and ASAS partial remission
The ASAS20 is defined as an improvement of at least 20% and absolute improvement of at least 
1 unit on a 0 to 10 NRS in at least 3 of the 4 following domains:
•
PGADA (see Section 9.2)
•
Pain assessment (the total spinal pain NRS score; Section 9.3)
•
Function (represented by BASFI, Section 9.4)
•
Inflammation (the mean of the BASDAI questions 5 and 6, [see Section 9.5] 
 
) 
and absence of deterioration in the potential remaining domain [deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit].
The ASAS criteria for 40% improvement are defined as relative improvements of at least 40%, 
and absolute improvement of at least 2 units on a 0 to 10 NRS in at least 3 of the 4 domains and 
no worsening at all in the remaining domain.
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 68 of 143
9.10
MASES
Enthesitis is assessed with MASES. The MASES is an index that measures the severity (ie, 
intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 1 and then summed for a possible 
score of 0 to 13.
9.11
PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 10=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities. 
This assessment by the Investigator should be made blind to the PGADA.
The subject should be asked to consider both joint and skin components in their response to this 
question.
9.12
SF-36
The SF-36 (Version 2, standard recall) is a 36-item generic health-related quality of life 
(HRQoL) instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as 
follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General 
Health (5 items),Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), 
Mental Health (5 items), and 1 item for perceived stability or change in health (Health 
Transition) during the last year. The concepts represented by these domains contribute to 
physical, mental, and social aspects of HRQoL.
In addition to domain scores, the Physical Component Summary and Mental Component 
Summary scores are calculated from the 8 domains (excluding the Health Transition item). 
Component scores appreciate the impact of each domain on physical and mental health status 
(Maruish, 2011). Each of the 8 domain scores and the component summary scores range from 0 
to 100, with a higher score indicating a better health status. The 2 component summary scores 
are standardized with a mean of 50 and a standard deviation (SD) of 10 in the general US 
population. 
9.13
MOS-12
The MOS Sleep Scale is a validated generic self-administered scale measuring specific aspects 
of sleep. The frequency with which each problem has been experienced during the previous 
4 weeks is rated on a 6-point scale ranging from “none of the time” to “all of the time,” except 
sleep quantity, which is reported in hours. All scores are transformed linearly to range from 0 to 
100, again with the exception of the sleep quantity subscale, which is scored in hours. Higher 
scores indicate more of the attribute implied by the scale name (eg, more sleep disturbance, more 
adequate sleep, and greater sleep quantity). The psychometric properties of the MOS Sleep Scale 
have been found to be satisfactory by Hays and colleagues (Hays et al, 2005). The domains of 
interest for this study are the Sleep Disturbance and the Sleep Problems Index II domains. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 69 of 143
9.14
ASQoL
The ASQoL, a validated disease-specific 18-item questionnaire, has been developed specifically 
for measuring HRQoL in subjects with AS (Doward et al, 2003). The ASQoL has been used and 
has shown to be responsive in axSpA (Barkham et al, 2009; Haibel et al, 2008). The ASQoL 
score ranges from 0 to 18 with higher score indicating worse HRQoL. 
9.15
MRI Assessment (SPARCC and ASspiMRI)
While radiography can detect chronic bony changes (eg, sclerosis, erosions, bridging, and 
ankyloses), structural changes generally occur slowly and x-rays are insensitive; therefore, 
changes are difficult to detect in the relatively short duration of a randomized clinical trial. 
Unlike radiography, MRI can be used to visualize inflammation in the SI joints and spine in 
addition to structural lesions. Inflammation of the SI joints and spine is a key feature of AS that 
is potentially amenable to treatment with bimekizumab. If bimekizumab is effective, it is 
expected that reduction in inflammation in the SI joints and spine can be detected using MRI 
within the 48-week Treatment Period of this study. Recently a Danish study demonstrated 
significant changes in in ASspiMRI-a (Berlin modification) and SPARCC MRI-assessed 
inflammation scores and in SPARCC MRI-assessed erosion scores within 12 weeks after 
initiation of adalimumab (see below for further description of these MRI scoring methods). The 
researchers concluded that MRI-assessed structural lesions change rapidly and may have value 
for assessing the effects of disease-modifying treatment in clinical trials (Pedersen SJ et al, 
2016). 
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
20 subjects per treatment arm at Baseline. A central reader will assess Baseline MRIs to identify 
MRI-positive subjects as per the ASAS-Outcome Measures in Rheumatology Clinical Trials 
(OMERACT) criteria. An MRI at Week 12 and Week 48 will be performed for those subjects
who were MRI-positive at Baseline. The Baseline MRI should be performed after confirmation 
of eligibility based on screening assessments for the study and before the first bimekizumab 
injection. Magnetic resonance imaging at Week 12 and Week 48 should be performed as close to 
the Week 12/Week 48 Visit as possible. Additional details for standardized performance and 
processing of MRIs will be provided in an MRI manual. The MRIs will be read centrally by 
readers who are blinded to treatment assignment and chronological order of the MRIs according 
to a charter for independent imaging assessment.  
The following 2 different scoring systems will be utilized to determine changes from Screening 
(Lukas et al, 2007): 
ASspiMRI-a (Berlin modification) score 
This method is a scoring system with a concentration on short-tau-inversion recovery (STIR)
sequences which quantifies changes in 23 disco-vertebral units (DVU) of the spine. A DVU is
defined as the region between 2 virtual lines through the middle of each vertebra. Active 
inflammation is scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension 
on 1 or more consecutive slices that represent the highest level of inflammation in a particular 
VU. There is no grading for erosion in the Berlin modification. The total spine ASspiMRI-a 
score in the Berlin modification can range from 0 to 69. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 70 of 143
SPARCC SI Joint score
This method is a scoring system for assessing the SI joint based on STIR sequences. An 
abnormal increased signal on the STIR sequence represents bone marrow edema. The SI joint is 
divided into 4 quadrants (upper iliac, lower iliac, upper sacral, and lower sacral). The presence of 
increased signal on STIR in each of these 4 quadrants is scored as either 0=normal signal or 
1=increased signal. The maximum score for abnormal signal in the 2 SI joints of 1 coronal slice 
is therefore 8. Joints that include a lesion exhibiting intense signal are each given an additional 
score of 1 per slice (that demonstrate this feature). Each SI joint that includes a lesion 
demonstrating continuous increase signal of depth ≥1cm from the articular surface is also given 
an additional score of 1. The maximum score for a single coronal slice is 12. Scoring is repeated 
in each of 6 consecutive coronal slices, so that the total SI joint SPARCC MRI score can range 
from 0 to 72. 
9.16
Hospital Anxiety and Depression Scale
The HADS was chosen for its well-established psychometric properties and its use in clinical 
research on biological therapy in subjects with chronic plaque psoriasis (Langley et al, 2010; 
Dauden et al, 2009). The HADS scores for anxiety and for depression range from 0 to 21 with 
higher scores indicating worse state. A score below 8 is considered to be normal whereas a score 
of 15 and above is considered severe (Snaith and Zigmond, 1994).
10
ASSESSMENT OF PHARMACOKINETIC, 
PHARMACODYNAMIC, PHARMACOGENOMIC, AND 
PROTEOMIC VARIABLES
Plasma concentrations of bimekizumab, population PK variables (CL/F, V/F) and dose-exposure 
responses (for ASAS40 response) are the PK variables. 
The PD variables are the concentrations of cytokines of relevance to IL-17A/F signaling pathway 
and AS biology. Where local regulations permit, additional blood samples will be collected from 
consenting subjects at specific time points and stored at -80°C for up to 20 years to allow for 
potential exploratory analyses of genomic, genetic/epigenetic, proteomic, and metabolite
biomarkers relevant to the disease biology, disease progression, response to therapy, and 
inflammatory and immune response processes
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5‒1. When these samples are required at a visit during which the subject is 
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. Detailed information on 
sample analysis will be provided in a bioanalytical report.
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES
The immunological variables comprise detection of anti-bimekizumab antibodies related to 
immunogenicity, serum complement concentrations, mononuclear cell subtypes (analyzed by 
flow cytometry/fluorescence-activated cell sorting), and other exploratory biomarkers.
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5‒1. When these samples are required at a visit during which the subject is 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 71 of 143
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. The presence of antibodies to 
bimekizumab will be determined using a validated bioanalytical method. Detailed information on 
sample analysis will be provided in a bioanalytical report.
12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent Form), including any pretreatment and posttreatment 
periods required by the protocol, must be reported in the eCRF even if no IMP was taken but 
specific study procedures were conducted. This includes all AEs not present prior to the initial 
visit and all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
12.1.2
Adverse events of special interest
An AE of special interest (AESI) is any AE that a regulatory authority has mandated be reported 
on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AESI (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should then be reported if an 
alternative etiology is identified during investigation and monitoring of the subject.
12.1.3
Adverse events for special monitoring
UCB has identified AEs for special monitoring (AESM). An AESM is an AE or safety topic for 
which special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB), are considered appropriate. Identified AESM can be of particular 
concern based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or comorbidities and risk factors prevalent in the 
study population.
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 12.6.5), cytopenias, hypersensitivities, suicide 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 72 of 143
ideation or behavior (assessed using the eC-SSRS), depression and anxiety (assessed using the 
HADS, see Section 9.16), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin; see Section 12.5.1), malignancies, and inflammatory bowel 
diseases.
12.1.4
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
12.1.5
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the intensity of an AE in the eCRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria:
•
Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere with 
his/her usual activities and/or is of no clinical consequence
•
Moderate: the AE interferes with the usual activities of the subject or it is of some clinical 
consequence
•
Severe: the subject is unable to work normally or to carry out his/her usual activities, or the 
AE is of definite clinical consequency
Details for completion of the Adverse Event eCRF (including judgment of intensity and 
relationship to IMP) are described in the eCRF Completion Guidelines.
12.1.6
Follow-up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 12.5.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the Patient Safety (PS) database without 
limitation of time.
If an AE is ongoing at the end of the study for a subject, follow-up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow-up. If no follow-up is provided, the 
Investigator must provide a justification. The follow-up will usually be continued for 20 weeks 
after the subject has discontinued his/her IMP.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 73 of 143
12.1.7
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:
•
The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”
•
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
12.1.8
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by providing the completed 
Pregnancy Report and Outcome Form (for contact details see SAE reporting information at the 
beginning of this protocol). The subject should be withdrawn from the study as soon as 
pregnancy is known (by positive pregnancy test), and the following should be completed:
•
The subject should return for the ET Visit.
•
The subject should immediately stop the intake of the IMP.
•
An SFU Visit should be scheduled 20 weeks after the subject has discontinued her IMP.
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome Form provided to the
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome Form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow-up is continued for a period longer than 30 days. If 
the subject is lost to follow-up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s Drug Safety department is the primary contact for any questions related to the data 
collection for the pregnancy, eventual birth, and follow-up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent Form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/ CRO contract monitor for the study. The Investigator will 
complete the Pregnancy Report and Outcome Form and send it to UCB’s PS department (for 
contact details see SAE reporting information at the beginning of this protocol) only after the 
partner has agreed that additional information can be captured and has provided the signed 
Partner Pregnancy Consent Form. UCB’s PS department is also the primary contact for any 
questions related to the data collection for the partner pregnancy, eventual birth, and follow-up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective abortion 
when medically indicated (eg, when pregnancy is endangering life or health of woman or when 
fetus will be born with severe abnormalities), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 74 of 143
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally 
reported using the Investigator SAE Report form.
12.1.9
Suspected transmission of an infectious agent via a medicinal 
product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
12.1.10
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if 
there are associated clinical signs and symptoms or if the act of taking the excess medicine itself 
is an AE or SAE (eg, suicide attempt).
12.1.11
Safety signal detection
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory or ECG results) for which data will be periodically reviewed during the course 
of the study.
In addition, an independent DMC will periodically review and monitor the safety data from this 
study and advise UCB. The DMC membership includes clinicians knowledgeable about the 
disease or the treatment. All members have experience and expertise in clinical trials. Board 
members may not participate in the study as principal or co-Investigators, or as study subject 
care physicians. The duration of membership for the DMC will be inclusive of planned analyses 
for AS0008. The DMC may also be asked to provide a review of final study results, as deemed 
appropriate. The DMC procedures will ensure that data remain blind to the study team and 
Investigators at all times throughout the conduct of the study. The detailed role, scope, 
responsibilities, and complete procedures, as well as the identity of the DMC members, will be 
described in a separate charter document. A cardiovascular adjudication committee will be in 
place for this study. Specific procedures will be outlined in the charter, which will be developed 
by the committee members.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 75 of 143
12.2
Serious adverse events
12.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
•
Death
•
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)
•
Significant or persistent disability/incapacity
•
Congenital anomaly/birth defect (including that occurring in a fetus)
•
Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious.
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 12.1.2], allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.)
•
Initial inpatient hospitalization or prolongation of hospitalization
A patient admitted to a hospital, even if he/she is released on the same day, meets the criteria 
for the initial inpatient hospitalization. An emergency room visit that results in admission to 
the hospital would also qualify for the initial inpatient hospitalization criteria. However, 
emergency room visits that do not result in admission to the hospital would not qualify for 
this criteria and, instead, should be evaluated for 1 of the other criteria in the definition of 
serious (eg, life-threatening adverse experience, important medical event).
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.
Note: Confirmed active TB is always to be considered as an SAE and must be captured on an 
SAE Report Form and provided to the Sponsor in accordance with SAE reporting requirements.
12.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the SAE Reporting section at the 
front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
completed “Investigator SAE Report Form for Development Drug” (SAE report Form) provided 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 76 of 143
by UCB, even if the data are incomplete, or if it is obvious that more data will be needed in order 
to draw any conclusions. Information recorded on this form will be entered into the global PS 
database.
An Investigator SAE report Form will be provided to the Investigator. The Investigator SAE 
Report Form must be completed in English. 
It is important for the Investigator, when completing the SAE report Form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report Form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE report Form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the IB.
12.2.3
Follow-up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 12.5.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the PS database without limitation of time.
12.3
Immediate reporting of adverse events
The following AEs must be reported immediately:
•
SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality
•
Suspected transmission of an infectious agent via a medicinal product
•
AEs of special interest as defined in Section 12.1.2
12.4
Anticipated serious adverse events
The following list of Anticipated SAEs (Table 12‒1) has been identified, as these events are 
anticipated to occur in the population studied in this protocol at some frequency that is 
independent of drug exposure. This original list will remain in effect for the duration of the 
protocol. Note that listed events will not be regarded as anticipated SAEs if they are life 
threatening or if they result in the death of the study subject.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 77 of 143
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 12.2.2.
Table 12‒1: Anticipated serious adverse events for the population of subjects 
with ankylosing spondylitis
MedDRA system organ class
MedDRA preferred term
Skin and subcutaneous tissue disorders
Psoriasis
Eye disorders
Uveitis
Musculoskeletal and connective tissue disorders
Dactylitis
Tendonitis
Atlantoaxial instability
Gastrointestinal disorders
Colitis ulcerative
Crohn's disease
Cardiac disorders
Aortic valve incompetence
Atrial tachycardia
Atrioventricular block
Bundle branch block
Cardiomyopathy
Vascular disorders
Aortitis
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
Nervous system disorders
Cauda equina syndrome
Injury, poisoning and procedural complications
Spinal cord injury
Spinal fracture
Cervical Vertebral fracture
Lumbar Vertebral fracture 
Thoracic Vertebral fracture
Immune system disorders
Amyloidosis
Psychiatric disorders
Depression
MedDRA=Medical Dictionary for Regulatory Activities
Note: Exception: Listed events will not be regarded as anticipated SAEs if they are life threatening or if they result 
in the death of the study subject. 
12.5
Laboratory measurements
Clinical laboratory assessments consist of serum chemistry, hematology, and urinalysis, and 
pregnancy tests (serum or urine) (Table 12‒2). A centralized laboratory will be used to supply all 
laboratory test supplies and analyze all blood and urine samples for hematology, biochemistry 
and urinalysis measurements. Any unscheduled laboratory testing should also be collected using 
the central laboratory. Testing to rule out hepatitis B, hepatitis C, and HIV (see Exclusion 
Criterion #9, Section 6.2) will be performed at Screening in addition to those measurements 
listed in Table 12‒2. 
Specific details regarding the handling and processing of serum chemistry, hematology, and 
urinalysis samples are provided in the study laboratory manuals.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 78 of 143
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
a A serum pregnancy test will be performed at Screening for all women of childbearing potential. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles and 
women during menopause. Natural menopause is recognized to have occurred after 12 consecutive months of 
amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause 
Society [IMS], 2015). A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A 
urine pregnancy test will also be performed at any study visit where there has been a delay in menses. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. 
Pregnancy test results must be negative prior to administering IMP. 
b Both CRP and hs-CRP will be tested at specified visits per Table 5‒1.
12.5.1
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 79 of 143
reported as an AE of special interest (see Section 12.1.2), and, if applicable, also reported as an 
SAE (see Section 12.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.5.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 12.5.1.5). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Table 12‒3 summarizes the approach to investigate PDILI.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 80 of 143
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or AST
Total 
bilirubin
Symptomsa of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consultc
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 12.5.1.4); 
recommended to occur 
at the site with HCP.
Monitoring of liver 
chemistry values at least 
twice per week until values 
normalize, stabilize, or 
return to within baseline 
valuesd
≥3xULN
NA
Yes
≥5xULN
NA
NA
Need for hepatology 
consult to be discussed.( 
required if ALT or AST 
≥8xULN)
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation
≥3xULN (and 
≥2x baseline) 
and <5xULN 
(and ≥2x 
baseline)
<2xULN
No
Discussion with Medical 
Monitor required.
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow-
up requirements).c
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 12.5.1.2).
IMP discontinuation 
required if any of the 
following occur:
•
Subject cannot 
comply with 
monitoring schedule. 
Essential: Every 
attempt must be made 
to have repeat liver 
chemistry values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.5.1.4).
Monitoring of liver 
chemistry values at least 
twice per week for 2 weeks.d
•
Immediate IMP 
discontinuation required 
if liver chemistry values 
continue to increase.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 81 of 143
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or AST
Total 
bilirubin
Symptomsa of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
•
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values continue to 
increase 
•
Liver chemistry 
values remain 
≥3xULN (and 
≥2x baseline) after 2 
weeks of monitoring 
without evidence of 
resolution
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liver chemistry values:
•
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levels remain ≥3xULN 
(and ≥2x baseline) 
without evidence of 
resolutiond
Continue to monitor until 
values normalize, stabilize, 
or return to within baseline 
values.d
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 12.5.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 82 of 143
12.5.1.1
Consultation with Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 12.5.1.4) and SAE report (if applicable).
12.5.1.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring. 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 12‒3 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
12.5.1.3
IMP restart/rechallenge
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, maybe 
fatal, and must not occur.
12.5.1.4
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are included but not 
limited to those listed in Table 12‒4 (laboratory measurements) and Table 12‒5 (additional 
information). Results of the laboratory measurements and information collected are to be 
submitted to the sponsor on the corresponding eCRF. If the medical history of the subject 
indicates a requirement for other assessments not included below, these additional assessments 
should be completed and submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The following measurements are to be assessed (Table 12‒4):
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 83 of 143
Table 12‒4: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophil 
antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
ALT, AST
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 84 of 143
The following additional information is to be collected (Table 12‒5):
Table 12‒5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included.
Pertinent medical history, including the following:
•
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)
•
Adverse reactions to drugs
•
Allergies
•
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)
•
Recent travel 
•
Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, 
should not be used as an explanation for significant AST and/or ALT elevations.)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function
Alcohol and illicit drug use
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury
12.5.1.5
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 12‒3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to baseline. Determination of stabilization is at the discretion of the Investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
12.6
Other safety measurements
12.6.1
Vital signs
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 85 of 143
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing.
12.6.2
Body weight and height
Height is collected at Screening only. The Investigator or designee will measure the height of the 
subject with shoes removed in meters and the weight of the subject in kilograms. The same scale 
should be utilized throughout the study where possible. 
12.6.3
Physical examination
The physical examination should be conducted by the Investigator or designee at the time points 
listed in Table 5‒1 and will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; GI; musculoskeletal; hepatic; neurological (including limb 
reflexes); and mental status. Findings considered clinically significant changes since the physical 
examination at the Screening Visit will be recorded as AEs.  
12.6.4
12-lead electrocardiogram
The Investigator or designee will perform the ECG. The ECGs will be read locally.
12.6.5
Tuberculosis and TB risk factor assessment and management
All subjects will be assessed for TB at Screening and at the time points specified in the Schedule 
of Assessments (Table 5‒1) through physical examination for signs and symptoms of TB, chest 
x-ray (Section 12.6.5.2), laboratory testing (Section 12.6.5.1), and subject questionnaire 
(Section 12.6.5.3). 
At Screening, all subjects will have an IGRA test (QuantiFERON TB GOLD is recommended), a 
chest x-ray (unless already performed within 3 months of screening) and examination for signs 
and symptoms of TB. In addition, each subject will complete a TB questionnaire with questions 
directed at symptoms of TB and potential exposure to TB. 
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen.
Following consultation with the Medical Monitor, subjects may be rescreened after completion 
of at least 8 weeks of LTBI prophylactic therapy.
a.
Known TB infection whether present or past is defined as:
−
Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra-pulmonary)
−
History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection, unless adequately treated and proven to be fully 
recovered upon consult with a TB specialist.
−
Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject’s medical history
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 86 of 143
b. High risk of acquiring TB infection is defined as:
−
Known exposure to another person with active TB infection within the 3 months prior to 
Screening
−
Time spent in a healthcare delivery setting or institution where individuals infected with 
TB are housed and where the risk of transmission of infection is high
c.
Latent TB infection (unless appropriate prophylaxis is initiated at least 8 weeks prior to study 
treatment and continued to completion of prophylaxis) is defined as:
−
The absence of signs, symptoms (ie, evidence of organ-specific involvement), or physical 
findings suggestive of TB infection with a positive IGRA test (or 2 indeterminate IGRA 
test results) and a chest x-ray (or other imaging) without evidence of TB infection. If the 
result of the IGRA test is indeterminate, the particular IGRA test previously performed 
may be repeated once; if positive or indeterminate on retest, the subject may not be 
randomized to IMP without further evaluation, treatment and discussion with Study 
Physician, if Latent TB infection is identified. The retest must be done during the 
protocol-defined Screening window.
Note: If available, respiratory or other specimens must also be smear and culture 
negative for TB (Centers for Disease Control [CDC] diagnosis of LTB infection) 
http://www.cdc.gov/TB/topic /testing/default.htm)
d. Current or history of NTMB infection despite prior or current therapy.
Signs and Symptoms
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s medical or social history. 
The most common primary focus of TB is the lung. Other sites may include gastrointestinal 
system, bone/joints, lymph glands and meninges, etc. However, in immune compromised 
patients and/or patients treated with TNF inhibitors, extra-pulmonary manifestations of TB are
common compared to normal population.
Some common symptoms that the subject may present are dependent on the primary focus of 
infection and may include cough, blood in sputum, night sweats, lymphadenitis, joint 
pain/swelling, spinal deformity, headache/confusion, abdominal pain (mimicking inflammatory 
bowel disease), etc. Unusual presentations should always be considered.
Latent tuberculosis infection is defined in the “Exclusion Criteria” above. If the result of the
IGRA is indeterminate, the particular IGRA previously performed may be repeated once; if 
positive or indeterminate on retest, the subject may not be randomized to IMP without further 
evaluation by a TB specialist. If LTBI or active TB is identified, subject must undergo 
appropriate study specified withdrawal procedures. The retest must be done during the protocol-
defined Screening window. Laboratory diagnosis should be undertaken via mycobacteria culture 
media (or if available by preferred nucleic acid amplification test such as the Xpert 
mycobacterium tuberculosis [MTB] rifampin [RIF] test) and result must be negative for TB 
inducing pathogens.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 87 of 143
Test Conversion
Tuberculosis test conversion is defined as a positive IGRA result for the current test, when 
previous IGRA test results were negative. All subjects with TB test conversion must immediately
stop IMP administration. In case of a TB test conversion, the subject must be considered as 
having either a suspected new latent or an active TB infection and be promptly referred to an 
appropriate specialist (eg, pulmonologist, infectious disease specialist) for further evaluation. If 
test conversion indicates LTBI, active TB, or NTMB then, per UCB TB working instructions, 
TB test conversion (confirmed) should be classified adequately, either as due to LTBI, active TB 
infection, or NTMB, respectively. Additional assessments (eg, blood tests or IGRA, chest x-rays, 
or other imaging) should be performed where medically relevant and documented. Such 
conversions should be reported to the UCB PS function.
Latent TB
In case the evaluation by the appropriate specialist indicates a new LTBI during the study, a 
prophylactic TB treatment should be initiated and the IMP can be continued no sooner than 
4 weeks after start of prophylactic TB treatment, if it is deemed likely by the Investigator that 
prophylactic TB treatment is continued to completion.
If prophylaxis is not initiated, the subject must be withdrawn.
Every related action should be discussed in advance with the Medical Monitor. 
Once withdrawn from study treatment, subjects should return for the ET Visit, complete all 
ET Visit assessments, and complete a SFU Visit (20 weeks after the last dose of IMP).
Active TB or NTMB infection 
Subjects who develop active TB or NTMB infection during the study must be withdrawn from 
the study. The subject must be immediately discontinued from IMP and an ET Visit must be 
scheduled as soon as possible, but no later than the next scheduled visit. The subject should be 
encouraged to keep the SFU Visit as specified by the protocol. Treatment should be started 
immediately.
Note that subjects with history of NTMB or active NTMB infection are excluded from the study 
regardless of prior or current therapy for this condition. 
12.6.5.1
Tuberculosis assessment by IGRA
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD is 
recommended) will be performed at Screening and should be repeated at Week 44, ET, and 
SFU Visits for all subjects. The test results will be reported as positive, negative, or 
indeterminate. UCB also recommends that a TB specialist be consulted where TB (latent or 
active) is suspected or if there are doubts regarding test results. If latent or active TB is 
identified, subject must undergo appropriate study-specified withdrawal procedures. The retest 
during Screening must be done during the protocol-defined Screening window.
12.6.5.2
Chest x-ray for tuberculosis
A plain posteroanterior chest x-ray must be performed in the Screening Period unless one has 
been performed within 3 months prior to the Screening Visit. The chest x-ray (or, if done, 
Computed Axial Tomography of the Chest) must be clear of signs of TB infection (previous or 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 89 of 143
study must be withdrawn and scheduled to return for the ET Visit as soon as possible but no later 
than the next scheduled study visit and complete all ET Visit assessments. 
The subject should be encouraged to complete a SFU Visit (20 weeks after the last dose of IMP).
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed.
12.6.6
Pregnancy testing
A serum pregnancy test will be performed at Screening for all women of childbearing potential. 
This recommendation also applies to women of childbearing potential with infrequent or 
irregular menstrual cycles and women during menopause. Natural menopause is recognized to 
have occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015). 
A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. 
A urine pregnancy test will also be performed at any study visit where there has been a 
delay in menses. This recommendation also applies to women of childbearing potential with 
infrequent or irregular menstrual cycles. 
Pregnancy test results (serum and urine) must be negative prior to administering IMP.
12.6.7
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed by trained study personnel using the eC-SSRS.  
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the eC-SSRS assessments will be performed are specified in the schedule of 
study assessments (Section 5.2). 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Posner et al, 2011; Mundt et al, 2010). 
Subjects respond to standardized clinical questions that are presented in a uniform fashion. The 
eC-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The eC-SSRS takes approximately 3 to 10 minutes to complete.
Refer to Section 6.3 for eC-SSRS-related withdrawal criteria.
13
OTHER STUDY MEASUREMENTS
13.1
Demography
The Investigator or designee will collect demographic information for all subjects according to 
local rules and regulations. This will include age, gender, race and ethnicity. Information on 
demographics will be collected according to local rules and regulations. Demographic 
information will be recorded in the eCRF.
13.2
Medical history
The Investigator or designee will obtain a complete medical history of AS as part of the 
screening assessment and include all clinically relevant past or coexisting medical conditions, 
responses to AS treatment as available, and surgeries. Findings will be recorded in the eCRF.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 90 of 143
13.3
Ankylosing spondylitis history
The Investigator or designee will obtain a detailed history of AS, including the date of onset and 
past treatments for AS. Specific information related to AS history will be recorded in the eCRF.
13.4
Prior and concomitant medications
As part of the medical history, the Investigator or designee will determine prior and concomitant 
medications and record these in the eCRF. 
14
STUDY MANAGEMENT AND ADMINISTRATION 
14.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the CPM of the Sponsor
within 24 hours and follow any local regulatory requirements.
14.2
Monitoring
UCB (or designee) will monitor the study to meet the CRO’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate. Monitoring of the study may be 
delegated by UCB to a CRO or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
14.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of CRFs are not considered acceptable source 
documents. Source documents are original records in which raw data are first recorded. These 
may include hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, 
printouts, pharmacy records, care records, ECG or other printouts, completed scales, or quality of 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 91 of 143
life questionnaires, for example. Source documents should be kept in a secure, limited access 
area.
Sponsor or designee will review to ensure that computerized source documents produced by the 
site are compliant with Food and Drug Administration (FDA) Part 11 requirements and 
document appropriately. Source documents that are computer generated and stored electronically 
must be printed for review by the monitor (eg, ECG reports). Once printed, these copies should 
be signed and dated by the Investigator and become a permanent part of the subject’s source 
documents. The Investigator will facilitate the process for enabling the monitor to compare the 
content of the printout and the data stored in the computer to ensure all data are consistent.
Electronic data records must be saved and stored as instructed by UCB (or designee).
14.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 14.2.1.
14.3
Data handling
14.3.1
Case Report Form completion
This study will use electronic data capture (EDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRF and in all required reports.
This study will also use an electronic device (Site Tablet) to capture patient reported outcomes.
Serious AE reporting will be done using the SAE Report Form (see Section 12.2.2) while also 
entering the event in the appropriate eCRF section. The safety database and the clinical database 
will be reconciled during the study and discrepancies will be corrected as needed.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Access to the EDC will be given after training has been received. A training certificate will be 
provided and filed.
Detailed instructions on the use of the EDC will be provided in the eCRF Completion 
Guidelines.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be re-approved by the Investigator. Any change or correction 
to the eCRF after saving must be accompanied by a reason for the change.
14.3.2
Database entry and reconciliation
Case Report Forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. This study is performed using EDC. The data are entered into the eCRFs once and are 
subsequently verified.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 92 of 143
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in a Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
14.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
14.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
study master file.
14.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 93 of 143
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and applicable regulatory 
requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
14.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
15
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP).
15.1
Definition of analysis sets
The following analysis sets were defined:
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
The Randomized Set (RS) will consist of all randomized subjects.
The Safety Set (SS) will consist of all randomized subjects who received at least 1 dose of IMP.
The Full Analysis Set (FAS) will consist of all randomized subjects who received at least 1 dose 
of IMP and have a valid measurement of the primary efficacy variable at Baseline.
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who had no important protocol 
deviation affecting the primary efficacy variable. The subjects with important protocol deviations 
will be predefined and evaluated during a data evaluation meeting prior to unblinding of the data.
The Pharmacokinetic Per Protocol Set (PK-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations affecting the pharmacokinetic variables, as 
confirmed during ongoing data cleaning meetings prior to database lock.
The Pharmacodynamic Per Protocol Set (PD-PPS) will consist of all randomized subjects who 
took at least 1 dose of IMP and provide at least 1 PD measurement postdose that is without 
important protocol deviation affecting that time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period including the dose at Week 12.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 94 of 143
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36.
15.2
General statistical considerations
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, summary statistics will consist of number of available observations, arithmetic mean, 
SD, median, minimum, and maximum unless stated otherwise.
All statistical tests will be performed 2-sided at a 5% level of significance unless stated 
otherwise.
15.3
Planned efficacy analyses
15.3.1
Analysis of the primary efficacy variable
The primary efficacy variable will be analyzed for all subjects in the FAS.
The dose-response relationship between treatment and ASAS40 response will be assessed with 
an ordered categorical analysis using a non-parametric correlation statistic of Mantel and 
Haenszel (Mantel and Haenszel, 1959) and modified ridit scores with the corresponding p-value. 
The analysis will include region and prior TNF inhibitor exposure as stratification factors. Prior 
TNF inhibitor exposure will be used as stratification factor as it may have an impact on efficacy. 
The use of region as stratification factor is intended to combine study centers in similar 
geographic regions. The geographic regions to be used will be defined in the IXRS and in the 
SAP. The correlation between dose and ASAS40 response will be evaluated at a significance 
level of α=0.05. This evaluation of dose-response will constitute the primary efficacy analysis.
As a supportive analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model
will include fixed effects for treatment, region, and prior TNF inhibitor exposure (yes/no). If the 
logistic regression model is unable to converge, then region may be dropped from the model to 
facilitate convergence. Comparisons will be made for each dose vs placebo at a 2-sided 
significance level of α=0.05. For each dose, the odds ratio vs placebo, the 95% confidence 
interval, and the corresponding p-value will be calculated. 
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a 2-sided significance 
level of α=0.05. This procedure will control the overall Type I error rate. If the dose response 
relationship fails to reach significance at a significance level of α=0.05, then no further testing 
will be conducted and the pairwise comparisons are seen as nonsignificant.
Nonresponder imputation will be used to account for missing data in the primary analysis. That 
is, subjects with a missing ASAS40 score at Week 12 or who discontinued study treatment prior 
to the Week 12 visit will be considered nonresponders for the primary analysis.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
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Page 95 of 143
15.3.1.1
Supportive analyses
The following supportive analyses for the primary endpoint are planned: 
1. The primary dose-response analysis and pairwise comparisons will be repeated for all 
subjects in the PPS to evaluate the effect of important protocol deviations on the analysis. 
2. The primary dose response analysis and pairwise comparisons will be repeated for all 
subjects in the RS to evaluate the consistency of the FAS with the intent-to-treat (ITT) 
principle. Subjects with no valid measurement of the primary efficacy variable at Baseline 
will be included as nonresponders.
3. The primary dose response analysis and pairwise comparisons will also be repeated for all 
individual components of the ASAS40 response to explore the effect of the signs and 
symptoms of the individual components on the composite endpoint. Since all ASAS 
components are continuous variables (eg, change from Baseline in PGADA), and analysis of 
covariance (ANCOVA) with treatment, region, and prior TNF inhibitor exposure as fixed 
effects and the Baseline values as covariate will be used for the analysis.
Additional sensitivity analyses to evaluate the assumptions related to the handling of missing 
data for the primary efficacy variable will be performed and are described in Section 15.7.
15.3.2
Other efficacy analyses
15.3.2.1
Analysis of the secondary efficacy variables
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, ASAS20 response and ASAS5/6) will be analyzed for treatment 
effects using pairwise comparisons based on the same method as that for the primary efficacy 
variable.
All continuous variables (ie, ASDAS-CRP, ASDAS, BASDAI, and BASFI) will be analyzed for 
treatment effects using pairwise comparisons based on an analysis of covariance (ANCOVA) 
model with treatment, region, and biologic prior treatment as fixed effects and the Baseline value 
as covariate.
Pairwise testing of each bimekizumab dose versus placebo will account for multiplicity by using 
a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from 
the highest dose to the lowest dose as described in Section 15.3.1.
Dose and exposure response will be assessed using a nonlinear mixed effects modeling to 
characterize the relationship between dose, exposure and ASAS response. The model will be 
partitioned into structural and stochastic models. The structural model describes the main trends 
and dependencies in the data, for example how drug concentrations depend on dose and time, or 
how ASAS response depend on drug exposure. The stochastic part of the model is further 
divided into the interindividual variability (IIV) and the residual unexplained variability (RUV). 
The IIV describes how individual specific parameters differ from the typical individual. The 
RUV describes the differences between the observations and the predictions from the model. 
Further details will be given in a separate data analysis plan and reported in a separate document.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
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15.3.2.2
Analysis of the other efficacy variables
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS and ESS.
All categorical variables will be summarized using frequency tables by each visit.
All continuous variables will be summarized using descriptive statistics by each visit.
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in days from Baseline until the first date when the response is achieved. 
Subjects who discontinue study treatment prior to achieving a response will be censored at the 
date of study treatment discontinuation. Subjects who reach the Week 12 visit without achieving 
a response will be censored at the date of the Week 12 visit. 
The median time to response including the 2-sided 95% confidence interval will be calculated for 
each treatment. Between group differences (each bimekizumab dose vs placebo will be analyzed 
with the log-rank statistic.
All other efficacy variables will be analyzed using observed cases as treated and imputed with 
NRI for binary variables and multiple imputation (MI) for continuous variables (see 
Section 15.7).
Subjects in the ESS who discontinue with bimekizumab treatment during the Dose-Blind Period 
will be treated as missing and categorical/continuous variables will be imputed.
15.4
Subgroup analyses
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: 
•
Age
•
Gender
•
Region
•
Anti-bimekizumab antibody status
•
TNF inhibitor exposure
•
Concomitant synthetic DMARDs vs no concomitant synthetic DMARDs
•
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
15.5
Planned safety and other analyses
15.5.1
Safety analyses
All safety variables will be analyzed for all subjects in the SS. In addition, safety analyses during 
the Dose-Blind Period will be conducted on all subjects in the DBS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 97 of 143
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®). Adverse events will be summarized descriptively by treatment group, primary 
system organ class, high level term, and preferred term. Additional tables will summarize AEs 
by intensity and relationship to IMP, AEs leading to withdrawal from the study, SAEs, and 
deaths. 
Treatment-emergent AEs will be defined as events that have a start date on or following the first 
administration of study treatment through the final administration of study treatment +140 days 
(covering the 20-week SFU Period). 
Laboratory values, urinary values, ECGs, vital signs, and extent of exposure will be presented 
descriptively by treatment group.
15.5.2
Other analyses
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS. Pharmacodynamic 
variables will be analyzed for all subjects in the PD-PPS.
Pharmacokinetic and PD analyses including the calculation of population estimates for total body 
clearance (CL/F) and volume of distribution (V/F) will be detailed in a separate data analysis 
plan and reported in a separate document. Plasma concentration-time data of bimekizumab and 
ASAS40 responder rates will be used as the PK and PD response. If data merits, a further PK/PD 
analysis on other PD variables may be performed.
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit.
Anti-bimekizumab antibody status will be summarized for each treatment at each scheduled 
visit.
The biomarker data including IL-17A, IL-17F, IL-6, and IL-23 concentrations will be 
summarized for each treatment at each scheduled visit.
In addition to the PD variables, whole blood will be stored to isolate deoxyribonucleic acid 
(DNA) which may be used to examine genetic and epigenetic changes. Analysis will include, but 
not be limited to genotyping of HLA alleles (HLA Cw6, HLAB27, etc).
15.6
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the primary efficacy, key safety, or PK/PD outcomes 
for an individual subject. The criteria for identifying important protocol deviations will be 
defined within the appropriate protocol-specific document. Important protocol deviations will be 
reviewed as part of the ongoing data cleaning process and all important deviations will be 
identified and documented prior to unblinding to confirm exclusion from analysis sets
15.7
Handling of dropouts or missing data
The analysis for the binary primary and secondary efficacy variables will use NRI for handling 
missing data. In NRI, each subject with missing data or who has discontinued double-blind study 
treatment prior to Week 12 will be counted as a nonresponder. Continuous secondary efficacy 
variables will be imputed using MI assuming that missingness is missing at random (MAR).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
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Page 98 of 143
Two sensitivity analyses will be performed for the primary dose response analysis and for the 
supportive analysis (3) (Section 15.3.1.1):
1. An analysis will be performed in which all available data at Week 12 will be considered. 
This analysis will be based on the ordered categorical analysis to evaluate dose-response as 
specified in the primary analysis. However, in this case, subjects will be analyzed according 
to their randomized treatment, even if they discontinued prior to Week 12 and were no longer 
on the randomized study treatment when the assessment was performed at Week 12. Even 
though efforts will be made to collect the primary outcome data for all subjects at Week 12, 
there may still be some subjects for whom Week 12 efficacy data cannot be obtained. In this 
case, the subjects will be assumed to be nonresponders. The estimand here is the difference 
in outcome improvement at the planned endpoint for all randomized participants 
(Mallinckrodt, 2012). This is an estimand of effectiveness to evaluate the de facto hypothesis. 
It should be noted that this measures something different from the primary analysis and could 
be confounded by placebo subjects who withdraw and are subsequently on another active 
medication at the time of the Week 12 assessment. Therefore, the results of this analysis 
should be interpreted in the appropriate context.
An additional sensitivity analysis will be based on observed data only for subjects who are 
still on the initially randomized treatment at Week 12. Subjects with missing data or who 
have prematurely discontinued study treatment will be excluded from the analysis. The same 
procedure described for the primary efficacy analysis of dose response will be used.
Sensitivity analyses will also be performed for the pairwise comparisons of bimekizumab doses 
versus placebo based on ASAS40 response at Week 12. The following analyses will be 
conducted:
1. Missing data will be imputed using MI. In MI, the missing value is replaced by a set of 
plausible values, where each value is a Bayesian draw from the conditional distribution of the 
missing data given the observed data. Intermittent missing data will be imputed using the 
Markov-Chain Monte Carlo [MCMC] method, followed by monotone regression for 
monotone missing data to evaluate the effect of the method for handling missing data on the 
analysis. The ASAS components will be imputed individually and then the ASAS response 
will be calculated using the complete datasets. The multiply imputed data sets will be 
analyzed using a logistic regression model with fixed effects fixed effects for treatment, 
region, and prior TNF inhibitor exposure. Finally, the results will be combined into a single 
inference using Rubin’s rule (Carpenter and Kenward, 2013). This procedure assumes a 
MAR pattern of missingness and corresponds to an estimand of what has been called the 
difference in outcome improvement if all subjects tolerated or adhered to treatment 
(Mallinckrodt et al, 2012).
2. The logistic regression model will be applied where all available data at Week 12 will be 
considered, as described in sensitivity analysis (1) for the primary dose-response efficacy 
analysis.
3. The logistic regression model will be applied where only observed data for subjects still on 
the initially randomized treatment at Week 12 will be considered, as described in sensitivity 
analysis (2) for the primary dose-response efficacy analysis.
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Clinical Study Protocol
Bimekizumab
AS0008
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Page 99 of 143
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model.
Other binary efficacy variables will be imputed using NRI and other continuous efficacy 
variables will be imputed using MI as described above.
15.8
Planned interim analysis and data monitoring
There is 1 interim analysis planned for this study. The interim analysis will be performed after all 
enrolled subjects have completed the 12 weeks Double-Blind Period. 
The objectives of this interim analysis are (i) to analyze the dose:exposure response for the 
ASAS response criteria to determine the optimal therapeutic dose(s) for subsequent studies, and 
(ii) to perform a comprehensive evaluation of all double-blind data of the study. 
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48. 
Safety data will be provided to an independent DMC. The DMC will review those safety data 
periodically. It is not planned for the DMC to review efficacy data, and no formal stopping rules 
will be applied.
15.9
Determination of sample size
A total of 285 subjects (57 in each treatment group) are planned to be randomized in this study. 
The primary efficacy analysis will be based on the FAS. While some randomized subjects may 
not be in the FAS, it is expected that this number will not impact the following calculations.
The sample size is calculated based on the ASAS40 response data from the Phase 3 studies in 
subjects with AS treated with secukinumab (MEASURE 1 and 2; Baeten et al, 2015). The 
ASAS40 response rates at Week 12 were reported to be 40% in both studies for the 
secukinumab 150mg dose while placebo response rates were 18% (MEASURE 1) and 9% 
(MEASURE 2). 
Based on those ASAS40 response rates and preliminary information on the bimekizumab
dose-response profile, ASAS40 response rates of 40.0%, 36.0%, 20.0%, 15.0%, and 12.0% at the 
end of a 12-week Treatment Period for bimekizumab 320mg, bimekizumab 160mg, 
bimekizumab 64mg, bimekizumab 16mg, and placebo have been assumed, respectively. Since 
the loading dose regimen of MEASURE 1 (iv) was different from MEASURE 2 (sc), the 
assumption for placebo response was based primarily on MEASURE 2, but with a weighting 
towards the higher placebo response rate of MEASURE 1.
The sample size for the primary objective of evaluating the dose-response relationship was 
calculated using a 2-sided test for detecting a linear trend across proportions (Nam, 1987) at a 
2-sided significance level of 0.05. Assuming 57 subjects in each treatment group, the test for 
detecting the overall dose response based on ASAS40 response is powered at >99% for the 
subjects with diagnosis of AS (ie, 57 subjects per group).
The sample size calculations were performed using the software nQuery Advisor® 7.0.
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Clinical Study Protocol
Bimekizumab
AS0008
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Page 100 of 143
16
ETHICS AND REGULATORY REQUIREMENTS
16.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the written Informed Consent Form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who conducted 
the informed consent discussion (Investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent Form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection.
If the Informed Consent Form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent Form by the IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization Form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent Form. An
eCRF must not be started, nor may any study specific procedure be performed for a given 
subject, without having obtained his/her written consent to participate in the study.
16.2
Subject identification cards
Upon signing the Informed Consent, the subject or legal representative will be provided with a 
subject identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times.
16.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, Informed
Consent Form, IB, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 101 of 143
and all other subject-related documents to be used for the study to the IRB/IEC for its review and 
approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification.
16.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
16.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 102 of 143
17
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
18
REFERENCES
Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an 
Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373:2534-48.
Barkham N, Keen HI, Coates LC, O'Connor P, Hensor E, Fraser AD, et al. Clinical and imaging 
efficacy of infliximab in HLA–B27–Positive patients with magnetic resonance imaging–
determined early sacroiliitis. Arthritis Rheum. 2009;60:946-54.
Braun J. Axial spondyloarthritis: thoughts about nomenclature and treatment targets. Clin Exp 
Rheumatol. 2012;30:S132-5.
Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379-90.
Braun J, Baraliakos X. Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann 
Rheum Dis. 2011;70(Suppl 1):i97-103.
Braun J, Baraliakos X, Golder W, Brandt J, Rudwaleit M, Listing J, et al. Magnetic resonance 
imaging examinations of the spine in patients with ankylosing spondylitis, before and after 
successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum. 
2003;48:1126-36.
Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 
2010 update of the ASAS/EULAR recommendations for the management of ankylosing 
spondylitis. Ann Rheum Dis. 2011;70:896-904.
Braun J, van der Heijde D. Imaging and scoring in ankylosing spondylitis. Best Pract Res Clin 
Rheumatol. 2002;16:573-604.
Braun J, Zochling J, Baraliakos X, Alten R, Burmester G, Grasedyck K, et al. Efficacy of 
sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis 
and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis. 
2006;65:1147-53.
Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, et al. A new approach to 
defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing 
Spondylitis Functional Index. J Rheumatol. 1994;2:2281-5.
Carpenter JR, Kenward MG. Multiple imputation and its application. Chichester: John Wiley & 
Sons Ltd; 2013.CPMP/EWP/556/95. Points to consider on the clinical investigation of medicinal 
products other than NSAIDS for the treatment of RA. June 2004.
CPMP/ICH/135/95. Note for guidance on good clinical practice. July 2002. 
Dauden E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or
paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol 
Venereol. 2009;23(12):1374-82.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 103 of 143
Diderichsen PM, Cox E (Quantitative Solutions BV, Breda, NL). Comparative effectiveness 
modeling of treatment in ankylosing spondylitis. Final Report. UCB Celltech; 2016 Feb. Project 
report No.: UCB-MBMA-AS-164.
Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, et al. Development of 
the ASQL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 
2003;62:20-6.
Food and Drug Administration. Guidance for Industry. Drug-induced liver injury: premarketing 
clinical evaluation. US Dept of Health and Human Services, Center for Drug Evaluation and 
Research, Center for Biologics Evaluation and Research, 07/2009.
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to 
defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease 
Activity Index. J Rheumatol. 1994;21:2286-91.
Haibel H, Brandt HC, Song IH, Brandt A, Listing J, Rudwaleit M, et al. No efficacy of 
subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann 
Rheum Dis. 2007;66:419-21.
Haibel H, Rudwaleit M, Braun J, Sieper J. Six months open label trial of leflunomide in active 
ankylosing spondylitis. Ann Rheum Dis. 2005;64:124-6.
Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, et al. Efficacy of 
adalimumab in the treatment of axial spondyloarthritis without radiographically defined 
sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial by an 
open-label extension up to week fifty-two. Arthritis Rheum. 2008;58:1981-91. 
Hays RD, Martin SA, Sesti AM, Spritzer KL. Psychometric properties of the Medical Outcomes 
study sleep measure. Sleep Med. 2005;6:41-4.
Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh KC, et al. Estimates of the 
prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis 
Rheum. 2008;58:15-25.
Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewé R, van der Tempel H, Mielants 
H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62:127-32.
International Menopause Society. Cornwall, UK: Menopause Terminology; c2015. 
http://www.imsociety.org/menopause_terminology.php. Accessed 25 Jan 2016.
Ivanov II, Frutos Rde L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, et al. Specific 
microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small 
intestine. Cell Host Microbe. 2008;4:337–49.
Langley RG, Feldman SR, Han C, Schenkel B, Szapary P, Hsu MC, et al. Ustekinumab 
significantly improves symptoms of anxiety, depression, and skin-related quality of life in 
patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-
controlled phase III trial. J Am Acad Dermatol. 2010;63(3):457-65. 
Lukas C, Braun J, van der Heijde D, Hermann K-G A, Rudwaleit M, Ostergaard M, et al. 
Scoring inflammatory activity of the spine by magnetic resonance imaging in ankylosing 
spondylitis: a multireader experiment. J of Rheum. 2007;34:862-70. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 104 of 143
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an 
ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann 
Rheum Dis. 2009;68:18-24.
Mantel N, Haenszel W. Statistical aspects of the Analysis of Data From Retrospective Studies of 
Disease. J Natl Cancer Inst. 1959; 22:719-48.
Maruish ME, editor. User’s manual for the SF-36v2 Health Survey. 3rd ed. Lincoln, RI: 
QualityMetric Incorporated; 2011.
Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG. Feasibility and 
Validation of a Computer-Automated Columbia-Suicide severity Rating Scale Using Interactive 
Voice Response Technology. J Psychiatr Res. 2010;44(16):1224-8.
Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of 
rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007. Arthritis 
Rheum. 2010;62:1576-82.
Nam, JM. A simple approximation for calculating sample sizes for detecting linear trend in 
proportions. Biometrics. 1987;43(3):701-5.
National Research Council Panel on Handling Missing Data in Clinical Trials. The prevention 
and treatment of missing data in clinical trials. Washington DC: National Academies Press. 
2010. Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. 
2015;41(4):545-68.
Pavy S, Brophy S, Calin A. Establishment of the minimum clinically important difference for the 
bath ankylosing spondylitis indices: a prospective study. J Rheumatol. 2005;32:80-5.
Pedersen SJ, Poddubmyy D, Sorensen IJ, Loft A-G, Hindrup JS, Thamsborg G, et al. Course of 
Magnetic Resonance Imaging-Detected Inflammation and Structural Lesions in the Sacroiliac 
Joints of Patients in the Randomized, Double-Blind, Placebo-Controlled Danish Multicenter 
Study of Adalimumab in Spondyloarthritis, as Assessed by the Berlin and Spondyloarthritis 
Research Consortium of Canada Methods. Arthritis and Rheumatology. 2016;68:418-29. 
Poddubnyy D. Axial spondyloarthritis: is there a treatment of choice? Ther Adv Musculoskelet 
Dis. 2013;5:45-54.
Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Märker-Hermann E, Zeidler H, et al. Effect of 
non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial 
spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis. 
2012;71:1616-22.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The 
Columbia-Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From 
Three Multisite Studies With Adolescents and Adults. Am J Psychiatry. 2011;168(12):1266-77.
Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondyloarthritis in the United States: 
estimates from a cross-sectional survey. Arthritis Care Res (Hoboken). 2012;64:905-10.
Rudwaleit M. New approaches to diagnosis and classification of axial and peripheral 
spondyloarthritis. Curr Opin Rheumatol. 2010;22:375-80.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 105 of 143
Rudwaleit M, Haibel H, Baraliakos X, Listing J, Märker-Hermann E, Zeidler H, et al. The early 
disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception 
Cohort. Arthritis Rheum. 2009a;60:717-27.
Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT, et al. The 
Assessment of SpondyloArthritis International Society classification criteria for peripheral 
spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2011;70:25-31.
Rudwaleit M, Landewé R, van der Heijde D, Listing J, Brandt J, Braun J, et al. The development
of Assessment of SpondyloArthritis international Society classification criteria for axial 
spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty 
appraisal. Ann Rheum Dis. 2009b;68:770-6.
Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment 
of SpondyloArthritis International Society (ASAS) handbook: a guide to assess 
spondyloarthritis. Ann Rheum Dis. 2009;68(Supple 2):ii1-44.
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the irritability-
depression-anxiety scale and the Leeds situational anxiety scale manual. 1994.
Woodworth T, Furst DE, Alten R, Bingham C, Yocum D, Sloan V, et al. Standardizing 
assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology 
Common Toxicity Criteria v.2.0. J Rheumatol. 2007;34:1401-14.
van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. 
Assessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of 
America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis 
Rheum. 2005;52:386-94.
van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, et al. Adalimumab 
effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: 
long-term results from the ATLAS trial. Ann Rheum Dis. 2009;68:922-9.
van Tubergen A, Black PM, Coteur G. Are patient-reported outcome instruments for ankylosing 
spondylitis fit-for-purpose for the axial spondyloarthritis patient? A Qualitative and 
Psychometric Analysis. Rheum. 2015;54:1842-51.
van Tubergen A, Debats I, Ryser L, Londoño J, Burgos-Vargas R, Cardiel MH, et al. Use of a 
numerical rating scale as an answer modality in ankylosing spondylitis-specific questionnaires. 
Arthritis Rheum. 2002a;47:242-8.
van Tubergen A, Coenen J, Landewé R, Spoorenberg A, Chorus A, Boonen A, et al. Assessment 
of fatigue in patients with ankylosing spondylitis: a psychometric analysis. Arthritis Rheum. 
2002b;47:8-16.
Ware JE, Kosinski M, Keller SD. SF-36 Physical and Mental Health Summary scales: a user’s 
manual; 1994.
Wells G, Li T, Maxwell L, MacLean R, Tugwell P. Determining the minimal clinically 
important differences in activity, fatigue, and sleep quality in patients with rheumatoid arthritis. J 
Rheumatol. 2007;34:280-9.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 106 of 143
19
APPENDICES
19.1
Modified New York (mNY) Classification Criteria for AS
Table 19‒1: Modified New York (mNY) Classification Criteria for AS
Diagnosis
Clinical criteria:
a.
Low back pain and stiffness for more than 3 months which improves with exercise, but is 
not relieved by rest 
b.
Limitation of motion of the lumbar spine in both the sagittal and frontal planes.
c.
Limitation of chest expansion relative to normal values corrected for age and sex.
Radiologic criterion:
Sacroiliitis grade ≥2 bilaterally or grade 3 to 4 unilaterally
Grading
Definite ankylosing spondylitis if the radiologic criterion is associated with at least 1 clinical 
criterion
AS=ankylosing spondylitis; mNY=modified New York Criteria
Note: A second grading of “probable ankylosing spondylitis” is part of the modified NY criteria, but it is not
applicable for this study. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 107 of 143
19.2
Markedly abnormal laboratory values
Table 19‒2: Definitions of markedly abnormal hematology values
Parameter (RCTC units)
Markedly Abnormal Definition
Low
High
Hemoglobin (g/dL)
<LLN 
AND 
>2.0 decrease from baseline
N/A
Hemoglobin (g/dL)
<8.0
N/A
Leukocytes (total x 1000)
<2.0
N/A
Lymphocytes (x 1000)
<0.5
N/A
Neutrophils (x 1000)
<1.0
N/A
Platelets (x 1000)
<50
N/A
LLN=lower limit of normal; N/A = Not Applicable; RCTC=Rheumatology Common Toxicity Criteria
Data source: modified from Appendix Rheumatology Common Toxicity Criteria v.2.0 presented in 
Woodworth et al, 2007
a Withdrawal criteria for neutrophils is <0.5 (Section 6.3).
Table 19‒3: Definitions of markedly abnormal biochemistry values
Parameter (RCTC units)
Markedly Abnormal Definition
Low 
High
Alkaline Phosphatase
N/A
>3 x ULN
ALT
N/A
>3 x ULN
AST
N/A
>3 x ULN
Calcium (mg/dL)
<7.0
>12.5
Creatinine (mg/dL)
N/A
>1.8 x ULN
Glucose (mg/dL)
<40
>250
Potassium (mmol/L)
<3.0
>6.4
Sodium (mmol/L)
<125
N/A
Total bilirubin
N/A
≥2 x ULN
Uric acid
N/A
≥3 x ULN
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; RCTC=Rheumatology 
Common Toxicity Criteria; ULN=upper limit of normal
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 108 of 143
19.3
Protocol Amendment 1
Rationale for the amendment
The purpose of this protocol amendment is the following:
•
The SAE reporting fax number for the US and Canada was updated.
•
The extra-articular manifestations variable was removed from the other efficacy variables, as 
these will be assessed as AEs. In addition, the other objective regarding extra-articular 
manifestations was updated to be specific to enthesitis. 
•
The number of subjects to be included in the imaging evaluation was increased from 
10 subjects to 20 subjects at Baseline. The MRIs at Weeks 12 and 48 will be performed only 
for subjects who were classified as MRI-positive as per ASAS-OMERACT Criteria at 
Baseline. An MRI can be used to visualize inflammation in the SI joints and spine in addition 
to structural lesions. Inflammation of the SI joints and spine is a key feature of AS that is 
potentially amenable to treatment with bimekizumab. It is expected that reduction in 
inflammation in the SI joints and spine in MRI-positive subjects at Baseline can be detected 
within the 48-week Treatment Period. This effect can not be demonstrated for subjects who 
are MRI-negative at Baseline. Thus, MRI-negative subjects are excluded from the substudy.
•
A clarification that MRI assessments will occur at the Baseline Visit was added to all 
relevant sections.
•
Criteria for the definition of AE intensity were added in response to a regulatory agency 
request. 
•
All study variables have been rearranged for clarification reasons. 
In addition, minor typographical errors were corrected.
Modifications and changes
Global change #1
Abbreviations within the protocol and in the list of abbreviations have been adjusted as needed.
Global change #2
The following global change was made for all visits from Week 4 (Section 8.3.3) through 
Week 44 (Section 8.4.8).
•
Collect pulse and BP once after dosing (any time).
Has been changed to:
•
Collect pulse and BP once after dosing (any time).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 109 of 143
Global change #3
The following appendices and respective in-text references have been removed from the 
protocol.
•
Section 19.3: PGADA (NRS)
•
Section 19.4: Total spinal pain NRS and nocturnal spinal pain NRS
•
Section 19.5: Bath Ankylosing Spondylitis Functional Index (BASFI)
•
Section 19.6: Bath Ankylosing Disease Activity Index (BASDAI)
•
Section 19.7: Lateral spinal flexion
•
Section 19.8: BASMI – linear function
•
Section 19.9: ShortForm (SF36) Questionnaire
•
Section 19.10: MOS Sleep Scale Questionnaire
•
Section 19.11: ASQoL
•
Section 19.12: Tuberculosis Questionnaire
Specific changes
Change #1
Original text: 
Serious adverse event reporting
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA: +1 800 880 6949
or +1 866 890 3175
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 110 of 143
Change #2
Section 1 Summary
Original text:
The secondary objectives of the study are to assess the efficacy of the individual dose regimens 
of bimekizumab compared to placebo, safety and tolerability, PK, PD, immunogenicity, and the 
exposure:response relationship of bimekizumab as it relates to efficacy and safety. The 
secondary efficacy variables include: Change from Baseline in Ankylosing Spondylitis Disease 
Activity Score  C reactive protein (ASDAS-CRP), Assessment in Axial SpondyloArthritis 
International Society 20% response criteria (ASAS20) response, Assessment in Axial 
SpondyloArthritis International Society 5 out of 6 response criteria (ASAS5/6) response, Change 
from Baseline in BASDAI, and Change from Baseline in BASFI, all at Week 12. Safety 
variables include incidence of adverse events (AEs) and serious adverse events (SAEs), 
withdrawal due to AEs, change from Baseline in vital signs, body weight, physical examination, 
ECG, and clinical laboratory variables.
Other objectives are to assess the impact on patient-reported quality of life (fatigue, sleep, and 
pain), extra-articular disease manifestations (uveitis, inflammatory bowel disease [IBD], and 
psoriasis), the impact of administration of bimekizumab on biological pathways relating to 
disease biology and response to therapy via candidate biomarker analysis and to enable genomic 
and proteomic analysis of subject samples and evaluation of the potential for subject 
stratification approaches, and to assess the impact of bimekizumab on inflammatory changes in 
the spine and sacroiliac (SI) joint using magnetic resonance imaging (MRI) in a subset of 
subjects (approximately 10 subjects per treatment arm). 
Has been changed to: 
The secondary objectives of the study are to assess the efficacy of the individual dose regimens 
of bimekizumab compared to placebo, safety and tolerability, PK, PD, immunogenicity, and the 
exposure:response relationship of bimekizumab as it relates to efficacy and safety. The 
secondary efficacy variables include: Change from Baseline in Ankylosing Spondylitis Disease 
Activity Score C-reactive protein (ASDAS-CRP), Assessment in Axial SpondyloArthritis 
International Society 20% response criteria (ASAS20) response, Assessment in Axial 
SpondyloArthritis International Society 5 out of 6 response criteria (ASAS5/6) response, Change 
from Baseline in BASDAI, and Change from Baseline in BASFI, all at Week 12. Safety 
variables include incidence of adverse events (AEs), serious adverse events (SAEs), and 
withdrawal due to AEs as secondary safety variables and change from Baseline in vital signs, 
body weight, physical examination, ECG, and clinical laboratory variables as other safety 
variables.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 111 of 143
Other objectives are to assess the impact on patient-reported quality of life (fatigue, sleep, and 
pain), extra articular disease manifestations (uveitis, inflammatory bowel disease [IBD], and 
psoriasis), the impact of administration of bimekizumab on biological pathways relating to 
disease biology and response to therapy via candidate biomarker analysis, and to enable genomic 
and proteomic analysis of subject samples and evaluation of the potential for subject 
stratification approaches, and to assess the impact of bimekizumab on inflammatory changes in 
the spine and sacroiliac (SI) joint using magnetic resonance imaging (MRI) in a subset of 
subjects (approximately 10 subjects per treatment arm at Baseline). 
Change #3 
Section 2.1.1 Clinical studies
Original text: 
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, and PA0007 in 53 subjects with 
PsA.
Has been changed to: 
Four clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, PA0007 in 53 subjects with PsA, 
and UP0031 in 12 healthy volunteers.
Change #4
Section 2.1.1 Clinical studies
The following text has been added: 
UP0031 was a Phase 1, open-label, parallel-group, randomized, single-dose study to evaluate the 
BA, PK, and tolerability of 2 different formulations of bimekizumab in healthy subjects. There 
were no treatment-emergent adverse events (TEAEs) leading to discontinuation, and no SAEs or 
fatalities were reported. 
Change #5
Section 2.1.1 Clinical studies
Original text: 
Two additional studies of bimekizumab are ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
(CZP; Cimzia®) therapy in subjects with moderate to severe RA. UP0031 is an open-label, 
parallel-group, single-dose study designed to evaluate the relative bioavailability and tolerability
of 2 dose levels of UCB4940 (bimekizumab) given as 2 x80mg or 1x 160mg given via sc 
injection in healthy subjects.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 112 of 143
Has been changed to: 
One additional study of bimekizumab is ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
(CZP; Cimzia®) therapy in subjects with moderate to severe RA. UP0031 is an open label, 
parallel group, single dose study designed to evaluate the relative bioavailability and tolerability
of 2 dose levels of UCB4940 (bimekizumab) given as 2 x80mg or 1x 160mg given via sc 
injection in healthy subjects.
Change #6
Section 3.3 Other objectives
Original text: 
To assess extra-articular disease manifestations (enthesitis, uveitis, inflammatory bowel disease, 
and psoriasis)
Has been changed to: 
To assess the impact on extra articular disease manifestations (enthesitis, uveitis, inflammatory 
bowel disease, and psoriasis) enthesitis
Change #7
Section 4 Study Variables
Original text: 
4
STUDY VARIABLES
4.1 Efficacy variable(s)
4.1.1 Primary efficacy variable
The primary efficacy variable for this study is as follows:
•
ASAS40 response at Week 12 
4.1.2 Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Change from Baseline in ASDAS-CRP at Week 12
•
ASAS20 response at Week 12
•
ASAS5/6 response at Week 12
•
Change from Baseline in BASDAI at Week 12 
•
Change from Baseline in BASFI at Week 12
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 113 of 143
4.1.3 Other efficacy variables
Other efficacy variables will be assessed as specified in Table 5‒1 (analyses at all time points not 
specified in Section 4.1.1 or Section 4.2.1 are exploratory):
•
ASAS40 response
•
Time to ASAS40 response
•
Change from Baseline in ASDAS-CRP
•
ASDAS status (eg, inactive disease, moderate, high and very high disease activity)
•
ASAS20 response 
•
Time to ASAS20 response
•
ASAS5/6 response
•
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) 
•
ASAS partial remission 
•
Change from Baseline in BASDAI 
•
Change from Baseline in BASFI 
•
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
•
Occurrence of extra-articular manifestations
−
Uveitis flares (as determined by an ophthalmologist or other eye specialist, as 
appropriate)
−
Inflammatory bowel disease flares (as determined by a gastroenterologist, as appropriate)
−
Psoriasis disease activity
•
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
•
Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Change from Baseline in total and nocturnal spinal pain (NRS)
•
Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
•
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey) 
•
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
•
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 114 of 143
•
Change from Baseline in: 
−
Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index for Assessment 
of Spinal Inflammation in AS, and 
−
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score 
•
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores 
•
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.2 PK and PD variables
4.2.1 PK variables
The PK variables are plasma concentrations of bimekizumab, total body clearance (CL/F), and 
volume of distribution (V/F)
4.2.2 PD variables
The PD variables are concentrations of cytokines of relevance to the IL-17A/F signaling pathway 
and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-6, and TNFα 
4.3 Pharmacogenomic variables
4.3.1 Genomic, proteomic, and metabolite variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes. 
4.4 Immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers. 
•
Anti-bimekizumab antibody detection prior to and following study treatment
•
Serum complement concentrations.
•
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
CD19, CD4, CD8, and CD69 (using fluorescence activated cell sorting). 
•
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 115 of 143
4.5 Safety variables
Safety variables to be assessed as specified in Table 5‒1 are as follows: 
•
Incidence of AEs and SAEs
•
Withdrawal due to AEs
•
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight 
•
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas [QTcB and QTcF]), 
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Has been changed to:
4
STUDY VARIABLES
4.1 Primary variable(s)
4.1.1 Primary efficacy variable
The primary efficacy variable for this study is as follows:
•
ASAS40 response at Week 12 
4.2 Secondary variables
4.2.1 Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Change from Baseline in ASDAS-CRP at Week 12
•
ASAS20 response at Week 12
•
ASAS5/6 response at Week 12
•
Change from Baseline in BASDAI at Week 12 
•
Change from Baseline in BASFI at Week 12
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 116 of 143
4.2.2 Secondary safety variables
Assessment time points for safety variables are specified in Table 5‒1. Variables are as follows: 
•
Incidence of AEs and SAEs
•
Withdrawal due to AEs
4.3 Other variables
4.3.1 Other efficacy variables
Assessment time points for the other efficacy variables are specified in Table 5‒1 (analyses at 
all time points not specified in Section 4.1.1 or Section 4.2.1 are exploratory). Variables are as 
follows:
•
ASAS40 response
•
Time to ASAS40 response
•
Change from Baseline in ASDAS-CRP
•
ASDAS status (eg, inactive disease, moderate, high and very high disease activity)
•
ASAS20 response 
•
Time to ASAS20 response
•
ASAS5/6 response
•
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) 
•
ASAS partial remission 
•
Change from Baseline in BASDAI 
•
Change from Baseline in BASFI 
•
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
•
Occurrence of extra articular manifestations
Uveitis flares (as determined by an ophthalmologist or other eye specialist, as 
appropriate)
−
Inflammatory bowel disease flares (as determined by a gastroenterologist, as appropriate)
Psoriasis disease activity
•
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
•
Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
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Change from Baseline in total and nocturnal spinal pain (NRS)
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Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 117 of 143
•
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey) 
•
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
•
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
•
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−
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of Spinal Inflammation in AS, and 
−
Ankylosing Spondylitis spine MRI- activity (ASspiMRI-a) in the Berlin modification 
score 
•
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores 
•
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.3.2 Other safety variables
Assessment time points for other safety variables are specified in Table 5‒1. Variables are as 
follows: 
•
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight 
•
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas [QTcB and QTcF]), 
including changes from Baseline Electrocardiogram (ECG) variables 
•
Change from Baseline in clinical laboratory variables (hematology, biochemistry, and 
urinalysis)
4.3.3 Other PK and PD variables
•
The PK variables are plasma concentrations of bimekizumab, total body clearance (CL/F), 
and volume of distribution (V/F).
•
The PD variables are concentrations of cytokines of relevance to the IL-17A/F signaling 
pathway and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-6, and 
TNFα. 
4.3.4 Other immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers. 
•
Anti-bimekizumab antibody detection prior to and following study treatment
•
Serum complement concentrations.
•
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
CD19, CD4, CD8, and CD69 (using fluorescence activated cell sorting). 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 118 of 143
4.3.5 Other pharmacogenomic, proteomic, and metabolite variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes. 
Change #8
Section 5.1.2 Double-Blind Period
Original text: 
At Baseline/Day 1, subjects will be randomized 1:1:1:1:1 (stratified by region and prior TNF 
inhibitor exposure) to receive the following blinded IMP treatment regimens at the clinical site. 
The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% of 
the total study population. Therefore, each arm will have approximately 18 TNF inhibitor 
experienced subjects in a total of 57 subjects per arm.
Has been changed to:
At Baseline/Day 1, subjects will be randomized 1:1:1:1:1 (stratified by region and prior TNF 
inhibitor exposure) to receive the following blinded IMP treatment regimens at the clinical site. 
The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% of 
the total study population. Therefore, each arm will have approximately 18 TNF inhibitor 
experienced subjects in a total of 57 subjects per arm.
Change #9
Section 5.1.7 Radiographic evaluation
Original text: 
5.1.7 Radiographic evaluation
In a subpopulation of AS0008, MRIs of the spine and SI joints will be performed in 
approximately 10 subjects per treatment arm at Baseline, Week 12, and Week 48. Analyses will 
be exploratory in nature and will be performed at selected sites.
Has been changed to:
5.1.7 Imaging evaluation
In a subpopulation of AS0008, MRIs of the spine and SI joints will be performed in 
approximately 20 subjects per treatment arm at Baseline. Magnetic resonance imaging at
Week 12 and Week 48 will be performed only for subjects who are MRI-positive at Baseline
based on an ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) 
assessment. The Baseline MRI should be performed after confirmation of eligibility for the 
study based on screening assessments and before the first bimekizumab injection. Magnetic 
resonance imaging at Week 12 and Week 48 should be performed as close to the 
Week 12/Week 48 Visit as possible. Further details are provided in Section 9.15. Analyses 
will be exploratory in nature and will be performed at selected sites.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 119 of 143
Change #10
Section 5.2 Table 5-1, footnote d
Original text: 
d At Baseline/Day 1 and Week 1, collect pulse and BP prior to drug administration and then at 30 minutes and 1 
hour after dosing. At all other visits collect pulse and BP prior to drug administration and once after dosing (any 
time). All other procedures are done prior to dosing. 
Has been changed to:
d At Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 30 minutes and 1 
hour after dosing. At all other visits collect pulse and BP prior to drug administration and once after dosing (any 
time). All other procedures are done prior to dosing. 
Change #11
Section 5.2 Table 5-1, footnote n and p
Original text: 
n An MRI of the spine and sacroiliac joints will be performed in a subpopulation of approximately 10 subjects per 
treatment arm for exploratory purposes at Screening, Week 12, and Week 48. The MRI will be read centrally. 
p The minimum time between doses during the Double-Blind Period should be no less than 26 days and no more 
than 30 days and during the Dose-Blind Period should be no less than 24 days and no more than 32 days.
Has been changed to:
n An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 20 subjects per 
treatment arm at Screening Baseline. A central reader will assess Baseline MRIs to identify MRI-positive 
subjects as per the ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria. An 
MRI at Week 12 and Week 48 will be performed for those subjects who were MRI-positive at Baseline. The 
Baseline MRI should be performed after confirmation of eligibility based on screening assessments for the 
study and before the first bimekizumab injection. Magnetic resonance imaging at Week 12 and Week 48 
should be performed as close to the Week 12/Week 48 Visit as possible. For logistical reasons, it may not be 
possible to schedule the MRIs at the actual visit date and an additional visit for the MRI may be required.
p The minimum time between doses during the Double-Blind Period should be no less than 25 days and no more 
than 31 days and during the Dose-Blind Period should be no less than 24 days and no more than 32 days.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 120 of 143
Change #12
Section 6.2 Inclusion criterion 11
Original text: 
11. Subjects taking sulfasalazine (up to 3mg/day) or hydroxychloroquine (up to 400mg per day 
total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, 
with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule 
should remain stable up to Week 16.  
Has been changed to: 
11. Subjects taking sulfasalazine (up to 3mg/day) or hydroxychloroquine (up to 400mg per day
total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, 
with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule 
should remain stable up to Week 16
Change #13
Section 6.2, Inclusion criterion 12
Original text: 
12. Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have: 
−
experienced an inadequate response to previous treatment given for at least 3 months 
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
−
lost access to TNF inhibitor for other reasons
Has been changed to: 
12. Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have: 
−
experienced an inadequate response to previous treatment given for at least 3 months
12 weeks
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
−
lost access to TNF inhibitor for other reasons
Change #14
Section 6.2 Exclusion criterion 3
Original text: 
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 3 months or at least 5 half-lives whichever is greater.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 121 of 143
Has been changed to:
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 3 months 12 weeks or at least 5 half-lives whichever is greater.
Change #15
Section 6.2 Exclusion criterion 10
Original text: 
10. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), 
Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
Has been changed to:
12. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), 
Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
Change #16
Section 6.3 Withdrawal criterion 8
Original text: 
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 6.3.1; neutropenia <0.5x109/mL; lymphopenia <0.5x109/mL. Any 
laboratory value or change judged to be clinically significant by the Investigator, and/or any 
lab values meeting the Rheumatology Common Toxicity Criteria (RCTC) Grade 4 criteria 
(with the exception of neutrophils which will be permitted with the above withdrawal 
criterion [neutropenia <0.5x109/mL]; Table 19‒2 and Table 19‒3) must be discussed with the 
medical monitor before the subject is dosed again. (Refer to Section 6.3.1 for withdrawal 
criteria in relation to potential drug-induced liver injury [PDILI].)
Has been changed to: 
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 6.3.1; neutropenia <0.5x109/mL; lymphopenia <0.5x109/mL. Any
laboratory value or change judged to be clinically significant by the Investigator should 
prompt consideration of whether the subject should continue on IMP. For clarification, 
laboratory values that are markedly abnormal as per Table 19-2 and Table 19‒3 will be 
flagged to the Investigator and to the medical monitor but do not trigger mandatory 
withdrawal unless listed above and/or any lab values meeting the Rheumatology Common 
Toxicity Criteria (RCTC) Grade 4 criteria (with the exception of neutrophils, which will be 
permitted with the above withdraw criterion [neutropenia <0.5x109/mL]; Table 19 2 and 
Table 19 3) must be discussed with the medical monitor before the subject is dosed again
(Refer to Section 6.3.1 for withdrawal criteria in relation to potential drug induced liver 
injury [PDILI].)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 122 of 143
Change #17
Section 7.3 Packaging
The following text has been added: 
Bimekizumab and placebo will be packaged and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. They will be suitably 
packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in 
the IMP Handling Manual.
Change #18
Section 7.8.2 Prohibited concomitant treatments (medications and therapies), 
Table 7-1
Original text: 
Drug class
Dose
Exclusion criteria
Analgesics, including opioid analgesics 
(acetaminophen/paracetamol, etc)
Any dose 
Any ad hoc use in the 24 hours prior to any 
study visit. 
Stable doses of analgesics permitted.
NSAIDs/COX-2 inhibitors
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Oral corticosteroids
Any dose regimen
Any change in dose/dose regimen in the 
28 days prior to the Baseline Visit
Intramuscular (im)/intravenous (iv)/
intra-articular (ia) corticosteroids/bursal 
corticosteroids 
Any dose 
Use in the 28 days prior to the Baseline 
Visit. 
Intra-articular hyaluronic acid 
Any dose 
Any use in the 6 months prior to the 
Baseline Visit. 
DMARDs:
-azathioprine
-cyclosporine,
-cyclophosphamide,
-mycophenolic acid,
-mycophenylate mofetil
-any other small molecule DMARDs 
(eg tofacitinib, apremilast)
Any dose
Use within 12 weeks prior to the Baseline 
Visit.
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #10 is met
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 123 of 143
Drug class
Dose
Exclusion criteria
DMARDs:
-leflunomide 
Any dose 
Use in the 6 months prior to the Baseline 
Visit unless a cholestyramine washout has 
been performed; in which case, use up to 
28 days prior to the Baseline Visit is 
acceptable. 
TNF inhibitors
-infliximab (IFX)
-adalimumab (ADA)
-etanercept (ETN)
-golimumab (GOL)
-certolizumab pegol (CZP)
Any dose
For IFX, ADA, GOL, and CZP, any use 
within the 3 months prior to the Baseline 
Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
This applies to biosimilar versions of any 
TNF inhibitors.
Has been changed to: 
Drug class
Dose
Exclusion criteria
Analgesics, including opioid analgesics 
(acetaminophen/paracetamol, etc)
Any dose 
Any ad hoc use in the 24 hours prior to any 
study visit. 
Stable doses of analgesics permitted.
NSAIDs/COX-2 inhibitors
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Oral corticosteroids
Any dose regimen
Any change in dose/dose regimen in the 28
14 days prior to the Baseline Visit
Intramuscular (im)/intravenous (iv)/
intra-articular (ia) corticosteroids/bursal 
corticosteroids 
Any dose 
Use in the 28 days prior to the Baseline 
Visit. 
Intra-articular hyaluronic acid 
Any dose 
Any use in the 6 months prior to the 
Baseline Visit. 
DMARDs:
-azathioprine
-cyclosporine,
-cyclophosphamide,
-mycophenolic acid,
-mycophenylate mofetil
-any other small molecule DMARDs 
(eg tofacitinib, apremilast)
Any dose
Use within 12 weeks prior to the Baseline 
Visit.
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #10 is met
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 124 of 143
Drug class
Dose
Exclusion criteria
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
DMARDs:
-leflunomide 
Any dose 
Use in the 6 months prior to the Baseline 
Visit unless a cholestyramine washout has 
been performed; in which case, use up to 
28 days prior to the Baseline Visit is 
acceptable. 
TNF inhibitors
-infliximab (IFX)
-adalimumab (ADA)
-etanercept (ETN)
-golimumab (GOL)
-certolizumab pegol (CZP)
Any dose
For IFX, ADA, GOL, and CZP, any use 
within the 3 months 12 weeks prior to the 
Baseline Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
This applies to biosimilar versions of any 
TNF inhibitors.
Change #19
Section 8.1 Screening (Visit 1)
The following paragraphs have been added: 
Subjects who initially fail to meet selected eligibility criteria (including but not limited to 
documented completion of LTBI prophylactic therapy) or for whom eligibility assessments 
could not be completed as planned may be rescreened once after discussion with the 
Medical Monitor.
The MRI (done at selected sites) can be performed prior to the Baseline (Day 1, first dose of 
IMP, Visit 2) if eligibility is confirmed based on screening assessments, and before the first 
dose of IMP.
Change #20
Section 8.2 Baseline (Day 1, first dose of IMP) (Visit 2)
Original text:
•
Obtain MRI of spine and the SI joint if the subject is participating in the MRI substudy. 
Has been changed to: 
•
Obtain MRI of spine and the SI joint if the subject is participating in the MRI substudy. The 
Baseline MRI should be performed after confirmation of eligibility based on screening 
assessments for the study and before the first bimekizumab injection.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 125 of 143
Change #21
Section 8.3.5 Week 12 (+/-3 days) (Visit 7)
Original text: 
The following procedures of assessments will be completed prior to administration of IMP:
…
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy. 
…
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing (any time).
Has been changed to: 
The following procedures of assessments will be completed prior to administration of IMP:
…
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 12 
should be performed as close to the Week 12 Visit as possible.
…
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing (any time pulse and BP to be collected 30 minutes 
and 1 hour after dosing).
Change #22
Section 8.4.9 Week 48 (+/-4 days) (Visit 16)
Original text: 
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 126 of 143
Has been changed to: 
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 48 
should be performed as close to the Week 48 Visit as possible.
Change #23
Section 9.1 ASAS20, 40, ASAS 5/6 response, and ASAS partial remission
Original text: 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and CRP as more objective measures (Brandt et al, 2004).
Has been changed to: 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and hs-CRP as more objective measures (Brandt et al, 
2004).
Change #24
Section 9.7 Spinal mobility
Original text: 
Lateral spinal flexion is measured with the subject’s heels and back resting against the wall with 
no flexion in the knees and no bending forward. The subject lets the arm hang normally with the 
palm of the hand resting against the outer thigh and the fingers extended. A mark is drawn on the 
thigh at the tip of the middle finger. The subject is then asked to bend sideways without bending 
the knees or lifting the heels, while sliding the hand down the thigh. At the point of furthest 
reach, another mark is drawn at the tip of the middle finger. The distance between the first and 
second mark is measured to the nearest 0.1cm. An alternative method is to measure the distances 
to the 2 lines from the floor and record the difference. The better of 2 tries is recorded for left 
and right separately. The mean of the left and right is reported for lateral spine flexion (in cm to 
the nearest 0.1cm) (Sieper et al, 2009) (Appendix Section 19.7).
Has been deleted. 
Change #25
Original text: 
Section 9.10 BASFI
The BASFI is described in Section 9.4 above.
Has been deleted. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 127 of 143
Change #26
Section 9.12 Extra-articular manifestations
Original sections and text:
Information regarding uveitis, enthesitis, inflammatory bowel disease, and psoriasis disease 
activity will be captured. Enthesitis is assessed via MASES.
Section 9.13 MASES
The MASES is an index that measures the severity (ie, intensity and extent) of enthesitis through 
the assessment of 13 entheses (bilateral costochondral 1, costochondral 7, anterior superior iliac 
spine, posterior iliac spine, iliac crest and proximal insertion of the Achilles tendon sites, and the 
fifth lumbar vertebral body spinous process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 
1 and then summed for a possible score of 0 to 13.
Have been merged and changed to: 
Section 9.12 Extra artucilar manifestations
Information regarding uveitis, enthesitis, inflammatory bowel disease, and psoriasis disease 
activity will be captured. Enthesitis is assessed via MASES.
Section 9.10 MASES
Enthesitis is assessed with MASES. The MASES is an index that measures the severity (ie, 
intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 1 and then summed for a possible 
score of 0 to 13.
Change #27
Section 9.12 PhGADA
Original text: 
9.14 PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 100=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 128 of 143
Has been changed to: 
9.11 PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 100 10=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities.
Change #28
Original text: 
Section 9.15 Total and nocturnal spinal pain
Assessment of total and nocturnal spinal pain was described above in Section 9.3.
Has been deleted. 
Change #29
Section 9.15 MRI Assessment (SPARCC and ASspiMRI), paragraph 2
Original text: 
9.19 MRI Assessment (SPARCC and ASspiMRI)
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
10 subjects per treatment arm at Screening, Week 12, and Week 48. Additional details for 
standardized performance and processing of MRIs will be provided in an MRI manual. The 
MRIs will be read centrally by readers who are blinded to treatment assignment and 
chronological order of the MRIs according to a charter for independent imaging assessment.  
Has been changed to:
9.15 MRI Assessment (SPARCC and ASspiMRI)
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
20 subjects per treatment arm at Screening Baseline. A central reader will assess Baseline 
MRIs to identify MRI-positive subjects as per the ASAS-Outcome Measures in 
Rheumatology Clinical Trials (OMERACT) criteria. An MRI at Week 12 and Week 48 will 
be performed for those subjects who were MRI-positive at Baseline. The Baseline MRI 
should be performed after confirmation of eligibility based on screening assessments for 
the study and before the first bimekizumab injection. Magnetic resonance imaging at 
Week 12 and Week 48 should be performed as close to the Week 12/Week 48 Visit as 
possible. Additional details for standardized performance and processing of MRIs will be 
provided in an MRI manual. The MRIs will be read centrally by readers who are blinded to 
treatment assignment and chronological order of the MRIs according to a charter for independent 
imaging assessment.  
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 129 of 143
Change #30
Section 12.1.5 Description of adverse events
Original text:
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines.
Has been changed to:
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the intensity of an AE in the eCRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria:
•
Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere 
with his/her usual activities and/or is of no clinical consequence
•
Moderate: the AE interferes with the usual activities of the subject or it is of some 
clinical consequence
•
Severe: the subject is unable to work normally or to carry out his/her usual activities, or 
the AE is of definite clinical consequency
Details for completion of the Adverse Event eCRF (including judgment of intensity and
relationship to IMP) are described in the eCRF Completion Guidelines.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 130 of 143
Change #31
Section 12.5 Laboratory measurements, Table 12-2
Original text:
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
Has been changed to:
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 131 of 143
Hematology
Chemistry
Urinalysis
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
Change #32
Section 12.6.1 Vital signs
Original text:
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 1, collect pulse and BP prior to drug administration and then at 
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing (any time).
Has been changed to:
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing (any time).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 132 of 143
Change #33
Section 12.6.5 Tuberculosis and TB risk factor assessment and management, 
Exclusion criteria at Screening
Original text:
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen. 
Has been changed to:
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen. 
Following consultation with the Medical Monitor, subjects may be rescreened after 
completion at least 8 weeks of LTBI prophylactic therapy.
Change #34
Section 15.1 Definition of analysis sets
Original text:
The PK-PPS will consist of all randomized subjects who took at least 1 dose of IMP and provide 
at least 1 quantifiable plasma concentration postdose.
The PD-PPS will consist of all randomized subjects who took at least 1 dose of IMP and provide 
at least 1 PD measurement postdose that is without important protocol deviation affecting that 
time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. Subjects who are eligible for the ESS, but do not receive 
rescue medication, remain in the DBRS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 133 of 143
Has been changed to:
The Pharmacokinetic Per Protocol Set (PK-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations affecting the pharmacokinetic 
variables, as confirmed during ongoing data cleaning meetings prior to database lock. 
The Pharmacodynamic Per Protocol Set (PD-PPS) will consist of all randomized subjects who 
took at least 1 dose of IMP and provide at least 1 PD measurement postdose that is without 
important protocol deviation affecting that time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period including the dose at 
Week 12.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. Subjects who are eligible for the ESS, but do not receive 
rescue medication, remain in the DBRS.
Change #35
Section 15.4 Subgroup analyses
Original text:
•
BASDAI (≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Has been changed to:
•
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Change #36
Section 15.5.1 Safety analyses
The following paragraph has been added:
Treatment-emergent AEs will be defined as events that have a start date on or following 
the first administration of study treatment through the final administration of study 
treatment +140 days (covering the 20 week SFU Period).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 134 of 143
Change #37
Section 15.5.2 Other analyses
Original text:
Pharmacokinetic and PD analyses will be detailed in a separate data analysis plan and reported in 
a separate document. Plasma concentration-time data of bimekizumab and ASAS40 responder 
rates will be used as the PK and PD response. If data merits, a further PK/PD analysis on other 
PD variables may be performed.
Has been changed to:
Pharmacokinetic and PD analyses including the calculation of population estimates for total 
body clearance (CL/F) and volume of distribution (V/F) will be detailed in a separate data 
analysis plan and reported in a separate document. Plasma concentration-time data of 
bimekizumab and ASAS40 responder rates will be used as the PK and PD response. If data 
merits, a further PK/PD analysis on other PD variables may be performed.
Change #38
Table 19-1 Table footnote
Original text:
Note: A second grading of “probably ankylosing spondylitis” is part of the modified NY criteria, but it is not 
applicable for this study. It is included here for completeness. The grading will be probable ankylosing spondylitis if 
3 clinical criteria are present and the radiologic criterion is present without any signs or symptoms satisfying the 
clinical criteria (other causes of sacroiliitis should be considered).
Has been changed to:
AS=ankylosing spondylitis; mNY=modified New York Criteria
Note: A second grading of “probable ankylosing spondylitis” is part of the modified NY criteria, but it is not 
applicable for this study. It is included here for completeness. The grading will be probable ankylosing spondylitis if 
3 clinical criteria are present and the radiologic criterion is present without any signs or symptoms satisfying the 
clinical criteria (other causes of sacroiliitis should be considered).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 135 of 143
19.4
Protocol Amendment 2
Rationale for the amendment
The purpose of this substantial protocol amendment is the following:
•
To update the study contact details for the sponsor study physician and clinical trial 
biostatistician.
•
To revise the withdrawal criteria section to provide instructions for the management of 
subjects with newly diagnosed IBD or with IBD flares during the study.
•
Amend the time window between doses during the Double-Blind Period of the study.
•
To revise and clarify the SAE criteria for pregnancy for consistency.
•
Amend the table for identification/exclusion of alternative etiology to include ALT and AST.
Modifications and changes
Global changes
No global changes have been made. Specific changes are listed below.
Specific changes
Change #1
LIST OF ABBREVIATIONS
The following abbreviation and definition was added: 
RCTC
Rheumatology Common Toxicity Criteria
Change #2
STUDY CONTACT INFORMATION
Original text:
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Has been changed to: 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 136 of 143
Name:
, MD, MSc, PhD
, MD
Address:
UCB Pharma Ltd. UCB BIOSCIENCES Inc.
208 Bath Road 8010 Arco Corporate Drive
Slough, SL1 3WE Raleigh, NC 27617
UNITED KINGDOM UNITED STATES
Phone:
Change #3
STUDY CONTACT INFORMATION
Original text: 
Clinical Trial Biostatistician
Name:
Dr. 
, Senior Biostatistician
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str.10
40789 Monheim am Rhein
GERMANY
Phone:
Has been changed to: 
Clinical Trial Biostatistician
Name:
, MSDr. 
, Senior 
Biostatistician
Address:
UCB BIOSCIENCES Inc.GmbH
8010 Arco Corporate Drive Alfred Nobel Str.10
Raleigh, NC 2761740789 Monheim am Rhein
UNITED STATESGERMANY 
Phone:
Change #4
Section 6.3 Withdrawal Criteria
The following was added to the withdrawal criteria:
11. Subjects with newly diagnosed IBD or with IBD flares during the study must:
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 137 of 143
−
Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist
−
Discontinue IMP and be followed-up until resolution of active IBD symptoms
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact the 
Medical Monitor and UCB study physician to confirm the subject's suitability for continued 
participation in the study.
Change #5
Section 7.2 Treatments to be administered, paragraph 2
Original text: 
The IMP (bimekizumab and placebo) will be administered at the times indicated in Table 5‒1. 
The minimum time between doses during the Double-Blind Period should be no less than 26 
days and no more than 30 days and during the Dose-Blind Period should be no less than 24 days 
and no more than 32 days.
Has been changed to: 
The IMP (bimekizumab and placebo) will be administered at the times indicated in Table 5‒1. 
The minimum time between doses during the Double-Blind Period should be no less than 256
days and no more than 310 days and during the Dose-Blind Period should be no less than 24 
days and no more than 32 days.
Change #6
Section 7.3 Packaging
Original text: 
Bimekizumab and placebo will be packaged and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. They will be suitably packaged in 
such a way as to protect the product from deterioration during transport and storage. Further 
information regarding storage and transport conditions are provided in the IMP Handling 
Manual.
Has been changed to: 
Bimekizumab and placebo will be manufactured, packaged and labeled according to Good 
Manufacturing Practice (GMP) guidelines and applicable laws or regulations. They will be 
suitably packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in the IMP 
Handling Manual.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 138 of 143
Change #7
Section 12.1.8 Pregnancy, paragraph 5
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective for 
a medical condition or spontaneous), unintended pregnancy after hormonal contraceptive failure 
(if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal demise, or any 
congenital anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report Form.
Has been changed to: 
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective 
abortion when medically indicated (e.g. when pregnancy is endangering life or health of 
woman or when fetus will be born with severe abnormalities), unintended pregnancy after 
hormonal contraceptive failure (if the hormonal contraceptive was correctly used), ectopic 
pregnancy, fetal demise, or any congenital anomaly/birth defect of the baby. Those SAEs 
must be additionally reported using the Investigator SAE Report form.
Change #8
Section 12.5.1.4
Testing: identification/exclusion of alternative etiology, Table 
12-4 
Original table: 
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
body
body
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 139 of 143
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
Has been changed to: 
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
ALT, AST
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 140 of 143
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
Change #9
Section 17.1
Markedly abnormal laboratory values, Tables 17-1 (Definitions of markedly 
abnormal hematology values) and 17-2 (Definitions of markedly abnormal biochemistry values)
Amended units in both table headers: 
Parameter (SI units)
Markedly Abnormal Definition
Low
High
Has been changed to:
Parameter (SIRCTC units)
Markedly Abnormal Definition
Low
High
Change #10
Section 17.1
Markedly abnormal laboratory values, Table 17-1 (Definitions of markedly 
abnormal hematology values), abbreviations in table footer:
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international
Has been changed to:
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international RCTC= 
Rheumatology Common Toxicity Criteria
Change #11
Section 17.1
Markedly abnormal laboratory values, Table 17-2 (Definitions of markedly 
abnormal biochemistry values), abbreviations in table footer:
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 141 of 143
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; 
SI=standard international; ULN=upper limit of normal
Has been changed to:
LLN=lower limit of normal; N/A = Not Applicable; SI=standard international RCTC=
Rheumatology Common Toxicity Criteria
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 142 of 143
20
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
REDACTED COPY
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 143 of 143
21
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.