Conditions: Ankylosing Spondylitis
Keywords: Ankylosing Spondylitis Bimekizumab AS Certolizumab Pegol Cimzia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 76
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate the efficacy and safety of bimekizumab compared to certolizumab pegol in the treatment of subjects with active ankylosing spondylitis (AS).

Detailed description:

Arms:
arm 1: Subjects will receive several bimekizumab administrations on pre-defined time points. Placebo will be provided in this arm to mask the certolizumab pegol loading dose. arm 2: Subjects will receive several certolizumab pegol administrations on pre-defined time points.

Interventions: intervention 1: Bimekizumab intervention 2: Certolizumab pegol intervention 3: Placebo
Intervention descriptions: intervention 1: One bimekizumab dose will be administered. intervention 2: Two certolizumab pegol doses will be administered. One of these doses is a loading dose. intervention 3: Placebo will be provided to maintain the blinding.

Protocol document:
Prot_000.pdf: 
UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 1 of 136
PROTOCOL AS0013 AMENDMENT 3
A MULTICENTER, PHASE 2A, RANDOMIZED, 
INVESTIGATOR-BLIND, SUBJECT-BLIND, PARALLEL-GROUP 
STUDY TO EVALUATE THE EFFICACY AND SAFETY OF 
BIMEKIZUMAB AND CERTOLIZUMAB PEGOL IN SUBJECTS 
WITH ACTIVE ANKYLOSING SPONDYLITIS
PHASE 2A
EudraCT Number: 2017-000957-37
IND Number: 128708
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of amendment
Final protocol
19 Apr 2017
Not applicable
Protocol amendment 1
30 May 2017
Nonsubstantial
Protocol amendment 1.1 (CZ)
07 Sep 2017
Substantial
Protocol amendment 1.1 (DE)
09 Oct 2017
Nonsubstantial
Protocol amendment 1.1 (NL)
18 Sep 2017
Substantial
Protocol amendment 2
05 Mar 2018
Substantial
Protocol amendment 2.1 (CZ)
07 Mar 2018
Substantial
Protocol amendment 2.2 (DE)
07 Mar 2018
Substantial
Protocol amendment 2.3 (NL)
27 Apr 2018
Substantial
Protocol amendment 2.4 (CZ)
03 Jul 2018
Substantial
Protocol amendment 3
27 Feb 2019
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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 2 of 136
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
Exploratory Project Manager
Name:
Address:
Alfred-Nobel-Str 10, 40789 Monheim, Germany
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International (IRL) Limited
Address:
One Kilmainham Square, Inchicore Road, Kilmainham, Dublin 8, Ireland
Phone:
+353 1 473 9500
Fax:
+353 1 473 9501
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 3 of 136
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
US and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com 
PUBLIC COPY 
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This document cannot be used to support any marketing aut
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 4 of 136
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................10
1
SUMMARY.....................................................................................................................15
2
INTRODUCTION ...........................................................................................................16
2.1 Axial spondyloarthritis.....................................................................................................16
2.2 Bimekizumab ...................................................................................................................17
2.2.1
Clinical experience with bimekizumab................................................................18
2.2.2
Nonclinical studies with bimekizumab................................................................19
2.3 Certolizumab pegol..........................................................................................................19
2.3.1
Clinical experience with CZP..............................................................................20
2.4 Study rationale .................................................................................................................20
3
STUDY OBJECTIVE(S).................................................................................................21
3.1 Primary objective.............................................................................................................21
3.2 Secondary objective.........................................................................................................21
3.3 Other exploratory objectives............................................................................................21
4
STUDY VARIABLES.....................................................................................................21
4.1 Efficacy variables.............................................................................................................21
4.1.1
Primary efficacy variable.....................................................................................21
4.1.2
Secondary efficacy variables ...............................................................................21
4.1.3
Other efficacy variables.......................................................................................22
4.2 Safety variables................................................................................................................22
4.2.1
Primary safety variables ......................................................................................22
4.2.2
Other safety variables ..........................................................................................22
4.3 Other PK and PD variables..............................................................................................22
4.3.1
Other PK variables...............................................................................................22
4.3.2
Other PD variables...............................................................................................22
4.4 Other immunological variable(s) .....................................................................................23
4.5 Other nonhereditary pharmacogenomic variables ...........................................................23
4.6 Other pharmacogenetic variables.....................................................................................23
5
STUDY DESIGN.............................................................................................................23
5.1 Study description .............................................................................................................23
5.1.1
Screening Period (minimum of 2 and up to 4 weeks)..........................................24
5.1.2
Treatment Period (Week 0 to Week 12)..............................................................24
5.1.3
Treatment Extension Period (Week 12 to Week 48)...........................................24
5.1.4
Safety Follow-up Period (Week 48 to Week 64).................................................25
5.2 Safety monitoring strategy...............................................................................................25
5.3 Imaging evaluation...........................................................................................................25
5.4 Study duration per subject................................................................................................25
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 5 of 136
5.5 Planned number of subjects and site(s)............................................................................25
5.6 Anticipated regions and countries....................................................................................25
5.7 Schedule of assessments ..................................................................................................26
5.8 Schematic diagram...........................................................................................................31
5.9 Rationale for study design and selection of dose.............................................................32
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................33
6.1 Inclusion criteria ..............................................................................................................33
6.2 Exclusion criteria .............................................................................................................35
6.3 Withdrawal criteria ..........................................................................................................38
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................40
6.4 Study stopping rules.........................................................................................................41
6.5 Retesting/rescreening.......................................................................................................41
7
STUDY TREATMENT(S) ..............................................................................................42
7.1 Description of investigational medicinal product(s)........................................................42
7.2 Treatment(s) to be administered ......................................................................................42
7.3 Packaging.........................................................................................................................43
7.4 Labeling ...........................................................................................................................43
7.5 Handling and storage requirements..................................................................................43
7.6 Drug accountability..........................................................................................................44
7.7 Procedures for monitoring subject compliance................................................................44
7.8 Concomitant medication(s)/treatment(s)..........................................................................44
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................45
7.8.2
Prohibited concomitant treatments (medications and therapies).........................45
7.8.3
Rescue medication...............................................................................................47
7.9 Blinding............................................................................................................................47
7.9.1
Procedures for maintaining and breaking the treatment blind.............................47
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......................................................................48
8
STUDY PROCEDURES BY VISIT ...............................................................................49
8.1 Screening Visit (Visit 1) ..................................................................................................49
8.2 Baseline (Visit 2, Week 0)...............................................................................................51
8.3 Week 2 (Visit 3)...............................................................................................................52
8.4 Week 4 (Visit 4)...............................................................................................................52
8.5 Week 6 (Visit 5)...............................................................................................................53
8.6 Week 8 (Visit 6)...............................................................................................................53
8.7 Week 10 (Visit 7).............................................................................................................54
8.8 Week 12 (Visit 8).............................................................................................................54
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 6 of 136
8.9 Week 16 (Visit 9), Week 20 (Visit 10), Week 28 (Visit 12), Week 32 (Visit 13), Week 
40 (Visit 15), and Week 44 (Visit 16)..............................................................................55
8.10 Week 24 (Visit 11) and Week 36 (Visit 14) ....................................................................56
8.11 Week 48 (Visit 17)/Early Withdrawal Visit ....................................................................57
8.12 Safety Follow-Up Visit (Week 64, Visit 18, 20 weeks after the final dose of IMP).......58
8.13 Early Withdrawal Visit ....................................................................................................58
8.14 Unscheduled Visit............................................................................................................58
9
ASSESSMENT OF EFFICACY......................................................................................59
9.1 ASDAS ............................................................................................................................59
9.2 ASAS20, ASAS40, and ASAS partial remission ............................................................60
9.3 BASDAI...........................................................................................................................60
9.4 Inflammation – BASDAI (mean of Questions 5 and 6) ..................................................61
9.5 Function – BASFI............................................................................................................61
9.6 Patient global assessment (PGADA) ...............................................................................61
9.7 PhGADA..........................................................................................................................61
9.8 Total and nocturnal spinal pain........................................................................................62
9.9 hs-CRP .............................................................................................................................62
9.10 Hospital Anxiety and Depression Scale...........................................................................62
9.11 PET-MRI or PET-CT scan...............................................................................................62
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC/ PHARMACOGENETIC 
VARIABLE(S) ................................................................................................................62
10.1 Pharmacokinetic variables ...............................................................................................62
10.2 Pharmacodynamic variables ............................................................................................63
10.3 Nonhereditary pharmacogenomic variables.....................................................................63
10.4 Pharmacogenetic variables...............................................................................................63
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLE(S) ............................................63
12
ASSESSMENT OF SAFETY..........................................................................................64
12.1 Adverse events.................................................................................................................64
12.1.1
Definitions ...........................................................................................................64
12.1.1.1
Adverse event............................................................................................64
12.1.1.2
Serious adverse event ................................................................................64
12.1.1.3
Adverse events of special interest .............................................................66
12.1.1.4
Adverse events for special monitoring......................................................67
12.1.2
Procedures for reporting and recording adverse events.......................................67
12.1.2.1
Description of adverse events....................................................................67
12.1.2.2
Rule for repetition of an adverse event......................................................68
12.1.2.3
Additional procedures for reporting serious adverse events .....................68
12.1.3
Follow up of adverse events ................................................................................68
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 7 of 136
12.2 Pregnancy.........................................................................................................................69
12.3 Suspected transmission of an infectious agent.................................................................70
12.4 Overdose of investigational medicinal product ...............................................................70
12.5 Safety signal detection .....................................................................................................70
12.6 Laboratory measurements................................................................................................70
12.6.1
Evaluation of PDILI ............................................................................................72
12.6.1.1
Consultation with Medical Monitor and local hepatologist ......................77
12.6.1.2
Immediate action: Determination of IMP discontinuation........................77
12.6.1.3
Testing: Identification/exclusion of alternative etiology...........................77
12.6.1.4
Follow-up evaluation.................................................................................79
12.7 Other safety measurements..............................................................................................79
12.7.1
Vital signs ............................................................................................................79
12.7.2
Body weight and height.......................................................................................80
12.7.3
Physical examination...........................................................................................80
12.7.4
12-lead electrocardiogram ...................................................................................80
12.7.5
Tuberculosis and TB risk factor assessment and management ...........................80
12.7.5.1
Tuberculosis assessment by IGRA............................................................82
12.7.5.2
Chest X-ray for tuberculosis......................................................................82
12.7.5.3
Tuberculosis questionnaire........................................................................83
12.7.5.4
Tuberculosis management.........................................................................83
12.7.6
Pregnancy testing.................................................................................................84
12.7.7
Assessment of suicidal ideation and behavior.....................................................84
13
OTHER STUDY MEASUREMENTS ............................................................................84
13.1 Demographic and Baseline characteristics ......................................................................84
13.2 Medical history ................................................................................................................84
13.3 Ankylosing spondylitis history ........................................................................................84
13.4 Prior and concomitant medications..................................................................................84
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................85
14.1 Adherence to protocol......................................................................................................85
14.2 Monitoring .......................................................................................................................85
14.2.1
Definition of source data .....................................................................................85
14.2.2
Source data verification .......................................................................................86
14.3 Data handling...................................................................................................................86
14.3.1
Case Report Form completion.............................................................................86
14.3.2
Database entry and reconciliation........................................................................86
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............86
14.4 Termination of the study..................................................................................................87
14.5 Archiving and data retention............................................................................................87
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 8 of 136
14.6 Audit and inspection ........................................................................................................87
14.7 Good Clinical Practice .....................................................................................................88
15
STATISTICS ...................................................................................................................88
15.1 Definition of analysis sets................................................................................................88
15.2 General statistical considerations.....................................................................................88
15.3 Subject disposition...........................................................................................................89
15.4 Subject characteristics......................................................................................................89
15.5 Planned efficacy analyses ................................................................................................89
15.5.1
Analysis of the primary efficacy variable............................................................89
15.5.2
Supportive analysis of the primary efficacy variable ..........................................90
15.5.3
Analysis of the secondary efficacy variables.......................................................90
15.5.4
Analysis of the other efficacy variables...............................................................90
15.6 Pharmacokinetic analyses ................................................................................................90
15.7 Immunological analyses...................................................................................................91
15.8 Planned safety and other analyses....................................................................................91
15.8.1
Safety analyses.....................................................................................................91
15.9 Handling of protocol deviations.......................................................................................91
15.10
Handling of dropouts or missing data....................................................................91
15.11
Planned interim analysis and data monitoring.......................................................91
15.12
Determination of sample size.................................................................................92
16
ETHICS AND REGULATORY REQUIREMENTS......................................................92
16.1 Informed consent .............................................................................................................92
16.2 Subject identification cards..............................................................................................93
16.3 Institutional Review Boards and Independent Ethics Committees..................................93
16.4 Subject privacy.................................................................................................................94
16.5 Protocol amendments.......................................................................................................94
17
FINANCE, INSURANCE, AND PUBLICATION.........................................................94
18
REFERENCES ................................................................................................................94
19
APPENDICES .................................................................................................................99
19.1 Modified New York (mNY) Classification Criteria for AS ............................................99
19.2 Markedly abnormal laboratory values ...........................................................................100
19.3 Protocol Amendment 1 ..................................................................................................101
19.4 Protocol Amendment 2 ..................................................................................................107
19.5 Protocol Amendment 3 ..................................................................................................117
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................135
21
SPONSOR DECLARATION ........................................................................................136
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 9 of 136
LIST OF TABLES
Table 5‒1:
Schedule of assessments ..................................................................................26
Table 5‒2:
Exposure to bimekizumab by dose ..................................................................33
Table 7‒1:
Treatments administered..................................................................................43
Table 7‒2:
Prohibited or restricted medications and required wash-out periods prior 
to Baseline........................................................................................................45
Table 12‒1:
Anticipated serious adverse events for the population of subjects with AS....65
Table 12‒2:
Laboratory measurements................................................................................71
Table 12‒3:
Required investigations and follow-up for PDILI ...........................................74
Table 12‒4:
PDILI laboratory measurements......................................................................77
Table 12‒5:
PDILI information to be collected ...................................................................79
Table 19‒1:
Modified New York (mNY) Classification Criteria for AS ............................99
Table 19‒2:
Definitions of markedly abnormal hematology values..................................100
Table 19‒3:
Definitions of markedly abnormal biochemistry values................................100
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................31
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 10 of 136
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
Ankylosing Spondylitis Disease Activity Score
ASDAS-ID
Ankylosing Spondylitis Disease Activity Score inactive disease
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score major improvement
AST
aspartate aminotransferase
axSpA
axial spondyloarthritis
BA
bioavailability
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BCG
Bacille Calmette-Guérin
BMI
body mass index
BP
blood pressure
BSA
body surface area
CD
cluster of differentiation
CDC 
Centers for Disease Control 
CDMS
clinical data management system
CHO
Chinese Hamster Ovarian
CI
confidence interval
COX-2 inhibitor
cyclooxygenase 2 inhibitor
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
CRP
C-reactive protein
CSR
clinical study report
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 11 of 136
C-SSRS
Columbia-Suicide Severity Rating Scale
CT
computed tomography
CZP
certolizumab pegol
DMARD
disease-modifying antirheumatic drug
DMC
Data Monitoring Committee
DVU
disco-vertebral unit
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
EPM
Exploratory Project Manager
ES
Enrolled Set
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
follicle-stimulation hormone
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GI
gastrointestinal
GMP
Good Manufacturing Practice
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
hs-CRP
high sensitivity C-reactive protein
hPDSC
human periosteum-derived stem cell
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
ICH
International Council for Harmonisation
ICF
Informed Consent form
IEC
Independent Ethics Committee
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 12 of 136
IGRA
Interferon-Gamma Release Assay
IIV
interindividual variability
IL
interleukin
im
intramuscular
IMP
investigational medicinal product
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
im
intramuscular
iv
intravenous
IRT
interactive response technology
LTB
latent tuberculosis
LTBI
latent tuberculosis infection 
MAR
missing at random
MCID
minimal clinically important difference
MCP-Mod
multiple comparison procedure – modeling
MCS
mental component summary
MedDRA®
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MMP
matrix metalloproteinase
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
OPV
oral polio vaccine
PCS
physical component summary
PD
pharmacodynamics
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 13 of 136
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamics Per-Protocol Set
PET
positron-emission tomography
PET-CT
positron-emission tomography – computed tomography
PET-MRI
positron-emission tomography – magnetic resonance imaging
PFS
pre-filled syringe
PGADA
Patient’s Global Assessment of Disease Activity
PhGADA
Physician’s Global Assessment of Disease Activity
PK
pharmacokinetics
PK-PPS
Pharmacokinetics Per-Protocol Set
PPS
Per-Protocol Set
PS
Patient Safety
PsA
psoriatic arthritis
PSO
psoriasis
Q2W
every 2 weeks
Q4W
every 4 weeks (monthly)
QTcF
QT interval corrected for heart rate using Fridericia’s formula 
RA
rheumatoid arthritis
RCTC
Rheumatology Common Toxicity Criteria
RIF
mycobacterium tuberculosis rifampin
RNA
ribonucleic acid
RS
Randomized Set
RUV
residual unexplained variability
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous(ly)
SD
standard deviation
SFU
Safety Follow-up
SI
sacroiliac
SpA
spondyloarthritis
SOP
standard operating procedure
SS
Safety Set
SSZ
sulfasalazine
STIR
short-tau-inversion recovery
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 14 of 136
SUVAUC
standardized uptake value by area under the curve
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
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.


UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 15 of 136
1
SUMMARY
This is a Phase 2a, multicenter, randomized, subject-blind, investigator-blind, parallel-group, 
study to investigate the efficacy and safety of bimekizumab (also known as UCB4940) and 
certolizumab pegol ([CZP]; Cimzia®) in adult subjects with active ankylosing spondylitis (AS).
Eligible subjects will have active AS, determined by documented radiologic evidence (X-ray) 
fulfilling the Modified New York criteria for AS (van der Linden et al, 1984), including 
symptoms for ≥3 months and age of onset <45 years. Furthermore, subjects will have moderate 
to severe active disease at Screening (Bath Ankylosing Spondylitis Disease Activity Index 
[BASDAI] ≥4 and spinal pain ≥4 [BASDAI Question 2]). 
The primary objective of the study is to evaluate the efficacy of bimekizumab administered 
subcutaneously (sc) every 2 weeks (Q2W) for 12 weeks compared to CZP in the treatment of 
subjects with active AS. The primary efficacy variable is the change from Baseline in 
Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12. The secondary objective 
of the study is to assess the safety and tolerability of bimekizumab. The secondary efficacy 
variables include the determination of ASDAS inactive disease (ASDAS-ID) and ASDAS major 
improvement (ASDAS-MI) at Week 12. Primary safety variables include the incidence of 
adverse events (AEs), serious adverse events (SAEs), and AEs leading to withdrawal from 
investigational medicinal product (IMP).
Other exploratory objectives of the study are to evaluate the effect of bimekizumab or CZP on 
changes in bone formation, to assess the pharmacokinetics (PK) and immunogenicity of 
bimekizumab, to obtain additional biomarkers and clinical and imaging data as applicable, and to 
assess the efficacy and safety of bimekizumab or CZP during the Treatment Period and the 
Treatment Extension Period.
Multiple sites in North America, Europe, and the Asian-Pacific (APAC) region will randomize at 
least 60 subjects in a 2:1 ratio to receive either bimekizumab or CZP. 
The study consists of a Screening Period (2 to 4 weeks), Treatment Period (12 weeks), Treatment 
Extension Period (36 weeks), and a Safety Follow-up (SFU) Period (20 weeks after the final 
dose of the IMP). Therefore, the maximum duration of the study is 68 weeks. 
Screening Period
The Screening Period will last for a minimum of 2 weeks and up to 4 weeks. 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. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 16 of 136
Treatment Period
At Baseline/Day 1, subjects will be randomized in a 2:1 ratio to receive the following blinded 
study treatments during the Treatment Period:

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in 
order to maintain the blind vs the certolizumab pegol (CZP) loading dose at these visits. 

Certolizumab pegol 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 
200mg sc Q2W in Weeks 6 to 10.
The IMP will be administered sc in the clinic by trained site personnel. 
Treatment Extension Period
After completing the 12-week Treatment Period, subjects will enter a 36-week Treatment 
Extension Period and will receive the following treatments:

Subjects randomized to bimekizumab during the Treatment Period will receive bimekizumab 
320mg sc every 4 weeks (Q4W) from Week 12 to Week 44. 

Subjects randomized to CZP during the Treatment Period will receive CZP 400mg Q4W 
from Week 12 to Week 44. 
Subjects not responding to treatment will be withdrawn from the study as per Investigator’s 
discretion.
Safety Follow-Up Period
All subjects who complete the study or who discontinue early, including those withdrawn from 
study treatment, will have a SFU Visit at 20 weeks after their final 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 Assessment of SpondyloArthritis International Society (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 (sacroiliac [SI] joints and spine), 
including AS diagnosed with radiographic involvement and nonradiographic axSpA (nr-axSpA). 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 17 of 136
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 an magnetic resonance 
imaging (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 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 nonsteroidal 
anti-inflammatory drugs (NSAIDs), or those in whom NSAIDs are contraindicated, have 
approved treatment options such as tumor necrosis factor (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. 
Treatment with tumor necrosis factor alpha (TNFα)-antagonists has demonstrated marked 
improvement in almost all features of AS, a subset of the axSpA population. For AS, many of the 
processes which lead to inflammation and subsequent damage, as in RA, are driven by 
dysregulated TNFα production, including extracellular matrix degradation due to matrix 
metalloproteinase (MMP) production (Davis and Mease, 2008).
2.2
Bimekizumab
Bimekizumab (UCB4940) is an engineered, humanized full length monoclonal antibody of 
immunoglobulin (Ig)G1 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, psoriasis (PSO), and axSpA. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 18 of 136
2.2.1
Clinical experience with bimekizumab
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, First-in-Human (FIH) randomized, subject-blind, investigator-blind, 
placebo-controlled, single-dose, dose-escalating study in 39 subjects with mild-to-moderate 
plaque PSO. In this study bimekizumab was administered by intravenous (iv) infusion of 
single ascending doses and was well tolerated at doses of up to 640mg. The maximum 
tolerated dose was not reached, and no safety issues were identified. Dose-proportional PK 
was displayed between bimekizumab 8mg and 640mg. The median t½ ranged between 
17.00 days and 25.55 days across the treatment groups. Dose-dependent improvements in the 
psoriatic lesion of interest were observed after bimekizumab administration for all features of 
plaque PSO in the study. 

RA0124 was an open-label, parallel-group, single-dose study to evaluate the absolute 
bioavailability (BA), dose proportionality, and safety and tolerability of 2 dose levels of 
bimekizumab given by sc injection versus bimekizumab given by iv infusion in 30 healthy 
subjects. Similar BA was observed for the 2 doses tested (0.656 and 0.631 for the 
bimekizumab 80mg and bimekizumab 160mg doses, respectively). No new safety issues 
were observed versus previous studies when bimekizumab was administered sc as a single 
dose of 80mg or 160mg, or iv at a dose of 160mg.

PA0007 was a randomized, subject-blind, investigator-blind, placebo-controlled, 
multiple-dose administration study to evaluate the safety, PK, and pharmacodynamic (PD) 
profiles of bimekizumab administered iv to subjects with active PsA who had an inadequate 
response to at least 1 nonbiologic disease-modifying antirheumatic drug (DMARD) and/or 
1 approved biologic DMARD. Bimekizumab was administered to 4 cohorts of subjects as a 
loading dose of 240mg, 80mg, 160mg, or 560mg followed by 2 maintenance doses at 
3-weekly intervals of 160mg, 40mg, 80mg, or 320mg, respectively. There were no 
unexpected clinically relevant safety findings and all doses were well tolerated.

UP0031, evaluated the relative bioavailability, safety and tolerability of 2 bimekizumab 
formulations (a histidine-based formulation 2x80mg and an acetate-based formulation 
1x160mg) administered by sc injection to healthy volunteers. Results showed similar 
geometric means for AUC between the 2 bimekizumab formulations 
(2x80mg=653.8day*μg/mL; 1x160mg=628.3day*μg/mL) and the relative BA for the 
bimekizumab 1x160mg versus 2x80mg formulations was calculated as 96.1% with a 95% 
confidence interval (CI): 72.7,127.0. The wide 95% CI was expected due to the small sample 
size in UP0031.
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 CZP therapy in 
subjects with moderate to severe RA. UC0011 is a Phase 2a study, which will evaluate the 
efficacy, safety, tolerability, and PK of an iv loading dose and 2 sc maintenance doses of 
bimekizumab in subjects with moderate to severe active ulcerative colitis. PS0010, PS0011, 
PS0016, and PS0018 are Phase 2 studies, which will evaluate the PD, PK, safety, and/or efficacy 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 19 of 136
of bimekizumab administered sc to subjects with PSO. PA0008 and AS0008 are Phase 2b 
double-blind, randomized, placebo-controlled, multiple-dose studies to evaluate the efficacy and 
safety of bimekizumab in subjects with active PsA or AS, respectively.
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
2.2.2
Nonclinical studies with bimekizumab
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.
2.3
Certolizumab pegol
Treatment with TNFα-antagonists has demonstrated marked improvement in almost all features 
of AS, a subset of the axSpA population. For AS, many of the processes which lead to 
inflammation and subsequent damage, as in RA, are driven by dysregulated TNFα production, 
including extracellular matrix degradation due to matrix metalloproteinase (MMP) production 
(Davis and Mease, 2008). 
The RAPID-axSpA study enrolled subjects with active axSpA with objective signs of 
inflammation, and the results indicated that baseline disease burden was similar between the AS 
and nr-axSpA subpopulations (Landewe et al, 2014; Sieper et al, 2013b). In the RAPID-axSpA 
study it was shown that CZP rapidly reduced the signs and symptoms of axSpA over 24 weeks of 
double-blind treatment in the broad axSpA population, including in the AS and the nr-axSpA 
subpopulations, and that the responses to the treatment were similar in both subpopulations 
(Landewe et al, 2014; Sieper et al, 2013b) and maintained up to Week 96 (Mease et al, 2014; 
Sieper et al, 2014).
Certolizumab pegol has a high affinity for human TNFα and binds with a dissociation constant 
(KD) of 90pM. Tumor necrosis factor alpha (TNFα) is a key pro-inflammatory cytokine with a 
central role in inflammatory processes. 
Certolizumab pegol does not contain a fragment crystallizable (Fc) region, which is normally 
present in a complete antibody, and therefore does not fix complement or cause 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 20 of 136
antibody-dependent cell-mediated cytotoxicity in vitro. It does not induce apoptosis in vitro in 
human peripheral blood-derived monocytes or lymphocytes, or neutrophil degranulation.
2.3.1
Clinical experience with CZP
Certolizumab pegol is indicated for the treatment of adult patients with active AS in multiple 
countries around the world.
After the loading dose, the recommended maintenance dose of CZP for adult subjects with AS is 
CZP 200mg Q2W or CZP 400mg Q4W.
Additional information on the clinical data for CZP is available in the current version of the IB 
and the product information available in each country.
2.4
Study rationale
The first TNF blockers used for the treatment of patients with active AS showed great promise. 
(Brandt et al, 2000). However, despite good effects on signs and symptoms, C-reactive protein 
and inflammation as detected by MRI, the TNFα inhibitors did not appear to prevent new bone 
formation in the spine (van der Heijde et al, 2008). A 12-year longitudinal study shows that the 
higher the disease activity, the more the structural damage in the spine, and thus concluding that 
inflammation and new bone formation are related (Ramiro et al, 2014). Understanding the role of 
different cytokines in driving new bone formation allows for improved treatments for AS 
patients. There is a growing association, and interest, for the involvement of IL-17 signaling in 
bone pathology during spondyloarthritis disease progression. The role of IL-17A in driving bone 
loss and destruction is well documented (Chabaud et al, 2001). More recently, in vitro studies 
demonstrated that mesenchymal cells incubated in the presence of IL 17A and bone 
differentiation medium leads to the formation of extracellular calcified bone matrix with an 
increase in alkaline phosphatase activation (Osta et al, 2014), suggesting that IL-17A may have a 
role not only in bone destruction, but under the right conditions in driving new bone formation. 
Wein et al, demonstrated in in vivo mouse models that in the absence of Schnurri3, a key gene in 
osteoblast differentiation, leads to increased bone mass; a response enhanced in the presence of 
IL-17A (Wein et al, 2012). The presence of Schnurri3 and osteoclasts activation at a site of bone 
inflammation leads to bone destruction, however in the absence of these, the same inflammation 
will induce new bone formation. In the AS patient at the syndesmophytes when mesenchymal 
cells from vertebral ligaments are inflamed in the physical absence of osteoclasts, this will 
induce new bone formation (Miossec, 2017). Recently, IL 17-producing γδ-T cells have been 
associated with periosteal bone formation for fracture repair (Ono et al, 2016); the periosteum is 
also implicated in pathologic bone formation in SpA (Lories et al, 2009). Using a biomimetic 
human periosteum-derived stem cell (hPDSC) model of osteogenic differentiation demonstrated 
that either/both IL-17A or/and IL-17F are able to drive pathologic bone formation (Shah et al, 
2017). Inhibiting both IL-17A and IL-17F has the potential to impact the pathophysiology of 
new bone formation in AS patients.
AS0013, the current subject-blind and investigator-blind study has been designed to evaluate the 
efficacy and safety of bimekizumab in a clinical setting in subjects with AS. The features of bone 
lesions are both erosive and neo-appositive and it is not clear if the inflammatory and erosive 
process precedes the new formation of bone. 18F-fluoride positron-emission tomography –
computed tomography (PET-CT) or 18F-fluoride positron-emission tomography – magnetic 
resonance imaging (PET-MRI) will be used to investigate the effects of bimekizumab on the 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 21 of 136
process of osteoproliferation as determined by the inhibition of osteoblast activity. Based on data 
showing that TNFα blockers have limited effect on osteoblast metabolism, the current study uses 
a TNFα inhibitor to show a potential differential inhibition of osteoblast activity between 
bimekizumab and CZP. 
3
STUDY OBJECTIVE(S)
This is a Phase 2a, multicenter, randomized, subject-blind and investigator-blind, parallel-group 
study to evaluate the efficacy and safety of bimekizumab compared to CZP in subjects with 
active AS. The effect of study treatments on the process of osteoproliferation will be evaluated in 
a subgroup of subjects at selected sites.
3.1
Primary objective
The primary objective of the study is to evaluate the efficacy of bimekizumab administered sc 
Q2W for 12 weeks compared to CZP in the treatment of subjects with active AS.
3.2
Secondary objective
The secondary objective of the study is as follows:

To assess the safety and tolerability of bimekizumab
3.3
Other exploratory objectives
The other exploratory objectives of the study are as follows:

To evaluate the effect of bimekizumab or CZP on changes in bone formation 

To assess the PK and immunogenicity of bimekizumab

To assess additional biomarker, clinical, and imaging data as available

To assess the efficacy and safety of bimekizumab or CZP during the Treatment Extension 
Period
4
STUDY VARIABLES
4.1
Efficacy variables
4.1.1
Primary efficacy variable
The primary efficacy variable for this study is as follows:

Change from Baseline in ASDAS at Week 12
4.1.2
Secondary efficacy variables
The secondary efficacy variables for this study are as follows:

ASDAS-ID at Week 12

ASDAS-MI at Week 12
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 22 of 136
4.1.3
Other efficacy variables 
Assessment time points for the other efficacy variables are specified in Table 5‒1. The following 
efficacy variables are exploratory and are assessed over the Treatment Period and Treatment 
Extension Period, as applicable:

Change from Baseline in ASDAS

ASAS20 response

ASAS40 response

Time to ASAS20 response

Time to ASAS40 response

ASAS partial remission

Change from Baseline in BASDAI

Changes in bone formation as measured by standardized uptake value by area under the 
curve (SUVAUC) and derived from PET-MRI or PET-CT at Baseline, Week 12, and Week 48 
4.2
Safety variables
4.2.1
Primary safety variables
The primary safety variables for this study are as follows:

Incidence of AEs and SAEs

Adverse events leading to withdrawal from IMP
4.2.2
Other safety variables
The other safety variables for this study are as follows:

Change from Baseline in vital signs (blood pressure, temperature, pulse rate) and body 
weight

Change from Baseline in physical examination

Change from Baseline in standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, 
QT, and QT intervals corrected for heart rate using Fridericia’s formula [QTcF]) 

Change from Baseline in clinical laboratory values (hematology, biochemistry, and 
urinalysis)
4.3
Other PK and PD variables
4.3.1
Other PK variables
The PK variables are plasma concentrations of bimekizumab and CZP.
4.3.2
Other PD variables
The PD variables assessed at time points specified in Table 5‒1 are the blood or blood derivative 
(eg, plasma) concentrations of cytokines and chemokines of relevance to IL-17A/F signaling 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 23 of 136
pathway, TNF signaling pathway, AS biology, and bone metabolism. Additional variables may 
include, but will not be limited to, serum complement concentrations and mononuclear cell 
subtypes.
4.4
Other immunological variable(s)
Immunological variables will allow evaluation of immunogenicity as well as immunological 
biomarkers. Anti-bimekizumab antibody and anti-CZP antibody detection prior to and following 
study treatment will be evaluated.
4.5
Other nonhereditary pharmacogenomic variables
Where local regulations permit, blood and urine will be collected at specific time points specified 
in Table 5‒1 and stored for up to 20 years to allow for potential exploratory analyses of 
ribonucleic acid (RNA), proteins, and metabolite biomarkers relevant to AS, bone metabolism. 
and the inflammatory and immune response processes. The nature and format of these tentative 
analyses will be determined at a later stage. 
4.6
Other pharmacogenetic variables 
Additional blood samples will be collected from subjects who consent to participate in the 
pharmacogenetic substudy at specific time points specified in Table 5‒1 and stored at -80°C for 
up to 20 years. Pharmacogenetic biomarkers may be measured to evaluate the relationship to 
response to treatment with bimekizumab, AS disease biology, bone metabolism, and 
inflammatory and immune response processes. The nature and format of these tentative 
sub-study analyses will be determined when the results of the main study are made available.
5
STUDY DESIGN
5.1
Study description
AS0013 is a multicenter, randomized, subject-blind and investigator-blind, parallel-group study 
to evaluate the efficacy and safety of bimekizumab compared to CZP in adult subjects with 
active adult-onset AS. 
To be eligible to participate, subjects must meet the following key inclusion criteria: 

Subjects will have active adult-onset AS, meeting Modified New York criteria for AS with: 

BASDAI score ≥4

Spinal pain score ≥4 (from BASDAI Question 2). 

hs-CRP levels should be above the upper limit of normal (ULN) at the Screening Visit. One 
re-test of hs-CRP is permitted during the Screening Period upon discretion of the 
Investigator.

Subject must have had an inadequate response to, have a contraindication to, or has been 
intolerant to at least 2 NSAIDs (inadequate response to an NSAID is defined as lack of 
response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the 
administered NSAID.) If taking NSAIDs at study entry, subjects must be on a stable dose for 
2 weeks prior to Baseline. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 24 of 136

In addition, the subject may not have been exposed to more than 1 TNF antagonist prior to 
the Baseline Visit and may not be a primary failure to any TNF antagonist therapy (defined 
as no response within the first 12 weeks of treatment with the TNF antagonist.
At least 60 subjects will be randomized to 1 of 2 treatment arms in a 2:1 ratio and will receive 
either bimekizumab or CZP up to Week 44 (final dose of IMP). 
AS0013 will include a Screening Period of 2 to 4 weeks, a 12-week Treatment Period, a 36-week 
Treatment Extension Period, and a 20-week Safety Follow-up Period (after the final dose of 
IMP). 
In approximately 25 subjects at selected sites, a PET-MRI or PET-CT scan will be performed at 
Screening and during the study at Week 12 and Week 48/Early Withdrawal Visit if PET-positive 
lesions were observed in the previous scan.
5.1.1
Screening Period (minimum of 2 and up to 4 weeks)
Assessments of eligibility as described in Section 6 will be initiated during the 2- to 4-week 
Screening Period. The informed consent will be obtained as described in Section 8.1. The 
Screening Period will also enable the washout of medications not permitted for use during the 
study.
The assessments at the Screening Visit are presented in Table 5‒1.
5.1.2
Treatment Period (Week 0 to Week 12)
Eligible subjects will be randomized in a 2:1 ratio to receive the following blinded study 
treatments: 

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in 
order to maintain the blind vs the CZP loading dose at these visits. 

CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10.
Study treatments will be prepared and administered by appropriately trained unblinded site 
personnel. 
5.1.3
Treatment Extension Period (Week 12 to Week 48)
After completing the 12-week Treatment Period, subjects will enter a 36-week Treatment 
Extension Period and will receive the following treatments:

Subjects randomized to bimekizumab during the Treatment Period will receive bimekizumab 
320mg sc Q4W from Week 12 to Week 44. 

Subjects randomized to CZP during the Treatment Period will receive CZP 400mg Q4W 
from Week 12 to Week 44. 
Subjects not responding to treatment during the Treatment Period will be withdrawn from the 
study as per Investigator’s discretion and will not enter the Treatment Extension Period.
The assessments during the Treatment Extension Period are presented in Table 5‒1.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 25 of 136
5.1.4
Safety Follow-up Period (Week 48 to Week 64)
All subjects who complete the study or who discontinue from the study early, including those 
withdrawn from the 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.
5.2
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. Cardiovascular and Neuropsychiatric 
Adjudication Committees will review and monitor cardiovascular and neuropsychiatric events. 
Further details are provided in Section 12.5.
5.3
Imaging evaluation
In a subpopulation of AS0013, a PET-MRI or PET-CT scan of the entire spine will be performed 
at selected sites in approximately 25 subjects at Screening, and during the study at Week 12 and 
Week 48/Early Withdrawal Visit if PET-positive lesions were observed in the previous scan. 
The PET-MRI or PET-CT scan should be performed after confirmation of eligibility for the 
study based on screening assessments. All subjects at selected sites are eligible provided that a 
separate Informed Consent form (ICF) for the imaging evaluation has been signed.
5.4
Study duration per subject
For each subject, the study will last a maximum of up to 68 weeks, as follows:

Screening Period: minimum of 2 weeks and up to 4 weeks

Treatment Period: 12 weeks

Treatment Extension Period: 36 weeks

Safety Follow-up Period: 20 weeks after the final dose of IMP for subjects completing the 
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.
5.5
Planned number of subjects and site(s)
It is anticipated that approximately 120 subjects will be screened in order to enroll at least 
60 subjects in the main study and at least 25 subjects in the PET-CT or PET-MRI substudy at 
multiple sites.
5.6
Anticipated regions and countries
The study sites will be located in North America, Europe, and APAC countries with possible 
extension to other regions.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 26 of 136
5.7
Schedule of assessments
Table 5‒1:
Schedule of assessments
Study Period
SCr
Treatment Period
Treatment Extension Period
SFUa
Visitb/Week 
(Visit window ±3 days)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
V18
Procedures
SV
BL 
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
/WD
W64
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consentc
X
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X
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X
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criteria 
X
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diseases
X
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medicationsf
X
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X
X
X
X
X
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X
X
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X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
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X
X
X
X
X
X
X
X
X
X
X
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X
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X
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X
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 27 of 136
Table 5‒1:
Schedule of assessments
Study Period
SCr
Treatment Period
Treatment Extension Period
SFUa
Visitb/Week 
(Visit window ±3 days)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
V18
Procedures
SV
BL 
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
/WD
W64
Physical examination 
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weight)g
X
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X
X
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X
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X
X
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X
X
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X
X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tuberculosis 
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X
X
X
X
X
X
IGRA TB testi
X
X
Pregnancy testj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology/
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X
X
X
X
X
X
X
X
X
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 28 of 136
Table 5‒1:
Schedule of assessments
Study Period
SCr
Treatment Period
Treatment Extension Period
SFUa
Visitb/Week 
(Visit window ±3 days)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
V18
Procedures
SV
BL 
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
/WD
W64
Blood sample for 
hs-CRPk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood samples for 
pharmacogenetic 
variables
X
X
X
Blood samples for 
nonhereditary 
pharmacogenomic 
variables
X
X
X
X
X
Urine samples for 
biomarker research
X
X
X
X
Chest X-ray or CT scan 
of chest m
X
X
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X
PET-MRI or PET-CT 
scan as a substudy at 
selected siteso
X
X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
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AS=ankylosing spondylitis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; 
BL=Baseline; BP=blood pressure; CT=computed tomography; C-SSRS=Columbia Suicide Severity Rating Scale; CZP=certolizumab pegol; 
ECG=electrocardiogram; HADS=Hospital Anxiety and Depression Scale; HCV=hepatitis C virus; HIV=human immunodeficiency virus; HLA-B27=human 
leukocyten antigen B27; hs-CRP=high sensitivity C-reactive protein; IGRA=Interferon-Gamma Release Assay; IMP=investigational medicinal product; 
IRT=interactive response technology; NRS=numeric rating scale; PET-CT=positron-emission tomography-computer tomography; PET-MRI=positron-emission 
tomography – magnetic resonance imaging; PGADA=Patient’s Global Assessment of Disease Activity; PhGADA=Physician’s Global Assessment of Disease 
Activity; Q2W=every 2 weeks; Q4W=every 4 weeks; SCr=Screening; SFU=Safety Follow-Up; SV=Screening Visit; TB=tuberculosis; V=Visit; W=Week; 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 29 of 136
Table 5‒1:
Schedule of assessments
Study Period
SCr
Treatment Period
Treatment Extension Period
SFUa
Visitb/Week 
(Visit window ±3 days)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
V18
Procedures
SV
BL 
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
/WD
W64
WD=Early Withdrawal Visit; WHO=World Health Organization
a Safety Follow-Up Visit occurs 20 weeks after the final dose for all subjects who complete the study or who discontinue early, including those withdrawn from 
study treatment. 
b Visit windows of ±3 days from the first dose at all visits through Week 48. The SFU Visit window is -3 and +7 days from the final dose.
c A separate Informed Consent Form is required for subjects participating in the 2 sub-studies: 1) with biomarker, pharmacogenetic and nonhereditary 
pharmacogenomic blood-samples and 2) PET-MRI or PET-CT scans.
d Ensure there are no significant changes in medical history that would exclude the subject based on the exclusion criteria.
e Ensure that there are no significant changes in the medical history.
f Prior and concomitant medication at Screening and Baseline; concomitant medication only at all other visits.
g The physical examination includes the evaluation of signs and symptoms of active TB, risk for exposure to TB, height (Screening only) and weight (Screening, 
Week 12 and Week 48/WD only).
h Vital signs (blood pressure, pulse rate, and temperature) are to be measured prior to drug administration at all visits and at 30 minutes and 1 hour after dosing at 
Baseline/Day 1.
i QuantiFERON TB test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB test is not locally available. 
j Pregnancy testing will performed on serum at Screening and on urine at all other visits. Pregnancy test results must be negative prior to administering IMP. 
k At dosing visits, all blood samples are taken prior to dosing. Blood samples for IMP and anti-IMP antibody detection will be processed as per instructions in the 
laboratory manual. After Screening, until Week 12, hs-CRP data will not be sent to the Investigator to protect the blinded nature of the treatment assignments.
l Subjects who have evidence of or test positive for hepatitis B by any of the following criteria: 1) positive for hepatitis B surface antigen (HBsAg+); 2) positive 
for anti-hepatitis B core antibody (HBcAb+) are excluded; a positive test for HCV is defined as: 1) positive for hepatitis C antibody (anti-HCV Ab), and 2) 
positive via a confirmatory test for HCV (for example, HCV polymerase chain reaction) are also excluded.
m If a subject has had a recent radiograph or CT scan of the chest within 3 months prior to the Screening Visit, it may be used as the Screening chest X-ray. The 
chest X-ray/CT scan of the chest at Week 48/WD is to be done if medically indicated only (eg, positive TB-test).
n 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.
o A PET-MRI or PET-CT scan should be done up to 2 weeks before Baseline and within 2 weeks after the W12 and W48/WD Visit if PET-positive lesions are 
observed in the previous scan. If a subject withdraws from the study early, the PET-MRI or PET-CT scan must be repeated at the WD visit only, if the prior 
examination was done more than 12 weeks prior to the WD visit and the previous PET-scan showed positive lesions.
p CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in Weeks 6 to 10 and 400mg Q4W from Week 12 to Week 44. 
Bimekizumab will be administered at a dose of 160mg sc Q2W from Week 0 through Week 10 and 320mg sc Q4W from Week 12 to Week 44. The IMP will be 
administered at the end of the visit after all assessments have been completed. Subjects randomized to bimekizumab will receive 1 placebo injection at Baseline 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 30 of 136
Table 5‒1:
Schedule of assessments
Study Period
SCr
Treatment Period
Treatment Extension Period
SFUa
Visitb/Week 
(Visit window ±3 days)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
V18
Procedures
SV
BL 
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
/WD
W64
(Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4). 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 31 of 136
5.8
Schematic diagram
Figure 5‒1: Schematic diagram
CZP=certolizumab pegol; N=number of subjects; Q2W=every two weeks; Q4W=every 4 weeks; sc=subcutaneous(ly); SFU=Safety Follow-up, W=week
a Subjects not responding to treatment during the Treatment Period will be withdrawn from the study as per Investigator’s discretion and will not enter the 
Treatment Extension Period.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 32 of 136
5.9
Rationale for study design and selection of dose
AS0013 is a Phase 2a, multicenter, randomized, subject-blind and investigator-blind study to 
evaluate the efficacy and safety of bimekizumab and CZP in adult subjects with active AS. 
AS0013 includes a 12–week Treatment Period, a 36-week Treatment Extension Period, and a 
20-week SFU Period. Rationales for the study design, selected population, and bimekizumab 
doses are provided below.
Study design
AS0013 was designed to evaluate the efficacy, safety and the process of osteoproliferation using 
PET imaging techniques at Screening and after 12 and 48 weeks of treatment. The scientific 
rationale suggesting a role for IL-17A treatment in bone formation as compared to TNFα 
treatment is provided in detail in Section 2.4.
While the primary evaluation will be conducted after 12 weeks, a 36-week Treatment Extension 
Period has been added in order to maintain the treatment blind after subjects have reached 
Week 12 (ie, the evaluation of the primary efficacy variable) and to allow continued access to 
IMP for subjects responding to treatment. This extension also allows further evaluation of the 
inhibition of the osteoproliferative effect of bimekizumab and CZP at Week 48 and to compare 
this to Baseline and Week 12.
Population
AS0013 was designed to evaluate the potential benefit of bimekizumab to prevent bone 
formation in subjects at risk of new bone formation (disease progression) and comparing the 
outcome to treatment with CZP. Inclusion criteria will ensure that all subjects have active AS. 
Some exclusion criteria are intended to eliminate subjects who may present an unacceptable 
safety risk were they to participate in this investigational study program. Active AS is defined by 
a BASDAI score ≥4 and a spinal pain score ≥4 (from BASDAI Question 2). The full list of 
inclusion and exclusion criteria is provided in Section 6.
Dose selection
The following dose regimens of bimekizumab and CZP will be evaluated during the Treatment 
Period:

Bimekizumab 160mg sc Q2W from Week 0 through Week 10 

CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10.
Exposure levels up to 8-fold greater than 160mg Q2W 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. Additionally, in 
the above clinical studies (UP0008 and PA0007), bimekizumab was administered iv and the 
current study proposes to administer the compound sc. The exposure of the drug is expected to 
be lower than after iv administration due to lower bioavailability following sc administration 
and, therefore, the dose regimens are expected to be safe. No safety concerns have been reported 
in ongoing clinical studies evaluating cumulative monthly doses of bimekizumab 320mg in other 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 33 of 136
populations including PA0008 in subjects with active PsA, AS0008 in subjects with active AS, 
and several ongoing studies in subjects with PSO. 
Simulations were performed using a model to predict the dose response of ASAS20/40 at 
Week 12, ie, for a different endpoint than the primary efficacy endpoint being proposed in this 
study (Diderichsen and Cox, 2016). These simulations indicated that increasing doses above 
bimekizumab 320mg Q4W may not provide additional benefit in terms of efficacy. 
The dose selected in the current study is bimekizumab 160mg Q2W instead of 320mg Q4W. 
Given that the PK of bimekizumab has been established to be linear in the exposure range 
(UP0008 and PA0007), the proposed dose of bimekizumab 160mg Q2W is expected to provide 
similar overall exposure and hence response compared to a dose of 320mg Q4W. Table 5‒2
shows a comparable AUCtau between bimekizumab 320Q4W and 160mg Q2W calculated over a 
period of similar time (14 days). In conclusion, the existing data suggest that at the proposed 
dose level, bimekizumab is well tolerated and the analysis suggests that maximum benefit is 
achieved at this exposure level.
Table 5‒2:
Exposure to bimekizumab by dose
Parameter
Bimekizumab dose
160mg Q2W sc
320mg Q4W sc
640mg SD iv from 
UP0008
AUCtau or AUC0-inf (µg*day/mL)
442a,b
445a,b
3787c,d
Cmax (µg/mL)
33a
38a
260c
iv=intravenous; Q2W=every 2 weeks; Q4W=every 4 weeks; sc=subcutaneous, SD=single dose
a Median model predicted 
b Calculated over a period of 14 days 
c Median observed in UP0008 
d AUC0-inf
The dose and regimen proposed for CZP is one of the currently approved dose regimens in 
axSpA (CZP 400mg loading dose + CZP 200mg maintenance dose Q2W) and has been widely 
tested in the clinic, and is in line with the dosing guidance from the labeling. The proposed dose 
of CZP has been tested in Phase 3 studies in subjects with axSpA. The results of these studies 
have shown a favorable risk-benefit profile for the treatment of subjects with axSpA.
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. 
2. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand 
and complete diaries), visit schedule, and medication intake according to the judgment of the 
Investigator.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 34 of 136
3. Subject is male or female and at least 18 years of age.
4. Subject has a documented diagnosis of adult-onset AS as defined by documented radiologic 
evidence (X-ray) fulfilling the Modified New York criteria for AS (1984) of at least 
3 months’ symptom duration and age of onset <45 years. 
5. Subject has moderate to severe active disease at the Screening Visit as defined by each of the 
following:

BASDAI score ≥4

Spinal pain score ≥4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2)
6. Subject must have had an inadequate response to, have a contraindication to, or has been 
intolerant to at least 2 NSAIDs (inadequate response to an NSAID is defined as lack of 
response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the 
administered NSAID).
7. Subject may not have been exposed to more than 1 TNF antagonist prior to the Baseline Visit 
and may not be a primary failure to any TNF antagonist therapy (defined as no response 
within the first 12 weeks of treatment with the TNF antagonist.
8. Subject has hs-CRP levels above the ULN at the Screening Visit. One re-test of hs-CRP is 
permitted during the Screening Period upon discretion of the Investigator. 
9. 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 (where postvasectomy testing had demonstrated sperm clearance)

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 final dose of IMP (anticipated 5 
half-lifes of bimekizumab). Study personnel must confirm the continued use of 
abstinence is still in accordance with the subject’s lifestyle at regular intervals during the 
study.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 35 of 136
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up until 20 weeks after the last administration of IMP (anticipated 5 half-
lives).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Female subject who is breastfeeding, pregnant, or planning to become pregnant during the 
study or within 20 weeks following final dose of study drug. Male subject who is planning a 
partner pregnancy during the study or within 20 weeks following the final dose.
2. Subject who has previously received bimekizumab or CZP.
3. Subject has participated in another study of a medication under investigation within the last 3 
months or at least 5 half-lives of the IMP, whichever is greater, or is currently participating in 
another study of a medication under investigation.
4. Subject has a known hypersensitivity to any excipients of bimekizumab or CZP.
5. Subject has received previous treatment with a polyethylene glycolylated (PEGylated) 
compound that resulted in a severe hypersensitivity reaction or an anaphylactic reaction
6. Subject has a total ankylosis of the spine or a diagnosis of any other inflammatory arthritis 
eg, RA, systemic lupus erythematosus, sardoidosis, psoriatic arthritis, or reactive arthritis. 
Subjects with a diagnosis of Crohn’s disease or ulcerative colitis are allowed as long as they 
have no active symptomatic disease at Screening or Baseline.
7. Subject has a secondary, noninflammatory condition (eg, osteoarthritis, fibromyalgia) that in 
the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of 
study drug on the subject’s primary diagnosis of active AS.
8. Subject has received previous or current biological treatment other than TNFα inhibitor 
treatment.
9. Subjects must not have used medications in the manner as detailed by the exclusion criteria 
in Table 7‒2.
10. Subject has: 

a history of chronic or recurrent infections (eg, more than 3 episodes requiring systemic 
antibiotics or antivirals during the preceding year). Minor illnesses like common cold or 
transient, localized infections that may have been treated with a short course of antibiotic 
therapy (up to 7 days) need not count in this assessment.

a serious or life-threatening infection within the 6 months prior to the Baseline Visit 
(including herpes zoster) or hospitalization for any infection in the last 6 months.

any current sign or symptom that may indicate an active infection (except for common 
cold), or has had an infection requiring systemic antibiotics within 2 weeks prior to 
Baseline.

a high risk of infection in the Investigator’s opinion (eg, subjects with leg ulcers, 
indwelling urinary catheter, prior prosthetic joint infection at any time, subjects who are 
permanently bedridden or wheelchair assisted).
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 36 of 136
11. Subject has a 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)
12. Subject has acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) 
infection. Subjects who have evidence of, or test positive for, hepatitis B or hepatitis C are 
excluded as follows: 

A positive test for the hepatitis B virus (HBV) is defined as: 1) positive for hepatitis B 
surface antigen (HBsAg+), or 2) positive for anti-hepatitis B core antibody (HBcAb+). 

A positive test for the hepatitis C virus (HCV) is defined as: 1) positive for hepatitis C 
antibody (anti-HCV Ab), and 2) positive via a confirmatory test for HCV (for example, 
HCV polymerase chain reaction).
13. 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 12.7.5 for details 
on determining full TB exclusion criteria). 
14. Subject has a primary immunosuppressive condition, including taking immunosuppressive 
therapy following an organ transplant or has had a splenectomy.
15. 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
16. Subject has a history of a lymphoproliferative disorder including lymphoma or current signs 
and symptoms suggestive of lymphoproliferative disease.
17. Subject has a history of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
18. Subject has 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.
19. Subjects has 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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 37 of 136
20. Subjects with presence of significant uncontrolled neuropsychiatric disorder, active suicidal 
ideation, or positive suicide behavior using the “Baseline” version of the Columbia-Suicide 
Severity Rating Scale (C-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 C-SSRS at screening.

HADS Depression score ≥10 or Anxiety score ≥15.
21. 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 a 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.
22. Subjects with clinically significant laboratory abnormalities (eg, creatinine >1.5xULN, 
neutropenia <1.5x109/L, hemoglobin <8.5g/dL, lymphocytes <1.0 x109/L, white blood cell 
(WBC) count <3.0x109, platelets <100 x109/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. 
23. Subject has an estimated glomerular filtration rate (GFR) as measured by Chronic Kidney 
Disease Epidemiology Collaboration <60mL/min/1.73m2
24. Subject has a 12-lead ECG with changes considered to be clinically significant upon medical 
review (eg, QT corrected for heart rate [QTc] using Fridericia’s correction [QTcF] >450ms, 
bundle branch block, evidence of myocardial ischemia).
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 38 of 136
25. Subjects has received any live (includes attenuated) vaccination within the 8 weeks prior to 
Baseline (12 months prior to Baseline for the TB Bacille Calmette-Guérin [BCG] vaccine) 
(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 final 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 (within 12 months prior to Baseline)

Typhoid live oral vaccine

Varicella vaccine

Yellow fever vaccine
26. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
27. Subjects has any other condition which, in the Investigator's judgment, would make the 
subject unsuitable for inclusion in the study.
28. Subject is Investigator site personnel directly affiliated with this study and/or their immediate 
families. Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted.
29. 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 and encouraged to come for the SFU Visit 
(20 weeks after the last received dose of IMP) if any of the following events occur:
1. Subject withdraws his/her consent.
2. The sponsor or a regulatory agency requests withdrawal of the subject.
3. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
4. Subject develops an illness that would interfere with his/her continued participation.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 39 of 136
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 Early Withdrawal Visit must be scheduled as soon as 
possible, but not later than the next regular visit.
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 Section 12.7.5.
6. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
7. Subject uses prohibited concomitant medications as defined in this protocol (see 
Section 7.8.2) that may present a risk to the safety of the subject in the opinion of the 
Investigator and/or the Medical Monitor.
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 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 C-SSRS. The subject should be referred immediately to a Mental Healthcare 
Professional and must be withdrawn from the study.
10. Subjects with a Hospital Anxiety and Depression Scale—Depression (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 judgement 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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 40 of 136
In an attempt to prevent missing data during the study, efforts will be made to collect data from 
subjects who withdraw early from the study (NRC, 2010). If a subject withdraws from study 
treatment for any of the above criteria prior to Week 48, they will be asked to return for the study 
termination assessments as laid down at the Week 48/WD Visit and for the SFU Visit (20 weeks 
after final dose administration). 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 must be closely 
monitored. If a subject at any time has had an ALT and/or AST >5xULN, additional monitoring 
of hepatic markers will be performed every week or 2 weeks until resolution of the event, the 
event is considered stable, or they have reached the end of the SFU Period.
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.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
The PDILI criteria below require immediate discontinuation of IMP: 
Subjects with either of the following:

ALT or AST ≥5ULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator. 

Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness).
Evaluation of PDILI must be initiated as described in Section 12.6.1. 
If subjects are unable to comply with the applicable monitoring schedule, IMP must be 
discontinued immediately.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 41 of 136
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The eCRF must document the primary 
reason for IMP discontinuation.
6.4
Study stopping rules
During the study, planned dosing and procedures may be discontinued or suspended for all 
subjects in any part of the study and appropriate follow-up procedures established. Where it is 
possible to do so without threatening the safety of subjects, such discontinuation/suspension 
should be discussed with the UCB Study Physician prior to its implementation.
Possible reasons for discontinuation or suspension of the study include (but are not limited to):

A pattern of AEs occurs that contraindicates the further dosing of enrolled/additional 
subjects, including (but not limited to):

More than 1 subject meets any individual Withdrawal Criteria #5, #9, ro #10, or (as 
provided in Section 6.3), regardless of whether they met the same or different criteria.

Once a second subject meets any of those criteria, referral to the DMC may not be 
delayed while awaiting the outcome of either case.
If the above criteria are reached, the DMC will meet as soon as possible to determine whether 
discontinuation or suspension of the study should occur and to determine what investigations, 
analyses, procedural amendments, or other actions should occur, before making any 
recommendation regarding the possibility of recommencing the study. Further details on the role 
of the DMC are provided in Section 12.5. 

If the Sponsor or designees judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations, and Good Clinical Practice (GCP).
6.5
Retesting/rescreening
In the event of an isolated laboratory value outside the laboratory’s normal range, the evaluation 
may be repeated on 1 occasion during the Screening Period. If a value from the repeated test is 
within the screening-specified ranges, the subject maybe enrolled. 
Subjects whose Screening Period expires may be rescreened following discussion with the 
Sponsor.
Subjects who withdraw from the study may be replaced, up to a maximum of 10 subjects. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 42 of 136
7
STUDY TREATMENT(S)
7.1
Description of investigational medicinal product(s)
The IMPs used in this study are bimekizumab and CZP.
Bimekizumab will be supplied as a vial or in a pre-filled syringe (PFS) form as described below: 

Vial: a clear to opalescent, colorless to slightly brown, sterile, preservative-free solution in 
2mL Type I, colorless glass vials (1.0mL extractable volume) closed with a rubber stopper 
and sealed with an aluminum cap overseal. Each single-use dose vial will contain 160mg/mL 
bimekizumab in 
mM sodium acetate,
mM glycine, and 
 (w/v) polysorbate 80 at 
pH 

PFS: 1mL PFS at a concentration of 160mg/mL (
mM sodium acetate, 
mM glycine, 
 polysorbate 80 at pH 
) for sc injection.
Certolizumab pegol will be supplied as a sterile, clear, colorless-to-slightly yellow solution at 
pH
 in 1mL single-use glass PFS for sc injection. Each syringe contains an extractable volume 
of 1.0mL at a concentration of CZP 200mg/mL in 
mM sodium acetate buffer and 
mM 
sodium chloride as a tonicity agent. The syringes are stored at 2 to 8ºC, not frozen, and protected 
from light.
Placebo will be supplied as 0.9% sodium chloride aqueous solution (physiological saline, 
preservative free) of pharmacopoeia (United States Pharmacopoeia/European Pharmacopoeia) 
quality appropriate for injection.
Further details of the IMPs and their specifications are provided in the IMP Handling Manual.
7.2
Treatment(s) to be administered
The IMP is to be administered in the clinic by trained 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 or CZP) will be administered at time points indicated in Table 5‒1.
At Baseline, eligible subjects will be randomized in a 2:1 ratio to the following bimekizumab or 
CZP treatment arms and will receive IMP as shown in Table 7‒1.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 43 of 136
Table 7‒1:
Treatments administered
IMP
Study period
Treatment Period 
Treatment Extension Period 
Bimekizumab
160mg sc Q2Wa
320mg sc Q4W
CZP
Loading doses of 400mg sc Q2W at Weeks 0, 2, 
and 4 followed by CZP 200mg sc Q2W
400mg sc Q4W
CZP=certolizumab pegol; IMP=investigational medicinal product, Q2W=every 2 weeks; Q4W=every 4 weeks; 
sc=subcutaneous
a In addition, subjects will receive 1 placebo injection at Baseline, Week 2, and Week 4 in order to maintain the 
blind vs the CZP loading dose at these visits.
The minimum time between doses should be no less than 10 days during the Treatment Period 
and no less than 22 days during the Treatment Extension Period. 
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing.
7.3
Packaging
Bimekizumab and CZP 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.
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 GMP 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 according to the storage conditions mentioned on the label.
Appropriate storage conditions must be ensured either by controlling the temperature (eg, room, 
refrigeration unit) or by completion of a temperature log in accordance with local requirements 
on a regular basis (eg, once a week), showing actual and minimum/maximum temperatures 
reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 44 of 136
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, damaged (due to breakage or wastage), not used, partially 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 response technology [IRT] 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. 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)/partially used, unused, damaged, and/or expired IMP must be reconciled and 
destroyed at the site according to local laws, regulations, and UCB standard operating procedures 
(SOPs). 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 theTreatment Period and the Treatment Extension Period, 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 electronic Case 
Report Form (eCRF). This record should include the name of the drug, the dose, the route and 
date(s) of administration, and the indication for use.
The Investigator should examine the acceptability of all concomitant procedures, medications, 
topical preparations and dietary supplements not explicitly prohibited in this study, and if 
necessary, discuss with the Medical Monitor.
In order to ensure that appropriate concomitant therapy is administered, subjects will be 
instructed to consult with the Investigator prior to taking any medication (either 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 45 of 136
self-administered non-prescription drugs or prescription therapy prescribed by another 
physician).
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications are permitted during the study:
Subjects may use NSAIDs under the following conditions:

Subjects who are already receiving an established NSAID regimen and have been on a stable 
dose for at least 2 weeks prior to Baseline may continue their use during the study. However, 
initiation of, or increase in dosage of NSAIDs during the study (especially in subjects with a 
history of GI intolerance to NSAIDs or a history of GI ulceration) should be done with 
caution and must not occur until after the Week 12 Visit.
Subjects may use corticosteroids under the following conditions:

Oral (maximum allowed ≤10mg daily total prednisone equivalent)—subjects are permitted to 
decrease their oral corticosteroid therapy dose equivalent and/or alter their regimen only after 
Week 12.
Subjects may use MTX, sulfasalazine (SSZ), or hydroxychloroquine (HCQ) under the following 
conditions:

No change in dose or dose regimen of these agents is allowed during the study except for 
reasons of intolerance/AEs. No increase of the dose is permitted. No change is permitted in 
the route of administration for MTX (intramuscular [im], sc, or oral). It is strongly 
recommended that subjects taking MTX are also taking folic acid supplements. No 
combinations of DMARDs are permitted during the study.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications are prohibited during the study:
Table 7‒2:
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. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 46 of 136
Table 7‒2:
Prohibited or restricted medications and required wash-out periods 
prior to Baseline
Drug class
Dose
Exclusion criteria
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, SSZ, and HCQ
Maximum allowed: 
SSZ ≤3g daily 
HCQ ≤400mg daily 
MTX ≤25mg weekly
Use initiated and/or any change in the dose 
regimen in the 28 days prior to the Baseline 
Visit. No change is permitted in the route of 
administration for MTX (im, sc, or oral) in 
the 28 days prior to the Baseline Visit.
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, and GOL, any use within 
the 12 weeks prior to the Baseline Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
For CZP, any previous use
This applies to biosimilar versions of any 
TNF inhibitors.
Any non-TNF biologic medications
Any dose
Any exposure history.
ADA=adalimumab; ia=intra-articular; COX-2=cyclooxygenase 2; CZP=certolizumab pegol; 
DMARD=disease-modifying antirheumatic drug; ETN=etanercept; GOL=golimumab; 
HCQ=hydroxychloroquine; IFX=infliximab; 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 antidepressant regimen should be on a stable dose of 
anti-depressant for 12 weeks prior to Baseline.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 47 of 136
Subjects who take prohibited medications, except topical therapies, may be withdrawn from 
study treatment, but followed until the Safety Follow-Up Visit (20 weeks after the final dose of 
IMP). The decision to withdraw a subject for taking prohibited medications should be made in 
consultation with the Medical Monitor. As noted above, subjects who use prohibited topical 
medications will be allowed to stay in the study but will be counseled to not use them further.
Vaccines
Administration of live, attenuated vaccines is not allowed during the conduct of the study or for 
20 weeks after the final dose of study drug. Subjects receiving BCG vaccinations within 
12 months prior to study drug administration are excluded (see Exclusion Criterion #25,
Section 6.2).
7.8.3
Rescue medication
There are no absolute restrictions on the use of concomitant medications to “rescue” subjects 
whose AS deteriorates during the course of the study. While the objectives of the study should be 
protected as much as possible through observance of the restrictions detailed in Table 7‒2, the 
wellbeing of the subject will always take priority, and subjects should be managed as deemed 
appropriate by the Investigator. If use of any prohibited medications is anticipated, this should be 
discussed with the Sponsor's Study Physician first, wherever possible.
7.9
Blinding
Due to differences in presentation of the IMPs (bimekizumab and CZP), special precautions will 
be taken to ensure study blinding. Subjects randomized to bimekizumab will receive placebo at 
Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in order to maintain the blind vs the 
CZP loading dose at these visits. 
Investigational medicinal product injections will be prepared at the investigational sites by 
unblinded, dedicated study personnel. 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 drug to the subjects.
During the study, the Sponsor will provide blinded and unblinded site monitors for the purposes 
of verifying safety, efficacy, and study drug administration and documentation records. Blinded 
study monitors and study site personnel, blinded to treatment assignment, will not discuss or 
have access to any study drug-related information.
Further details are provided in the study manuals and site blinding plan. 
7.9.1
Procedures for maintaining and breaking the treatment blind
The IMP handling manual describes the handling of bimekizumab and CZP. Appropriate training 
will be given to the site personnel to avoid any unblinding. In case the Investigator becomes 
unblinded for any subject, another assessor will perform the remaining evaluations for that 
subject.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 48 of 136
All Sponsor and Investigator site personnel involved in the study will be blinded to the 
randomized IMP (bimekizumab or CZP) assignment with the following exceptions:

Sponsor Clinical Study Supplies manager and qualified personnel

Sponsor Patient Safety (PS) staff reporting SAEs to the regulatory authorities

Site pharmacist involved in IMP preparation and dispensing

Unblinded monitor who reviews the IMP related documentation and drug accountability

Bioanalytical staff analyzing blood samples for PK and immunogenicity, and biomarkers

Any Sponsor staff and/or designee who is responsible for data analyses for the unblinded 
DMC and interim analyses. These individuals will be separate from the main blinded study 
team.

Unblinded team at PAREXEL for the purpose of sending unblinded output for the planned 
interim analyses
If necessary, the results of any planned analysis may be shared with key Sponsor’s personnel in 
order to facilitate additional Clinical Planning or Portfolio Management decisions. Only 
unblinded summary results will be provided, and individual subject data will be kept blinded. All 
individuals seeing unblinded summary data will be documented in the Trial Master File (TMF).
7.9.1.1
Maintenance of study treatment blind
All subject treatment details (bimekizumab or CZP) will be allocated and maintained by the 
interactive response technology (IRT) system.
7.9.1.2
Breaking the treatment blind in an emergency situation
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the subject has been allocated by contacting the IRT. 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 Exploratory Project Manager (EPM) will be informed immediately via the IRT 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.
7.10
Randomization and numbering of subjects
An IRT will be used for assigning eligible subjects to a treatment regimen (as applicable) based 
on a predetermined production randomization and/or packaging schedule provided by UCB (or 
designee). The randomization schedule will be produced by the IRT vendor. The IRT will 
generate individual assignments for subject kits of IMP, as appropriate, according to the visit 
schedule. To enroll a subject at Visit 1, the Investigator or designee will contact the IRT and 
provide brief details about the subject to be enrolled. Each subject will receive a 5-digit number 
assigned at screening 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 IRT 
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IRT. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 49 of 136
To randomize a subject at Visit 2, the Investigator or designee will contact the IRT and provide 
brief details about the subject to be randomized. The IRT will automatically inform the 
Investigator or designee of the subject’s randomization number. The IRT will allocate kit 
numbers to the subject based on the subject number during the course of the study. The 
randomization number must be incorporated into the eCRF.
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 of ±3 days on either side of the scheduled dosing are permitted; however, the 
Investigator should try to keep the subjects on the original dosing schedule. The window of 
±3 days is relative to Baseline and applicable for all subsequent visits. Changes to the dosing 
schedule outside of the 3-day window must be discussed with the Medical Monitor.

For the SFU Visit (20 weeks after the final dose of IMP), 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 to +7 days).
8.1
Screening Visit (Visit 1)
Prior to any study specific activities, subjects will be asked to read, sign, and date an 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.
Two additional ICFs for substudies will be required:

Where local regulations permit, subjects will also be given the option to participate in the 
pharmacogenetic and pharmacogenomic substudy. Subjects agreeing to participate in the 
substudy will be required to complete a separate ICF. The ICF must be signed prior to 
collecting any samples for the substudy. The substudy will only be conducted where ethically 
accepted and authorized by the regulatory agencies. Refusal to participate in the substudy 
will not affect a subject’s ability to participate in the main AS0013 study.

Subjects will also be given the option to participate in the PET-MRI or PET-CT substudy at 
selected sites. 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 AS0013 study.
The following procedures or assessments will be performed at the Screening Visit:

Obtain written informed consent. 

Collect demographic and Baseline characteristics data (including lifestyle and child bearing 
potential as applicable).

Collect AS history. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 50 of 136

Assess if all inclusion criteria and no exclusion criteria are met.

Collect significant past medical history and concomitant diseases.

Record prior and concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the Bath Ankylosing Spondylitis Functional Index (BASFI).

Total and nocturnal spinal pain (NRS).

Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB, weight and height.

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Administer the tuberculosis questionnaire.

Perform an IGRA tuberculosis test (QuantiFERON TB test).

Perform a serum pregnancy test.

Collect samples for hematology/biochemistry/urinalysis.

Collect samples for hs-CRP.

Collect samples for HIV, hepatitis B and C, and HLA-B27 serology. 

Perform a sacroiliac joint X-ray (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 the Screening Visit. 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).

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks prior to Baseline.

Obtain a chest radiograph or computer tomography (CT) scan, unless one has been obtained 
within 3 months prior to the Screening Visit.

Register the subject using the interactive response technology (IRT).
Individual screening tests for which the results are borderline for inclusion in the study may be 
repeated if necessary without complete rescreening of all tests.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 51 of 136
8.2
Baseline (Visit 2, Week 0)
The following procedures or assessments will be performed/recorded prior to administration of 
the IMP:

Verify if all inclusion criteria and no exclusion criteria are met.

Verify significant past medical history and concomitant diseases.

Record prior and concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.

Perform the Patient’s Global Assessment of Disease Activity (PGADA).

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure) prior to IMP administration and 
then at 30 minutes and 1 hour after dosing.

Perform a 12-lead ECG.

Perform a urine pregnancy test.

Collect samples for: 

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.

If the respective ICF has been provided collect blood samples for: 

Cytokines, complement, and biomarker analyses 

Pharmacogenetic variables.

Nonhereditary pharmacogenomic variables.

Collect urine samples for biomarker research if the respective ICF has been provided.

Contact the IRT for randomization.

Administer IMP after all other visit assessments are completed.

Record visit in the IRT.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 52 of 136
8.3
Week 2 (Visit 3)
The following procedures or assessments will be performed/recorded:

Record concomitant medications. 

Assess adverse events.

C-SSRS.

Determine the BASDAI. 

Determine the BASFI.

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8.4
Week 4 (Visit 4)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.

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
Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Perform a urine pregnancy test.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 53 of 136

Collect samples for:

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.

If the respective ICF has been provided collect blood samples for:

Cytokines, complement, and biomarker analyses.

Nonhereditary pharmacogenomic variables.

Collect urine samples for biomarker research if the respective ICF has been provided.

Administer IMP.

Record visit in the IRT.
8.5
Week 6 (Visit 5)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Collect samples for hematology/biochemistry/urinalysis.

Administer IMP.

Record visit in the IRT.
8.6
Week 8 (Visit 6)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 54 of 136

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Perform a urine pregnancy test.

Collect samples for: 

Hematology/biochemistry/urinalysis.

hs-CRP.

Administer IMP.

Record visit in the IRT.
8.7
Week 10 (Visit 7)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Collect samples for hematology/biochemistry/urinalysis.

Administer IMP.

Record visit in the IRT.
8.8
Week 12 (Visit 8)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 55 of 136

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB and weight.

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Administer the tuberculosis questionnaire.

Perform a urine pregnancy test.

Collect samples for:

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.

If the respective ICF has been provided collect blood samples for:

Cytokines, complement, and biomarker analyses.

Pharmacogenetic variables.

Nonhereditary pharmacogenomic variables.

Collect urine samples for biomarker research if the respective ICF has been provided.

Perform a PET-MRI or PET-CT scan in at least 25 subjects at selected sites within 2 weeks 
after Week 12 Visit if PET-positive lesions were observed in the previous scan.

Administer IMP.

Record visit in the IRT.
8.9
Week 16 (Visit 9), Week 20 (Visit 10), Week 28 (Visit 12), Week 32 
(Visit 13), Week 40 (Visit 15), and Week 44 (Visit 16)

Record concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 56 of 136

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Blood sample for hs-CRP.

Perform a urine pregnancy test.

Administer IMP.

Record visit in the IRT.
8.10
Week 24 (Visit 11) and Week 36 (Visit 14)

Record prior and concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB.

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Administer the tuberculosis questionnaire.

Perform a urine pregnancy test.

Collect samples for:

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 57 of 136

If the respective ICF has been provided collect blood samples for:

Cytokines, complement, and biomarker analyses.

Administer IMP.

Record visit in the IRT.
8.11
Week 48 (Visit 17)/Early Withdrawal Visit

Record prior and concomitant medications. 

Assess adverse events.

C-SSRS.

HADS.

Determine the BASDAI. 

Determine the BASFI.

Perform the PGADA.

Perform the PhGADA.

Total and nocturnal spinal pain (NRS).

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB and weight.

Perform a 12-lead ECG.

Administer the tuberculosis questionnaire.

Perform an IGRA tuberculosis test (QuantiFERON TB test).

Perform a urine pregnancy test.

Collect samples for:

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.

If the respective ICF has been provided collect blood samples for:

Cytokines, complement, and biomarker analyses.

Pharmacogenetic variables.

Nonhereditary pharmacogenomic variables.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 58 of 136

Collect urine samples for biomarker research if the respective ICF has been provided.

Obtain a X-ray or CT scan of the chest if the QuantiFERON TB test returned a positive 
result. 

Perform a PET-MRI or PET-CT scan in at least 25 subjects at selected sites within 2 weeks 
after the Week 48/WD Visit if PET-positive lesions were observed in the previous scan. At 
the WD Visit, the PET-MRI or PET-CT must be done only, if the previous imaging 
evaluation occurred more than 12 weeks ago and if PET-positive lesions were observed in 
the previous scan.

Record visit in the IRT.
8.12
Safety Follow-Up Visit (Week 64, Visit 18, 20 weeks after the 
final dose of IMP)

Record concomitant medications. 

Assess adverse events.

Measure vital signs (temperature, pulse, and blood pressure).

Perform a 12-lead ECG.

Administer the tuberculosis questionnaire.

Perform a urine pregnancy test.

Collect samples for:

Hematology/biochemistry/urinalysis.

Bimekizumab and CZP plasma concentrations.

Anti-bimekizumab and anti-CZP antibody detection.

hs-CRP.

If the respective ICF has been provided collect blood samples for:

Cytokines, complement, and biomarker analyses.

Nonhereditary pharmacogenomic variables.

Record visit in the IRT.
8.13
Early Withdrawal Visit
Subjects withdrawing early from the study (see Section 6.3) should undergo the same 
assessments scheduled for the Week 48 Visit (see Section 8.11) as soon as possible after 
withdrawal (as an Early Withdrawal Visit) and then enter the SFU Period, completing study 
participation with the SFU Visit 20 weeks after their final dose of study medication.
8.14
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. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 59 of 136
If an Unscheduled Visit is conducted due to safety or efficacy reasons, a C-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, repeated collection of a laboratory specimen due to 
collection or analysis issues), an C-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:

Vital signs (temperature, pulse, and blood pressure).

C-SSRS. 

Other patient-reported outcomes (HADS, BASDAI, BASFI, PhGADA, PGADA, total and 
nocturnal spinal pain) as required. 

Administer the tuberculosis questionnaire.

Perform a physical examination, including an evaluation for signs and symptoms of active 
TB and risk for exposure to TB and weight.

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).

Record concomitant medication.

Record AEs.
9
ASSESSMENT OF EFFICACY
The timing for all assessments described below is specified in the Schedule of Assessments 
(Table 5‒1).
9.1
ASDAS
The ASDAS is comprised of a number of assessments which are scored by the subject and 
Investigator and multiplied by a validated formula (van der Heijde et al, 2009) as listed:

0.121 x Total spinal pain (BASDAI Question 2 result, Section 9.3)

0.058 x Duration of morning stiffness (BASDAI Question 6 result, Section 9.3) 

0.110 x PGADA (Section 9.6)

0.073 x Peripheral pain/swelling (BASDAI Question 3 result, Section 9.4)

0.579 x (natural logarithm of the CRP [mg/L] + 1)
Spinal pain, PGADA, duration of morning stiffness, and peripheral pain/swelling are all assessed 
on a numerical scale (0 to 10 units) (Lukas et al, 2009). The results of these calculations are 
summed to calculate the ASDAS.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 60 of 136
The following definitions apply to ASDAS Disease Activity categories:

ASDAS-Inactive Disease: ASDAS <1.3

ASDAS-Moderate Disease activity: ASDAS ≥1.3, <2.1

ASDAS-High Disease activity: ASDAS ≥2.1; ≤3.5

ASDAS-Very High Disease activity: ASDAS >3.5
9.2
ASAS20, ASAS40, and ASAS partial remission
The ASAS20 response 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 9.6)

Pain assessment (the total spinal pain NRS score; Section 9.8)

Function (represented by BASFI, Section 9.5)

Inflammation (the mean of the BASDAI Questions 5 and 6 results, [see Section 9.4] 
concerning morning stiffness intensity and duration)
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 ASAS40 response is defined as an improvement 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 above and no worsening at all 
in the remaining domain.
The ASAS partial remission response is defined as a score of ≤2 units on a 0 to 10 unit NRS 
scale in all 4 domains listed above for ASAS20.
9.3
BASDAI
The most common instrument used to measure the disease activity of AS from the subject’s 
perspective is the BASDAI (Garrett et al, 1994). The BASDAI is a validated self-reported 
instrument which consists of six 10 unit horizontal NRSs to measure severity of fatigue, spinal 
and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and 
duration, respectively) over the last week (van Tubergen et al, 2015). The BASDAI score ranges 
from 0 to 10, with lower scores indicating lower disease activity. Question 2 of the BASDAI 
asks 
 Question 3 of 
the BASDAI asks 
 Question 6 of the BASDAI asks 
 
The BASDAI is calculated as follows: 
𝐵𝐴𝑆𝐷𝐴𝐼=
Q1 + Q2 + Q3 + Q4 + (𝑄5 + 𝑄6
2
)
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 61 of 136
Fatigue item of the BASDAI
Fatigue as a major symptom of AS can effectively be measured with single-item questions such 
as the BASDAI item (van Tubergen et al, 2002b). This item has shown moderate to good 
reliability and responsiveness (van Tubergen et al, 2002b). The same minimal clinically 
important difference (MCID) will be used for the fatigue item of the BASDAI as for the 
BASDAI score, ie, a change of 1 unit on the NRS.
9.4
Inflammation – BASDAI (mean of Questions 5 and 6)
Question 5 of the BASDAI (described completely in Section 9.3) measures intensity of morning 
stiffness. The subject considers the previous week and responds to the question, 
The response is indicated on a 10-point NRS in which 0=None and 10=Very severe. Question 6 
of the BASDAI measures duration of morning stiffness. The subject considers the previous week 
and responds to the question, 
The response is indicated on a 10-point NRS in which 0=0 hours, 5=1 hour, and 10=2 
or more hours. The ratings for each question are summed and divided by 2 to provide the mean 
of Questions 5 and 6. This is used in the definition of the ASAS response variables defined in 
Section 9.2.
9.5
Function – BASFI
The BASFI is a validated disease-specific instrument for assessing physical function (van der 
Heijde et al, 2005; Calin et al, 1994). The BASFI comprises 10 items relating to the past week. 
The NRS version will be used for the answering options of each item on a scale of 0 (“Easy”) to 
10 (“Impossible”) (van Tubergen et al, 2015 and van Tubergen et al, 2002a). The BASFI is the 
mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating 
better physical function. The MCID used to interpret scores is 7mm on a 0 to 100mm visual 
analog scale (VAS) or 17.5% of the Baseline score (Pavy et al, 2005); an MCID of 1 unit will be 
used for the NRS version. This is used in the definition of the ASAS response variables defined 
in Section 9.2.
9.6
Patient global assessment (PGADA)
Subjects will provide their global assessment of their disease activity in response to the question 
“How active was your spondylitis on average during the last week?” using a NRS where 0 is 
“not active” and 10 is “very active” (van Tubergen et al, 2015).
This is used in the calculation of ASDAS (Section 9.1) and the definition of the ASAS response 
variables defined in Section 9.2.
9.7
PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity 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.
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 62 of 136
9.8
Total and nocturnal spinal pain
The pain experienced by AS subjects is adequately measured by 2 separate questions: 1) total 
pain in the spine due to AS (ie, “How much pain of your spine due to spondylitis do you have?”); 
and 2) pain in the spine at night due to AS (ie, “How much pain of your spine due to spondylitis 
do you have at night?”) (Sieper et al, 2009; van der Heijde et al, 2005; Committee for Proprietary 
Medicinal Product [CPMP]/EWP/556/95). When responding to each question, the subject is to 
consider the average amount of pain in the preceding week. The total pain score is used in the 
definition of the ASAS response variables defined in Section 9.2.
9.9
hs-CRP
Blood will be collected for measurement of hs-CRP. After Screening, the hs-CRP data will not 
be sent to the Investigator to protect the blinded nature of the treatment assignments. The hs-CRP 
will be used in the calculation of ASDAS (Section 9.1).
9.10
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).
9.11
PET-MRI or PET-CT scan
High bone turnover assessed by nuclear medicine methods may detect osteoproliferative 
processes regardless of the inflammatory or noninflammatory origin.
While exact localization of regions of radionuclide uptake is difficult with conventional 
scintigraphy,18F-fluoride PET-CT or PET-MRI has a much better spatial resolution and 
sensitivity (Strobel et al, 2010; Even-Sapir et al, 2007). In the present study, UCB will assess the 
regions of high bone turnover as detected by 18F PET-MRI or 18F PET-CT within the spine and 
the sacroiliac joints. 
The 18F-fluoride PET-MRIs of the whole spine will be performed by using a whole-body 
PET/MRI system. Alternatively, subjects will be examined in supine position on a combined 
PET-CT system permitting the acquisition of co-registered CT and PET images in the same 
session. The PET-MRI or PET-CT scan will be performed at time points provided in Table 5‒1
in at least 25 subjects at selected sites.
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC/ 
PHARMACOGENETIC VARIABLE(S)
Plasma concentrations of bimekizumab and CZP are the PK variables. 
10.1
Pharmacokinetic variables
Blood samples for measurement of PK variables will be collected at the time points specified in 
the Table 5‒1. At dosing visits, blood samples will be drawn prior to dosing, and will be drawn 
at the same time of the sampling for clinical laboratory tests. The time and date of collection will 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 63 of 136
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.
10.2
Pharmacodynamic variables
Blood samples for measurement of PD variables will be collected at the time points specified in 
Table 5‒1. Flow cytometry by fluorescence-activated cell sorting (FACS) analysis might 
include, but is not limited to: cluster of differentiation (CD)3, CD19, CD4, CD8, and CD69. 
Candidate biomarkers might include, but are not limited to: IL-17A/IL17-F pathway signaling, 
TNF signaling pathway, bone metabolism and AS (eg, IL-17A, IL-17F, IL-23, IL-6, TNF, DC-
STAMP, and circulating osteoclast precursors). At dosing visits, blood samples will be drawn 
prior to dosing, and will 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.
10.3
Nonhereditary pharmacogenomic variables
Where local regulation permit, blood samples will be drawn for exploratory RNA, proteins and 
metabolites biomarker analysis at the time points specified in Table 5‒1. Where local regulation 
permit, urine samples will be drawn for exploratory proteins and metabolites biomarker analysis 
at the time points specified in the schedule of study assessments. Collection of these samples will 
enable evaluation of biomarkers relative to disease biology and progression, drug treatment, bone 
metabolism and inflammatory and immune response processes. Instructions pertaining to sample 
collection, processing, storage, labeling, and shipping are provided in the laboratory manual for 
this study. The nature and format of these tentative analyses will be determined at a later stage. 
The samples will be stored at the secure long-term storage facility selected by UCB for up to 
20 years. 
10.4
Pharmacogenetic variables
For individuals consenting to the pharmacogenetic substudy, blood samples will be drawn for 
exploratory genetic/epigenetic, analyses at the time points specified in Table 5‒1. Collection of 
these samples will enable evaluation of genetics/epigenetics biomarkers relative to disease 
biology and progression, drug treatment, bone metabolism and inflammatory and immune 
response processes. The nature and format of these tentative analyses will be determined when 
the results of the main study are made available. A separate ICF will be required for those 
subjects who agree to participate in the pharmacogenetics substudy. The substudy will be 
conducted only where ethically accepted and authorized by the regulatory agencies. Refusal to 
participate in the substudy will not affect a subject’s ability to participate in the main study. The 
samples will be stored at -80°C at the central biorepository for up to 20 years. 
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLE(S)
The immunological variables comprise detection of anti-bimekizumab and anti-CZP antibodies 
related to immunogenicity, serum complement concentrations, mononuclear cell subtypes 
(analyzed by flow cytometry/fluorescence-activated cell sorting), and other exploratory 
biomarkers.
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Clinical Study Protocol
Bimekizumab
AS0013
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Page 64 of 136
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. The presence of antibodies to 
bimekizumab or CZP 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
Definitions
12.1.1.1
Adverse event
An adverse event (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. 
12.1.1.2
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
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 65 of 136
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 12.1.1.3], 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.)
12.1.1.2.1
Anticipated serious adverse events
The following Anticipated SAEs are anticipated to occur in the population studied in this 
protocol at some frequency that is independent of drug exposure. 
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 12.1.2.3.
Table 12‒1: Anticipated serious adverse events for the population of subjects 
with AS
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
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 66 of 136
Table 12‒1: Anticipated serious adverse events for the population of subjects 
with AS
MedDRA system organ class
MedDRA preferred term
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
AS=ankylosing spondylitis; MedDRA=Medical Dictionary for Regulatory Activities; SAE=serious adverse 
event
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.
12.1.1.3
Adverse events of special interest
An AE of special interest 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 AE of 
special interest (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.
In addition, events that are considered as Adverse Events of Interest for CZP include:

Serious infections including opportunistic infections

Malignancies including lymphoma

Congestive heart failure

Demyelinating-like disorders

Aplastic anaemia, pancytopenia, thrombocytopenia, neutropenia and leucopenia
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 67 of 136

Serious bleeding events

Lupus and lupus-like illness

Serious skin reactions (e.g. Stevens Johnson syndrome, toxic epidermal necrolysis, and 
erythema multiforme)
12.1.1.4
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: infections (serious, opportunistic, 
fungal, and TB, see Section 12.7.5), neutropenia, hypersensitivity, suicidal ideation and behavior 
(assessed using the C-SSRS), depression, (assessed using the HADS, see Section 9.10), major 
cardiovascular events, liver function test changes/enzyme elevations (ALT, AST, and bilirubin; 
see Section 12.6.1), malignancies, and inflammatory bowel diseases (with gastroenterology 
referral as appropriate).
12.1.2
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.
12.1.2.1
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 relationship to IMP) 
are described in the eCRF Completion Guidelines.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 68 of 136
12.1.2.2
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
12.1.2.3
Additional 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 Serious Adverse Event 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 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 safety 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.
12.1.3
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, and AEs of special interest; further details 
regarding follow up of PDILI events is provided in Section 12.6.1.4. 
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 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 69 of 136
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.
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time.
12.2
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 an early discontinuation visit.

The subject should immediately stop the intake of the IMP 

A Safety Follow-Up Visit should be scheduled 20 weeks after the subject has discontinued 
his/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 PS 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/Contract Research Organization (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, abortion (elective or 
spontaneous), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 70 of 136
anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report form.
12.3
Suspected transmission of an infectious agent
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.
12.4
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).
12.5
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 AS0013. 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 and a Neuropsychiatric 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.
12.6
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 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 71 of 136
the central laboratory. Testing to rule out hepatitis B, hepatitis C, and HIV (see Exclusion 
Criterion #12, 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.
The following laboratory parameters will be measured:
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Serology
Basophils
Bicarbonate
Albumin
HIV
Eosinophils 
Calcium
Bacteria
HLA-B27
Lymphocytes 
Chloride
Crystals
Hepatitis B
Atypical lymphocytes 
hs-CRPa
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pH
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RBC
Hematocrit
Sodium
WBC
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pregnancy testingb
MCH 
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MCHC 
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MCV 
AST
Platelet count 
ALT
RBC count 
ALP
WBC count 
GGT
Total bilirubinc
LDH
Uric acid
Total cholesterol
Serum FSH testingd
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 72 of 136
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Serology
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; FSH=follicle-stimulating hormone; GGT=gamma glutamyltransferase; HIV=human 
immunodeficiency virus; HLA-B27=human leukocyte antigen B27; hs-CRP=high sensitivity C-reactive 
protein; IMP=investigational medicinal product; LDH=lactate dehydrogenase; MCH=mean corpuscular 
hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; 
RBC=red blood cell; ULN=upper limit of normal; WBC=white blood cell
a hs-CRP will be tested at specified visits per Table 5‒1.
b A serum pregnancy test will be conducted at Screening – all other pregnancy tests will be performed on urine. 
Pregnancy results must be negative prior to administering IMP.
c If total bilirubin is >ULN, a direct bilirubin estimation (%) will be performed.
d A serum FSH test will be performed at Screening for all female subjects whose last menstrual cycle occurred 
between 12 and 24 months prior to the Screening Visit. 
12.6.1
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 
reported as an AE of special interest (see Section 12.1.1.3), and, if applicable, also reported as an 
SAE (see Section 12.1.1.2). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12‒4 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.6.1.1). 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 12.6.1.4). 
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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 73 of 136
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.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.


UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 74 of 136
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.c
Medical Monitor 
must be notified 
within 24 hours 
(eg, by laboratory 
alert) and subject 
discussed with 
Medical Monitor 
ASAP.
Immediate IMP 
discontinuationd.
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 12.6.1.3); 
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 
values.e
Monitoring of liver chemistry 
values at least twice per week 
for 2 weeks.e

Immediate IMP 
≥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 
24hours (eg, by 
laboratory alert) and 
subject discussed 
with Medical Monitor 
ASAP.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 75 of 136
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥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 12.6.1.2).
IMP discontinuation 
required if any of 
the following occur:

Subject cannot 
comply with 
monitoring 
schedule. 

Liver chemistry 
values continue 
to increase 

Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 
after 2 weeks of 
monitoring 
without 
evidence of 
resolution
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48hours at 
the site with HCP 
(see Section 
12.6.1.3).
discontinuation required if 
liver chemistry values 
continue to increase. After 2 
weeks of monitoring liver 
chemistry values: 

Discontinue IMP if levels 
remain ≥3xULN (and ≥2x 
baseline) without evidence 
of resolutione
Continue to monitor until values 
normalize, stabilize, or return to 
within baseline valuese.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 76 of 136
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
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 12.6.1.1. 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 Details are provided in Section 12.6.1.2.1.
e 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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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 77 of 136
12.6.1.1
Consultation with Medical Monitor and local hepatologist 
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24hours (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 12.6.1.3) and SAE report (if applicable).
12.6.1.2
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 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. 
12.6.1.2.1
IMP restart/rechallenge
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
12.6.1.3
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: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 78 of 136
Table 12‒4: PDILI laboratory measurements
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 screen
Chemistry
Amylase
Sodium, potassium, chloride, glucose, BUN, creatinine
Total bilirubin, ALP, AST, ALT, GGT, total cholesterol, albumin
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/INRa
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 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).
The following additional information is to be collected:
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 79 of 136
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
12.6.1.4
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.
12.7
Other safety measurements
12.7.1
Vital signs
The Investigator or designee should measure all vital signs (systolic and diastolic blood 
pressure (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, pulse and BP should be collected prior to IMP administration 
and then at 30 minutes and 1 hour after dosing. At all other visits pulse and BP should be 
collected prior to IMP administration.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 80 of 136
12.7.2
Body weight and height
Height is collected at the Screening Visit only. Body weight will be measured by the Investigator 
or designee at the time points listed in Table 5‒1. 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.
12.7.3
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.
12.7.4
12-lead electrocardiogram
The Investigator or designee will perform the ECG at time points specified in Table 5‒1. The 
ECGs will be read locally. The RR, PR, QRS, QT, and QT intervals corrected for heart rate using 
Fridericia’s formula (QTcF) including changes from Baseline ECG variables will be evaluated.
12.7.5
Tuberculosis and TB risk factor assessment and management
All subjects will be assessed for TB at the Screening Visit and at the time points specified in 
Table 5‒1 through physical examination for signs and symptoms of TB, chest X-ray or CT 
(Section 12.7.5.2), laboratory testing (Section 12.7.5.1), and subject questionnaire 
(Section 12.7.5.3). 
At the Screening Visit, all subjects will have an IGRA test (QuantiFERON TB test is 
recommended), a chest X-ray or CT (unless already performed within 3 months of screening) 
and an 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.
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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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 81 of 136
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 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 latent tuberculosis [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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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 82 of 136
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 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 WD Visit, complete all 
WD Visit assessments, and complete a SFU Visit (20 weeks after the final 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 WD 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. 
12.7.5.1
Tuberculosis assessment by IGRA
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB test is 
recommended) will be performed at Screening and should be repeated at the SFU Visit 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.
12.7.5.2
Chest X-ray for tuberculosis
A plain posteroanterior chest X-ray must be performed during 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 
current) before first IMP administration. All chest imaging (particularly X-rays) should be 
available for review by the Investigator before randomization of the subject. The chest X-ray 
should be repeated only if the TB test was confirmed positive or any further evidence is 
suggestive of potential lung TB infection (eg, exposure). Radiographic findings suggestive of 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 83 of 136
inactive TB or active TB may include but are not limited to: apical fibrosis, pleural thickening, 
pulmonary nodules, fibrotic scars, calcified granulomas, upper lobe infiltrates, cavitations and 
pleural effusions, calcified lung nodules, calcified hilar lymph nodes, and pericardial 
calcification.
The chest imaging must be negative for any old or recent TB infection as determined by a 
qualified radiologist and/or pulmonary physician. Any new clinically significant findings post 
Baseline on chest X-ray must be documented in the source documents and the eCRF as an AE.
12.7.5.3
Tuberculosis questionnaire 
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will be completed at the Screening Visit, Weeks 12, 24, 
and 36, and the SFU Visit. The questionnaire will assist with the identification of subjects who 
may require therapy for TB. A subject who answers “Yes” to the question “Has the subject been 
in close contact with an individual with active TB, or an individual who has recently been treated 
for TB?” at Screening is excluded. A “Yes” response to any of the other questions within the 
questionnaire at Screening should trigger further careful assessment to determine if subject has 
LTB or active TB (see Exclusion Criterion #13, Section 6.2). A “Yes” response to any of the 
questions during the study should trigger further assessments to determine if the subject has 
either LTB or active TB infection. 
Subjects with a latent or active TB infection must be withdrawn from the study.
12.7.5.4
Tuberculosis management
LTB infection and active TB identified during study
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of IMP and will be referred to an appropriate TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Evidence of 
LTB infection is defined as subject’s IGRA test converts to positive or indeterminate (and 
confirmed indeterminate on repeat), or the subject’s questionnaire or history and physical 
indicates that TB infection or exposure may have occurred. Evidence of active TB includes, in 
addition to the aforementioned tests, signs and symptoms of organ involvement. In either 
situation, the subject should be carefully assessed by a TB specialist for active TB. Subjects 
diagnosed with active TB or LTB infection should be withdrawn from the study and receive 
appropriate TB or prophylaxis therapy. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Confirmed active 
TB must be reported as an SAE. The Investigator is to complete and submit the TB follow-up 
Form provided.
The subject should be transferred to the care of his/her physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the WD Visit as soon as possible but no 
later than the next scheduled study visit and complete all WD Visit assessments. 
The subject should be encouraged to complete a SFU Visit (20 weeks after the final dose of 
IMP).
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 84 of 136
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed.
12.7.6
Pregnancy testing
A serum human chorionic gonadotropin (hCG) pregnancy test for all women of childbearing 
potential will be performed at the Screening Visit. 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).
Pregnancy testing will performed on urine at all other visits. Pregnancy test results (serum and 
urine) must be negative prior to administering IMP.
12.7.7
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed by trained study personnel using the C-SSRS. 
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the C-SSRS assessments will be performed are specified in the schedule of 
study assessments (Table 5‒1).
The C-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 
C-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The C-SSRS takes approximately 3 to 10 minutes to complete. 
Refer to Section 6.3 for C-SSRS-related withdrawal criteria.
13
OTHER STUDY MEASUREMENTS
13.1
Demographic and Baseline characteristics
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 will 
also be collected on Baseline characteristics for subjects including lifestyle, child bearing 
potential, as applicable, height, weight, and body mass index (BMI). Demographic and baseline 
characteristics 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.
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. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 85 of 136
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 EPM of the sponsor 
within 24 hours and follow any local regulatory requirements.
14.2
Monitoring
Monitoring of the study will be delegated by UCB to a CRO. The CRO 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. 
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 and/or printouts of eCRFs 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, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area.
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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 86 of 136
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
The study will use electronic data capture (EDC); the Investigator will be responsible for prompt 
reporting of accurate, complete, and legible data in the eCRFs and in all required reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator.
The Investigator should maintain a list of personnel authorized to enter data into the electronic 
eCRF. Access to the EDC will be given after training has been received. A training certificate 
will be provided and filed.
Serious AE reporting will be done using the SAE Report Form (see Section 12.1.2.3) 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.
Detailed instructions will be provided in the eCRF Completion Guidelines.
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. The data will be entered into the eCRFs once and will be subsequently verified if the 
study is performed using electronic data capture.
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 the 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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 87 of 136
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 
trial 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.
The main purposes of an audit or inspection are to confirm that the rights and wellbeing 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).
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 88 of 136
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 SAP. 
Deviations from the original SAP will be documented in the clinical study report (CSR).
15.1
Definition of analysis sets
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 subjects who receive at least 1 dose of the IMP.
The Full Analysis Set (FAS) will consist of all randomized subjects who receive at least 1 dose 
of the IMP and have a valid measurement of the primary efficacy variable at Baseline and at 
least 1 post-baseline efficacy assessment. 
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who have 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 Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of all randomized subjects who 
receive at least 1 dose of the IMP and have at least 1 quantifiable post-dose plasma 
concentration. 
The PET Per-Protocol Set (PET-PPS) will consist of all randomized subjects who receive at least 
1 dose of the IMP and have evaluable PET-CT or PET-MRI scan data at Baseline and at 
at least 1 of the post-Baseline assessments.
Further details of each analysis set along with specifications of analyses by analysis set will be 
provided in the SAP.
15.2
General statistical considerations
Statistical evaluation will be performed by PAREXEL and supervised by the Exploratory 
Statistics and Global Statistical Sciences Departments of UCB.
All analyses will be performed using SAS® Version 9.2 or later (SAS Institute, Cary, NC, USA) 
or R Version 2.10.1 (R Development Core Team) or later, or OpenBUGS Version 3.0.6 or later.
Descriptive statistics will be used to provide an overview of the Baseline, efficacy and safety 
results. For categorical parameters, the number and percentage of subjects in each category will 
be presented by treatment group. The denominator for the percentages will be based on the 
number of subjects appropriate for the purpose of analysis. Unless otherwise noted, all 
percentages will be expressed to 1 decimal place. For continuous parameters, descriptive 
statistics will include n, mean, standard deviation (SD), median, minimum, and maximum. Two-
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 89 of 136
sided 95% confidence intervals, geometric means, and coefficient of variation (CV) will be 
presented for selected variables as appropriate.
Baseline for each assessment is defined as either the value obtained at Baseline (Visit 2) or the 
last available value obtained prior to treatment administration at the Screening Visit (Visit 1) 
(details to be specified in the SAP).
Formal statistical testing will be conducted for this study for the primary efficacy variable. Other 
efficacy variables will be summarized descriptively by treatment group. Additional exploratory 
analyses will be conducted as deemed appropriate. 
15.3
Subject disposition 
The number of subjects who were screened, subjects included in each analysis set, and subjects 
who completed/prematurely discontinued the study, as well as the primary reason for 
discontinuation, will be presented by treatment group, and overall using frequency counts and 
percentages.
15.4
Subject characteristics
The following subject characteristics will summarized and listed as appropriate:

Demographics (including gender, age, race, and ethnicity)

Baseline characteristics (including lifestyle, childbearing potential, height, weight, and BMI) 

Medical/procedure history

Prior and concomitant medications/medical procedures 

Baseline disease characteristics
15.5
Planned efficacy analyses
The primary efficacy analyses will be based on the PPS.
15.5.1
Analysis of the primary efficacy variable
The primary efficacy analysis will be the comparison of the change from Baseline in ASDAS at 
Week 12 in the bimekizumab treatment group versus the CZP treatment group. Summary 
statistics will be presented by treatment group for ASDAS at each time point together with the 
changes from Baseline. 
The statistical analysis of the primary efficacy variable will be conducted following a Bayesian 
paradigm. An informative prior will be used for the model intercept coefficient which in the 
primary model is equal to the mean change from Baseline in ASDAS in the CZP group when 
centered Baseline is observed at its mean of zero (βCZP ~ Normal [-1.78, var=0.0605]). Vague 
priors will be used for all other model coefficients. All priors will be fully documented in the 
SAP and in the interim analysis SAP.
The Bayesian analysis will employ a linear regression model including treatment group and 
Baseline ASDAS (mean centered).
The posterior distributions of the mean changes from Baseline in ASDAS in the CZP and 
bimekizumab groups and of the difference in mean changes from Baseline between the treatment 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 90 of 136
groups (CZP - bimekizumab) will be summarized with means, standard deviations, 95% credible
intervals and 95% Highest Posterior Density intervals. The posterior probability that the 
difference between treatment groups in the mean change from Baseline in ASDAS is greater than 
zero will also be presented. The posterior probability that bimekizumab achieves a lower 
ASDAS score at Week 12 compared to CZP will be derived from this distribution.
The study will be considered a success if the posterior probability of the difference in the mean 
change from Baseline in ASDAS between the CZP and bimekizumab treatment groups (CZP -
bimekizumab) being greater than zero is at least 97.5% (ie, the lower bound of the 95% credible 
interval of the difference between treatment groups in the mean change from Baseline in ASDAS 
is zero or greater).
If further information (independent to this study) regarding the CZP treatment group response 
comes to light subsequent to writing this protocol then this prior may be updated prior to study 
unblinding, and details of this will be supplied in the SAP and the CSR. Note that the prior will 
not be updated based upon accrued study data at any time point.
15.5.2
Supportive analysis of the primary efficacy variable
A sensitivity analysis on the choice of the prior distribution for the CZP treatment arm will be 
conducted by repeating the primary analysis assuming vague priors for all parameters of the 
model. 
Additional sensitivity analyses will assess the primary efficacy for alternative analysis sets.
Further analyses may be performed for the primary efficacy variable adjusting for other Baseline 
covariates (to be defined in the SAP). Results from any additional analyses will not be used as a 
substitute for the planned analyses, but may be used as supplemental information for the CSR.
15.5.3
Analysis of the secondary efficacy variables
The secondary efficacy variables are listed in Section 4.1.2.
All secondary efficacy variables will be summarized descriptively by treatment group and time 
point. Estimated effects relating to the categorical variables ASDAS-MI and ASDAS-ID will be 
derived from the primary Bayesian analysis. Further details of the analysis methods for 
secondary efficacy variables will be included in the SAP.
15.5.4
Analysis of the other efficacy variables
The other efficacy variables are listed in Section 4.1.3.
The other efficacy variables will be listed and summarized descriptively by treatment group and 
time point. Any formal statistical analyses of the other efficacy variables will be described in 
more detail in the SAP.
Details of the summaries and analyses of efficacy data assessed during the Treatment Extension 
Period, will be provided in the SAP.
15.6
Pharmacokinetic analyses
Bimekizumab and CZP trough plasma concentrations will be listed and summarized by treatment 
group at each time point for all subjects in the PK-PPS using descriptive statistics. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 91 of 136
15.7
Immunological analyses
Immunological variables will be analyzed for all subjects in the PK-PPS.
Anti-bimekizumab and anti-CZP antibody data will be summarized at each scheduled visit, and 
the rate of ADA positive subjects for each treatment group will be calculated and presented.
15.8
Planned safety and other analyses
15.8.1
Safety analyses
All safety variables will be analyzed for all subjects in the SS.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®, version 19.0). The incidence of treatment-emergent adverse events (TEAEs) will be 
summarized descriptively by MedDRA system organ class, preferred term, and treatment group. 
Additional tables will summarize TEAEs by intensity and relationship to IMP, TEAEs leading to 
withdrawal from the study, serious TEAEs, and deaths. All AE information will be listed.
Laboratory values, ECGs, vital signs, physical examination, and extent of exposure will be 
presented descriptively by treatment group. The C-SSRS data will be listed only.
15.9
Handling of protocol deviations
After all data have been verified/coded/entered into a database, a data review will be performed. 
The purpose of this review will be to check all protocol deviations, define the PPS, and check the 
quality of the data. The review will also help decide how to manage problems in the subjects’ 
data (eg, missing values, withdrawals, dropouts, and protocol deviations). 
Accepted deviations from theoretical time points will be described in the appropriate documents 
and included in the Study Master File. After the pre-analysis review, resolution of all issues, and 
documentation of all decisions, the database will be locked.
15.10
Handling of dropouts or missing data
Appropriate missing data imputation methods will be used according to the variable being 
analyzed. Details will be included in the SAP.
15.11
Planned interim analysis and data monitoring
This study will include 3 informal unblinded interim analyses; the first after approximately 
45 subjects have completed 4 weeks of the study, the second when the last randomized subject 
not participating in the PET-MRI or PET-CT substudy has completed the Week 12 Visit at the 
end of the Treatment Period or has withdrawn prematurely from the study, and the third when 
the last randomized subject has completed the Week 12 Visit at the end of the Treatment Period 
or this subject’s participation has ended prematurely. 
The purpose of these interim analyses is for Sponsor key personnel to review results from the 
primary efficacy analysis and a subset of the analyses of secondary efficacy and safety outcomes 
to facilitate additional Clinical Planning or Portfolio Management decisions; consequently, none 
of the interim analyses will lead to any formal decision to alter or terminate the study. 
Interim analyses will be conducted by an unblinded study team and will follow internal SOPs for 
the formal process to control the unblinding of the study for interim analysis purposes. This 
process will ensure that no unnecessary or unintentional unblinding occurs. The unblinded team 
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 92 of 136
will not disclose any unblinded information to the blinded study team and the storage of all 
unblinded documentation will be held securely and separately from the rest of the study 
documentation and outputs up until the end of the study.
All analyses and unblinding instructions will be prespecified in the interim SAP.
15.12
Determination of sample size
A sufficient number of subjects will be enrolled in order to ensure at least 60 subjects are 
available at Week 12 to compare the change from Baseline in ASDAS between bimekizumab 
and CZP and at least 25 subjects will be enrolled into the PET-CT/MRI substudy.
Subjects will be randomized in a 2:1 ratio to receive bimekizumab or CZP respectively. 
The sample size was calculated to provide at least 80% power to detect a difference between 
treatment groups in the mean change from Baseline in ASDAS at Week 12 of 0.89 (group mean 
change from Baseline for CZP and bimekizumab being -1.78 and -2.67 respectively) with a 
common standard deviation of 1.17 using frequentist methods for the comparison of the 
treatment group mean change from Baseline in ASDAS at Week 12 with Baseline ASDAS as a 
covariate (Overall and Starbuck, 1979). The correlation between Baseline and Week 12 raw 
ASDAS was assumed to be 0.35. Note that the informative prior for the model intercept to be 
used in the Bayesian modelling of the primary efficacy variable, given by βCZP ~ Normal (-
1.78,var=0.0605), contributes an effective sample size of approximately 20 CZP subjects. A 
prior data conflict test will be performed and a vague prior will be used for the model intercept 
coefficient if this test indicates prior data conflict.
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 Informed Consent form should be signed and personally 
dated by the subject and by the person who conducted the informed consent discussion 
(Investigator or designee). The subject 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.
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 93 of 136
Separate ICFs will be required for subjects participating in the pharmacogenetic and 
pharmacogenomic substudy and in the PET-MRI or PET-CT substudy conducted at selected 
sites.
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 form, the subject 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), 
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. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 94 of 136
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.
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
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auth
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Clinical Study Protocol
Bimekizumab
AS0013
Confidential
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Bimekizumab
AS0013
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Page 97 of 136
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non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial 
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Bimekizumab
AS0013
Confidential
Page 98 of 136
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Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 99 of 136
19
APPENDICES
19.1
Modified New York (mNY) Classification Criteria for AS
Table 19‒1: Modified New York (mNY) Classification Criteria for AS
Diagnosis
1. 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.
2. Radiologic criterion:
Sacroiliitis grade ≥2 bilaterally or grade 3 to 4 unilaterally
Grading
1. 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 “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).
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Clinical Study Protocol
Bimekizumab
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Page 100 of 136
19.2
Markedly abnormal laboratory values
Table 19‒2: Definitions of markedly abnormal hematology values
Parameter (SI 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: SI=standard international
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 (SI 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; SI=standard international; 
ULN=upper limit of normal
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UCB
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Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 101 of 136
19.3
Protocol Amendment 1
Rationale for the amendment
The purpose of this protocol amendment is the following: 

Sections summarizing the use of concomitant DMARDs have been updated for internal 
consistency.

hs-CRP was added to the assessments at Screening.
In addition, minor clarifications were made and typographical errors were corrected.
Modifications and changes
Global changes
No global changes have been made.
Specific changes
Change #1 
Section 1, Summary, paragraph 8

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 3) in 
order to maintain the blind vs the certolizumab pegol (CZP) loading dose at these visits. 
Has been changed to:

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in 
order to maintain the blind vs the certolizumab pegol (CZP) loading dose at these visits. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 102 of 136
Change #2
Table 5-1, Schedule of assessments, Screening
Study Period
S
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Study Period
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Change #3
Table 5-1, Schedule of assessments, footnote g
g The physical examination includes the evaluation of signs and symptoms of active TB, risk for exposure to TB, 
height (Screening only) and weight (Baseline, Week 12 and Week 48/WD only).
Has been changed to:
g The physical examination includes the evaluation of signs and symptoms of active TB, risk for exposure to TB, 
height (Screening only) and weight (Screening, Week 12 and Week 48/WD only).
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UCB
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Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 103 of 136
Change #4
Section 7.8.1 Permitted concomitant treatments (medications and 
therapies)
The following concomitant medications are permitted during the study:
Subjects may use NSAIDs under the following conditions:

Subjects who are already receiving an established NSAID regimen and have been on a stable 
dose for at least 2 weeks prior to Baseline may continue their use during the study. However, 
initiation of, or increase in dosage of NSAIDs during the study (especially in subjects with a 
history of GI intolerance to NSAIDs or a history of GI ulceration) should be done with 
caution and must not occur until after the Week 12 Visit.
Subjects may use corticosteroids under the following conditions:

Oral (maximum allowed ≤10mg daily total prednisone equivalent)—subjects are permitted to 
decrease their oral corticosteroid therapy dose equivalent and/or alter their regimen only after 
Week 12
Subjects may use sulfasalazine and/or hydroxychloroquine under the following conditions:

Sulfasalazine (maximum SSZ ≤3g daily) and/or hydroxychloroquine (≤400mg daily) are 
allowed. No change in dose or dose regimen is allowed during the study except for reasons of 
intolerance, where the DMARD dose may be reduced or discontinued.
Subjects may use MTX under the following conditions:

No change in dose or dose regimen of MTX is allowed during the study except for reasons of 
intolerance/AEs. No increase of the MTX dose is permitted. No change is permitted in the 
route of administration for MTX (intramuscular [im], sc, or oral). It is strongly recommended 
that subjects taking MTX are also taking folic acid supplements. No combinations of 
DMARDs are permitted during the study.
Has been changed to: 
The following concomitant medications are permitted during the study:
Subjects may use NSAIDs under the following conditions:

Subjects who are already receiving an established NSAID regimen and have been on a stable 
dose for at least 2 weeks prior to Baseline may continue their use during the study. However, 
initiation of, or increase in dosage of NSAIDs during the study (especially in subjects with a 
history of GI intolerance to NSAIDs or a history of GI ulceration) should be done with 
caution and must not occur until after the Week 12 Visit.
Subjects may use corticosteroids under the following conditions:

Oral (maximum allowed ≤10mg daily total prednisone equivalent)—subjects are permitted to 
decrease their oral corticosteroid therapy dose equivalent and/or alter their regimen only after 
Week 12
Subjects may use MTX, sulfasalazine (SSZ), or hydroxychloroquine (HCQ) under the following 
conditions:
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 104 of 136

No change in dose or dose regimen of these agents is allowed during the study except for 
reasons of intolerance/AEs. No increase of the dose is permitted. No change is permitted in 
the route of administration for MTX (intramuscular [im], sc, or oral). It is strongly 
recommended that subjects taking MTX are also taking folic acid supplements. No 
combinations of DMARDs are permitted during the study.
Change #5 
Table 7-2, Prohibited or restricted medications and required wash-out 
periods prior to Baseline (MTX, SSZ, and HCQ)
Drug class
Dose
Exclusion criteria
…
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit 
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit 
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit 
…
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 
Has been changed to:
Drug class
Dose
Exclusion criteria
…
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit 
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit 
MTX, SSZ, and HCQ
Maximum allowed: 
SSZ ≤3g daily 
HCQ ≤400mg daily 
MTX ≤25mg weekly
Use initiated and/or any change in the 
dose regimen in the 28 days prior to the 
Baseline Visit. No change is permitted in 
the route of administration for MTX (im, 
sc, or oral) in the 28 days prior to the 
Baseline Visit.
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit 
…
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 105 of 136
Drug class
Dose
Exclusion criteria
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 
Change #6
Section 8.1, Screening Visit (Visit 1)
The following bullet has been added:

Collect samples for hs-CRP.
Change #7
Section 8.1, Screening Visit (Visit 1)

Measure vital signs (temperature, pulse, and blood pressure) prior to IMP administration and 
then at 30 minutes and 1 hour after dosing.
Has been changed to:

Measure vital signs (temperature, pulse, and blood pressure).
Change #8
Section 8.2, Baseline (Visit 2, Week 0)

Measure vital signs (temperature, pulse, and blood pressure).
Has been changed to:

Measure vital signs (temperature, pulse, and blood pressure) prior to IMP administration and 
then at 30 minutes and 1 hour after dosing.
Change #9
Section 12.7.5, Tuberculosis and TB risk factor assessment and 
management), latent TB
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.
Has been changed to:
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 106 of 136
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 subject must be withdrawn.
Change #10
Section 12.7.5.4, Tuberculosis management, LTB infection and active TB 
identified during study, paragraph 2
If a TB specialist excludes an active TB infection the subject can proceed with the IMP no earlier 
than 4 weeks after the start of an appropriate prophylactic therapy.
Has been deleted.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
no earlier 
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application and any extensions or variations thereof.


UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 107 of 136
19.4
Protocol Amendment 2
Rationale for the amendment
The purpose of this amendment is 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.
In the statistical analysis section of the protocol, text describing the planned analysis of the 
primary efficacy variable was updated, and text describing the planned interim analyses and 
sample size re-estimation was revised. The rationale for this is that the observed pattern of 
subject recruitment is not as expected at the time of study planning. Consequently, an insufficient 
number of subjects will have completed the Week 12 visit and be evaluable for response at the 
time of the first interim analysis. The risk of performing an analysis with a very small amount of 
data is that the estimates obtained from the analysis will be unstable and the risk of committing a 
Type II error will be inflated. To mitigate these risks it was decided to remove the formal futility 
and sample size re-estimation aspects from the first interim analysis.
In addition, it was further clarifed that PET-MRI or PET-CT scans for subjects at selected sites 
participating in the substudy will be performed at Screening and during the study at Week 12 and 
Week 48/Early Withdrawal Visit if PET positive lesions were observed in the previous scan.
Modifications and changes
Global changes
No global changes have been made.
Specific changes
Change #1
STUDY CONTACT INFORMATION
The Sponsor study physician and Clinical Trial Biostatistician have been 
changed:
Sponsor Study Physician
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
PUBLIC COPY 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 108 of 136
Clinical Trial Biostatistician
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
Change #2 
Section 5.1, Study description
A new paragraph has been added at the end of this section:
In approximately 25 subjects at selected sites, a PET-MRI or PET-CT scan will be performed at 
Screening and during the study at Week 12 and Week 48/Early Withdrawal Visit if PET positive 
lesions were observed in the previous scan.
Change #3 
Section 5.1.2, Treatment Period (Week 0 to Week 12), bullet #1
Eligible subjects will be randomized in a 2:1 ratio to receive the following blinded study 
treatments: 

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 3) in 
order to maintain the blind vs the CZP loading dose at these visits. 

CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10.
Study treatments will be prepared and administered by appropriately trained unblinded site 
personnel. 
A formal unblinded interim analysis will be conducted when approximately 45 subjects have 
completed the Week 4 Visit during the Treatment Period. In addition, an informal unblinded 
interim analysis of the primary efficacy variable is planned when the last randomized subject has 
completed the Week 12 Visit or the subject has discontinued prematurely from the study. Further 
details on the interim analyses planned for this study are included in Section 15.11 and in the 
interim Statistical Analysis Plan (SAP).
Has been changed to: 
Eligible subjects will be randomized in a 2:1 ratio to to receive the following blinded study 
treatments: 

Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will 
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in 
order to maintain the blind vs the CZP loading dose at these visits. 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 109 of 136

CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10.
Study treatments will be prepared and administered by appropriately trained unblinded site 
personnel. 
Change #4 
Section 5.3, Imaging evaluation, paragraph 1
In a subpopulation of AS0013, a PET-MRI or PET-CT scan of the entire spine will be performed 
at selected sites in approximately 25 subjects at Screening, Week 12, and at Week 48/Early 
Withdrawal Visit. 
Has been changed to: 
In a subpopulation of AS0013, a PET-MRI or PET-CT scan of the entire spine will be performed 
at selected sites in approximately 25 subjects at Screening, and during the study at Week 12 and 
Week 48/Early Withdrawal Visit if PET positive lesions were observed in the previous scan. 
Change #5 
Section 5.7, Schedule of assessments, Table 5-1, footnote c
A separate Informed Consent Form is required for subjects participating in the 2 sub-studies: 
1) with biomarker, pharmacogenomic and nonhereditary pharmacogenomic blood-samples and 
2) PET-MRI or PET-CT scans.
Has been changed to: 
A separate Informed Consent Form is required for subjects participating in the 2 sub-studies: 
1) with biomarker, pharmacogenetic and nonhereditary pharmacogenomic blood-samples and 
2) PET-MRI or PET-CT scans.
Change #6 
Section 5.7, Schedule of assessments, Table 5-1, footnote o
A PET-MRI or Pet-CT scan should be done up to 2 weeks before Baseline and within 2 weeks 
after the W12 and W48/WD Visit. If a subject withdraws from the study early, the PET-MRI or 
PET-CT scan must be repeated at the WD visit only, if the prior examination was done more 
than 12 weeks prior to the WD visit.
Has been changed to: 
A PET-MRI or PET-CT scan should be done up to 2 weeks before Baseline and within 2 weeks 
after the W12 and W48/WD Visit if PET-positive lesions are observed in the previous scan. If 
a subject withdraws from the study early, the PET-MRI or PET-CT scan must be repeated at the 
WD visit only, if the prior examination was done more than 12 weeks prior to the WD visit and 
the previous PET-scan showed positive lesions.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 110 of 136
Change #7
Section 5.7, Table 5-1 Schedule of assessments, footnote p
CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10 and 400mg Q4W from Week 12 to Week 44. Bimekizumab will be administered 
at a dose of 160mg sc Q2W from Week 0 through Week 10 and 320mg sc Q4W from Week 12 
to Week 44. The IMP will be administered at the end of the visit after all assessments have been 
completed. Subjects randomized to bimekizumab will receive 1 placebo injection at Baseline 
(Visit 2), Week 2 (Visit 3), and Week 4 (Visit 3). 
Has been changed to: 
CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W in 
Weeks 6 to 10 and 400mg Q4W from Week 12 to Week 44. Bimekizumab will be administered 
at a dose of 160mg sc Q2W from Week 0 through Week 10 and 320mg sc Q4W from Week 12 
to Week 44. The IMP will be administered at the end of the visit after all assessments have been 
completed. Subjects randomized to bimekizumab will receive 1 placebo injection at Baseline 
(Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4).
Change #8
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:

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 judgement 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 #9
Section 7.2, Treatments to be administered, paragraph 1
The IMP is to be administered in the clinic by trained study site staff as 2 sc injections. Suitable 
areas for sc injections are the lateral abdominal wall, upper outer thigh, and upper arm. 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.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 111 of 136
Has been changed to: 
The IMP is to be administered in the clinic by trained 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.
Change #10 
Section 7.9, Blinding, paragraph 1
Due to differences in presentation of the IMPs (bimekizumab and CZP), special precautions will 
be taken to ensure study blinding. Subjects randomized to bimekizumab will receive placebo at 
Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 3) in order to maintain the blind vs the 
CZP loading dose at these visits. 
Has been changed to: 
Due to differences in presentation of the IMPs (bimekizumab and CZP), special precautions will 
be taken to ensure study blinding. Subjects randomized to bimekizumab will receive placebo at 
Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 4) in order to maintain the blind vs the 
CZP loading dose at these visits. 
Change #11 
Section 7.9.1, Procedures for maintaining and breaking the treatment blind, 
last 2 paragraphs

Any Sponsor staff and/or designee who is responsible for data analyses for the unblinded 
DMC and interim analysis. These individuals will be separate from the main blinded study 
team.

Unblinded programming team at PAREXEL for the purpose of sending unblinded data cuts
Has been changed to: 

Any Sponsor staff and/or designee who is responsible for data analyses for the unblinded 
DMC and interim analyses. These individuals will be separate from the main blinded study 
team.

Unblinded team at PAREXEL for the purpose of sending unblinded output for the planned 
interim analyses
Change #12
Section 8.8, Week 12 (Visit 8), bullet #18

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks after Week 12 Visit.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 112 of 136
Has been changed to: 

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks after Week 12 Visit if PET positive lesions were observed in the previous scan.
Change #13
Section 8.11, Week 48 (Visit 17)/Early Withdrawal Visit, bullet #21

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks after the Week 48/WD Visit. At the WD Visit, the PET-MRI or PET-CT must be 
done only, if the previous imaging evaluation occurred more than 12 weeks ago
Has been changed to: 

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks after the Week 48/WD Visit if PET positive lesions were observed in the previous 
scan. At the WD Visit, the PET-MRI or PET-CT must be done only, if the previous imaging 
evaluation occurred more than 12 weeks ago and if PET positive lesions were observed in 
the previous scan.
Change #14 
Section 9.7, PhGADA, paragraph 1
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.
Has been changed to: 
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity 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.
Change #15
Section 10, ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC VARIABLE(S) 
Has been changed to: 
Section 10, ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC/PHARMACOGENETIC
VARIABLE(S) 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 113 of 136
Change #16
Section 12.6.1.3, Table 12-4 PDILI laboratory measurements
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Has been changed to: 
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
And the following was added to the list of abbreviations: 
AST=aspartate aminotransferase;
Change #17
Section 15.5.1, Analysis of the primary efficacy variable 
The primary efficacy analysis will be the comparison of the change from Baseline in ASDAS at 
Week 12 in the bimekizumab treatment group versus the CZP treatment group. Summary 
statistics will be presented by treatment group for ASDAS at each time point together with the 
changes from Baseline. 
The statistical analysis of the primary efficacy variable will be conducted following a Bayesian 
paradigm. Informative priors will be assumed for the mean change from Baseline in ASDAS in 
the CZP treatment arm and for the effect of Baseline ASDAS. These will be derived from an 
internal UCB study (AS0001). A vague prior will be applied to the mean change from Baseline 
in ASDAS in the bimekizumab treatment group. All priors will be fully documented in the SAP 
and in the interim analysis SAP.
The Bayesian analysis will employ a linear regression model including treatment group and 
adjusting for Baseline ASDAS.
The posterior distributions of the mean changes from Baseline in ASDAS in the CZP and 
bimekizumab groups and of the difference in mean changes from Baseline between the treatment 
groups (CZP - bimekizumab) will be summarized with means, standard deviations, 95% credible 
intervals and 95% Highest Posterior Density intervals. The posterior probability that the 
difference between treatment groups in the mean change from Baseline in ASDAS is greater than 
zero will also be presented. The posterior probability that bimekizumab achieves a lower 
ASDAS score at Week 12 compared to CZP will be derived from this distribution.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 114 of 136
The study will be considered a success if this posterior probability is at least 97.5% (ie, the lower
bound of the 95% credible interval of the difference between treatment groups in the mean 
change from Baseline in ASDAS is greater than zero). 
If further information (independent to this study) regarding the CZP treatment group response 
comes to light subsequent to writing this protocol then this prior may be updated prior to study 
unblinding, and details of this will be supplied in the SAP and the CSR. Note that the prior will 
not be updated based upon accrued study data at any time point.
Has been changed to: 
The primary efficacy analysis will be the comparison of the change from Baseline in ASDAS at 
Week 12 in the bimekizumab treatment group versus the CZP treatment group. Summary 
statistics will be presented by treatment group for ASDAS at each time point together with the 
changes from Baseline. 
The statistical analysis of the primary efficacy variable will be conducted following a Bayesian 
paradigm. An informative prior will be used for the model intercept coefficient which in the 
primary model is equal to the mean change from Baseline in ASDAS in the CZP group when 
centered Baseline is observed at its mean of zero (βCZP ~ Normal [-1.78, var=0.0605)). Vague 
priors will be used for all other model coefficients. All priors will be fully documented in the 
SAP and in the interim analysis SAP.
The Bayesian analysis will employ a linear regression model including treatment group and 
Baseline ASDAS (mean centered).
The posterior distributions of the mean changes from Baseline in ASDAS in the CZP and 
bimekizumab groups and of the difference in mean changes from Baseline between the treatment 
groups (CZP - bimekizumab) will be summarized with means, standard deviations, 95% credible 
intervals and 95% Highest Posterior Density intervals. The posterior probability that the 
difference between treatment groups in the mean change from Baseline in ASDAS is greater than 
zero will also be presented. The posterior probability that bimekizumab achieves a lower 
ASDAS score at Week 12 compared to CZP will be derived from this distribution.
The study will be considered a success if the posterior probability of the difference in the mean 
change from Baseline in ASDAS between the CZP and bimekizumab treatment groups (CZP -
bimekizumab) being greater than zero is at least 97.5% (ie, the lower bound of the 95% credible 
interval of the difference between treatment groups in the mean change from Baseline in ASDAS 
is zero or greater).
If further information (independent to this study) regarding the CZP treatment group response 
comes to light subsequent to writing this protocol then this prior may be updated prior to study 
unblinding, and details of this will be supplied in the SAP and the CSR. Note that the prior will 
not be updated based upon accrued study data at any time point.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 115 of 136
Change #18
Section 15.11, Planned interim analysis and data monitoring 
A formal unblinded interim analysis will be conducted after approximately 45 subjects have 
completed 4 weeks of the study. During this interim analysis, the sample size assumptions will 
be checked and the final sample size may be modified. 
The study may be stopped for futility. Futility rules and operating characteristics will be detailed 
in the interim SAP. The futility rule will be chosen such that the overall power of the study 
remains high.
An informal unblinded interim analysis will be performed when the last randomized subject for 
this study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely. The purpose of this informal interim analysis is for the 
Sponsor key personnel to review results from the primary efficacy analysis and a subset of the 
analyses of secondary efficacy and safety outcomes to facilitate additional Clinical Planning or 
Portfolio Management decisions.
All analyses and unblinding instructions will be prespecified in the interim SAP.
Has been changed to: 
This study will include two unblinded interim analyses, the first after approximately 45 subjects 
have completed 4 weeks of the study and the second when the last randomized subject for this 
study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely. The purpose of these interim analyses is for Sponsor key 
personnel to review results from the primary efficacy analysis and a subset of the analyses of 
secondary efficacy and safety outcomes to facilitate additional Clinical Planning or Portfolio 
Management decisions; consequently, neither analysis and will lead to any formal decision to 
alter or terminate the trial. Interim analyses will be conducted by an unblinded study team and 
will follow internal SOPs for the formal process to control the unblinding of the study for interim 
analysis purposes. This process will ensure that no unnecessary or unintentional unblinding 
occurs. The unblinded team will not disclose any unblinded information to the blinded study 
team and the storage of all unblinded documentation will be held securely and separately from 
the rest of the study documentation and outputs up until the end of the study.
All analyses and unblinding instructions will be prespecified in the interim SAP.
Change #19
Section 15.12, Determination of sample size, paragraph 3
The sample size was calculated to provide at least 80% power to detect a difference between 
treatment groups in the mean change from Baseline in ASDAS at Week 12 of 0.89 (group means 
for CZP and bimekizumab change from baseline being -1.78 and -2.67 respectively) with a 
common standard deviation of 1.17 using frequentist methods for the comparison of group 
means with baseline as covariate (Overall and Starbuck, 1979). The correlation between Baseline 
and Week 12 raw ASDAS was assumed to be 0.35. UCB considers this sample size conservative 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 116 of 136
as the Bayesian analysis with the informative priors described in Section 15.5.1 will improve the 
probability of study success for an effective drug.
Has been changed to: 
The sample size was calculated to provide at least 80% power to detect a difference between 
treatment groups in the mean change from Baseline in ASDAS at Week 12 of 0.89 (group mean 
change from Baseline for CZP and bimekizumab being -1.78 and -2.67 respectively) with a 
common standard deviation of 1.17 using frequentist methods for the comparison of the 
treatment group mean change from Baseline in ASDAS at Week 12 with Baseline ASDAS as a 
covariate (Overall and Starbuck, 1979). The correlation between Baseline and Week 12 raw 
ASDAS was assumed to be 0.35. Note that the informative prior for the model intercept to be 
used in the Bayesian modelling of the primary efficacy variable, given by βCZP ~ Normal (-
1.78,var=0.0605), contributes an effective sample size of approximately 20 CZP subjects. A 
prior data conflict test will be performed and a vague prior will be used for the model intercept 
coefficient if this test indicates prior data conflict.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 117 of 136
19.5
Protocol Amendment 3
Rationale for the amendment
The major purpose of this protocol amendment is the following: 

Secondary and other study objectives and variables have been updated to evaluate the effect 
of bimekizumab or CZP on changes in bone formation as an “other” exploratory variable. 
It is convention that clinical study research is divided into 2 broad areas of evaluations: 
1) prospectively declared analyses and 2) hypothesis-generating or exploratory analyses. 
Prospectively declared evaluations are partitioned into primary analyses (where type I error is 
conserved) and secondary analyses that are prospectively declared in order to offer 
unambiguous interpretation. Owing to the novelty of PET-CT/MRI assessments within this 
disease indication, it is not possible to prospectively define the analyses as we are continuing 
to develop UCB’s understanding of the specific data and endpoints yielded from the imaging 
software, the distribution and covariance of these endpoints and the hypothesized difference 
owing to treatment. As a result, the analyses of the PET-CT/MRI data in this study will 
primarily be descriptive and exploratory and this is now updated in the study objectives, ie, 
the evaluation of the effect of bimekizumab or CZP on changes in bone formation is now an 
other exploratory objective or variable instead of a secondary objective or variable.

A clarification regarding the sample size is required in this protocol amendment. The planned 
sample size of 60 subjects provides sufficient power to detect meaningful treatment 
differences in the primary efficacy variable whilst also providing at least 25 subjects for the 
PET-CT/MRI substudy. However, due to complexities in the initiation of sites capable of 
performing PET-CT or PET-MRI scans, more than the planned 35 non-PET-CT/MRI 
substudy subjects were screened and randomized before it was possible to close enrolment at 
the sites not participating in the substudy. Owing to the novelty of the PET-CT/MRI 
outcomes within this disease area, it is considered important to ensure at least 25 evaluable 
subjects are included in the assessment of this exploratory objective to maximize the 
possibility of identifying the salient factors or variables that might differ between the 
treatment groups and, therefore, the total sample size is increased to at least 72 subjects. This 
sample size increase will not negatively impact the power to detect a difference in the 
primary efficacy variable at Week 12 (ie, it will remain >80%), but will ensure that the target 
number of subjects are included in the exploratory analysis of changes in bone formation at 
Week 12 and Week 48. Since the analyses of PET-CT/MRI data are exploratory and 
treatment effect sizes are unknown, formal power calculations were not performed. Clinical 
expertise does, however, indicate that a sample size of at least 25 subjects in the substudy 
will characterize broad differences between treatment groups.

Objectives related to PK and immunogenicity were downgraded from “secondary” objectives 
to “other” objectives for consistency with the classification of the corresponding variables.

Nonhereditary pharmacogenomic variables and pharmacogenetic variables are considered 
exploratory in nature and have been labelled as “other”.

A PFS as described in Section 7.1 is available for administration in addition to the vial and 
corresponding text has been added. The PFS use is expected to improve the subject 
experience.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 118 of 136

The section describing AEs of special monitoring have been updated to reflect the 
development process and to maintain consistency with other protocols. 

A third informal unblinded interim analysis when the last randomized subject has completed 
the Week 12 Visit at the end of the Treatment Period or this subject’s participation has ended 
prematurely, has been added to facilitate additional Clinical Planning or Portfolio 
Management decisions. 

Study contact details have been updated.
In addition, a few minor updates including consistency changes for PDILI-related text and a few 
clarifications and corrections of typographical errors have been made. The occurrence of 
abbreviations was updated.
Modifications and changes
Global changes
The specification of the IGRA TB test has been changed from “QuantiFERON TB GOLD test” 
to “QuantiFERON TB test”.
Specific changes
Change #1
Sponsor Study Physician
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
Has been changed to: 
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
Change #2
Section 1, Summary, paragraphs 3, 4, and 5
The primary objective of the study is to evaluate the efficacy of bimekizumab administered 
subcutaneously (sc) every 2 weeks (Q2W) for 12 weeks compared to CZP in the treatment of 
subjects with active AS. The primary efficacy variable is the change from Baseline in 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 119 of 136
Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12. The secondary objectives 
of the study are to evaluate the effect of bimekizumab or CZP on changes in osteoblastic activity, 
to assess the safety and tolerability of bimekizumab, and to assess the pharmacokinetics (PK) 
and immunogenicity of bimekizumab. The secondary efficacy variables include the 
determination of ASDAS inactive disease (ASDAS-ID) at Week 12, ASDAS major 
improvement (ASDAS-MI) at Week 12, and osteoblastic activity as detected by 
positron-emission tomography-magnetic resonance imaging (PET-MRI) or positron-emission 
tomography computed tomography (PET-CT) at Week 12 and Week 48. Primary safety variables 
include the incidence of adverse events (AEs), serious adverse events (SAEs), and withdrawal 
due to AEs.
Other objectives of the study are to obtain additional biomarkers and clinical and imaging data as 
applicable and to assess the efficacy and safety of bimekizumab or CZP during the Treatment 
Extension Period.
Multiple sites in North America, Europe, and the Asian-Pacific (APAC) region will randomize 
approximately 60 subjects in a 2:1 ratio to receive either bimekizumab or CZP. 
Has been changed to: 
The primary objective of the study is to evaluate the efficacy of bimekizumab administered 
subcutaneously (sc) every 2 weeks (Q2W) for 12 weeks compared to CZP in the treatment of 
subjects with active AS. The primary efficacy variable is the change from Baseline in 
Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12. The secondary objective 
of the study is to assess the safety and tolerability of bimekizumab. The secondary efficacy 
variables include the determination of ASDAS inactive disease (ASDAS-ID) and ASDAS major 
improvement (ASDAS-MI) at Week 12. Primary safety variables include the incidence of 
adverse events (AEs), serious adverse events (SAEs), and AEs leading to withdrawal from 
investigational medicinal product (IMP).
Other exploratory objectives of the study are to evaluate the effect of bimekizumab or CZP 
on changes in bone formation, to assess the pharmacokinetics (PK) and immunogenicity of 
bimekizumab, to obtain additional biomarkers and clinical and imaging data as applicable, and 
to assess the efficacy and safety of bimekizumab or CZP during the Treatment Period and the 
Treatment Extension Period.
Multiple sites in North America, Europe, and the Asian-Pacific (APAC) region will randomize at 
least 60 subjects in a 2:1 ratio to receive either bimekizumab or CZP. 
Change #3
Section 3.2, Secondary objectives
The secondary objectives of the study are as follows:

To evaluate the effect of bimekizumab or CZP on changes in osteoblastic activity 

To assess the safety and tolerability of bimekizumab

To assess the PK and immunogenicity of bimekizumab
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 120 of 136
Has been changed to: 
Section 3.2, Secondary objective
The secondary objective of the study is as follows:

To assess the safety and tolerability of bimekizumab
Change #4
Section 3.3, Other objectives
The other objectives of the study are as follows:

To assess additional biomarker, clinical, and imaging data as available

To assess the efficacy and safety of bimekizumab or CZP during the Treatment Extension 
Period
Has been changed to: 
Section 3.3, Other exploratory objectives
The other exploratory objectives of the study are as follows:

To evaluate the effect of bimekizumab or CZP on changes in bone formation 

To assess the PK and immunogenicity of bimekizumab

To assess additional biomarker, clinical, and imaging data as available

To assess the efficacy and safety of bimekizumab or CZP during the Treatment Extension 
Period
Change #5
Section 4.1.2, Secondary efficacy variables
The secondary efficacy variables for this study are as follows:

ASDAS-ID at Week 12

ASDAS-MI at Week 12

Osteoblastic activity as detected by PET-MRI or PET-CT at Week 12 and Week 48 
Has been changed to: 
The secondary efficacy variables for this study are as follows:

ASDAS-ID at Week 12

ASDAS-MI at Week 12
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 121 of 136
Change #6
Section 4.1.3, Other efficacy variables
Assessment time points for the other efficacy variables are specified in Table 5‒1. Other efficacy 
variables are as follows:

Change from Baseline in ASDAS

ASAS20 response

ASAS40 response

Time to ASAS20 response

Time to ASAS40 response

ASAS partial remission

Change from Baseline in BASDAI
Has been changed to: 
Section 4.1.3, Other efficacy variables
Assessment time points for the other efficacy variables are specified in Table 5‒1. The following 
efficacy variables are exploratory and are assessed over the Treatment Period and 
Treatment Extension Period, as applicable:

Change from Baseline in ASDAS

ASAS20 response

ASAS40 response

Time to ASAS20 response

Time to ASAS40 response

ASAS partial remission

Change from Baseline in BASDAI

Changes in bone formation as measured by standardized uptake value by area under 
the curve (SUVAUC) and derived from PET-MRI or PET-CT at Baseline, Week 12, and 
Week 48 
Change #7, Primary safety variables
The primary safety variables for this study are as follows:

Incidence of AEs and SAEs

Withdrawal due to AEs
Has been changed to: 
The primary safety variables for this study are as follows:
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 122 of 136

Incidence of AEs and SAEs

Adverse events leading to withdrawal from IMP
Change #8, Section header
4.5
Nonhereditary pharmacogenomic variables
Has been changed to: 
4.5
Other nonhereditary pharmacogenomic variables
Change #9, Section header
4.6
Pharmacogenetic variables
Has been changed to: 
4.6
Other pharmacogenetic variables 
Change #10
Section 5.1, Study description, paragraph 3
Approximately 60 subjects will be randomized to 1 of 2 treatment arms in a 2:1 ratio and will 
receive either bimekizumab or CZP up to Week 44 (final dose of IMP). 
Has been changed to: 
At least 60 subjects will be randomized to 1 of 2 treatment arms in a 2:1 ratio and will receive 
either bimekizumab or CZP up to Week 44 (final dose of IMP). 
Change #11
Section 5.5, Planned number of subjects and site(s)
It is anticipated that approximately 120 subjects will be screened in order to enroll approximately 
60 subjects at multiple sites.
Has been changed to: 
It is anticipated that approximately 120 subjects will be screened in order to enroll at least
60 subjects in the main study and at least 25 subjects in the PET-CT or PET-MRI substudy 
at multiple sites.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 123 of 136
Change #12
Section 6.3.1, Potential drug-induced liver injury IMP discontinuation 
criteria, paragraph 2
The PDILI criteria below require immediate and permanent discontinuation of IMP: 
Subjects with either of the following:

ALT or AST ≥5ULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness. Hypersensitivity symptoms include fever (without clear alternative cause), 
rash, or eosinophilia (ie, >5%).
Has been changed to: 
The PDILI criteria below require immediate discontinuation of IMP: 
Subjects with either of the following:

ALT or AST ≥5ULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
Change #13
Section 7.1, Description of investigational medicinal product(s), 
paragraphs 1 and 2
The IMPs used in this study are bimekizumab and CZP.
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative-free solution in 2mL Type I, colorless glass vials (1.0mL extractable volume) closed 
with a rubber stopper and sealed with an aluminum cap overseal. Each single-use dose vial will 
contain 160mg/mL bimekizumab in 
mM sodium acetate,
mM glycine and 
 (w/v) 
polysorbate 80 at pH 
.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 124 of 136
Has been changed to: 
The IMPs used in this study are bimekizumab and CZP.
Bimekizumab will be supplied as a vial or in a pre-filled syringe (PFS) form as described 
below: 

Vial: a clear to opalescent, colorless to slightly brown, sterile, preservative-free solution in 
2mL Type I, colorless glass vials (1.0mL extractable volume) closed with a rubber stopper 
and sealed with an aluminum cap overseal. Each single-use dose vial will contain 160mg/mL 
bimekizumab in 
mM sodium acetate, 
mM glycine, and 
 (w/v) polysorbate 80 at 
pH 

PFS: 1mL PFS at a concentration of 160mg/mL 
mM sodium acetate, 
mM 
glycine, 
 polysorbate 80 at pH 
) for sc injection.
Change #14
Section 8.8, Week 12 (Visit 8), PET-MRI/PET-CT scan bullet

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 
2 weeks after Week 12 Visit if PET positive lesions were observed in the previous scan.
Has been changed to: 

Perform a PET-MRI or PET-CT scan in at least 25 subjects at selected sites within 2 weeks 
after Week 12 Visit if PET-positive lesions were observed in the previous scan.
Change #15
Section 8.11, Week 48 (Visit 17), PET-MRI/PET-CT scan bullet

Perform a PET-MRI or PET-CT scan in approximately 25 subjects at selected sites within 2 
weeks after the Week 48/WD Visit if PET positive lesions were observed in the previous 
scan. At the WD Visit, the PET-MRI or PET-CT must be done only, if the previous imaging 
evaluation occurred more than 12 weeks ago and if PET positive lesions were observed in the 
previous scan.
Has been changed to: 

Perform a PET-MRI or PET-CT scan in at least 25 subjects at selected sites within 2 weeks 
after the Week 48/WD Visit if PET-positive lesions were observed in the previous scan. At 
the WD Visit, the PET-MRI or PET-CT must be done only, if the previous imaging 
evaluation occurred more than 12 weeks ago and if PET-positive lesions were observed in 
the previous scan.
Change #16
Section 9.11, PET-MRI or PET-CT scan, last paragraph
The 18F-fluoride PET-MRIs of the whole spines will be performed by using a whole-body 
PET/MRI system. Alternatively, subjects will be examined in supine position on a combined 
PET-CT system permitting the acquisition of co-registered CT and PET images in the same 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 125 of 136
session. The PET-MRI or PET-CT scan will be performed at time points provided in Table 5‒1
in approximately 25 subjects at selected sites.
Has been changed to: 
The 18F-fluoride PET-MRIs of the whole spine will be performed by using a whole-body 
PET/MRI system. Alternatively, subjects will be examined in supine position on a combined 
PET-CT system permitting the acquisition of co-registered CT and PET images in the same 
session. The PET-MRI or PET-CT scan will be performed at time points provided in Table 5‒1
in at least 25 subjects at selected sites.
Change #17
Section 12.1.14, Adverse events for special monitoring, section header and 
paragraph 2
12.1.1.4
Adverse events for special monitoring
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 12.7.5), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the C-SSRS), depression and anxiety (assessed using the 
HADS, see Section 9.10), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin; see Section 12.6.1), malignancies, and inflammatory bowel 
diseases.
Has been changed to: 
12.1.1.4
Adverse events for special monitoring
Adverse events for special monitoring for this study include: infections (serious, opportunistic, 
fungal, and TB, see Section 12.7.5), neutropenia, hypersensitivity, suicidal ideation and
behavior (assessed using the C-SSRS), depression, (assessed using the HADS, see Section 9.10), 
major cardiovascular events, liver function test changes/enzyme elevations (ALT, AST, and 
bilirubin; see Section 12.6.1), malignancies, and inflammatory bowel diseases (with 
gastroenterology referral as appropriate).
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 126 of 136
Change #18
Section 12.6.1, Evaluation of PDILI, Table 12-3
Table 12‒3:
Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.b
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 12.6.1.3); 
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 
values.b
Monitoring of liver chemistry 
values at least twice per week 
for 2 weeks.d

Immediate IMP 
discontinuation required if 
liver chemistry values
≥3xULN
NA
Yes
≥5xULN
NA
NA
Need for hepatology 
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discussed. (required 
if ALT or AST 
≥8xULN) Medical 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 127 of 136
Table 12‒3:
Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥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 12.6.1.2).
IMP discontinuation 
required if any of 
the following occur:

Subject cannot 
comply with 
monitoring 
schedule. 

Liver chemistry 
values continue 
to increase 

Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 
after 2 weeks of 
monitoring 
without 
evidence of 
resolution 
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48hours at 
the site with HCP 
(see Section 
12.6.1.3).
continue to increase. After 2 
weeks of monitoring liver 
chemistry values:

Discontinue IMP if levels 
remain ≥3xULN (and ≥2x 
baseline) without evidence 
of resolutiond 
Continue to monitor until values 
normalize, stabilize, or return to 
within baseline valuesd.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 128 of 136
Table 12‒3:
Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
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 12.6.1.1. 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.
Has been changed to: 
Table 12-3:Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.c
Medical Monitor 
must be notified 
within 24 hours 
(eg, by laboratory 
alert) and subject 
discussed with 
Medical Monitor 
ASAP.
Immediate IMP 
discontinuationd.
Essential: Must 
have repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 12.6.1.3); 
recommended to 
occur at the site 
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.e
≥3xULN
NA
Yes
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 129 of 136
Table 12-3:Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥5xULN
NA
NA
Need for hepatology 
consult to be 
discussed. (required 
if ALT or AST 
≥8xULN). Medical 
Monitor must be 
notified within 
24hours (eg, by 
laboratory alert) and 
subject discussed 
with Medical Monitor 
ASAP.
with HCP.
Monitoring of liver chemistry 
values at least twice per week 
for 2 weeks.e

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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 130 of 136
Table 12-3:Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥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 12.6.1.2).
IMP discontinuation 
required if any of 
the following occur:

Subject cannot 
comply with 
monitoring 
schedule. 

Liver chemistry 
values continue 
to increase 

Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 
after 2 weeks of 
monitoring 
without 
evidence of 
resolution 
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48hours at 
the site with HCP 
(see Section 
12.6.1.3).
discontinuation required if 
liver chemistry values
continue to increase. After 2 
weeks of monitoring liver 
chemistry values:

Discontinue IMP if levels 
remain ≥3xULN (and ≥2x 
baseline) without evidence 
of resolutione
Continue to monitor until values 
normalize, stabilize, or return to 
within baseline valuese.
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 131 of 136
Table 12-3:Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
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 12.6.1.1. 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 Details are provided in Section 12.6.1.2.1.
e 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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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 132 of 136
Change #19
Section 12.6.1.2, Immediate action: Determination of IMP discontinuation, 
paragraph 2
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).
Has been changed to: 
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 discontinuation (see Section 6.3.1 and Table 12‒3 for details).
Change #20
Section 12.6.1.3, Testing: Identification/exclusion of alternative etiology, 
Table 12-4, chemistry
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
Has been changed to: 
Chemistry
Amylase
Sodium, potassium, chloride, glucose, BUN, creatinine
Total bilirubin, ALP, AST, ALT, GGT, total cholesterol, albumin
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Change #21
Section 15.1, Definition of analysis sets
The following analysis set has been added: 
The PET Per-Protocol Set (PET-PPS) will consist of all randomized subjects who receive at 
least 1 dose of the IMP and have evaluable PET-CT or PET-MRI scan data at Baseline and 
at at least 1 of the post-Baseline assessments.
Change #22
Section 15.8.1, Safety analyses, paragraph 2
Adverse events will be coded according to the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA®). The incidence of treatment-emergent adverse events 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 133 of 136
(TEAEs) will be summarized descriptively by MedDRA system organ class, preferred term, and 
treatment group. Additional tables will summarize TEAEs by intensity and relationship to IMP, 
TEAEs leading to withdrawal from the study, serious TEAEs, and deaths. All AE information 
will be listed.
Has been changed to: 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®, version 19.0). The incidence of treatment-emergent adverse events (TEAEs) will be 
summarized descriptively by MedDRA system organ class, preferred term, and treatment group. 
Additional tables will summarize TEAEs by intensity and relationship to IMP, TEAEs leading to 
withdrawal from the study, serious TEAEs, and deaths. All AE information will be listed.
Change #23
Section 15.11, Planned interim analysis and data monitoring
This study will include two unblinded interim analyses, the first after approximately 45 subjects 
have completed 4 weeks of the study and the second when the last randomized subject for this 
study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely. The purpose of these interim analyses is for Sponsor key 
personnel to review results from the primary efficacy analysis and a subset of the analyses of 
secondary efficacy and safety outcomes to facilitate additional Clinical Planning or Portfolio 
Management decisions; consequently, neither analysis and will lead to any formal decision to 
alter or terminate the trial. Interim analyses will be conducted by an unblinded study team and 
will follow internal SOPs for the formal process to control the unblinding of the study for interim 
analysis purposes. This process will ensure that no unnecessary or unintentional unblinding 
occurs. The unblinded team will not disclose any unblinded information to the blinded study 
team and the storage of all unblinded documentation will be held securely and separately from 
the rest of the study documentation and outputs up until the end of the study.
All analyses and unblinding instructions will be prespecified in the interim SAP.
Has been changed to: 
This study will include 3 informal unblinded interim analyses; the first after approximately 
45 subjects have completed 4 weeks of the study, the second when the last randomized subject 
not participating in the PET-MRI or PET-CT substudy has completed the Week 12 Visit at 
the end of the Treatment Period or has withdrawn prematurely from the study, and the third 
when the last randomized subject has completed the Week 12 Visit at the end of the 
Treatment Period or this subject’s participation has ended prematurely. 
The purpose of these interim analyses is for Sponsor key personnel to review results from the 
primary efficacy analysis and a subset of the analyses of secondary efficacy and safety outcomes 
to facilitate additional Clinical Planning or Portfolio Management decisions; consequently, none 
of the interim analyses will lead to any formal decision to alter or terminate the study. 
Interim analyses will be conducted by an unblinded study team and will follow internal SOPs for 
the formal process to control the unblinding of the study for interim analysis purposes. This 
process will ensure that no unnecessary or unintentional unblinding occurs. The unblinded team 
will not disclose any unblinded information to the blinded study team and the storage of all 
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UCB
27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 134 of 136
unblinded documentation will be held securely and separately from the rest of the study 
documentation and outputs up until the end of the study.
All analyses and unblinding instructions will be prespecified in the interim SAP.
Change #24
Section 15.12, Determination of sample size, first paragraph
A sufficient number of subjects will be enrolled in order to ensure 60 subjects are available at 
Week 12 to compare the change from Baseline in ASDAS between bimekizumab and CZP.
Has been changed to: 
A sufficient number of subjects will be enrolled in order to ensure at least 60 subjects are 
available at Week 12 to compare the change from Baseline in ASDAS between bimekizumab 
and CZP and at least 25 subjects will be enrolled into the PET-CT/MRI substudy.
PUBLIC COPY 
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UCB
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Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 135 of 136
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
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Date
CO
Date
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ing authorization 
be treated
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27 Feb 2019
Clinical Study Protocol
Bimekizumab
AS0013
Confidential
Page 136 of 136
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.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.


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SAP_001.pdf: 
UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 1 of 86
STATISTICAL ANALYSIS PLAN 
Study: AS0013
Product: Bimekizumab
A MULTICENTER, PHASE 2A, RANDOMIZED,
INVESTIGATOR-BLIND, SUBJECT-BLIND, 
PARALLEL-GROUP
STUDY TO EVALUATE THE EFFICACY AND SAFETY OF
BIMEKIZUMAB AND CERTOLIZUMAB PEGOL IN SUBJECTS
WITH ACTIVE ANKYLOSING SPONDYLITIS
SAP/Amendment Number
Date
Final SAP
17 January 2018
Amendment 1
15 August 2018
Amendment 2
23 May 2019
Amendment 3
19 June 2020
Confidentiality Statement
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.
PUBLIC COPY 
IN
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 2 of 86
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................7
1
INTRODUCTION ...........................................................................................................11
2
PROTOCOL SUMMARY...............................................................................................11
2.1
Study objectives...........................................................................................................11
2.1.1
Primary objective.................................................................................................11
2.1.2
Secondary objectives ...........................................................................................11
2.1.3
Other objectives...................................................................................................11
2.2
Study variables.............................................................................................................12
2.2.1
Efficacy variables ................................................................................................12
2.2.1.1
Primary efficacy variable ..........................................................................12
2.2.1.2
Secondary efficacy variables.....................................................................12
2.2.1.3
Other efficacy variables.............................................................................12
2.2.2
Safety variables....................................................................................................12
2.2.2.1
Primary safety variables ............................................................................12
2.2.2.2
Other safety variables................................................................................13
2.2.3
Pharmacokinetic variables...................................................................................13
2.2.4
Pharmacodynamic variables ................................................................................13
2.2.5
Immunological variables .....................................................................................13
2.2.6
Nonhereditary pharmacogenomic variables ........................................................13
2.2.7
Pharmacogenetic variables ..................................................................................13
2.3
Study design and conduct ............................................................................................14
2.4
Determination of sample size.......................................................................................15
3
DATA ANALYSIS CONSIDERATIONS......................................................................16
3.1
General presentation of summaries and analyses ........................................................16
3.2
General study level definitions ....................................................................................18
3.2.1
Relative day .........................................................................................................18
3.2.2
Study periods .......................................................................................................18
3.3
Definition of Baseline values.......................................................................................18
3.4
Protocol deviations.......................................................................................................20
3.5
Analysis sets.................................................................................................................21
3.5.1
Enrolled Set .........................................................................................................21
3.5.2
Randomized Set...................................................................................................21
3.5.3
Safety Set.............................................................................................................21
3.5.4
Full Analysis Set..................................................................................................21
3.5.5
Per-Protocol Set...................................................................................................21
3.5.6
Pharmacokinetics Per-Protocol Set......................................................................21
3.5.7
Pharmacodynamics Per-Protocol Set...................................................................22
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 3 of 86
3.5.8
PET Per-Protocol Set...........................................................................................22
3.6
Treatment assignment and treatment groups ...............................................................22
3.7
Center pooling strategy................................................................................................23
3.8
Coding dictionaries ......................................................................................................23
3.9
Changes to protocol-defined analyses .........................................................................23
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................24
4.1
Adjustments for covariates ..........................................................................................24
4.2
Handling of dropouts or missing data..........................................................................24
4.2.1
Efficacy data ........................................................................................................24
4.2.1.1
ASDAS derivation.....................................................................................24
4.2.1.2
hs-CRP.......................................................................................................24
4.2.1.3
ASDAS component data ...........................................................................24
4.2.1.4
ASAS20, ASAS40 and ASAS-PR ............................................................25
4.2.1.5
BASFI data................................................................................................25
4.2.1.6
HADS data ................................................................................................25
4.2.1.7
Spinal pain and PhGADA data..................................................................25
4.2.2
Pharmacodynamic data........................................................................................25
4.2.3
Safety laboratory data..........................................................................................25
4.2.4
Pharmacokinetic data...........................................................................................25
4.2.5
Dates and times....................................................................................................26
4.3
Handling of repeated and unscheduled measurements ................................................27
4.4
Handling of measurements obtained at the EW visit...................................................27
4.5
Interim analyses and data monitoring..........................................................................28
4.5.1
Data monitoring committee .................................................................................28
4.5.2
Interim analyses...................................................................................................28
4.6
Multicenter studies.......................................................................................................29
4.7
Multiple comparisons/multiplicity...............................................................................29
4.8
Use of an efficacy subset of subjects ...........................................................................29
4.9
Active-control studies intended to show equivalence..................................................29
4.10
Examination of subgroups ...........................................................................................29
5
STUDY POPULATION CHARACTERISTICS.............................................................29
5.1
Subject disposition.......................................................................................................29
5.2
Protocol deviations.......................................................................................................30
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................31
6.1
Derivation of variables.................................................................................................31
6.1.1
Calculation of body mass index...........................................................................31
6.1.2
Classification of age categories ...........................................................................31
6.1.3
Duration of disease ..............................................................................................31
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 4 of 86
6.2
Demographics ..............................................................................................................31
6.3
Other Baseline characteristics......................................................................................32
6.4
Medical history and concomitant diseases...................................................................33
6.5
Ankylosing spondylitis history ....................................................................................33
6.6
Prior and concomitant medications..............................................................................33
6.6.1
Prior medication definition..................................................................................34
6.6.2
Concomitant medication definition .....................................................................34
7
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................34
8
EFFICACY ANALYSES ................................................................................................34
8.1
Primary efficacy variable.............................................................................................34
8.1.1
Derivation of the primary efficacy variable.........................................................34
8.1.1.1
Bath Ankylosing Spondylitis Disease Activity Index...............................34
8.1.1.2
Patient’s Global Assessment of Disease Activity .....................................35
8.1.1.3
High-sensitivity C-reactive protein ...........................................................35
8.1.1.4
Calculation of Ankylosing Spondylitis Disease Activity Score................35
8.1.2
Primary analysis of the primary efficacy variable...............................................36
8.1.2.1
Bayesian modeling ....................................................................................36
8.1.2.2
Building the prior ......................................................................................37
8.1.2.3
Prior data conflict ......................................................................................38
8.1.3
Presentation of the primary analysis of the primary efficacy variable ................38
8.1.4
Presentation of Ankylosing Spondylitis Disease Activity Score.........................38
8.1.5
Presentation of component variables of Ankylosing Spondylitis Disease Activity 
Score ....................................................................................................................38
8.1.5.1
Bath Ankylosing Spondylitis Disease Activity Index...............................38
8.1.5.2
Patient’s Global Assessment of Disease Activity .....................................39
8.1.5.3
High sensitivity C-reactive protein............................................................39
8.1.6
Supportive analysis of the primary efficacy variable ..........................................40
8.1.6.1
Alternative analysis sets ............................................................................40
8.1.6.2
Alternative prior distributions ...................................................................40
8.1.6.3
Frequentist analysis – Analysis of Covariance..........................................40
8.1.6.4
Frequentist analysis – Mixed Model Repeated Measures.........................40
8.1.6.5
Frequentist analysis – Mixed Model Repeated Measures with Baseline by 
treatment group interaction .......................................................................41
8.2
Secondary efficacy variables .......................................................................................41
8.2.1
ASDAS Disease Activity States and Improvement.............................................41
8.2.1.1
Derivation of ASDAS Disease Activity States and Improvement ............41
8.2.1.2
Analysis of ASDAS Disease Activity States and Improvement ...............41
8.3
Other efficacy variables ...............................................................................................42
8.3.1
Derivation of Assessment in SpondyloArthritis International Society Response42
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 5 of 86
8.3.2
Presentation of Assessment in SpondyloArthritis International Society Response43
8.3.2.1
ASAS20 and ASAS40 response................................................................43
8.3.2.2
Time to ASAS20 and ASAS40 response ..................................................43
8.3.2.3
ASAS-PR...................................................................................................44
8.3.3
Presentation of components of Assessment in SpondyloArthritis International 
Society .................................................................................................................44
8.3.3.1
Bath Ankylosing Spondylitis Functional Index ........................................44
8.3.3.2
Total and nocturnal spinal pain numeric rating scale................................44
8.3.4
Physician’s Global Assessment of Disease Activity ...........................................45
8.3.5
Hospital Anxiety and Depression Scale ..............................................................45
8.3.6
Change in Bone Formation (PET-MRI/PET-CT Substudy)................................45
8.3.6.1
Eligibility assessment................................................................................45
8.3.6.2
Efficacy assessment...................................................................................46
9
PHARMACOKINETICS AND PHARMACODYNAMICS ..........................................49
9.1
Pharmacokinetics .........................................................................................................49
9.2
Pharmacodynamics ......................................................................................................50
10
IMMUNOLOGICAL ANALYSES.................................................................................50
11
SAFETY ANALYSES.....................................................................................................51
11.1
Extent of exposure .......................................................................................................51
11.2
Adverse events.............................................................................................................51
11.3
Clinical laboratory evaluations ....................................................................................54
11.4
Vital signs, physical findings, and other observations related to safety......................56
11.4.1
Vital signs ............................................................................................................56
11.4.2
Electrocardiograms..............................................................................................57
11.4.3
Other safety variables ..........................................................................................58
11.4.3.1
C-SSRS......................................................................................................58
11.4.3.2
Physical examination.................................................................................58
11.4.3.3
Chest X-ray/CT scan and TB questionnaire..............................................58
12
OTHER ANALYSES ......................................................................................................58
13
REFERENCES ................................................................................................................59
14
APPENDICES .................................................................................................................60
14.1
Bath Ankylosing Spondylitis Disease Activity Index .................................................60
14.2
Bath Ankylosing Spondylitis Functional Index...........................................................60
14.3
Hospital Anxiety and Depression Scale.......................................................................61
14.4
Treatment group assignment for the TFLs...................................................................61
14.5
Adverse events for special monitoring ........................................................................62
14.5.1
Major cardiovascular events................................................................................62
14.5.2
Serious infections, including opportunistic infections and tuberculosis .............63
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 6 of 86
14.5.2.1
Serious infections ......................................................................................63
14.5.2.2
Fungal infections .......................................................................................63
14.5.2.3
Opportunistic infections ............................................................................63
14.5.3
Malignancies including lymphoma......................................................................64
14.5.4
Cytopenias ...........................................................................................................64
14.5.5
Neuropsychiatric events.......................................................................................64
14.5.6
Inflammatory bowel disease................................................................................65
14.5.7
Anaphylactic reaction ..........................................................................................65
14.5.7.1
Anaphylactic reaction algorithm ...............................................................65
14.5.8
Hepatic events and drug-induced liver injury......................................................69
14.6
Treatment-emergent markedly abnormal laboratory values........................................69
14.7
Treatment-emergent abnormal liver values .................................................................70
14.8
Treatment-emergent markedly abnormal vital signs values ........................................71
15
AMENDMENTS TO THE SAP......................................................................................72
15.1
Amendment 2...............................................................................................................72
15.1.1
Rationale for the amendment...............................................................................72
15.1.2
List of changes.....................................................................................................72
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................86
LIST OF TABLES
Table 3‒1:
Definition of Baseline......................................................................................18
Table 3‒2:
Administration of investigational medicinal product ......................................22
Table 4‒1:
Calculation rules for duration of adverse events..............................................27
Table 11‒1:
Clinical laboratory measurements....................................................................55
Table 14‒1:
Bath Ankylosing Spondylitis Disease Activity Index .....................................60
Table 14‒2:
Bath Ankylosing Spondylitis Functional Index...............................................60
Table 14‒3:
Hospital Anxiety and Depression Scale...........................................................61
Table 14‒4:
Treatment group assignment for TFLs ............................................................61
Table 14‒5:
Definition of TEMA values for hematology....................................................69
Table 14‒6:
Definition of TEMA values for chemistry.......................................................69
Table 14‒7:
Definition of treatment-emergent liver function values...................................70
Table 14‒8:
TEMA/PCS criteria for vital signs...................................................................71
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 7 of 86
LIST OF ABBREVIATIONS
ACP
above cut point
ADA
anti-drug antibodies
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ALQ
above the limit of quantification
AS
ankylosing spondylitis
ASAS
Assessment in SpondyloArthritis International Society
ASAS-PR
Assessment in SpondyloArthritis International Society partial remission
ASAS20
Assessment in SpondyloArthritis International Society 20%
ASAS40
Assessment in SpondyloArthritis International Society 40%
ASDAS
Ankylosing Spondylitis Disease Activity Score
ASDAS-CII
Ankylosing Spondylitis Disease Activity Score – clinically important improvement
ASDAS-HD
Ankylosing Spondylitis Disease Activity Score – high disease activity
ASDAS-ID
Ankylosing Spondylitis Disease Activity Score – inactive disease
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score – major improvement
ASDAS-vHD
Ankylosing Spondylitis Disease Activity Score – very high disease activity
AST
aspartate aminotransferase
ATC
anatomical therapeutic chemical
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BCP
below cut point
BKZ
bimekizumab
BLQ
below the limit of quantification
BMI
body mass index
BP
blood pressure
CI
confidence intervals 
CP
confirmed positive
C-SSRS
Columbia-Suicide Severity Rating Scale 
CSR
clinical study report
CT
controlled terminology
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 8 of 86
CZP
certolizumab pegol
DEM
data evaluation meeting
DMC
data monitoring committee
ECG
electrocardiogram
eCRF
electronic case report form
ES
enrolled set
EW
early withdrawal
FAS
full analysis set
FDA
Food and Drug Administration
geoCV
geometric coefficient of variation
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale – Anxiety
HADS-D
Hospital Anxiety and Depression Scale – Depression
HIV
human immunodeficiency virus
HLA-B27
human leukocyte antigen B27
HLGT
high level group term
HLT
high level term
hs-CRP
high sensitivity C-reactive protein
IA1
Interim Analysis 1
IA2
Interim Analysis 2
IA3
Interim Analysis 3
ICH
International Council for Harmonization
IL-17A
interleukin 17-A
IL-17F
interleukin 17-F
IMP
investigational medicinal product
IPD
important protocol deviation
LLN
lower limit of normal
LLT
low level term
LLOQ
lower limit of quantification
LSMeans
least squares means
MACE
major adverse cardiovascular event
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed Model Repeated Measures
mNY
modified New York
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 9 of 86
n
number of available observations
NCP
not confirmed positive
NRS
numeric rating scale
PCS
potentially clinically significant
PD
pharmacodynamics
PDILI
potential drug-induced liver injury
PD-PPS
pharmacodynamics per-protocol set
PET-CT
positron emission tomography-computed tomography
PET-MRI
positron emission tomography-magnetic resonance imaging
PhGADA
physician’s global assessment of disease activity
PK
pharmacokinetics
PK-PPS
pharmacokinetic per-protocol set
PoC
proof-of-concept
PPS
per-protocol set
PT
preferred term
Q2W
every 2 weeks
Q4W
every 4 weeks
QTcF
Fridericia’s QTc interval
RCTC
Rheumatology Common Toxicity Criteria
RS
randomized set
SAE
serious adverse event
SAP
statistical analysis plan
Sc
subcutaneous
SD
standard deviation
SDTM
Study Data Tabulation Model
SE
standard error
SFU
safety follow-up
SIJ 
sacroiliac joint
SMQ
standardized MedDRA query
SOC
system organ class
SS
safety set
SUVauc
standard uptake value corrected for individual integrated whole blood activity
concentration
TB
tuberculosis
TEAE
treatment-emergent adverse event
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 10 of 86
TEMA
treatment-emergent markedly abnormal
TFLs
tables, figures and listings
TNF
tumor necrosis factor
ULN
upper limit of normal
VOI
volume of interest
VUMC
VU University Medical Center
WHODD
World Health Organization Drug Dictionary
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.


UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 11 of 86
1
INTRODUCTION
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the required statistical analysis of study AS0013. It also defines the summary tables, 
figures and listings (TFLs) to be included in the final clinical study report (CSR) according to the 
protocol.
This SAP is based on, and assumes familiarity with, the following documents:
•
Protocol amendment 1, dated 30 May 2017
•
Protocol amendment 2, dated 5 March 2018
•
Protocol amendment 3, dated 27 February 2019
Unless specified in the sections below, the study will be analyzed as described in the most recent 
version of the protocol. If a future protocol amendment necessitates a substantial change to the 
statistical analysis of the study data, this SAP will be amended accordingly. In addition, if 
analysis definitions need to be modified or updated prior to database lock, a SAP amendment 
will be required. If, after database lock, additional analyses are required to supplement the 
planned analyses described in this SAP, these changes will be described in the CSR together with 
the associated rationale.
The content of this SAP is compatible with the International Council for Harmonization 
(ICH)/Food and Drug Administration (FDA) E9 Guidance documents (ICH, 1998).
UCB is the Sponsor and PAREXEL is the Contract Research Organization for this study.
2
PROTOCOL SUMMARY
2.1
Study objectives
2.1.1
Primary objective
The primary objective of the study is to evaluate the efficacy of bimekizumab (BKZ) 
administered subcutaneously (sc) every 2 weeks (Q2W) for 12 weeks compared to certolizumab 
pegol (CZP; Cimzia®) in the treatment of adult subjects with active ankylosing spondylitis (AS).
2.1.2
Secondary objectives
The secondary objectives of the study are as follows: 
•
To assess the safety and tolerability of BKZ
2.1.3
Other objectives
The other objectives of the study are as follows:
•
To evaluate the effect of BKZ or CZP on changes in bone formation
•
To assess the pharmacokinetics (PK) and immunogenicity of BKZ
•
To assess additional biomarker, clinical, and imaging data as available
•
To assess the efficacy and safety of BKZ or CZP during the Treatment Extension Period
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 12 of 86
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variable
The primary efficacy variable for this study is the change from Baseline in Ankylosing 
Spondylitis Disease Activity Score (ASDAS) at Week 12.
2.2.1.2
Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) at Week 12
•
Ankylosing Spondylitis Disease Activity Score-major improvement (ASDAS-MI) at 
Week 12
2.2.1.3
Other efficacy variables
Other efficacy variables, assessed over the Treatment Period and Treatment Extension Period,
are as follows: 
•
Change from Baseline in ASDAS
•
Assessment in SpondyloArthritis International Society (ASAS) 20% (ASAS20) response
•
ASAS 40% (ASAS40) response
•
Time to ASAS20 response
•
Time to ASAS40 response
•
ASAS partial remission
•
Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
•
Change from Baseline in total Hospital Anxiety and Depression Scale – Anxiety (HADS-A)
and total Hospital Anxiety and Depression Scale – Depression (HADS-D)
•
Change from Baseline in Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Changes in bone formation as measured by standardized uptake value corrected for 
individual integrated whole blood activity concentration (SUVauc) for each PET-positive 
lesion identified together with the maximum of the SUVauc values  across all lesions within 
the spine and sacroiliac joint (SIJ).  SUVauc will be derived from positron-emission 
tomography magnetic resonance imaging (PET-MRI) or positron-emission tomography 
computed tomography (PET-CT) scans at Baseline, Week 12, and Week 48
2.2.2
Safety variables
2.2.2.1
Primary safety variables
The primary safety variables for this study are as follows:
•
Incidence of adverse events (AEs) and serious adverse events (SAEs)
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 13 of 86
•
Withdrawal due to AEs
2.2.2.2
Other safety variables
The other safety variables for this study are as follows:
•
Change from Baseline in vital signs (blood pressure, temperature, pulse rate) and body 
weight
•
Change from Baseline in physical examination
•
Change from Baseline in standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS,
QT, and QT intervals corrected for heart rate using Fridericia’s formula [QTcF])
•
Change from Baseline in clinical laboratory values (hematology, biochemistry, and 
urinalysis)
2.2.3
Pharmacokinetic variables
The PK variables are plasma concentrations of BKZ and CZP.
2.2.4
Pharmacodynamic variables
The pharmacodynamic (PD) variables are the blood or blood derivative (eg, plasma) 
concentrations of cytokines and chemokines of relevance to interleukin-17A (IL-17A) or 
interleukin-17F (IL-17F) signaling pathway, tumor necrosis factor (TNF) signaling pathway, AS 
biology, and bone metabolism. Additional variables may include, but will not be limited to, 
serum complement concentrations and mononuclear cell subtypes.
2.2.5
Immunological variables
Anti-BKZ antibody and anti-CZP antibody (collectively anti-drug antibody [ADA]) detection 
prior to and following study treatment will be evaluated.
2.2.6
Nonhereditary pharmacogenomic variables
Where local regulations permit, blood and urine will be collected and stored for up to 20 years to 
allow for potential exploratory analyses of ribonucleic acid, proteins, and metabolite biomarkers 
relevant to AS, bone metabolism, and the inflammatory and immune response processes. The 
nature and format of these tentative analyses will be determined at a later stage and will not form 
part of the CSR and are not further described in this SAP.
2.2.7
Pharmacogenetic variables
Additional blood samples will be collected from subjects who consent to participate in the
pharmacogenetic substudy and stored at -80°C for up to 20 years. Pharmacogenetic biomarkers 
may be measured to evaluate the relationship to response to treatment with BKZ, AS disease 
biology, bone metabolism, and inflammatory and immune response processes. The nature and 
format of these tentative substudy analyses will be determined when the results of the main study 
are made available. The results of these analyses will not form part of the CSR and are not 
further described in this SAP.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 14 of 86
2.3
Study design and conduct
AS0013 is a multicenter, randomized, subject-blind and investigator-blind, parallel-group study 
to evaluate the efficacy and safety of BKZ compared to CZP in adult subjects with active 
adult-onset AS. 
It is planned that at least 60 subjects will be randomized to 1 of 2 treatment arms in a 2:1 ratio 
and will receive either BKZ or CZP up to Week 44 (final dose of investigational medicinal 
product [IMP]).
The study will include a Screening Period of 2 to 4 weeks, a 12-week Treatment Period, a 
36-week Treatment Extension Period, and a 20-week Safety Follow-up (SFU) Period (starting 
after the final dose of IMP). Therefore, the maximum duration of the study will be 68 weeks.
At the start of the Treatment Period, eligible subjects will be randomized in a 2:1 ratio to receive 
the following blinded study treatments:
•
BKZ 160mg sc Q2W from Week 0 through Week 10. In addition, subjects will receive 1 
placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4 (Visit 3) in order to 
maintain the blind versus the CZP loading dose at these visits.
•
CZP 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200mg sc Q2W at 
Weeks 6 to 10.
After completing the 12-week Treatment Period, subjects will enter a 36-week Treatment
Extension Period and will receive the following treatments:
•
Subjects randomized to BKZ during the Treatment Period will receive BKZ 320mg sc every 
4 weeks (Q4W) from Week 12 to Week 44.
•
Subjects randomized to CZP during the Treatment Period will receive CZP 400mg Q4W 
from Week 12 to Week 44.
Subjects not responding to treatment during the Treatment Period will be withdrawn from the 
study as per Investigator’s discretion and will not enter the Treatment Extension Period. 
In a substudy of AS0013, a PET-MRI or PET-CT scan of the entire spine will be performed at 
selected sites in approximately 25 subjects at Screening and during the study at Week 12 and 
Week 48 or Early Withdrawal Visit if PET positive lesions were observed in the previous scan.
All subjects who complete the study or who discontinue from the study early, including those 
withdrawn from the IMP treatment, will have a SFU Visit at 20 weeks after their final dose of 
IMP. 
Three unblinded interim analyses will be conducted:
•
Interim Analysis 1 (IA1): when approximately 45 subjects have completed the Week 4 visit 
during the Treatment Period. 
•
Interim Analysis 2 (IA2): when all subjects not participating in the PET-MRI/PET-CT 
sub-study have completed the Week 12 visit at the end of the Treatment Period.
•
Interim Analysis 3 (IA3): when the last randomized subject has completed the Week 12 visit
at the end of the Treatment Period, or the subject has discontinued prematurely from the 
study. 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 15 of 86
Further details on the interim analyses planned for this study are included in the interim SAP.
A data monitoring committee (DMC) will review the data on an ongoing basis. The composition
and roles of the DMC are described in a separate DMC Charter. The analyses required and data
to be presented are described in a separate DMC SAP.
2.4
Determination of sample size
A sufficient number of subjects will be enrolled to ensure that at least 60 subjects are available in 
the main study at Week 12 to compare the change from Baseline in ASDAS between BKZ and 
CZP.  This will also provide at least 25 subjects enrolled in the PET-CT or PET-MRI substudy 
from multiple sites. Subjects will be randomized in a 2:1 ratio to receive BKZ or CZP 
respectively.
The sample size was calculated to provide at least 80% power to detect a difference between
treatment groups in the mean change from Baseline in ASDAS at Week 12 of 0.89 (group mean
change from Baseline for CZP and BKZ being -1.78 and -2.67 respectively) with a common 
standard deviation (SD) of 1.17 using frequentist methods for the comparison of the treatment 
group mean change from Baseline in ASDAS at Week 12 with Baseline ASDAS as a covariate 
(Overall and Starbuck, 1979).
The correlation between Baseline and Week 12 raw ASDAS was assumed to be 0.35. Note that 
the informative prior for the model intercept to be used in the Bayesian modelling of the primary 
efficacy variable, given by 𝛽𝐶𝑍𝑃~ Normal (-1.78, var=0.0605), contributes an effective sample 
size of approximately 20 CZP subjects. Prior data conflict will be investigated, and a vague prior 
will be used for the model intercept coefficient if prior data conflict is evident.
Note that a clarification regarding the sample size for this study was provided in protocol 
amendment 3. As indicated above, the planned sample size of at least 60 subjects provides 
sufficient power to detect meaningful treatment differences in the primary efficacy variable 
whilst also providing at least 25 subjects for the PET-MRI or PET-CT substudy. However, due 
to complexities in the initiation of sites capable of performing PET-MRI or PET-CT scans, more 
than the planned 35 non-PET-MRI/CT substudy subjects were screened and randomized before it 
was possible to close enrolment at the sites not participating in the substudy. Owing to the 
novelty of the PET-MRI/CT outcomes within this disease area, it is considered important to 
ensure at least 25 evaluable subjects are included in the assessment of this exploratory objective 
to maximize the possibility of identifying the salient factors or variables that might differ 
between the treatment groups and, therefore, the total sample size is increased to at least 72 
subjects. This sample size increase will not negatively impact the power to detect a difference in 
the primary efficacy variable at Week 12 (ie, it will remain >80%), but will ensure that the target 
number of subjects are included in the exploratory analysis of changes in bone formation at 
Week 12 and Week 48. Since the analyses of PET-MRI/CT data are exploratory and treatment 
effect sizes are unknown, formal power calculations were not performed. Clinical expertise does, 
however, indicate that a sample size of at least 25 subjects in the substudy will characterize 
broad differences between treatment groups.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 16 of 86
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
Statistical evaluation will be performed by PAREXEL and supervised by the Exploratory 
Statistics and Global Statistical Sciences Departments of UCB.
The datasets will follow the UCB analysis data model data specifications.
All analyses will be performed using SAS version 9.2 or higher (SAS Institute, Cary, North 
Carolina, USA). R Version 2.10.1 (R Development Core Team) or later, and/or OpenBUGS 
Version 3.0.6 or later may be used for complementary analysis.
Descriptive statistics will be used to provide an overview of the Baseline, efficacy, PD, PK and 
safety results.  Formal statistical testing will be conducted for the primary and secondary efficacy 
variables only in this study.  Other efficacy variables will be summarized descriptively by 
treatment group. 
Continuous variables will be summarized by treatment, visit and time point (where applicable) 
including number of subjects (n), mean, SD, median, minimum and maximum. First and third 
quartiles (Q1 and Q3 respectively) and 95% confidence intervals (CI) for the mean will also be 
included where stated in the SAP. 
Categorical variables will be summarized by treatment, visit and time point (where applicable) 
with frequency counts and percentages. Geometric coefficient of variation (geoCV), geometric 
mean and 95% CI for the geometric mean will also be presented in the descriptive statistics for 
the PK concentration and hs-CRP data. In all outputs the 95% confidence limits will be restricted 
to the possible values that the variable can take.
When reporting relative frequencies or other percentage values, the following rules apply:
•
For values where all subjects fulfill certain criteria, the percentage value will be displayed as 
100
•
For values where the absolute frequency is zero, there will be no percentage displayed at all
•
All other percentage displays will use 1 decimal place
•
Unless otherwise stated, the denominator for the percentages will be based on the number of 
subjects in the respective analysis set and treatment group. 
Percentages displayed based on continuous data (eg, percentage changes from Baseline) will be 
displayed to 1 decimal place. 
When reporting descriptive statistics, the following rules will apply in general (with the 
exception of PK and hs-CRP data, for which additional rules are stated below):
•
n will be an integer
•
Mean, SD, median and CIs will use 1 decimal place more (or 1 more significant figure, 
depending on the original data reporting format) than the original data
•
Coefficient of variation will be reported as a percentage to 1 decimal place
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 17 of 86
•
Minimum and maximum will be reported using the same number of decimal places as the 
original data
•
If no subjects have data at a given time point, then only n=0 will be presented. If n<3, then 
only n, minimum and maximum will be presented. If n=3, then only n, median, minimum 
and maximum will be presented. The other descriptive statistics will be left blank.
When reporting individual values and descriptive statistics for PK concentration and hs-CRP 
data, the following rules will apply with regard to rounding and precision: 
•
Individual values will be reported to the same level of precision as received from the 
bioanalytical laboratory
•
Descriptive statistics will be reported to the same level of precision as the individual data for
the minimum and maximum, to 1 additional significant figure for the mean (arithmetic and
geometric), median, Q1, Q3, SD, and to 2 additional significant figures for the 95% CI for
the geometric mean
•
The geoCV will be reported as a percentage to 1 decimal place
All statistical tests will be carried out 2-tailed at the 5% level of significance unless otherwise 
stated. The following rules will apply for the presentation of any results relating to inferential 
statistical analysis:
•
P-values will be presented to 4 decimal places; p-values less than 0.0001 will be presented as 
“<0.0001” and p-values greater than 0.9999 will be presented as “>0.9999”
•
Posterior probabilities associated with the Bayesian analyses will be presented as percentages 
to 1 decimal place
•
Means, SDs, medians, 95% credible intervals and highest posterior density intervals obtained 
from the Bayesian analyses will be presented to 1 decimal place 
All statistical output will be presented in statistical appendices where appropriate.
Time to response data (Section 8.3.2.2) will be analyzed for the Treatment Period and across the 
study (Treatment Period + Treatment Extension Period). All other data tabulations will be 
performed by treatment group, visit and time point (where applicable) and no separate analyses 
based on study period will be presented.
The treatment groups will be displayed as follows in the TFLs, where BKZ refers to 
bimekizumab and CZP refers to certolizumab pegol:
•
BKZ 
•
CZP
Data listings containing all documented data and all derived data will be generated.  Subjects 
enrolled in the PET-MRI/PET-CT substudy will be flagged in the data listings.
If Study Data Tabulation Model (SDTM) controlled terminology (CT) is defined for selected 
variables, it will be displayed similarly in the TFLs.
Yes/No responses will be presented as Y/N consistent with the YN CT and Male and Female will 
be replaced with M/F respectively in the TFLs.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 18 of 86
3.2
General study level definitions
3.2.1
Relative day
Relative day for an event will be derived with the date of the first administration of IMP as 
reference date.
Relative day for an event or measurement occurring before the reference date will be calculated 
as follows:
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒𝐷𝑎𝑦= 𝐸𝑣𝑒𝑛𝑡𝐷𝑎𝑡𝑒−𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒𝐷𝑎𝑡𝑒
The relative day for an event or measurement occurring on or after the reference date, up to the 
date of the last administration of IMP, will be calculated as follows:
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒𝐷𝑎𝑦= (𝐸𝑣𝑒𝑛𝑡𝐷𝑎𝑡𝑒−𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒𝐷𝑎𝑡𝑒) + 1
For events or measurements occurring after the date of the last administration of IMP, relative 
day will be prefixed with ‘+’ in the data listings and will be calculated as follows:
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒𝐷𝑎𝑦= 𝐸𝑣𝑒𝑛𝑡𝐷𝑎𝑡𝑒−𝐷𝑎𝑡𝑒𝑜𝑓𝐿𝑎𝑠𝑡𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛
There is no relative Day 0. Relative day will not be calculated for partial dates in cases where 
relative day is shown in a subject data listing. In such cases, relative day should be presented as 
‘-‘ in the subject data listings.
3.2.2
Study periods
For each subject completing the study, the maximum study duration will be 68 weeks and will 
comprise the following: 
•
Screening Period: ≥2 weeks with a maximum of 4 weeks prior to randomization
•
Treatment Period: 12 weeks
•
Treatment Extension Period: 36 weeks
•
Safety Follow-Up Period: 20 weeks after the last dose of IMP (scheduled at Week 44, 4 
weeks prior to the end of the Treatment Extension Period)
The end of the study is defined as the date of the last visit of the last subject in the study.
3.3
Definition of Baseline values
Baseline will be the last available value prior to the first administration of IMP. Scheduled or
unscheduled measurements can be used as the Baseline value. Measurement-specific Baseline
definitions (based on the schedule of assessments in the protocol) are presented in Table 3‒1.
Table 3‒1:
Definition of Baseline
Category
Measurement
Definition of Baseline
Efficacy
BASDAI
Visit 2 (Week 0); Screening result if 
missing at Week 0
PGADA
Visit 2 (Week 0)
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 19 of 86
Table 3‒1:
Definition of Baseline
Category
Measurement
Definition of Baseline
hs-CRP
Visit 2 (Week 0); Screening result if 
missing at Week 0
PET-MRI/PET-CT
Visit 1 (Screening)
BASFI
Visit 2 (Week 0); Screening if missing 
at Week 0
Total and nocturnal spinal pain 
numeric rating scale (NRS)
Visit 2 (Week 0); Screening if missing 
at Week 0
PhGADA
Visit 2 (Week 0)
HADS
Visit 2 (Week 0); Screening if missing 
at Week 0
Safety
Vital signs
Visit 2 (Week 0); Screening if missing 
at Week 0
12-lead ECG
Visit 2 (Week 0); Screening if missing 
at Week 0
Clinical laboratory tests
Visit 2 (Week 0); Screening if missing 
at Week 0
Body weight
Visit 1 (Screening)
C-SSRS
Visit 2 (Week 0); Screening if missing 
at Week 0
Immunological
ADA
Visit 2 (Week 0)
Pharmacodynamic
Cytokines, chemokines, serum 
complement levels, mononuclear 
cell subtypes
Visit 2 (Week 0)
ADA=anti-drug antibody; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing 
Spondylitis Functional Index; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; 
HADS=Hospital Anxiety and Depression Scale; hs-CRP=high sensitivity C-reactive protein;
PET-CT=positron-emission tomography-computed tomography; PET-MRI=positron-emission 
tomography-magnetic resonance imaging; PGADA=Patient’s Global Assessment of Disease Activity;
PhGADA=Physician’s global assessment of disease activity.
The change from Baseline to any subsequent post-Baseline visit will be calculated as the simple 
difference between that post-Baseline visit’s value and the Baseline value, as below:
𝑃𝑜𝑠𝑡𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒𝑉𝑖𝑠𝑖𝑡𝑉𝑎𝑙𝑢𝑒−𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒𝑉𝑖𝑠𝑖𝑡𝑉𝑎𝑙𝑢𝑒
The percentage change from Baseline to any subsequent post-Baseline visit will be calculated as
follows:
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 20 of 86
The same Baseline value will be used in the calculations of changes from Baseline and 
percentage changes from Baseline at all visits during the Treatment Period and Treatment 
Extension Period.
3.4
Protocol deviations
Important protocol deviations (IPDs) are deviations from the protocol which potentially could 
have a meaningful impact on the primary objective of the study. The criteria for identifying such 
protocol deviations will be defined within the IPD document which is part of the data cleaning 
plan. Important protocol deviations will be classified according to the following categories: 
•
Inclusion/exclusion criteria deviations
•
Administration of prohibited concomitant medications
•
Deviations relating to withdrawal criteria
•
Visit schedule deviations
•
Study IMP administration deviations (including incorrect treatment received, handling and 
storage deviations and incorrect dosage received)
•
Treatment non-compliance
•
Procedural non-compliance
•
Missing data
•
Other
Important protocol deviations will be reviewed as part of the ongoing data cleaning process and 
data evaluation. 
At least 4 data evaluation meetings (DEMs) will be performed at the following times, prior to 
each of the following analysis milestones:
•
IA1
•
IA2
•
IA3
•
The final analysis after all data have been verified/coded/entered into the database 
Additional DEMs may be conducted as deemed necessary.
The purpose of these DEM reviews will be to review all protocol deviations, define the analysis 
sets as defined in Section 3.5, and check the quality of the data. The reviews will also help 
decide how to manage problems in the subjects’ data (eg, missing values and withdrawals).
Accepted deviations from theoretical (scheduled) time points will be described in the appropriate 
documents and included in the Study Master File. After the pre-analysis review, resolution of all 
issues, and documentation of all decisions (including inclusion into each of the analysis sets) at 
the final DEM, the database will be locked.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 21 of 86
3.5
Analysis sets
3.5.1
Enrolled Set
The Enrolled Set (ES) will consist of all subjects who have given informed consent (ie, all 
subjects screened). The ES will therefore include screening failures.
3.5.2
Randomized Set
The Randomized Set (RS) will consist of all randomized subjects.
3.5.3
Safety Set
The Safety Set (SS) will consist of all randomized subjects who receive at least 1 dose (full or 
partial) of the IMP. The safety analysis will be conducted on the SS.
3.5.4
Full Analysis Set
The Full Analysis Set (FAS) will consist of all randomized subjects who received at least 1 dose 
(full or partial) of the IMP and had a valid Baseline and a post-Baseline measurement for at least 
one efficacy variable (as defined in Section 2.2.1). The FAS will be used for the supportive and 
sensitivity analyses of the primary efficacy variable, the analyses of the secondary efficacy 
variables, other efficacy variables and the primary efficacy component data.
3.5.5
Per-Protocol Set
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who have no IPDs affecting 
the primary efficacy variable. The subjects with IPDs will be predefined and evaluated during a 
DEM prior to unblinding of the data. The PPS will be used for the primary analyses and 
supportive and sensitivity analyses of the primary efficacy variable, for the analysis of the 
component variables of the primary efficacy variable and for the analysis of the secondary 
efficacy variables.
Protocol deviations will be reviewed at the DEMs and any exclusions from analysis sets will be 
documented as described in Section 3.4. It is anticipated that the PPS for the final analysis will 
differ from the PPS defined at the interim analyses due to additional information obtained on 
subjects during the SFU Period. Similarly, the PPS as defined at IA1, IA2 and IA3 may differ 
across the 3 IAs, due to potential additional data or information obtained during the time between 
each analysis. 
Following the final DEM, the inclusion into each of the analysis sets for all subjects will be 
confirmed. The DEM minutes will document the final agreed PPS to be applied to the final 
analysis, as well as document any changes to the PPS relative to the previously agreed PPS at the 
interim(s), if applicable.
3.5.6
Pharmacokinetics Per-Protocol Set
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of all randomized subjects who 
receive at least 1 dose (full or partial) of the IMP and have at least 1 quantifiable post-dose 
plasma concentration. The summaries of the PK concentration data and the immunological data 
will be based on the PK-PPS.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 22 of 86
3.5.7
Pharmacodynamics Per-Protocol Set
The Pharmacodynamics Per-Protocol Set (PD-PPS) is a subset of the FAS, consisting of those 
subjects who had no IPDs potentially affecting the PD data, as confirmed during a pre-analysis 
review of the data prior to database lock. 
3.5.8
PET Per-Protocol Set
The PET Per-Protocol Set (PET-PPS) will consist of all randomized subjects who receive at least 
1 dose of the IMP and have evaluable PET-MRI or PET-CT scan data at Baseline and at least 1 
of the post-Baseline assessments.
3.6
Treatment assignment and treatment groups
Listings and summaries will be presented by treatment group and/or overall, as applicable
(Table 14‒4). 
The following order will be used in the TFLs:
•
Not randomized
•
CZP
•
BKZ
•
All subjects
The dosing schedule and number of injections given at each visit for each treatment group are 
described in Table 3‒2.  
The IMP will be administered in the clinic as 2 sc injections. Suitable areas for sc injection are 
the lateral abdominal wall, upper outer thigh, and upper arm. During each dosing visit, each of 
the 2 injections will be administered at a separate injection site.
In addition, subjects randomized to BKZ will receive 1 placebo injection at Baseline, Week 2, 
and Week 4 in order to maintain the blind vs the CZP loading dose at these visits.
The minimum time between doses should be no less than 10 days during the Treatment Period
and no less than 22 days during the Treatment Extension Period.
Table 3‒2:
Administration of investigational medicinal product
Visit
Treatment group
Bimekizumab
Certolizumab Pegol
Treatment Period
Baseline, Weeks 2, 4
160mg 
400mg
Weeks 6, 8, 10
160mg
200mg
Treatment Extension Period
Weeks 12 to 44, every 4 
weeks
320mg
400mg
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 23 of 86
In the case of dosing administration errors during the Treatment Period, all statistical analyses of 
safety data will be conducted according to the actual treatment received, ie, treatment assignment 
for the SS will be based on actual treatment with the following rule:
•
Subjects who received any doses of a treatment to which they were not randomized will be 
assessed at the DEM for the treatment group assignment, as it will depend on how many 
doses of each of the treatments were taken and at what time point during the study
Subjects receiving the incorrect treatment at a particular visit will be excluded from the PPS, 
PD-PPS and the PK-PPS as this would be considered as an IPD. Subjects may be excluded from 
the analysis at a particular visit (or visits) only or overall, following discussion at the DEMs, and 
will be included in the analyses according to their randomized treatment (which would be 
equivalent to an analysis according to their actual treatment).
All summaries of the PK and immunological data will be conducted according to the actual 
treatment received, ie, treatment assignment for the PK-PPS will be based on actual treatment.
Similarly, all statistical analyses of the PD data will be conducted according to the actual 
treatment received, ie, treatment assignment for the PD-PPS will be based on actual treatment.
3.7
Center pooling strategy
Due to the small number of subjects per site, it is planned to pool all subjects within the study.
The data summaries and statistical analyses will not be performed by site or country.
3.8
Coding dictionaries
Adverse events and medical history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA®) version 19.0.
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD) version SEP2015. Medical procedures will not be coded.
3.9
Changes to protocol-defined analyses
The following changes relative to the protocol-defined analyses have been included in the SAP:
•
The PD-PPS was included as an additional analysis set in the SAP and was not part of the 
clinical study protocol. This was added as it was deemed appropriate to review protocol 
deviations separately in relation to the PD data and to define a separate analysis set 
accordingly.
•
The HADS data are not included under the list of Other efficacy variables in the protocol.  
These data are, however, collected as supportive efficacy data and therefore the changes from 
Baseline in the total HADS-A and HADS-D scores are included in this SAP under 
Section 2.2.1.3 for Other efficacy variables.
•
The PhGADA data are not included under the list of Other efficacy variables in the protocol.  
These data are, however, collected as supportive efficacy data and therefore the change from 
Baseline in PhGADA is included in this SAP under Section 2.2.1.3 for Other efficacy 
variables.
•
The protocol defines the FAS as all randomized subjects who receive at least 1 dose of the 
IMP and have a valid measurement of the primary efficacy variable at Baseline and at least 1 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 24 of 86
post-Baseline efficacy assessment.  The definition of the FAS in the SAP has been updated to 
include all randomized subjects who received at least 1 dose (full or partial) of the IMP and 
had a valid Baseline and a post-Baseline measurement for at least 1 efficacy variable. Since 
the primary efficacy variable is a composite endpoint based on BASDAI, PGADA and 
hs-CRP, the use of the protocol definition would omit any subjects with at least one missing 
component of the composite endpoint from the efficacy analyses.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
The Bayesian analyses will employ a linear regression model adjusting for Baseline ASDAS as a 
covariate. Further exploratory analyses may be performed for the primary efficacy variable 
adjusting for other Baseline covariates.
4.2
Handling of dropouts or missing data
4.2.1
Efficacy data
4.2.1.1
ASDAS derivation
If 1 component for the ASDAS is missing at a given visit, and the visit prior to the visit with the 
missing component data is not the Baseline or Screening visit, the following will apply: the 
missing component will be imputed by carrying the last observation for the given component 
forward, and the ASDAS will be calculated accordingly.
If no value is available for that component before the missing visit, or if the visit prior to the visit 
with the missing component data is either the Baseline or Screening visit, then the next 
observation will be carried backwards, and the ASDAS will be calculated accordingly.
If an unscheduled or repeat visit with non-missing data for the given ASDAS component is 
available and this visit is closer to the scheduled visit where the component data is missing, then 
the component data from the unscheduled/repeat visit will be used in the derivation of the 
ASDAS score.
If more than one component for the ASDAS is missing, ASDAS will not be calculated and 
treated as missing.
Any measurements of hs-CRP that are below 2 mg/L will be imputed with a fixed value of 2 
mg/L for the purpose of deriving the ASDAS. 
The statistical analysis will be performed based on the resulting derived values of ASDAS.
4.2.1.2
hs-CRP
Any measurements of hs-CRP that are below the limit of quantification (BLQ) will be imputed 
with the midpoint between zero and the lower limit of quantification (LLOQ) for the purpose of 
the calculation of summary statistics and changes from Baseline. Measurements for hs-CRP that 
are above the upper limit of quantification (ALQ), if applicable, will be imputed to the upper 
quantification limit.
4.2.1.3
ASDAS component data
Except for the descriptive statistics of hs-CRP as described above, no imputation of missing data 
will be performed for the summaries of the ASDAS component efficacy variables.
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 25 of 86
4.2.1.4
ASAS20, ASAS40 and ASAS-PR
For all non-missed visits, in the calculation of ASAS20, ASAS40 and ASAS-PR responses, if 
any of the component data are missing, then the following rules will be applied:
•
If all the component values are missing from Baseline to the post-Baseline visit being 
considered, the percentage change from Baseline to that visit for the given component will be 
imputed as 0%. The unit improvement will be imputed as 0.
•
If the component value at a given post-Baseline visit is missing and the Baseline value is 
present, the missing component will be replaced by the last non-missing post-Baseline 
observation (LOCF) for that component.
4.2.1.5
BASFI data
In case of missing answers to 1 or 2 of the single items within the BASFI questionnaire, the 
BASFI score will be calculated by imputing missing items with the mean of the completed items. 
Then, the BASFI score will be calculated as described in Section 8.3.3.1. If more than 2 of the 
items are missing, the BASFI score will be left missing.
4.2.1.6
HADS data
Any missing data for the total score for HADS-A and HADS-D will be handled as follows:
•
If a maximum of 1 item is missing in HADS-A or HADS-D, the missing item will be
imputed with the mean score from the remaining completed items within the HADS-A or
HADS-D respectively.
•
If more than 1 item is missing in HADS-A or HADS-D, the total score will not be calculated.
4.2.1.7
Spinal pain and PhGADA data
Missing data for Total and nocturnal spinal pain NRS and PhGADA data will not be imputed and 
will be analyzed as far as data are available.
4.2.2
Pharmacodynamic data
For the PD data, measurements that are BLQ will be imputed with half of the LLOQ for the 
purpose of calculating summary statistics and changes from Baseline. Measurements that are 
ALQ, if applicable, will be imputed to the upper quantification limit.
4.2.3
Safety laboratory data
The rules for handling values that are BLQ or ALQ in the safety laboratory data will be the same 
as those described for PD data in Section 4.2.2.
4.2.4
Pharmacokinetic data
Concentrations that are BLQ will be imputed with half of the LLOQ for the respective analyte 
(BKZ or CZP) for the purpose of calculating the geometric mean and its 95% CI, the geoCV, the 
arithmetic mean and SD for summaries and figures. 
For the individual figures, any concentrations that are BLQ will be regarded as missing, with the 
exception of pre-dose BLQ concentrations at Visit 2 (Week 0), which will be imputed with zero 
for linear scale plots.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 26 of 86
4.2.5
Dates and times
Partial dates may be imputed for the following reasons:
•
Classification of AEs as treatment-emergent
•
Classification of medications as prior or concomitant
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the
database.
The following rules will be applied for partial start dates:
•
If only the month and year are specified and the month and year of the first dose of IMP is 
not the same as the month and year of the start date then the 1st of the month will be used, or 
the date of Screening if this is later (if the latter imputation results in an end date that is 
earlier than the start date, then the 1st of the month will be used). If time is missing this will 
be imputed as 00:00 h
•
If only the month and year are specified and the month and year of the first dose of IMP is 
the same as the month and year of the start date, then the date of the first dose of IMP will be 
used. If this results in an imputed start date that is after the specified end date, then the 1st of 
the month will be used, or the date of Screening if this is later (if the latter imputation results 
in an end date that is earlier than the start date, then the 1st of the month will be used). If the 
imputed date is the same as the date of the first dose of IMP then time will be imputed as the 
start time of the first injection (ie, an AE will be regarded as treatment-emergent and a 
medication will be classified as concomitant)
•
If only the year is specified, and the year of the first dose of IMP is not the same as the year 
of the start date then January 01 of the year of the start date will be used. If time is missing 
this will be imputed as 00:00 h
•
If only the year is specified, and the year of the first dose of IMP is the same as the year of 
the start date, then the date of the first dose of IMP will be used. If this results in an imputed 
start date that is after the specified end date, then January 01 of the year of the start date will 
be used, or the date of Screening if this is later (if the latter imputation results in an end date 
that is earlier than the start date, then January 01 will be used). If the imputed date is the 
same as the date of the first dose of IMP then time will be imputed as the start time of the 
injection (ie, an AE will be regarded as treatment-emergent and a medication will be 
classified as concomitant)
The following rules will be applied to partial stop dates:
•
If only the month and year are specified, then the last day of the month will be used
•
If only the year is specified, then December 31 of the known year will be used
•
If the stop date is completely unknown, the stop date will not be imputed
Missing or partially missing dates and/or times will be imputed as described in Table 4‒1 for the 
calculation of duration of each AE. AE duration will be computed in and reported in day and 
time format: xx d hh:mm.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 27 of 86
Table 4‒1:
Calculation rules for duration of adverse events
Data availability
Onset 
date/time
Outcome 
date/time
Calculation rules
Complete data
D1/T1
D2/T2
Duration = [(D2 – D1)*24 + (T2 – T1)]/24 d
End time missing
D1/T1
D2/--
End time is substituted by time 23:59h (=23.98 in 
decimal format) 
Duration = <[(D2 – D1)*24 + (23.98 – T1)]/24 d
Start time missing
D1/--
D2/T2
Onset time is substituted by time 00:00h
Duration = <[(D2 – D1)*24 + T2]/24 d
Start and end time 
missing
D1/--
D2/--
Duration = <D2 – D1 + 1
Start day and time 
missing
--/--
D2/T2
Duration = [(D2 – D0)*24 + (T2 – T0)]/24 d
For a subject in the SS, D0 and T0 are the date and 
time of first administration of IMP and for screen 
failures, D0 is the date of the Screening visit and T0 = 
00:00h
End day and time 
missing
D1/T1
--/--
If the stop date is missing, duration will not be 
calculated.
Start and end date 
missing
--/--
--/--
If the stop date is missing, duration will not be 
calculated.
4.3
Handling of repeated and unscheduled measurements
All repeated and unscheduled measurements will be presented in the data listings, where 
applicable. The following general rules will apply to all repeated and unscheduled 
measurements:
•
For repeated measurements obtained prior to the first dose of IMP the latest value (which
may be scheduled or unscheduled) will be used in the calculation of the descriptive statistics
•
For repeated measurements obtained at the designated Baseline visit, the latest value (which 
may be scheduled or unscheduled) will be defined as the Baseline provided that this occurred 
prior to the first dose of IMP
•
For repeated measurements obtained at any time point after the first dose of IMP, the values 
will not be included in the calculation of descriptive statistics or changes from Baseline.
•
Unscheduled measurements performed for the Early Withdrawal (EW) visit will be assigned
to the appropriate visit (Section 4.4) and analyzed accordingly
4.4
Handling of measurements obtained at the EW visit
Subjects withdrawing early from the study should undergo the same assessments scheduled for 
the Week 48 visit as soon as possible after withdrawal (as an EW visit) and then enter the SFU 
Period, completing study participation with the SFU Visit 20 weeks after their final dose of IMP. 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 28 of 86
The following rules will apply with regard to the inclusion of the results obtained at the EW visit
in the descriptive summaries:
•
Any measurements conducted at the EW visit should be included in the summaries for the 
respective scheduled visit, if the EW visit occurs at the time of the next scheduled visit. For 
example, if the EW visit occurs on Day 42, the results would be summarized together with 
the Visit 6 (Week 6, Day 42) results
•
If the EW visit does not correspond to the day of a scheduled visit, the assessments of the 
EW visit should be mapped to the nearest scheduled visit, relative to the Baseline visit date, 
following the last scheduled visit where assessments are available
•
If the date of the EW visit is equidistant between 2 scheduled visits at which no scheduled 
assessments were performed, the assessments from the EW visit will be mapped to the 
earliest of these visits
•
If an EW visit mapping results in data being mapped to a visit where the specific assessment 
is not actually collected per the protocol schedule of assessments, these data will not be 
included in the summary statistics and will be listed only
•
The only exception to the above rule is for ADA (for both BKZ and CZP) assessments, in 
which all early withdrawal visit assessments will be assigned to the next scheduled visit at 
which ADA are assessed. The rationale for this is that ADA positivity is summarized over a 
given study period. As part of that summary, a table indicating the first visit at which ADA
positivity is observed will be presented. In order to match the number of subjects who were 
ADA positive at specific visits with the overall positivity for the period, it is necessary to 
ensure that ADA positivity is attributed to a visit where ADA antibody assessments were 
performed
Assessments from the EW visit will be displayed as the mapped visit and will be flagged in the
by-visit data listings.
4.5
Interim analyses and data monitoring
4.5.1
Data monitoring committee
The conduct of the study and monitoring of the safety data will be supervised by an independent 
DMC to optimize subjects’ safety and to identify any safety signals. Full details of the 
composition and roles of the DMC will be provided in a separate DMC Charter.
The data to be reviewed by the DMC will be as detailed in the DMC Charter and will include 
unblinded safety data. The details regarding the outputs to be produced and the analyses to be
performed will be provided in a separate DMC SAP.
4.5.2
Interim analyses
Three unblinded informal IAs are planned for this study. 
IA1 will be performed when approximately 45 subjects have completed the Week 4 visit. 
IA2 will be performed when the last randomized subject not participating in the 
PET-MRI/PET-CT has completed the Week 12 visit at the end of the Treatment Period or has 
withdrawn prematurely from the study.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 29 of 86
IA3 will be performed when the last randomized subject has completed the Week 12 visit at the 
end of the Treatment Period or has withdrawn prematurely from the study.
The purpose of the IAs is for key Sponsor personnel to review the results of the primary efficacy, 
selected secondary and other efficacy analyses and safety outcomes to facilitate additional 
Clinical Planning or Portfolio Management decisions.
All analyses and unblinding instructions will be pre-specified in the Interim Analysis SAP.
4.6
Multicenter studies
The data summaries and statistical analyses will not be performed by center.
4.7
Multiple comparisons/multiplicity
Not applicable.
4.8
Use of an efficacy subset of subjects
In order to investigate the impact on the efficacy analyses, the PPS will be used to evaluate the 
subset of subjects in the FAS with no IPDs.
4.9
Active-control studies intended to show equivalence
Not applicable.
4.10
Examination of subgroups
Not applicable.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
The number and percentage of subjects who were randomized into the study (and into the PET-
MRI/PET-CT substudy), subjects who completed or prematurely discontinued the study, as well 
as the primary reason for discontinuation will be presented by treatment group and for all 
subjects, based on the RS. A subject who completed the study is defined as a subject who 
completed all visits up to the last scheduled study visit, ie, Visit 18 (Week 64). An additional 
summary of subject disposition in the PET-MRI/PET-CT substudy will also be presented
separately by treatment group and for all subjects, based on the RS.
In addition, disposition of subjects during the Treatment Period and Treatment Extension Period 
will be summarized separately. The number and percentage of subjects who completed Week 4 
and Week 12 of the Treatment Period, or prematurely discontinued the study during the 
Treatment Period, together with the primary reason for discontinuation will be presented by 
treatment group.  The number and percentage of subjects who completed Week 48 (ie, the 
Treatment Extension Period) or prematurely discontinued during the Treatment Extension 
Period, together with the primary reason for discontinuation will be presented by treatment 
group. A subject is defined as completing Week 4, Week 12 and Week 48, respectively, if 
adequate efficacy data are available in the database to calculate the primary efficacy variable at 
the respective visit.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 30 of 86
The number and percentage of subjects who discontinued due to AEs will be separately 
summarized by treatment group and for all subjects, based on the RS. This will be used for 
European Union Drug Regulating Authorities Clinical Trials (EudraCT) reporting.
The number and percentage of subjects included into each of the analysis sets will be 
summarized by treatment group and for all subjects based on all subjects screened. Percentages 
will be based on the RS for the purpose of this summary.
Screen failure reasons will be summarized, based on all subjects screened. A listing of subjects 
who did not meet study eligibility criteria (including glossary) will also be presented for all 
subjects screened.
In addition, the following listings will be presented by treatment group:
•
Subject disposition (ES [all subjects screened])
•
Study discontinuation (RS)
•
Visit dates (SS)
•
Subject analysis sets (ES [all subjects screened])
The listing of subject disposition will include:
•
the date of informed consent
•
for subjects participating in the respective pharmacogenomics, pharmacogenetic and PET
MRI/CT substudies: date of respective informed consent
•
date and time of first and last dose of IMP
•
date of premature study termination and primary reason (if applicable)
•
date of final contact
•
if applicable, the date and reason for premature unblinding
The listing of study discontinuation will include the reason for discontinuation and the number of 
days on IMP.
The number of days on IMP will be calculated as follows:
𝑁𝑢𝑚𝑏𝑒𝑟𝑜𝑓𝑑𝑎𝑦𝑠𝑜𝑛𝐼𝑀𝑃= (𝐷𝑎𝑡𝑒𝑜𝑓𝐿𝑎𝑠𝑡𝐷𝑜𝑠𝑒𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑−𝐷𝑎𝑡𝑒𝑜𝑓𝐹𝑖𝑟𝑠𝑡𝐷𝑜𝑠𝑒𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑) + 1
5.2
Protocol deviations
Important protocol deviations will be identified and classified by the deviations types listed in 
the IPD document.
A listing of all IPDs will be presented for all subjects in the RS and will include the deviation 
type and description.
The number and percentage of subjects with IPDs will be summarized by treatment group and 
for all subjects for each deviation type, based on the RS. This summary will be repeated for the 
FAS (if this analysis set is different to the RS).
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 31 of 86
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Derivation of variables
6.1.1
Calculation of body mass index
The body mass index (BMI) in kg/m2 is calculated based on the height (in m) and the weight (in 
kg) using the following formula: 
𝐵𝑀𝐼=
𝑊𝑒𝑖𝑔ℎ𝑡
(𝐻𝑒𝑖𝑔ℎ𝑡)2
The BMI will be automatically derived by and recorded on the electronic case report form 
(eCRF).
6.1.2
Classification of age categories
Age will be classified into categories based on requirements for European Union Drug 
Regulating Authorities Clinical Trials (EudraCT) and clinicaltrials.gov reporting.
For the EudraCT reporting, the categories will include:
•
18 to <65 years
•
65 to <85 years
•
≥85 years
For the clinicaltrials.gov reporting, the categories will include:
•
≤18 years
•
19 to <65 years
•
≥65 years
6.1.3
Duration of disease
The duration of disease will be calculated as follows and will be presented in years to 1 decimal 
place:
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛= 𝐷𝑎𝑡𝑒𝑜𝑓𝑆𝑐𝑟𝑒𝑒𝑛𝑖𝑛𝑔−𝐷𝑎𝑡𝑒𝑜𝑓𝐷𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠
In the event that the date of diagnosis is incomplete, it will be imputed to the most recent feasible 
date (ie, the imputed date must be before the date of Screening):
•
If only the day is missing, it will be imputed to the last day of the known month
•
If the day and month are missing, it will be imputed to December 31 in the known year
•
If the date of diagnosis is completely missing or if the imputed date is not feasible, the 
duration of disease will not be calculated
6.2
Demographics
A by-subject listing of Baseline demographic characteristics will be presented by treatment 
group. This will include the year of birth (if available), age (in years), sex, race, ethnicity, height
(in cm), weight at Screening (in kg) and body mass index (BMI) for all subjects screened. The 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
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age and BMI will be obtained from the electronic case report form (eCRF) and will not be 
re-calculated for the reporting of demographic data. 
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by treatment group and for all subjects based on the SS. The summary of age will 
include descriptive statistics and categorical summaries, the latter based on requirements for 
EudraCT and clinicaltrials.gov reporting. This summary will be repeated for subjects in the SS 
who were randomized in the PET-MRI/CT substudy. Childbearing potential will be listed for the 
SS.
6.3
Other Baseline characteristics
The following Baseline disease characteristics will be presented in a by-subject listing for the SS:
•
Duration of disease (as calculated in Section 6.1.3), including confirmation of sacroiliac joint 
X-ray and the date on which the sacroiliac joint X-ray was performed
•
hs-CRP
•
BASDAI score
•
PGADA
•
ASDAS
•
ASDAS disease activity states (ASDAS-ID, ASDAS-Moderate Disease activity 
[ASDAS-MD], ASDAS-High Disease activity [ASDAS-HD] and ASDAS-Very High 
Disease activity [ASDAS-vHD])
•
BASFI score
•
Total and nocturnal spinal pain NRS
•
PhGADA
•
Total HADS-A and HADS-D scores
The calculation of Baseline ASDAS and the classification of the ASDAS disease activity states 
will be based on the Baseline BASDAI, PGADA and hs-CRP values. The Baseline for each of 
the variables listed above is defined in Table 3‒1.
Baseline disease characteristics will be summarized using descriptive statistics by treatment 
group and for all subjects based on the SS.  This summary will be repeated for subjects in the SS 
who were randomized in the PET-MRI/PET-CT substudy and will also include summary 
statistics for SUVauc in the SIJ and spine at Baseline derived from the PET-MRI/PET-CT scans 
performed at Screening. SUVauc values for each of the PET-positive lesions identified in the SIJ 
and spine will be pooled across subjects and across the SIJ and anatomical locations in the spine 
for the purpose of this summary.  In addition, the maximum SUVauc value across the SIJ and 
spine for each subject at Baseline will be summarized.
The above Baseline disease characteristics will be listed for the SS.
Subject lifestyle details (alcohol use, smoking history and caffeine use) will be listed, based on 
the SS.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
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6.4
Medical history and concomitant diseases
Medical history (except for AS) will be listed for the RS and summarized for the SS by treatment 
group and for all subjects, MedDRA® system organ class (SOC) and preferred term (PT). The 
reported term will be included in the listing. The summary will include the number and 
percentage of subjects and will be sorted alphabetically by SOC and by descending incidence of 
PT within each SOC, based on the ‘All Subjects’ column. This summary will be repeated for 
subjects in the SS who were randomized in the PET-MRI/CT substudy. A glossary of all medical 
history conditions will be presented for the RS including the SOC, PT and reported term.
Procedure history will be listed separately for the RS by treatment group for previous procedures
relating to AS and previous procedures not relating to AS.  Concomitant medical procedures 
performed during the study will be listed for the RS.
6.5
Ankylosing spondylitis history
Date of initial diagnosis of AS and the date that AS symptoms first started will be listed.
6.6
Prior and concomitant medications
Prior and concomitant medications (Section 6.6.1 and Section 6.6.2) will be listed for the RS by 
treatment group and subject, and summarized for the SS by WHODD Anatomical Main Group 
(Level 1), Pharmacological Subgroup (Level 3) and PT. The reported term will be included in 
the listing, together with flags to identify AS, rescue and prohibited medications, respectively. 
The flags for prohibited, AS and rescue medications will be confirmed and documented at the 
final DEM.
Prohibited medications will be listed separately.
Separate summaries will be presented for prior medications and concomitant medications and 
these will be presented by treatment group and for all subjects. Prior medications which 
continued into the study period are also classified as concomitant and are included in both 
summaries.  
Separate summaries will be presented for the following, identified using WHODD Anatomical 
Main Group codes, the indication recorded on the eCRF and medical review of the recorded 
data:
•
Prior and concomitant AS medications
•
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All AS medications and rescue medication given during the study will be identified via medical 
review of the concomitant medications and confirmed at the DEMs prior to unblinding.
These summaries will be repeated for subjects in the SS who were randomized in the PET-
MRI/PET-CT substudy.
All tabulations will be sorted alphabetically by Level 1 term, alphabetical Level 3 term within 
Level 1 and decreasing frequency of PT in the ‘All Subjects’ column. 
A glossary of all prior and concomitant medications will be presented for the SS including the 
Anatomical Main Group (Level 1), Pharmacological Subgroup (Level 3), PT and reported Term.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 34 of 86
Any medications with partially missing dates and/or times will be handled as described in 
Section 4.2.5 to classify them as prior or concomitant.
6.6.1
Prior medication definition
A medication with a start date that is prior to the date of first dose of IMP will be classified as a
‘prior medication’. 
6.6.2
Concomitant medication definition
A medication with a start date that is on or after the date of first dose of IMP will be classified as 
a ‘concomitant medication’.
Any medication that started prior to the first dose of IMP and continued after will be classified as 
both prior and concomitant. Such medications will therefore be counted in the tabulations for 
both prior and concomitant medication.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
During the Treatment Period of this study, IMP will be administered in the clinic and compliance 
will be determined at the visit by study personnel. 
The number of injections administered at each visit will be included in the listing of IMP
administration as specified in Section 11.1.
In addition, the percentage of planned injections administered will be calculated and presented 
on the listing.  
This will be calculated as follows:
% 𝑃𝑙𝑎𝑛𝑛𝑒𝑑𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛𝑠𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑= 𝑇𝑜𝑡𝑎𝑙𝑁𝑢𝑚𝑏𝑒𝑟𝑜𝑓𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛𝑠𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑
𝑇𝑜𝑡𝑎𝑙𝑁𝑢𝑚𝑏𝑒𝑟𝑜𝑓𝑃𝑙𝑎𝑛𝑛𝑒𝑑𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛𝑠× 100
where the planned number of injections for subjects who have completed the study is 14 for the 
Treatment Period and 16 for the Treatment Period (total of 30 injections).  For subjects who have 
discontinued prematurely from the study, the planned number of injections will be the number of 
planned injections up to the date of discontinuation.
Any deviations from the planned dosing schedule will be addressed at the DEMs (including 
evaluation of any impact on the statistical analysis) and described in the CSR. No formal 
calculations of compliance will be presented as all IMP will be administered on site.
8
EFFICACY ANALYSES
8.1
Primary efficacy variable
8.1.1
Derivation of the primary efficacy variable
The ASDAS will be calculated based on individual component assessments of spinal pain, 
duration of morning stiffness and peripheral pain/swelling from the BASDAI together with the 
PGADA and hs-CRP values at the corresponding visit.  
8.1.1.1
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI is the most commonly used instrument to measure the disease activity of AS from 
the subject’s perspective. The BASDAI is a validated self-reported instrument which consists of 
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 35 of 86
6 questions scored on a 0 to 10-unit horizontal numeric rating scale (NRS) to measure the 
severity of the 5 major symptoms: fatigue, spinal and peripheral joint pain and swelling, 
enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. 
Questions 2, 3 and 6 of the BASDAI are used in the calculation of ASDAS.  
Question 2 asks 
Question 3 of the BASDAI 
Question 6 of the BASDAI 
(Section 8.1.1.4).  
The full BASDAI questionnaire is shown in Section 14.1.
8.1.1.2
Patient’s Global Assessment of Disease Activity
Subjects will provide a global assessment of their disease activity in response to the question 
“How active was your spondylitis on average during the last week?” using a NRS where 0 is 
“not active” and 10 is “very active”.
8.1.1.3
High-sensitivity C-reactive protein
Blood will be collected for the measurement of hs-CRP. 
8.1.1.4
Calculation of Ankylosing Spondylitis Disease Activity Score
Each of the individual component assessments described above in Section 8.1.1.1,
Section 8.1.1.2 and Section 8.1.1.3 are multiplied by a validated factor (van der Heijde et al, 
2005) as listed below:
•
0.121 x Total spinal pain (BASDAI Question 2 result)
•
0.058 x Duration of morning stiffness (BASDAI Question 6 result) 
•
0.110 x PGADA 
•
0.073 x Peripheral pain/swelling (BASDAI Question 3 result)
•
0.579 x (natural logarithm of the hs-CRP [mg/L] + 1)
The results of these individual calculations or weighted components are then summed to obtain 
the ASDAS.
Handling of missing data and values of hs-CRP that are below 2 mg/L will be handled as 
described in Section 4.2.1.1.
ASDAS will be calculated at Baseline and at each post-Baseline visit per the schedule of 
assessments in the protocol.
The primary efficacy analysis will be based on the change from Baseline in ASDAS at Week 12.
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Statistical Analysis Plan Amendment 3
Bimekizumab
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8.1.2
Primary analysis of the primary efficacy variable
The primary efficacy analysis of the primary efficacy variable will be based on the PPS.
The primary efficacy analysis is the comparison of the change from Baseline in ASDAS at 
Week 12 in the BKZ treatment group versus the CZP treatment group in the PPS. 
8.1.2.1
Bayesian modeling
The primary statistical analysis of the primary efficacy variable at Week 12 will be conducted 
following a Bayesian paradigm.  The Bayesian analysis will be performed using a linear
regression model including treatment group and Baseline ASDAS (mean centered using the 
overall ASDAS mean). The model will be parameterized such that the effect of CZP is 
represented by the intercept parameter whilst the effect of BKZ is additive to this. An
informative prior will be used for the model for the intercept coefficient which, in the primary 
model, is equal to the mean change from Baseline in ASDAS in the CZP group when the 
centered Baseline mean is zero (βCZP ~ Normal [-1.78, var=0.0605]). Vague priors will be used
for the other model coefficients, ie, centered Baseline coefficient and additive effect of BKZ. 
Proof of Concept (PoC) will be declared if the posterior probability of a positive difference in the 
mean change from Baseline in ASDAS at Week 12 between the CZP and BKZ treatment groups 
(CZP-BKZ) is 0.975 or greater (ie, the lower bound of the 95% credible interval of the difference 
between treatment groups in the mean change from Baseline in ASDAS is zero or greater).
The model to be used is as follows:
𝑦𝑖~𝛽𝐶𝑍𝑃+ 𝛽𝑏𝑙𝑥𝑖,𝑏𝑙+ 𝛽𝐵𝐾𝑍𝑥𝑖,𝐵𝐾𝑍
Where 𝑖indexes the 𝑖= 1, … , 𝑁subjects, 𝑦𝑖is the change from Baseline in ASDAS at Week 12 
for subject 𝑖, 𝑥𝑖,𝑏𝑙is the centered Baseline ASDAS for subject 𝑖, 𝑥𝑖,B𝐾𝑍is a variable equal to 1 if 
subject 𝑖was randomized to the BKZ group and 0 if not, 𝛽𝐶𝑍𝑃is the model intercept, 𝛽𝑏𝑙is the 
coefficient for the centered Baseline ASDAS, and 𝛽𝐵𝐾𝑍is the additive effect of BKZ in addition 
to the effect of CZP.
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where the prior for 𝛽𝐶𝑍𝑃is worth approximately 20 subjects (Section 2.4). The sample sizing for 
this study was based on the assumption that 𝜎2=1.1 which was based on the CZP data available 
from a single internal study (Section 8.1.2.2). 
In addition to the primary Bayesian analysis where subjects with missing data will be excluded 
from the analysis, a supportive analysis based on imputed or predicted values for the change 
from Baseline in ASDAS at Week 12 will be performed.
Predicted Week 12 values for the subjects who do not have ASDAS values for the Week 12 visit 
will be obtained from a Mixed Model Repeated Measures (MMRM) analysis. The model will 
include treatment group, visit and the treatment group by visit interaction as fixed effects (visit as 
a categorical variable) and Baseline ASDAS as a continuous covariate. Subject-level random 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
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unstructured covariance matrix for these random effects will be used, along with a simple 
covariance structure for the within-subject errors.
If the model fails to converge then the simpler subject-level model including the intercept as only 
random effect will be fitted. If there are still problems with convergence and/or if the estimated 
response covariance matrices (random effects and response) are not positive definite, then 
alternative models will be considered, eg, allowing the random effects covariance parameters to 
be unbounded, or modelling the response covariance structure without using random effects.
The combination of observed and predicted values of change from Baseline in ASDAS at Week 
12 obtained from the MMRM will then be modelled as the response variable in this supportive 
Bayesian analysis.
8.1.2.2
Building the prior
The CZP prior for this study has been built based on UCB study AS0001.
Study AS0001 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study 
to evaluate the efficacy and safety of 2 dose regimens of CZP in subjects with active axial 
spondyloArthritis (axial SpA).  Subjects were randomized in a 1:1:1 ratio to receive one of three 
treatment regimens:
•
CZP administered subcutaneously (sc) at the dose of CZP 400mg every 2 weeks (Q2W) at 
Weeks 0, 2, and 4 followed by CZP 200mg Q2W sc; 
•
CZP administered sc at the dose of CZP 400mg Q2W at Weeks 0, 2, and 4 followed by CZP 
400mg every 4 weeks (Q4W) sc; 
•
Placebo.
In this study AS0001, one of the secondary efficacy variables was the change from Baseline in 
ASDAS; the primary efficacy variable for the current study AS0013.
To build the prior using these data, subjects in the CZP 400mg treatment group were removed 
since their CZP responses were sufficiently different from those of the CZP 200mg subjects 
(leaving 105 CZP 200mg subjects with Baseline and Week 12 data available), and the linear 
model detailed in Section 8.1.2.1 was fitted to just the Placebo and CZP 200mg treatment groups 
with Placebo as the additive treatment effect (a treatment group by Baseline ASDAS interaction 
was also included in the model for this historical).
The estimated model was used to estimate the distribution 𝛽𝐶𝑍𝑃~𝑁(−1.78, 𝜎𝐶𝑍𝑃
2
= 0.0078) and 
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expected study to study variation in the estimated CZP parameter 𝛽𝐶𝑍𝑃, this prior was discounted 
(the SD was inflated) to arrive at the prior given in Section 8.1.2.1 (by inflating the SD by 2.788 
to give an effective sample size of approximately 20 subjects).
The historical data in study AS0001 gave the opportunity to build an informative prior for the 
overall effect of Baseline ASDAS in the proposed study (ignoring treatment group since a 
Baseline by treatment group interaction is not expected).  However, since the AS0001 study only 
included Placebo and CZP treatment group data there is currently no data available with which to 
confirm whether or not the estimated Baseline ASDAS coefficient of -0.66 for CZP is also 
similar for BKZ. Accordingly, whilst a Baseline by treatment group interaction in the proposed 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 38 of 86
study is not expected, to account for this uncertainty a non-informative prior was used for the 
Baseline ASDAS coefficient. 
8.1.2.3
Prior data conflict
Prior data conflict will be investigated for all informative priors through use of graphical 
displays.  If there is evidence of prior data conflict for a given parameter, then a vague prior will 
be used for that parameter.
8.1.3
Presentation of the primary analysis of the primary efficacy variable
The Bayesian analysis will be implemented using multiple chains each utilizing different starting 
values for the model specified parameters. The posterior samples from each chain will be 
combined into one dataset from which the posterior summaries will be estimated. Missing data 
will be handled as described in Section 4.2.1
The posterior distributions of the mean changes from Baseline in ASDAS in the CZP and BKZ
groups and of the difference in mean changes from Baseline between the treatment groups 
(CZP – BKZ) will be summarized using means, medians, SDs, 95% credible intervals and 95% 
highest posterior density intervals. The posterior probability that the difference between 
treatment groups in the mean change from Baseline in ASDAS at Week 12 is greater than zero 
will also be presented.
The posterior probability that BKZ achieves a lower ASDAS score at Week 12 compared to CZP 
will be derived from this distribution.  
8.1.4
Presentation of Ankylosing Spondylitis Disease Activity Score
All component data, the derived ASDAS values and changes from Baseline at each visit will be 
listed by treatment group and subject, including each of the ASDAS disease activity states and 
disease improvement categories defined in Section 8.2.1.1, based on the FAS. Observed ASDAS 
values and changes from Baseline will be summarized by treatment group and visit, using 
descriptive statistics, based on the PPS and repeated for the FAS.
Observed mean values and changes from Baseline, including 95% CI for the means, will be 
plotted versus time, with both treatment groups overlaid on the same axes, based on the PPS and 
repeated for the FAS.
8.1.5
Presentation of component variables of Ankylosing Spondylitis 
Disease Activity Score
All data presentations in this section will be based on the PPS and repeated for the FAS.
8.1.5.1
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity.
The BASDAI questionnaire contains 6 questions, each of which has a possible value ranging 
from 0 to 10, and the overall score is calculated as follows:
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Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
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Page 39 of 86
To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness 
(questions 5 and 6) is taken. The sum of the scores from questions 1 to 4 and the average of the 
scores from questions 5 and 6 result in a total score ranging from 0 to 50.  This is divided by 5 to 
give a final BASDAI score between 0 and 10, with lower scores indicating lower disease 
activity.
The individual question responses from the BASDAI together with the derived BASDAI score 
will be listed by treatment group and visit for each subject, including changes from Baseline for 
the BASDAI score. Additionally, for each subject the mean result from questions 5 and 6, 
together with the change from Baseline and percentage change from Baseline in this mean value, 
will be listed.
The observed BASDAI score and changes from Baseline will be summarized by treatment group 
and visit.
Additionally, the mean of question 5 and 6, together with the corresponding changes from 
Baseline and percentage changes from Baseline will be summarized by treatment group and visit.
Observed mean BASDAI score and changes from Baseline, including 95% CI for the means, will 
be plotted versus time, with both treatment groups overlaid on the same axes.
The full BASDAI questionnaire is shown in Section 14.1. A glossary of the BASDAI 
questionnaire will be presented.
8.1.5.2
Patient’s Global Assessment of Disease Activity
Patient’s Global Assessment of Disease Activity will be listed by treatment group, subject and 
visit, including changes from Baseline and percentage changes from Baseline.
Observed values, changes from Baseline and percentage changes from Baseline will be 
summarized by treatment group and visit.
Observed mean PGADA and changes from Baseline, including 95% CI for the means, will be 
plotted versus time, with both treatment groups overlaid on the same axes.
8.1.5.3
High sensitivity C-reactive protein
Measurements of hs-CRP will be listed by treatment group, subject and visit for each subject 
including changes from Baseline and ratio to Baseline. The latter will be calculated as follows:
𝑅𝑎𝑡𝑖𝑜𝑡𝑜𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒= ℎ𝑠--– -𝐶𝑅𝑃𝑎𝑡𝑃𝑜𝑠𝑡– 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒𝑉𝑖𝑠𝑖𝑡/ ℎ𝑠– -𝐶𝑅𝑃𝑎𝑡𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒𝑉𝑖𝑠𝑖𝑡
Observed values, changes from Baseline and ratio to Baseline will be summarized by treatment 
group and visit. Summary statistics will include n, arithmetic mean, SD, geometric mean, 95% 
CI for the means, geoCV, median, Q1, Q3, minimum and maximum. 
The geoCV will be calculated as a percentage as: 
𝑔𝑒𝑜𝐶𝑉(%) = 100 × √exp(𝑆𝐷𝐿
2) −1,
where SDL represents the standard deviation of the natural logarithm transformed value.  
Observed mean hs-CRP values, changes from Baseline and ratio to Baseline, including 95% CI 
for the means, will be plotted versus time, with both treatment groups overlaid on the same axes.
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Bimekizumab
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The rules for handling any observed concentration values that are BLQ or ALQ are described in 
Section 4.2.1.2.
8.1.6
Supportive analysis of the primary efficacy variable
8.1.6.1
Alternative analysis sets
The primary efficacy analysis set is the PPS; however, the primary analysis and all supportive 
analyses of the primary efficacy variable will be repeated using the FAS.  These analyses will be 
performed in order to evaluate the effect that any IPDs may have had on the results of the 
analysis. The results will be presented as specified in Section 8.1.3.
8.1.6.2
Alternative prior distributions
The primary analysis will be repeated for each of the following prior distribution alternatives:
•
A vague prior distribution for all parameters in the model (including the CZP effect).
•
An informative prior for the Baseline effect [𝛽𝑏𝑙~𝑁(−0.66, 𝜎𝑏l
2 = 25)] and an informative 
prior for the CZP effect.
•
An informative prior for the Baseline effect [𝛽𝑏𝑙~𝑁(−0.66, 𝜎𝑏𝑙
2 = 25)] and a vague prior for 
the CZP effect [𝛽𝐶𝑍𝑃~𝑁(0, 𝜎𝐶𝑍𝑃
2
= 106)].
The results will be presented as specified in Section 8.1.3.
8.1.6.3
Frequentist analysis – Analysis of Covariance
A frequentist analysis of the change from Baseline in ASDAS at Week 12 will be performed 
using an analysis of covariance (ANCOVA).  The ANCOVA model will match the Bayesian 
model, ie, including treatment group (CZP and BKZ) as a fixed effect and Baseline ASDAS as a 
covariate.
Least squares means (LSMeans), SEs and associated 95% CIs for the changes from Baseline in 
ASDAS at Week 12 in each treatment group will be presented.  In addition, the estimated 
treatment difference in LSMeans (CZP – BKZ), SE, corresponding 95% CI, and p-value for the 
treatment comparison will be presented.
8.1.6.4
Frequentist analysis – Mixed Model Repeated Measures
A frequentist analysis of the change from Baseline in ASDAS will be performed using a 
MMRM.  This model will use all available change from Baseline in ASDAS data at all post-
Baseline visits during the Treatment Period up to and including Week 12.  Treatment group 
(CZP and BKZ), visit, and the treatment group by visit interaction will be included as fixed 
effects and Baseline ASDAS will be included as a covariate.
An unstructured covariance matrix will be used to model the within-subject errors.  If the model 
fails to converge, and/or if the estimated unstructured covariance matrix is not positive definite, 
then simpler alternative covariance structures will be considered (eg, compound symmetry).
Least squares means, SEs and associated 95% CIs for the changes from Baseline in ASDAS in 
each treatment group will be presented by visit.  In addition, the estimated treatment difference 
in LSMeans (BKZ – CZP), SE, corresponding 95% CI, and p-value for the treatment comparison 
will be presented for each visit.  Week 12 will be the primary time point of interest from this 
analysis.
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UCB
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Statistical Analysis Plan Amendment 3
Bimekizumab
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The LSMeans for the changes from Baseline, including 95% CI, will be plotted versus time, with 
both treatment groups overlaid on the same axes.
8.1.6.5
Frequentist analysis – Mixed Model Repeated Measures with 
Baseline by treatment group interaction
A frequentist analysis of the change from Baseline in ASDAS will be performed using a MMRM 
as specified in Section 8.1.6.4.  In addition, the model will include the Baseline ASDAS by 
treatment group interaction. 
The results presentation, and the covariance matrix structures, as specified in Section 8.1.6.4,
will be applied.
8.2
Secondary efficacy variables
Secondary efficacy variables will be listed and summarized by treatment group and visit for the 
PPS and repeated for the FAS.
8.2.1
ASDAS Disease Activity States and Improvement
8.2.1.1
Derivation of ASDAS Disease Activity States and Improvement
Cut-offs for 4 disease activity states based on ASDAS will be defined for each subject at 
Baseline and at each post-Baseline visit as follows:
•
ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3
•
ASDAS-Moderate Disease activity (ASDAS-MD): ASDAS ≥1.3 to < 2.1
•
ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥2.1 to ≤3.5
•
ASDAS-Very High Disease activity (ASDAS-vHD): ASDAS > 3.5
In addition, the following cut-offs for 2 levels of improvement in ASDAS will be defined for 
each subject at each post-Baseline visit based on the change from Baseline in ASDAS:
•
ASDAS Clinically Important Improvement (ASDAS-CII): a reduction (improvement) from 
Baseline in ASDAS ≥ 1.1 units
•
ASDAS Major Improvement (ASDAS-MI): a reduction (improvement) from Baseline in 
ASDAS ≥ 2.0 units 
ASDAS-Inactive Disease (ASDAS-ID) and ASDAS-Major Improvement (ASDAS-MI) at Week 
12 are the secondary efficacy variables defined for this study. Subjects with missing ASDAS at 
Week 12 will not be classified in terms of their ASDAS disease activity state or improvement 
according to the above definitions.
8.2.1.2
Analysis of ASDAS Disease Activity States and Improvement
The number and percentage of subjects classified in each of the disease activity state categories 
(ASDAS-ID, ASDAS-MD, ASDAS-HD and ASDAS-vHD) and each disease improvement 
category (ASDAS-CII [yes/no] and ASDAS-MI [yes/no]) and will be tabulated by treatment 
group and visit including the 95% CIs calculated using a Wilson approximation.
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Additionally, inferential treatment effects for ASDAS-ID and ASDAS-MI at Week 12 will be 
derived from the Bayesian analysis as described in Section 8.1.2.1.  ASDAS-ID and ASDAS-MI 
rates at Week 12 will be presented.
8.3
Other efficacy variables
8.3.1
Derivation of Assessment in SpondyloArthritis International Society
Response
The following ASAS-based variables will be derived:
•
ASAS20 response is defined as an improvement of at least 20% (percentage change from 
Baseline of -20% or more negative), and an absolute improvement of at least 1 unit (change 
from Baseline of -1 or more negative) in at least 3 of the 4 following domains: 
−
PGADA (Section 8.1.5.2)
−
Function (represented by BASFI, Section 8.3.3.1)
−
Pain assessment (the total spinal pain NRS score, Section 8.3.3.2)
−
Inflammation (the mean of the BASDAI Questions 5 and 6 results, Section 8.1.5.1,
concerning morning stiffness intensity and duration)
In addition, absence of deterioration in the potential remaining domain is required. 
Deterioration is defined as the presence of both of the following:
−
percentage change from Baseline of 20% or more;
−
change from Baseline of 1 unit or more.
•
The ASAS40 response is defined as an improvement of at least 40% (percentage change 
from Baseline of -40% or more negative), and an absolute improvement of at least 2 units 
(change from Baseline of -2 or more negative) in at least 3 of the 4 domains above. In 
addition, no worsening (a change from Baseline that is non-positive [ie, negative or zero]) in 
the remaining domain is required.
•
Time to ASAS20 response: defined as the time (in days) from the first dose of IMP to the 
first instance (if more than one instance) of an ASAS20 response.
−
This will be calculated for the Treatment Period and across the entire study period 
(Treatment Period + Treatment Extension Period) separately.
−
For time to ASAS20 response during the Treatment Period: 
−
Subjects who discontinue early prior to an ASAS20 response will be censored on 
the date of their last efficacy assessment during the Treatment Period.
−
Subjects who do not have an ASAS20 response during the Treatment Period will be 
censored on the date of their Week 12 efficacy assessment (ie, end of the Treatment 
Period).
−
For time to ASAS20 response during the study (Treatment Period + Treatment Extension 
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−
Subjects who discontinue early prior to an ASAS20 response will be censored on 
the date of their last efficacy assessment during the study (Treatment Period + 
Treatment Extension Period).
−
Subjects who do not have an ASAS20 response during the study will be censored 
on the date of their Week 48 efficacy assessment (ie, end of the Treatment
Extension Period).
•
Time to ASAS40 response: defined as the time (in days) from the first dose of IMP to the 
first instance (if more than one instance) of an ASAS40 response. As described above for 
time to ASAS20 response, time to ASAS40 response will be calculated based on the 
Treatment Period and also across the study period (Treatment Period + Treatment Extension 
Period) separately and the same censoring rules will be applied.
•
The ASAS partial remission (ASAS-PR) response is defined as a score of ≤2 units in all 4 
domains listed above.
In order for a subject to be defined as a responder (ASAS20, ASAS40 or ASAS-PR, 
respectively) at a given visit, the criteria stated must be met all together that visit.
Missing component data for the derivation of the ASAS20, ASAS40 and ASAS-PR will be 
handled as described in Section 4.2.1.4.
8.3.2
Presentation of Assessment in SpondyloArthritis International 
Society Response
8.3.2.1
ASAS20 and ASAS40 response
A by-subject listing showing ASAS20 and ASAS40 response status will be presented by 
treatment group and visit for the FAS. 
The number and percentage of subjects classified as ASAS20 and ASAS40 at each post-Baseline 
visit will be tabulated by treatment group for the FAS including the 95% CI calculated using a 
Wilson approximation.
8.3.2.2
Time to ASAS20 and ASAS40 response
A by-subject listing showing time to ASAS20 response and time to ASAS40 response will be 
presented by treatment group and visit for the FAS. This listing will include flags for censored 
observations.
The time to ASAS20 response and time to ASAS40 response during the Treatment Period and 
during the study (Treatment Period + Treatment Extension Period) will be summarized for the 
FAS separately using the following statistics:
•
Number and percentage of subjects that are responders
•
Number and percentage of subjects that are censored
•
Minimum, maximum and Kaplan-Meier estimates of the 25th percentile, median and 75th
percentile, with corresponding 95% CIs
Kaplan-Meier response rates for ASAS20 and ASAS40 will be presented for each treatment, 
including the cumulative number of events and the number of subjects at risk at each study visit. 
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This will be presented separately for the Treatment period and across the study (Treatment 
Period + Treatment Extension Period). 
Kaplan-Meier curves will be presented for time to ASAS20 response and time to ASAS40 
response for the Treatment Period and across the study (Treatment Period + Treatment Extension 
Period) separately, with both treatment groups overlaid on each plot. The plot will start at zero 
(ie, no responders at time zero) and be non-decreasing.
8.3.2.3
ASAS-PR
A by-subject listing showing ASAS-PR response status will be presented by treatment group and 
visit for the FAS.
The number and percentage of subjects classified as ASAS-PR at each post-Baseline visit will be 
tabulated by treatment group for the FAS including the 95% CI calculated using a Wilson 
approximation.
8.3.3
Presentation of components of Assessment in SpondyloArthritis 
International Society
8.3.3.1
Bath Ankylosing Spondylitis Functional Index
The BASFI is a validated index used to determine the degree of functional limitation in subjects 
with AS.  The BASFI questionnaire comprises 10 questions, each of which has a possible value 
ranging from 0 ("Easy") to 10 ("Impossible").  The first 8 questions evaluate activities related to 
functional anatomical limitations due to AS and the final 2 questions evaluate a subject's ability 
to cope with everyday life.  The BASFI will be administered at all visits per the schedule of 
events. 
The BASFI score is the arithmetic mean of the 10 individual scores giving a value between 0 and 
10, with lower scores indicating better physical function.
Missing data for the BASFI questionnaire will be handled as described in Section 4.2.1.5.
The BASFI results will be listed by treatment group and visit for each subject in the FAS
including the results from each of the individual 10 questions, the BASFI score, changes from 
Baseline and percentage changes from Baseline in the BASFI score.
The full BASFI questionnaire is shown in Section 14.2. A glossary of the BASFI questionnaire 
will be presented.
Observed values, changes from Baseline and percentage changes from Baseline in the BASFI 
score will be summarized by treatment group and visit for the FAS.
8.3.3.2
Total and nocturnal spinal pain numeric rating scale
The pain experienced by subjects due to AS will be assessed by the following questions, 
referring to the average experience over the past week:
•
Total pain in the spine: How much pain of your spine due to spondylitis do you have?
•
Nocturnal spinal pain: How much pain of your spine due to spondylitis do you have at night?
The response to these questions will be rated by the subjects on a scale from 0 (no pain) to 10 
(most severe pain) and the response will be recorded on the eCRF.
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The Total and Nocturnal spinal pain scores will be listed by treatment group and visit for each 
subject in the FAS including changes from Baseline and percentage changes from Baseline. 
Observed values, changes from Baseline and percentage changes from Baseline will be 
summarized by treatment group and visit for the FAS for each of Total and Nocturnal spinal pain 
scores.
8.3.4
Physician’s Global Assessment of Disease Activity
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 
where 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. 
A by-subject listing will present the PhGADA results by treatment group and visit for the FAS, 
including changes from Baseline.  Observed values and changes from Baseline will be 
summarized by treatment group and visit for the FAS.
8.3.5
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 other inflammatory skin diseases (Dauden et al, 
2009; Langley et al, 2010). 
The HADS is a commonly used instrument to determine the levels of anxiety and depression that 
a subject is experiencing. The HADS is a 14-item scale that generates ordinal data. Seven items 
relate to anxiety (assessed in the HADS-A) and seven relate to depression (assessed in the 
HADS-D). Individual item scores range from 0 to 3 and are summed to give a total score on each 
of the individual HADS-A and HADS-D scales. These total scores range from 0 to 21 with 
higher scores indicating a worse state.
In case of missing data, the rules in Section 4.2.1.6 will apply.
The full HADS questionnaire is shown in Section 14.3. A glossary of the HADS questionnaire 
will be presented.
Scores for each item on the HADS-A and HADS-D will be listed at each visit by treatment group 
for each subject in the FAS. This listing will also include the total HADS-A and HADS-D scores 
together with the changes from Baseline in the total HADS-A and total HADS-D scores at each 
visit. Summary statistics will be presented by treatment group for the observed total HADS-A 
and HADS-D scores together with changes from Baseline at each visit for the FAS.
8.3.6
Change in Bone Formation (PET-MRI/PET-CT Substudy)
To evaluate the effect of BKZ or CZP on changes in bone formation, an independent assessment 
of SIJ radiographs at Screening (to assess eligibility of subjects for the PET-MRI/PET-CT 
substudy) and PET-MRI/PET-CT scans of the entire spine and SIJ (to assess positivity and 
efficacy in subjects eligible for the substudy) at Baseline, Week 12 and Week 48 will be 
conducted.
8.3.6.1
Eligibility assessment
SIJ radiographs at Screening will be independently assessed in a blinded fashion by two 
reviewers.  An image quality assessment will be performed, modified New York (mNY) scores 
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recorded and a subject’s eligibility determined (subjects must be mNY-positive to be randomized
into the substudy).  If there is disagreement between the two primary reviewers in the assessment 
of eligibility, then a third reviewer will perform an adjudication based on an independent 
assessment of the images.  The results of the adjudication of eligibility will be considered as the 
final assessment.
All data recorded for the eligibility assessment, including imaging date, quality of image, right 
and left SIJ sacroiliitis scoring and radiograph assessment (mNY-positive/negative) will be listed 
by treatment group for each primary reviewer and for the adjudicator (if applicable).  The listing 
will include all subjects in the SS who were randomized into the PET-MRI/PET-CT substudy.
8.3.6.2
Efficacy assessment
SIJ and spine PET-CT and PET-MRI scans will be independently assessed at each time point 
(Baseline, Week 12 and Week 48) in a blinded fashion by two reviewers, with an additional 
adjudication read by a third reviewer, if applicable.  Independent reviewers will assess PET-
MRI/PET-CT examinations quantitatively using VU University Medical Center (VUMC)’s in-
house software (ACCURATE).
Initially, two primary readers will independently assess the images visually to identify PET-
positive lesions in the SIJ and spine.  The readers will dichotomously score the presence or 
absence (1 versus 0) of PET-positive lesions in each side of the SIJ (Left and Right) and at each 
of the 24 spinal levels and 4 spinal regional levels [C2-C7 (Cervical), T1-T12 (Thoracic), L1-L5
(Lumbar), Sacrum] in each of the following 8 spinal locations:
•
Process spinosus
•
Costo-vertebral (right)
•
Costo-vertebral (left)
•
Facet joint (right)
•
Facet joint (left)
•
Anterior vertebra
•
Posterior vertebra
•
Vertebra (other)
For each subject, PET-positive lesions may be identified in one or both sides of the SIJ and in 
one or more of the 192 possible anatomical locations (spinal location/level combinations).  It is 
expected that only one lesion for a subject may be separated/identified in each side of the SIJ or
individual anatomical location in the spine, therefore, there is a direct mapping of a subject’s 
lesion to a SIJ side or spinal location/level.
If there is a discrepancy between the two primary readers in the presence of PET-positive lesion 
assessment (Yes versus No for lesions in any side of the SIJ and 1 versus 0 for lesions in any 
spinal location), a consensus adjudication will take place with a third reader who will also be 
blinded to the clinical data. This reader will make an independent assessment and the results of 
the adjudication will be considered as the final assessment of the presence of PET-positive 
lesions.
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Another reader who has not been involved in the visual identification of the PET-positive 
lesions, either as a primary reader or an adjudicator, will then draw volumes of interest (VOIs) 
on the pre-identified PET-positive lesions. In the case that no PET-positive lesions have been 
identified for a subject, then the final review step to draw VOIs will not occur. Efficacy PET-
MRI/PET-CT review will occur provided that an acceptable PET-CT or PET-MRI scan is 
available and that PET-positive lesions were identified on the previous scan (for the Week 12 
and Week 48 visits). During the PET-positive lesion VOI review, the independent reviewer will
perform a quantitative assessment in ACCURATE and record the standard uptake values of 18F-
fluoride in VOIs, corrected for both body weight and individual integrated whole blood activity 
concentration (SUVauc) for each PET-positive lesion identified during the PET-positive lesion 
identification review.
Data from the visual identification of PET-positive lesions and the results of the quantitative VOI 
review (i.e. SUVauc) will be listed, for each independent reader and adjudicator (if applicable), 
for each anatomical location in the spine, and for each side of the SIJ, by treatment group and 
visit for subjects in the SS who were enrolled into the PET-MRI/PET-CT substudy.
No formal statistical modelling of the PET-MRI/PET-CT imaging data will be performed for this 
substudy; only summaries will be presented together with 95% CIs for mean values, as 
applicable. 
The summaries described below based on the visual identification of PET-positive lesions will 
include the final assessment data, ie, if adjudication was performed, then the adjudicated data 
will be summarized, otherwise data from one of the primary reviewers will be summarized.
All summaries will be presented for the PET-PPS.
Since the attenuation correction and quantification is variable in PET-MRI scans, PET-MRI 
imaging data will be listed but will not be aggregated with the PET-CT imaging data in the 
summaries.
Due to the predicted sparseness of the number of PET-positive lesions in each of the individual 
anatomical locations of the spine, data will be pooled as follows for the purpose of some of the 
summaries:
•
In the SIJ and spine overall (across the SIJ and all anatomical locations in the spine);
•
In the SIJ overall (across both sides), and split by Left and Right side;
•
In the spine overall (across all anatomical locations in the spine), and split by spinal 
regional level (Cervical, Thoracic, Lumbar, Sacrum), and, depending on the 
distribution of lesions across the spine, further by spinal levels and spinal locations in 
which at least 1 PET-positive lesion is identified.
An overview of the total number of PET-positive lesions identified in the spine across all 
subjects in each of the individual anatomical locations will be presented by visit.
The presence of PET-positive lesions identified in the SIJ and spine will be summarized by visit.  
The summary will include the number and percentage of subjects at each visit with any PET-
positive lesions in the spine or the SIJ, in both the spine and the SIJ, in the SIJ overall (and split 
by Left and Right side) and in the spine overall [and split by spinal regional level (Cervical, 
Thoracic, Lumbar and Sacrum) and level/location, as applicable].  This summary will also 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 48 of 86
include a total count of PET-positive lesions across subjects for each of the pooled locations 
described above.  In the spine, the incidence and the total number of lesions will only be 
presented for the anatomical locations in which at least 1 PET-positive lesion is identified.
The number of PET-positive lesions per subject in the SIJ and spine (overall and in pooled 
locations, as described above) will be calculated and summarized by visit using frequency counts 
and percentages, and/or descriptive statistics, as applicable. In addition, in the spine and SIJ 
overall, in the spine overall and in each spinal regional level, the changes in the number of PET-
positive lesions per subject from Baseline to Week 12 and Week 48, and the changes from Week 
12 to Week 48 will be summarized using descriptive statistics.
Bar charts summarizing the total number of PET-positive lesions identified in the SIJ and in the 
spine will be presented by treatment group and visit for each of the pooled locations described 
above. 
Observed SUVauc values for each lesion will be pooled across subjects and summarized by visit 
for each of the pooled locations, as described above.  In the spine, the observed SUVauc values
will only be summarized for the anatomical locations in which at least 1 PET-positive lesion is 
identified. Descriptive statistics will be presented including 95% CIs for the mean observed 
SUVauc values.  In addition, changes and percentage changes in SUVauc values between visits 
will be calculated for each subject’s PET-positive lesion in the SIJ and spine, i.e. Week 12 -
Baseline, Week 48 - Baseline and Week 48 - Week 12.  These changes in SUVauc values will be
pooled across subjects and summarized by visit for each of the pooled locations described above. 
Descriptive statistics will be presented including 95% CIs for mean changes and percentage 
changes in SUVauc values between visits. 
Spaghetti plots of observed SUVauc values for lesions in the SIJ and spine will be presented over 
time for the SIJ overall, the spine overall, and for each spinal regional level (Cervical, Thoracic, 
Lumbar, Sacrum) by treatment group.
In addition, percentage changes in SUVauc values for lesions in the SIJ and spine will be 
summarized using waterfall plots.  These plots will identify subjects’ lesions by treatment group 
and will be presented by pooled location (as described above, as applicable) and for each visit 
comparison (Week 12 – Baseline, Week 48 – Baseline and Week 48 – Week 12).
The maximum of a subject’s observed SUVauc values will be calculated across the pooled 
locations described above. This maximum SUVauc value per subject will be summarized at each 
visit together with changes and percentage changes from Baseline between visits. Descriptive 
statistics will be presented including 95% CIs for the mean and the mean changes/percentage 
changes in the maximum SUVauc values.
The mean and 95% CI for the maximum SUVauc values per subject in the SIJ and spine over 
scheduled time will also be presented by treatment group.  The same plot will be repeated for the 
changes and percentage changes in the maximum SUVauc value per subject with treatment group 
overlaid on the same plot.
In addition, percentage changes in the maximum of SUVauc values per subject in the SIJ and 
spine will be summarized using waterfall plots.  These plots will identify subjects by treatment 
group and will be presented for each visit comparison (Week 12 – Baseline, Week 48 – Baseline 
and Week 48 – Week 12).
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 49 of 86
Additional exploratory analyses may include examining the relationship between changes from 
Baseline in bone formation and changes from Baseline in ASDAS at Week 12 (primary efficacy 
variable) and Week 48, and also whether there are any differences in bone formation in clinical 
responders according to ASAS20 versus clinical non-responders at Weeks 12 and 48. Statistical 
modelling which accounts for multiple PET-positive lesions per subject may be used in these 
analyses.
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
There will be no calculation of PK parameters for this study. The analysis of PK data for this 
study will focus on the concentrations of CZP and BKZ only. Any additional PK analyses will be 
performed only if required.
The actual blood sampling times for BKZ and CZP concentrations will be obtained in days 
relative to the start time of the first administration of IMP for all sampling time points. 
Individual blood sampling times and concentrations of BKZ and CZP will be listed by treatment 
group for the SS and will include the actual sampling time in days relative to the first. 
Individual concentrations will be summarized at each scheduled time point based on the PK-PPS, 
using n, mean, median, SD, minimum, maximum, geometric mean and 95% CI, and geoCV 
(assuming log-normally distributed data). 
Individual concentration versus time (day) profiles will be presented graphically on linear and 
semi-logarithmic scales with all subjects overlaid on the same plot (spaghetti plots). Geometric 
mean profiles, separately for BKZ and CZP, will also be presented on both linear and 
semi-logarithmic scales respectively with and without the corresponding lower and upper limit of 
the 95% CI. All semi-logarithmic plots will include the respective LLOQ marked on the y-axis.
The following rules will apply for PK data listings and summaries:
•
Values below the LLOQ will be reported as BLQ in the listings
•
Descriptive statistics of concentrations will be calculated if at most ⅓ of the individual data 
points are missing or are not quantifiable (<LLOQ). Values that are BLQ will be replaced by 
the numerical values of the LLOQ/2 in this instance. However, if n≤3, then only n, minimum
and maximum will be presented (where ‘n’ refers to the number of quantifiable values). The 
other descriptive statistics will be left blank.
•
The 95% CI for the geometric mean will be left blank if the SD is 0
The geoCV (%) will be calculated using the following formula where SDL is the standard 
deviation from the log-transformed data:
𝑔𝑒𝑜𝐶𝑉(%) = 100 × √exp(𝑆𝐷𝐿
2) −1
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 50 of 86
9.2
Pharmacodynamics
All PD variables will be listed by treatment group, subject and visit including changes from 
Baseline, based on the SS. 
Observed values and changes from Baseline will be summarized by treatment group and visit 
based on the PD-PPS. 
Figures of mean and mean changes from Baseline over time will be presented with separate plots 
for each variable and both treatment groups overlaid on the same plot.
The rules for handling any values that are BLQ or ALQ are described in Section 4.2.2.
10
IMMUNOLOGICAL ANALYSES
The results for the ADA measurements will be listed by treatment group and time point based on 
the SS, including the Screening assay, confirmatory assay and titre (if applicable).
A cut point will be determined by the bioanalytical laboratory that will be used to determine the 
status of ADA as above the cut point (ACP) or below the cut point (BCP). For any ADA levels 
that are ACP, a further confirmatory assay will be performed, the results of which will be 
determined as either ‘confirmed positive’ (CP) or ‘not confirmed positive’ (NCP). For samples 
that are CP, a further titre assay will be performed and the ADA titre will be reported. The
following definitions will be applied:
•
An ADA status for a given time point of positive will be concluded for any subject with an 
ADA level that is ACP and CP at any time point
•
An ADA status of negative for a given time point will be concluded for any subject with an 
ADA level that is either BCP or ACP and NCP at any time points
•
A subject will be classified as having ADA positivity at Baseline if the Visit 2 (Week 0), 
pre-dose result is ACP and CP
•
A subject will be classified as having treatment-induced ADA positivity when meeting 1 of 
the following criteria:
−
The Baseline result is either BCP or ACP and NCP, and at least 1 post-Baseline time
point is ACP and CP
−
The Baseline result is positive (ACP and CP) and at least 1 post-Baseline measurement 
shows a pre-defined fold increase in titre from the Baseline value (the fold increase from 
Baseline required to meet this criterion will be defined with the development of the assay 
and will be included in the TFLs)
•
A subject will be classified as overall positive if at least 1 post-Baseline measurement is ACP 
and CP (this includes subject who have negative results at Baseline)
•
A subject will be classified as overall negative if at all post-Baseline visits the ADA status is 
negative (this includes subjects who have positive [ACP and CP] results at Baseline)
The ADA status (positive/negative) will be summarized as a categorical endpoint (number and 
percentage of subjects) by treatment group, for all time points and overall, based on the PK-PPS. 
In addition, the first occurrence of treatment-induced ADA positivity (based on the definitions 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 51 of 86
above) will be summarized by treatment group (number and percentage of subjects) at each 
post-Baseline visit, based on the PK-PPS. This tabulation will count the number of subjects at 
each post-Baseline visit who fulfill at least 1 of the above defined criteria for treatment-induced 
positivity; subjects will be counted in the numerator based on the earliest visit at which 1 of these 
criteria is fulfilled. At other visits, subjects will be counted in the denominator (assuming a 
measurement is available).  For all tabulations, percentages will be based on the number of 
observations at each visit.
Separate listings will be presented (based on the PK-PPS) showing the BKZ and CZP
concentrations and ADA measurements in the same output in adjacent columns. The listing will 
include the BKZ and CZP concentration, ADA status (ACP or BCP) and confirmatory assay 
results if applicable (NCP or CP), together with the titre for results that are CP. In addition, the 
time since the previous administration of IMP will be reported (in days). 
Finally, individual subject plots (based on the PK-PPS) will be presented displaying ADA titre, 
BKZ and CZP concentrations overlaid on the same figure using a semi-logarithmic scale.
The rules for handling values that are BLQ in the BKZ and CZP concentration data are described 
in Section 4.2.4. For the ADA data, any negative results for which there are no titres available at 
a specific visit will be substituted with 0.001 for the purpose of the figure.
11
SAFETY ANALYSES
All analysis of safety variables will be performed using the SS.
11.1
Extent of exposure
All IMP administration details (including date and time of administration, body site and side of 
administration) will be listed. Additionally, the time between each dose will be listed.
The duration of exposure to BKZ (days) will be calculated separately for the Treatment Period 
and the Treatment Extension Period, where the last and first dose in each equation will be the last 
and first dose of IMP within the Treatment Period and Treatment Extension Period respectively:
𝐸𝑥𝑝𝑜𝑠𝑢𝑟𝑒= (𝐷𝑎𝑡𝑒𝑜𝑓𝐿𝑎𝑠𝑡𝐷𝑜𝑠𝑒−𝐷𝑎𝑡𝑒𝑜𝑓𝐹𝑖𝑟𝑠𝑡𝐷𝑜𝑠𝑒) + 140 𝑑𝑎𝑦𝑠
The duration of exposure to CZP (days) will be calculated as follows:
𝐸𝑥𝑝𝑜𝑠𝑢𝑟𝑒= (𝐷𝑎𝑡𝑒𝑜𝑓𝐿𝑎𝑠𝑡𝐷𝑜𝑠𝑒−𝐷𝑎𝑡𝑒𝑜𝑓𝐹𝑖𝑟𝑠𝑡𝐷𝑜𝑠𝑒) + 70 𝑑𝑎𝑦𝑠
The number of days added to the BKZ and CZP exposure calculations are 5 times the half-life of 
each drug, respectively: 5 x 28 days for BKZ and 5 x 14 days for CZP. 
Missed doses will not be accounted for in the calculation above. 
The number of injections received and duration of exposure will be listed for each subject and 
summarized by treatment group for the Treatment Period and Treatment Extension Period 
separately using descriptive statistics. This summary will be repeated for subjects in the SS who 
were randomized in the PET-MRI/CT substudy.
11.2
Adverse events
Adverse events with start date prior to the first dose of IMP are defined as pre-treatment AEs. 
Adverse events with a start date prior to the first dose of IMP will be defined as pre-treatment 
AEs. A treatment-emergent AE (TEAE) is defined as any AE with a start date/time at the time of 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 52 of 86
or after the first dose of IMP up until 140 days after the last dose of IMP. Any AE with onset 
later than 140 days after the last dose of IMP will not be considered as treatment-emergent and 
therefore will not be included in the tabulations of TEAEs. Selected summaries will be presented 
separately for TEAEs during the Treatment Period (any AE with a start date/time at the time or 
after the first dose of IMP up until the Week 12 Visit) and TEAEs during the study (as per the 
definition of TEAEs given above).
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent, 
unless there is clear evidence to suggest that the AE started prior to dosing or later than 140 days 
post-last dose. Handling of missing dates/times for classification of AEs as TEAEs is described 
in Section 4.2.5.
All AEs will be recorded in the eCRF from informed consent until study completion or 
termination. All AEs will be coded and categorized by intensity (mild/moderate/severe) and 
relationship to IMP (related/not related).
An overview of the number and percentage of subjects who experience TEAEs will be presented 
by treatment group, based on the SS. Separate tabulations will be presented for TEAEs during 
the Treatment Period and TEAEs during the study and will include the number and percentage of 
subjects with any TEAEs, serious TEAEs, related TEAEs, discontinuation due to TEAEs, severe 
TEAEs, AEs leading to death and TEAEs leading to death; event counts will also be included.  
The summary of TEAEs during the study will be repeated for subjects in the SS who were 
randomized in the PET-MRI/PET-CT substudy.
In addition, the following summaries will be presented by treatment group, SOC, high level term 
(HLT) and PT, based on the SS:
•
Incidence of TEAEs[a] [b]
•
Incidence of TEAEs, stratified by overall ADA status (positive/negative) as defined in 
Section 10
•
Incidence of serious TEAEs[a] [b]
•
Incidence of non-serious TEAEs[b]
•
Incidence of TEAEs by relationship
•
Incidence of TEAEs by maximum relationship
•
Incidence of TEAEs by maximum intensity
•
Incidence of fatal TEAEs by relationship
•
Incidence of non-serious TEAEs by relationship
•
Incidence of serious TEAEs by relationship
•
Incidence of non-serious TEAEs above threshold of 5% of subjects
•
Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship
•
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 53 of 86
[a] These summaries will be presented separately for TEAEs during the Treatment Period and 
TEAEs during the study.
[b] These summaries will be repeated for subjects in the SS who were randomized in the PET-
MRI/PET-CT substudy and will be based on TEAEs during the study
In addition, separate summaries by treatment group, SOC, HLT and PT will be included for the 
following AEs for special monitoring (AESM): 
•
Major cardiovascular events
•
Serious infections, including opportunistic infections and tuberculosis (TB)
•
Malignancies including lymphoma
•
Cytopenias
•
Neuropsychiatric events
•
Inflammatory bowel disease
•
Anaphylactic reaction (hypersensitivity and anaphylactic reactions)
•
Hepatic events and drug-induced liver injury
The criteria for identifying and additional criteria for reporting AESM are provided in
Section 14.5.
All summary tables (including those for AESM) will contain the number and percentage of 
subjects and the number of events where applicable. A subject who has multiple events in the 
same SOC, HLT and PT will be counted only once in the subjects counts but all events will be 
included.
In summaries including relationship to IMP, the following relationship categories will be 
included:
•
Related
•
Not related
Subjects who experience the same event multiple times will be included in the most related 
category for tabulations by maximum relationship. Events with missing relationship will be 
considered as ‘Related’ for summary purposes but shown as missing in the data listings. 
In summaries including intensity, the following categories will be summarized:
•
Mild
•
Moderate
•
Severe
Subjects who experience the same event multiple times will be included in the most severe 
category for tabulations by maximum intensity. Events with missing intensity will be considered 
as ‘Severe’ for summary purposes. All data will be presented as recorded in the database for the 
listings.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 54 of 86
Adverse event summaries will be ordered by alphabetical SOC, alphabetical HLT within SOC 
and decreasing frequency of PT in the ‘BKZ’ column for tables including event counts. For 
tables including only number and percentage of subjects, summaries will be ordered by 
alphabetical SOC, alphabetical HLT within SOC and decreasing incidence of PT within HLT 
and SOC in the ‘BKZ’ column. 
Listings will be presented by treatment group and subject for all AEs, serious adverse events 
(SAEs), AEs leading to death and AEs leading to withdrawal. Listings will include the onset 
date/time and outcome date/time of the event (including relative days), the AE duration 
(derived), days since first dose of IMP, days since most recent dose of IMP, pattern of event, 
intensity, relationship, action taken and outcome. In addition, the listing will flag AEs that led to 
discontinuation, TEAEs, AESM and SAEs. All AE listings will be based on all subjects 
screened.
A glossary of all TEAE terms will be provided including the SOC, HLT, PT and reported term.
11.3
Clinical laboratory evaluations
Laboratory data (chemistry, hematology, and urinalysis) and changes from Baseline (if 
applicable) for numeric variables will be listed by treatment group and visit. Any laboratory 
variables that are BLQ or ALQ will be handled as described in Section 4.2.3. Values outside the 
reference range for the numeric variables will be flagged in the listings and, in addition, will be 
listed separately. The reference ranges will also be reported in the listings. 
Chemistry and hematology variables presented in Table 11‒1 will be summarized by treatment 
group at each visit, for both observed values and changes from Baseline. Figures of mean and 
mean change from Baseline will be presented by treatment for the absolute neutrophil count 
(ANC). All treatment groups will be overlaid on the same plot and the plot will include the error 
bars based on the SD (ie, mean +/-SD).
Laboratory variables will be grouped according to the laboratory function panel and categorized 
as normal, high or low, if applicable, based on the reference range supplied by the analytical 
laboratory. For selected variables that are identified in Table 11‒1, the change in category from 
Baseline will be presented in shift tables at all post-Baseline visits.
The number and percentage of subjects with treatment-emergent markedly abnormal (TEMA) 
values will be tabulated by treatment group and visit. Markedly abnormal laboratory values will 
generally be defined as those categorized as Grade 3 or Grade 4 as per the Rheumatology 
Common Toxicity Criteria (RCTC). Communication with the lead author of the RCTC 
publication has revealed that the reference ranges for absolute lymphocyte counts (ALC) are in 
error, therefore ALC criteria will follow the ranges defined as per the Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03 (United States Department of Health and 
Human Services, 2010). Additional laboratory variables (not present in the RCTC publication) 
will also be categorized as per the CTCAE Version 4.03. The criteria for identifying TEMA 
values are presented in Table 14‒5 and Table 14‒6 for hematology and chemistry values 
respectively.
Laboratory measurements meeting the criteria for TEMA will be listed separately for 
hematology and chemistry. The listings will include all measurements for any variable with at 
least one TEMA result for each subject. 
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 55 of 86
Any additional laboratory variables not included in the outputs described previously will be 
listed separately. These will include the following:
•
Serology
•
Urine drug screen
•
Pregnancy tests (serum and urine)
•
Follicle stimulating hormone (FSH) (only for women whose last menstrual cycle occurred 
between 12 and 24 months prior to the Screening Visit)
•
The results of the Quantiferon tuberculosis (TB) Gold test will be listed separately.
Subjects with treatment-emergent liver function test abnormalities at any post-Baseline visit will 
be summarized (number and percentage of subjects) by treatment group. The criteria for this 
tabulation are presented in Table 14‒7.
Table 11‒1: Clinical laboratory measurements
Category
Panel
Variable
Serology
Serology
human immunodeficiency virus 
(HIV), Hepatitis B and C, human 
leukocyte antigen (HLA)-B27
(HLA-B27)
Hematology
Red blood cell
red blood cell counta, 
hemoglobina, hematocrit
Red blood cell indices
mean corpuscular hemoglobin, 
mean corpuscular hemoglobin 
concentration, mean corpuscular 
volume
Platelet
Platelet
White blood cell
white blood cell counta
White blood cell differential
Absolute counts: absolute 
neutrophilsa, basophils, 
eosinophils, absolute 
lymphocytes, monocytes; 
atypical lymphocytes
Percentages:
neutrophils/leukocytesa,
basophils/leukocytesa,
eosinophils/leukocytesa,
lymphocytes/leukocytesa,
monocytes/leukocytesa.
Chemistry
Electrolytes
Sodium, chloride, potassium, 
magnesium, total calcium, 
bicarbonate
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 56 of 86
Table 11‒1: Clinical laboratory measurements
Category
Panel
Variable
Kidney function
BUN, creatinine, uric acid, 
glomerular filtration rate
Proteins
hs-CRPbc
Liver function
ASTa, ALTa, GGTa, ALPa, LDHa, 
total bilirubin, direct bilirubin (if 
indicated), indirect bilirubin (if 
indicated)
Lipids
Total cholesterola
Hormones
FSH (postmenopausal females 
only)
Fertility
Pregnancy testd
Substrates
Glucose
Urinalysis
Dipstick
pH, albumin, glucose, blood 
(RBC, WBC)
Urine sediment
RBC, WBC, crystals, bacteria 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; GGT=gamma glutamyl transferase; FSH=follicle stimulating hormone; HIV=human immunodeficiency 
virus; HLA-B27= human leukocyte antigen B27; hs-CRP=high sensitivity C-reactive protein; LDH=lactate 
dehydrogenase; RBC=red blood cell; WBC=white blood cell
a Shift tables will be presented for these variables.
b hs‑CRP will be included in the listings and tabulations for the efficacy data and will not be included in the safety
data outputs.
c hs-CRP will be tested at specified visits per the study schedule of events.
d Serum pregnancy test to be performed at Screening; urine pregnancy test to be performed at subsequent.
11.4
Vital signs, physical findings, and other observations related to 
safety
11.4.1
Vital signs
The following vital signs measurements will be obtained:
•
Pulse rate
•
Systolic and diastolic blood pressure
•
Temperature
A by-subject listing of all vital sign measurements and changes from Baseline will be presented 
by treatment group and visit. The listing will include a flag for measurements identified as 
TEMA/potentially clinically significant (PCS) as calculated by the criteria outlined in Table 14‒
8. Body weight will be included in the listing.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 57 of 86
Descriptive statistics will be reported for all vital sign measurements. Observed values and 
changes from Baseline will be summarized by treatment group for each vital signs variable and 
visit.
Figures of mean change from Baseline over time will be presented for each variable by treatment 
group.
The number and percentage of subjects with TEMA/PCS vital sign values will be summarized by 
treatment group at each visit. The denominator for the percentages will be the number of subjects 
with a non-missing measurement for the variable at the specific visit.
11.4.2
Electrocardiograms
The following ECG variables will be reported together with the Investigator’s interpretation of 
the ECG profile:
•
PR interval
•
RR interval
•
QRS interval
•
QT interval
•
Heart rate
•
QT corrected for heart rate using Fridericia’s formula (QTcF)
Electrocardiogram results will be reported in the by-subject listings. The listing will also include 
the changes from Baseline and percentage changes from Baseline and will be presented by 
treatment group and visit. 
Observed results, changes and percentage changes from Baseline will be summarized for each 
ECG variable by treatment group and visit. 
The following cut points in QTcF (observed data and change from Baseline) will be summarized 
categorically by treatment group (number and percentage of subjects) and visit. The denominator 
for the percentages will be the number of subjects with a non-missing measurement for the 
variable at the specific visit.
Observed QTcF data:
•
<450msec
•
≥450msec to <480msec
•
≥480msec to <500msec
•
≥500msec
Change from Baseline in QTcF:
•
<30msec
•
≥30msec to <60msec
•
≥60msec
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 58 of 86
Electrocardiogram findings including the Investigator’s interpretation will be listed separately.
11.4.3
Other safety variables
11.4.3.1
C-SSRS
The C-SSRS is divided into 2 time intervals and further sub divided as shown:
•
C-SSRS at Baseline – assessed at the Screening visit
−
Suicidal Ideation – over Lifetime and over Past 6 Months
−
Intensity of Ideation – over Lifetime and over Past 6 Months
−
Suicidal Behavior – over Lifetime and over Past 2 Years
•
C-SSRS Since Last Visit – assessed at all visits after Screening
−
Suicidal Ideation – Since Last Visit
−
Intensity of Ideation – Since Last Visit
−
Suicidal Behavior – Since Last Visit
For Suicidal Ideation questions, only those questions where “Yes” has been answered will be 
listed. For Intensity of Ideation questions and Suicidal Behavior questions, any question for 
which an answer has been recorded will be listed. 
Results, as specified above, will be listed by treatment group, subject and visit.
11.4.3.2
Physical examination
Subjects with abnormalities in the physical examination will be listed including details of the 
abnormality.
11.4.3.3
Chest X-ray/CT scan and TB questionnaire
The results of the chest X-ray and the TB questionnaire will be listed for each subject.
12
OTHER ANALYSES 
Not applicable.
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
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13
REFERENCES
Common Terminology Criteria for Adverse Events (CTCAE); Version 4.03 June 2010.U.S.
Department of Health and Human Services
Guidance for Industry: E9 Statistical Principles for Clinical Trials. US Department of Health and 
Human Services, Food and Drug Administration. ICH 1998.
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.
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.
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the irritability 
depression anxiety scale and the Leeds situational anxiety scale manual. 1994.
Van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of 
scoring methods. Ann Rheum Dis. 2005;64;ii61-ii64. 
PUBLIC COPY 
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al. 1994.
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1994.
This document cannot be used to support any m
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 60 of 86
14
APPENDICES
14.1
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI is shown in Table 14‒1. All questions are answered on a scale from 0 to 10; for 
questions 1 to 5, 0 = none and 10 = very severe; for question 6, 0 = 0 hours, 10 = 2 or more 
hours.
14.2
Bath Ankylosing Spondylitis Functional Index
The BASFI is shown in Table 14‒2. All items are scored on a scale from 0 (“Easy”) to 10
(“Impossible”). The first 8 items evaluate activities related to functional anatomical limitations 
due to ankylosing spondylitis and the final 2 items evaluate a subject's ability to cope with 
everyday life.
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 61 of 86
14.3
Hospital Anxiety and Depression Scale
The individual items on the HADS-A and HADS-D scales are listed in Table 14‒3.
14.4
Treatment group assignment for the TFLs
Data will be summarized in the TFLs according to the treatment groupings as displayed in
Table 14‒4.
Table 14‒4: Treatment group assignment for TFLs
TFL group
CZP
BKZ
All Subjects
Subject disposition 
X
X
X
Protocol deviations
X
X
X
Demographics
X
X
X
AS history and Baseline
Disease characteristics
X
X
X
Medical history
X
X
X
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 62 of 86
Table 14‒4: Treatment group assignment for TFLs
TFL group
CZP
BKZ
All Subjects
Prior/concomitant 
medications
X
X
X
AEs
X
X
Safety data (including 
vital signs, ECG, 
laboratory tests, 
physical examination,
body weight, C-SSRS)
X
X
Pharmacodynamic data
X
X
Efficacy data
X
X
Pharmacokinetic data
X
X
ADA
X
X
ADA= anti-drug antibodies; AE=adverse event; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram
14.5
Adverse events for special monitoring
The following AESM are defined for BKZ and will be summarized separately as described in 
Section 11.2:
•
Major cardiovascular events
•
Serious infections, including opportunistic infections and TB
•
Malignancies including lymphoma
•
Cytopenias
•
Neuropsychiatric events
•
Inflammatory bowel disease
•
Anaphylactic reaction (hypersensitivity and anaphylactic reactions)
•
Hepatic events and drug-induced liver injury
14.5.1
Major cardiovascular events
Major adverse cardiovascular events (MACE) will be tabulated separately and will be identified
using the following UCB-defined search criteria:
•
All serious TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow
groups of the following standardized MedDRA queries (SMQ):
−
Haemorrhagic central nervous system vascular disorders
−
Ischaemic central nervous system vascular disorders
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 63 of 86
•
All serious TEAEs which code to a PT included in the HLT = ‘Ischaemic coronary artery
disorders’ except events coding to PT = ‘Chest pain’ or PT = ‘Chest discomfort’
•
All serious TEAEs which code to a PT = ‘Cardiac failure congestive’
14.5.2
Serious infections, including opportunistic infections and 
tuberculosis
14.5.2.1
Serious infections
Serious infections are based on MedDRA classification using the SOC = ‘Infections and
Infestations’. Such events will be included in the tabulations of SAEs and no separate summary
tabulations will be presented.
14.5.2.2
Fungal infections
Fungal infections will be summarized separately based on all TEAEs coding to the high level
group term (HLGT) = ‘Fungal infectious disorders’.
14.5.2.3
Opportunistic infections
Opportunistic infections (including TB) will be summarized in a separate table including all
TEAEs identified using search criteria defined by UCB.
Opportunistic infections are identified in 2 steps:
•
Step 1: Refer to column B of the spreadsheet which identifies the PTs to be classified as 
opportunistic infections using either a single ‘x’ or a double ‘xx’
−
All TEAEs which code to a PT flagged with a single ‘x’ need to also be serious in order
to be considered an opportunistic infection
−
All TEAEs which code to a PT flagged with a double ‘xx’ are considered to be an
opportunistic infection, regardless of seriousness.
All serious TEAEs in the study database which code to a PT flagged with a single ‘x’ and all
TEAEs in the study database which code to a PT flagged with a double ‘xx’ will be summarized
as an opportunistic infection in the stand-alone table.
•
Step 2: Refer to column C of the spreadsheet which identifies the PTs that need to be
evaluated on a case-by-case basis by the study physician in order to determine whether it is a
true opportunistic infection or not. The process for physician review is as follows:
−
Study programming team creates a spreadsheet which lists all of the subjects with a
TEAE present in the database which codes to a PT identified as needing case-by-case
review. Information from the AE dataset to be included in the spreadsheet: Subject ID,
AE verbatim term, SOC, HLT, Low Level Term (LLT), PT, AE start date, AE end date,
seriousness, severity, relationship to IMP, action taken. Additionally, a column will be 
included where the study physician can document their decision on the case
−
Study physician reviews the cases in the spreadsheet and indicates in the additional
column which AEs are confirmed to be opportunistic infections via a single ‘x’
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 64 of 86
−
Study programming team incorporates these decisions into the ADAE dataset by merging
the study physician decisions for individual subjects / PTs and flagging the confirmed
opportunistic infections as such in the dataset
All subjects with an AE reported that has been confirmed by the study physician to be an 
opportunistic infection (based on case-by-case review) will be summarized as such in the 
stand-alone table, together with all of the events identified in Step 1 of this process.
Following the initial physician review of case-by-case events, subsequent reviews will be based 
on the cumulative set of case-by-case events present in the database at each time point of 
spreadsheet creation. Physician decisions from previous runs should be retained in each 
subsequent run. The final run of the spreadsheet, with all study physician decisions on the full set 
of case-by-case events, will be archived at the end of the study.
14.5.3
Malignancies including lymphoma
Malignancies will be presented in 2 separate tables based on the following SMQs:
•
Malignant or unspecified tumors
•
Malignant tumors
Events included in the ‘Malignant tumors’ tabulation will be a subset of the events in the 
‘Malignant or unspecified tumors’ tabulation. The SMQ search should include all TEAEs which 
code to a PT included in the Scope=Narrow group within each SMQ.
The output tables will include 2 different overall incidence rows:
•
The first overall incidence row will summarize ‘Any malignancies (including unspecified)’ 
or ‘Any malignancies’ (depending on the table) and this row will summarize the incidence of 
all AEs flagged for inclusion in the table, regardless of the HLT it codes to
•
The second overall incidence row will summarize ‘Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)’ or ‘Any malignancy (excluding non-melanomic 
skin cancers)’ (depending on the table) and this row will summarize the incidence of AEs 
flagged for inclusion in the table, excluding those which code to an HLT of ‘skin neoplasms 
malignant and unspecified (excl melanoma)’
14.5.4
Cytopenias
Cytopenias will be tabulated separately based on the SMQ = ‘Haematopoietic cytopenias’. Only
serious TEAEs will be included in the tabulation. The SMQ search should include all serious 
TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow groups within 
the SMQ.
14.5.5
Neuropsychiatric events
Neuropsychiatric events (in particular depression, anxiety and suicide ideation or behavior) will 
be tabulated separately based on the SMQ = ‘Depression and suicide/self-injury’. The SMQ 
search should include all TEAEs which code to a PT included in the Scope=Broad and/or 
Scope=Narrow groups within the SMQ.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 65 of 86
14.5.6
Inflammatory bowel disease
Inflammatory bowel disease events will be tabulated separately, based on the HLGT = ‘Colitis 
excl infective’.
14.5.7
Anaphylactic reaction
Anaphylactic reactions will be summarized together in a stand-alone table with the following 
incidence rows:
•
The first row within the body of the table will be labeled ‘Any hypersensitivity/anaphylactic 
reaction’ and will represent the overall incidence of subjects who reported at least one 
hypersensitivity reaction or at least one anaphylactic reaction
•
The second row within the body of the table will be labeled ‘Any hypersensitivity reaction’ 
and will represent the overall incidence of subjects who reported at least one hypersensitivity 
reaction
•
The third row within the body of the table will be labeled ‘Any anaphylactic reaction’ and 
will represent the overall incidence of subjects who reported at least one anaphylactic 
reaction 
Following these three overall incidence rows, all TEAEs that have been identified as either a 
hypersensitivity reaction or an anaphylactic reaction will be summarized by SOC, HLT and PT 
(these will not be presented by subcategory). 
Hypersensitivity reactions and anaphylactic reactions will be identified as follows:
•
Hypersensitivity reactions: all TEAEs with onset (start date/time) within 24 hours after any 
administration of IMP, which code to a PT which contains the term ‘hypersensitivity’ will be 
considered as a hypersensitivity reaction and included in the summary table.
•
Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs that are 
considered to be anaphylactic reactions. Preferred terms are separated into 4 distinct 
categories (A, B, C, D) prior to the algorithmic approach being applied.
All TEAEs with onset (start date/time) within 24 hours after any administration of IMP, and 
which fulfill any of the 3 criteria described in Section 14.5.7.1 will be included in the summary 
table.
Any TEAEs with missing start time will be assumed to have occurred at the time of or after 
dosing for this purpose, if the event date is on the same day as a dosing date.
14.5.7.1
Anaphylactic reaction algorithm
The SMQ = ‘anaphylactic reaction’ consists of 3 parts:
•
A narrow search containing PTs that represent core anaphylactic reaction terms. If a subject 
reports any TEAE which codes to a PT included in Category A, then the event will be 
flagged as an anaphylactic reaction and summarized as such in the table
−
Category A
1. Anaphylactic reaction
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 66 of 86
2. Anaphylactic shock
3. Anaphylactic transfusion reaction
4. Anaphylactoid reaction
5. Anaphylactoid shock
6. Circulatory collapse
7. Dialysis membrane reaction
8. Kounis syndrome
9. Shock
10. Shock symptom
11. Type I hypersensitivity
•
A broad search: If a subject reports any TEAE which codes to a PT included in Category B 
AND reports any TEAE which codes to a PT included in Category C, and both TEAEs have 
the same start date, then both events will be flagged as anaphylactic reactions and 
summarized as such in the table
−
Category B
1. Acute respiratory failure
2. Asthma
3. Bronchial oedema
4. Bronchospasm
5. Cardio-respiratory distress
6. Chest discomfort
7. Choking
8. Choking sensation
9. Circumoral oedema
10. Cough
11. Cyanosis
12. Dyspnoea
13. Hyperventilation
14. Irregular breathing
15. Laryngeal dyspnea
16. Laryngeal oedema
17. Laryngospasm
18. Laryngotracheal oedema
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 67 of 86
19. Mouth swelling
20. Nasal obstruction
21. Oedema mouth
22. Oropharyngeal spasm
23. Oropharyngeal swelling
24. Respiratory arrest
25. Respiratory distress
26. Respiratory dyskinesia
27. Respiratory failure
28. Reversible airways obstruction
29. Sensation of foreign body
30. Sneezing
31. Stridor
32. Swollen tongue
33. Tachypnoea
34. Throat tightness
35. Tongue oedema
36. Tracheal obstruction
37. Tracheal oedema
38. Upper airway obstruction
39. Wheezing
−
Category C
1. Allergic oedema
2. Angioedema
3. Erythema
4. Eye oedema
5. Eye pruritis
6. Eye swelling
7. Eyelid oedema
8. Face oedema
9. Flushing
10. Generalized erythema
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 68 of 86
11. Injection site urticarial
12. Lip oedema
13. Lip swelling
14. Nodular rash
15. Ocular hyperaemia
16. Oedema
17. Periorbital oedema
18. Pruritis
19. Pruritis allergic
20. Pruritis generalized
21. Rash
22. Rash erythematous
23. Rash generalized
24. Rash pruritic
25. Skin swelling
26. Swelling
27. Swelling face
28. Urticaria
29. Urticaria popular
−
Category D
1. Blood pressure decreased
2. Blood pressure diastolic decreased
3. Blood pressure systolic decreased
4. Cardiac arrest
5. Cardio-respiratory arrest
6. Cardiovascular insufficiency
7. Diastolic hypertension
8. Hypotension
•
An algorithmic approach: If a subject reports any TEAE which codes to a PT included in 
Category D AND reports (either a TEAE which codes to a PT included in Category B OR a 
TEAE which codes to a PT included in Category C), and both TEAEs have the same start 
date, then both events will be flagged as anaphylactic reactions and summarized as such in 
the table.
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Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
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14.5.8
Hepatic events and drug-induced liver injury
Hepatic events will include:
•
Events based on the SMQ = ‘Drug related hepatic disorders - comprehensive search’ 
(excluding sub-SMQs = ‘Liver neoplasms, benign [incl cysts and polyps]’ and ‘Liver 
neoplasms, malignant and unspecified’). All AEs should be included in the tabulation 
(including those considered both related and not related to the IMP) which code to a PT 
included in the Scope=Narrow group within each SMQ
•
Hy’s Law cases will also be summarized separately in a table of liver function abnormalities 
as described in Section 11.3 (with adjudication for potential drug-induced liver injury 
[PDILI] cases)
14.6
Treatment-emergent markedly abnormal laboratory values
The criteria for identifying TEMA laboratory values are provided for hematology in Table 14‒5
and for chemistry in Table 14‒6.
Table 14‒5: Definition of TEMA values for hematology
Variable (SI units)
Source
Markedly abnormal definition
Low Grade 4
Low Grade 3
High Grade 3
High Grade 4
Hemoglobin (g/L)
RCTC
<70 OR 
decrease from 
Baseline of 
≥30
70 to <80 OR 
value <LLN 
and decrease 
from Baseline 
of 21 to 29
NA
NA
ALC (10^9/L)
CTCAE
<0.2
0.2 to <0.5
NA
NA
ANC (10^9/L)
RCTC
<0.5
0.5 to <1.0
NA
NA
WBC (10^9/L)
RCTC
<1.0
1.0 to <2.0
NA
NA
Platelets (10^9/L)
RCTC
<2.0
20 to <50
NA
NA
ALC=absolute lymphocyte count; ANC=absolute neutrophil count; CTCAE=Common Terminology Criteria for
Adverse Events (CTCAE 2010); LLN=lower limit of normal; NA=not applicable; RCTC=Rheumatology Common
Toxicity Criteria; WBC=white blood cell.
Table 14‒6: Definition of TEMA values for chemistry
Variable (SI 
units)
Source
Markedly abnormal definition
Low Grade 4
Low Grade 3
High Grade 3
High Grade 4
ALP (U/L)
RCTC
NA
NA
>3.0 to 5.0 x 
ULN
>5.0 x ULN
ALT (U/L)
RCTC
NA
NA
>3.0 to 8.0 x 
ULN
>8.0 x ULN
AST (U/L)
RCTC
NA
NA
>3.0 to 8.0 x 
ULN
>8.0 x ULN
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 70 of 86
Table 14‒6: Definition of TEMA values for chemistry
Variable (SI 
units)
Source
Markedly abnormal definition
Low Grade 4
Low Grade 3
High Grade 3
High Grade 4
Creatinine 
(μmol/L)
RCTC
NA
NA
>1.8 to 3.0 x 
ULN
>3.0 x ULN
GGT (U/L)
CTCAE
NA
NA
>5.0 to 20.0 x 
ULN
>20.0 x ULN
Potassium
(mmol/L)
RCTC
<2.5
2.5 to <3.0
>6.4 to 7.0
>7.0
Sodium
(mmol/L)a
RCTC
<120
120 to <125
>155 to 160
>160
Total bilirubin 
(μmol/L)
RCTC
NA
NA
≥2.0 to 3.0 x 
ULN
>3.0 x ULN
Calcium
(mmol/L)
RCTC
<1.63
1.63 to <1.75
>3.125 to 
3.375
>3.375
Cholesterol 
(total) 
(mmol/L)
CTCAE
NA
NA
>10.34 to 
12.92
>12.92
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common
Terminology Criteria for Adverse Events (CTCAE 2010); GGT=gamma glutamyl transferase; NA=not applicable;
RCTC=Rheumatology Common Toxicity Criteria; ULN=upper limit of normal.
a For sodium High Grade 3 and 4 are taken from CTCAE.
14.7
Treatment-emergent abnormal liver values
The criteria for identifying treatment-emergent liver function abnormalities are presented in 
Table 14‒7. Subjects will be counted in all applicable categories for the tabulations ie, a subject 
with ≥5 x upper limit of normal (ULN) in AST will also be counted in the ≥3 x ULN in AST 
category, the ≥3 x ULN in aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
category and the ≥5x ULN in AST or ALT category.
Table 14‒7: Definition of treatment-emergent liver function values
Criterion
≥3 x ULN increase for AST
≥5 x ULN increase for AST
≥10 x ULN increase for AST
≥20 x ULN increase for AST
≥3 x ULN increase for ALT
≥5 x ULN increase for ALT
≥10 x ULN increase for ALT
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 71 of 86
Table 14‒7: Definition of treatment-emergent liver function values
Criterion
≥20 x ULN increase for ALT
≥3 x ULN increase for AST or ALT
≥5 x ULN increase for AST or ALT
≥10 x ULN increase for AST or ALT
≥20 x ULN increase for AST or ALT
≥1 x ULN increase for bilirubin
≥1.5 x ULN increase for bilirubin
≥1.5 x ULN increase for ALP
≥1 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit)
≥2 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit)
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of 
normal.
14.8
Treatment-emergent markedly abnormal vital signs values
The criteria for identifying TEMA/PCS vital signs values are provided in Table 14‒8.
Table 14‒8: TEMA/PCS criteria for vital signs
Variable
Unit
Lowa
Higha
Systolic blood pressure
mmHg
Value ≤90 and ≥30 
decrease from Baseline
Value ≥180 and ≥40 
increase from Baseline
Diastolic blood pressure
mmHg
Value ≤50 and ≥20 
decrease from Baseline
Value ≥105 and ≥30 
increase from Baseline
Pulse rate
bpm
Value ≤50 and ≥30 
decrease from Baseline
Value ≥120 and ≥30 
increase from Baseline
bpm=beats per minute; mmHg=millimeters of mercury; PCS=potentially clinically significant; TEMA=treatment-
emergent markedly abnormal.
Note: the change in measurement (increase or decrease) will be calculated relative to the value obtained at Baseline.
a Both conditions must be satisfied for a measurement to be considered PCS.
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 72 of 86
15
AMENDMENTS TO THE SAP
15.1
Amendment 2
15.1.1
Rationale for the amendment
Various updates were suggested with the introduction of the PET-MRI/PET-CT substudy, and to 
align with the changes made to protocol amendment 3.
15.1.2
List of changes
Change #1
List of Abbreviations
The following abbreviations were added to the list:
•
CSR = clinical study report
•
mNY = modified New York
•
SIJ = sacroiliac joint
•
SUVauc = standard uptake value corrected for individual integrated whole blood activity 
concentration
•
VOI = volume of interest
•
VUMC = VU University Medical Center
Change #2
Secondary objectives (Section 2.1.2)
The following bullets were removed:-
•
To evaluate the effect of BKZ or CZP on changes in osteoblastic activity
•
To assess the pharmacokinetics (PK) and immunogenicity of BKZ
Change #3
Other objectives (Section 2.1.3)
The following bullets were added:
•
To evaluate the effect of BKZ or CZP on changes in bone formation
•
To assess the pharmacokinetics (PK) and immunogenicity of BKZ
Change #4
Other Efficacy Variables (Section 2.2.1.3)
The following bullets were added to the end:
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Changes in bone formation as measured by standardized uptake value corrected for 
individual integrated whole blood activity concentration (SUVauc) for each PET-positive 
lesion identified together with the maximum SUVauc value across all lesions within the spine 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 73 of 86
and sacroiliac joint (SIJ).  SUVauc will be derived from positron-emission tomography 
magnetic resonance imaging (PET MRI) or positron-emission tomography computed 
tomography (PET CT) scans at Baseline, Week 12, and Week 48
Change #5
Study design and conduct (Section 2.3)
The second paragraph was changed to:
It is planned that at least 60 subjects will be randomized to 1 of 2 treatment arms in a 2:1 
ratio and will receive either BKZ or CZP up to Week 44 (final dose of investigational 
medicinal product [IMP]).
Change #6
Determination of sample size (Section 2.4)
This section was rewritten to:
A sufficient number of subjects will be enrolled to ensure that at least 60 subjects are available in 
the main study at Week 12 to compare the change from Baseline in ASDAS between BKZ and 
CZP.  This will also provide at least 25 subjects enrolled in the PET-CT or PET-MRI substudy 
from multiple sites. Subjects will be randomized in a 2:1 ratio to receive BKZ or CZP 
respectively.
The sample size was calculated to provide at least 80% power to detect a difference between
treatment groups in the mean change from Baseline in ASDAS at Week 12 of 0.89 (group mean
change from Baseline for CZP and BKZ being -1.78 and -2.67 respectively) with a common 
standard deviation (SD) of 1.17 using frequentist methods for the comparison of the treatment 
group mean change from Baseline in ASDAS at Week 12 with Baseline ASDAS as a covariate 
(Overall and Starbuck, 1979).
The correlation between Baseline and Week 12 raw ASDAS was assumed to be 0.35. Note that 
the informative prior for the model intercept to be used in the Bayesian modelling of the primary 
efficacy variable, given by 𝛽𝐶𝑍𝑃~ Normal (-1.78, var=0.0605), contributes an effective sample 
size of approximately 20 CZP subjects. Prior data conflict will be investigated and a vague prior 
will be used for the model intercept coefficient if prior data conflict is evident.
Note that a clarification regarding the sample size for this study was provided in protocol 
amendment 3. As indicated above, the planned sample size of at least 60 subjects provides 
sufficient power to detect meaningful treatment differences in the primary efficacy variable 
whilst also providing at least 25 subjects for the PET-MRI or PET-CT substudy. However, due 
to complexities in the initiation of sites capable of performing PET-MRI or PET-CT scans, more 
than the planned 35 non-PET-MRI/CT substudy subjects were screened and randomized before it 
was possible to close enrolment at the sites not participating in the substudy. Owing to the 
novelty of the PET-MRI/CT outcomes within this disease area, it is considered important to 
ensure at least 25 evaluable subjects are included in the assessment of this exploratory objective 
to maximize the possibility of identifying the salient factors or variables that might differ 
between the treatment groups and, therefore, the total sample size is increased to at least 72 
subjects. This sample size increase will not negatively impact the power to detect a difference in 
the primary efficacy variable at Week 12 (ie, it will remain >80%), but will ensure that the target 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 74 of 86
number of subjects are included in the exploratory analysis of changes in bone formation at 
Week 12 and Week 48. Since the analyses of PET-MRI/CT data are exploratory and treatment 
effect sizes are unknown, formal power calculations were not performed. Clinical expertise does, 
however, indicate that a sample size of at least 25 subjects in the substudy will characterize 
broad differences between treatment groups.
Change #7
Determination of sample size (Section 2.4)
The following paragraph was added at the end:
Note that a clarification regarding the sample size for this study was provided in protocol 
amendment 3. As indicated above, the planned sample size of at least 60 subjects provides 
sufficient power to detect meaningful treatment differences in the primary efficacy variable 
whilst also providing at least 25 subjects for the PET-MRI or PET-CT substudy. However, due 
to complexities in the initiation of sites capable of performing PET-MRI or PET-CT scans, more 
than the planned 35 non-PET-MRI/CT substudy subjects were screened and randomized before it 
was possible to close enrolment at the sites not participating in the substudy. Owing to the 
novelty of the PET-MRI/CT outcomes within this disease area, it is considered important to 
ensure at least 25 evaluable subjects are included in the assessment of this exploratory objective 
to maximize the possibility of identifying the salient factors or variables that might differ 
between the treatment groups and, therefore, the total sample size is increased to at least 72 
subjects. This sample size increase will not negatively impact the power to detect a difference in 
the primary efficacy variable at Week 12 (ie, it will remain >80%), but will ensure that the target 
number of subjects are included in the exploratory analysis of changes in bone formation at 
Week 12 and Week 48. Since the analyses of PET-MRI/CT data are exploratory and treatment 
effect sizes are unknown, formal power calculations were not performed. Clinical expertise does, 
however, indicate that a sample size of at least 25 subjects in the substudy will characterize 
broad differences between treatment groups.
Change #8
General presentation of summaries and analyses (Section 3.1)
The following paragraph was extended to:
Data listings containing all documented data and all derived data will be generated.  Subjects 
enrolled in the PET-MRI/PET-CT substudy will be flagged in the data listings.
Change #9
The following section was added:
PET Per-Protocol Set (Section 3.5.8)
The PET Per-Protocol Set (PET-PPS) will consist of all randomized subjects who receive at least 
1 dose of the IMP and have evaluable PET-MRI or PET-CT scan data at Baseline and at least 1 
of the post-Baseline assessments.
Change #10
Subject Disposition (Section 5.1)
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 75 of 86
The opening paragraph was changed to:
The number and percentage of subjects who were randomized into the study (and into the PET-
MRI/PET-CT substudy), subjects who completed or prematurely discontinued the study, as well 
as the primary reason for discontinuation will be presented by treatment group and for all 
subjects, based on the RS. A subject who completed the study is defined as a subject who 
completed all visits up to the last scheduled study visit, ie, Visit 18 (Week 64). An additional 
summary of subject disposition in the PET-MRI/PET-CT substudy will also be presented 
separately by treatment group and for all subjects, based on the RS.
Change #11
Subject Disposition (Section 5.1)
The second bullet of the seventh paragraph was changed to:
•
for subjects participating in the respective pharmacogenomics, pharmacogenetic and PET 
MRI/CT substudies: date of respective informed consent
Change #12
Classification of age categories (Section 6.1.2)
The opening paragraph was changed to:
Age will be classified into categories based on requirements for European Union Drug 
Regulating Authorities Clinical Trials (EudraCT) and clinicaltrials.gov reporting.
Change #13
Demographics (Section 6.2)
The second paragraph was changed to:
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by treatment group and for all subjects based on the SS. The summary of age will 
include descriptive statistics and categorical summaries, the latter based on requirements for 
EudraCT and clinicaltrials.gov reporting. This summary will be repeated for subjects in the SS 
who were randomized in the PET-MRI/CT substudy. Childbearing potential will be listed for the 
SS.
Change #14
Other Baseline characteristics (Section 6.3)
The section was changed to:
The following Baseline disease characteristics will be presented in a by-subject listing for the SS:
•
Duration of disease (as calculated in Section 6.1.3), including confirmation of sacroiliac joint 
X-ray and the date on which the sacroiliac joint X-ray was performed
•
hs-CRP
•
BASDAI score
•
PGADA
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
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•
ASDAS
•
ASDAS disease activity states (ASDAS-ID, ASDAS-Moderate Disease activity 
[ASDAS-MD], ASDAS-High Disease activity [ASDAS-HD] and ASDAS-Very High 
Disease activity [ASDAS-vHD])
•
BASFI score
•
Total and nocturnal spinal pain NRS
•
PhGADA
•
Total HADS-A and HADS-D scores
The calculation of Baseline ASDAS and the classification of the ASDAS disease activity states 
will be based on the Baseline BASDAI, PGADA and hs-CRP values. The Baseline for each of 
the variables listed above is defined in Table 3‒1.
Baseline disease characteristics will be summarized using descriptive statistics by treatment 
group and for all subjects based on the SS.  This summary will be repeated for subjects in the SS 
who were randomized in the PET-MRI/PET-CT substudy and will also include summary 
statistics for SUVauc in the spine and in the SIJ at Baseline derived from the PET-MRI/PET-CT 
scans performed at Screening. SUVauc will be summarized in each SIJ quadrant and in each 
anatomical location of the spine together with the maximum SUVauc value in the SIJ and spine 
for each subject.
In addition, the above Baseline disease characteristics will be listed for the SS including SUVauc
and the maximum of the SUVauc values in the SIJ and spine.
Subject lifestyle details (alcohol use, smoking history and caffeine use) will be listed, based on 
the SS.
Change #15
Medical History (Section 6.4)
The opening paragraph was changed to:
Medical history will be listed for the RS and summarized for the SS by treatment group and for 
all subjects, MedDRA® system organ class (SOC) and preferred term (PT). The reported term 
will be included in the listing. The summary will include the number and percentage of subjects 
and will be sorted alphabetically by SOC and by descending incidence of PT within each SOC, 
based on the ‘All Subjects’ column. This summary will be repeated for subjects in the RS who 
were randomized in the PET-MRI/CT substudy. A glossary of all medical history conditions will 
be presented for the RS including the SOC, PT and reported term.
Change #16
Ankylosing spondylitis history (Section 6.5)
This section was shortened to:
Date of initial diagnosis of AS and the date that AS symptoms first started will be listed.
Change #17
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 77 of 86
Prior and concomitant medications (Section 6.6)
The opening paragraph was changed to:
Prior and concomitant medications (Section 6.6.1 and Section 6.6.2) will be listed for the RS by 
treatment group and subject, and summarized for the SS by WHODD Anatomical Main Group 
(Level 1), Pharmacological Subgroup (Level 3) and PT. The reported term will be included in 
the listing, together with flags to identify AS, rescue and prohibited medications, respectively. 
The flags for prohibited, AS and rescue medications will be confirmed and documented at the 
final DEM.
Change #18
Prior and concomitant medications (Section 6.6)
The second bullet of the fourth paragraph was changed to:
•
Rescue medication during study
Change #19
Prior and concomitant medications (Section 6.6)
The following paragraph was added:
These summaries will be repeated for subjects in the SS who were randomized in the PET-
MRI/PET-CT substudy.
Change #20
This section was removed:
Positron-emission tomography-magnetic resonance imaging/positron-emission tomography 
computed tomography
Change #21
Other efficacy variables (Section 8.3)
This sentence at the start was removed:
Results of the other efficacy variables will be listed and summarized by treatment group and visit
for the FAS.
Change #22
The phrase “for the FAS” was added for various requested outputs in the following sections:
•
Presentation of Assessment in SpondyloArthritis International Society Response (Section 
8.3.2)
•
Presentation of components of Assessment in SpondyloArthritis International Society 
(Section 8.3.3)
•
Physician’s Global Assessment of Disease Activity (Section 8.3.4)
•
Hospital Anxiety and Depression Scale (Section 8.3.5)
Change #23
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Statistical Analysis Plan Amendment 3
Bimekizumab
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Change in Bone Formation (PET-MRI/PET-CT Substudy) (Section 8.3.6)
The entire section was added (see above).
Change #24
Extent of Exposure (Section 11.1)
The final paragraph was extended to:
The number of injections received and duration of exposure will be listed for each subject and 
summarized by treatment group for the Treatment Period and Treatment Extension Period 
separately using descriptive statistics.  This summary will be repeated for subjects in the SS who 
were randomized in the PET-MRI/CT substudy.
Change #25
Adverse Events (Section 11.2)
The fourth and fifth paragraphs were changed to:
An overview of the number and percentage of subjects who experience TEAEs will be presented 
by treatment group, based on the SS. This tabulation will include the number and percentage of 
subjects with any TEAEs, serious TEAEs, related TEAEs, discontinuation due to TEAEs, severe 
TEAEs, AEs leading to death and TEAEs leading to death; event counts will also be included.  
This summary will be repeated for subjects in the SS who were randomized in the PET-
MRI/PET-CT substudy.
In addition, the following summaries will be presented by treatment group, SOC, high level term 
(HLT) and PT, based on the SS:
•
Incidence of TEAEs[a]
•
Incidence of TEAEs, stratified by overall ADA status (positive/negative) as defined in 
Section 10
•
Incidence of serious TEAEs[a]
•
Incidence of non-serious TEAEs
•
Incidence of TEAEs by relationship
•
Incidence of TEAEs by maximum relationship
•
Incidence of TEAEs by maximum intensity
•
Incidence of fatal TEAEs by relationship
•
Incidence of non-serious TEAEs by relationship
•
Incidence of serious TEAEs by relationship
•
Incidence of non-serious TEAEs above threshold of 5% of subjects
•
Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship
•
Incidence of TEAEs by SOC and PT (including the number and percentage of subjects and 
individual subject numbers for each PT stratified by intensity, relationship and seriousness) 
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
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[a] These summaries will be repeated for subjects in the SS who were randomized in the PET-
MRI/PET-CT substudy.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.


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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 80 of 86
15.2
Amendment 3
15.2.1
Rationale for the amendment
Updates to the description of the exploratory analysis of the PET-MRI/PET-CT imaging data 
were required based on a further understanding of the data expected for this study.  Other 
clarifications have also been incorporated into this amendment.
15.2.2
List of changes
Change #1
List of Abbreviations
The SUVmax definition has been removed.
Change #2
Protocol deviations (Section 5.2)
The third paragraph in this section has been changed to:
The number and percentage of subjects with IPDs will be summarized by treatment group 
and for all subjects for each deviation type, based on the RS. This summary will be 
repeated for the FAS (if this analysis set is different to the RS).
Change #3
Other baseline characteristics (Section 6.2)
The third and fourth paragraphs in this section have been changed to:
Baseline disease characteristics will be summarized using descriptive statistics by treatment 
group and for all subjects based on the SS.  This summary will be repeated for subjects in 
the SS who were randomized in the PET-MRI/PET-CT substudy and will also include 
summary statistics for SUVauc in the SIJ and spine at Baseline derived from the 
PET-MRI/PET-CT scans performed at Screening. SUVauc values for each of the PET-
positive lesions identified in the SIJ and spine will be pooled across subjects and across the 
SIJ and anatomical locations in the spine for the purpose of this summary.  In addition, the 
maximum SUVauc value across the SIJ and spine for each subject at Baseline will be 
summarized.
The above Baseline disease characteristics will be listed for the SS.
Change #4
Medical history and concomitant diseases (Section 6.4)
This section was amended as follows:
Medical history (except for AS) will be listed for the RS and summarized for the SS by 
treatment group and for all subjects, MedDRA® system organ class (SOC) and preferred 
term (PT). The reported term will be included in the listing. The summary will include the 
number and percentage of subjects and will be sorted alphabetically by SOC and by 
descending incidence of PT within each SOC, based on the ‘All Subjects’ column. This 
summary will be repeated for subjects in the SS who were randomized in the PET-MRI/CT
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19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 81 of 86
substudy. A glossary of all medical history conditions will be presented for the RS 
including the SOC, PT and reported term.
Procedure history will be listed separately for the RS by treatment group for previous 
procedures relating to AS and previous procedures not relating to AS.  Concomitant 
medical procedures performed during the study will be listed for the RS.
Change #5
Efficacy assessment (Section 8.3.6.2)
The section was amended as follows:
SIJ and spine PET-CT and PET-MRI scans will be independently assessed at each time 
point (Baseline, Week 12 and Week 48) in a blinded fashion by two reviewers, with an 
additional adjudication read by a third reviewer, if applicable.  Independent reviewers will 
assess PET-MRI/PET-CT examinations quantitatively using VU University Medical Center 
(VUMC)’s in-house software (ACCURATE).
Initially, two primary readers will independently assess the images visually to identify 
PET-positive lesions in the SIJ and spine.  The readers will dichotomously score the 
presence or absence (1 versus 0) of PET-positive lesions in each side of the SIJ (Left and 
Right) and at each of the 24 spinal levels and 4 spinal regional levels [C2-C7 (Cervical), T1-
T12 (Thoracic), L1-L5 (Lumbar), Sacrum] in each of the following 8 spinal locations:
•
Process spinosus
•
Costo-vertebral (right)
•
Costo-vertebral (left)
•
Facet joint (right)
•
Facet joint (left)
•
Anterior vertebra
•
Posterior vertebra
•
Vertebra (other)
For each subject, PET-positive lesions may be identified in one or both sides of the SIJ and 
in one or more of the 192 possible anatomical locations (spinal location/level combinations).  
It is expected that only one lesion for a subject may be separated/identified in each side of 
the SIJ or individual anatomical location in the spine, therefore, there is a direct mapping 
of a subject’s lesion to a SIJ side or spinal location/level.
If there is a discrepancy between the two primary readers in the presence of PET-positive 
lesion assessment (Yes versus No for lesions in any side of the SIJ and 1 versus 0 for lesions 
in any spinal location), a consensus adjudication will take place with a third reader who 
will also be blinded to the clinical data. This reader will make an independent assessment 
and the results of the adjudication will be considered as the final assessment of the presence 
of PET-positive lesions.
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Statistical Analysis Plan Amendment 3
Bimekizumab
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Another reader who has not been involved in the visual identification of the PET-positive 
lesions, either as a primary reader or an adjudicator, will then draw volumes of interest 
(VOIs) on the pre-identified PET-positive lesions. In the case that no PET-positive lesions 
have been identified for a subject, then the final review step to draw VOIs will not occur. 
Efficacy PET-MRI/PET-CT review will occur provided that an acceptable PET-CT or 
PET-MRI scan is available and that PET-positive lesions were identified on the previous 
scan (for the Week 12 and Week 48 visits). During the PET-positive lesion VOI review, the 
independent reviewer will perform a quantitative assessment in ACCURATE and record 
the standard uptake values of 18F-fluoride in VOIs, corrected for both body weight and 
individual integrated whole blood activity concentration (SUVauc) for each PET-positive 
lesion identified during the PET-positive lesion identification review.
Data from the visual identification of PET-positive lesions and the results of the 
quantitative VOI review (i.e. SUVauc) will be listed, for each independent reader and 
adjudicator (if applicable), for each anatomical location in the spine, and for each side of 
the SIJ, by treatment group and visit for subjects in the SS who were enrolled into the 
PET-MRI/PET-CT substudy. 
No formal statistical modelling of the PET-MRI/PET-CT imaging data will be performed 
for this substudy; only summaries will be presented together with 95% CIs for mean 
values, as applicable. 
The summaries described below based on the visual identification of PET-positive lesions 
will include the final assessment data, ie, if adjudication was performed, then the 
adjudicated data will be summarized, otherwise data from one of the primary reviewers 
will be summarized.
All summaries will be presented for the PET-PPS.
Since the attenuation correction and quantification is variable in PET-MRI scans, PET-
MRI imaging data will be listed but will not be aggregated with the PET-CT imaging data 
in the summaries.
Due to the predicted sparseness of the number of PET-positive lesions in each of the 
individual anatomical locations of the spine, data will be pooled as follows for the purpose 
of some of the summaries:
•
In the SIJ and spine overall (across the SIJ and all anatomical locations in the 
spine);
•
In the SIJ overall (across both sides), and split by Left and Right side;
•
In the spine overall (across all anatomical locations in the spine), and split by 
spinal regional level (Cervical, Thoracic, Lumbar, Sacrum), and, depending on 
the distribution of lesions across the spine, further by spinal levels and spinal 
locations in which at least 1 PET-positive lesion is identified.
An overview of the total number of PET-positive lesions identified in the spine across all 
subjects in each of the individual anatomical locations will be presented by visit.
The presence of PET-positive lesions identified in the SIJ and spine will be summarized by 
visit.  The summary will include the number and percentage of subjects at each visit with 
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UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 83 of 86
any PET-positive lesions in the spine or the SIJ, in both the spine and the SIJ, in the SIJ 
overall (and split by Left and Right side) and in the spine overall [and split by spinal 
regional level (Cervical, Thoracic, Lumbar and Sacrum) and level/location, as applicable].  
This summary will also include a total count of PET-positive lesions across subjects for 
each of the pooled locations described above.  In the spine, the incidence and the total 
number of lesions will only be presented for the anatomical locations in which at least 1 
PET-positive lesion is identified.
The number of PET-positive lesions per subject in the SIJ and spine (overall and in pooled 
locations, as described above) will be calculated and summarized by visit using frequency 
counts and percentages, and/or descriptive statistics, as applicable.  In addition, in the 
spine and SIJ overall, in the spine overall and in each spinal regional level, the changes in 
the number of PET-positive lesions per subject from Baseline to Week 12 and Week 48, 
and the changes from Week 12 to Week 48 will be summarized using descriptive statistics.
Bar charts summarizing the total number of PET-positive lesions identified in the SIJ and 
in the spine will be presented by treatment group and visit for each of the pooled locations 
described above. 
Observed SUVauc values for each lesion will be pooled across subjects and summarized by 
visit for each of the pooled locations, as described above.  In the spine, the observed SUVauc
values will only be summarized for the anatomical locations in which at least 1 PET-
positive lesion is identified. Descriptive statistics will be presented including 95% CIs for 
the mean observed SUVauc values.  In addition, changes and percentage changes in SUVauc
values between visits will be calculated for each subject’s PET-positive lesion in the SIJ and 
spine, i.e. Week 12 - Baseline, Week 48 - Baseline and Week 48 - Week 12.  These changes 
in SUVauc values will be pooled across subjects and summarized by visit for each of the 
pooled locations described above. Descriptive statistics will be presented including 95% CIs 
for mean changes and percentage changes in SUVauc values between visits. 
Spaghetti plots of observed SUVauc values for lesions in the SIJ and spine will be presented 
over time for the SIJ overall, the spine overall, and for each spinal regional level (Cervical, 
Thoracic, Lumbar, Sacrum) by treatment group.
In addition, percentage changes in SUVauc values for lesions in the SIJ and spine will be 
summarized using waterfall plots.  These plots will identify subjects’ lesions by treatment 
group and will be presented by pooled location (as described above, as applicable) and for 
each visit comparison (Week 12 – Baseline, Week 48 – Baseline and Week 48 – Week 12).
The maximum of a subject’s observed SUVauc values will be calculated across the pooled 
locations described above. This maximum SUVauc value per subject will be summarized at 
each visit together with changes and percentage changes from Baseline between visits. 
Descriptive statistics will be presented including 95% CIs for the mean and the mean 
changes/percentage changes in the maximum SUVauc values.
The mean and 95% CI for the maximum SUVauc values per subject in the SIJ and spine 
over scheduled time will also be presented by treatment group.  The same plot will be 
repeated for the changes and percentage changes in the maximum SUVauc value per subject 
with treatment group overlaid on the same plot.
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a


UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 84 of 86
In addition, percentage changes in the maximum of SUVauc values per subject in the SIJ 
and spine will be summarized using waterfall plots.  These plots will identify subjects by 
treatment group and will be presented for each visit comparison (Week 12 – Baseline, 
Week 48 – Baseline and Week 48 – Week 12).
Additional exploratory analyses may include examining the relationship between changes 
from Baseline in bone formation and changes from Baseline in ASDAS at Week 12 
(primary efficacy variable) and Week 48, and also whether there are any differences in 
bone formation in clinical responders according to ASAS20 versus clinical non-responders 
at Weeks 12 and 48. Statistical modelling which accounts for multiple PET-positive lesions 
per subject may be used in these analyses.
Change #6
Adverse events (Section 11.2)
The first paragraph was changed to:
Adverse events with start date prior to the first dose of IMP are defined as pre-treatment 
AEs. Adverse events with a start date prior to the first dose of IMP will be defined as 
pre-treatment AEs. A treatment-emergent AE (TEAE) is defined as any AE with a start 
date/time at the time of or after the first dose of IMP up until 140 days after the last dose of 
IMP. Any AE with onset later than 140 days after the last dose of IMP will not be 
considered as treatment-emergent and therefore will not be included in the tabulations of 
TEAEs. Selected summaries will be presented separately for TEAEs during the Treatment
Period (any AE with a start date/time at the time or after the first dose of IMP up until the 
Week 12 Visit) and TEAEs during the study (as per the definition of TEAEs given above).
The fourth and fifth paragraphs were changed to:
An overview of the number and percentage of subjects who experience TEAEs will be 
presented by treatment group, based on the SS. Separate tabulations will be presented for 
TEAEs during the Treatment Period and TEAEs during the study and will include the 
number and percentage of subjects with any TEAEs, serious TEAEs, related TEAEs, 
discontinuation due to TEAEs, severe TEAEs, AEs leading to death and TEAEs leading to 
death; event counts will also be included.  The summary of TEAEs during the study will be 
repeated for subjects in the SS who were randomized in the PET-MRI/PET-CT substudy.
In addition, the following summaries will be presented by treatment group, SOC, high level 
term (HLT) and PT, based on the SS:
•
Incidence of TEAEs[a] [b]
•
Incidence of TEAEs, stratified by overall ADA status (positive/negative) as defined in 
Section 10
•
Incidence of serious TEAEs[a] [b]
•
Incidence of non-serious TEAEs[b]
•
Incidence of TEAEs by relationship
•
Incidence of TEAEs by maximum relationship
PUBLIC COPY
EAE) 
PY 
EAE) 
f IMP u
OPY
f IMP u
s after t
COP
s after t
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s were c
PU
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P
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This document cannot be used to support any marketing authorization 
onders
hori
onders
ve lesions
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ve lesions
e defined 
mar
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of IMP w
y m
of IMP w
defined a
ny 
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idence o
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application and any extensions or variations thereof.
d as pre
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40 days a
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on
a
n 10
ap
10


UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 85 of 86
•
Incidence of TEAEs by maximum intensity
•
Incidence of fatal TEAEs by relationship
•
Incidence of non-serious TEAEs by relationship
•
Incidence of serious TEAEs by relationship
•
Incidence of non-serious TEAEs above threshold of 5% of subjects
•
Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship
•
Incidence of TEAEs by SOC and PT (including the number and percentage of subjects 
and individual subject numbers for each PT stratified by intensity, relationship and 
seriousness) 
[a] These summaries will be presented separately for TEAEs during the Treatment Period 
and TEAEs during the study.
[b] These summaries will be repeated for subjects in the SS who were randomized in the 
PET-MRI/PET-CT substudy and will be based on TEAEs during the study
PUBLIC COPY 
ing authorization 
ip
h
ip
of subject
uth
of subject
nship and
au
nship and
marketi
Treatme
eting
Treatme
were rand
ark
were rand
This document cannot be used to support any m
ring the s
ma
ring the s
reof.
d
of
d
application and any extensions or variations the
ent Perio
here
ent Perio
domized 
ns 
domized 
study
ion
study


UCB
19 June 2020
Statistical Analysis Plan Amendment 3
Bimekizumab
AS0013
Confidential
Page 86 of 86
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.