Clinical trial NCT02963506
Conditions: Ankylosing Spondylitis
Keywords: AS Ankylosing Spondylitis Bimekizumab
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2016-10-01; Completion date: 2018-08-01
Enrollment: 303 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study to evaluate the efficacy and safety of different doses of bimekizumab in subjects with active Ankylosing Spondylitis (AS).

Detailed description:

Arms: arm 1: Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. arm 2: Subjects will receive for 12 Weeks Bimekizumab Dose 1 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. arm 3: Subjects will receive for 12 Weeks Bimekizumab Dose 2 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. arm 4: Subjects will receive for 48 Weeks Bimekizumab Dose 3. arm 5: Subjects will receive for 48 Weeks Bimekizumab Dose 4.
Interventions: intervention 1: Placebo intervention 2: Bimekizumab
Intervention descriptions: intervention 1: None intervention 2: Bimekizumab in different dosages.

Protocol documents:
Prot_000.pdf: 
UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 1 of 143
PROTOCOL AS0008 AMENDMENT 2
A MULTICENTER, PHASE 2B, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP, DOSE-RANGING STUDY TO EVALUATE 
THE EFFICACY AND SAFETY OF BIMEKIZUMAB IN 
SUBJECTS WITH ACTIVE ANKYLOSING SPONDYLITIS
PHASE 2B
EudraCT Number: 2016-001102-42
IND Number: 128708
UCB BIOPHARMA SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
29 Jul 2016
Not applicable
Protocol Amendment 1
15 Mar 2017
Nonsubstantial
Protocol Amendment 2
09 Mar 2018
Substantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
REDACTED COPY 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 2 of 143
STUDY CONTACT INFORMATION
Sponsor
UCB BIOPHARMA SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
, MD, MSc, PhD
Address:
UCB Pharma Ltd.
208 Bath Road
Slough, SL1 3WE
UNITED KINGDOM
Phone:
Clinical Project Manager
Name:
, PharmD, PhD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str.10
40789 Monheim am Rhein
GERMANY
Phone:
Clinical Trial Biostatistician
Name:
, MS
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 3 of 143
Clinical Monitoring Contract Research Organization
Name:
PRA Health Sciences
Address:
4130 Park Lake Avenue, Suite 400
Raleigh, NC 27612
UNITED STATES
Phone:
Fax:
REDACTED COPY 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 4 of 143
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or 
or variations 
v
thereof. 


UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 5 of 143
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................16
2
INTRODUCTION ...........................................................................................................18
2.1 Axial spondyloarthritis.....................................................................................................18
2.1.1
Clinical studies.....................................................................................................19
2.1.2
Nonclinical studies...............................................................................................21
3
STUDY OBJECTIVES....................................................................................................21
3.1 Primary objective.............................................................................................................21
3.2 Secondary objectives .......................................................................................................22
3.3 Other objectives ...............................................................................................................22
4
STUDY VARIABLES.....................................................................................................22
4.1 Primary variable(s)...........................................................................................................22
4.1.1
Primary efficacy variable.....................................................................................22
4.2 Secondary variables .........................................................................................................22
4.2.1
Secondary efficacy variables ...............................................................................22
4.2.2
Secondary safety variables ..................................................................................23
4.3 Other variables.................................................................................................................23
4.3.1
Other efficacy variables.......................................................................................23
4.3.2
Other safety variables ..........................................................................................24
4.3.3
Other PK and PD variables..................................................................................24
4.3.4
Other immunological variables............................................................................24
4.3.5
Other pharmacogenomic, proteomic, and metabolite variables ..........................24
5
STUDY DESIGN.............................................................................................................25
5.1 Study description .............................................................................................................25
5.1.1
Screening Period/Baseline...................................................................................25
5.1.2
Double-Blind Period............................................................................................26
5.1.3
Dose-Blind Period ...............................................................................................26
5.1.4
Rescue therapy.....................................................................................................27
5.1.5
Safety Follow-Up Visit........................................................................................27
5.1.6
Safety monitoring strategy...................................................................................27
5.1.7
Imaging evaluation ..............................................................................................28
5.1.8
Study duration per subject ...................................................................................28
5.1.9
Planned number of subjects and site(s) ...............................................................28
5.1.10
Anticipated regions and countries .......................................................................28
5.2 Schedule of study assessments.........................................................................................28
5.3 Schematic diagram...........................................................................................................34
5.4 Rationale for study design and selection of dose.............................................................35
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 6 of 143
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................35
6.1 Inclusion criteria ..............................................................................................................35
6.2 Exclusion criteria .............................................................................................................37
6.3 Withdrawal criteria ..........................................................................................................41
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................43
7
STUDY TREATMENTS.................................................................................................43
7.1 Description of investigational medicinal products ..........................................................43
7.2 Treatments to be administered.........................................................................................44
7.3 Packaging.........................................................................................................................44
7.4 Labeling ...........................................................................................................................44
7.5 Handling and storage requirements..................................................................................44
7.6 Drug accountability..........................................................................................................45
7.7 Procedures for monitoring subject compliance................................................................45
7.8 Concomitant medication(s)/treatment(s)..........................................................................45
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................46
7.8.2
Prohibited concomitant treatments (medications and therapies).........................46
7.9 Blinding............................................................................................................................47
7.9.1
Procedures for maintaining and breaking the treatment blind.............................48
7.9.1.1
Maintenance of study treatment blind.......................................................48
7.9.1.2
Breaking the treatment blind in an emergency situation...........................48
7.10 Randomization and numbering of subjects......................................................................49
8
STUDY PROCEDURES BY VISIT ...............................................................................49
8.1 Screening (Visit 1) ...........................................................................................................49
8.2 Baseline (Day 1, first dose of IMP) (Visit 2)...................................................................51
8.3 Double-Blind Period (Week 1 to Week 12).....................................................................52
8.3.1
Week 1 (+/-3 days) (Visit 3)................................................................................52
8.3.2
Week 2 (+/-3 days) (Visit 4)................................................................................53
8.3.3
Week 4 (+/-3 days) (Visit 5)................................................................................53
8.3.4
Week 8 (+/-3 days) (Visit 6)................................................................................54
8.3.5
Week 12 (+/-3 days) (Visit 7)..............................................................................55
8.4 Dose-Blind Period (Week 16 to Week 48) ......................................................................56
8.4.1
Week 16 (+/-4 days) (Visit 8)..............................................................................56
8.4.2
Week 20 (+/-4 days) (Visit 9)..............................................................................57
8.4.3
Week 24 (+/-4 days) (Visit 10)............................................................................57
8.4.4
Week 28 (+/-4 days) (Visit 11)............................................................................59
8.4.5
Week 32 (+/-4 days) (Visit 12)............................................................................59
8.4.6
Week 36 (+/-4 days) (Visit 13)............................................................................60
8.4.7
Week 40 (+/-4 days) (Visit 14)............................................................................60
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 7 of 143
8.4.8
Week 44 (+/-4 days) (Visit 15)............................................................................61
8.4.9
Week 48 (+/-4 days) (Visit 16)............................................................................61
8.5 Early Termination Visit ...................................................................................................62
8.6 Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final dose)......................64
8.7 Unscheduled Visit............................................................................................................65
9
ASSESSMENT OF EFFICACY......................................................................................65
9.1 ASAS20, 40, ASAS 5/6 response, and ASAS partial remission .....................................65
9.2 Patient global assessment.................................................................................................66
9.3 Total and nocturnal spinal pain........................................................................................66
9.4 Function – BASFI............................................................................................................66
9.5 Inflammation – BASDAI (mean of questions 5 and 6) ...................................................66
9.6 CRP 66
9.7 ASDAS-CRP....................................................................................................................67
9.8 BASDAI...........................................................................................................................67
9.9 BASMI.............................................................................................................................67
9.10 MASES ............................................................................................................................68
9.11 PhGADA..........................................................................................................................68
9.12 SF-3668
9.13 MOS-12............................................................................................................................68
9.14 ASQoL.............................................................................................................................69
9.15 MRI Assessment (SPARCC and ASspiMRI)..................................................................69
9.16 Hospital Anxiety and Depression Scale...........................................................................70
10
ASSESSMENT OF PHARMACOKINETIC, PHARMACODYNAMIC, 
PHARMACOGENOMIC, AND PROTEOMIC VARIABLES......................................70
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................70
12
ASSESSMENT OF SAFETY..........................................................................................71
12.1 Adverse events.................................................................................................................71
12.1.1
Definition of adverse event..................................................................................71
12.1.2
Adverse events of special interest........................................................................71
12.1.3
Adverse events for special monitoring ................................................................71
12.1.4
Procedures for reporting and recording adverse events.......................................72
12.1.5
Description of adverse events..............................................................................72
12.1.6
Follow-up of adverse events................................................................................72
12.1.7
Rule for repetition of an adverse event................................................................73
12.1.8
Pregnancy ............................................................................................................73
12.1.9
Suspected transmission of an infectious agent via a medicinal product..............74
12.1.10
Overdose of investigational medicinal product ...................................................74
12.1.11
Safety signal detection.........................................................................................74
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 8 of 143
12.2 Serious adverse events .....................................................................................................75
12.2.1
Definition of serious adverse event .....................................................................75
12.2.2
Procedures for reporting serious adverse events .................................................75
12.2.3
Follow-up of serious adverse events....................................................................76
12.3 Immediate reporting of adverse events............................................................................76
12.4 Anticipated serious adverse events ..................................................................................76
12.5 Laboratory measurements................................................................................................77
12.5.1
Evaluation of PDILI ............................................................................................78
12.5.1.1
Consultation with Medical Monitor and local hepatologist ......................82
12.5.1.2
Immediate action: determination of IMP discontinuation.........................82
12.5.1.3
IMP restart/rechallenge .............................................................................82
12.5.1.4
Testing: identification/exclusion of alternative etiology...........................82
12.5.1.5
Follow-up evaluation.................................................................................84
12.6 Other safety measurements..............................................................................................84
12.6.1
Vital signs ............................................................................................................84
12.6.2
Body weight and height.......................................................................................85
12.6.3
Physical examination...........................................................................................85
12.6.4
12-lead electrocardiogram ...................................................................................85
12.6.5
Tuberculosis and TB risk factor assessment and management ...........................85
12.6.5.1
Tuberculosis assessment by IGRA............................................................87
12.6.5.2
Chest x-ray for tuberculosis ......................................................................87
12.6.5.3
Tuberculosis questionnaire........................................................................88
12.6.5.4
Tuberculosis management.........................................................................88
12.6.6
Pregnancy testing.................................................................................................89
12.6.7
Assessment of suicidal ideation and behavior.....................................................89
13
OTHER STUDY MEASUREMENTS ............................................................................89
13.1 Demography.....................................................................................................................89
13.2 Medical history ................................................................................................................89
13.3 Ankylosing spondylitis history ........................................................................................90
13.4 Prior and concomitant medications..................................................................................90
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................90
14.1 Adherence to protocol......................................................................................................90
14.2 Monitoring .......................................................................................................................90
14.2.1
Definition of source data .....................................................................................90
14.2.2
Source data verification .......................................................................................91
14.3 Data handling...................................................................................................................91
14.3.1
Case Report Form completion.............................................................................91
14.3.2
Database entry and reconciliation........................................................................91
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 9 of 143
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............92
14.4 Termination of the study..................................................................................................92
14.5 Archiving and data retention............................................................................................92
14.6 Audit and inspection ........................................................................................................92
14.7 Good Clinical Practice .....................................................................................................93
15
STATISTICS ...................................................................................................................93
15.1 Definition of analysis sets................................................................................................93
15.2 General statistical considerations.....................................................................................94
15.3 Planned efficacy analyses ................................................................................................94
15.3.1
Analysis of the primary efficacy variable............................................................94
15.3.1.1
Supportive analyses...................................................................................95
15.3.2
Other efficacy analyses........................................................................................95
15.3.2.1
Analysis of the secondary efficacy variables ............................................95
15.3.2.2
Analysis of the other efficacy variables ....................................................96
15.4 Subgroup analyses ...........................................................................................................96
15.5 Planned safety and other analyses....................................................................................96
15.5.1
Safety analyses.....................................................................................................96
15.5.2
Other analyses......................................................................................................97
15.6 Handling of protocol deviations.......................................................................................97
15.7 Handling of dropouts or missing data..............................................................................97
15.8 Planned interim analysis and data monitoring.................................................................99
15.9 Determination of sample size...........................................................................................99
16
ETHICS AND REGULATORY REQUIREMENTS....................................................100
16.1 Informed consent ...........................................................................................................100
16.2 Subject identification cards............................................................................................100
16.3 Institutional Review Boards and Independent Ethics Committees................................100
16.4 Subject privacy...............................................................................................................101
16.5 Protocol amendments.....................................................................................................101
17
FINANCE, INSURANCE, AND PUBLICATION.......................................................102
18
REFERENCES ..............................................................................................................102
19
APPENDICES ...............................................................................................................106
19.1 Modified New York (mNY) Classification Criteria for AS ..........................................106
19.2 Markedly abnormal laboratory values ...........................................................................107
19.3 Protocol Amendment 1 ..................................................................................................108
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................142
21
SPONSOR DECLARATION ........................................................................................143
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 10 of 143
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................29
Table 7‒1:
Prohibited or restricted medications and required wash-out periods prior 
to Baseline........................................................................................................46
Table 7‒2:
Preparation of placebo and bimekizumab injections .......................................48
Table 12‒1:
Anticipated serious adverse events for the population of subjects with 
ankylosing spondylitis .....................................................................................77
Table 12‒2:
Laboratory measurements................................................................................78
Table 12‒3:
Required investigations and follow-up for PDILI ...........................................80
Table 12‒4:
PDILI laboratory measurements......................................................................83
Table 12‒5:
PDILI information to be collected...................................................................84
Table 19‒1:
Modified New York (mNY) Classification Criteria for AS ..........................106
Table 19‒2:
Definitions of markedly abnormal hematology values..................................107
Table 19‒3:
Definitions of markedly abnormal biochemistry values................................107
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................34
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 11 of 143
LIST OF ABBREVIATIONS
AE
adverse event
AESI
adverse event of special interest
AESM
adverse event for special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AS
ankylosing spondylitis
ASAS
Assessment of SpondyloArthritis International Society
ASAS20, 40, 5/6
Assessment in SpondyloArthritis International Society 20%, 40%, 5 out
of 6 response criteria
ASDAS-CRP
Ankylosing Spondylitis Disease Activity Score-C-reactive protein
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score major improvement
ASspiMRI-a
Ankylosing Spondylitis spine Magnetic Resonance Imagine-activity
ASQoL
Ankylosing Spondylitis Quality of Life
AST
aspartate aminotransferase
axSpA
axial spondyloarthritis
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BASMI
Bath Ankylosing Spondylitis Metrology Index
BSA
body surface area
CDC 
Centers for Disease Control 
CDMS
clinical data management system
CHO
Chinese Hamster Ovarian
CL/F
total body clearance
COX-2 inhibitor
cyclooxygenase 2 inhibitor
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
CRP
C-reactive protein
C-SSRS/eC-SSRS
Columbia-Suicide Severity Rating Scale/electronic C-SSRS
CZP
certolizumab pegol
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 12 of 143
DBRS
Dose-Blind Responder Set
DBS
Dose-Blind Set
DMARD
disease-modifying antirheumatic drug
DMC
Data Monitoring Committee
DVU
disco-vertebral unit
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
ES
Enrolled Set
ESS
Escape Subject Set
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GI
gastrointestinal
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale—Anxiety 
HADS-D
Hospital Anxiety and Depression Scale—Depression 
HbcAg
hepatitis B core antibody
HbsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
HRQoL
health-related quality of life
hs-CRP
high sensitivity C-reactive protein
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
ICH
International Council for Harmonisation
ICF
Informed Consent Form
IEC
Independent Ethics Committee
IGRA
Interferon-Gamma Release Assay
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 13 of 143
IIV
interindividual variability
IL
interleukin
im
intramuscular
IMP
investigational medicinal product
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
iv
intravenous
IXRS
interactive voice or web response system 
LTB
latent tuberculosis
LTBI
latent tuberculosis infection 
MAR
missing at random
MASES
Maastricht Ankylosing Spondylitis Enthesitis Index
MCID
minimal clinically important difference
MCP-Mod
multiple comparison procedure – modeling
MCS
mental component summary
MedDRA®
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MMR
measles-mumps-rubella
mNY
Modified New York (criteria)
MOS
Medical Outcomes Study
MRI
magnetic resonance imaging
MTB
mycobacterium tuberculosis 
MTX
methotrexate
nr-axSpA
nonradiographic-axial spondyloarthritis
NRI
nonresponder imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
NTMB
nontuberculous mycobacteria
NYHA
New York Heart Association
OMERACT
Outcome Measures in Rheumatology Clinical Trials
OPV
oral polio vaccine
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 14 of 143
PCS
physical component summary
PD
pharmacodynamics
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamics Per-Protocol Set
PGADA
Patient’s Global Assessment of Disease Activity
PhGADA
Physician’s Global Assessment of Disease Activity
PK
pharmacokinetics
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per-Protocol Set
PS
Patient Safety
PsA
psoriatic arthritis
Q4W
every 4 weeks (monthly)
QTcB
QT interval corrected for heart rate using Bazett’s formula 
QTcF
QT interval corrected for heart rate using Fridericia’s formula 
RA
rheumatoid arthritis
RIF
mycobacterium tuberculosis rifampicin
RS
Randomized Set
RCTC
Rheumatology Common Toxicity Criteria
RUV
residual unexplained variability
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous(ly)
SD
standard deviation
SF-36
Short-Form 36-item Health Survey
SFU
Safety Follow-up
SI
sacroiliac
SpA
spondyloarthritis
SPARCC
Spondyloarthritis Research Consortium of Canada
SOP
standard operating procedure
SS
Safety Set
SSZ
sulfasalazine
STIR
short-tau-inversion recovery
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 15 of 143
t½
half-life
TB
tuberculosis
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
TNFα
tumor necrosis factor alpha
ULN
upper limit of normal
VAS
visual analog scale
V/F
volume of distribution
VU
vertebral unit
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


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


UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 68 of 143
9.10
MASES
Enthesitis is assessed with MASES. The MASES is an index that measures the severity (ie, 
intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 1 and then summed for a possible 
score of 0 to 13.
9.11
PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 10=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities. 
This assessment by the Investigator should be made blind to the PGADA.
The subject should be asked to consider both joint and skin components in their response to this 
question.
9.12
SF-36
The SF-36 (Version 2, standard recall) is a 36-item generic health-related quality of life 
(HRQoL) instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as 
follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General 
Health (5 items),Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), 
Mental Health (5 items), and 1 item for perceived stability or change in health (Health 
Transition) during the last year. The concepts represented by these domains contribute to 
physical, mental, and social aspects of HRQoL.
In addition to domain scores, the Physical Component Summary and Mental Component 
Summary scores are calculated from the 8 domains (excluding the Health Transition item). 
Component scores appreciate the impact of each domain on physical and mental health status 
(Maruish, 2011). Each of the 8 domain scores and the component summary scores range from 0 
to 100, with a higher score indicating a better health status. The 2 component summary scores 
are standardized with a mean of 50 and a standard deviation (SD) of 10 in the general US 
population. 
9.13
MOS-12
The MOS Sleep Scale is a validated generic self-administered scale measuring specific aspects 
of sleep. The frequency with which each problem has been experienced during the previous 
4 weeks is rated on a 6-point scale ranging from “none of the time” to “all of the time,” except 
sleep quantity, which is reported in hours. All scores are transformed linearly to range from 0 to 
100, again with the exception of the sleep quantity subscale, which is scored in hours. Higher 
scores indicate more of the attribute implied by the scale name (eg, more sleep disturbance, more 
adequate sleep, and greater sleep quantity). The psychometric properties of the MOS Sleep Scale 
have been found to be satisfactory by Hays and colleagues (Hays et al, 2005). The domains of 
interest for this study are the Sleep Disturbance and the Sleep Problems Index II domains. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 69 of 143
9.14
ASQoL
The ASQoL, a validated disease-specific 18-item questionnaire, has been developed specifically 
for measuring HRQoL in subjects with AS (Doward et al, 2003). The ASQoL has been used and 
has shown to be responsive in axSpA (Barkham et al, 2009; Haibel et al, 2008). The ASQoL 
score ranges from 0 to 18 with higher score indicating worse HRQoL. 
9.15
MRI Assessment (SPARCC and ASspiMRI)
While radiography can detect chronic bony changes (eg, sclerosis, erosions, bridging, and 
ankyloses), structural changes generally occur slowly and x-rays are insensitive; therefore, 
changes are difficult to detect in the relatively short duration of a randomized clinical trial. 
Unlike radiography, MRI can be used to visualize inflammation in the SI joints and spine in 
addition to structural lesions. Inflammation of the SI joints and spine is a key feature of AS that 
is potentially amenable to treatment with bimekizumab. If bimekizumab is effective, it is 
expected that reduction in inflammation in the SI joints and spine can be detected using MRI 
within the 48-week Treatment Period of this study. Recently a Danish study demonstrated 
significant changes in in ASspiMRI-a (Berlin modification) and SPARCC MRI-assessed 
inflammation scores and in SPARCC MRI-assessed erosion scores within 12 weeks after 
initiation of adalimumab (see below for further description of these MRI scoring methods). The 
researchers concluded that MRI-assessed structural lesions change rapidly and may have value 
for assessing the effects of disease-modifying treatment in clinical trials (Pedersen SJ et al, 
2016). 
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
20 subjects per treatment arm at Baseline. A central reader will assess Baseline MRIs to identify 
MRI-positive subjects as per the ASAS-Outcome Measures in Rheumatology Clinical Trials 
(OMERACT) criteria. An MRI at Week 12 and Week 48 will be performed for those subjects
who were MRI-positive at Baseline. The Baseline MRI should be performed after confirmation 
of eligibility based on screening assessments for the study and before the first bimekizumab 
injection. Magnetic resonance imaging at Week 12 and Week 48 should be performed as close to 
the Week 12/Week 48 Visit as possible. Additional details for standardized performance and 
processing of MRIs will be provided in an MRI manual. The MRIs will be read centrally by 
readers who are blinded to treatment assignment and chronological order of the MRIs according 
to a charter for independent imaging assessment.  
The following 2 different scoring systems will be utilized to determine changes from Screening 
(Lukas et al, 2007): 
ASspiMRI-a (Berlin modification) score 
This method is a scoring system with a concentration on short-tau-inversion recovery (STIR)
sequences which quantifies changes in 23 disco-vertebral units (DVU) of the spine. A DVU is
defined as the region between 2 virtual lines through the middle of each vertebra. Active 
inflammation is scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension 
on 1 or more consecutive slices that represent the highest level of inflammation in a particular 
VU. There is no grading for erosion in the Berlin modification. The total spine ASspiMRI-a 
score in the Berlin modification can range from 0 to 69. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 70 of 143
SPARCC SI Joint score
This method is a scoring system for assessing the SI joint based on STIR sequences. An 
abnormal increased signal on the STIR sequence represents bone marrow edema. The SI joint is 
divided into 4 quadrants (upper iliac, lower iliac, upper sacral, and lower sacral). The presence of 
increased signal on STIR in each of these 4 quadrants is scored as either 0=normal signal or 
1=increased signal. The maximum score for abnormal signal in the 2 SI joints of 1 coronal slice 
is therefore 8. Joints that include a lesion exhibiting intense signal are each given an additional 
score of 1 per slice (that demonstrate this feature). Each SI joint that includes a lesion 
demonstrating continuous increase signal of depth ≥1cm from the articular surface is also given 
an additional score of 1. The maximum score for a single coronal slice is 12. Scoring is repeated 
in each of 6 consecutive coronal slices, so that the total SI joint SPARCC MRI score can range 
from 0 to 72. 
9.16
Hospital Anxiety and Depression Scale
The HADS was chosen for its well-established psychometric properties and its use in clinical 
research on biological therapy in subjects with chronic plaque psoriasis (Langley et al, 2010; 
Dauden et al, 2009). The HADS scores for anxiety and for depression range from 0 to 21 with 
higher scores indicating worse state. A score below 8 is considered to be normal whereas a score 
of 15 and above is considered severe (Snaith and Zigmond, 1994).
10
ASSESSMENT OF PHARMACOKINETIC, 
PHARMACODYNAMIC, PHARMACOGENOMIC, AND 
PROTEOMIC VARIABLES
Plasma concentrations of bimekizumab, population PK variables (CL/F, V/F) and dose-exposure 
responses (for ASAS40 response) are the PK variables. 
The PD variables are the concentrations of cytokines of relevance to IL-17A/F signaling pathway 
and AS biology. Where local regulations permit, additional blood samples will be collected from 
consenting subjects at specific time points and stored at -80°C for up to 20 years to allow for 
potential exploratory analyses of genomic, genetic/epigenetic, proteomic, and metabolite
biomarkers relevant to the disease biology, disease progression, response to therapy, and 
inflammatory and immune response processes
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5‒1. When these samples are required at a visit during which the subject is 
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. Detailed information on 
sample analysis will be provided in a bioanalytical report.
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES
The immunological variables comprise detection of anti-bimekizumab antibodies related to 
immunogenicity, serum complement concentrations, mononuclear cell subtypes (analyzed by 
flow cytometry/fluorescence-activated cell sorting), and other exploratory biomarkers.
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5‒1. When these samples are required at a visit during which the subject is 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 71 of 143
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. The presence of antibodies to 
bimekizumab will be determined using a validated bioanalytical method. Detailed information on 
sample analysis will be provided in a bioanalytical report.
12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent Form), including any pretreatment and posttreatment 
periods required by the protocol, must be reported in the eCRF even if no IMP was taken but 
specific study procedures were conducted. This includes all AEs not present prior to the initial 
visit and all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
12.1.2
Adverse events of special interest
An AE of special interest (AESI) is any AE that a regulatory authority has mandated be reported 
on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AESI (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should then be reported if an 
alternative etiology is identified during investigation and monitoring of the subject.
12.1.3
Adverse events for special monitoring
UCB has identified AEs for special monitoring (AESM). An AESM is an AE or safety topic for 
which special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB), are considered appropriate. Identified AESM can be of particular 
concern based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or comorbidities and risk factors prevalent in the 
study population.
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 12.6.5), cytopenias, hypersensitivities, suicide 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 72 of 143
ideation or behavior (assessed using the eC-SSRS), depression and anxiety (assessed using the 
HADS, see Section 9.16), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin; see Section 12.5.1), malignancies, and inflammatory bowel 
diseases.
12.1.4
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
12.1.5
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the intensity of an AE in the eCRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria:
•
Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere with 
his/her usual activities and/or is of no clinical consequence
•
Moderate: the AE interferes with the usual activities of the subject or it is of some clinical 
consequence
•
Severe: the subject is unable to work normally or to carry out his/her usual activities, or the 
AE is of definite clinical consequency
Details for completion of the Adverse Event eCRF (including judgment of intensity and 
relationship to IMP) are described in the eCRF Completion Guidelines.
12.1.6
Follow-up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 12.5.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the Patient Safety (PS) database without 
limitation of time.
If an AE is ongoing at the end of the study for a subject, follow-up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow-up. If no follow-up is provided, the 
Investigator must provide a justification. The follow-up will usually be continued for 20 weeks 
after the subject has discontinued his/her IMP.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 73 of 143
12.1.7
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:
•
The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”
•
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
12.1.8
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by providing the completed 
Pregnancy Report and Outcome Form (for contact details see SAE reporting information at the 
beginning of this protocol). The subject should be withdrawn from the study as soon as 
pregnancy is known (by positive pregnancy test), and the following should be completed:
•
The subject should return for the ET Visit.
•
The subject should immediately stop the intake of the IMP.
•
An SFU Visit should be scheduled 20 weeks after the subject has discontinued her IMP.
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome Form provided to the
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome Form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow-up is continued for a period longer than 30 days. If 
the subject is lost to follow-up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s Drug Safety department is the primary contact for any questions related to the data 
collection for the pregnancy, eventual birth, and follow-up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent Form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/ CRO contract monitor for the study. The Investigator will 
complete the Pregnancy Report and Outcome Form and send it to UCB’s PS department (for 
contact details see SAE reporting information at the beginning of this protocol) only after the 
partner has agreed that additional information can be captured and has provided the signed 
Partner Pregnancy Consent Form. UCB’s PS department is also the primary contact for any 
questions related to the data collection for the partner pregnancy, eventual birth, and follow-up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective abortion 
when medically indicated (eg, when pregnancy is endangering life or health of woman or when 
fetus will be born with severe abnormalities), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 74 of 143
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally 
reported using the Investigator SAE Report form.
12.1.9
Suspected transmission of an infectious agent via a medicinal 
product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
12.1.10
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if 
there are associated clinical signs and symptoms or if the act of taking the excess medicine itself 
is an AE or SAE (eg, suicide attempt).
12.1.11
Safety signal detection
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory or ECG results) for which data will be periodically reviewed during the course 
of the study.
In addition, an independent DMC will periodically review and monitor the safety data from this 
study and advise UCB. The DMC membership includes clinicians knowledgeable about the 
disease or the treatment. All members have experience and expertise in clinical trials. Board 
members may not participate in the study as principal or co-Investigators, or as study subject 
care physicians. The duration of membership for the DMC will be inclusive of planned analyses 
for AS0008. The DMC may also be asked to provide a review of final study results, as deemed 
appropriate. The DMC procedures will ensure that data remain blind to the study team and 
Investigators at all times throughout the conduct of the study. The detailed role, scope, 
responsibilities, and complete procedures, as well as the identity of the DMC members, will be 
described in a separate charter document. A cardiovascular adjudication committee will be in 
place for this study. Specific procedures will be outlined in the charter, which will be developed 
by the committee members.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 75 of 143
12.2
Serious adverse events
12.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
•
Death
•
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)
•
Significant or persistent disability/incapacity
•
Congenital anomaly/birth defect (including that occurring in a fetus)
•
Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious.
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 12.1.2], allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.)
•
Initial inpatient hospitalization or prolongation of hospitalization
A patient admitted to a hospital, even if he/she is released on the same day, meets the criteria 
for the initial inpatient hospitalization. An emergency room visit that results in admission to 
the hospital would also qualify for the initial inpatient hospitalization criteria. However, 
emergency room visits that do not result in admission to the hospital would not qualify for 
this criteria and, instead, should be evaluated for 1 of the other criteria in the definition of 
serious (eg, life-threatening adverse experience, important medical event).
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.
Note: Confirmed active TB is always to be considered as an SAE and must be captured on an 
SAE Report Form and provided to the Sponsor in accordance with SAE reporting requirements.
12.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the SAE Reporting section at the 
front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
completed “Investigator SAE Report Form for Development Drug” (SAE report Form) provided 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 76 of 143
by UCB, even if the data are incomplete, or if it is obvious that more data will be needed in order 
to draw any conclusions. Information recorded on this form will be entered into the global PS 
database.
An Investigator SAE report Form will be provided to the Investigator. The Investigator SAE 
Report Form must be completed in English. 
It is important for the Investigator, when completing the SAE report Form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report Form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE report Form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the IB.
12.2.3
Follow-up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 12.5.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the PS database without limitation of time.
12.3
Immediate reporting of adverse events
The following AEs must be reported immediately:
•
SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality
•
Suspected transmission of an infectious agent via a medicinal product
•
AEs of special interest as defined in Section 12.1.2
12.4
Anticipated serious adverse events
The following list of Anticipated SAEs (Table 12‒1) has been identified, as these events are 
anticipated to occur in the population studied in this protocol at some frequency that is 
independent of drug exposure. This original list will remain in effect for the duration of the 
protocol. Note that listed events will not be regarded as anticipated SAEs if they are life 
threatening or if they result in the death of the study subject.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 77 of 143
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 12.2.2.
Table 12‒1: Anticipated serious adverse events for the population of subjects 
with ankylosing spondylitis
MedDRA system organ class
MedDRA preferred term
Skin and subcutaneous tissue disorders
Psoriasis
Eye disorders
Uveitis
Musculoskeletal and connective tissue disorders
Dactylitis
Tendonitis
Atlantoaxial instability
Gastrointestinal disorders
Colitis ulcerative
Crohn's disease
Cardiac disorders
Aortic valve incompetence
Atrial tachycardia
Atrioventricular block
Bundle branch block
Cardiomyopathy
Vascular disorders
Aortitis
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
Nervous system disorders
Cauda equina syndrome
Injury, poisoning and procedural complications
Spinal cord injury
Spinal fracture
Cervical Vertebral fracture
Lumbar Vertebral fracture 
Thoracic Vertebral fracture
Immune system disorders
Amyloidosis
Psychiatric disorders
Depression
MedDRA=Medical Dictionary for Regulatory Activities
Note: Exception: Listed events will not be regarded as anticipated SAEs if they are life threatening or if they result 
in the death of the study subject. 
12.5
Laboratory measurements
Clinical laboratory assessments consist of serum chemistry, hematology, and urinalysis, and 
pregnancy tests (serum or urine) (Table 12‒2). A centralized laboratory will be used to supply all 
laboratory test supplies and analyze all blood and urine samples for hematology, biochemistry 
and urinalysis measurements. Any unscheduled laboratory testing should also be collected using 
the central laboratory. Testing to rule out hepatitis B, hepatitis C, and HIV (see Exclusion 
Criterion #9, Section 6.2) will be performed at Screening in addition to those measurements 
listed in Table 12‒2. 
Specific details regarding the handling and processing of serum chemistry, hematology, and 
urinalysis samples are provided in the study laboratory manuals.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 78 of 143
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
a A serum pregnancy test will be performed at Screening for all women of childbearing potential. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles and 
women during menopause. Natural menopause is recognized to have occurred after 12 consecutive months of 
amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause 
Society [IMS], 2015). A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A 
urine pregnancy test will also be performed at any study visit where there has been a delay in menses. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. 
Pregnancy test results must be negative prior to administering IMP. 
b Both CRP and hs-CRP will be tested at specified visits per Table 5‒1.
12.5.1
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 79 of 143
reported as an AE of special interest (see Section 12.1.2), and, if applicable, also reported as an 
SAE (see Section 12.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.5.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 12.5.1.5). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Table 12‒3 summarizes the approach to investigate PDILI.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 80 of 143
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or AST
Total 
bilirubin
Symptomsa of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consultc
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 12.5.1.4); 
recommended to occur 
at the site with HCP.
Monitoring of liver 
chemistry values at least 
twice per week until values 
normalize, stabilize, or 
return to within baseline 
valuesd
≥3xULN
NA
Yes
≥5xULN
NA
NA
Need for hepatology 
consult to be discussed.( 
required if ALT or AST 
≥8xULN)
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation
≥3xULN (and 
≥2x baseline) 
and <5xULN 
(and ≥2x 
baseline)
<2xULN
No
Discussion with Medical 
Monitor required.
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow-
up requirements).c
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 12.5.1.2).
IMP discontinuation 
required if any of the 
following occur:
•
Subject cannot 
comply with 
monitoring schedule. 
Essential: Every 
attempt must be made 
to have repeat liver 
chemistry values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.5.1.4).
Monitoring of liver 
chemistry values at least 
twice per week for 2 weeks.d
•
Immediate IMP 
discontinuation required 
if liver chemistry values 
continue to increase.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 81 of 143
Table 12‒3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or AST
Total 
bilirubin
Symptomsa of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
•
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values continue to 
increase 
•
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values remain 
≥3xULN (and 
≥2x baseline) after 2 
weeks of monitoring 
without evidence of 
resolution
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liver chemistry values:
•
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levels remain ≥3xULN 
(and ≥2x baseline) 
without evidence of 
resolutiond
Continue to monitor until 
values normalize, stabilize, 
or return to within baseline 
values.d
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 12.5.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 82 of 143
12.5.1.1
Consultation with Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 12.5.1.4) and SAE report (if applicable).
12.5.1.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring. 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 12‒3 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
12.5.1.3
IMP restart/rechallenge
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, maybe 
fatal, and must not occur.
12.5.1.4
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are included but not 
limited to those listed in Table 12‒4 (laboratory measurements) and Table 12‒5 (additional 
information). Results of the laboratory measurements and information collected are to be 
submitted to the sponsor on the corresponding eCRF. If the medical history of the subject 
indicates a requirement for other assessments not included below, these additional assessments 
should be completed and submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The following measurements are to be assessed (Table 12‒4):
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 83 of 143
Table 12‒4: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophil 
antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
ALT, AST
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 84 of 143
The following additional information is to be collected (Table 12‒5):
Table 12‒5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included.
Pertinent medical history, including the following:
•
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)
•
Adverse reactions to drugs
•
Allergies
•
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)
•
Recent travel 
•
Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, 
should not be used as an explanation for significant AST and/or ALT elevations.)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function
Alcohol and illicit drug use
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury
12.5.1.5
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 12‒3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to baseline. Determination of stabilization is at the discretion of the Investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
12.6
Other safety measurements
12.6.1
Vital signs
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 85 of 143
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing.
12.6.2
Body weight and height
Height is collected at Screening only. The Investigator or designee will measure the height of the 
subject with shoes removed in meters and the weight of the subject in kilograms. The same scale 
should be utilized throughout the study where possible. 
12.6.3
Physical examination
The physical examination should be conducted by the Investigator or designee at the time points 
listed in Table 5‒1 and will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; GI; musculoskeletal; hepatic; neurological (including limb 
reflexes); and mental status. Findings considered clinically significant changes since the physical 
examination at the Screening Visit will be recorded as AEs.  
12.6.4
12-lead electrocardiogram
The Investigator or designee will perform the ECG. The ECGs will be read locally.
12.6.5
Tuberculosis and TB risk factor assessment and management
All subjects will be assessed for TB at Screening and at the time points specified in the Schedule 
of Assessments (Table 5‒1) through physical examination for signs and symptoms of TB, chest 
x-ray (Section 12.6.5.2), laboratory testing (Section 12.6.5.1), and subject questionnaire 
(Section 12.6.5.3). 
At Screening, all subjects will have an IGRA test (QuantiFERON TB GOLD is recommended), a 
chest x-ray (unless already performed within 3 months of screening) and examination for signs 
and symptoms of TB. In addition, each subject will complete a TB questionnaire with questions 
directed at symptoms of TB and potential exposure to TB. 
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen.
Following consultation with the Medical Monitor, subjects may be rescreened after completion 
of at least 8 weeks of LTBI prophylactic therapy.
a.
Known TB infection whether present or past is defined as:
−
Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra-pulmonary)
−
History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection, unless adequately treated and proven to be fully 
recovered upon consult with a TB specialist.
−
Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject’s medical history
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 86 of 143
b. High risk of acquiring TB infection is defined as:
−
Known exposure to another person with active TB infection within the 3 months prior to 
Screening
−
Time spent in a healthcare delivery setting or institution where individuals infected with 
TB are housed and where the risk of transmission of infection is high
c.
Latent TB infection (unless appropriate prophylaxis is initiated at least 8 weeks prior to study 
treatment and continued to completion of prophylaxis) is defined as:
−
The absence of signs, symptoms (ie, evidence of organ-specific involvement), or physical 
findings suggestive of TB infection with a positive IGRA test (or 2 indeterminate IGRA 
test results) and a chest x-ray (or other imaging) without evidence of TB infection. If the 
result of the IGRA test is indeterminate, the particular IGRA test previously performed 
may be repeated once; if positive or indeterminate on retest, the subject may not be 
randomized to IMP without further evaluation, treatment and discussion with Study 
Physician, if Latent TB infection is identified. The retest must be done during the 
protocol-defined Screening window.
Note: If available, respiratory or other specimens must also be smear and culture 
negative for TB (Centers for Disease Control [CDC] diagnosis of LTB infection) 
http://www.cdc.gov/TB/topic /testing/default.htm)
d. Current or history of NTMB infection despite prior or current therapy.
Signs and Symptoms
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s medical or social history. 
The most common primary focus of TB is the lung. Other sites may include gastrointestinal 
system, bone/joints, lymph glands and meninges, etc. However, in immune compromised 
patients and/or patients treated with TNF inhibitors, extra-pulmonary manifestations of TB are
common compared to normal population.
Some common symptoms that the subject may present are dependent on the primary focus of 
infection and may include cough, blood in sputum, night sweats, lymphadenitis, joint 
pain/swelling, spinal deformity, headache/confusion, abdominal pain (mimicking inflammatory 
bowel disease), etc. Unusual presentations should always be considered.
Latent tuberculosis infection is defined in the “Exclusion Criteria” above. If the result of the
IGRA is indeterminate, the particular IGRA previously performed may be repeated once; if 
positive or indeterminate on retest, the subject may not be randomized to IMP without further 
evaluation by a TB specialist. If LTBI or active TB is identified, subject must undergo 
appropriate study specified withdrawal procedures. The retest must be done during the protocol-
defined Screening window. Laboratory diagnosis should be undertaken via mycobacteria culture 
media (or if available by preferred nucleic acid amplification test such as the Xpert 
mycobacterium tuberculosis [MTB] rifampin [RIF] test) and result must be negative for TB 
inducing pathogens.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 87 of 143
Test Conversion
Tuberculosis test conversion is defined as a positive IGRA result for the current test, when 
previous IGRA test results were negative. All subjects with TB test conversion must immediately
stop IMP administration. In case of a TB test conversion, the subject must be considered as 
having either a suspected new latent or an active TB infection and be promptly referred to an 
appropriate specialist (eg, pulmonologist, infectious disease specialist) for further evaluation. If 
test conversion indicates LTBI, active TB, or NTMB then, per UCB TB working instructions, 
TB test conversion (confirmed) should be classified adequately, either as due to LTBI, active TB 
infection, or NTMB, respectively. Additional assessments (eg, blood tests or IGRA, chest x-rays, 
or other imaging) should be performed where medically relevant and documented. Such 
conversions should be reported to the UCB PS function.
Latent TB
In case the evaluation by the appropriate specialist indicates a new LTBI during the study, a 
prophylactic TB treatment should be initiated and the IMP can be continued no sooner than 
4 weeks after start of prophylactic TB treatment, if it is deemed likely by the Investigator that 
prophylactic TB treatment is continued to completion.
If prophylaxis is not initiated, the subject must be withdrawn.
Every related action should be discussed in advance with the Medical Monitor. 
Once withdrawn from study treatment, subjects should return for the ET Visit, complete all 
ET Visit assessments, and complete a SFU Visit (20 weeks after the last dose of IMP).
Active TB or NTMB infection 
Subjects who develop active TB or NTMB infection during the study must be withdrawn from 
the study. The subject must be immediately discontinued from IMP and an ET Visit must be 
scheduled as soon as possible, but no later than the next scheduled visit. The subject should be 
encouraged to keep the SFU Visit as specified by the protocol. Treatment should be started 
immediately.
Note that subjects with history of NTMB or active NTMB infection are excluded from the study 
regardless of prior or current therapy for this condition. 
12.6.5.1
Tuberculosis assessment by IGRA
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD is 
recommended) will be performed at Screening and should be repeated at Week 44, ET, and 
SFU Visits for all subjects. The test results will be reported as positive, negative, or 
indeterminate. UCB also recommends that a TB specialist be consulted where TB (latent or 
active) is suspected or if there are doubts regarding test results. If latent or active TB is 
identified, subject must undergo appropriate study-specified withdrawal procedures. The retest 
during Screening must be done during the protocol-defined Screening window.
12.6.5.2
Chest x-ray for tuberculosis
A plain posteroanterior chest x-ray must be performed in the Screening Period unless one has 
been performed within 3 months prior to the Screening Visit. The chest x-ray (or, if done, 
Computed Axial Tomography of the Chest) must be clear of signs of TB infection (previous or 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 89 of 143
study must be withdrawn and scheduled to return for the ET Visit as soon as possible but no later 
than the next scheduled study visit and complete all ET Visit assessments. 
The subject should be encouraged to complete a SFU Visit (20 weeks after the last dose of IMP).
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed.
12.6.6
Pregnancy testing
A serum pregnancy test will be performed at Screening for all women of childbearing potential. 
This recommendation also applies to women of childbearing potential with infrequent or 
irregular menstrual cycles and women during menopause. Natural menopause is recognized to 
have occurred after 12 consecutive months of amenorrhea, for which there is no other obvious 
pathological or physiological cause (International Menopause Society, 2015). 
A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. 
A urine pregnancy test will also be performed at any study visit where there has been a 
delay in menses. This recommendation also applies to women of childbearing potential with 
infrequent or irregular menstrual cycles. 
Pregnancy test results (serum and urine) must be negative prior to administering IMP.
12.6.7
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed by trained study personnel using the eC-SSRS.  
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the eC-SSRS assessments will be performed are specified in the schedule of 
study assessments (Section 5.2). 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Posner et al, 2011; Mundt et al, 2010). 
Subjects respond to standardized clinical questions that are presented in a uniform fashion. The 
eC-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The eC-SSRS takes approximately 3 to 10 minutes to complete.
Refer to Section 6.3 for eC-SSRS-related withdrawal criteria.
13
OTHER STUDY MEASUREMENTS
13.1
Demography
The Investigator or designee will collect demographic information for all subjects according to 
local rules and regulations. This will include age, gender, race and ethnicity. Information on 
demographics will be collected according to local rules and regulations. Demographic 
information will be recorded in the eCRF.
13.2
Medical history
The Investigator or designee will obtain a complete medical history of AS as part of the 
screening assessment and include all clinically relevant past or coexisting medical conditions, 
responses to AS treatment as available, and surgeries. Findings will be recorded in the eCRF.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 90 of 143
13.3
Ankylosing spondylitis history
The Investigator or designee will obtain a detailed history of AS, including the date of onset and 
past treatments for AS. Specific information related to AS history will be recorded in the eCRF.
13.4
Prior and concomitant medications
As part of the medical history, the Investigator or designee will determine prior and concomitant 
medications and record these in the eCRF. 
14
STUDY MANAGEMENT AND ADMINISTRATION 
14.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the CPM of the Sponsor
within 24 hours and follow any local regulatory requirements.
14.2
Monitoring
UCB (or designee) will monitor the study to meet the CRO’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate. Monitoring of the study may be 
delegated by UCB to a CRO or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
14.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of CRFs are not considered acceptable source 
documents. Source documents are original records in which raw data are first recorded. These 
may include hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, 
printouts, pharmacy records, care records, ECG or other printouts, completed scales, or quality of 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 91 of 143
life questionnaires, for example. Source documents should be kept in a secure, limited access 
area.
Sponsor or designee will review to ensure that computerized source documents produced by the 
site are compliant with Food and Drug Administration (FDA) Part 11 requirements and 
document appropriately. Source documents that are computer generated and stored electronically 
must be printed for review by the monitor (eg, ECG reports). Once printed, these copies should 
be signed and dated by the Investigator and become a permanent part of the subject’s source 
documents. The Investigator will facilitate the process for enabling the monitor to compare the 
content of the printout and the data stored in the computer to ensure all data are consistent.
Electronic data records must be saved and stored as instructed by UCB (or designee).
14.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 14.2.1.
14.3
Data handling
14.3.1
Case Report Form completion
This study will use electronic data capture (EDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRF and in all required reports.
This study will also use an electronic device (Site Tablet) to capture patient reported outcomes.
Serious AE reporting will be done using the SAE Report Form (see Section 12.2.2) while also 
entering the event in the appropriate eCRF section. The safety database and the clinical database 
will be reconciled during the study and discrepancies will be corrected as needed.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Access to the EDC will be given after training has been received. A training certificate will be 
provided and filed.
Detailed instructions on the use of the EDC will be provided in the eCRF Completion 
Guidelines.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be re-approved by the Investigator. Any change or correction 
to the eCRF after saving must be accompanied by a reason for the change.
14.3.2
Database entry and reconciliation
Case Report Forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. This study is performed using EDC. The data are entered into the eCRFs once and are 
subsequently verified.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 92 of 143
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in a Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
14.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
14.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
study master file.
14.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 93 of 143
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and applicable regulatory 
requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
14.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
15
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP).
15.1
Definition of analysis sets
The following analysis sets were defined:
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
The Randomized Set (RS) will consist of all randomized subjects.
The Safety Set (SS) will consist of all randomized subjects who received at least 1 dose of IMP.
The Full Analysis Set (FAS) will consist of all randomized subjects who received at least 1 dose 
of IMP and have a valid measurement of the primary efficacy variable at Baseline.
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who had no important protocol 
deviation affecting the primary efficacy variable. The subjects with important protocol deviations 
will be predefined and evaluated during a data evaluation meeting prior to unblinding of the data.
The Pharmacokinetic Per Protocol Set (PK-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations affecting the pharmacokinetic variables, as 
confirmed during ongoing data cleaning meetings prior to database lock.
The Pharmacodynamic Per Protocol Set (PD-PPS) will consist of all randomized subjects who 
took at least 1 dose of IMP and provide at least 1 PD measurement postdose that is without 
important protocol deviation affecting that time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period including the dose at Week 12.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 94 of 143
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36.
15.2
General statistical considerations
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, summary statistics will consist of number of available observations, arithmetic mean, 
SD, median, minimum, and maximum unless stated otherwise.
All statistical tests will be performed 2-sided at a 5% level of significance unless stated 
otherwise.
15.3
Planned efficacy analyses
15.3.1
Analysis of the primary efficacy variable
The primary efficacy variable will be analyzed for all subjects in the FAS.
The dose-response relationship between treatment and ASAS40 response will be assessed with 
an ordered categorical analysis using a non-parametric correlation statistic of Mantel and 
Haenszel (Mantel and Haenszel, 1959) and modified ridit scores with the corresponding p-value. 
The analysis will include region and prior TNF inhibitor exposure as stratification factors. Prior 
TNF inhibitor exposure will be used as stratification factor as it may have an impact on efficacy. 
The use of region as stratification factor is intended to combine study centers in similar 
geographic regions. The geographic regions to be used will be defined in the IXRS and in the 
SAP. The correlation between dose and ASAS40 response will be evaluated at a significance 
level of α=0.05. This evaluation of dose-response will constitute the primary efficacy analysis.
As a supportive analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model
will include fixed effects for treatment, region, and prior TNF inhibitor exposure (yes/no). If the 
logistic regression model is unable to converge, then region may be dropped from the model to 
facilitate convergence. Comparisons will be made for each dose vs placebo at a 2-sided 
significance level of α=0.05. For each dose, the odds ratio vs placebo, the 95% confidence 
interval, and the corresponding p-value will be calculated. 
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a 2-sided significance 
level of α=0.05. This procedure will control the overall Type I error rate. If the dose response 
relationship fails to reach significance at a significance level of α=0.05, then no further testing 
will be conducted and the pairwise comparisons are seen as nonsignificant.
Nonresponder imputation will be used to account for missing data in the primary analysis. That 
is, subjects with a missing ASAS40 score at Week 12 or who discontinued study treatment prior 
to the Week 12 visit will be considered nonresponders for the primary analysis.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 95 of 143
15.3.1.1
Supportive analyses
The following supportive analyses for the primary endpoint are planned: 
1. The primary dose-response analysis and pairwise comparisons will be repeated for all 
subjects in the PPS to evaluate the effect of important protocol deviations on the analysis. 
2. The primary dose response analysis and pairwise comparisons will be repeated for all 
subjects in the RS to evaluate the consistency of the FAS with the intent-to-treat (ITT) 
principle. Subjects with no valid measurement of the primary efficacy variable at Baseline 
will be included as nonresponders.
3. The primary dose response analysis and pairwise comparisons will also be repeated for all 
individual components of the ASAS40 response to explore the effect of the signs and 
symptoms of the individual components on the composite endpoint. Since all ASAS 
components are continuous variables (eg, change from Baseline in PGADA), and analysis of 
covariance (ANCOVA) with treatment, region, and prior TNF inhibitor exposure as fixed 
effects and the Baseline values as covariate will be used for the analysis.
Additional sensitivity analyses to evaluate the assumptions related to the handling of missing 
data for the primary efficacy variable will be performed and are described in Section 15.7.
15.3.2
Other efficacy analyses
15.3.2.1
Analysis of the secondary efficacy variables
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, ASAS20 response and ASAS5/6) will be analyzed for treatment 
effects using pairwise comparisons based on the same method as that for the primary efficacy 
variable.
All continuous variables (ie, ASDAS-CRP, ASDAS, BASDAI, and BASFI) will be analyzed for 
treatment effects using pairwise comparisons based on an analysis of covariance (ANCOVA) 
model with treatment, region, and biologic prior treatment as fixed effects and the Baseline value 
as covariate.
Pairwise testing of each bimekizumab dose versus placebo will account for multiplicity by using 
a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from 
the highest dose to the lowest dose as described in Section 15.3.1.
Dose and exposure response will be assessed using a nonlinear mixed effects modeling to 
characterize the relationship between dose, exposure and ASAS response. The model will be 
partitioned into structural and stochastic models. The structural model describes the main trends 
and dependencies in the data, for example how drug concentrations depend on dose and time, or 
how ASAS response depend on drug exposure. The stochastic part of the model is further 
divided into the interindividual variability (IIV) and the residual unexplained variability (RUV). 
The IIV describes how individual specific parameters differ from the typical individual. The 
RUV describes the differences between the observations and the predictions from the model. 
Further details will be given in a separate data analysis plan and reported in a separate document.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 96 of 143
15.3.2.2
Analysis of the other efficacy variables
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS and ESS.
All categorical variables will be summarized using frequency tables by each visit.
All continuous variables will be summarized using descriptive statistics by each visit.
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in days from Baseline until the first date when the response is achieved. 
Subjects who discontinue study treatment prior to achieving a response will be censored at the 
date of study treatment discontinuation. Subjects who reach the Week 12 visit without achieving 
a response will be censored at the date of the Week 12 visit. 
The median time to response including the 2-sided 95% confidence interval will be calculated for 
each treatment. Between group differences (each bimekizumab dose vs placebo will be analyzed 
with the log-rank statistic.
All other efficacy variables will be analyzed using observed cases as treated and imputed with 
NRI for binary variables and multiple imputation (MI) for continuous variables (see 
Section 15.7).
Subjects in the ESS who discontinue with bimekizumab treatment during the Dose-Blind Period 
will be treated as missing and categorical/continuous variables will be imputed.
15.4
Subgroup analyses
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: 
•
Age
•
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•
Region
•
Anti-bimekizumab antibody status
•
TNF inhibitor exposure
•
Concomitant synthetic DMARDs vs no concomitant synthetic DMARDs
•
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
15.5
Planned safety and other analyses
15.5.1
Safety analyses
All safety variables will be analyzed for all subjects in the SS. In addition, safety analyses during 
the Dose-Blind Period will be conducted on all subjects in the DBS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 97 of 143
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®). Adverse events will be summarized descriptively by treatment group, primary 
system organ class, high level term, and preferred term. Additional tables will summarize AEs 
by intensity and relationship to IMP, AEs leading to withdrawal from the study, SAEs, and 
deaths. 
Treatment-emergent AEs will be defined as events that have a start date on or following the first 
administration of study treatment through the final administration of study treatment +140 days 
(covering the 20-week SFU Period). 
Laboratory values, urinary values, ECGs, vital signs, and extent of exposure will be presented 
descriptively by treatment group.
15.5.2
Other analyses
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS. Pharmacodynamic 
variables will be analyzed for all subjects in the PD-PPS.
Pharmacokinetic and PD analyses including the calculation of population estimates for total body 
clearance (CL/F) and volume of distribution (V/F) will be detailed in a separate data analysis 
plan and reported in a separate document. Plasma concentration-time data of bimekizumab and 
ASAS40 responder rates will be used as the PK and PD response. If data merits, a further PK/PD 
analysis on other PD variables may be performed.
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit.
Anti-bimekizumab antibody status will be summarized for each treatment at each scheduled 
visit.
The biomarker data including IL-17A, IL-17F, IL-6, and IL-23 concentrations will be 
summarized for each treatment at each scheduled visit.
In addition to the PD variables, whole blood will be stored to isolate deoxyribonucleic acid 
(DNA) which may be used to examine genetic and epigenetic changes. Analysis will include, but 
not be limited to genotyping of HLA alleles (HLA Cw6, HLAB27, etc).
15.6
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the primary efficacy, key safety, or PK/PD outcomes 
for an individual subject. The criteria for identifying important protocol deviations will be 
defined within the appropriate protocol-specific document. Important protocol deviations will be 
reviewed as part of the ongoing data cleaning process and all important deviations will be 
identified and documented prior to unblinding to confirm exclusion from analysis sets
15.7
Handling of dropouts or missing data
The analysis for the binary primary and secondary efficacy variables will use NRI for handling 
missing data. In NRI, each subject with missing data or who has discontinued double-blind study 
treatment prior to Week 12 will be counted as a nonresponder. Continuous secondary efficacy 
variables will be imputed using MI assuming that missingness is missing at random (MAR).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 98 of 143
Two sensitivity analyses will be performed for the primary dose response analysis and for the 
supportive analysis (3) (Section 15.3.1.1):
1. An analysis will be performed in which all available data at Week 12 will be considered. 
This analysis will be based on the ordered categorical analysis to evaluate dose-response as 
specified in the primary analysis. However, in this case, subjects will be analyzed according 
to their randomized treatment, even if they discontinued prior to Week 12 and were no longer 
on the randomized study treatment when the assessment was performed at Week 12. Even 
though efforts will be made to collect the primary outcome data for all subjects at Week 12, 
there may still be some subjects for whom Week 12 efficacy data cannot be obtained. In this 
case, the subjects will be assumed to be nonresponders. The estimand here is the difference 
in outcome improvement at the planned endpoint for all randomized participants 
(Mallinckrodt, 2012). This is an estimand of effectiveness to evaluate the de facto hypothesis. 
It should be noted that this measures something different from the primary analysis and could 
be confounded by placebo subjects who withdraw and are subsequently on another active 
medication at the time of the Week 12 assessment. Therefore, the results of this analysis 
should be interpreted in the appropriate context.
An additional sensitivity analysis will be based on observed data only for subjects who are 
still on the initially randomized treatment at Week 12. Subjects with missing data or who 
have prematurely discontinued study treatment will be excluded from the analysis. The same 
procedure described for the primary efficacy analysis of dose response will be used.
Sensitivity analyses will also be performed for the pairwise comparisons of bimekizumab doses 
versus placebo based on ASAS40 response at Week 12. The following analyses will be 
conducted:
1. Missing data will be imputed using MI. In MI, the missing value is replaced by a set of 
plausible values, where each value is a Bayesian draw from the conditional distribution of the 
missing data given the observed data. Intermittent missing data will be imputed using the 
Markov-Chain Monte Carlo [MCMC] method, followed by monotone regression for 
monotone missing data to evaluate the effect of the method for handling missing data on the 
analysis. The ASAS components will be imputed individually and then the ASAS response 
will be calculated using the complete datasets. The multiply imputed data sets will be 
analyzed using a logistic regression model with fixed effects fixed effects for treatment, 
region, and prior TNF inhibitor exposure. Finally, the results will be combined into a single 
inference using Rubin’s rule (Carpenter and Kenward, 2013). This procedure assumes a 
MAR pattern of missingness and corresponds to an estimand of what has been called the 
difference in outcome improvement if all subjects tolerated or adhered to treatment 
(Mallinckrodt et al, 2012).
2. The logistic regression model will be applied where all available data at Week 12 will be 
considered, as described in sensitivity analysis (1) for the primary dose-response efficacy 
analysis.
3. The logistic regression model will be applied where only observed data for subjects still on 
the initially randomized treatment at Week 12 will be considered, as described in sensitivity 
analysis (2) for the primary dose-response efficacy analysis.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 99 of 143
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model.
Other binary efficacy variables will be imputed using NRI and other continuous efficacy 
variables will be imputed using MI as described above.
15.8
Planned interim analysis and data monitoring
There is 1 interim analysis planned for this study. The interim analysis will be performed after all 
enrolled subjects have completed the 12 weeks Double-Blind Period. 
The objectives of this interim analysis are (i) to analyze the dose:exposure response for the 
ASAS response criteria to determine the optimal therapeutic dose(s) for subsequent studies, and 
(ii) to perform a comprehensive evaluation of all double-blind data of the study. 
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48. 
Safety data will be provided to an independent DMC. The DMC will review those safety data 
periodically. It is not planned for the DMC to review efficacy data, and no formal stopping rules 
will be applied.
15.9
Determination of sample size
A total of 285 subjects (57 in each treatment group) are planned to be randomized in this study. 
The primary efficacy analysis will be based on the FAS. While some randomized subjects may 
not be in the FAS, it is expected that this number will not impact the following calculations.
The sample size is calculated based on the ASAS40 response data from the Phase 3 studies in 
subjects with AS treated with secukinumab (MEASURE 1 and 2; Baeten et al, 2015). The 
ASAS40 response rates at Week 12 were reported to be 40% in both studies for the 
secukinumab 150mg dose while placebo response rates were 18% (MEASURE 1) and 9% 
(MEASURE 2). 
Based on those ASAS40 response rates and preliminary information on the bimekizumab
dose-response profile, ASAS40 response rates of 40.0%, 36.0%, 20.0%, 15.0%, and 12.0% at the 
end of a 12-week Treatment Period for bimekizumab 320mg, bimekizumab 160mg, 
bimekizumab 64mg, bimekizumab 16mg, and placebo have been assumed, respectively. Since 
the loading dose regimen of MEASURE 1 (iv) was different from MEASURE 2 (sc), the 
assumption for placebo response was based primarily on MEASURE 2, but with a weighting 
towards the higher placebo response rate of MEASURE 1.
The sample size for the primary objective of evaluating the dose-response relationship was 
calculated using a 2-sided test for detecting a linear trend across proportions (Nam, 1987) at a 
2-sided significance level of 0.05. Assuming 57 subjects in each treatment group, the test for 
detecting the overall dose response based on ASAS40 response is powered at >99% for the 
subjects with diagnosis of AS (ie, 57 subjects per group).
The sample size calculations were performed using the software nQuery Advisor® 7.0.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 100 of 143
16
ETHICS AND REGULATORY REQUIREMENTS
16.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the written Informed Consent Form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who conducted 
the informed consent discussion (Investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent Form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection.
If the Informed Consent Form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent Form by the IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization Form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent Form. An
eCRF must not be started, nor may any study specific procedure be performed for a given 
subject, without having obtained his/her written consent to participate in the study.
16.2
Subject identification cards
Upon signing the Informed Consent, the subject or legal representative will be provided with a 
subject identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times.
16.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, Informed
Consent Form, IB, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 101 of 143
and all other subject-related documents to be used for the study to the IRB/IEC for its review and 
approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification.
16.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
16.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 102 of 143
17
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
18
REFERENCES
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Barkham N, Keen HI, Coates LC, O'Connor P, Hensor E, Fraser AD, et al. Clinical and imaging 
efficacy of infliximab in HLA–B27–Positive patients with magnetic resonance imaging–
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Braun J. Axial spondyloarthritis: thoughts about nomenclature and treatment targets. Clin Exp 
Rheumatol. 2012;30:S132-5.
Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379-90.
Braun J, Baraliakos X. Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann 
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Braun J, Baraliakos X, Golder W, Brandt J, Rudwaleit M, Listing J, et al. Magnetic resonance 
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Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 103 of 143
Diderichsen PM, Cox E (Quantitative Solutions BV, Breda, NL). Comparative effectiveness 
modeling of treatment in ankylosing spondylitis. Final Report. UCB Celltech; 2016 Feb. Project 
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Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, et al. Development of 
the ASQL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 
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Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to 
defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease 
Activity Index. J Rheumatol. 1994;21:2286-91.
Haibel H, Brandt HC, Song IH, Brandt A, Listing J, Rudwaleit M, et al. No efficacy of 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 104 of 143
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 105 of 143
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 106 of 143
19
APPENDICES
19.1
Modified New York (mNY) Classification Criteria for AS
Table 19‒1: Modified New York (mNY) Classification Criteria for AS
Diagnosis
Clinical criteria:
a.
Low back pain and stiffness for more than 3 months which improves with exercise, but is 
not relieved by rest 
b.
Limitation of motion of the lumbar spine in both the sagittal and frontal planes.
c.
Limitation of chest expansion relative to normal values corrected for age and sex.
Radiologic criterion:
Sacroiliitis grade ≥2 bilaterally or grade 3 to 4 unilaterally
Grading
Definite ankylosing spondylitis if the radiologic criterion is associated with at least 1 clinical 
criterion
AS=ankylosing spondylitis; mNY=modified New York Criteria
Note: A second grading of “probable ankylosing spondylitis” is part of the modified NY criteria, but it is not
applicable for this study. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 107 of 143
19.2
Markedly abnormal laboratory values
Table 19‒2: Definitions of markedly abnormal hematology values
Parameter (RCTC units)
Markedly Abnormal Definition
Low
High
Hemoglobin (g/dL)
<LLN 
AND 
>2.0 decrease from baseline
N/A
Hemoglobin (g/dL)
<8.0
N/A
Leukocytes (total x 1000)
<2.0
N/A
Lymphocytes (x 1000)
<0.5
N/A
Neutrophils (x 1000)
<1.0
N/A
Platelets (x 1000)
<50
N/A
LLN=lower limit of normal; N/A = Not Applicable; RCTC=Rheumatology Common Toxicity Criteria
Data source: modified from Appendix Rheumatology Common Toxicity Criteria v.2.0 presented in 
Woodworth et al, 2007
a Withdrawal criteria for neutrophils is <0.5 (Section 6.3).
Table 19‒3: Definitions of markedly abnormal biochemistry values
Parameter (RCTC units)
Markedly Abnormal Definition
Low 
High
Alkaline Phosphatase
N/A
>3 x ULN
ALT
N/A
>3 x ULN
AST
N/A
>3 x ULN
Calcium (mg/dL)
<7.0
>12.5
Creatinine (mg/dL)
N/A
>1.8 x ULN
Glucose (mg/dL)
<40
>250
Potassium (mmol/L)
<3.0
>6.4
Sodium (mmol/L)
<125
N/A
Total bilirubin
N/A
≥2 x ULN
Uric acid
N/A
≥3 x ULN
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; RCTC=Rheumatology 
Common Toxicity Criteria; ULN=upper limit of normal
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 108 of 143
19.3
Protocol Amendment 1
Rationale for the amendment
The purpose of this protocol amendment is the following:
•
The SAE reporting fax number for the US and Canada was updated.
•
The extra-articular manifestations variable was removed from the other efficacy variables, as 
these will be assessed as AEs. In addition, the other objective regarding extra-articular 
manifestations was updated to be specific to enthesitis. 
•
The number of subjects to be included in the imaging evaluation was increased from 
10 subjects to 20 subjects at Baseline. The MRIs at Weeks 12 and 48 will be performed only 
for subjects who were classified as MRI-positive as per ASAS-OMERACT Criteria at 
Baseline. An MRI can be used to visualize inflammation in the SI joints and spine in addition 
to structural lesions. Inflammation of the SI joints and spine is a key feature of AS that is 
potentially amenable to treatment with bimekizumab. It is expected that reduction in 
inflammation in the SI joints and spine in MRI-positive subjects at Baseline can be detected 
within the 48-week Treatment Period. This effect can not be demonstrated for subjects who 
are MRI-negative at Baseline. Thus, MRI-negative subjects are excluded from the substudy.
•
A clarification that MRI assessments will occur at the Baseline Visit was added to all 
relevant sections.
•
Criteria for the definition of AE intensity were added in response to a regulatory agency 
request. 
•
All study variables have been rearranged for clarification reasons. 
In addition, minor typographical errors were corrected.
Modifications and changes
Global change #1
Abbreviations within the protocol and in the list of abbreviations have been adjusted as needed.
Global change #2
The following global change was made for all visits from Week 4 (Section 8.3.3) through 
Week 44 (Section 8.4.8).
•
Collect pulse and BP once after dosing (any time).
Has been changed to:
•
Collect pulse and BP once after dosing (any time).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 109 of 143
Global change #3
The following appendices and respective in-text references have been removed from the 
protocol.
•
Section 19.3: PGADA (NRS)
•
Section 19.4: Total spinal pain NRS and nocturnal spinal pain NRS
•
Section 19.5: Bath Ankylosing Spondylitis Functional Index (BASFI)
•
Section 19.6: Bath Ankylosing Disease Activity Index (BASDAI)
•
Section 19.7: Lateral spinal flexion
•
Section 19.8: BASMI – linear function
•
Section 19.9: ShortForm (SF36) Questionnaire
•
Section 19.10: MOS Sleep Scale Questionnaire
•
Section 19.11: ASQoL
•
Section 19.12: Tuberculosis Questionnaire
Specific changes
Change #1
Original text: 
Serious adverse event reporting
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA: +1 800 880 6949
or +1 866 890 3175
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 2421
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 110 of 143
Change #2
Section 1 Summary
Original text:
The secondary objectives of the study are to assess the efficacy of the individual dose regimens 
of bimekizumab compared to placebo, safety and tolerability, PK, PD, immunogenicity, and the 
exposure:response relationship of bimekizumab as it relates to efficacy and safety. The 
secondary efficacy variables include: Change from Baseline in Ankylosing Spondylitis Disease 
Activity Score  C reactive protein (ASDAS-CRP), Assessment in Axial SpondyloArthritis 
International Society 20% response criteria (ASAS20) response, Assessment in Axial 
SpondyloArthritis International Society 5 out of 6 response criteria (ASAS5/6) response, Change 
from Baseline in BASDAI, and Change from Baseline in BASFI, all at Week 12. Safety 
variables include incidence of adverse events (AEs) and serious adverse events (SAEs), 
withdrawal due to AEs, change from Baseline in vital signs, body weight, physical examination, 
ECG, and clinical laboratory variables.
Other objectives are to assess the impact on patient-reported quality of life (fatigue, sleep, and 
pain), extra-articular disease manifestations (uveitis, inflammatory bowel disease [IBD], and 
psoriasis), the impact of administration of bimekizumab on biological pathways relating to 
disease biology and response to therapy via candidate biomarker analysis and to enable genomic 
and proteomic analysis of subject samples and evaluation of the potential for subject 
stratification approaches, and to assess the impact of bimekizumab on inflammatory changes in 
the spine and sacroiliac (SI) joint using magnetic resonance imaging (MRI) in a subset of 
subjects (approximately 10 subjects per treatment arm). 
Has been changed to: 
The secondary objectives of the study are to assess the efficacy of the individual dose regimens 
of bimekizumab compared to placebo, safety and tolerability, PK, PD, immunogenicity, and the 
exposure:response relationship of bimekizumab as it relates to efficacy and safety. The 
secondary efficacy variables include: Change from Baseline in Ankylosing Spondylitis Disease 
Activity Score C-reactive protein (ASDAS-CRP), Assessment in Axial SpondyloArthritis 
International Society 20% response criteria (ASAS20) response, Assessment in Axial 
SpondyloArthritis International Society 5 out of 6 response criteria (ASAS5/6) response, Change 
from Baseline in BASDAI, and Change from Baseline in BASFI, all at Week 12. Safety 
variables include incidence of adverse events (AEs), serious adverse events (SAEs), and 
withdrawal due to AEs as secondary safety variables and change from Baseline in vital signs, 
body weight, physical examination, ECG, and clinical laboratory variables as other safety 
variables.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 111 of 143
Other objectives are to assess the impact on patient-reported quality of life (fatigue, sleep, and 
pain), extra articular disease manifestations (uveitis, inflammatory bowel disease [IBD], and 
psoriasis), the impact of administration of bimekizumab on biological pathways relating to 
disease biology and response to therapy via candidate biomarker analysis, and to enable genomic 
and proteomic analysis of subject samples and evaluation of the potential for subject 
stratification approaches, and to assess the impact of bimekizumab on inflammatory changes in 
the spine and sacroiliac (SI) joint using magnetic resonance imaging (MRI) in a subset of 
subjects (approximately 10 subjects per treatment arm at Baseline). 
Change #3 
Section 2.1.1 Clinical studies
Original text: 
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, and PA0007 in 53 subjects with 
PsA.
Has been changed to: 
Four clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, PA0007 in 53 subjects with PsA, 
and UP0031 in 12 healthy volunteers.
Change #4
Section 2.1.1 Clinical studies
The following text has been added: 
UP0031 was a Phase 1, open-label, parallel-group, randomized, single-dose study to evaluate the 
BA, PK, and tolerability of 2 different formulations of bimekizumab in healthy subjects. There 
were no treatment-emergent adverse events (TEAEs) leading to discontinuation, and no SAEs or 
fatalities were reported. 
Change #5
Section 2.1.1 Clinical studies
Original text: 
Two additional studies of bimekizumab are ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
(CZP; Cimzia®) therapy in subjects with moderate to severe RA. UP0031 is an open-label, 
parallel-group, single-dose study designed to evaluate the relative bioavailability and tolerability
of 2 dose levels of UCB4940 (bimekizumab) given as 2 x80mg or 1x 160mg given via sc 
injection in healthy subjects.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 112 of 143
Has been changed to: 
One additional study of bimekizumab is ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
(CZP; Cimzia®) therapy in subjects with moderate to severe RA. UP0031 is an open label, 
parallel group, single dose study designed to evaluate the relative bioavailability and tolerability
of 2 dose levels of UCB4940 (bimekizumab) given as 2 x80mg or 1x 160mg given via sc 
injection in healthy subjects.
Change #6
Section 3.3 Other objectives
Original text: 
To assess extra-articular disease manifestations (enthesitis, uveitis, inflammatory bowel disease, 
and psoriasis)
Has been changed to: 
To assess the impact on extra articular disease manifestations (enthesitis, uveitis, inflammatory 
bowel disease, and psoriasis) enthesitis
Change #7
Section 4 Study Variables
Original text: 
4
STUDY VARIABLES
4.1 Efficacy variable(s)
4.1.1 Primary efficacy variable
The primary efficacy variable for this study is as follows:
•
ASAS40 response at Week 12 
4.1.2 Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Change from Baseline in ASDAS-CRP at Week 12
•
ASAS20 response at Week 12
•
ASAS5/6 response at Week 12
•
Change from Baseline in BASDAI at Week 12 
•
Change from Baseline in BASFI at Week 12
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 113 of 143
4.1.3 Other efficacy variables
Other efficacy variables will be assessed as specified in Table 5‒1 (analyses at all time points not 
specified in Section 4.1.1 or Section 4.2.1 are exploratory):
•
ASAS40 response
•
Time to ASAS40 response
•
Change from Baseline in ASDAS-CRP
•
ASDAS status (eg, inactive disease, moderate, high and very high disease activity)
•
ASAS20 response 
•
Time to ASAS20 response
•
ASAS5/6 response
•
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) 
•
ASAS partial remission 
•
Change from Baseline in BASDAI 
•
Change from Baseline in BASFI 
•
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
•
Occurrence of extra-articular manifestations
−
Uveitis flares (as determined by an ophthalmologist or other eye specialist, as 
appropriate)
−
Inflammatory bowel disease flares (as determined by a gastroenterologist, as appropriate)
−
Psoriasis disease activity
•
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
•
Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Change from Baseline in total and nocturnal spinal pain (NRS)
•
Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
•
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey) 
•
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
•
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 114 of 143
•
Change from Baseline in: 
−
Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index for Assessment 
of Spinal Inflammation in AS, and 
−
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score 
•
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores 
•
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.2 PK and PD variables
4.2.1 PK variables
The PK variables are plasma concentrations of bimekizumab, total body clearance (CL/F), and 
volume of distribution (V/F)
4.2.2 PD variables
The PD variables are concentrations of cytokines of relevance to the IL-17A/F signaling pathway 
and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-6, and TNFα 
4.3 Pharmacogenomic variables
4.3.1 Genomic, proteomic, and metabolite variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes. 
4.4 Immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers. 
•
Anti-bimekizumab antibody detection prior to and following study treatment
•
Serum complement concentrations.
•
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
CD19, CD4, CD8, and CD69 (using fluorescence activated cell sorting). 
•
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 115 of 143
4.5 Safety variables
Safety variables to be assessed as specified in Table 5‒1 are as follows: 
•
Incidence of AEs and SAEs
•
Withdrawal due to AEs
•
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight 
•
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas [QTcB and QTcF]), 
including changes from Baseline Electrocardiogram (ECG) variables 
•
Change from Baseline in clinical laboratory variables (hematology, biochemistry, and 
urinalysis)
Has been changed to:
4
STUDY VARIABLES
4.1 Primary variable(s)
4.1.1 Primary efficacy variable
The primary efficacy variable for this study is as follows:
•
ASAS40 response at Week 12 
4.2 Secondary variables
4.2.1 Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
•
Change from Baseline in ASDAS-CRP at Week 12
•
ASAS20 response at Week 12
•
ASAS5/6 response at Week 12
•
Change from Baseline in BASDAI at Week 12 
•
Change from Baseline in BASFI at Week 12
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 116 of 143
4.2.2 Secondary safety variables
Assessment time points for safety variables are specified in Table 5‒1. Variables are as follows: 
•
Incidence of AEs and SAEs
•
Withdrawal due to AEs
4.3 Other variables
4.3.1 Other efficacy variables
Assessment time points for the other efficacy variables are specified in Table 5‒1 (analyses at 
all time points not specified in Section 4.1.1 or Section 4.2.1 are exploratory). Variables are as 
follows:
•
ASAS40 response
•
Time to ASAS40 response
•
Change from Baseline in ASDAS-CRP
•
ASDAS status (eg, inactive disease, moderate, high and very high disease activity)
•
ASAS20 response 
•
Time to ASAS20 response
•
ASAS5/6 response
•
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) 
•
ASAS partial remission 
•
Change from Baseline in BASDAI 
•
Change from Baseline in BASFI 
•
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
•
Occurrence of extra articular manifestations
Uveitis flares (as determined by an ophthalmologist or other eye specialist, as 
appropriate)
−
Inflammatory bowel disease flares (as determined by a gastroenterologist, as appropriate)
Psoriasis disease activity
•
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
•
Physician’s Global Assessment of Disease Activity (PhGADA)
•
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA)
•
Change from Baseline in total and nocturnal spinal pain (NRS)
•
Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 117 of 143
•
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey) 
•
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
•
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
•
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−
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of Spinal Inflammation in AS, and 
−
Ankylosing Spondylitis spine MRI- activity (ASspiMRI-a) in the Berlin modification 
score 
•
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores 
•
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.3.2 Other safety variables
Assessment time points for other safety variables are specified in Table 5‒1. Variables are as 
follows: 
•
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight 
•
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas [QTcB and QTcF]), 
including changes from Baseline Electrocardiogram (ECG) variables 
•
Change from Baseline in clinical laboratory variables (hematology, biochemistry, and 
urinalysis)
4.3.3 Other PK and PD variables
•
The PK variables are plasma concentrations of bimekizumab, total body clearance (CL/F), 
and volume of distribution (V/F).
•
The PD variables are concentrations of cytokines of relevance to the IL-17A/F signaling 
pathway and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-6, and 
TNFα. 
4.3.4 Other immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers. 
•
Anti-bimekizumab antibody detection prior to and following study treatment
•
Serum complement concentrations.
•
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 118 of 143
4.3.5 Other pharmacogenomic, proteomic, and metabolite variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes. 
Change #8
Section 5.1.2 Double-Blind Period
Original text: 
At Baseline/Day 1, subjects will be randomized 1:1:1:1:1 (stratified by region and prior TNF 
inhibitor exposure) to receive the following blinded IMP treatment regimens at the clinical site. 
The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% of 
the total study population. Therefore, each arm will have approximately 18 TNF inhibitor 
experienced subjects in a total of 57 subjects per arm.
Has been changed to:
At Baseline/Day 1, subjects will be randomized 1:1:1:1:1 (stratified by region and prior TNF 
inhibitor exposure) to receive the following blinded IMP treatment regimens at the clinical site. 
The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% of 
the total study population. Therefore, each arm will have approximately 18 TNF inhibitor 
experienced subjects in a total of 57 subjects per arm.
Change #9
Section 5.1.7 Radiographic evaluation
Original text: 
5.1.7 Radiographic evaluation
In a subpopulation of AS0008, MRIs of the spine and SI joints will be performed in 
approximately 10 subjects per treatment arm at Baseline, Week 12, and Week 48. Analyses will 
be exploratory in nature and will be performed at selected sites.
Has been changed to:
5.1.7 Imaging evaluation
In a subpopulation of AS0008, MRIs of the spine and SI joints will be performed in 
approximately 20 subjects per treatment arm at Baseline. Magnetic resonance imaging at
Week 12 and Week 48 will be performed only for subjects who are MRI-positive at Baseline
based on an ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) 
assessment. The Baseline MRI should be performed after confirmation of eligibility for the 
study based on screening assessments and before the first bimekizumab injection. Magnetic 
resonance imaging at Week 12 and Week 48 should be performed as close to the 
Week 12/Week 48 Visit as possible. Further details are provided in Section 9.15. Analyses 
will be exploratory in nature and will be performed at selected sites.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 119 of 143
Change #10
Section 5.2 Table 5-1, footnote d
Original text: 
d At Baseline/Day 1 and Week 1, collect pulse and BP prior to drug administration and then at 30 minutes and 1 
hour after dosing. At all other visits collect pulse and BP prior to drug administration and once after dosing (any 
time). All other procedures are done prior to dosing. 
Has been changed to:
d At Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 30 minutes and 1 
hour after dosing. At all other visits collect pulse and BP prior to drug administration and once after dosing (any 
time). All other procedures are done prior to dosing. 
Change #11
Section 5.2 Table 5-1, footnote n and p
Original text: 
n An MRI of the spine and sacroiliac joints will be performed in a subpopulation of approximately 10 subjects per 
treatment arm for exploratory purposes at Screening, Week 12, and Week 48. The MRI will be read centrally. 
p The minimum time between doses during the Double-Blind Period should be no less than 26 days and no more 
than 30 days and during the Dose-Blind Period should be no less than 24 days and no more than 32 days.
Has been changed to:
n An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 20 subjects per 
treatment arm at Screening Baseline. A central reader will assess Baseline MRIs to identify MRI-positive 
subjects as per the ASAS-Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria. An 
MRI at Week 12 and Week 48 will be performed for those subjects who were MRI-positive at Baseline. The 
Baseline MRI should be performed after confirmation of eligibility based on screening assessments for the 
study and before the first bimekizumab injection. Magnetic resonance imaging at Week 12 and Week 48 
should be performed as close to the Week 12/Week 48 Visit as possible. For logistical reasons, it may not be 
possible to schedule the MRIs at the actual visit date and an additional visit for the MRI may be required.
p The minimum time between doses during the Double-Blind Period should be no less than 25 days and no more 
than 31 days and during the Dose-Blind Period should be no less than 24 days and no more than 32 days.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 120 of 143
Change #12
Section 6.2 Inclusion criterion 11
Original text: 
11. Subjects taking sulfasalazine (up to 3mg/day) or hydroxychloroquine (up to 400mg per day 
total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, 
with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule 
should remain stable up to Week 16.  
Has been changed to: 
11. Subjects taking sulfasalazine (up to 3mg/day) or hydroxychloroquine (up to 400mg per day
total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, 
with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule 
should remain stable up to Week 16
Change #13
Section 6.2, Inclusion criterion 12
Original text: 
12. Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have: 
−
experienced an inadequate response to previous treatment given for at least 3 months 
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
−
lost access to TNF inhibitor for other reasons
Has been changed to: 
12. Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have: 
−
experienced an inadequate response to previous treatment given for at least 3 months
12 weeks
−
been intolerant to administration (eg, had a side effect/AE that led to discontinuation) 
−
lost access to TNF inhibitor for other reasons
Change #14
Section 6.2 Exclusion criterion 3
Original text: 
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 3 months or at least 5 half-lives whichever is greater.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 121 of 143
Has been changed to:
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 3 months 12 weeks or at least 5 half-lives whichever is greater.
Change #15
Section 6.2 Exclusion criterion 10
Original text: 
10. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), 
Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
Has been changed to:
12. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), 
Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
Change #16
Section 6.3 Withdrawal criterion 8
Original text: 
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 6.3.1; neutropenia <0.5x109/mL; lymphopenia <0.5x109/mL. Any 
laboratory value or change judged to be clinically significant by the Investigator, and/or any 
lab values meeting the Rheumatology Common Toxicity Criteria (RCTC) Grade 4 criteria 
(with the exception of neutrophils which will be permitted with the above withdrawal 
criterion [neutropenia <0.5x109/mL]; Table 19‒2 and Table 19‒3) must be discussed with the 
medical monitor before the subject is dosed again. (Refer to Section 6.3.1 for withdrawal 
criteria in relation to potential drug-induced liver injury [PDILI].)
Has been changed to: 
8. Subject develops laboratory abnormalities (with or without clinical symptoms) of ALT or 
AST as defined in Section 6.3.1; neutropenia <0.5x109/mL; lymphopenia <0.5x109/mL. Any
laboratory value or change judged to be clinically significant by the Investigator should 
prompt consideration of whether the subject should continue on IMP. For clarification, 
laboratory values that are markedly abnormal as per Table 19-2 and Table 19‒3 will be 
flagged to the Investigator and to the medical monitor but do not trigger mandatory 
withdrawal unless listed above and/or any lab values meeting the Rheumatology Common 
Toxicity Criteria (RCTC) Grade 4 criteria (with the exception of neutrophils, which will be 
permitted with the above withdraw criterion [neutropenia <0.5x109/mL]; Table 19 2 and 
Table 19 3) must be discussed with the medical monitor before the subject is dosed again
(Refer to Section 6.3.1 for withdrawal criteria in relation to potential drug induced liver 
injury [PDILI].)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 122 of 143
Change #17
Section 7.3 Packaging
The following text has been added: 
Bimekizumab and placebo will be packaged and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. They will be suitably 
packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in 
the IMP Handling Manual.
Change #18
Section 7.8.2 Prohibited concomitant treatments (medications and therapies), 
Table 7-1
Original text: 
Drug class
Dose
Exclusion criteria
Analgesics, including opioid analgesics 
(acetaminophen/paracetamol, etc)
Any dose 
Any ad hoc use in the 24 hours prior to any 
study visit. 
Stable doses of analgesics permitted.
NSAIDs/COX-2 inhibitors
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Oral corticosteroids
Any dose regimen
Any change in dose/dose regimen in the 
28 days prior to the Baseline Visit
Intramuscular (im)/intravenous (iv)/
intra-articular (ia) corticosteroids/bursal 
corticosteroids 
Any dose 
Use in the 28 days prior to the Baseline 
Visit. 
Intra-articular hyaluronic acid 
Any dose 
Any use in the 6 months prior to the 
Baseline Visit. 
DMARDs:
-azathioprine
-cyclosporine,
-cyclophosphamide,
-mycophenolic acid,
-mycophenylate mofetil
-any other small molecule DMARDs 
(eg tofacitinib, apremilast)
Any dose
Use within 12 weeks prior to the Baseline 
Visit.
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #10 is met
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 123 of 143
Drug class
Dose
Exclusion criteria
DMARDs:
-leflunomide 
Any dose 
Use in the 6 months prior to the Baseline 
Visit unless a cholestyramine washout has 
been performed; in which case, use up to 
28 days prior to the Baseline Visit is 
acceptable. 
TNF inhibitors
-infliximab (IFX)
-adalimumab (ADA)
-etanercept (ETN)
-golimumab (GOL)
-certolizumab pegol (CZP)
Any dose
For IFX, ADA, GOL, and CZP, any use 
within the 3 months prior to the Baseline 
Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
This applies to biosimilar versions of any 
TNF inhibitors.
Has been changed to: 
Drug class
Dose
Exclusion criteria
Analgesics, including opioid analgesics 
(acetaminophen/paracetamol, etc)
Any dose 
Any ad hoc use in the 24 hours prior to any 
study visit. 
Stable doses of analgesics permitted.
NSAIDs/COX-2 inhibitors
Any dose regimen
Any change in dose/dose regimen in the 
14 days prior to the Baseline Visit
Oral corticosteroids
Any dose regimen
Any change in dose/dose regimen in the 28
14 days prior to the Baseline Visit
Intramuscular (im)/intravenous (iv)/
intra-articular (ia) corticosteroids/bursal 
corticosteroids 
Any dose 
Use in the 28 days prior to the Baseline 
Visit. 
Intra-articular hyaluronic acid 
Any dose 
Any use in the 6 months prior to the 
Baseline Visit. 
DMARDs:
-azathioprine
-cyclosporine,
-cyclophosphamide,
-mycophenolic acid,
-mycophenylate mofetil
-any other small molecule DMARDs 
(eg tofacitinib, apremilast)
Any dose
Use within 12 weeks prior to the Baseline 
Visit.
MTX
Any dose regimen
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #10 is met
SSZ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 124 of 143
Drug class
Dose
Exclusion criteria
HCQ
Any dose
Use within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met
DMARDs:
-leflunomide 
Any dose 
Use in the 6 months prior to the Baseline 
Visit unless a cholestyramine washout has 
been performed; in which case, use up to 
28 days prior to the Baseline Visit is 
acceptable. 
TNF inhibitors
-infliximab (IFX)
-adalimumab (ADA)
-etanercept (ETN)
-golimumab (GOL)
-certolizumab pegol (CZP)
Any dose
For IFX, ADA, GOL, and CZP, any use 
within the 3 months 12 weeks prior to the 
Baseline Visit
For ETN, use within the 28 days prior to 
the Baseline Visit.
This applies to biosimilar versions of any 
TNF inhibitors.
Change #19
Section 8.1 Screening (Visit 1)
The following paragraphs have been added: 
Subjects who initially fail to meet selected eligibility criteria (including but not limited to 
documented completion of LTBI prophylactic therapy) or for whom eligibility assessments 
could not be completed as planned may be rescreened once after discussion with the 
Medical Monitor.
The MRI (done at selected sites) can be performed prior to the Baseline (Day 1, first dose of 
IMP, Visit 2) if eligibility is confirmed based on screening assessments, and before the first 
dose of IMP.
Change #20
Section 8.2 Baseline (Day 1, first dose of IMP) (Visit 2)
Original text:
•
Obtain MRI of spine and the SI joint if the subject is participating in the MRI substudy. 
Has been changed to: 
•
Obtain MRI of spine and the SI joint if the subject is participating in the MRI substudy. The 
Baseline MRI should be performed after confirmation of eligibility based on screening 
assessments for the study and before the first bimekizumab injection.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 125 of 143
Change #21
Section 8.3.5 Week 12 (+/-3 days) (Visit 7)
Original text: 
The following procedures of assessments will be completed prior to administration of IMP:
…
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy. 
…
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing (any time).
Has been changed to: 
The following procedures of assessments will be completed prior to administration of IMP:
…
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 12 
should be performed as close to the Week 12 Visit as possible.
…
The following procedures of assessments will be completed following administration of IMP:
•
Collect pulse and BP once after dosing (any time pulse and BP to be collected 30 minutes 
and 1 hour after dosing).
Change #22
Section 8.4.9 Week 48 (+/-4 days) (Visit 16)
Original text: 
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 126 of 143
Has been changed to: 
•
Obtain MRI of spine and the sacroiliac joint if the subject is participating in the MRI 
substudy and is MRI-positive at Baseline. Magnetic resonance imaging at Week 48 
should be performed as close to the Week 48 Visit as possible.
Change #23
Section 9.1 ASAS20, 40, ASAS 5/6 response, and ASAS partial remission
Original text: 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and CRP as more objective measures (Brandt et al, 2004).
Has been changed to: 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and hs-CRP as more objective measures (Brandt et al, 
2004).
Change #24
Section 9.7 Spinal mobility
Original text: 
Lateral spinal flexion is measured with the subject’s heels and back resting against the wall with 
no flexion in the knees and no bending forward. The subject lets the arm hang normally with the 
palm of the hand resting against the outer thigh and the fingers extended. A mark is drawn on the 
thigh at the tip of the middle finger. The subject is then asked to bend sideways without bending 
the knees or lifting the heels, while sliding the hand down the thigh. At the point of furthest 
reach, another mark is drawn at the tip of the middle finger. The distance between the first and 
second mark is measured to the nearest 0.1cm. An alternative method is to measure the distances 
to the 2 lines from the floor and record the difference. The better of 2 tries is recorded for left 
and right separately. The mean of the left and right is reported for lateral spine flexion (in cm to 
the nearest 0.1cm) (Sieper et al, 2009) (Appendix Section 19.7).
Has been deleted. 
Change #25
Original text: 
Section 9.10 BASFI
The BASFI is described in Section 9.4 above.
Has been deleted. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 127 of 143
Change #26
Section 9.12 Extra-articular manifestations
Original sections and text:
Information regarding uveitis, enthesitis, inflammatory bowel disease, and psoriasis disease 
activity will be captured. Enthesitis is assessed via MASES.
Section 9.13 MASES
The MASES is an index that measures the severity (ie, intensity and extent) of enthesitis through 
the assessment of 13 entheses (bilateral costochondral 1, costochondral 7, anterior superior iliac 
spine, posterior iliac spine, iliac crest and proximal insertion of the Achilles tendon sites, and the 
fifth lumbar vertebral body spinous process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 
1 and then summed for a possible score of 0 to 13.
Have been merged and changed to: 
Section 9.12 Extra artucilar manifestations
Information regarding uveitis, enthesitis, inflammatory bowel disease, and psoriasis disease 
activity will be captured. Enthesitis is assessed via MASES.
Section 9.10 MASES
Enthesitis is assessed with MASES. The MASES is an index that measures the severity (ie, 
intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 1 and then summed for a possible 
score of 0 to 13.
Change #27
Section 9.12 PhGADA
Original text: 
9.14 PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 100=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 128 of 143
Has been changed to: 
9.11 PhGADA
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in 
which 0=very good, asymptomatic and no limitations of normal activities and 100 10=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities.
Change #28
Original text: 
Section 9.15 Total and nocturnal spinal pain
Assessment of total and nocturnal spinal pain was described above in Section 9.3.
Has been deleted. 
Change #29
Section 9.15 MRI Assessment (SPARCC and ASspiMRI), paragraph 2
Original text: 
9.19 MRI Assessment (SPARCC and ASspiMRI)
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
10 subjects per treatment arm at Screening, Week 12, and Week 48. Additional details for 
standardized performance and processing of MRIs will be provided in an MRI manual. The 
MRIs will be read centrally by readers who are blinded to treatment assignment and 
chronological order of the MRIs according to a charter for independent imaging assessment.  
Has been changed to:
9.15 MRI Assessment (SPARCC and ASspiMRI)
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 
20 subjects per treatment arm at Screening Baseline. A central reader will assess Baseline 
MRIs to identify MRI-positive subjects as per the ASAS-Outcome Measures in 
Rheumatology Clinical Trials (OMERACT) criteria. An MRI at Week 12 and Week 48 will 
be performed for those subjects who were MRI-positive at Baseline. The Baseline MRI 
should be performed after confirmation of eligibility based on screening assessments for 
the study and before the first bimekizumab injection. Magnetic resonance imaging at 
Week 12 and Week 48 should be performed as close to the Week 12/Week 48 Visit as 
possible. Additional details for standardized performance and processing of MRIs will be 
provided in an MRI manual. The MRIs will be read centrally by readers who are blinded to 
treatment assignment and chronological order of the MRIs according to a charter for independent 
imaging assessment.  
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 129 of 143
Change #30
Section 12.1.5 Description of adverse events
Original text:
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines.
Has been changed to:
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the intensity of an AE in the eCRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria:
•
Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere 
with his/her usual activities and/or is of no clinical consequence
•
Moderate: the AE interferes with the usual activities of the subject or it is of some 
clinical consequence
•
Severe: the subject is unable to work normally or to carry out his/her usual activities, or 
the AE is of definite clinical consequency
Details for completion of the Adverse Event eCRF (including judgment of intensity and
relationship to IMP) are described in the eCRF Completion Guidelines.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 130 of 143
Change #31
Section 12.5 Laboratory measurements, Table 12-2
Original text:
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
Has been changed to:
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 131 of 143
Hematology
Chemistry
Urinalysis
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
Change #32
Section 12.6.1 Vital signs
Original text:
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 1, collect pulse and BP prior to drug administration and then at 
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing (any time).
Has been changed to:
The Investigator or designee should measure all vital signs (systolic and diastolic BP, 
temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
Baseline/Day 1 and Week 12, collect pulse and BP prior to drug administration and then at 
30 minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing (any time).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 132 of 143
Change #33
Section 12.6.5 Tuberculosis and TB risk factor assessment and management, 
Exclusion criteria at Screening
Original text:
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen. 
Has been changed to:
Exclusion Criteria at Screening
Subjects with known TB infection, at high risk of acquiring TB infection, with LTBI*, or current 
or history of NTMB infection.
*Subjects with LTBI may enter the study only after they have completed at least 8 weeks of 
appropriate prophylactic therapy and thereafter, will continue and complete the entire regimen. 
Following consultation with the Medical Monitor, subjects may be rescreened after 
completion at least 8 weeks of LTBI prophylactic therapy.
Change #34
Section 15.1 Definition of analysis sets
Original text:
The PK-PPS will consist of all randomized subjects who took at least 1 dose of IMP and provide 
at least 1 quantifiable plasma concentration postdose.
The PD-PPS will consist of all randomized subjects who took at least 1 dose of IMP and provide 
at least 1 PD measurement postdose that is without important protocol deviation affecting that 
time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. Subjects who are eligible for the ESS, but do not receive 
rescue medication, remain in the DBRS.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 133 of 143
Has been changed to:
The Pharmacokinetic Per Protocol Set (PK-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations affecting the pharmacokinetic 
variables, as confirmed during ongoing data cleaning meetings prior to database lock. 
The Pharmacodynamic Per Protocol Set (PD-PPS) will consist of all randomized subjects who 
took at least 1 dose of IMP and provide at least 1 PD measurement postdose that is without 
important protocol deviation affecting that time point.
The Dose-Blind Set (DBS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period including the dose at 
Week 12.
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved an 
at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period 
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved an at least 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. Subjects who are eligible for the ESS, but do not receive 
rescue medication, remain in the DBRS.
Change #35
Section 15.4 Subgroup analyses
Original text:
•
BASDAI (≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Has been changed to:
•
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Change #36
Section 15.5.1 Safety analyses
The following paragraph has been added:
Treatment-emergent AEs will be defined as events that have a start date on or following 
the first administration of study treatment through the final administration of study 
treatment +140 days (covering the 20 week SFU Period).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 134 of 143
Change #37
Section 15.5.2 Other analyses
Original text:
Pharmacokinetic and PD analyses will be detailed in a separate data analysis plan and reported in 
a separate document. Plasma concentration-time data of bimekizumab and ASAS40 responder 
rates will be used as the PK and PD response. If data merits, a further PK/PD analysis on other 
PD variables may be performed.
Has been changed to:
Pharmacokinetic and PD analyses including the calculation of population estimates for total 
body clearance (CL/F) and volume of distribution (V/F) will be detailed in a separate data 
analysis plan and reported in a separate document. Plasma concentration-time data of 
bimekizumab and ASAS40 responder rates will be used as the PK and PD response. If data 
merits, a further PK/PD analysis on other PD variables may be performed.
Change #38
Table 19-1 Table footnote
Original text:
Note: A second grading of “probably ankylosing spondylitis” is part of the modified NY criteria, but it is not 
applicable for this study. It is included here for completeness. The grading will be probable ankylosing spondylitis if 
3 clinical criteria are present and the radiologic criterion is present without any signs or symptoms satisfying the 
clinical criteria (other causes of sacroiliitis should be considered).
Has been changed to:
AS=ankylosing spondylitis; mNY=modified New York Criteria
Note: A second grading of “probable ankylosing spondylitis” is part of the modified NY criteria, but it is not 
applicable for this study. It is included here for completeness. The grading will be probable ankylosing spondylitis if 
3 clinical criteria are present and the radiologic criterion is present without any signs or symptoms satisfying the 
clinical criteria (other causes of sacroiliitis should be considered).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 135 of 143
19.4
Protocol Amendment 2
Rationale for the amendment
The purpose of this substantial protocol amendment is the following:
•
To update the study contact details for the sponsor study physician and clinical trial 
biostatistician.
•
To revise the withdrawal criteria section to provide instructions for the management of 
subjects with newly diagnosed IBD or with IBD flares during the study.
•
Amend the time window between doses during the Double-Blind Period of the study.
•
To revise and clarify the SAE criteria for pregnancy for consistency.
•
Amend the table for identification/exclusion of alternative etiology to include ALT and AST.
Modifications and changes
Global changes
No global changes have been made. Specific changes are listed below.
Specific changes
Change #1
LIST OF ABBREVIATIONS
The following abbreviation and definition was added: 
RCTC
Rheumatology Common Toxicity Criteria
Change #2
STUDY CONTACT INFORMATION
Original text:
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Has been changed to: 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 136 of 143
Name:
, MD, MSc, PhD
, MD
Address:
UCB Pharma Ltd. UCB BIOSCIENCES Inc.
208 Bath Road 8010 Arco Corporate Drive
Slough, SL1 3WE Raleigh, NC 27617
UNITED KINGDOM UNITED STATES
Phone:
Change #3
STUDY CONTACT INFORMATION
Original text: 
Clinical Trial Biostatistician
Name:
Dr. 
, Senior Biostatistician
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str.10
40789 Monheim am Rhein
GERMANY
Phone:
Has been changed to: 
Clinical Trial Biostatistician
Name:
, MSDr. 
, Senior 
Biostatistician
Address:
UCB BIOSCIENCES Inc.GmbH
8010 Arco Corporate Drive Alfred Nobel Str.10
Raleigh, NC 2761740789 Monheim am Rhein
UNITED STATESGERMANY 
Phone:
Change #4
Section 6.3 Withdrawal Criteria
The following was added to the withdrawal criteria:
11. Subjects with newly diagnosed IBD or with IBD flares during the study must:
REDACTED
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 137 of 143
−
Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist
−
Discontinue IMP and be followed-up until resolution of active IBD symptoms
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact the 
Medical Monitor and UCB study physician to confirm the subject's suitability for continued 
participation in the study.
Change #5
Section 7.2 Treatments to be administered, paragraph 2
Original text: 
The IMP (bimekizumab and placebo) will be administered at the times indicated in Table 5‒1. 
The minimum time between doses during the Double-Blind Period should be no less than 26 
days and no more than 30 days and during the Dose-Blind Period should be no less than 24 days 
and no more than 32 days.
Has been changed to: 
The IMP (bimekizumab and placebo) will be administered at the times indicated in Table 5‒1. 
The minimum time between doses during the Double-Blind Period should be no less than 256
days and no more than 310 days and during the Dose-Blind Period should be no less than 24 
days and no more than 32 days.
Change #6
Section 7.3 Packaging
Original text: 
Bimekizumab and placebo will be packaged and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. They will be suitably packaged in 
such a way as to protect the product from deterioration during transport and storage. Further 
information regarding storage and transport conditions are provided in the IMP Handling 
Manual.
Has been changed to: 
Bimekizumab and placebo will be manufactured, packaged and labeled according to Good 
Manufacturing Practice (GMP) guidelines and applicable laws or regulations. They will be 
suitably packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in the IMP 
Handling Manual.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 138 of 143
Change #7
Section 12.1.8 Pregnancy, paragraph 5
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective for 
a medical condition or spontaneous), unintended pregnancy after hormonal contraceptive failure 
(if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal demise, or any 
congenital anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report Form.
Has been changed to: 
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective 
abortion when medically indicated (e.g. when pregnancy is endangering life or health of 
woman or when fetus will be born with severe abnormalities), unintended pregnancy after 
hormonal contraceptive failure (if the hormonal contraceptive was correctly used), ectopic 
pregnancy, fetal demise, or any congenital anomaly/birth defect of the baby. Those SAEs 
must be additionally reported using the Investigator SAE Report form.
Change #8
Section 12.5.1.4
Testing: identification/exclusion of alternative etiology, Table 
12-4 
Original table: 
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
body
body
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 139 of 143
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
Has been changed to: 
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
ALT, AST
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 140 of 143
Additional
Prothrombin time/INR
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
Change #9
Section 17.1
Markedly abnormal laboratory values, Tables 17-1 (Definitions of markedly 
abnormal hematology values) and 17-2 (Definitions of markedly abnormal biochemistry values)
Amended units in both table headers: 
Parameter (SI units)
Markedly Abnormal Definition
Low
High
Has been changed to:
Parameter (SIRCTC units)
Markedly Abnormal Definition
Low
High
Change #10
Section 17.1
Markedly abnormal laboratory values, Table 17-1 (Definitions of markedly 
abnormal hematology values), abbreviations in table footer:
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international
Has been changed to:
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international RCTC= 
Rheumatology Common Toxicity Criteria
Change #11
Section 17.1
Markedly abnormal laboratory values, Table 17-2 (Definitions of markedly 
abnormal biochemistry values), abbreviations in table footer:
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 141 of 143
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; 
SI=standard international; ULN=upper limit of normal
Has been changed to:
LLN=lower limit of normal; N/A = Not Applicable; SI=standard international RCTC=
Rheumatology Common Toxicity Criteria
REDACTED COPY 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 142 of 143
20
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
REDACTED COPY
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
AS0008
Confidential
Page 143 of 143
21
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

SAP_001.pdf: 
UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 1 of 194
STATISTICAL ANALYSIS PLAN AMENDMENT 5
Study: AS0008
Product: Bimekizumab
A multicenter, Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose 
ranging study to evaluate the efficacy and safety of bimekizumab in subjects with active 
ankylosing spondylitis
SAP/Amendment Number
Date
Final SAP
Amendment 1
4 Apr 2017
16 Aug 2017
Amendment 2
06 Nov 2017
Amendment 3
02 Mar 2018
Amendment 4
30 Jul 2018
Amendment 5
07 Sep 2018
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.
REDACTED COPY 
7
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 2 of 194
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................7 
1 
INTRODUCTION ...........................................................................................................12 
2 
PROTOCOL SUMMARY...............................................................................................12 
2.1 
Study objectives...........................................................................................................12 
2.1.1 
Primary objective.................................................................................................12 
2.1.2 
Secondary objectives ...........................................................................................12 
2.1.3 
Other objectives...................................................................................................13 
2.2 
Study variables.............................................................................................................13 
2.2.1 
Efficacy variables ................................................................................................13 
2.2.1.1 
Primary efficacy variable ..........................................................................13 
2.2.1.2 
Secondary efficacy variables.....................................................................13 
2.2.1.3 
Other efficacy variables.............................................................................13 
2.2.2 
Pharmacokinetic/pharmacodynamic variables ....................................................15 
2.2.2.1 
Pharmacokinetic and pharmacodynamic variables ...................................15 
2.2.3 
Pharmacogenomic variables ................................................................................15 
2.2.4 
Immunological variables .....................................................................................15 
2.2.5 
Safety variables....................................................................................................15 
2.3 
Study design and conduct ............................................................................................15 
2.4 
Determination of sample size.......................................................................................17 
3 
DATA ANALYSIS CONSIDERATIONS......................................................................18 
3.1 
General presentation of summaries and analyses ........................................................18 
3.2 
General study level definitions ....................................................................................19 
3.2.1 
Relative day .........................................................................................................19 
3.2.2 
Study Periods.......................................................................................................19 
3.3 
Definition of Baseline values.......................................................................................20 
3.4 
Protocol deviations.......................................................................................................20 
3.5 
Mapping of assessments performed at early termination visit.....................................20 
3.6 
Analysis sets.................................................................................................................21 
3.6.1 
Enrolled Set (ES) .................................................................................................21 
3.6.2 
Randomized Set (RS) ..........................................................................................21 
3.6.3 
Safety Set (SS).....................................................................................................21 
3.6.4 
Full Analysis Set (FAS).......................................................................................21 
3.6.5 
Per-Protocol Set (PPS).........................................................................................21 
3.6.6 
Pharmacokinetics Per-Protocol Set (PK-PPS).....................................................21 
3.6.7 
Pharmacodynamics Per-Protocol Set (PD-PPS)..................................................22 
3.6.8 
Dose-Blind Set (DBS) .........................................................................................22 
3.6.9 
Escape Subject Set (ESS) ....................................................................................22 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 3 of 194
3.6.10 
Dose-Blind Responder Set (DBRS).....................................................................22 
3.6.11 
Corrected Escape Subject Set (cESS)..................................................................22 
3.6.12 
Corrected Dose-Blind Responder Set (cDBRS)..................................................22 
3.7 
Treatment assignment and treatment groups ...............................................................22 
3.8 
Center pooling strategy................................................................................................23 
3.9 
Coding dictionaries ......................................................................................................23 
3.10 
Changes to protocol-defined analyses .........................................................................23 
4 
STATISTICAL/ANALYTICAL ISSUES.......................................................................23 
4.1 
Adjustments for covariates ..........................................................................................23 
4.2 
Handling of dropouts or missing data..........................................................................23 
4.2.1 
Handling of missing data for efficacy analysis....................................................23 
4.2.2 
Handling of missing data for adverse events (AEs) ............................................26 
4.2.3 
Handling of missing data for prior and concomitant medication ........................27 
4.3 
Interim analyses and data monitoring..........................................................................28 
4.3.1 
Interim analysis Week 12 ....................................................................................28 
4.3.1.1 
Changes from interim analysis Week 12 to SAP-defined analyses ..........30 
4.3.1.2 
Search and selection criteria for AE of special monitoring for interim 
analysis Week 12.......................................................................................30 
4.3.2 
Interim analysis Week 48 ....................................................................................32 
4.3.2.1 
Changes from interim analysis to SAP-defined analyses..........................32 
4.3.2.2 
Changes during interim analysis to SAP-defined analyses.......................32 
4.4 
Multicenter studies.......................................................................................................33 
4.5 
Multiple comparisons/multiplicity...............................................................................33 
4.6 
Use of an efficacy subset of subjects ...........................................................................33 
4.7 
Active-control studies intended to show equivalence..................................................33 
4.8 
Examination of subgroups ...........................................................................................33 
5 
STUDY POPULATION CHARACTERISTICS.............................................................34 
5.1 
Subject disposition.......................................................................................................34 
5.2 
Protocol deviations.......................................................................................................34 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................34 
6.1 
Demographics ..............................................................................................................34 
6.2 
Other Baseline characteristics......................................................................................35 
6.3 
Medical history and concomitant diseases...................................................................36 
6.4 
Prior and concomitant medications..............................................................................36 
6.5 
Prohibited medication and rescue medication .............................................................36 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................37 
8 
EFFICACY ANALYSES ................................................................................................37 
8.1 
Statistical analysis of the primary efficacy variable ....................................................37 
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Statistical Analysis Plan
Bimekizumab
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Page 4 of 194
8.1.1 
Derivations of ASAS score and response............................................................37 
8.1.1.1 
Patient’s Global Assessment of Disease Activity (PGADA)....................38 
8.1.1.2 
Total and nocturnal spinal pain .................................................................39 
8.1.1.3 
Bath Ankylosing Spondylitis Functional Index (BASFI) .........................39 
8.1.1.4 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ............39 
8.1.2 
Primary analysis of the primary efficacy variable...............................................40 
8.1.3 
Secondary analyses of the primary efficacy variable ..........................................40 
8.1.4 
Supportive analyses of the primary efficacy variable..........................................41 
8.1.5 
Sensitivity analyses of the primary efficacy variable..........................................41 
8.2 
Statistical analysis of the secondary efficacy variables ...............................................42 
8.2.1 
Derivations of ASDAS-CRP, ASDAS-MI, and ASDAS Status .........................43 
8.3 
Statistical analysis of other efficacy variables.............................................................44 
8.3.1 
Bath Ankylosing Spondylitis Metrology Index (BASMI)...................................45 
8.3.2 
Physician’s Global Assessment of Disease Activity (PhGADA)........................45 
8.3.3 
Short Form – 36 Items Health Survey.................................................................45 
8.3.4 
Medical Outcomes Study (MOS) Sleep Scale.....................................................46 
8.3.5 
Ankylosing Spondylitis Quality of Life (ASQoL) ..............................................47 
8.3.6 
Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index .........................47 
8.3.7 
MRI assessment...................................................................................................48 
SPARCC MRI (SI joint) score.......................................................................................48 
ASspiMRI-a (Berlin modification) score ......................................................................48 
8.3.8 
Hospital Anxiety and Depression Scale (HADS)................................................49 
8.3.9 
C-reactive protein (CRP) and high-sensitivity C-reactive protein (CRP) ...........49 
8.4 
Subgroup analysis ........................................................................................................49 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS ..........................................50 
9.1 
Pharmacokinetics .........................................................................................................50 
9.2 
Pharmacodynamics and Immunogenicity....................................................................50 
10 SAFETY ANALYSES.....................................................................................................51 
10.1 
Extent of exposure .......................................................................................................51 
10.2 
Adverse events (AEs) ..................................................................................................55 
10.2.1 
Exposure duration................................................................................................56 
10.2.2 
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER) ................................................................................................................57 
10.2.3 
AE of Special Interest and AE of Special Monitoring ........................................58 
10.3 
Clinical laboratory evaluations ....................................................................................59 
10.4 
Potential drug-induced liver injury (PDILI) assessment .............................................62 
10.5 
Vital signs, physical findings, and other observations related to safety......................64 
10.5.1 
Vital signs ............................................................................................................64 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 5 of 194
10.5.2 
Electrocardiograms..............................................................................................65 
10.5.3 
Other safety variables ..........................................................................................65 
Physical Examination ....................................................................................................65 
Assessment of Tuberculosis...........................................................................................65 
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)...................................65 
11 REFERENCES ................................................................................................................67 
12 APPENDICES .................................................................................................................69 
12.1 
Calculation rules for duration of adverse events..........................................................69 
12.2 
Treatment group assignment for tables and figures.....................................................69 
12.3 
Hematology and biochemistry variables for the interim analysis................................70 
12.4 
Physician’s Global Assessment of Disease Activity (PGADA) questionnaire ...........71 
12.5 
Total and nocturnal spinal pain questionnaire .............................................................71 
12.6 
Bath Ankylosing Spondylitis Functional Index (BASFI) questionnaire .....................72 
12.7 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire ........73 
12.8 
SF-36 questionnaire .....................................................................................................74 
12.9 
Classification of the SF-36 questionnaire....................................................................79 
12.10 Medical Outcomes Study (MOS) Sleep Scale questionnaire ......................................81 
12.11 Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire................................83 
12.12 Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) questionnaire ...........85 
12.13 Identification of Opportunistic infections....................................................................85 
12.14 MedDRA algorithmic approach to anaphylaxis ..........................................................86 
13 AMENDMENT TO THE STATISTICIAL ANALYSIS PLAN.....................................88 
13.1 
Amendment 1...............................................................................................................88 
13.1.1 
Rationale for the amendment...............................................................................88 
13.1.2 
Modifications and changes ..................................................................................88 
13.2 
Amendment 2.............................................................................................................119 
13.2.1 
Rationale for the amendment.............................................................................119 
13.2.2 
Modifications and changes ................................................................................119 
13.3 
Amendment 3.............................................................................................................136 
13.3.1 
Rationale for the amendment.............................................................................136 
13.3.2 
Modifications and changes ................................................................................136 
13.4 
Amendment 4.............................................................................................................157 
13.4.1 
Rationale for the amendment.............................................................................157 
13.4.2 
Modifications and changes ................................................................................157 
13.5 
Amendment 5.............................................................................................................176 
13.5.1 
Rationale for the amendment.............................................................................176 
13.5.2 
Modifications and changes ................................................................................176 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE...................................................194 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 7 of 194
LIST OF ABBREVIATIONS
A
Assessment
AbAb
Anti-bimekizumab antibody
ACP
Above the cut point
ADR
Adverse drug reaction
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
ANCOVA
Analysis of covariance
AS
Ankylosing spondylitis
ASAS20,40,5/6
Assessment in SpondyloArthritis International 
Society 20%, 40%, 5 out of 6 response criteria
ASDAS-CRP
Ankylosing Spondylitis Disease Activity Score-C-
reactive protein
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score 
major improvement
ASQoL
Ankylosing Spondylitis Quality of Life
ASspiMRI-a
Ankylosing Spondylitis spine Magnetic Resonance 
Imagine-activity
AST
Aspartate aminotransferase
ATC
Anatomical therapeutic chemical
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BASMI
Bath Ankylosing Spondylitis Metrology Index
BCP
Below the cut point
BKZ
Bimekizumab
BLQ
Below the level of quantification
BMI
Body mass index
BUN
Blood urea nitrogen
cDBRS
corrected Dose-Blind Responder Set
CDISC
Clinical Data Interchange Standards Consortium
cESS
corrected Escape Subject Set
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 8 of 194
CP
Confirmed positive
CPK
Creatine phosphokinase
CRP
C-reactive protein
CV
Coefficient of variance 
DBRS
Dose-Blind Responder Set
DBS
Dose-Blind Set
DEM
Data evaluation meeting
DMARD
Disease-modifying antirheumatic drug
DMC
Data Monitoring Committee
EAER
Exposure adjusted event rate
EAIR
Exposure adjusted incidence rate
ECG
Electrocardiogram
eCRF
Electronic Case Report Form 
eC-SSRS
Electronic Columbia-Suicide Severity Rating Scale
ES
Enrolled Set
ESS
Escape Subject Set
GGT
Gamma glutamyltransferase
H
High
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale—Anxiety
HADS-D
Hospital Anxiety and Depression Scale—
Depression
HBcAb-IgM
Hepatitis B core antibody-IgM
HBsAg
Hepatitis B surface antigen
HIV
Human immunodeficiency virus
HLA
Human leukocyte antigen
HLGT
High-level group terms
HLT
High Level Terms
hs-CRP
High sensitivity C-reactive protein
IIT
Intent-to-treat
IL
Interleukin
IMP
Investigational medicinal product
INR
International normalized ratio
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 9 of 194
FAS
Full Analysis Set
L
Low
LDH
Lactate dehydrogenase
IgM
Immunoglobulin M
LLN
Lower limit of normal
LLOQ
Lower limit of quantification
LOCF
Last non-missing observation
MAR
Missing at random
MASES
Maastricht Ankylosing Spondylitis Enthesitis Index
MCH
Mean corpuscular hemoglobin
MCHC
Mean corpuscular hemoglobin concentration
MCMC
Markov-Chain Monte Carlo
MCS
Mental component summary
MCV
Mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple imputation
MOS
Medical Outcomes Study
MRI
Magnetic resonance imaging
N/A
Not applicable
N
Number of subjects
n
Number of observations 
NCP
Not confirmed positive
NRI
Non-responder imputation
NRS
Numeric rating scale
NSAID
Nonsteroidal anti-inflammatory drug
OMERACT
Outcome Measures in Rheumatology Clinical Trials
OR
Odds ratio
PCS
Physical component summary
PD
Pharmacodynamics
PDILI
Potential drug-induced liver injury
PD-PPS
Pharmacodynamics Per-Protocol Set
PGADA
Patient’s Global Assessment of Disease Activity
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 10 of 194
PhGADA
Physician’s Global Assessment of Disease Activity
PK
Pharmacokinetic
PK-PPS
Pharmacokinetic Per Protocol Set
PPS
Per Protocol Set
PT
Preferred term
Q4W
Every 4 weeks (monthly)
QTcB
QT interval corrected for heart rate using Bazett’s 
formula
QTcF
QT interval corrected for heart rate using 
Fridericia’s formula
RBC
Red blood cell
RCTC
Rheumatology Common Toxicity Criteria
RNA
Ribonucleic acid
RS
Randomized Set
S
Score
SAE
Serious adverse event
SAP
Statistical analysis plan
sc
Subcutaneous(ly)
SD
Standard deviation
SE
Standard error
SF-36
Short-Form 36-item Health Survey
SFU
Safety Follow-up
SI
Sacroiliac
SOC
System organ class
SMQ
Standard MedDRA query
SPARCC
Spondyloarthritis Research Consortium of Canada
SS
Safety Set
STIR
Short-tau-inversion recovery
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
TFLs
tables, figures, and listings
TNF
Tumor necrosis factor
TNFα
Tumor necrosis factor alpha
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 11 of 194
LCL
Lower confidence limit
UCL
Upper confidence limit
ULN
Upper limit of normal
VU
Vertebral units
WBC
White blood cell
WHO-DD
World Health Organization Drug Dictionary
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 12 of 194
1
INTRODUCTION
The purpose of this statistical analysis plan (SAP) is to provide all necessary information to 
perform the required interim and final statistical analysis for study AS0008. It also defines the 
summary tables, figures, and listings (TFLs) to be generated in the clinical study report 
according to the final protocol (29 Jul 2016), Protocol Amendment 1 (15 Mar 2017), and 
Protocol Amendment 2 (09 Mar 2018).
The content of this SAP is compatible with the International Conference on Harmonization/
Food and Drug Administration E9 Guidance documents (1998).
2
PROTOCOL SUMMARY
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to investigate the efficacy, safety, pharmacokinetics (PK), and 
pharmacodynamics (PD) of bimekizumab (also known as UCB4940) compared with placebo in 
adult subjects with active ankylosing spondylitis (AS) in order to guide the selection of doses 
and clinical indices in the Phase 3 development program. 
Eligible subjects will have active AS, determined by documented radiologic evidence (X-ray) 
fulfilling the Modified New York criteria for AS, including symptoms for ≥3 months and age of 
onset <45. Furthermore, subjects will have moderate to severe active disease (Bath Ankylosing 
Spondylitis Disease Activity Index [BASDAI] ≥4 and spinal pain ≥4 [BASDAI Question 2]). 
Subjects must have at least 1 of the following: 1) inadequate response to nonsteroidal anti-
inflammatory drug (NSAID) therapy, 2) intolerance to administration of at least 1 NSAID, or 3) 
contraindication(s) to NSAID therapy. Inadequate response to an NSAID is defined as lack of 
response for at least 4 weeks of continuous NSAID therapy at the highest tolerated dose of the 
administered NSAID or the lack of response to treatment with at least 2 NSAIDs at the 
maximum tolerated dose for at least 4 weeks total duration. Subjects may be tumor necrosis 
factor (TNF) inhibitor-naïve or may have received 1 prior TNF inhibitor.
An estimated 100 sites in Europe and North America will randomize 285 subjects (57 subjects 
per treatment arm). The enrollment of TNF inhibitor-experienced subjects will be limited to 30% 
of the total study population. 
The study consists of a Screening Period (up to 28 days), Double-Blind Period (12 weeks), Dose-
Blind Period (36 weeks) and Safety Follow-up (SFU) Period (20 weeks, only for subjects who do 
not enter the extension study). Therefore, the maximum duration of the study is 68 weeks.
2.1
Study objectives
2.1.1
Primary objective
The primary objective is to assess the dose-response based on the efficacy of bimekizumab 
administered subcutaneously (sc) every 4 weeks (Q4W) for 12 weeks in the treatment of subjects 
with active AS.
2.1.2
Secondary objectives
The secondary objectives of the study are as follow:
x
To assess the efficacy of the individual dose regimens of bimekizumab compared to placebo
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 13 of 194
x
To assess the safety and tolerability of bimekizumab
x
To assess the PK of bimekizumab
x
To assess the PD of bimekizumab
x
To assess the immunogenicity of bimekizumab
x
To assess the exposure:response relationship of bimekizumab as it related to efficacy and 
safety
2.1.3
Other objectives
x
To assess disease activity
x
To assess the impact on patient-reported quality of life (function, fatigue, sleep, and pain)
x
To assess the impact on enthesitis
x
To assess the impact of administration of bimekizumab on biological pathways relating to 
disease biology, progression, and response to therapy via biomarker analysis, and to enable 
genomic and related approaches for analysis of subject samples and evaluation of the 
potential for subject stratification approaches
x
To assess the impact of bimekizumab on inflammatory changes in the spine and sacroiliac 
(SI) joint using magnetic resonance imaging (MRI) in a subset of subjects
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variable
The primary efficacy variable for this study is a follows:
x
Assessment in SpondyloArthritis International Society 40% (ASAS40) response at Week 12 
2.2.1.2
Secondary efficacy variables
The secondary efficacy variable for this study is as follows:
x
Change from Baseline in Ankylosing Spondylitis Disease Activity Score-C-reactive protein
(ASDAS-CRP) at Week 12
x
Assessment in SpondyloArthritis International Society 20% (ASAS20) response at Week 12
x
Assessment in SpondyloArthritis International Society 5 out of 6 response criteria 
(ASAS5/6) response at Week 12
x
Change from Baseline in BASDAI at Week 12
x
Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12
2.2.1.3
Other efficacy variables
Other efficacy variables will be assessed as specified in Section 8.3.
x
ASAS40 response (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Time to ASAS40 response
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 14 of 194
x
Change from Baseline in ASDAS-CRP (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
ASDAS status (eg, inactive disease, moderate, high and very high disease activity) (Week 1, 
2, 4, 8, 12, 16, 24, 36, 48)
x
ASAS20 response (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Time to ASAS20 response
x
ASAS5/6 response (Week 4, 8, 12, 16, 24, 36, 48)
x
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) (Week 1, 
2, 4, 8, 12, 16, 24, 36, 48)
x
ASAS partial remission (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in BASDAI (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in BASFI (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (Week 4, 
8, 12, 16, 24, 36, 48)
x
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
(Week 4, 12, 48)
x
Physician’s Global Assessment of Disease Activity (PhGADA) (Week 4, 8, 12, 16, 24, 36, 
48)
x
Change from Baseline in Patient’s Global Assessment of Disease Activity (PGADA) (Week 
1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in total and nocturnal spinal pain (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in the average of Questions 5 and 6 of the BASDAI 
 
(Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
x
Change from Baseline in Physical Component Summary (PCS) and Mental Component
Summary (MCS) of the Short-Form 36-Item Health Survey (SF-36) (Week 4, 12, 16, 24, 36, 
48)
x
Change from Baseline in Sleep quality (Medical Outcomes Study [MOS]-12 item scale)
(Week 4, 12, 16, 24, 36, 48)
x
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) (Week 4, 8, 12, 
16, 24, 36, 48)
x
Change from Baseline (Week 12, 48) in:

Spondyloarthritis Research Consortium of Canada (SPARCC) MRI (SI Joint) score, and

Ankylosing Spondylitis spine MRI- activity (ASspiMRI-a) (Berlin modification) score
x
Change from Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) and 
Hospital Anxiety and Depression Scale - Depression (HADS-D) scores (Week 2, 4, 8, 12, 16, 
20, 24, 28, 32, 36, 40, 44, 48)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 15 of 194
x
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores) (Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
2.2.2
Pharmacokinetic/pharmacodynamic variables
2.2.2.1
Pharmacokinetic and pharmacodynamic variables
The PK variables are plasma concentration of bimekizumab.
The PD variables are concentrations of cytokines of relevance to the interleukin (IL)-17A/F 
signaling pathway and AS biology, and include but are not limited to IL-17A, IL-17F, IL-23, IL-
6, and tumor necrosis factor alpha (TNFα).
2.2.3
Pharmacogenomic variables
Where local regulations permit, additional blood samples will be collected from consenting 
subjects at specific time points and stored at -80°C for up to 20 years to allow for potential, 
exploratory analyses of genomic, genetic, proteomic, and metabolomic biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes.
Analysis will include, but not be limited to genotyping of human leukocyte antigen (HLA)
alleles (HLA Cw6, HLAB27, etc.).
2.2.4
Immunological variables
Immunological variables allow evaluation of immunogenicity as well as immunological 
biomarkers.
x
Anti-bimekizumab antibody (AbAb) detection prior to and following study treatment
x
Serum complement concentrations
x
Flow cytometry analysis of key immune cell populations, including but not limited to CD3, 
CD19, CD4, CD8, and CD69 (using fluorescence activated cell sorting)
x
Cytokines and other exploratory markers
2.2.5
Safety variables
Safety variables to be assessed as specified in Section 10 are as follows:
x
Incidence of adverse events (AEs) and serious adverse events (SAEs)
x
Withdrawal due to AEs
x
Change from Baseline in vital signs (blood pressure, pulse rate) and body weight
x
Standard 12-lead electrocardiogram (ECG) intervals (RR, PR, QRS, QT, and QT intervals 
corrected for heart rate using Bazett’s and Fridericia’s formulas (QTcB and QTcF), including 
changes from Baseline ECG variables
x
Change from Baseline in clinical laboratory variables (hematology, biochemistry, and 
urinalysis)
2.3
Study design and conduct
To be eligible to participate in this study, subjects must meet the following key inclusion criteria:
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 16 of 194
x
Subject has active AS, determined by documented radiologic evidence (X-ray) fulfilling the 
Modified New York criteria for AS, including symptoms for ≥3 months and age of onset <45 
years.
x
Subject has moderate to severe active disease as defined by each of the following:
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x
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x
Subjects may be TNF inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects 
who have been on a TNF inhibitor previously must have:

experienced an inadequate response to previous treatment given for at least 12 weeks

been intolerant to administration (eg, had a side effect/AE that led to discontinuation)

lost access to TNF inhibitor for other reasons
Approximately 285 eligible subjects will be randomized to 1 of 5 treatment arms to receive 
treatment according to their randomized placebo or bimekizumab dose regimen until Week 12. 
Thereafter, subjects randomized to bimekizumab 160mg Q4W or bimekizumab 320mg Q4W 
will remain on their randomized dose and subjects randomized to placebo, bimekizumab 16mg 
Q4W, and bimekizumab 64mg Q4W, will be re-randomized in a 1:1 fashion to bimekizumab 
160mg Q4W or bimekizumab 320mg Q4W. The total duration of treatment is 48 weeks.
Screening Period/ Baseline
During the Screening Period, the Investigator will assess the eligibility of subjects according to 
the inclusion and exclusion criteria. The Screening Period will also enable washout of any 
medications not permitted for use during the study and allow initiation of latent tuberculosis 
(TB) treatment where necessary and appropriate. The Screening Period will be up to 28 days.
Double-Blind Period
At Baseline subjects will be randomized in a 1:1:1:1:1 ratio (stratified by region and prior TNF 
inhibitor exposure) to receive the following blinded study treatment regimens during the Double-
Blind Period: 
x
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 17 of 194
The enrollment of TNF inhibitor-experienced subjects will be limited to approximately 30% of 
the total study population. 
The investigational medicinal product (IMP) will be administered sc in the clinic at Baseline, 
Week 4, Week 8, and Week 12. Additional study visits in the Double-Blind Period (without 
dosing) will occur at Week 1 and Week 2. At Week 12, subjects will transition from the Double-
Blind Period into the 36-week Dose-Blind Period.
Subjects withdrawing early from the study will undergo the Early Termination Visit assessments 
and will enter the SFU Period.
Dose-Blind Period
The Dose-Blind Period lasts from Week 12 to Week 48. Subjects randomized to bimekizumab 
160mg Q4W or bimekizumab 320mg Q4W will remain on their randomized dose and subjects 
randomized to placebo, bimekizumab 16mg Q4W, and bimekizumab 64mg Q4W, will be 
rerandomized in a 1:1 fashion to bimekizumab 160mg Q4W or bimekizumab 320mg Q4W. The 
total duration of treatment is 48 weeks.
During the 36-week Dose-Blind Period, subjects will be evaluated for eligibility to rescue 
treatment at defined time points. Subjects who do not show an improvement in both PGADA and 
spinal pain compared to Baseline will be eligible to receive rescue therapy as defined in 
Section 6.5.
Safety Follow-Up Visit/Extension study
At the completion of the Dose-Blind Period, subjects will be given the opportunity to enter an 
extension study at Week 48. All subjects who complete the study and do not enter the extension 
study or who discontinue early, including those withdrawn from study treatment, will have a 
SFU Visit at 20 weeks after their last dose of IMP.
2.4
Determination of sample size
A total of 285 subjects (57 in each treatment group) are planned to be randomized in this study. 
The primary efficacy analysis will be based on the Full Analysis Set (FAS). While some 
randomized subjects may not be in the FAS, it is expected that this number will not impact the 
following calculations. 
The sample size is calculated based on the ASAS40 response data from the Phase 3 studies in 
subjects with AS treated with secukinumab (MEASURE 1 and 2; Baeten et al, 2015). The 
ASAS40 response rates at Week 12 were reported to be 40% in both studies for the secukinumab 
150mg dose while placebo response rates were 18% (MEASURE 1) and 9% (MEASURE 2).
Based on those ASAS40 response rates and preliminary information on the bimekizumab dose-
response profile, ASAS40 response rates of 40.0%, 36.0%, 20.0%, 15.0%, and 12.0% at the end 
of a 12-week Treatment Period for bimekizumab 320mg, bimekizumab 160mg, bimekizumab 
64mg, bimekizumab 16mg, and placebo have been assumed, respectively. Since the loading dose 
regimen of MEASURE 1 (iv) was different from MEASURE 2 (sc), the assumption for placebo 
response was based primarily on MEASURE 2, but with a weighting towards the higher placebo 
response rate of MEASURE 1.
The sample size for the primary objective of evaluating the dose-response relationship was 
calculated using a 2-sided test for detecting a linear trend across proportions (Nam, 1987) at a 2-
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 18 of 194
sided significance level of 0.05. Assuming 57 subjects in each treatment group, the test for 
detecting the overall dose response based on ASAS40 response is powered at >99% for the 
subjects with diagnosis of AS (ie, 57 subjects per group).
The sample size calculations were performed using the software nQuery Advisor® 7.0.
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
All computations and generation of outputs will be performed using SAS® Version 9.3 or later. 
All tables and listing will use Courier New font size 9.
All original and derived variables will be listed and described using summary statistics (number 
of observations [n], mean, standard deviation [SD], median, minimum and maximum, unless 
otherwise stated) or frequency counts (number of subjects [N] and percentages). For multiple 
post-Baseline assessments at a specific visit, the first non-missing measurement will be used for 
summary statistics or frequency counts. 
Descriptive statistics will be displayed to provide an overview of the study results. For 
categorical variables, the number and percentage of subjects in each category will be presented. 
The denominator for percentages will be based on the number of subjects appropriate for the 
purpose of analysis. Unless otherwise noted, all percentages will be displayed to 1 decimal place. 
No percentage will be displayed for zero counts, and no decimal will be presented when the 
percentage is 100%. For continuous variables, descriptive statistics will include number of 
subjects with available measurements (n), mean, SD, median, minimum, and maximum.
Decimal places for descriptive statistics will always apply the following rules:
x
“n” will be an integer.
x
Mean, SD, and median will use 1 additional decimal place compared to the original data.
x
Coefficient of variance (CV [%]) will be presented with 1 decimal place.
x
Minimum and maximum will have the same number of decimal places as the original value.
Statistical tests of efficacy variables will be presented as 2-sided p-values rounded to 3 decimal 
places. P-values less than 0.001 will be presented as “<0.001” and p-values greater than 0.999 
will be presented as “>0.999”. Statistical comparisons will be performed by two-sided statistical 
tests at the 0.050 level of significance.
The SAS output for Cochran-Mantel-Haenszel test, logistics regression, and analysis of 
covariance (ANCOVA), as well as multiple imputation (MI) will be provided as a separate PDF 
document in addition to TFLs. The SAS output will be included in the ‘Documentation of 
Statistical Methods’ section of the clinical study report.
In the Double-Blind Period the order of treatment groups to be presented in tables from left to 
right will be Placebo, BKZ16mg, BKZ64mg, BKZ160mg, and BKZ320mg, where BKZ is the 
abbreviation for bimekizumab. The general principle is to go from the lowest to highest dose 
when moving from left to right. Tables may also include columns for all subjects or all subjects 
on bimekizumab. An overview of the treatment group assignment is available in Table 12‒2.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 19 of 194
Selected tables which are specified in the TFL shells will only use data from the Dose-Blind 
Period. For listings and the selected tables, the label and order of treatment groups will be 
presented as follows: Placebo-BKZ160mg, Placebo-BKZ320mg, BKZ16mg-BKZ160mg, 
BKZ16mg-BKZ320mg, BKZ64mg-BKZ160mg, BKZ64mg-BKZ320mg, BKZ160mg-
BKZ160mg, and BKZ320mg-BKZ320mg.
All subjects on bimekizumab will be labeled as “All BKZ“ in the TFLs.
A complete set of data listings containing all documented data and all derived data (eg, change 
from Baseline) will be generated.
Unless otherwise stated, listings will be sorted by treatment, subject number within each 
treatment group (not randomization number), variables (if applicable) and visit (if applicable; 
including timing relative to dosing if applicable). For listings including nonrandomized subjects, 
the nonrandomized subjects will be shown first in the listing, ordered by subject number. All 
listings will include repeat and unscheduled measurements; such measurements will appear in 
chronological order together with the scheduled visits, ie, a repeated measurement will appear 
directly after the visit and time relative to dosing for which the repeat measurement was 
performed. In all the listings dates will be presented in the format “YYYY-MM-DD” and times 
will be presented in 24h clock format as “hh:mm”.
3.2
General study level definitions
3.2.1
Relative day
Relative day will be calculated as the current date minus the date of first dose of study drug 
administration plus 1 for days on or after the day of first dose of study drug dose. Relative day 1 
is the date of first bimekizumab administration. 
Relative days before first administration of bimekizumab will have the prefix “-” and will be 
calculated as date of first dose of study drug administration minus the current date. 
For days after the last bimekizumab administration, relative day will be calculated as the current 
date minus the date of last dose of study drug administration including the prefix “+”.
Calculations of “Relative Day” should not include partial dates, but should be left blank in these 
instances.
For AEs, relative days for start and stop dates will be calculated as the number of days since the 
first injection of the medication. For non-treatment emergent AEs, relative day of onset will be 
negative if the event started and stopped before the first dose. A complete date must be 
established in order to correctly identify the AEs. Section 4.2.2 describes imputation rules in case 
of missing data for AEs.
3.2.2
Study Periods
The following study periods are defined for the classification by study period:
x
Pre-treatment period (Screening period): up to 28 days, ends with the visit date of the first 
dose of study medication (Visit 2)
x
Double-Blind treatment period: starts with the visit date of the first dose of study medication 
(Visit 2), ends at Week 12 visit date
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 20 of 194
x
Dose-Blind treatment period: starts at the Week 12 visit, ends at Week 48 visit
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Week 48 visit
3.3
Definition of Baseline values
The last valid measurement before first dose of study drug (Visit 2) will be used as the Baseline 
value. If a scheduled Baseline assessment is taken on the same day and after the first 
administration of study medication, it will be analyzed as the first post-Baseline assessment. If a 
scheduled Baseline assessment is taken on the same day as first administration of study 
medication and no time is collected, it will be assumed to have been taken prior to study 
medication. 
The exception of the above rule are the questionnaires collected from the vendor ERT and 
measurements for C-reactive protein (CRP) and high sensitivity C-reactive protein (hs-CRP). For 
those measurement, the last valid measurement at the same day as Visit 2 will be used as the 
Baseline value. 
However, for some variables, assessments may be scheduled for Screening only and not for 
Baseline. In this case the Screening value will be utilized as Baseline value. If a Baseline 
measurement is missing, and a Screening value available, the Screening value will be utilized as 
Baseline instead.
3.4
Protocol deviations
Important protocol deviations are defined as those deviations from the protocol likely to have a 
meaningful impact on the primary efficacy outcomes for an individual subject. Important 
protocol deviations will be identified and classified by the deviation types defined in the 
appropriate protocol-specific document. All protocol deviations will be reviewed as part of the 
ongoing data cleaning process and all important deviations will be identified and documented 
prior to unblinding to confirm exclusion from Per Protocol Set (PPS ), Pharmacokinetics Per-
Protocol Set (PK-PPS), and Pharmacodynamics Per-Protocol Set (PD-PPS). The exclusion from 
PPS is limited to the Double-Blind Period, ie. only subjects with important protocol deviations 
prior to re-randomization at Visit 7 (Week 12) will be excluded from PPS. Subjects with 
important protocol deviations after Visit 7 (Week 12) will not be excluded from PPS.
3.5
Mapping of assessments performed at early termination visit
Study assessments at an early termination visit where visit date matches the visit date of a 
scheduled visit will be summarized at the scheduled visit with the same visit date. Premature 
study termination visit assessments that do not have a scheduled visit with a matching date will 
be assigned to the next scheduled site visit following the last visit where assessments were 
available regardless whether or not there will be an assessment on this visit. The assessment of 
AbAb is an exception to this rule: AbAb will be mapped to the next visit where antibody levels 
are measured. For subjects who discontinue study treatment early and return for the Week 12 
visits as per the protocol, the assessments collected at that visit are summarized as Week 12 
assessments.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 21 of 194
3.6
Analysis sets
The primary efficacy variable will be analyzed for all subjects in the FAS. The supportive 
analysis for the primary efficacy variables will be performed for Randomized Set (RS), PPS, and 
FAS. All other efficacy variables will be based on the FAS. Demographics tables will be 
performed for FAS, Safety Set (SS), and Dose-Blind Set (DBS). Safety variables will be 
summarized using the SS. In addition, safety analyses during the Dose-Blind Period will be 
conducted on all subjects in the DBS. PK variables will be analyzed for all subjects in the 
Pharmacokinetics Per-Protocol Set (PK-PPS). PD variables will be analyzed for all subjects in 
the Pharmacodynamics Per-Protocol Set (PD-PPS).
At the time of the Week 48 interim it was discovered that the Dose-Blind Responder Set (DBRS) 
and Escape Subject Set (ESS) were defined incorrectly from the original intent. The original 
intent of the ESS analysis set was to have only those subjects that were eligible to receive rescue 
therapy, that went on to actually receive rescue therapy, with all other subjects remaining in the 
DBRS. As such, two extra sets, the Corrected Dose-Blind Responder Set (cDBRS) and Corrected 
Escape Subject Set (cESS) have been added. These analysis sets will correctly select out those 
subjects that were eligible and received rescue medication. All outputs created on the DBRS and 
ESS will also be produced on the cDBRS and cESS to give full transparency of the difference. 
Further all outputs using the DBRS and ESS will be repeated on the DBS and this analysis will 
be used as the main analysis of the Dose-Blind Period as this analysis set is the most unbiased 
set.
3.6.1
Enrolled Set (ES)
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
3.6.2
Randomized Set (RS)
The RS will consist of all randomized subjects.
3.6.3
Safety Set (SS)
The SS will consist of all randomized subjects who received at least 1 dose of IMP.
3.6.4
Full Analysis Set (FAS)
The FAS will consist of all randomized subjects who received at least 1 dose of IMP and have a 
valid measurement of the primary efficacy variable at Baseline.
3.6.5
Per-Protocol Set (PPS)
The PPS will consist of all subjects in the FAS who had no important protocol deviation
affecting the primary efficacy variable. The subjects with important protocol deviations will be 
predefined and evaluated during a data evaluation meeting prior to unblinding of the data.
3.6.6
Pharmacokinetics Per-Protocol Set (PK-PPS)
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations affecting the pharmacokinetic variables, as confirmed during ongoing data cleaning 
meetings prior to database lock.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 22 of 194
3.6.7
Pharmacodynamics Per-Protocol Set (PD-PPS)
The PD-PPS will consist of all randomized subjects who took at least 1 dose of IMP and provide 
at least 1 PD measurement postdose that is without important protocol deviation affecting that 
time point.
3.6.8
Dose-Blind Set (DBS)
The DBS consists of all subjects starting the Dose-Blind Period and who received at least 1 dose 
of the IMP during the Dose-Blind Period including the dose at Week 12.
3.6.9
Escape Subject Set (ESS)
The ESS consists of all subjects starting the Dose-Blind Period and who received at least 1 dose 
of the IMP during the Dose-Blind Period and who have not achieved at least a 10% reduction 
from Baseline in PGADA and total and nocturnal spinal pain at either Week 16, Week 24, or 
Week 36.
3.6.10
Dose-Blind Responder Set (DBRS)
The DBRS consists of all subjects starting the Dose-Blind Period and who received at least 1 
dose of the IMP during the Dose-Blind Period and who have achieved at least a 10% reduction 
from Baseline in PGADA and total and nocturnal spinal pain at Week 16, Week 24, and Week 
36.
3.6.11
Corrected Escape Subject Set (cESS)
The cESS is a corrected version of the ESS, which was incorrectly defined previously. The cESS 
consists of subjects that have shown less than a 10% improvement in SJC and TJC at either 
Week 16, Week 24, or Week 36 and received rescue therapy.
3.6.12
Corrected Dose-Blind Responder Set (cDBRS)
The cDBRS is a corrected version of the DBRS, which was incorrectly defined previously. The 
cDBRS consists of subjects that have shown at least a 10% improvement in SJC or TJC at Week 
16, Week 24 and Week 36. Subjects that would be in the cESS, including subjects that 
discontinue, that did not receive rescue therapy will be in the cDBRS.
3.7
Treatment assignment and treatment groups
It is expected that subjects receive treatment as randomized and hence safety analyses will be 
based on the SS, as randomized. However, if after unblinding it is determined that subjects 
randomized to placebo received bimekizumab at any time, then for safety analyses these subjects 
will be reallocated to the appropriate bimekizumab treatment group. Subjects randomized to 
bimekizumab will only be reallocated to the placebo treatment group if they did not receive 
bimekizumab at any time during the study.
Depending on the analysis sets, subjects will be summarized and listed based on the actual 
received treatment or according to the randomization which will be considered as planned 
treatment:
x
All subjects screened/ES: planned treatment
x
RS: planned treatment
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 23 of 194
x
SS: actual treatment
x
FAS: planned treatment
x
PPS: planned treatment
x
PK-PPS: actual treatment
x
PD-PPS: actual treatment
x
DBS: planned treatment (demographics, baseline characteristics, and efficacy analyses) or
actual treatment
x
ESS: planned treatment
x
DBRS: planned treatment
3.8
Center pooling strategy
Centers will be pooled into geographic regions for analysis purposes. Centers will be grouped in 
the geographic regions North America, Western and Eastern Europe.
3.9
Coding dictionaries
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 19.0. Previous and ongoing medical history will be classified by primary 
system organ class and preferred term (PT).
All AEs will be classified by primary system organ class, high level term and PT. Prior and 
concomitant medications will be coded using version SEP2015 of the World Health Organization 
Drug Dictionary (WHO-DD) and will be classified by Anatomical Main Group, Pharmacological 
Subgroup, and PT. Medical procedures will not be coded.
3.10
Changes to protocol-defined analyses
Instead of stopping the pairwise testing of each bimekizumab dose versus placebo once it failed 
to reach significance at a significance level of α=0.05, the pairwise testing will continue and 
further pairwise comparisons are seen as non-significant.
No fixed sequence testing will be used for the secondary efficacy variables. 
Time to a given response is defined as the length in weeks from Baseline until the first date when 
the response is achieved. In the definition the length was changed from days to weeks due to 
easier interpretation.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
The primary efficacy analysis and secondary analysis will be adjusted for treatment, geographic 
region, and prior TNF inhibitor exposure (yes/no).
4.2
Handling of dropouts or missing data
4.2.1
Handling of missing data for efficacy analysis
The analysis for the binary primary, secondary, and other efficacy variables will use non-
responder imputation (NRI) for handling missing data. In NRI, each subject with missing data or 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 24 of 194
who has discontinued Double-Blind study treatment prior to Week 12 will be counted as a non-
responder. 
Sensitivity analysis will be performed for the secondary analysis of the primary variable 
(ASAS40 response at Week 12) using MI assuming that missingness is missing at random 
(MAR). The MI method will be applied as follows:
1. Create a data set, sorted by treatment groups, of subjects with observed values and those 
needing estimation by multiple imputation. For the imputation step, missing values will be 
separated into non-monotone missing values (ie, intermittent missing values between 
completed assessments) and monotone missing values (ie, missing values after the patient 
dropped out). The procedure will sequentially estimate an imputation model for the ASAS 
components at each post-Baseline visit where ASAS components are collected, with 
geographic region, and prior TNF inhibitor exposure as covariates separated between the 
treatment groups.

For the imputation of intermediate missing values, the missing ASAS components in 
each data set will be filled in using the Markov-Chain Monte Carlo (MCMC) method
with multiple chains and monotone imputing. A total number of imputations will be 100. 
The seed used for these imputations will be 2017. 
Note: All other multiple imputation procedures described in this SAP will use this same 
seed as well.
Note: The imputation model based on the MCMC method will only allow continuous 
variables as predictors. Therefore, prior TNF inhibitor exposure and geographic region 
will be re-coded as numeric variables (with values of 0 or for the levels of TNF [1=prior 
inhibitor exposure, 0=non prior inhibitor exposure] and two binary variables for 
geographic region [Variable 1: 1=North America, 0=others, Variable 2: 1=Eastern 
Europe, 0=others] as representation of geographic region).
Note: To avoid that imputed values are outside of the pre-defined range of values for the 
ASAS components (eg, PGADA [0-10]) maximum and minimum values for imputed 
variable values are specified. Moreover, the rounding options for imputed values are used 
where appropriate.

Once the intermediate missing data are imputed, the monotone missing data will be 
imputed for all patients with monotone regression including geographic region, and prior 
TNF inhibitor exposure as covariates. The dataset is the output dataset of the partial 
imputation. Since this dataset already has 100 imputed values at each visit, only one 
imputation will be performed. 
Note: Maximum and minimum values (and rounding where appropriate) are specified for 
imputed variable values to avoid values outside of the pre-defined range of values. 
2. The ASAS40 response will be calculated using the complete datasets. That is, the values of 
the ASAS components at Week 12 based on the complete datasets will be compared to their 
corresponding Baseline values to calculate an ASAS40 response for each subject (as 
described in Section 8.1.1). Each complete data set will then be analyzed based on a logistic 
regression model with factors of treatment group, geographic region, and prior TNF inhibitor 
exposure. 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 25 of 194
3. The Week 12 results from the logistic regression analysis of each of the 100 imputed data 
sets will be combined for overall inference using Rubin’s rules, which account for the 
uncertainty associated with the imputed values (Rubin, 1987).
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below:
As the estimates of the odds ratios from the logistic regression model in step 3 follow a 
lognormal distribution, a log transformation is needed to normalize these estimates since the 
procedures for combining results from multiple imputed datasets are based on the assumption
that the statistics estimated from each imputed dataset are normally distributed. Therefore, the 
log of the odds ratio estimates from the logistic regression model are used when combining into a 
single inference (step 3). Additionally, the standard errors (SE) for the odds ratios are 
transformed as follows:
ܵܧൌሺܷܥܮሻെሺܮܥܮሻ
ʹܼןȀଶ
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where UCL and LCL are the upper and lower confidence limit, respectively, for the confidence 
interval of the odds ratio from the logistic regression model, and Zα/2 is the relevant critical value 
from the standard normal distribution (1.96 for a 95% confidence interval). The estimates of the 
log odds ratio for each bimekizumab dose relative to placebo and the corresponding upper and 
lower confidence limits will be provided. The odds ratio is estimated by exponentiating the 
estimate of the log odds ratio. The confidence limits of the odds ratio are then estimated as 
follows:
ܮܥܮൌܱܴכ ሺെܵܧכ ܼןȀଶሻ
(2)
ܷܥܮൌܱܴכ ሺܵܧכ ܼןȀଶሻ
(3)
where OR is the back-transformed estimate of the odds ratio just described, SE is the standard 
error of the log odds ratio and Zα/2 is the relevant critical value from the standard normal 
distribution (1.96 for a 95% confidence interval). These calculations will be done such that odds
ratios and corresponding confidence intervals are calculated for the odds ratio of each 
bimekizumab dose versus placebo. Note that the p-values presented in the tables are not 
impacted by the transformations described above.
The supportive analysis number 3 (analysis of the ASAS components), and all continuous 
secondary efficacy variables will use the same multiple imputation method as described above. 
Instead of using the logistic regression model the ANCOVA with treatment group, geographic 
region, and TNF inhibitor exposure as fixed effects and the Baseline values as covariate will be 
used. No log transformation is needed for the ANCOVA estimations.
Following Rubin (1987), multiple imputation estimates of descriptive statistics are computed by 
simply averaging the estimates from ݉ൌͳǡ ǥ ǡ ܯindependent repetitions of the imputation 
algorithm:
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 26 of 194
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The imputation model will be applied for each treatment group separately. However, in the event 
there are computational challenges with the imputation model (eg, due to a standard deviation of 
0 for responses of a given imputation), it is acceptable to modify the imputation model to include 
treatment as a variable in the model rather than running a separate model for each treatment 
group. It should be noted that doing so assumes that treatment does not interact with any of the 
other variables in the imputation model.
4.2.2
Handling of missing data for adverse events (AEs)
For analyses of AEs, a complete date must be established in order to correctly identify the AE as 
occurring during treatment or not. For purposes of imputing missing components of partially-
reported start and stop dates for AEs, the algorithms listed below will be followed. Start and stop 
dates of AEs will be displayed as reported in the subject data listings (ie, no imputed values will 
be displayed in data listings).
Partial AE start dates will be imputed as follows:
Imputation of Partial Start Dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the month and year are specified and the subject did switch treatment during that 
month and year, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
If only the year is specified, and the year of first dose is the same as the year the subject did 
switch treatment, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is the same as the year of the start date 
and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
If the date of first study medication or switch treatment is partial, then the above imputation 
approach will be applied:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 27 of 194
x
If only the day of first study medication or switch treatment administration is unknown, then 
this will be set to either the first of the month, or the day of first treatment allocation visit 
(excluding placebo run-in), whichever is later.
x
If both the day and month of first study medication or switch treatment are unknown, then 
this date will be imputed to be the date of first treatment allocation visit.
x
If first treatment allocation visit date is missing then the all activities events will be assumed 
to be treatment emergent.
Imputation of Partial Stop Dates:
x
If only the month and year are specified, then use the last day of the month.
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x
If the stop date is completely unknown, do not impute the stop date.
In the event of ambiguity or incomplete data which makes it impossible to determine whether the 
AE was treatment emergent, the AE will be considered treatment emergent.
If the intensity of an AE is unknown, it is considered as severe.
If the relationship to study drug is missing, it is considered as related.
The imputation rule for missing seriousness differ between the interim and final analysis. For the 
interim analysis no imputations rule will be applied. For the final analysis the worst case 
approach will be applied. If the seriousness of an AE is missing for the final analysis, it is 
considered as serious.
4.2.3
Handling of missing data for prior and concomitant medication
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant. Such imputations will only be 
performed for these classifications and calculations; in the listings all data will be shown as 
recorded on the electronic case report form (eCRF).
Imputation of Partial Start Dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
x
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the month and year of the start, then use the date of first dose.
x
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month and year, then use the date of first switch treatment.
x
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date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
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then use the date of first dose.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 28 of 194
x
If only the year is specified, and the year of first dose is the same as the year the subject did 
switch treatment, then use the date of first switch treatment.
x
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and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If only the year is specified and the end date is before date of first dose, then set the start date 
to the 1st of January of the year of the start date.
x
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considered and the month and day will be imputed with the rules above
x
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of first dose, then use the date of first dose.
x
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set the start date to the 1st of January of the year of the end date.
If the date of first study medication or switch treatment is partial, then the below imputation 
approach will be applied:
x
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this will be set to either the first of the month, or the day of first treatment allocation visit 
(excluding placebo run-in), whichever is later.
x
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this date will be imputed to be the date of first treatment allocation visit.
Imputation of Partial Stop Dates:
x
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x
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x
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There will be no imputation of any other missing data.
4.3
Interim analyses and data monitoring
Two interim analyses are planned for the study after the subjects have completed 12 and 48 
weeks.
4.3.1
Interim analysis Week 12
After all enrolled subjects have completed the 12 weeks Double-Blind Period, an interim 
analysis will be performed (i) to analyze the dose:exposure response for the ASAS40 response 
criteria to determine the optimal therapeutic dose(s) for subsequent studies, and (ii) to perform a 
comprehensive evaluation of all Double-Blind data of the study.
No separate SAP for the interim analysis will be provided. The interim analysis is a limited 
version of the final analysis and will focus on the primary and secondary efficacy analysis and 
comprise the results of the 12 weeks Double-Blind Period. The TFL shells for the interim and 
final analysis will be provided in two different documents.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 29 of 194
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS). Listings of AEs, hematology, biochemistry 
and C-SSRS data will be provided. Not all collected hematology and biochemistry laboratory 
variables will be displayed in the tables and listings. For the interim analysis only selected 
hematology and biochemistry variables will be provided as listed in Table 12‒3.
For efficacy the interim analysis will include following primary and secondary variables: 
ASAS40,20,5/6 response at Week 12, and change from Baseline in BASDAI, ASDAS-CRP, 
BASFI at Week 12. The variables will be analyzed using the same methods described in
Section 8.1.2 and Section 8.2 including supportive and sensitivity analyses (Section 8.1.3 and 
Section 8.1.4). In addition, summary tables for the primary and secondary efficacy variables, and 
the ASAS components will be provided. Categorical variables will be summarized using 
frequency tables by each visit. Continuous variables will be summarized using descriptive 
statistics by each visit. Time to onset of ASAS20 response and ASAS40 response will be 
summarized and plotted as described in Section 8.3.
PK and PD data will be analyzed in the interim analysis as described in Section 9.1 and
Section 9.2. PKPD will be analyzed as part of the exposure:response modeling outside of the 
scope of the SAP. Biomarker data will not be analyzed in the interim analysis.
The interim analysis includes selected data up to Week 12 and in addition data up to Week 16. 
The data up to Week 16 may include partial results up to the time the database for Week 12 was 
locked for ongoing subjects. All analyses for the period between Week 12 and Week 24 are only 
for those treatment groups that are not rerandomized. Following variables will be analyzed: 
ASAS40, ASAS20, ASDAS-CRP, BASDAI, PK, AbAb and TEAEs. It depends on the analysis 
how those additional time points will be presented in the interim analysis. Two summary tables 
for TEAE will be presented. The first table will include TEAEs with a relative TEAE start date 
less equal 84 (12*7) days by treatment group at Baseline. The second table will include TEAEs 
with a relative TEAE start date less equal 112 (16*7) days by the following treatment groups: 
bimekizumab 160mg and bimekizumab 320mg. The summary table for the other variables will 
present only data up to Week 12 for the Baseline treatment groups Placebo, bimekizumab 16mg, 
and bimekizumab 64mg. Data up to Week 16 will be presented for bimekizumab 160mg and 
bimekizumab 320mg. All Listings which include data up to Week 16 will use the same approach.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will be 
allocated to the Double-Blind treatment. An exception from this general rule is made for adverse 
drug reactions (ADRs), and AE of hypersensitivity reactions and anaphylactic reactions. If those 
AEs occur on the same days as the treatment switch, the AEs will be allocated to the Dose-Blind 
treatment and will not be presented for the interim analysis.
Exposure of study medication will not be summarized but a listing will be provided including 
following information: date of first dose, date of last dose, and duration of exposure. The last 
dose for the Double-Blind Period is planned on Visit 6 (Week 8). 
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
result
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 30 of 194
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48.
Further details are available in the AS0008 blinding plan.
Safety data will be provided to an independent Data Monitoring Committee (DMC). The DMC 
will review those safety data periodically. The composition and operation of the DMC will be 
defined in the DMC charter. The presentation and analysis of data for the DMC meetings is 
described within a separate DMC SAP.
4.3.1.1
Changes from interim analysis Week 12 to SAP-defined analyses
For TEAE two summary tables were presented as described in previous section with one 
modification: the first table was displaying all TEAE during the Double-Blind Period instead of 
limiting it TEAE with a relative TEAE start date less equal 84 days. 
The definitions of AE of special monitoring were updated with the third SAP Amendment after 
the interim analysis. The interim analysis used the previous definition which is displayed in 
Section 4.3.1.2. The interim analysis only displayed the overall number of AE of special 
monitoring by treatment group.
The baseline definition for CRP and hs-CRP measurements were updated with the fifth SAP 
Amendment after the interim analysis. The interim analysis used the previous definition: The last 
valid measurement before first dose of study drug (Visit 2) will be used as the Baseline value.
4.3.1.2
Search and selection criteria for AE of special monitoring for interim 
analysis Week 12
Following AEs are defined as TEAEs of special monitoring: 
x
Fungal infectious disorder 
x
Opportunistic infection (including TB) 
x
Malignant or unspecified tumor
x
Malignant tumor 
x
Major cardiovascular event
x
Haematopoietic cytopenias
x
Neuropsychiatric events 
x
Inflammatory bowel disease
x
Hypersensitivity and anaphylactic reaction
x
Hepatic events 
Fungal Infectious disorder
All TEAEs which code into the High Level Group Term (HLGT) of “Fungal infectious 
disorders” are classified as fungal infectious disorder.
Opportunistic infection
All TEAEs identified using UCB-defined search criteria as described in Section 12.13.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 31 of 194
Malignant or unspecified tumor
The search criteria is based on the Standardized MedDRA Query (SMQ) = “Malignant or 
unspecified tumours (SMQ)”. 
Malignant tumor         
The search criteria is based on the SMQ=”Malignant tumours (SMQ)”.
Major cardiovascular events
The major cardiovascular events are identified using the following UCB-defined search criteria:
x
All serious TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow 
groups of the following SMQs:

Haemorrhagic central nervous system vascular conditions (SMQ)

Ischaemic central nervous system vascular conditions (SMQ)
x
All serious TEAEs which code to a PT included in the HLT “Ischaemic coronary artery 
disorders” except events coding to PT “Chest Pain” or “Chest discomfort”
x
All serious TEAEs which code to a PT included in any of the following HLTs: “Heart 
Failures NEC”, “Left Ventricular Failures”, or “Right Ventricular Failures” and which also 
code to the SOC of “Cardiac Disorders” as Primary SOC.
Haematopoietic cytopenias 
The search criteria is based on the SMQ = “Haematopoietic cytopenias”. 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.
Neuropsychiatric events
The search criteria is based on the SMQ = “Depression and suicide/self-injury (SMQ)”. The 
SMQ search will include all TEAEs which code to a PT included in the Scope=Broad and/or 
Scope=Narrow groups within the SMQ.
Inflammatory bowel disease
All TEAEs which code into the HLT of “Colitis (excl infective)” are identified as inflammatory 
bowel disease.
Hypersensitivity reactions and anaphylactic reactions
Hypersensitivity reactions and anaphylactic reactions will be identified as follow:
a) Hypersensitivity reactions: All TEAEs that either emerged on the same day as when a 
study medication injection reaction was received, or that emerged one day after a study 
medication injection was received, which code to a PT which contains the term 
“hypersensitivity” will be considered to be a hypersensitivity reaction and included in the 
summary table as such.
b) Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs that are 
considered to be anaphylactic reactions. PTs are separated into the 4 distinct categories 
(A, B, C, D) prior to the algorithmic approach being applied.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 32 of 194
All TEAEs that either emerged on the same day as when a study medication injection reaction 
was received, or that emerged one day after a study medication injection was received, and 
which fulfill any of the 3 criteria described in Section 12.14 will be included in the summary 
table.
Hepatic events
The search criteria is based on all TEAEs in the SMQ “Drug related hepatic disorders -
comprehensive search (SMQ)”. Note that the following two sub-SMQs are to be excluded: 
“Liver neoplasms, benign (incl cysts and polyps)” and “Liver neoplasms, malignant and 
unspecified (SMQ)”.
The SMQ search should include all TEAEs (regardless of whether they have been judged as 
related to study medication or not) which code to a PT included in the Scope=Narrow group 
within each SMQ.
4.3.2
Interim analysis Week 48
After all enrolled subjects have completed the Week 48 or Early termination visit, a second 
interim analysis will be performed to analyze the key efficacy and safety data for the whole 
treatment period.
No separate SAP for that interim analysis will be provided. This interim analysis is a subset of 
the final analysis and will focus on the primary and secondary efficacy analysis. The TFL shells 
for the final analysis will be used.
The snapshot for the AS0008 interim analysis Week 48 will occur before all subjects have 
completed the AS0008 study. Specifically, subjects who do not enter the extension study will 
need to complete the SFU Visit, which occurs 20 weeks after the last dose of study treatment. 
The Week 48 interim database lock will be performed based on the last subject completing the 
Week 48 visit. It is anticipated that there will be some subjects still awaiting the SFU at that 
time. The number of subjects in the SFU period is expected to be low, and the minimal data to be 
collected from their SFU visits is not considered mandatory to evaluation of the key efficacy and 
safety objectives of the study.
4.3.2.1
Changes from interim analysis to SAP-defined analyses
The baseline definition for CRP and hs-CRP measurements were updated with the fifth SAP 
Amendment after the interim analysis. The interim analysis used the previous definition: The last 
valid measurement before first dose of study drug (Visit 2) will be used as the Baseline vale.
4.3.2.2
Changes during interim analysis to SAP-defined analyses
At the time of the Week 48 interim it was discovered that the DBRS and ESS were defined 
incorrectly from the original intent. The original intent of the ESS analysis set was to have only 
those subjects that were eligible to receive rescue therapy, that went on to actually receive rescue 
therapy, with all other subjects remaining in the DBRS. As such, two extra sets, the cDBRS and 
cESS have been added. These analysis sets will correctly select out those subjects that were 
eligible and received rescue medication. For the final analysis, all outputs created on the DBRS
and ESS will also be produced on the cDBRS and cESS to give full transparency of the 
difference. Further all outputs using the DBRS and ESS will be repeated on the DBS and this 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 33 of 194
analysis will be used as the main analysis of the Dose-Blind as this analysis set is the most 
unbiased set.
4.4
Multicenter studies
The data from all centers will be pooled for the purposes of the analysis. There will be no formal 
statistical evaluation of the effect of center on the results obtained.
4.5
Multiple comparisons/multiplicity
In order to control for the overall Type I error rate, the pairwise comparisons of bimekizumab 
will be formally evaluated for statistical significance only if the primary efficacy analysis is 
statistically significant at the two-sided 5% level. In addition, the pairwise comparisons will 
follow a sequential testing sequence and the formal evaluation of statistical significance of each 
comparison is dependent upon the previous comparison achieving statistical significance at the 
two-sided 5% level. If the sequential testing fails to reach significance at a significance level of 
α=0.05, then the pairwise testing will continue and the comparison are seen as non-significant. 
The p-values will be displayed as nominal p-values. More details can be found in Section 8.1.3.
4.6
Use of an efficacy subset of subjects
The primary dose-response analysis and pairwise comparisons will be repeated for (1) all 
subjects in the PPS, and (2) for all subjects in the RS as a supportive analysis. The purpose is (1) 
to evaluate the effect of important protocol deviations on the analysis, and (2) to evaluate the 
consistency of the FAS with the intent-to-treat (ITT) principle.
4.7
Active-control studies intended to show equivalence
Not applicable.
4.8
Examination of subgroups
The following variables for subgroup analyses will be used:
x
Age (<45 years, ≥45 years)
x
Gender (male, female)
x
Geographic region (North America, Eastern and Western Europe)
x
Treatment-emergent AbAb status (positive, negative)
x
Prior TNF inhibitor exposure (yes, no)
x
Current NSAIDs at Baseline (yes, no)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Subjects will be counted to have a positive treatment-emergent AbAb status in case the first 
AbAb positivity occurred up to Visit 7 (Week 12). The definition of first AbAb occurrence is 
described in Section 9.2.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 34 of 194
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
Summary tables of all subjects screened will be presented including reason for screen failures 
and disposition of subjects screened. The disposition of subjects screened will include the 
number of subjects included in each analysis set (ES, RS, SS, FAS, PPS, PK-PPS, PD-PPS, 
DBS, ESS, and DBRS) overall and by site.
The number and percentage of subjects who discontinued study medication, who discontinued 
the study, and who discontinued due to AEs will be summarized for subjects in the RS.
Study eligibility criteria will be listed and a separate listing of subjects who did not meet the 
eligibility criteria will be presented. Only failed criteria will be included in the former listing.
Subject disposition will be listed for all subjects screened and will include, inter alia, the 
following information: subject status, date of informed consent, randomization, first and last 
study medication, and primary reason for premature study termination. Listings of subject 
analysis sets, study and study medication discontinuation, and visit dates will be presented by 
subject including the relative study day (calculated as described in Section 3.2.1) for each visit.
5.2
Protocol deviations
Important protocol deviations will be identified and classified by the deviation types. Following 
different important protocol deviation types will be classified: inclusion criteria deviation, 
exclusion criteria deviation, withdrawal criteria deviation, prohibited concomitant medication 
use, incorrect treatment or dose, treatment non-compliance, and procedural non-compliance.
Summary tables of the number and percentage of subjects with an important protocol deviation 
will be provided including a summary of subjects excluded from the PPS, PK-PPS, and PD-PPS 
due to important protocol deviations. Summary tables will be presented for FAS analysis sets. 
A listing of all important protocol deviations identified at the data evaluation meeting will be 
presented by subject for all subjects in the RS, and will include deviation type and description.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
Tables with descriptive statistics (number of subjects, mean, SD, minimum, median, and 
maximum) and listings will be given for the demographic variables age (at time of informed 
consent), gender, racial group, ethnicity, weight at Screening, height at Screening, and body 
mass index (BMI). Age will be summarized as a continuous variable and as categorical variables 
based on the following categories: ≤18, 19-<65, ≥65 years (clinicaltrials.gov requirement) and 
18-<65, 65-<85, ≥85 years (EudraCT requirement).
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the formula:
For adults:
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 35 of 194
Even if they are available in the database, these variables are calculated during analysis (if 
applicable). These calculated values are used in the statistical analysis since they are considered 
more accurate. 
A frequency table for Lifestyle will be presented as well as a corresponding listing. Subjects of 
childbearing potential will only be listed. 
The summary tables will be performed on the SS and repeated using the FAS, and the DBS. If 
the SS and FAS analysis sets are identical the summaries will not be repeated. The Listing will 
be provided for all subjects screened, except the Lifestyle listing will use the RS.
6.2
Other Baseline characteristics
AS history will be summarized for subjects in the FAS and SS including the time since first 
diagnosis of AS, time since first symptoms of AS, and age at first diagnosis date. The history 
will be listed for all subjects in the RS.
Time since first diagnosis of AS will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ൅ͳ
͵͸ͷǤʹͷ
(6)
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are missing).
Time since first symptoms will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ൅ͳ
͵͸ͷǤʹͷ
(7)
Age at first diagnosis will be calculated as:
ܣ݃݁ܽݐ݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏൌܦܽݐ݁݋݂݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܾ݅ݎݐ݄
͵͸ͷǤʹͷ
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These formulas may result in incorrect ages after rounding if the birth day falls on the date of 
first diagnosis. In that case the age is calculated as the number of years between the year of birth 
and the year of the randomization visit. The age for individual subjects is presented with 1 
decimal. The rounding is done downwards. For subjects enrolled at German sites, only the year 
of birth may be entered into the eCRF for this study. For these subjects age will be calculated 
after imputing their date of birth to be 01 Jan XXXX.
Baseline characteristics (including scores relevant for inclusion and exclusion criteria) will be 
summarized by treatment group and overall for FAS, SS, and DBS. Following variables will be 
summarized:
x
BASDAI total score
x
BASDAI spinal pain (question 2)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 36 of 194
x
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x
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x
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x
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x
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x
NSAID therapy, synthetic DMARDs, methotrexate, sulfasalazine, and hydroxychloroquine
The corresponding listings will be presented for the RS.
6.3
Medical history and concomitant diseases
Medical history and ongoing medical conditions will be summarized by MedDRA system organ 
class (SOC) and PT by treatment and overall including the number and percentage of subjects 
with each condition. The denominator for the percentages will be the number of subjects in the 
SS and FAS for each treatment or overall.
Medical history and ongoing medical conditions will be listed by treatment and subject including 
the reported term, PT, and SOC for the RS. The start date (month and year only) and end date (or 
ongoing if applicable) will also be included in the listing. A glossary of all medical history 
conditions will also be presented including the reported term, PT and SOC.
6.4
Prior and concomitant medications
Prior medications include any medications that started and ended prior to the start date of study 
medication. Concomitant medications are medications taken at least one day in common with the 
study medication dosing period. For bimekizumab, the dosing period is typically from the date of 
first dose up to (but not including) one dosing interval post last dose. Thus, a concomitant 
medication is any medication whose start date is on or after the date of first study medication and 
prior to the date of last study medication administration + 28 days (1 dosing interval), or whose 
stop date is either missing, or on or after the date of first study medication administration. 
In the case of missing data, the classification of medications as prior or concomitant will be 
performed as described in Section 4.2.3.
The number and percentage of subjects taking prior medications will be summarized by 
treatment group, overall and by anatomical therapeutic chemical (ATC) class, presenting 
Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC level 3), and PT.
The number and percentage of subjects taking concomitant medications will be summarized 
similarly in two tables separating between AS concomitant medications and concomitant 
medications. AS concomitant medications includes the following list: NSAIDS, corticosteroid, 
methotrexate, sulfasalazine, hydroxychloroquine. Tables for prior and concomitant medications 
will be presented for SS and FAS. 
Prior and concomitant medications will be listed by treatment and subject for RS.
6.5
Prohibited medication and rescue medication
Prohibited medications are defined in the protocol (Section 7.8.2). 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 37 of 194
Rescue medication will be allowed for some subjects evaluated at weeks 16, 24, and 36. Further 
details are defined in the protocol (Section 5.1.4). The number and percentage of subjects who 
used rescue medication will be summarized and listed.
The SS and FAS will be used for the summary table and the RS will be used for the listing.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
Compliance will be summarized as the number of doses received relative to the number of doses
scheduled:
ܲ݁ݎܿ݁݊ݐܿ݋݉݌݈݅ܽ݊ܿ݁ൌͳͲͲ כ    
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where the total number of expected doses is derived relative to when the subject finishes 
treatment. If a subject completes treatment 12 doses are expected (Baseline and every 4th week 
afterwards until Week 44). If a subject discontinues early, then the number of expected doses is 
based on the time of early discontinuation relative to the dosing visits. If a dose is not completely 
given at a specific visit (eg, subject only received one injection instead of the two planned 
injections), then the subject will be considered to have no compliance for the visit. In the formula 
above it will be counted as no dose received at this visit.
A summary of percent treatment compliance categorized as ≤80% and >80% will be provided by 
treatment group for the overall treatment period as well as for Double-Blind treatment period.
For the Double-Blind treatment period compliance will refer to the first 12 weeks and will be 
presented by treatment received at baseline. For the overall treatment period, the compliance will 
be calculated for the following three groups: bimekizumab 160mg, bimekizumab 320mg, and all 
bimekizumab. Treatment compliance for the bimekizumab 160mg and 320mg group will be 
calculated for the time the subject receives 160mg or 320mg, eg for a subject who switches from 
Placebo or bimekizumab 16mg to bimekizumab 160mg at Week 12, the compliance will only be 
calculated for the time the subject receives bimekizumab 160mg. The all bimekizumab group 
will consist of all the doses of bimekizumab including bimekizumab 16mg, and will only 
exclude the time subjects receive Placebo.
A by-subject listing of treatment compliance will be provided, presenting percent compliance 
and numbers of expected and received doses for the Double-Blind Period and for treatment with 
any dose of bimekizumab.
8
EFFICACY ANALYSES
8.1
Statistical analysis of the primary efficacy variable
8.1.1
Derivations of ASAS score and response
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 numeric rating scale (NRS) in at least 3 of the 4 following domains 
(Anderson, 2001):
x
PGADA
x
Pain assessment (total spinal pain, question 1 from total and nocturnal spinal pain 
questionnaire)
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 38 of 194
x
Function (represented by the BASFI)
x
Inflammation (the mean of the BASDAI questions 5 and 6) c
and absence of deterioration in the potential remaining domain. Deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit.
The ASAS criteria for 40% improvement are defined as relative 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 and 
no worsening at all in the remaining domain.
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, which 
includes, in addition to the 4 domains above, spinal mobility (ie, lateral spinal flexion) and hs-
CRP as more objective measures (Brandt et al, 2004). If the hs-CRP value is below 2 mg/L, then 
it will be imputed as the constant value of 2 mg/L.
The ASAS partial remission response is defined as a score of ≤2 units on a 0 to 10 unit scale in 
all 4 domains. 
For all non-missed visits, if any of the component scores are missing, then the following rules 
will be applied:
x
If the component values are missing at Baseline, the percent improvement from Baseline to a 
visit for the given component will be imputed as 0%. The unit improvement will be imputed 
as 0.
x
If the component value at a given visit is missing and the Baseline value is present, the 
missing component will be replaced by the last non-missing observation (LOCF) for that 
component.
If the Baseline value of an ASAS component is 0, then for the purposes of calculating ASAS, the 
percent change from Baseline will be determined as follows (zero divisor rule):
x
If the post-Baseline component value is also 0, set the percent change equal to 0;
x
If the post-Baseline component value is >0, then calculate the percent change as though the 
Baseline value were 0.1.
If all ASAS components at Baseline are missing, no Screening observation will be used and the 
subject will be regarded as non-responder throughout the study.
With regards to the BASFI component see Section 8.1.1.3 for calculation in case of missing 
values of single questionnaire items.
With regards to the BASDAI component see Section 8.1.1.4 for calculation in case of missing 
values of single questionnaire items.
8.1.1.1
Patient’s Global Assessment of Disease Activity (PGADA)
Subjects will score 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) (Section 12.4).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 39 of 194
8.1.1.2
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/EWP/556/95) (Section 12.5).
The arithmetic mean of both questions describes the total and nocturnal spinal pain.
8.1.1.3
Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI contains 10 questions (Section 12.6). The first 8 questions evaluate activities related 
to functional anatomical limitations due to the course of this inflammatory disease. The final 2 
questions evaluate the subjects’ ability to cope with everyday life. An NRS ranging from 0 to 10 
is used to answer the questions on the test.
The arithmetic mean of the 10 scales gives the BASFI score, which is a value between 0 and 10. 
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 above. If more than 2 of the items are 
missing, the BASFI score will be left missing.
8.1.1.4
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is the most commonly used instrument to 
. The 
BASDAI is a validated self-reported instrument which consists of 6 NRSs, each with 10 units to 
measure the severity of the 5 major symptoms: 
 over the last week. The 
BASDAI questionnaire is available in Section 12.7. To give each symptom equal weighting, the 
average of the 2 scores relating to 
 is taken. The resulting 0 to 50 sum score is 
divided by 5 to give a final BASDAI score between 0 and 10, with lower scores indicating lower 
disease activity.
The BASDAI is calculated as follows:
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ASAS inflammation component, which is calculated as the average of the 2 
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If 1 major symptom of the BASDAI is missing, the sum score of the remaining symptoms will be 
divided by the number of symptoms assessed. If more than 1 major symptom is missing, the sum 
score will be set to missing.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 40 of 194
8.1.2
Primary analysis of the primary efficacy variable
The primary efficacy variable (ASAS40 at Week 12) will be analyzed for all subjects in the FAS. 
The dose-response relationship between treatment and ASAS40 response will be assessed with 
an ordered categorical analysis using a non-parametric correlation statistic of Mantel and 
Haenszel (Mantel and Haenszel, 1959) and modified ridit scores (Bross, 1958) with the 
corresponding p-value.
The analysis will include geographic region and prior TNF inhibitor exposure (yes/no) as 
stratification factors. Prior TNF inhibitor exposure will be used as stratification factor as it may 
have an impact on efficacy. The correlation between dose and ASAS40 response will be 
evaluated at a two-sided significance level of α=0.05. This evaluation of dose-response will 
constitute the primary efficacy analysis.
A table will present the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 160mg, BKZ 
320mg, and the correlation statistic of Mantel and Haenszel (ridit score) with the corresponding 
p-value. 
NRI will be used to account for missing data; ie, subjects with a missing ASAS40 score at Week 
12 or who discontinued study treatment prior to the Week 12 visit will be considered non-
responders for the primary analysis.
8.1.3
Secondary analyses of the primary efficacy variable
As the secondary analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure. To 
avoid the problem of the so-called monotone likelihood resulting in infinite large confidence 
intervals (eg, if one of the cell counts in the 2x2 table is equal to zero), a penalized maximum 
likelihood approach based on the modified score procedure of Firth (eg, Heinze and Schemper, 
2002) will be used in the logistic models. If the logistic regression model is unable to converge, 
then a 2-way categorical variable for geographic region (North America and Europe) will be 
used. Should the logistic regression model be is unable to converge even with this restriction, 
then geographic region may be dropped from the model to facilitate convergence. If the logistic 
regression model be unable to converge after dropping the geographic region, then prior TNF 
inhibitor exposure may be dropped as well. Comparisons will be made for each dose versus 
placebo at a 2-sided significance level of α=0.05. For each dose, the odds ratio versus placebo, 
the 95% confidence interval, and the corresponding p-value will be calculated. If the logistic 
regression model is unable to converge after dropping the geographic region, then prior TNF 
inhibitor exposure may be dropped as well. Comparisons will be made for each dose versus 
placebo at a 2-sided significance level of α=0.05. For each dose, the odds ratio versus placebo, 
the 95% confidence interval, and the corresponding p-value will be calculated.
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 41 of 194
If the dose-response relationship fails to reach significance at a significance level of α=0.05, then 
the further pairwise comparisons are seen as non-significant.
A table will present the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 160mg, BKZ 
320mg, and for each dose the odds ratios (differences to placebo), 95% confidence intervals, and 
corresponding p-values from the logistic regression.
NRI will be used to account for missing data; ie, subjects with a missing ASAS40 score at Week 
12 or who discontinued study treatment prior to the Week 12 visit will be considered non-
responders for the primary analysis.
8.1.4
Supportive analyses of the primary efficacy variable
The following supportive analyses for the primary endpoint are planned:
1. The primary dose-response analysis and pairwise comparisons will be repeated for all 
subjects in the PPS to evaluate the effect of important protocol deviations on the analysis.
2. The primary dose response analysis and pairwise comparisons will be repeated for all 
subjects in the RS to evaluate the consistency of the FAS with the ITT principle. Subjects 
with no valid measurement of the primary efficacy variable at Baseline will be included as 
non-responders. NRI will be used to account for missing data.
3. The change from Baseline in all ASAS components (ie, PGADA, total spinal pain, BASFI, 
and BASDAI) will be analyzed using the ANCOVA with treatment, geographic region, and
prior TNF inhibitor exposure as fixed effects and the Baseline values as covariate. MI will be 
used for missing data (Section 4.2.1).
For the supportive analysis number 1 and 2 two tables will be displayed. One table will present 
the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 160mg, BKZ 320mg, and the 
correlation statistic of Mantel and Haenszel (ridit score) with the corresponding p-value. The 
other table will present the responder rates, and for each dose the odds ratios (differences to 
placebo), 95% confidence intervals, and corresponding p-values from the logistic regression.
For the supportive analysis number 3 tables will present the least-square means and standard 
error for placebo and bimekizumab dose for the ANCOVA models. For the pairwise comparison 
between placebo and bimekizumab dose the least-square means, standard error, corresponding p-
values, and 95% confidence intervals for the contrasts will be provided.
8.1.5
Sensitivity analyses of the primary efficacy variable
Two sensitivity analyses will be performed for the primary dose response analysis and for the 
supportive analysis number 3:
1. This analysis evaluates the effectiveness of the treatment (de facto hypothesis) and will be 
based on the ordered categorical analysis to evaluate dose-response as specified in the 
primary analysis. In an attempt to prevent missing data during the study, efforts will be made 
to collect data from subjects that withdraw early from the study. An analysis will be 
performed in which all available data at Week 12 will be considered. In this case, subjects
will be analyzed according to their randomized treatment, even if they discontinued prior to 
Week 12 and were no longer on the randomized study treatment when the assessment was 
performed at Week 12. If Week 12 data for the ASAS response are not collected, the subject 
will be assumed to be a non-responder. It should be noted that this measures something 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 42 of 194
different from the primary analysis and could be confounded by placebo subjects who 
withdraw and are subsequently on another active medication at the time of the Week 12 
assessment.
2. An additional sensitivity analysis will be based on observed data only for subjects who are 
still on the initially randomized treatment at Week 12. Subjects with missing data or who 
have prematurely discontinued study treatment will be excluded from the analysis. The same 
procedure described for the primary efficacy analysis of dose response will be used.
The following sensitivity analyses will be performed for the secondary analysis for the primary 
efficacy variable (pairwise comparison analysis of the primary efficacy variable) in order to 
assess the missing data assumptions:
1. Missing data will be imputed using MI. In MI, the missing value is replaced by a set of 
plausible values, where each value is a Bayesian draw from the conditional distribution of the 
missing data given the observed data. Intermittent missing data will be imputed using the
MCMC method, followed by monotone regression for monotone missing data to evaluate the 
effect of the method for handling missing data on the analysis. The ASAS components will 
be imputed individually and then the ASAS response will be calculated using the complete 
datasets. The multiply imputed data sets will be analyzed using a logistic regression model 
with fixed effects fixed effects for treatment, region, and prior TNF inhibitor exposure. 
Finally, the results will be combined into a single inference using Rubin’s rule (Carpenter 
and Kenward, 2013). This procedure assumes a MAR pattern of missingness and corresponds 
to an estimand of what has been called the difference in outcome improvement if all subjects 
tolerated or adhered to treatment (Mallinckrodt et al, 2012). More details are available in 
Section 4.2.1.
2. The logistic regression model will be applied where all available data at Week 12 will be 
considered, as described in sensitivity analysis (1) for the primary efficacy variable.
3. The logistic regression model will be applied where only observed data for subjects still on 
the initially randomized treatment at Week 12 will be considered, as described in sensitivity 
analysis (2) for the primary efficacy variable.
The same tables as used for the primary and secondary efficacy analysis for the primary efficacy 
variable and for the supportive analysis number 3 with the different imputation analysis will be
presented.
8.2
Statistical analysis of the secondary efficacy variables
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, ASAS20 response and ASAS5/6) will be analyzed for treatment 
effects using pairwise comparisons based on the same method as that for the primary efficacy 
variable.
All continuous variables (ie, ASDAS-CRP, BASDAI, and BASFI) will be analyzed for treatment 
effects using pairwise comparisons based on an ANCOVA model with treatment, geographic 
region, and prior TNF inhibitor exposure as fixed effects and the Baseline value as covariate.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 43 of 194
For the categorical variables the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 
160mg, BKZ 320mg, and for each dose the odds ratios (differences to placebo), 95% confidence 
intervals, and corresponding p-values from the logistic regression will be provided.
For the continuous variables the least-square means and standard error for placebo and 
bimekizumab dose for the ANCOVA models will be displayed. To pairwise compare placebo 
and bimekizumab dose the least-square means, standard error, corresponding p-values, and 95% 
confidence intervals for the contrasts will be provided. The ANCOVA model results for BASFI 
will be located in the supportive analysis section for the ASAS component and not in the 
secondary analysis section.
All categorical efficacy variables will be analyzed using observed cases as treated and imputed 
with NRI and all continuous variables will be analyzed using the MI.
8.2.1
Derivations of ASDAS-CRP, ASDAS-MI, and ASDAS Status
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2009) as shown below:
x
0.121 x 
 (BASDAI question 2 result)
x
0.058 x 
 (BASDAI question 6 result)
x
0.110 x PGADA
x
0.073 x 
 (BASDAI question 3 result)
x
0.579 x (natural logarithm of the (hs-CRP [mg/L] + 1))
, PGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS-CRP.
If one component for the ASDAS-CRP is missing at a given visit, that component will be 
imputed by carrying the last observation forward, and the ASDAS-CRP will be calculated 
accordingly. If no value is available for that component before the missing time point, the next 
observation may be carried backwards. If more than one component for the ASDAS-CRP is
missing, ASDAS-CRP will be treated as missing.
If the hs-CRP value is below 2 mg/L, then it will be imputed as the constant value of 2 mg/L
(Machado et al, 2015).
ASDAS Status in defined in four disease activity categories based on ASDAS-CRP as follows:
x
Inactive Disease: ASDAS-CRP <1.3
x
Moderate Disease Activity: ASDAS-CRP >=1.3 to <2.1
x
High Disease Activity: ASDAS-CRP >=2.1 to <=3.5
x
Very High Disease Activity: ASDAS-CRP >3.5
ASDAS-MI is defined as ASDAS-CRP reduction (improvement) of ≥ 2.0 relative to Baseline.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 44 of 194
8.3
Statistical analysis of other efficacy variables
Other efficacy variables will be analyzed for all subjects in the FAS, DBRS, ESS, cDBRS, cESS, 
and DBS.
All categorical variables will be presented using frequency tables by each visit. All continuous
variables will be summarized using descriptive statistics by each visit.
The Hospital Anxiety and Depression Scale (HADS) will be analyzed separately for HADS-A
and HADS-D. The summary statistics for HADS-A and HADS-D will be presented in two 
different tables.
Times series plots will be provided for the response rate or change from Baseline for the primary 
and secondary efficacy variables. The plots will show the weekly response rate over the first 12 
weeks.
The MRI of the spine and sacroiliac joints will be performed in a substudy with subjects who 
were classified as MRI-positive at Baseline as per ASAS-Outcome Measures in Rheumatology 
Clinical Trials (OMERACT) criteria.
A subset of the FAS will be used for the analyses of MASES. The MASES Score will only be 
analyzed for subjects with enthesitis at Baseline (MASES > 0).
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in weeks from Baseline until the first date when the response is achieved.
Following derivation will be used: Days from Baseline until the first date divided by 7. There 
will be no rounding for the Kaplan Meier estimates. Subjects who discontinue study prior to 
achieving a response will be censored at the date of study discontinuation. Subjects who reach 
the Week 12 visit without achieving a response will be censored at the date of the Week 12 visit. 
Missing response data will be imputed with NRI.
The median time to response including the 2-sided 95% confidence interval will be calculated for 
each treatment. Between groups differences (each bimekizumab dose versus placebo) will be 
analyzed using a log-rank test stratified by geographic region and prior TNF inhibitor exposure.
Missing response data will be imputed with NRI.
Summary tables will be presented for the time to onset of ASAS20 response and ASAS40 
response including following information: number of subjects achieving ASAS20/ASAS40 
response, number of subjects censored, descriptive statistics (minimum, 25th percentile, median, 
75th percentile, maximum) for the Kaplan-Meier estimates including the p-value (difference to 
placebo). Additional Kaplan-Meier Plots will be provided.
All other efficacy variables will be analyzed using observed cases as treated and imputed with 
NRI for binary variables and MI for continuous variables.
Subjects in the ESS who discontinue with bimekizumab treatment during the Dose-Blind Period
will be treated as missing and categorical/continuous variables will be imputed.
In order to assess the potential bias of the potentially unblinded subjects based on data, the 
results of the final analysis will be utilized. Results of the ASAS40 response of the rerandomized 
320mg and 160mg treatment group at Week 48 will be compared to the potentially unblinded, 
randomized 320mg and 160mg treatment groups. If the percentage of ASAS40 responders is 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 45 of 194
comparable as assessed by overlapping 95% confidence intervals, the potential bias is estimated 
to be at minimum.
8.3.1
Bath Ankylosing Spondylitis Metrology Index (BASMI)
The BASMI characterizes the spinal mobility of a subject with AS and consists of 5 clinical 
measures to reflect axial status: cervical rotation; tragus-to- wall distance; lateral lumbar flexion; 
lumbar flexion (modified Schober); intermalleolar distance. Each of the 5 movements is scored 
according the linear BASMI definition (see bullet points below). The mean of the 5 scores 
provides the BASMI score. The higher the BASMI score, the more severe is the patient’s 
limitation of movement due to their AS.
BASMI linear definition (S=score, A=assessment):
x
Lateral lumbar flexion (mean right/left): S = (21.1 cm –A) / 2.1 cm
x
Tragus-to-wall distance (mean right/left): S = (A – 8 cm) / 3 cm
x
Lumbar flexion (modified Schober): S = (7.4 cm – A) /0.7 cm
x
Intermalleolar distance: S = (124.5 cm – A) / 10 cm
x
Cervical rotation (mean right/left): S = (89.3° - A) / 8.5°
The points above have all the additional condition 0 ≤ S ≤ 10.
For cervical rotation, tragus-to-wall distance and lumbar flexion, take the mean of the left and 
right measurements, if both are available. Otherwise, the available measurement will be used.
For the lumbar flexion (modified Schober), values greater than 9.0 cm (Maksymowych, 2006) 
will be flagged as invalid and treated as if they were missing values. The below imputation rules 
apply for BASMI.
If 1 or 2 clinical measures for the BASMI are missing at one visit, the missing measure will be 
imputed by carrying the last observation forward, and the BASMI will be calculated accordingly. 
If no value is available for the clinical measure before the missing time point, the next 
observation may be carried backwards. If more than 2 items are missing, the BASMI score will 
be treated as missing.
8.3.2
Physician’s Global Assessment of Disease Activity (PhGADA)
The Investigator will assess the overall status of the subject with respect to their AS signs and 
symptoms and functional capacity (considering both joint and skin components) using an NRS in
which 0=very good, asymptomatic and no limitations of normal activities and 10=very poor, 
very severe symptoms which are intolerable and inability to carry out normal activities.
8.3.3
Short Form – 36 Items Health Survey
The SF-36 measures the following 8 health domains as rated by the subjects over the past four 
weeks: Physical Functioning, role Physical, Bodily Pain, General Health, Vitality, Social 
Functioning, Role Emotional, and Mental Health. The questionnaire is available in Section 12.8.
The classification of the questionnaire items to the health domains is shown in Section 12.9.
The SF-36 PCS and MCS are used to measure the two broad components, or aspects, of health-
physical and mental. PCS and MCS are based on the aggregate of 8 health concepts described 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 46 of 194
above and all of the eight health domain scales are used to score both components summary 
measures.
One additional item asks respondents about health change over the past year.
The SF-36 will be used using QualityMetric’s Health Outcomes™ Scoring Software. The 
software uses updates 2009 U.S. population norms and applies a Full Missing Score Estimation 
method as follows:
x
A health domain score (except the physical functioning domain) will be estimated provided 
that at least one non-missing response is available within that domain.
x
For the physical functioning domain item response theory will be used to develop a model 
for estimates of the missing score.
x
Regression methods are then applied to estimate the PCS and the MCS on the basis of the 
available domains.
8.3.4
Medical Outcomes Study (MOS) Sleep Scale
The MOS Sleep Scale is a validated generic self-administered scale measuring specific aspects 
of sleep. The frequency with which each problem has been experienced during the previous 4 
weeks is rated on a 6-point scale ranging from “none of the time” to “all of the time”, except 
sleep quantity, which is reported in hours. All scores are transformed linearly to range from 0 to 
100, again with the exception of the sleep quantity subscale, which is scored in hours. Higher 
scores indicate more of the attribute implied by the scale name (eg, more sleep disturbance, more 
adequate sleep, or greater sleep quantity). The questionnaire is available in Section 12.10.
The item scores (1, and 3 through 12) are used to derive 7 different scale scores. In addition, the 
average number of hours slept over the past 4 weeks (Item 2) is used to create a raw and a 
dichotomized measure of sleep. The scale scores are created by averaging the respective rescaled 
item scores. Scales with at least 1 item answered can be used to generate a scale score. Items that 
are left blank (missing data) are not taken into account when calculating the scale scores. Scores 
represent the average for all items in the scale that the respondent answered. The domains of 
interest for this study are the Sleep Disturbance and the Sleep Problems Index II domains. The 
table below describes which items are used for both sleep scales.
Table 8‒1:
MOS Sleep Scale Scores
Scale description (Short name)
Item score
Sleep disturbance (SLPD4)
1, 3 (R), 7 (R), 8 (R)
Sleep problems Index II (SLP9)
1, 3 (R), 4, 5 (R), 6 (R), 7 (R), 8 (R), 9 (R), 12
(R) refers to a reversed item.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 47 of 194
Table 8‒2:
MOS Sleep Scale recoding of items
Item numbers
Original response
category
Re-coded value (not
reversed)
Re-coded value
(reversed)
1
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1
2
3
4
5
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0
25
50
75
100
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-- N/A --
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1
2
3
4
5
6
>6
-- N/A
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100
80
60
40
20
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5
6
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N/A=not applicable.
8.3.5
Ankylosing Spondylitis Quality of Life (ASQoL)
The ASQoL consists of 18 items, each with a score of 0 = no or 1 = yes, so that the sum score 
ranges from 0 to 18, with higher scores indicating worse quality of life. The questionnaire is 
available in Section 12.11.
If 3 or fewer items are missing, the missing responses will be imputed with the mean of the 
available responses from that visit to calculate a total score. If more than 3 items are missing, the 
total score will be left missing.
8.3.6
Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
The MASES Index comprises 13 items (bilateral costochondral 1, costochondral 7, anterior 
superior iliac spine, posterior iliac spine, iliac crest and proximal insertion of the achilles tendon 
sites, and the fifth lumbar vertebral body spinous process) (Heuft-Dorenbosch et al, 2003) each 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 48 of 194
scored as 0 = yes or 1 = no and then summed for a possible score of 0 to 13, with higher scores 
indicating worse enthesitis. The questionnaire is available in Section 12.12.
If 7 or more items are available, MASES will be imputed by dividing the sum score with the 
number of assessments and multiplying the result with 13. If less than 7 times are available, 
MASES will be treated as missing.
Presence of enthesitis at Baseline should be defined as a Baseline MASES score >0.
8.3.7
MRI assessment
An MRI of the spine and sacroiliac joints will be performed in a substudy with approximately 20
subjects per treatment group at Baseline. A central reader will assess Baseline MRIs to identify 
MRI-positive subjects as per the ASAS OMERACT criteria. An MRI at Week 12 and Week 48 
will be performed for those subjects who were MRI-positive at Baseline. The Baseline MRI 
should be performed after confirmation of eligibility based on screening assessments for the 
study and before the first bimekizumab injection. Magnetic resonance imaging at Week 12 and
Week 48 should be performed as close to the Week12/Week 48 Visit as possible. Additional 
details for standardized performance and processing of MRIs will be provided in an MRI 
manual. The MRIs will be read centrally by readers who are blinded to treatment assignment and 
chronological order of the MRIs according to a charter for independent imaging assessment.
The following 2 different scoring systems will be utilized to determine changes from Screening.
SPARCC MRI (SI joint) score
The SPARCC MRI (SI joint) scoring method for lesions found on the MRI is based on an 
abnormal increased signal on the short-tau-inversion recovery (STIR) sequence, representing 
bone marrow edema (defined as an increased signal in bone marrow on a T2-weighted sequence, 
reflecting an increased concentration of “free water” related to a bone lesion). Each SI joint is 
divided into 4 quadrants: upper iliac, lower iliac, upper sacral, and lower sacral. The presence of 
increased signal on STIR in each of these 4 quadrants are scored on a dichotomous basis, where 
1 = increased signal and 0 = normal signal. Joints that include a lesion exhibiting intense signal 
are each given an additional score of 1 per slice that demonstrated this feature. Similarly, each 
joint that included a lesion demonstrating continuous increased signal of depth greater or equal 1 
cm from the articular surface is also given an additional score of 1. The scoring is repeated in 
each of 6 consecutive coronal slices. Total SI joint SPARCC scores can range from 0 to 72.
ASspiMRI-a (Berlin modification) score
The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on STIR 
sequences without other fat saturation techniques. This scoring method quantifies active changes 
in 23 vertebral units (VU) of the spine (from C2 to S1). A VU is defined as the region between 2 
virtual lines through the middle of each vertebra. Active inflammation is scored by grading the 
degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that 
represent the highest level of inflammation in a particular VU. Total spine ASspiMRI-a score in 
the Berlin modification can range from 0 to 69.
The following imputation rules should be used for calculating the total for both SPARCC MRI 
(SI joint) scores and ASspiMRI-a (Berlin modification) score:
x
If all scores are NA at a visit, the imputed total is blank for that visit.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 49 of 194
x
Treat NA as 0 when computing the total score.
x
If ALL the Baseline scores are NA, then do not carry forward the Baseline scores. Treat the 
subsequent visit as a surrogate Baseline.
x
Carry the NA score from the Baseline visit forward to all follow-up visits unless all scores at 
Baseline are NA.
x
Carry the numeric score from the last visit with non-NA score forward if a score is NA at a 
follow-up visit (unless all scores are NA at follow-up).
8.3.8
Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (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).
8.3.9
C-reactive protein (CRP) and high-sensitivity C-reactive protein 
(CRP)
Blood will be collected for measurement of CRP and hs-CRP. CRP and hs-CRP are indicators 
for inflammation and are measured in the blood. Hs-CRP is a component of composite efficacy 
variables, and in addition is also summarized and analyzed as individual variables. For hs-CRP 
the summary statistics should contain n, geometric mean, geometric CV, median, first and third 
quartile (Q1 and Q3), minimum, and maximum, where the geometric CV (%) is calculated using:
ܥܸൌඥ݁ௌ஽೗೙
మെͳ
(11)
with SDln – the standard deviation of the ln-transformed hs-CRP values.
For descriptive statistics, the observed values and ratio to Baseline values will be displayed. 
hs-CRP and CRP values below the limit of quantification should be set to half the limit of 
quantification for the calculations. The limit of quantification for hs-CRP is 0.16 mg/L and 0.4 
mg/dL = 4.00 mg/L for CRP.
8.4
Subgroup analysis
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
variables for subgroup analyses are defined in Section 4.8.
Subjects will be counted to have a positive treatment-emergent AbAb status in case the first 
AbAb positivity occurred up to Visit 7 (Week 12). The definition of first AbAb occurrence is 
described in Section 9.2.
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 50 of 194
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit using the PK-PPS, and using a subset of the DBS which includes subjects that belong to 
both analysis sets, the DBS and the PK-PPS.
If bimekizumab plasma concentration measurements are deemed to be below the level of 
quantification (BLQ), then for calculation of the derived statistics this sample result will be set to 
half the LLOQ. The subjects with at least 1 result that is defined as BLQ will also be listed 
within the respective analysis table. Descriptive statistics will be calculated if at least 2/3 of the 
values are above the LLOQ. If this is not the case, only median, minimum, and maximum will be 
presented.
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group.
The bimekizumab concentrations will also be listed.
9.2
Pharmacodynamics and Immunogenicity
The biomarker data will be separated between LGC assays, mulitplex proinflammatory cytokine 
and chemokine analysis, flow cytometry - TBNK panel, and flow cytometry -
Th1/Th2/Th17/Th22 panel. Biomarker variables will be summarized and listed for each 
treatment at each scheduled visit using the PD-PPS, and using a subset of the DBS which 
includes subjects that belong to both analysis sets, the DBS and the PK-PPS.
In addition to the PD variables, whole blood will be stored to isolate deoxyribonucleic acid 
which may be used to examine genetic and epigenetic changes. The blood samples for genetic 
and epigenetic, and genomic, proteomic/metabolomics will not be analyzed in the interim or 
final analysis. Variables will be analyzed in a separate analysis as ad-hoc analysis. 
The AbAb status will be determined for each visit where samples are taken for drug 
concentration measures. A cut point will be determined by the bioanalytical laboratory and will 
be used to determine the AbAb status as “above the cut point” (ACP) or “below the cut point” 
(BCP). For any AbAb 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 AbAb 
titre will be reported.
At each visit:
x
Samples that are either BCP or ACP and NCP are defined as AbAb-
x
Samples that are ACP and CP are defined as AbAb+
In addition, overall AbAb status should be determined:
x
Subject AbAb positivity is defined as having with AbAb+ at any time in the treatment 
period. This does not include Baseline/pre-treatment
x
Subject AbAb negativity is defined with AbAb- at any time in the treatment period. This 
does also include AbAb+ at Baseline/pre-treatment
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07 Sep 2018
Statistical Analysis Plan
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AS0008
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Page 51 of 194
x
If there is AbAb+ at Baseline/pretreatment and there is a 4-fold increase in titre at least at one 
visit during the treatment period, then the subject has also an overall AbAb positivity status.
The visit of the first occurrence of AbAb positivity is defined as the visit when a subject is 
AbAb+ for the first time during treatment period excluding Baseline/pre-treatment. If there is 
AbAb+ at Baseline/pre-treatment and there is a 4-fold increase in titre at least at one visit during 
the treatment period, then the subject’s first occurrence visit is the Baseline Visit.
The number and percentage of subjects with AbAb levels above the specified cut point will be 
summarized. 
In addition, the time point of the first occurrence of AbAb positivity during the Double-Blind 
Period, and the entire treatment period (excluding Baseline and pre-treatment) will be 
summarized for each treatment group.
All individual subject-level AbAb results will be listed including the screening assay, 
confirmatory assay, and titres if applicable. Note, that titre results will only be available, if the 
confirmatory assay is positive.
Immunogenicity data will be summarized and listed using the PK-PPS analysis set.
10
SAFETY ANALYSES
All safety summaries and listings will be performed using all subjects in the SS.
10.1
Extent of exposure
The duration of exposure and time at risk will be summarized for the Double-Blind Period and 
the entire treatment period. For the entire treatment period the duration of exposure and time at 
risk will be calculated for bimekizumab 160mg, bimekizumab 320mg, and all bimekizumab. The 
calculation of exposure duration and time at risk for the all bimekizumab group is different from 
that of the other two groups. For all bimekizumab the duration of exposure and time at risk will 
include the time a subject received any dose of bimekizumab (including 16mg or 64mg) while 
for the other two treatment groups only the time a subject received 160mg, or 320mg will be 
included into the calculation. 
Duration of exposure Double-Blind Period
The duration of exposure (in days) during the Double-Blind Period will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
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(12)
28 days refer to one half-life of bimekizumab. 
Note: If the date of last injection (Double-Blind Period) + 28 extends to a date beyond the date of 
first injection (Dose-Blind Period), then this calculation reverts to
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07 Sep 2018
Statistical Analysis Plan
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AS0008
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ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
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(13)
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
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Duration of exposure entire treatment period
For subjects who do not switch study treatments, or who receive bimekizumab 16mg or 64mg 
will be summarized under all bimekizumab group:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
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Note: If the date of last injection +28 extends to a date beyond the final visit date (not including 
SFU), then this calculation reverts to:
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െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(16)
For subjects who die, then this calculation reverts to:
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(17)
For subjects who receive Placebo or bimekizumab 16mg or 64mg in the Double-Blind Period
and will be summarized under their Dose-Blind treatment in the overall table group 
bimekizumab 160mg or 320mg, or subjects who received Placebo and will be summarized in the 
overall table under their Dose-Blind treatment:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
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Note: If the date of last dose +28 extends to a date beyond the final visit date (not including 
SFU), then this calculation reverts to:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 53 of 194
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(19)
For subjects who die during the Dose-Blind Period, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(20)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose in Double-Blind Period, the date of first and last 
dose in Dose-Blind Period and the duration of exposure during Double-Blind Period and under 
bimekizumab treatment (any dose of bimekizumab) will be performed.
Time at risk Double-Blind Period
For subjects who complete the final visit of the Double-Blind Period and continue to the Dose-
Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(21)
For subjects who discontinue on or prior to the final visit of the Double-Blind Period, use the 
minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳͶͲ
(22)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(23)
ܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(24)
where 140 days refers to 5*half-life of bimekizumab.
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(25)
Time at risk entire treatment period
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 54 of 194
For subjects who do not switch study treatments, or who receive bimekizumab 16mg or 64mg 
and will be summarized under all bimekizumab group:
For subjects who complete the Dose-Blind Period and enter the extension study:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂ܸ݅ݏ݅ݐͳ͸ ሺܹ݁݁݇Ͷͺሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(26)
For subjects who die prior to the final visit:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(27)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(28)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(29)
For subjects who receive Placebo or bimekizumab 16mg or 64mg in the Double-Blind Period
and will be summarized under their Dose-Blind treatment in the overall table group 
bimekizumab 160mg or 320mg, or subjects who received Placebo and will be summarized in the 
overall table under their Dose-Blind treatment:
For subjects who complete the Dose-Blind Period and enter the extension study:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂ܸ݅ݏ݅ݐͳ͸ ሺܹ݁݁݇Ͷͺሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(30)
For subjects who die during the Dose-Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(31)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳͶͲ
(32)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(33)
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 55 of 194
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(34)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(35)
10.2
Adverse events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
AEs (including serious AEs) are characterized as either non-treatment or treatment emergent 
according to the following criteria:
x
Non-treatment emergent are the events with onset date and time prior to the very first 
administration of study medication (bimekizumab or placebo) or after a 140-day period after 
the final drug administration.
x
Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment emergent (eg, in the case of 
premature discontinuation or during the SFU period).
All AEs occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the eCRF. For each AE the following information will be recorded in the eCRF:
AE term (verbatim term), date of onset, whether or not the AE was classified as a SAE, as an AE 
of special interest, intensity, relationship to study medication, action taken with study 
medication, other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation.
ADRs are defined as a response to a drug which is noxious and unintended and which occurs at 
doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification 
of physiological function. Any AE that is considered “Related” to study treatment will be classed 
as an ADR.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will be 
allocated to the Double-Blind treatment. An exception from this general rule is made for adverse 
drug reactions (ADRs), and AE of hypersensitivity reactions and anaphylactic reactions. If those 
AEs occur on the same days as the treatment switch, the AEs will be allocated to the Dose-Blind 
treatment.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 56 of 194
The incidence of TEAEs will be summarized by MedDRA SOC, high level term, and PT. Tables 
with incidences of classified TEAEs by maximum intensity, by relationship, and by subject 
number will be provided. The incidence of non TEAEs, non-serious TEAEs above the reporting 
threshold of 5% of subjects and relationship will be summarized. Furthermore the incidence of 
all TEAEs, serious TEAEs, non-serious TEAEs, and TEAEs leading to study discontinuation 
and/or permanent withdrawal of study medication, adverse drug reactions, fungal infectious 
disorder TEAEs, opportunistic infection (including tuberculosis) TEAEs, malignant or 
unspecified tumor TEAEs, malignant tumor TEAEs, major cardiovascular event TEAEs, 
haematopoietic cytopenias TEAEs, neuropsychiatric events TEAEs, inflammatory bowel disease 
TEAEs, hypersensitivity and anaphylactic Reaction TEAEs, hepatic events TEAEs, and TEAEs 
by timing of onset relative to AbAb Status will be summarized. In addition, an overall summary 
table will be provided.
The tables will be split into the Double-Blind Period and the complete treatment period 
(exception non TEAE table and TEAEs by timing of onset relative to AbAb Status). 
Presentations for the Double-Blind Period will summarize AEs that start prior to or at Visit 7 
(see details given above) by treatment group as randomized for the Double-Blind Period.
Presentations for the complete treatment period will only summarize AEs that occur under 
treatment with bimekizumab, irrespective of the treatment period. For summaries of the
bimekizumab 160mg, and bimekizumab 320mg treatment groups, patients randomized to 
Placebo, bimekizumab 16mg or 64mg at Baseline will only be included with AEs that start in the 
Dose-Blind Period. The all bimekizumab treatment group will also present AEs occurring under 
bimekizumab 16mg or 64mg treatment in the Double-Blind Period. AEs for each subject will be 
summarized based on the treatment actually received at the onset of each particular AE.
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER) will only be 
calculated for the complete treatment period for following tables in the final analysis: all TEAEs, 
serious TEAEs, TEAEs leading to study discontinuation and/or permanent withdrawal, adverse 
drug reactions, fungal infectious disorder TEAEs, opportunistic infection (including 
tuberculosis) TEAEs, malignant or unspecified tumor TEAEs, malignant tumor TEAEs, major 
cardiovascular event TEAEs, haematopoietic cytopenias TEAEs, neuropsychiatric events 
TEAEs, inflammatory bowel disease TEAEs, hypersensitivity and anaphylactic Reaction 
TEAEs, hepatic events TEAEs, and TEAEs by timing of onset relative to AbAb Status.
10.2.1
Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(36)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2 and Table 12‒1.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(37)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 57 of 194
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(38)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (37 and 38) will be used but the date of first bimekizumab dose will be 
used instead of the date of first dose. The time to first dose and time to first bimekizumab dose 
differs only for those subjects who receive placebo at Baseline.
10.2.2
Exposure adjusted incidence rate (EAIR) and exposure adjusted 
event rate (EAER)
The EAIR is defined as the number of subjects (nAE) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊஺ா
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(39)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [36] in years) at the level of coding evaluated, nnoAE the number of subjects without the 
specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years (Section 10.1).
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (Section 10.1) in years is used. As indicated above, exposure-adjusted incidence rates will 
only be calculated for the overall treatment period. These presentations do not include AEs that 
occur under Placebo treatment. Therefore, a subject’s exposure time will only start at the first 
dose of bimekizumab in the Dose-Blind Period for subjects randomized to Placebo at Baseline. 
Also, for subject’s randomized to bimekizumab 16mg or 64mg at Baseline, exposure time will 
only be considered from the start of Dose-Blind Period, when presenting AEs for the 
bimekizumab 160mg, or bimekizumab 320mg groups. All exposure time on any bimekizumab 
dose is considered for the all bimekizumab column.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ಲಶǡఈ
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(40)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 58 of 194
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
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(42)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(43)
where nAE is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2, ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of 
interest (equation [36] in years) at the level of coding evaluated, nnoAE the number of subjects 
without the specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years 
(Section 10.1).
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෍
ܶோ௜௦௞ǡ௝
௡ಲ೗೗
௝ୀଵ
(44)
where NAE is the total number of AEs, ܶோ௜௦௞ǡ௝is a subject’s total time at risk in years and nAll the
number of subjects.
No confidence interval will be computed for EAER.
10.2.3
AE of Special Interest and AE of Special Monitoring
AE of special interest is any AE which meets the Hy’s Law criteria, defined as ≥3x upper limit 
of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with
coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with 
no alternative explanation for the biochemical abnormality.
AE of special monitoring for this study include: 
x
Infections (serious, opportunistic, fungal and TB) 
x
Malignancies, including lymphoma
x
Major cardiovascular events
x
Neutropenia
x
Neuropsychiatric events (in particular depression and suicide)
x
Inflammatory bowel disease
x
Anaphylactic reaction
x
Hepatic events 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 59 of 194
For the definitions of AE of special monitoring the Bimekizumab Safety Topics of Interest 
(Version date 19Feb2018) will be used.
The incidence of TEAEs of special monitoring will be summarized by MedDRA system organ 
class, high level term, and PT. EAIR with associated 95% CI and the EAER will be included in 
the summary tables. Serious infections are also classified as AE of special monitoring but no 
separate table will be produced.
The output table for the search criteria Standardized MedDRA Query (SMQ) = “Malignant or 
unspecified tumours (SMQ)” will include two different overall rows:
x
The first overall incidence row will summarize “Any malignancies (including unspecified)” 
and this row will summarize the incidence of all AEs flagged for inclusion in the table, 
regardless of the High Level Term (HLT) it codes to. 
x
The second overall incidence row will summarize “Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)” 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)”.
The output table for the search criteria SMQ=”Malignant tumours (SMQ)” will include two
different overall rows:
x
The first overall incidence row will summarize “Any malignancies” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table, regardless of the High 
Level Term (HLT) it codes to. 
x
The second overall incidence row will summarize “Any malignancy (excluding non-
melanomic skin cancers)” 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)”.
The output table for Anaphylactic reaction will include three different overall rows: 
x
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.
x
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.
x
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.
10.3
Clinical laboratory evaluations
The routine clinical laboratory evaluations specified in Table 10‒1 and will be summarized. If 
any additional analytes are also recorded then these will be listed only.
Different summary tables for hematology and biochemistry variables will be provided, based on
data from scheduled visits: observed values and change from Baseline, shift from Baseline to 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 60 of 194
maximum post-Baseline value (in Double-Blind Period), shift from Baseline to maximum post-
Baseline value (in Dose-Blind Period), shift from Baseline to minimum post-Baseline value (in 
Double-Blind Period), shift from Baseline to minimum post-Baseline value (in Dose-Blind 
Period), shift from Baseline to end of treatment (in Double-Blind Period), shift from Baseline to 
end of treatment (in Dose-Blind Period), and markedly abnormal laboratory data. 
End of treatment (in Double-Blind Period) will be defined as the last visit in the Double-Blind 
Period or the early termination assessment depending if the subject discontinued in the Double-
Blind Period.
End of treatment (in Dose-Blind Period) will be defined as the Week 48 visit or the early 
termination assessment depending if the subject discontinued early or not.
In addition, number of subjects who meet the Hy’s Law criteria (Section 10.2) will be described 
using frequencies.
All laboratory data will be listed by treatment, subject and visit including changes from Baseline
for numeric variables, flags for measurements outside the normal ranges, the relative study day, a 
flag for whether the test was not done and a flag for whether the subject was fasting.
Additional listings will be presented for Hepatitis B and C, human immunodeficiency virus 
(HIV), genomic proteomic/metabolomics, and genetic/epigenetic tests. CRP and hs-CRP will be 
tabulated and listed separately in the efficacy section.
Table 10‒1: Laboratory measurements
Hematology
Biochemistry
Urinalysis
Basophils 
Calcium
Bacteria
Eosinophils
Chloride
Crystals
Lymphocytes
Magnesium
Glucose
Monocytes
Potassium
pH
Neutrophils
Sodium
RBC
Hematocrit
Glucose
WBC
Hemoglobin
BUN
Urine dipstick for pregnancy testinga
MCH
Creatinine
MCHC
AST
MCV
ALT
Platelet count
ALP
RBC count
GGT
WBC count
Total bilirubin
LDH
Uric acid
Total cholesterol
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 61 of 194
Table 10‒1: Laboratory measurements
Hematology
Biochemistry
Urinalysis
Albumin
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
a A serum pregnancy test will be performed at Screening for all women of childbearing potential. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles and 
women during menopause. Natural menopause is recognized to have occurred after 12 consecutive months of 
amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause 
Society, 2015). A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A urine 
pregnancy test will also be performed at any study visit where there has been a delay in menses. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. 
Pregnancy test results must be negative prior to administering IMP.
b Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
Markedly abnormal values for biochemistry and hematology will be defined as laboratory values 
graded 3 or 4 according to the Rheumatology Common Toxicity Criteria (RCTC). Definitions of 
the markedly abnormal values are given in Table 10‒2 and Table 10‒3 and are based on the 
RCTC units. All units in the tables below will be converted to the standard international units 
based on Clinical Data Interchange Standards Consortium (CDISC) standards.
Values that are below the lower limit of the reference range will be flagged as “L” (low) and 
values that are above the upper limit of the reference range will be flagged as “H” (high) and 
listed as well. 
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. In the case where laboratory values are
below the lower limit of quantification, then these will be set to the midpoint between 0 and the 
lower limit of quantification for the purpose of summarizing the data.
Table 10‒2: Definitions of Markedly Abnormal Biochemistry Values
Variable (RCTC units)
Markedly abnormal definition
Low
High
ALP
N/A
>3 x ULN
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>3 x ULN
AST
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 62 of 194
Table 10‒2: Definitions of Markedly Abnormal Biochemistry Values
Variable (RCTC units)
Markedly abnormal definition
Low
High
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
ALP=alkaline phosphatase; AST=aspartate aminotransferase; N/A=Not applicable; RCTC= Rheumatology 
Common Toxicity Criteria; ULN=upper limit of normal.
Table 10‒3: Definitions of Markedly Abnormal Hematology Values
Variable (RCTC units)
Markedly abnormal definition
Low
High
Hemoglobin (g/dL)
<LLN
AND
>2.0 decrease from Baseline
N/A
Hemoglobin (g/dL)
<8.0
N/A
Leukocytes (total x 1000)
<2.0
N/A
Lymphocytes (x 1000)
<0.5
N/A
Neutrophils (x 1000)
<1.0
N/A
Platelets (x 1000)
<50
N/A
LLN=lower limit of normal; N/A = not applicable; RCTC= Rheumatology Common Toxicity Criteria.
10.4
Potential drug-induced liver injury (PDILI) assessment
All potential drug-induced liver injury (PDILI) events require immediate action, testing, and 
monitoring. 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 10‒4 (additional information) and Table 10‒5
(laboratory measurements).
PDILI laboratory results and additional PDILI information will only be listed by treatment group 
and subject. If specific PDILI information collected separately is matching to the entries in the 
standard eCRF pages collected for all subjects, the specific PDILI information will be added to 
the corresponding listing for the standard eCRF information (eg, lifestyle information is 
collected for all study subjects, the additional PDILI information for alcohol and illicit drug use 
will be included in the listings for lifestyle). For information collected on top (eg, family history 
of PDILI) a new listing will be generated.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 63 of 194
Table 10‒4: Additional PDILI information
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:
x
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty liver 
disease”)
x
Adverse reactions to drugs
x
Allergies
x
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)
x
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
Table 10‒5: PDILI laboratory measurements
Virology-related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophil antibody or monospot testing)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 64 of 194
Table 10‒5: PDILI laboratory measurements
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screena
Chemistry
Amylase
ALT, AST
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing 
transaminase elevation
Additional
Prothrombin time/INRb
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; 
hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative cause).
10.5
Vital signs, physical findings, and other observations related to 
safety
10.5.1
Vital signs
The following vital signs measurements will be assessed:
x
Systolic Blood Pressure (mmHg)
x
Diastolic Blood Pressure (mmHg)
x
Pulse Rate (bpm)
x
Temperature (C)
Vital signs measurements (absolute values and changes from Baseline) will be summarized and 
listed by visit and timing relative to dosing including changes from Baseline. The listing will also 
include details to abnormal values as defined in Table 10‒6. Temperature will only be listed and 
not summarized in a table. 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 65 of 194
Table 10‒6: Definitions of markedly abnormal blood pressure values
Variable (Unit)
Markedly abnormal low
Markedly abnormal high
Systolic blood pressure (mmHg) 
<90 and a decrease from 
Baseline of ≥20
>180 and an increase from
Baseline of ≥20
Diastolic blood pressure (mmHg)
<50 and a decrease from
Baseline of ≥15
>105 and an increase from
Baseline of ≥15
10.5.2
Electrocardiograms
The following ECG variables will be assessed:
x
PR interval (ms)
x
RR interval (ms)
x
QRS duration (ms)
x
QT interval (ms)
x
QTcF interval (ms)
x
QTcB interval (ms)
The date and time of the ECG will be recorded in the eCRF together with the Investigator 
interpretation and details of any abnormalities.
A summary of the number and percentage of subjects with normal, abnormal not clinically 
significant and abnormal clinically significant ECG results at all applicable visits will be 
presented.
All ECG variables will be summarized (absolute values and change from Baseline) and listed by 
visit.
10.5.3
Other safety variables
Physical Examination
Abnormal results of the physical examination together with details of abnormalities will be listed
by treatment group, subject, and visit.
Assessment of Tuberculosis
Listings of history of latent TB, TB test results and ‘Evaluation of signs and symptoms of 
tuberculosis’ questionnaire data will be provided by treatment and subject.
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
The eC-SSRS is an assessment tool that evaluates suicidal ideation and behavior. The eC-SSRS 
contains 9 categories with binary responses (yes/no): 
x
Category 1 –
x
Category 2 –
x
Category 3 –
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 66 of 194
x
Category 4 –
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Category 5 –
x
Category 6 –
x
Category 7 –
x
Category 8 –
x
Category 9 –
Following composite endpoints based on the above categories are defined as:
x
Suicidal ideation: A “yes” answer at any time during treatment to any one of the five suicidal 
ideation questions (Categories 1-5).
x
Suicidal behavior: A “yes” answer at any time during treatment to any one of the five 
suicidal behavior questions (Categories 6-9).
x
Suicidal ideation or behavior: A “yes” answer at any time during treatment to any one of the 
ten suicidal ideation and behavior questions (Categories 1-9).
The incidence of subjects with suicidal ideation, behavior and injuries including the composite 
endpoints will be summarized by treatment group and visit. A by-subject listing of the eC-SSRS
data will be provided.
Self-injurious behavior without suicidal intent is defined as event in the category non-suicidal 
self-injurious behavior.
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Statistical Analysis Plan
Bimekizumab
AS0008
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Page 67 of 194
11
REFERENCES
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Berglund P, Heeringa S. Multiple imputation of missing data using SAS®. Cary, NC: SAS 
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preselection of criteria for short term improvement after anti-TNFa treatment in ankylosing 
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Bross I. D. J. How to use ridit analysis. Biometrics. 1958;14 (1):18-38.
Carpenter JR, Kenward MG. Multiple imputation and its application. Chichester: John Wiley & 
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products other than NSAIDS for the treatment of RA. June 2004.
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practice. July 2002.
Daudén E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or 
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Venereol. 2009;23(12), 1374-82.
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Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewé R, van der Tempel H, Mielants 
H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62:127-32.
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documents; 1998. 
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Guideline.pdf
International Menopause Society. Cornwall, UK: Menopause Terminology; c2015. 
http://www.imsociety.org/menopause terminology.php. Accessed 25 Jan 2016.
Langley RG, Feldman SR, Han C, Schenkel B, Szapary P, Hsu MC, et al. Ustekinumab 
significantly improves symptoms of anxiety, depression, and skin-related quality of life in 
patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, 
placebocontrolled phase III trial. J Am Acad Dermatol. 2010;63(3):457-65.
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-
endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum 
Dis. 2009;68:18-24.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 68 of 194
Machado P, Navarro-Compan V, Landewe R, van Gaalen VA, Roux C, van der Heijde D. 
Calculating the Ankylosing Spondylitis Disease Activity Score If the Conventional C-Reactive 
Protein Level Is Below the Limit of Detection or If High-Sensitivity C-Reactive Protein Is Used: 
An Analysis in the DESIR Cohort. Arthritis Rheum. 2015 Feb;67(2):408-13.
Maksymowych WP, Mallon C, Richardson R, et al. Development and Validation of the 
Edmonton Ankylosing Spondylitis Metrology Index. Arthritis Rheum. 2006;55:575-82.
Mallinckrodt CH, Lin Q, Lipkovich I, Molenberghs G. A structured approach to choosing 
estimands and estimators in longitudinal clinical trials. Pharm Stat. 2012;11:456-61.
Mantel N, Haenszel W. Statistical aspects of the Analysis of Data From Retrospective Studies of 
Disease. J Natl Cancer Inst. 1959; 22:719-48.
Nam, JM. A simple approximation for calculating sample sizes for detecting linear trend in 
proportions. Biometrics. 1987;43(3):701-5.
Rubin D.B. 1987. Muliple Imputation for Nonresponse in Surveys. New York: John Wiley and 
Sons.
Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment 
of SpondyloArthritis International Society (ASAS) handbook: a guide to assess 
spondyloarthritis. Ann Rheum Dis. 2009;68(Supple 2):ii1-44.
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the 
irritabilitydepression-anxiety scale and the Leeds situational anxiety scale manual. 1994.
Ulm K. A simple method to calculate the confidence interval of a standardized mortality ratio. 
American Journal of Epidemiology. 1990;131, 373-375.
van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. 
Assessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of 
America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis 
Rheum. 2005;52:386-94.
van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, et al. Adalimumab 
effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-
term results from the ATLAS trial. Ann Rheum Dis. 2009;68:922-9.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 69 of 194
12
APPENDICES
12.1
Calculation rules for duration of adverse events
The calculation rules for duration of AEs are presented in Table 12‒1. AE duration is computed 
and reported in day.
Table 12‒1: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Complete data
D1
D2
Duration = D2 – D1 + 1
Start date missing
-
D2
Duration = < D2 – D0 +1
Where, for a subject in the SS, D0 is the date of the first 
intake of IMP, and for screen failures, D0 is the date of 
the Screening visit day 
End date missing
D1
-
Duration = > Final contact date – D1 + 1
For resolved and ongoing AE Duration
Start and end date 
missing
-
-
Duration = > Final contact date – D0 + 1
For resolved and ongoing AE Duration 
Where, for subjects in the SS, D0 is the date of the first 
intake of IMP, and for screen failures, D0 is the date of 
the Screening visit day
12.2
Treatment group assignment for tables and figures
Table 12‒2 displays the treatment group labels for each data type. This overview clarifies what 
kind of treatment groups will be used for producing the tables and figures separated between the 
different table types.
Table 12‒2: Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 160mg/ BKZ 
320mg
All BKZ
All 
subjects
Subject disposition
X
X
X
Important protocol deviation
X
X
X
Demographics/Lifestyle
X
X
X
Ankylosing spondylitis 
history
X
X
X
Baseline characteristics
X
X
X
TB testing
X
X
X
Previous and ongoing medical 
history
X
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 70 of 194
Table 12‒2: Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 160mg/ BKZ 
320mg
All BKZ
All 
subjects
Prior and concomitant 
medication
X
X
X
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medication
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X
Bimekizumab compliance
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Extent of exposure
X
X
X
Efficacy analysis
X
X
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X
Pharmacokinetic 
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X
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X
X
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X
X
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Physical examination
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X
X
eC-SSRS
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AbAb=Anti-bimekizumab antibody; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale.
12.3
Hematology and biochemistry variables for the interim analysis
Table 12‒3: Selected hematology and biochemistry variables for the interim 
analysis
Hematology
Biochemistry
Lymphocytes
AST
Neutrophils
ALT
Hematocrit
Total bilirubin
Hemoglobin
Platelet count
ALT=alanine aminotransferase; AST=aspartate aminotransferase.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 71 of 194
12.4
Physician’s Global Assessment of Disease Activity (PGADA) 
questionnaire
12.5
Total and nocturnal spinal pain questionnaire
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Statistical Analysis Plan
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12.12
Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) 
questionnaire
12.13
Identification of Opportunistic infections
Opportunistic infections are identified in two steps:
Step 1: Refer to column B of the spreadsheet (Opportunistic infections MedDRA v 19.xlsx) 
which identifies the PTs to be classified as opportunistic infections using either a single “x” or a 
double “xx”.
x
TEAEs which code to a PT flagged with a single “x” need to also be serious in order to be 
considered an opportunistic infection.
x
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 “x” 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:
1. 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 case-by-case. Information from the 
AE dataset to be included in the spreadsheet: Subject ID, AE verbatim term, SOC, High 
Level Term, Lower Level Term, PT, AE start date, AE end date, seriousness, severity, 
relationship to study medication, action taken. Additionally, a column will be included where 
the study physician can document their decision on the case.
2. 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”.
3. Study programming team incorporates these decisions into the AE dataset by merging the 
study physician decisions for individual subjects / PTs and flagging the confirmed 
opportunistic infections as such in the dataset.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
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All subjects with a case-by-case PT reported that has been confirmed by the study physician to 
be an opportunistic infection will be summarized as such in the stand-alone table, along with all 
of the events identified in Step 1 of this process.
The timing and frequency of Step 2 should be outlines and agreed to by the study team at the 
beginning of the study. It is suggested that this process be executed multiple times throughout the 
course of the study, more frequently in the weeks leading up to database lock, and one final time 
immediately prior to database lock.
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 conclusion of the study.
12.14
MedDRA algorithmic approach to anaphylaxis
The SMQ Anaphylactic reaction consists of three parts:
x
A narrow search: 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
x
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 87 of 194
Category C
Category D
x
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
Bimekizumab
AS0008
Confidential
Page 88 of 194
13
AMENDMENT TO THE STATISTICIAL ANALYSIS PLAN
13.1
Amendment 1
13.1.1
Rationale for the amendment
The main objectives of this SAP amendment are to provide more consistency between AS0008 
and the PA0008 study. The SAP has been amended to:
x
Update the AbAb analysis
x
Remove SAS notations from the multiple imputation text
x
Re-structure the AE section for a better overview
x
Add more information for the interim analysis
13.1.2
Modifications and changes
Change # 1
LIST OF ABBREVIATIONS
Has been changed to
…
AbAb
Anti-bimekizumab antibody
AE
Adverse event
…
BASMI
Bath Ankylosing Spondylitis Metrology Index
BKZ
Bimekizumab
…
BUN
Blood urea nitrogen
CPK
Creatine phosphokinase
…
n
Number of observations 
NRI
Non-responder imputation
…
AbAb
Anti-bimekizumab antibody
ACP
Above the cut point
ADR
Adverse drug reaction
AE
Adverse event
…
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
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Page 89 of 194
Change # 2
Section 3.4 Protocol deviations
Important protocol deviations are defined as those deviations from the protocol likely to have a 
meaningful impact on the primary efficacy outcomes for an individual subject. Important 
protocol deviations will be identified and classified by the deviation types defined in the 
appropriate protocol-specific document. All protocol deviations will be reviewed as part of the 
ongoing data cleaning process and all important deviations will be identified and documented 
prior to unblinding to confirm exclusion from Per Protocol Set (PPS). The exclusion from PPS is 
limited to the double-blind period, ie. only subjects with important protocol deviations prior to 
re-randomization at Visit 7 (Week 12) will be excluded from PPS. Subjects with important 
protocol deviations after Visit 7 (Week 12) will not be excluded from PPS.
Has been changed to
Important protocol deviations are defined as those deviations from the protocol likely to have a 
meaningful impact on the primary efficacy outcomes for an individual subject. Important 
protocol deviations will be identified and classified by the deviation types defined in the 
appropriate protocol-specific document. All protocol deviations will be reviewed as part of the 
ongoing data cleaning process and all important deviations will be identified and documented 
prior to unblinding to confirm exclusion from Per Protocol Set (PPS ), Pharmacokinetics Per-
Protocol Set (PK-PPS), and Pharmacodynamics Per-Protocol Set (PD-PPS). The exclusion 
from PPS is limited to the double-blind period, ie. only subjects with important protocol 
deviations prior to re-randomization at Visit 7 (Week 12) will be excluded from PPS. Subjects 
with important protocol deviations after Visit 7 (Week 12) will not be excluded from PPS.
Change # 3
3.10 Changes to protocol-defined analyses
There have been no changes to the protocol-defined analyses.
BASMI
Bath Ankylosing Spondylitis Metrology Index
BCP
Below the cut point
BKZ
Bimekizumab
…
BUN
Blood urea nitrogen
CP
Confirmed positive
CPK
Creatine phosphokinase
…
n
Number of observations 
NCP
Not confirmed positive
NRI
Non-responder imputation
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 90 of 194
Has been changed to
There have been no changes to the protocol defined analyses.
Instead of stopping the pairwise testing of each bimekizumab dose versus placebo once it 
failed to reach significance at a significance level of α=0.05, the pairwise testing will 
continue and further pairwise comparisons are seen as non-significant.
No fixed sequence testing will be used for the secondary efficacy variables. 
Time to a given response is defined as the length in weeks from Baseline until the first date 
when the response is achieved. In the definition the length was changed from days to weeks 
due to easier interpretation.
Change # 4
Section 4.2.1 Handling of missing data for efficacy analysis
The analysis for the binary primary, secondary, and other efficacy variables will use non-
responder imputation (NRI) for handling missing data. In NRI, each subject with missing data or 
who has discontinued double-blind study treatment prior to Week 12 will be counted as a non-
responder. 
Sensitivity analysis will be performed for the secondary analysis of the primary variable 
(ASAS40 response at Week 12) using MI assuming that missingness is missing at random 
(MAR). The MI method will be applied as follows:
1. Create a data set, sorted by treatment groups, of subjects with observed values and those 
needing estimation by multiple imputation. For the imputation step, missing values will be 
separated into non-monotone missing values (ie, intermittent missing values between 
completed assessments) and monotone missing values (ie, missing values after the patient 
dropped out). The procedure will sequentially estimate an imputation model for the ASAS 
components at each post-Baseline visit where ASAS components are collected, with 
geographic region, and prior TNF inhibitor exposure as covariates separated between the 
treatment groups.

For the imputation of intermediate missing values, the missing ASAS components in 
each data set will be filled in using the Markov-Chain Monte Carlo (MCMC) method in 
PROC MI with multiple chains and monotone imputing. To perform separate multiple 
imputation analyses for the treatment groups the BY statement in PROC MI will be used. 
A total number of imputations will be 100. The seed used for these imputations will be 
2017.
Note: All other multiple imputation procedures described in this SAP will use this same 
seed as well.
Note: The imputation model based on the MCMC method will only allow continuous 
variables as predictors. Therefore, prior TNF inhibitor exposure and geographic region 
will be re-coded as indicator variables (with values of 0 or 1 for each level of the 
variable).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 91 of 194
Note: To avoid that imputed values are outside of the pre-defined range of values for the 
ASAS components (eg, PGADA [0-10]) the MAXIMUM and MINIMUM options in 
PROC MI will be used. 

If the intermediate missing data are imputed, the monotone missing data will be imputed 
for all patients with monotone missing data (eg, patients that discontinued the studies). 
The multiple imputation will be done with the monotone regression option in PROC MI 
including geographic region, and prior TNF inhibitor exposure as covariates. The dataset 
is the output dataset of the partial imputation. Since this dataset already has 100 imputed
values at each visit, only one imputation will be performed. 
Note: MAXIMUM and MINIMUM options will be used as well to avoid values outside 
of the pre-defined range of values.
2. The ASAS40 response will be calculated using the complete datasets. That is, the values of 
the ASAS components at Week 12 based on the complete datasets will be compared to their 
corresponding Baseline values to calculate an ASAS40 response for each subject (as 
described in Section 8.1.1). Each complete data set will then be analyzed based on a logistic 
regression model with factors of treatment group, geographic region, and prior TNF inhibitor 
exposure. 
3. The Week 12 results from the logistic regression analysis of each of the 100 imputed data 
sets will be combined for overall inference using Rubin’s rules, which account for the 
uncertainty associated with the imputed values (Rubin, 1987). This will be done using SAS 
PROC MIANALYZE.
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below:
As the estimates of the odds ratios from the logistic regression model in step 3 follow a 
lognormal distribution, a log transformation is needed to normalize these estimates since the 
procedures for combining results from multiple imputed datasets are based on the assumption 
that the statistics estimated from each imputed dataset are normally distributed. Therefore, the 
log of the odds ratio estimates from the logistic regression model are used when combining into a 
single inference (the use of PROC MIANALYZE in step 3). Additionally, the standard errors 
(SE) for the odds ratios are transformed as follows:
ܵܧൌሺܷܥܮሻെሺܮܥܮሻ
ʹܼןȀଶ
(1)
where UCL and LCL are the upper and lower confidence limit, respectively, for the confidence 
interval of the odds ratio from the logistic regression model, and Zα/2 is the relevant critical value 
from the standard normal distribution (1.96 for a 95% confidence interval). The estimates of the 
log odds ratio for each bimekizumab dose relative to placebo and the corresponding upper and 
lower confidence limits will be provided. The odds ratio is estimated by exponentiating the 
estimate of the log odds ratio. The confidence limits of the odds ratio are then estimated as 
follows:
ܮܥܮൌܱܴכ ሺെܵܧכ ܼןȀଶሻ
(2)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 92 of 194
ܷܥܮൌܱܴכ ሺܵܧכ ܼןȀଶሻ
(3)
where OR is the back-transformed estimate of the odds ratio just described, SE is the standard 
error of the log odds ratio derived in PROC MIANALYZE and Zα/2 is the relevant critical value 
from the standard normal distribution (1.96 for a 95% confidence interval). These calculations
will be done such that odds ratios and corresponding confidence intervals are calculated for the 
odds ratio of each bimekizumab dose versus placebo. Note that the p-values presented in the 
tables will be the ones provided initially by PROC MIANALYZE and are not impacted by the 
transformations described above.
The supportive analysis number 3 (analysis of the ASAS components), and all continuous 
secondary efficacy variables will use the same multiple imputation method as described above. 
Instead of using the logistic regression model the ANCOVA with treatment group, geographic 
region, and TNF inhibitor exposure as fixed effects and the Baseline values as covariate will be 
used. No log transformation is needed for the ANCOVA estimations. 
The mean and standard error of the continuous other efficacy variables will be computed using 
SAS PROC UNIVARIATE. The imputed means and their standard errors will be summarized 
using PROC MIANALYZE as described above. Following Rubin (1987), multiple imputation 
estimates of descriptive statistics are computed by simply averaging the estimates from ݉ൌ
ͳǡ ǥ ǡ ܯindependent repetitions of the imputation algorithm:
ߠҧ ൌͳ
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Has been changed to
The analysis for the binary primary, secondary, and other efficacy variables will use non-
responder imputation (NRI) for handling missing data. In NRI, each subject with missing data or 
who has discontinued double-blind study treatment prior to Week 12 will be counted as a non-
responder. 
Sensitivity analysis will be performed for the secondary analysis of the primary variable 
(ASAS40 response at Week 12) using MI assuming that missingness is missing at random 
(MAR). The MI method will be applied as follows:
1. Create a data set, sorted by treatment groups, of subjects with observed values and those 
needing estimation by multiple imputation. For the imputation step, missing values will be 
separated into non-monotone missing values (ie, intermittent missing values between 
completed assessments) and monotone missing values (ie, missing values after the patient 
dropped out). The procedure will sequentially estimate an imputation model for the ASAS 
components at each post-Baseline visit where ASAS components are collected, with 
geographic region, and prior TNF inhibitor exposure as covariates separated between the 
treatment groups.

For the imputation of intermediate missing values, the missing ASAS components in 
each data set will be filled in using the Markov-Chain Monte Carlo (MCMC) method in
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 93 of 194
PROC MI with multiple chains and monotone imputing. To perform separate multiple 
imputation analyses for the treatment groups the BY statement in PROC MI will be used. 
A total number of imputations will be 100. The seed used for these imputations will be 
2017.
Note: All other multiple imputation procedures described in this SAP will use this same 
seed as well.
Note: The imputation model based on the MCMC method will only allow continuous 
variables as predictors. Therefore, prior TNF inhibitor exposure and geographic region 
will be re-coded as indicator variables (with values of 0 or 1 for each level of the 
variable).
Note: To avoid that imputed values are outside of the pre-defined range of values for the 
ASAS components (eg, PGADA [0-10]) maximum and minimum values for imputed 
variable values are specified. the MAXIMUM and MINIMUM options in PROC MI 
will be used. 

If the intermediate missing data are imputed, the monotone missing data will be imputed 
for all patients with monotone regression including geographic region, and prior TNF 
inhibitor exposure as covariates. missing data (eg, patients that discontinued the 
studies). The multiple imputation will be done with the monotone regression option in 
PROC MI including geographic region, and prior TNF inhibitor exposure as covariates.
The dataset is the output dataset of the partial imputation. Since this dataset already has 
100 imputed values at each visit, only one imputation will be performed. 
Note: MAXIMUM and MINIMUM options will be used as well Maximum and 
minimum values are specified for imputed variable values to avoid values outside of 
the pre-defined range of values.
2. The ASAS40 response will be calculated using the complete datasets. That is, the values of 
the ASAS components at Week 12 based on the complete datasets will be compared to their 
corresponding Baseline values to calculate an ASAS40 response for each subject (as 
described in Section 8.1.1). Each complete data set will then be analyzed based on a logistic 
regression model with factors of treatment group, geographic region, and prior TNF inhibitor 
exposure. 
3. The Week 12 results from the logistic regression analysis of each of the 100 imputed data 
sets will be combined for overall inference using Rubin’s rules, which account for the 
uncertainty associated with the imputed values (Rubin, 1987). This will be done using SAS 
PROC MIANALYZE.
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below:
As the estimates of the odds ratios from the logistic regression model in step 3 follow a 
lognormal distribution, a log transformation is needed to normalize these estimates since the 
procedures for combining results from multiple imputed datasets are based on the assumption 
that the statistics estimated from each imputed dataset are normally distributed. Therefore, the 
log of the odds ratio estimates from the logistic regression model are used when combining into a 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 94 of 194
single inference (the use of PROC MIANALYZE in step 3). Additionally, the standard errors 
(SE) for the odds ratios are transformed as follows:
ܵܧൌሺܷܥܮሻെሺܮܥܮሻ
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interval of the odds ratio from the logistic regression model, and Zα/2 is the relevant critical value 
from the standard normal distribution (1.96 for a 95% confidence interval). The estimates of the 
log odds ratio for each bimekizumab dose relative to placebo and the corresponding upper and 
lower confidence limits will be provided. The odds ratio is estimated by exponentiating the 
estimate of the log odds ratio. The confidence limits of the odds ratio are then estimated as 
follows:
ܮܥܮൌܱܴכ ሺെܵܧכ ܼןȀଶሻ
(2)
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where OR is the back-transformed estimate of the odds ratio just described, SE is the standard 
error of the log odds ratio derived in PROC MIANALYZE and Zα/2 is the relevant critical value 
from the standard normal distribution (1.96 for a 95% confidence interval). These calculations
will be done such that odds ratios and corresponding confidence intervals are calculated for the 
odds ratio of each bimekizumab dose versus placebo. Note that the p-values presented in the 
tables will be the ones provided initially by PROC MIANALYZE and are not impacted by the 
transformations described above.
The supportive analysis number 3 (analysis of the ASAS components), and all continuous 
secondary efficacy variables will use the same multiple imputation method as described above. 
Instead of using the logistic regression model the ANCOVA with treatment group, geographic 
region, and TNF inhibitor exposure as fixed effects and the Baseline values as covariate will be 
used. No log transformation is needed for the ANCOVA estimations. 
The mean and standard error of the continuous other efficacy variables will be computed using 
SAS PROC UNIVARIATE. The imputed means and their standard errors will be summarized 
using PROC MIANALYZE as described above. Following Rubin (1987), multiple imputation 
estimates of descriptive statistics are computed by simply averaging the estimates from ݉ൌ
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 95 of 194
Change # 5
Section 4.2.2 Handling of missing data for adverse events (AEs)
…
In the event of ambiguity or incomplete data which makes it impossible to determine whether the 
AE was treatment emergent, the AE will be considered treatment emergent.
Has been changed to
…
In the event of ambiguity or incomplete data which makes it impossible to determine whether the 
AE was treatment emergent, the AE will be considered treatment emergent.
If the intensity of an AE is unknown, it is considered as severe.
If the relationship to study drug is missing, it is considered as related.
The imputation rule for missing seriousness differ between the interim and final analysis. 
For the interim analysis no imputations rule will be applied. For the final analysis the 
worst case approach will be applied. If the seriousness of an AE is missing for the final 
analysis, it is considered as serious.
Change # 6
Section 4.3 Interim analysis and data monitoring
After all enrolled subjects have completed the 12 weeks Double-Blind Period, an interim 
analysis will be performed (i) to analyze the dose:exposure response for the ASAS response 
criteria to determine the optimal therapeutic dose(s) for subsequent studies, and (ii) to perform a 
comprehensive evaluation of all double-blind data of the study.
No separate SAP for the interim analysis will be provided. The interim analysis is a limited 
version of the final analysis and will focus on specific topics, eg, primary and secondary efficacy 
analysis and comprise the results of the 12 weeks Double-Blind Period only. The TFL shells for 
the interim and final analysis will be provided in two different documents.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS). Corresponding listings will be provided. 
Not all collected hematology and biochemistry laboratory variables will be summarized and 
listed. For the interim analysis only selected variables will be provided as listed in Table 
Table 12‒3.
The interim efficacy analysis will focus on the primary and secondary efficacy analyses 
including supportive and sensitivity analyses. In addition, summary tables for the primary and 
secondary efficacy variables, and the ASAS components will be provided. Categorical variables 
will be summarized using frequency tables by each visit. Continuous variables will be 
summarized using descriptive statistics by each visit. Time to onset of ASAS20 response and 
ASAS40 response will be summarized and plotted as described in Section 8.3.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 96 of 194
PK and PD data will not be analyzed in the interim analysis. A separate PKPD analysis including 
separate SAP will be performed after Week 12.
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48.
Safety data will be provided to an independent Data Monitoring Committee (DMC). The DMC 
will review those safety data periodically. The composition and operation of the DMC will be 
defined in the DMC charter. The presentation and analysis of data for the DMC meetings is 
described within a separate DMC SAP.
Has been changed to
After all enrolled subjects have completed the 12 weeks Double-Blind Period, an interim 
analysis will be performed (i) to analyze the dose:exposure response for the ASAS40 response 
criteria to determine the optimal therapeutic dose(s) for subsequent studies, and (ii) to perform a 
comprehensive evaluation of all double-blind data of the study.
No separate SAP for the interim analysis will be provided. The interim analysis is a limited 
version of the final analysis and will focus on specific topics, eg, the primary and secondary 
efficacy analysis and comprise the results of the 12 weeks Double-Blind Period only. The TFL 
shells for the interim and final analysis will be provided in two different documents.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent 
AEs (derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS). Corresponding listings will be provided. 
Not all collected hematology and biochemistry laboratory variables will be summarized and 
listed. For the interim analysis only selected hematology and biochemistry variables will be 
provided as listed in Table 12‒3. Listings of AEs, hematology, biochemistry and C-SSRS 
data will be provided.
The interim efficacy analysis will focus on the primary and secondary efficacy analyses 
including supportive and sensitivity analyses include following primary and secondary 
variables: ASAS40,20,5/6 response at Week 12, and change from Baseline in BASDAI, 
ASDAS-CRP, BASFI at Week 12. The variables will be analyzed using the same methods 
described in Section 8.1.2 and Section 8.2 including supportive and sensitivity analyses
(Section 8.1.3 and Section 8.1.4). In addition, summary tables for the primary and secondary 
efficacy variables, and the ASAS components will be provided. Categorical variables will be 
summarized using frequency tables by each visit. Continuous variables will be summarized using 
descriptive statistics by each visit. Time to onset of ASAS20 response and ASAS40 response 
will be summarized and plotted as described in Section 8.3.
PK and PD data will not be analyzed in the interim analysis as described in Section 9.1 and
Section 9.2. A separate PKPD analysis including separate SAP will be performed after Week 12.
PKPD will be analyzed as part of the exposure:response modeling outside of the scope of 
the SAP. Biomarker data will not be analyzed in the interim analysis.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 97 of 194
The interim analysis includes selected data up to Week 12 and in addition data up to Week 
16. The data up to Week 16 may include partial results up to the time the database for 
Week 12 was locked for ongoing subjects. All analyses for the period between Week 12 and 
Week 24 are only for those treatment groups that are not rerandomized. Following 
variables will be analyzed: ASAS40, ASAS20, ASDAS-CRP, BASDAI, PK, AbAb and 
TEAEs. It depends on the analysis how those additional time points will be presented in the 
interim analysis. Two summary tables for TEAE will be presented. The first table will 
include data up to Week 12 by treatment group at Baseline. The second table will include 
data up to Week 16 by following treatment groups: bimekizumab 160mg and bimekizumab 
320mg. The summary table for the other variables will present only data up to Week 12 for 
the Baseline treatment groups Placebo, bimekizumab 16mg, and bimekizumab 64mg. Data 
up to Week 16 will be presented for bimekizumab 160mg and bimekizumab 320mg. All 
Listings which include data up to Week 16 will use the same approach.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will 
be allocated to the Double-Blind treatment. An exception from this general rule is made for 
adverse drug reactions (ADRs), and AE of hypersensitivity reactions and anaphylactic 
reactions. If those AEs occur on the same days as the treatment switch, the AEs will be 
allocated to the Dose-Blind treatment and will not be presented for the interim analysis.
Exposure of study medication will not be summarized but a listing will be provided 
including following information: date of first dose, date of last dose, and duration of 
exposure. The last dose for the Double-Blind Period is planned on Visit 6 (Week 8). For 
subject who completed the Double-Blind Period the Week 8 date is the date of the last dose. 
If a subject discontinued within the Double-Blind Period, the discontinuation date will be 
presented for the date of last dose.
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48.
Safety data will be provided to an independent Data Monitoring Committee (DMC). The DMC 
will review those safety data periodically. The composition and operation of the DMC will be 
defined in the DMC charter. The presentation and analysis of data for the DMC meetings is 
described within a separate DMC SAP.
Change # 7
Section 4.5 Multiple comparisons/multiplicity
In order to control for the overall Type I error rate, the pairwise comparisons of bimekizumab 
will be formally evaluated for statistical significance only if the primary efficacy analysis is 
statistically significant at the two-sided 5% level. In addition, the pairwise comparisons will 
follow a sequential testing sequence and the formal evaluation of statistical significance of each 
comparison is dependent upon the previous comparison achieving statistical significance at the 
two-sided 5% level. More details can be found in Section 8.1.3.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 98 of 194
In order to control for the overall Type I error rate, the pairwise comparisons of bimekizumab
will be formally evaluated for statistical significance only if the primary efficacy analysis is 
statistically significant at the two-sided 5% level. In addition, the pairwise comparisons will 
follow a sequential testing sequence and the formal evaluation of statistical significance of each 
comparison is dependent upon the previous comparison achieving statistical significance at the 
two-sided 5% level. If the sequential testing fails to reach significance at a significance level 
of α=0.05, then the pairwise testing will continue and the comparison are seen as non-
significant. The p-values will be displayed as nominal p-values. More details can be found in 
Section 8.1.3.
Change # 8
Section 8.1.1 Derivations of ASAS score and response
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 numeric rating scale (NRS) in at least 3 of the 4 following domains 
(Anderson, 2001):
x
PGADA
x
Pain assessment (total spinal pain, question 1 from total and nocturnal spinal pain 
questionnaire)
x
Function (represented by the BASFI)
x
Inflammation (the mean of the BASDAI questions 5 and 6) concerning
and absence of deterioration in the potential remaining domain. Deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit.
The ASAS criteria for 40% improvement are defined as relative 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 and 
no worsening at all in the remaining domain.
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, which 
includes, in addition to the 4 domains above, spinal mobility (ie, lateral spinal flexion) and high 
sensitivity C-reactive protein (hs-CRP) as more objective measures (Brandt et al, 2004). If the 
hs-CRP value is below the lower limit of quantification (LLOQ), then it will be imputed as the 
midpoint between 0 and the LLOQ.
…
Has been changed to
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 numeric rating scale (NRS) in at least 3 of the 4 following domains 
(Anderson, 2001):
x
PGADA
x
Pain assessment (total spinal pain, question 1 from total and nocturnal spinal pain 
questionnaire)
x
Function (represented by the BASFI)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 99 of 194
x
Inflammation (the mean of the BASDAI questions 5 and 6) concerning 
and absence of deterioration in the potential remaining domain. Deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit.
The ASAS criteria for 40% improvement are defined as relative 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 and 
no worsening at all in the remaining domain.
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, which 
includes, in addition to the 4 domains above, spinal mobility (ie, lateral spinal flexion) and high 
sensitivity C-reactive protein (hs-CRP) as more objective measures (Brandt et al, 2004). If the 
hs CRP value is below the lower limit of quantification (LLOQ), then it will be imputed as the 
midpoint between 0 and the LLOQ. If the hs-CRP value is below 2 mg/L, then it will be 
imputed as the constant value of 2 mg/L.
…
Change # 9
Section 8.1.3 Secondary analysis of the primary efficacy variable
As the secondary analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure. If 
the logistic regression model is unable to converge, then region may be dropped from the model 
to facilitate convergence. Comparisons will be made for each dose versus placebo at a 2-sided
significance level of α=0.05. For each dose, the odds ratio versus placebo, the 95% confidence 
interval, and the corresponding p-value will be calculated.
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a 2-sided significance 
level of α=0.05. This procedure will control the overall Type I error rate. If the dose response 
relationship fails to reach significance at a significance level of α=0.05, then no further testing 
will be conducted and the pairwise comparisons are seen as non-significant.
…
Has been changed to
As the secondary analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure. To 
avoid the problem of the so-called monotone likelihood resulting in infinite large confidence 
intervals (eg, if one of the cell counts in the 2x2 table is equal to zero), a penalized 
maximum likelihood approach based on the modified score procedure of Firth (eg, Heinze 
and Schemper, 2002) will be used in the logistic models. If the logistic regression model is 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 100 of 194
unable to converge, then geographic region may be dropped from the model to facilitate 
convergence. If the logistic regression model is unable to converge after dropping the 
geographic region, then prior TNF inhibitor exposure may be dropped as well. Comparisons 
will be made for each dose versus placebo at a 2-sided significance level of α=0.05. For each 
dose, the odds ratio versus placebo, the 95% confidence interval, and the corresponding p-value 
will be calculated.
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a 2 sided significance 
level of α=0.05. This procedure will control the overall Type I error rate. If the dose response 
relationship fails to reach significance at a significance level of α=0.05, then no further testing 
will be conducted and the pairwise comparisons are seen as non significant. If the dose-
response relationship fails to reach significance at a significance level of α=0.05, then the 
further pairwise comparisons are seen as non-significant.
…
Change # 10
8.2 Statistical analysis of the secondary efficacy variables
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, ASAS20 response and ASAS5/6) will be analyzed for treatment 
effects using pairwise comparisons based on the same method as that for the primary efficacy 
variable.
All continuous variables (ie, ASDAS-CRP, BASDAI, and BASFI) will be analyzed for treatment 
effects using pairwise comparisons based on an ANCOVA model with treatment, geographic 
region, and prior TNF inhibitor exposure as fixed effects and the Baseline value as covariate.
Pairwise testing of each bimekizumab dose versus placebo will account for multiplicity by using 
a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from 
the highest dose to the lowest dose as described in Section 8.1.3.
For the categorical variables the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 
160mg, BKZ 320mg, and for each dose the odds ratios (differences to placebo), 95% confidence 
intervals, and corresponding p-values from the logistic regression will be provided.
…
Has been changed to
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, ASAS20 response and ASAS5/6) will be analyzed for treatment 
effects using pairwise comparisons based on the same method as that for the primary efficacy 
variable.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 101 of 194
All continuous variables (ie, ASDAS-CRP, BASDAI, and BASFI) will be analyzed for treatment 
effects using pairwise comparisons based on an ANCOVA model with treatment, geographic 
region, and prior TNF inhibitor exposure as fixed effects and the Baseline value as covariate.
Pairwise testing of each bimekizumab dose versus placebo will account for multiplicity by using 
a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from 
the highest dose to the lowest dose as described in Section 8.1.3.
For the categorical variables the responder rates for placebo, BKZ 16mg, BKZ 64mg, BKZ 
160mg, BKZ 320mg, and for each dose the odds ratios (differences to placebo), 95% confidence 
intervals, and corresponding p-values from the logistic regression will be provided.
…
Change # 11
Section 8.2.1 Derivations of ASDAS-CRP, ASDAS-MI, and ASDAS Status
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2009) as shown below:
x
0.121 x 
 (BASDAI question 2 result)
x
0.058 x 
 (BASDAI question 6 result)
x
0.110 x PGADA
x
0.073 x 
 (BASDAI question 3 result)
x
0.579 x (natural logarithm of the (hs-CRP [mg/L] + 1))
, PGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS-CRP.
If one component for the ASDAS-CRP is missing at a given visit, that component will be 
imputed by carrying the last observation forward, and the ASDAS-CRP will be calculated 
accordingly. If no value is available for that component before the missing time point, the next 
observation may be carried backwards. If more than one component for the ASDAS-CRP is 
missing, ASDAS-CRP will be treated as missing.
If the hs-CRP value is below the LLOQ, then it will be imputed as the midpoint between 0 and
the LLOQ.
…
Has been changed to
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2009) as shown below:
x
0.121 x 
 (BASDAI question 2 result)
x
0.058 x 
 (BASDAI question 6 result)
x
0.110 x PGADA
R
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 102 of 194
x
0.073 x 
 (BASDAI question 3 result)
x
0.579 x (natural logarithm of the (hs-CRP [mg/L] + 1))
, PGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS-CRP.
If one component for the ASDAS-CRP is missing at a given visit, that component will be 
imputed by carrying the last observation forward, and the ASDAS-CRP will be calculated 
accordingly. If no value is available for that component before the missing time point, the next 
observation may be carried backwards. If more than one component for the ASDAS-CRP is 
missing, ASDAS-CRP will be treated as missing.
If the hs CRP value is below the LLOQ, then it will be imputed as the midpoint between 0 and 
the LLOQ. If the hs-CRP value is below 2 mg/L, then it will be imputed as the constant 
value of 2 mg/L (Machado et al, 2015).
…
Change # 12
8.3 Statistical analysis of other efficacy variables
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
All categorical variables will be presented using frequency tables by each visit. All continuous 
variables will be summarized using descriptive statistics by each visit.
The Hospital Anxiety and Depression Scale (HADS) will be analyzed separately for HADS-A
and HADS-D. The summary statistics for HADS-A and HADS-D will be presented in two 
different tables.
Figures for the response rate or change from Baseline will be provided for the primary and 
secondary efficacy variables.
The MRI of the spine and sacroiliac joints will be performed in a substudy with subjects who 
were classified as MRI-positive at Baseline as per ASAS-Outcome Measures in Rheumatology 
Clinical Trials (OMERACT) criteria.
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in days from Baseline until the first date when the response is achieved. 
Subjects who discontinue study treatment prior to achieving a response will be censored at the 
date of study treatment discontinuation. Subjects who reach the Week 12 visit without achieving 
a response will be censored at the date of the Week 12 visit. Missing response data will be 
imputed with NRI.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 103 of 194
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
All categorical variables will be presented using frequency tables by each visit. All continuous 
variables will be summarized using descriptive statistics by each visit.
The Hospital Anxiety and Depression Scale (HADS) will be analyzed separately for HADS-A
and HADS-D. The summary statistics for HADS-A and HADS-D will be presented in two 
different tables.
Figures for the response rate or change from Baseline will be provided for the primary and 
secondary efficacy variables. Times series plots will be provided for the response rate or 
change from Baseline for the primary and secondary efficacy variables. The plots will show 
the weekly response rate over the first 12 weeks.
The MRI of the spine and sacroiliac joints will be performed in a substudy with subjects who 
were classified as MRI-positive at Baseline as per ASAS-Outcome Measures in Rheumatology 
Clinical Trials (OMERACT) criteria.
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in days weeks from Baseline until the first date when the response is 
achieved. Subjects who discontinue study treatment prior to achieving a response will be 
censored at the date of study treatment discontinuation. Subjects who reach the Week 12 visit 
without achieving a response will be censored at the date of the Week 12 visit. Missing response 
data will be imputed with NRI.
...
Change # 13
Section 8.3 Analysis of the other efficacy variables
…
All other efficacy variables will be analyzed using observed cases as treated and imputed with 
NRI for binary variables and MI for continuous variables.
Subjects in the ESS who discontinue with bimekizumab treatment during the Dose-Blind Period
will be treated as missing and categorical/continuous variables will be imputed.
Has been changed to
…
All other efficacy variables will be analyzed using observed cases as treated and imputed with 
NRI for binary variables and MI for continuous variables.
Subjects in the ESS who discontinue with bimekizumab treatment during the Dose-Blind Period
will be treated as missing and categorical/continuous variables will be imputed.
In order to assess the potential bias of the potentially unblinded subjects based on data, the 
results of the final analysis will be utilized. Results of the ASAS40 response of the 
rerandomized 320mg and 160mg treatment group at Week 48 will be compared to the 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 104 of 194
potentially unblinded, randomized 320mg and 160mg treatment groups. If the percentage 
of ASAS40 responders is comparable as assessed by overlapping 95% confidence intervals, 
the potential bias is estimated to be at minimum.
Change # 14
Section 8.3.9 C-reactive protein (CRP) and high-sensitivity C-reactive protein (CRP)
…
The values of hs-CRP values will be rounded to integers prior to calculating ratio to Baseline and 
values below the limit of quantification should be set to should be set to half the limit of 
quantification for the calculations. 
CRP values will not be summarized and only presented in listings.
Has been changed to
…
The values of hs-CRP and CRP values will be rounded to integers prior to calculating ratio to 
Baseline and values below the limit of quantification should be set to should be set to half the 
limit of quantification for the calculations. 
CRP values will not be summarized and only presented in listings.
Change # 15
Section 9.1 Pharmacokinetics
….
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group, and by cumulative antibody status (ie, positive, negative) for subjects 
randomized to bimekizumab.
The bimekizumab concentrations will also be listed.
Has been changed to
…
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group, and by cumulative antibody status (ie, positive, negative) for subjects 
randomized to bimekizumab as well as individual time curves of DAS28(CRP), bimekizumab 
concentration, and AbAb.
The bimekizumab concentrations will also be listed.
Change # 16
Section 9.2 Pharmacodynamics and Immunogenicity
The biomarker data will be separated between LGC assays, mulitplex proinflammatory cytokine 
and chemokine analysis, flow cytometry - TBNK panel, and flow cytometry -
Th1/Th2/Th17/Th22 panel. Biomarker variables will be summarized and listed for each 
treatment at each scheduled visit using the PD-PPS analysis set.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 105 of 194
In addition to the PD variables, whole blood will be stored to isolate deoxyribonucleic acid 
which may be used to examine genetic and epigenetic changes. The blood samples for genetic 
and epigenetic, and genomic, proteomic/metabolomics will not be analyzed in the interim or 
final analysis. Variables will be analyzed in a separate analysis as ad-hoc analysis. 
The AbAb status will be determined for each visit where samples are taken for drug 
concentration measures. At each visit:
x
Values ≤ predefined cut point are defined as AbAb-
x
Values > predefined cut point are defined as AbAb+
In addition, overall AbAb status should be determined: 
x
Subject AbAb positivity is defined as having a value > predefined cut point at any time in the
treatment period. This does not include Baseline/pre-treatment
x
Subject AbAb positivity at Baseline is defined as having a value > predefined cut point at 
Baseline
x
Treatment-emergent AbAb positivity is defined when a subject is having a value > 
predefined cut point for the first time during treatment period excluding Baseline/pre-
treatment.
x
AbAb- is defined as having no values > predefined cut point during the treatment period.
The cut point for determining whether the AbAb level is sufficiently high to be considered AbAb 
positive is not yet known. However, this will be determined prior to the database lock of the PK 
and AbAb data.
…
All individual subject-level AbAb results will be listed.
Immunogenicity data will be summarized and listed using the PK-PPS analysis set.
Has been changed to:
The biomarker data will be separated between LGC assays, mulitplex proinflammatory cytokine 
and chemokine analysis, flow cytometry - TBNK panel, and flow cytometry -
Th1/Th2/Th17/Th22 panel. Biomarker variables will be summarized and listed for each 
treatment at each scheduled visit using the PD-PPS analysis set.
In addition to the PD variables, whole blood will be stored to isolate deoxyribonucleic acid 
which may be used to examine genetic and epigenetic changes. The blood samples for genetic 
and epigenetic, and genomic, proteomic/metabolomics will not be analyzed in the interim or 
final analysis. Variables will be analyzed in a separate analysis as ad-hoc analysis. 
The AbAb status will be determined for each visit where samples are taken for drug 
concentration measures. A cut point will be determined by the bioanalytical laboratory and 
will be used to determine the AbAb status as “above the cut point” (ACP) or “below the cut 
point” (BCP). For any AbAb 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 AbAb titre will be reported.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 106 of 194
At each visit:
x
Samples that are either BCP or ACP and NCP are defined as AbAb-
x
Samples that are ACP and CP are defined as AbAb+
In addition, overall AbAb status should be determined:
x
Subject AbAb positivity is defined as having with AbAb+ at any time in the treatment 
period. This does not include Baseline/pre-treatment
x
Subject AbAb negativity is defined with AbAb- at any time in the treatment period. 
This does also include AbAb+ at Baseline/pre-treatment
x
Treatment-emergent AbAb positivity is defined when a subject is AbAb+ for the first time 
during treatment period excluding Baseline/pre-treatment. If there is AbAb+ at 
Baseline/pretreatment and there is a pre-defined fold increase in titre at least at one 
visit during the treatment period, then the subject has also a treatment-emergent AbAb 
positivity status.
Note: The fold increase from Baseline required will be defined with the development of the 
assay prior to database lock.
…
All individual subject-level AbAb results will be listed including the screening assay, 
confirmatory assay, and titres if applicable. Note, that titre results will only be available, if 
the confirmatory assay is positive.
Immunogenicity data will be summarized and listed using the PK-PPS analysis set.
Change # 17
Section 10.1 Extent of exposure
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(14)
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk is defined as:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 107 of 194
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(15)
where 140 days refers to 5*half-life of bimekizumab.
Has been changed to
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(14)
The sum over all duration of exposure (in years) will be calculated for the total subject-
years of duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(15)
where 140 days refers to 5*half-life of bimekizumab.
The sum over all time at risk (in years) will be calculated for the total subject-years of time 
at risk.
Change # 18
Section 10.2 Adverse events
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
AEs (including serious AEs) are characterized as either pretreatment or treatment emergent 
according to the following criteria:
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or variations 
2)
2)
thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 108 of 194
x
Pretreatment AEs are the events with onset date and time prior to the very first administration 
of study medication (bimekizumab or placebo).
x
Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment emergent (eg, in the case of 
premature discontinuation or during the SFU period).
If it is not possible (due to partial dates) to determine whether or not an AE is treatment emergent 
then it will be assumed to be a TEAE.
If the intensity of an AE is unknown, it is considered as severe.
If the relationship to study drug is missing, it is considered as related.
All AEs occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the eCRF. For each AE the following information will be recorded in the eCRF: 
AE term (verbatim term), date of onset, whether or not the AE was classified as a SAE, as an AE 
of special interest, intensity, relationship to study medication, action taken with study 
medication, other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation.
The following code lists will be used for AE recording:
x
Pattern of event: intermittent or continuous
x
Intensity of event: mild, moderate or severe
x
Relationship: related or not related
x
Action taken with IMP: dose not changed, dose reduced, dose increased, drug temporarily, 
interrupted, drug permanently withdrawn or not applicable
x
Outcome: resolving, not resolved, resolved, resolved with sequelae, worsened, fatal or 
unknown
For all TEAEs the following variables will be calculated:
x
Duration
x
Time since first dose
x
Time to last/latest dose
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݂݁݅݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ
(16)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁
(17)
Time to first dose will not be calculated for pretreatment AEs. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 109 of 194
The time to last dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݐ݋݈ܽݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݈ܽݏݐ݀݋ݏ݁െ݀ܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
(18)
The incidence of TEAEs will be summarized by MedDRA system organ class, high level term,
and PT. Tables with incidences of classified TEAEs by maximum intensity, by relationship, and 
by subject number will be provided. The incidence of non-serious TEAEs above the reporting 
threshold of 5% of subjects and relationship will be summarized. Furthermore the incidence of 
all TEAEs, serious TEAEs, non-serious TEAEs, and TEAEs leading to study discontinuation 
and/or permanent withdrawal of study medication will be summarized. In addition an overall 
summary table will be provided. 
AE of Special Interest and AE of Special Monitoring
AE of special interest is any AE which meets the Hy’s Law criteria, defined as ≥3x upper limit 
of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with 
coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with 
no alternative explanation for the biochemical abnormality.
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and TB), cytopenias, hypersensitivities, suicide ideation or behavior (assessed using 
the electronic Columbia-Suicide Severity Rating Scale [eC-SSRS]), depression and anxiety 
(assessed using the HADS), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin), malignancies, and inflammatory bowel diseases.
The incidence of TEAEs of special interest will be summarized by MedDRA system organ class, 
high level term, and PT. In addition, for some TEAEs and special monitoring separate incidence 
summary tables including exposure adjusted incidence rate (EAIR) with associated 95% CI, and 
the exposure adjusted event rate (EAER) will be provided:
x
Fungal infectious disorder 
x
Opportunistic infection (including TB) 
x
Malignant or unspecified tumor
x
Malignant tumor 
x
Major cardiovascular event
x
Haematopoietic cytopenias
x
Neuropsychiatric events 
x
Inflammatory bowel disease
x
Hypersensitivity and anaphylactic reaction
x
Hepatic events 
Fungal Infectious disorder
Fungal infections will be summarized in a stand-alone table which presents EAIR and EAER. 
The table will include all TEAEs which code into the High Level Group Term (HLGT) of 
“Fungal infectious disorders”.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 110 of 194
…
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER)
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊
෌
ܶா௫௣ǡ௜
௡
௜ୀଵ
(19)
If a subject has multiple events, the time of exposure is calculated to the first occurrence of the
AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(20)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(21)
where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෌
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(22)
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Has been changed to
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
AEs (including serious AEs) are characterized as either non-treatment or treatment emergent 
according to the following criteria:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 111 of 194
x
Non-treatment emergent are the events with onset date and time prior to the very first
administration of study medication (bimekizumab or placebo) or after a 140-day period 
after the final drug administration.
x
Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment emergent (eg, in the case of 
premature discontinuation or during the SFU period).
If it is not possible (due to partial dates) to determine whether or not an AE is treatment emergent 
then it will be assumed to be a TEAE.
If the intensity of an AE is unknown, it is considered as severe.
If the relationship to study drug is missing, it is considered as related.
All AEs occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the eCRF. For each AE the following information will be recorded in the eCRF: 
AE term (verbatim term), date of onset, whether or not the AE was classified as a SAE, as an AE 
of special interest, intensity, relationship to study medication, action taken with study 
medication, other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation.
The following code lists will be used for AE recording:
x
Pattern of event: intermittent or continuous
x
Intensity of event: mild, moderate or severe
x
Relationship: related or not related
x
Action taken with IMP: dose not changed, dose reduced, dose increased, drug temporarily, 
interrupted, drug permanently withdrawn or not applicable
x
Outcome: resolving, not resolved, resolved, resolved with sequelae, worsened, fatal or 
unknown
For all TEAEs the following variables will be calculated:
x
Duration
x
Time since first dose
x
Time to last/latest dose
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݂݁݅݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ
(16)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁
(17)
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or variations 
merge
merge
va
thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 112 of 194
Time to first dose will not be calculated for pretreatment AEs. 
The time to last dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݐ݋݈ܽݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݈ܽݏݐ݀݋ݏ݁െ݀ܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
(18)
Adverse drug reactions (ADRs) are defined as a response to a drug which is noxious and 
unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or 
therapy of disease or for modification of physiological function. Any AE that is considered 
“Related” to study treatment will be classed as an ADR.
The incidence of TEAEs will be summarized by MedDRA system organ class, high level term, 
and PT. Tables with incidences of classified TEAEs by maximum intensity, by relationship, and 
by subject number will be provided. The incidence of non-serious TEAEs above the reporting 
threshold of 5% of subjects and relationship will be summarized. Furthermore the incidence of 
all TEAEs, serious TEAEs, non-serious TEAEs, and TEAEs leading to study discontinuation 
and/or permanent withdrawal of study medication will be summarized. In addition an overall 
summary table will be provided. 
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER) will be 
calculated for following tables in the final analysis: all TEAEs, serious TEAEs, TEAEs 
leading to study discontinuation and/or permanent withdrawal, ADRs, fungal infectious 
disorder TEAEs, opportunistic infection (including tuberculosis) TEAEs, malignant or 
unspecified tumor TEAEs, malignant tumor TEAEs, major cardiovascular event TEAEs, 
haematopoietic cytopenias TEAEs, neuropsychiatric events TEAEs, inflammatory bowel 
disease TEAEs, hypersensitivity and anaphylactic Reaction TEAEs, hepatic events TEAEs, 
and TEAEs by timing of onset relative to AbAb Status.
10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ࡰ࢛࢘ࢇ࢚࢏࢕࢔ሺࢊࢇ࢙࢟ሻൌࡰࢇ࢚ࢋ࢕ࢌ࢕࢛࢚ࢉ࢕࢓ࢋെࡰࢇ࢚ࢋ࢕ࢌ࢕࢔࢙ࢋ࢚+ 1
(16)
For the calculation of duration for AEs with missing start dates, the dates will be imputed 
as described in Section 4.2.2.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ࢀ࢏࢓ࢋ࢙࢏࢔ࢉࢋࢌ࢏࢙࢚࢘ࢊ࢕࢙ࢋሺࢊࢇ࢙࢟ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌ࡭ࡱ࢕࢔࢙ࢋ࢚െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘ࢊ࢕࢙ࢋ൅૚
(17)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ࢀ࢏࢓ࢋ࢙࢏࢔ࢉࢋ࢓࢕࢙࢚࢘ࢋࢉࢋ࢔࢚ࢊ࢕࢙ࢋሺࢊࢇ࢙࢟ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌ࡭ࡱ࢕࢔࢙ࢋ࢚
െࡰࢇ࢚ࢋ࢕ࢌ࢓࢕࢙࢚࢘ࢋࢉࢋ࢔࢚ࢊ࢕࢙ࢋ࢖࢘࢏࢕࢚࢘࢕࡭ࡱ൅૚
(18)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
REDACTED
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 113 of 194
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose
the same formulas as above (17 and 18) will be used but the date of first bimekizumab dose 
will be used instead of the date of first dose. The time to first dose and time to first 
bimekizumab dose differs only for those subjects who receive placebo at Baseline.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ࡰࢇ࢙࢟࢕࢔࢚࢘ࢋࢇ࢚࢓ࢋ࢔࢚
ൌࡰࢇ࢚ࢋ࢕ࢌ࢒ࢇ࢙࢚Ȁ࢒ࢇ࢚ࢋ࢙࢚ࢊ࢕࢙ࢋ
െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘࢖࢒ࢇࢉࢋ࢈࢕࢕࢘࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈ࢊ࢕࢙ࢋ൅૚
(19)
ࡰࢇ࢙࢟࢕࢔࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈࢚࢘ࢋࢇ࢚࢓ࢋ࢔࢚
ൌࡰࢇ࢚ࢋ࢕ࢌ࢒ࢇ࢙࢚Ȁ࢒ࢇ࢚ࢋ࢙࢚ࢊ࢕࢙ࢋ
െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈ࢊ࢕࢙ࢋ൅૚
(20)
10.2.2 10.2.2 Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER)
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
ࡱ࡭ࡵࡾൌ૚૙૙כ
࢔
σ
ࢀࡱ࢞࢖ǡ࢏
࢔
࢏ୀ૚
(21)
where ࢀࡱ࢞࢖ǡ࢏is a subject’s exposure time in years up to the first occurrence of the AE of 
interest. 
If a subject has multiple events, the time of exposure is calculated to the first occurrence of 
the AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% CIs for incidence rates are calculated using the relationship between 
the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ࡸ࡯ࡸൌ
࣑૛࢔ǡࢻ
૛
૛
૛
(23)
ࢁ࡯ࡸൌ
࣑૛ሺ࢔ା૚ሻǡ૚ିࢻȀ૛
૛
૛
(23)
where n is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper 
tail probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 114 of 194
ࡱ࡭ࡱࡾൌ૚૙૙כ
ࡺ࡭ࡱ
σ
ࢀࡾ࢏࢙࢑ǡ࢏
࢔
࢏ୀ૚
(24)
where NAE is the total number of AEs and ࢀࡾ࢏࢙࢑ǡ࢏is a subject’s total time at risk in years.
No CI will be computed for EAER.
AE of Special Interest and AE of Special Monitoring
AE of special interest is any AE which meets the Hy’s Law criteria, defined as ≥3x upper limit 
of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with 
coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with 
no alternative explanation for the biochemical abnormality.
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and TB), cytopenias, hypersensitivities, suicide ideation or behavior (assessed using 
the electronic Columbia-Suicide Severity Rating Scale [eC-SSRS]), depression and anxiety 
(assessed using the HADS), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin), malignancies, and inflammatory bowel diseases.
The incidence of TEAEs of special monitoring will be summarized by MedDRA system 
organ class, high level term, and PT. EAIR with associated 95% CI, and the EAER will be 
included in the summary tables for following TEAEs of special monitoring:
The incidence of TEAEs of special interest will be summarized by MedDRA system organ class, 
high level term, and PT. In addition, for some TEAEs and special monitoring separate incidence 
summary tables including exposure adjusted incidence rate (EAIR) with associated 95% CI, and 
the exposure adjusted event rate (EAER) will be provided:
x
Fungal infectious disorder 
x
Opportunistic infection (including TB) 
x
Malignant or unspecified tumor
x
Malignant tumor 
x
Major cardiovascular event
x
Haematopoietic cytopenias
x
Neuropsychiatric events 
x
Inflammatory bowel disease
x
Hypersensitivity and anaphylactic reaction
x
Hepatic events 
Fungal Infectious disorder
Fungal infections will be summarized in a stand-alone table which presents EAIR and EAER. 
The table will include all TEAEs which code into the High Level Group Term (HLGT) of 
“Fungal infectious disorders”.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 115 of 194
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER)
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient years:
ܧܣܫܴൌͳͲͲ כ
݊
෌
ܶா௫௣ǡ௜
௡
௜ୀଵ
(19)
If a subject has multiple events, the time of exposure is calculated to the first occurrence of the 
AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(20)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵఈȀଶ
ଶ
ʹ
(21)
where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi square quantile for the upper tail 
probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෌
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(22)
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Change # 19
Section 11 References
…
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-
endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum 
Dis. 2009;68:18-24.
Maksymowych WP, Mallon C, Richardson R, et al. Development and Validation of the 
Edmonton Ankylosing Spondylitis Metrology Index. Arthritis Rheum. 2006;55:575-82.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 116 of 194
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-
endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum 
Dis. 2009;68:18-24.
Machado P, Navarro-Compan V, Landewe R, van Gaalen VA, Roux C, van der Heijde D.
Calculating the Ankylosing Spondylitis Disease Activity Score If the Conventional C-
Reactive Protein Level Is Below the Limit of Detection or If High-Sensitivity C-Reactive 
Protein Is Used: An Analysis in the DESIR Cohort. Arthritis Rheum. 2015 Feb;67(2):408-
13.
Maksymowych WP, Mallon C, Richardson R, et al. Development and Validation of the 
Edmonton Ankylosing Spondylitis Metrology Index. Arthritis Rheum. 2006;55:575-82.
…
Change # 20
Section 12.2 12.2 Treatment group assignment for tables and figures
Table 12‒2 displays the treatment group labels for each data type. This overview clarifies what 
kind of treatment groups will be used for producing the tables and figures separated between the 
different table types.
Table 12‒2:
Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 64mg/ BKZ 320mg
All BKZ
All 
subjects
Subject disposition
X
X
X
Important protocol deviation
X
X
X
Demographics/Lifestyle
X
X
X
Ankylosing spondylitis 
history
X
X
X
Baseline characteristics
X
X
X
TB testing
X
X
X
Previous and ongoing medical 
history
X
X
X
Prior and concomitant 
medication
X
X
X
Rescue and prohibited 
medication
X
X
X
Bimekizumab compliance
X
X
X
Extent of exposure
X
X
X
Efficacy analysis
X
X
Plasma/Bimekizumab 
concentration
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 117 of 194
Table 12‒2:
Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 64mg/ BKZ 320mg
All BKZ
All 
subjects
Pharmacokinetic 
variables/Biomarker 
data/AbAb
X
X
AEs
X
X
X
Safety laboratory tests
X
X
Vital signs/Body weight/ECG/ 
Physical examination
X
X
eC-SSRS
X
X
AbAb=Anti-bimekizumab antibody; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale.
Has been changed to
Table 12‒2 displays the treatment group labels for each data type. This overview clarifies what 
kind of treatment groups will be used for producing the tables and figures separated between the 
different table types.
Table 12‒2:
Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 160mg/ BKZ 
320mg
All BKZ
All 
subjects
Subject disposition
X
X
X
Important protocol deviation
X
X
X
Demographics/Lifestyle
X
X
X
Ankylosing spondylitis 
history
X
X
X
Baseline characteristics
X
X
X
TB testing
X
X
X
Previous and ongoing medical 
history
X
X
X
Prior and concomitant 
medication
X
X
X
Rescue and prohibited 
medication
X
X
X
Bimekizumab compliance
X
X
X
Extent of exposure
X
X
X
Efficacy analysis
X
X
Plasma/Bimekizumab 
concentration
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 118 of 194
Table 12‒2:
Treatment group assignment for tables and figures
Placebo
BKZ 16mg/ BKZ64mg/ 
BKZ 160mg/ BKZ 
320mg
All BKZ
All 
subjects
Pharmacokinetic 
variables/Biomarker 
data/AbAb
X
X
AEs
X
X
X
Safety laboratory tests
X
X
X
Vital signs/Body weight/ECG/ 
Physical examination
X
X
X
eC-SSRS
X
X
X
AbAb=Anti-bimekizumab antibody; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 119 of 194
13.2
Amendment 2
13.2.1
Rationale for the amendment
The SAP has been amended to:
x
Group the geographic region in North America, Western and Eastern Europe
x
Remove subgroup synthetic disease-modifying antirheumatic drugs (DMARDs) and add 
subgroup current NSAIDs at Baseline
x
Correct inflammatory bowel disease coding
x
Add rule for handling missing data for prior and concomitant medication
x
Modify Section 10
13.2.2
Modifications and changes
Section 3.8 Center pooling strategy
Centers will be pooled into geographic regions for analysis purposes. Centers will be grouped in 
the geographic regions North America and Europe.
Has been changed to
Centers will be pooled into geographic regions for analysis purposes. Centers will be grouped in 
the geographic regions North America, Western and Eastern Europe.
Section 4.2.1 Handling of missing data for efficacy analysis
The analysis for the binary primary, secondary, and other efficacy variables will use non-
responder imputation (NRI) for handling missing data. In NRI, each subject with missing data or 
who has discontinued double-blind study treatment prior to Week 12 will be counted as a non-
responder. 
Sensitivity analysis will be performed for the secondary analysis of the primary variable 
(ASAS40 response at Week 12) using MI assuming that missingness is missing at random 
(MAR). The MI method will be applied as follows:
1. Create a data set, sorted by treatment groups, of subjects with observed values and those 
needing estimation by multiple imputation. For the imputation step, missing values will be 
separated into non-monotone missing values (ie, intermittent missing values between 
completed assessments) and monotone missing values (ie, missing values after the patient 
dropped out). The procedure will sequentially estimate an imputation model for the ASAS 
components at each post-Baseline visit where ASAS components are collected, with 
geographic region, and prior TNF inhibitor exposure as covariates separated between the 
treatment groups.

For the imputation of intermediate missing values, the missing ASAS components in 
each data set will be filled in using the Markov-Chain Monte Carlo (MCMC) method 
with multiple chains and monotone imputing. A total number of imputations will be 100. 
The seed used for these imputations will be 2017. 
Note: All other multiple imputation procedures described in this SAP will use this same 
seed as well.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 120 of 194
Note: The imputation model based on the MCMC method will only allow continuous 
variables as predictors. Therefore, prior TNF inhibitor exposure and geographic region 
will be re-coded as indicator variables (with values of 0 or 1 for each level of the 
variable).
Note: To avoid that imputed values are outside of the pre-defined range of values for the 
ASAS components (eg, PGADA [0-10]) maximum and minimum values for imputed 
variable values are specified.

If the intermediate missing data are imputed, the monotone missing data will be imputed 
for all patients with monotone regression including geographic region, and prior TNF 
inhibitor exposure as covariates. The dataset is the output dataset of the partial 
imputation. Since this dataset already has 100 imputed values at each visit, only one 
imputation will be performed. 
Note: Maximum and minimum values are specified for imputed variable values to avoid 
values outside of the pre-defined range of values.
…
Has been changed to
The analysis for the binary primary, secondary, and other efficacy variables will use non-
responder imputation (NRI) for handling missing data. In NRI, each subject with missing data or 
who has discontinued double-blind study treatment prior to Week 12 will be counted as a non-
responder. 
Sensitivity analysis will be performed for the secondary analysis of the primary variable 
(ASAS40 response at Week 12) using MI assuming that missingness is missing at random 
(MAR). The MI method will be applied as follows:
1. Create a data set, sorted by treatment groups, of subjects with observed values and those 
needing estimation by multiple imputation. For the imputation step, missing values will be 
separated into non-monotone missing values (ie, intermittent missing values between 
completed assessments) and monotone missing values (ie, missing values after the patient 
dropped out). The procedure will sequentially estimate an imputation model for the ASAS 
components at each post-Baseline visit where ASAS components are collected, with 
geographic region, and prior TNF inhibitor exposure as covariates separated between the 
treatment groups.

For the imputation of intermediate missing values, the missing ASAS components in 
each data set will be filled in using the Markov-Chain Monte Carlo (MCMC) method 
with multiple chains and monotone imputing. A total number of imputations will be 100. 
The seed used for these imputations will be 2017. 
Note: All other multiple imputation procedures described in this SAP will use this same 
seed as well.
Note: The imputation model based on the MCMC method will only allow continuous 
variables as predictors. Therefore, prior TNF inhibitor exposure and geographic region 
will be re-coded as indicator numeric variables (with values of 0 or for the levels of 
TNF [1=prior inhibitor exposure, 0=non prior inhibitor exposure] and two binary 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 121 of 194
variables for geographic region [Variable 1: 1=North America, 0=others, Variable 
2: 1=Eastern Europe, 0=others] as representation of geographic region).
Note: To avoid that imputed values are outside of the pre-defined range of values for the 
ASAS components (eg, PGADA [0-10]) maximum and minimum values for imputed 
variable values are specified. Moreover, the rounding options for imputed values are
used where appropriate.

Once the intermediate missing data are imputed, the monotone missing data will be 
imputed for all patients with monotone regression including geographic region, and prior 
TNF inhibitor exposure as covariates. The dataset is the output dataset of the partial 
imputation. Since this dataset already has 100 imputed values at each visit, only one 
imputation will be performed. 
Note: Maximum and minimum values (and rounding where appropriate) are specified 
for imputed variable values to avoid values outside of the pre-defined range of values. 
…
Section 4.2.3 Handling of missing data for prior and concomitant medication
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days. Such imputations will only be performed for these classifications and calculations; in 
the listings all data will be shown as recorded on the electronic case report form (eCRF).
Imputation of partial start dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the month and year are specified and the subject did switch treatment during that
month and year, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
If only the year is specified, and the year of first dose is the same as the year the subject did
switch treatment, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is the same as the year of the start date 
and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 122 of 194
Has been changed to
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days. Such imputations will only be performed for these classifications and calculations; in 
the listings all data will be shown as recorded on the electronic case report form (eCRF).
Imputation of partial start dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the month and year are specified and the subject did switch treatment during that 
month and year, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
If only the year is specified, and the year of first dose is the same as the year the subject did 
switch treatment, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is the same as the year of the start date 
and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
x
If the start date is completely unknown and the stop date is prior to the date of first 
dose, then set the start date to the 1st of January of the year of the end date.
…
Section 4.3 Interim analyses and data monitoring
After all enrolled subjects have completed the 12 weeks Double-Blind Period, an interim 
analysis will be performed (i) to analyze the dose:exposure response for the ASAS40 response 
criteria to determine the optimal therapeutic dose(s) for subsequent studies, and (ii) to perform a 
comprehensive evaluation of all double-blind data of the study.
No separate SAP for the interim analysis will be provided. The interim analysis is a limited 
version of the final analysis and will focus on the primary and secondary efficacy analysis and 
comprise the results of the 12 weeks Double-Blind Period. The TFL shells for the interim and 
final analysis will be provided in two different documents.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 123 of 194
Columbia-Suicide Severity Rating Scale (eC-SSRS). Corresponding listings will be provided. 
Not all collected hematology and biochemistry laboratory variables will be summarized and 
listed. For the interim analysis only selected variables will be provided as listed in Table 12‒3.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS). Not all collected hematology and 
biochemistry laboratory variables will be summarized. For the interim analysis only selected 
hematology and biochemistry variables will be provided as listed in Table 12‒3. Listings of AEs, 
hematology, biochemistry and C-SSRS data will be provided.
The interim efficacy analysis will include following primary and secondary variables: 
ASAS40,20,5/6 response at Week 12, and change from Baseline in BASDAI, ASDAS-CRP, 
BASFI at Week 12. The variables will be analyzed using the same methods described in
Section 8.1.2 and Section 8.2 including supportive and sensitivity analyses (Section 8.1.3 and 
Section 8.1.4). In addition, summary tables for the primary and secondary efficacy variables, and 
the ASAS components will be provided. Categorical variables will be summarized using 
frequency tables by each visit. Continuous variables will be summarized using descriptive 
statistics by each visit. Time to onset of ASAS20 response and ASAS40 response will be 
summarized and plotted as described in Section 8.3.
PK and PD data will be analyzed in the interim analysis as described in Section 9.1 and
Section 9.2. PKPD will be analyzed as part of the exposure:response modeling outside of the 
scope of the SAP. Biomarker data will not be analyzed in the interim analysis.
The interim analysis includes selected data up to Week 12 and in addition data up to Week 16. 
The data up to Week 16 may include partial results up to the time the database for Week 12 was 
locked for ongoing subjects. All analyses for the period between Week 12 and Week 24 are only 
for those treatment groups that are not rerandomized. Following variables will be analyzed: 
ASAS40, ASAS20, ASDAS-CRP, BASDAI, PK, AbAb and TEAEs. It depends on the analysis 
how those additional time points will be presented in the interim analysis. Two summary tables 
for TEAE will be presented. The first table will include data up to Week 12 by treatment group 
at Baseline. The second table will include data up to Week 16 by following treatment groups: 
bimekizumab 160mg and bimekizumab 320mg. The summary table for the other variables will 
present only data up to Week 12 for the Baseline treatment groups Placebo, bimekizumab 16mg, 
and bimekizumab 64mg. Data up to Week 16 will be presented for bimekizumab 160mg and 
bimekizumab 320mg. All Listings which include data up to Week 16 will use the same approach.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will be 
allocated to the Double-Blind treatment. An exception from this general rule is made for adverse 
drug reactions (ADRs), and AE of hypersensitivity reactions and anaphylactic reactions. If those 
AEs occur on the same days as the treatment switch, the AEs will be allocated to the Dose-Blind 
treatment and will not be presented for the interim analysis.
Exposure of study medication will not be summarized but a listing will be provided including 
following information: date of first dose, date of last dose, and duration of exposure. The last 
dose for the Double-Blind Period is planned on Visit 6 (Week 8). For subject who completed the 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 124 of 194
Double-Blind Period the Week 8 date is the date of the last dose. If a subject discontinued within 
the Double-Blind Period, the discontinuation date will be presented for the date of last dose.
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48. 
Safety data will be provided to an independent Data Monitoring Committee (DMC). The DMC 
will review those safety data periodically. The composition and operation of the DMC will be 
defined in the DMC charter. The presentation and analysis of data for the DMC meetings is 
described within a separate DMC SAP.
Has been changed to
After all enrolled subjects have completed the 12 weeks Double-Blind Period, an interim 
analysis will be performed (i) to analyze the dose:exposure response for the ASAS40 response 
criteria to determine the optimal therapeutic dose(s) for subsequent studies, and (ii) to perform a 
comprehensive evaluation of all double-blind data of the study.
No separate SAP for the interim analysis will be provided. The interim analysis is a limited 
version of the final analysis and will focus on the primary and secondary efficacy analysis and 
comprise the results of the 12 weeks Double-Blind Period. The TFL shells for the interim and 
final analysis will be provided in two different documents.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia Suicide Severity Rating Scale (eC SSRS). Corresponding listings will be provided. 
Not all collected hematology and biochemistry laboratory variables will be summarized and 
listed. For the interim analysis only selected variables will be provided as listed in Table 
Table 12‒3.
The interim analysis will summarize disposition, demographics, AS history, Baseline 
characteristics, AS concomitant medication, efficacy analysis, AEs and treatment-emergent AEs 
(derivation Section 10.2), hematology and biochemistry laboratory data, and Electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS). Listings of AEs, hematology, biochemistry 
and C-SSRS data will be provided. Not all collected hematology and biochemistry laboratory 
variables will be summarized displayed in the tables and listings. For the interim analysis only 
selected hematology and biochemistry variables will be provided as listed in Table 12‒3.
The interim efficacy analysis will include following primary and secondary variables: For 
efficacy the interim analysis will include following primary and secondary variables: 
ASAS40,20,5/6 response at Week 12, and change from Baseline in BASDAI, ASDAS-CRP, 
BASFI at Week 12. The variables will be analyzed using the same methods described in
Section 8.1.2 and Section 8.2 including supportive and sensitivity analyses (Section 8.1.3 and 
Section 8.1.4). In addition, summary tables for the primary and secondary efficacy variables, and 
the ASAS components will be provided. Categorical variables will be summarized using 
frequency tables by each visit. Continuous variables will be summarized using descriptive 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 125 of 194
statistics by each visit. Time to onset of ASAS20 response and ASAS40 response will be 
summarized and plotted as described in Section 8.3.
PK and PD data will be analyzed in the interim analysis as described in Section 9.1 and
Section 9.2. PKPD will be analyzed as part of the exposure:response modeling outside of the 
scope of the SAP. Biomarker data will not be analyzed in the interim analysis.
The interim analysis includes selected data up to Week 12 and in addition data up to Week 16. 
The data up to Week 16 may include partial results up to the time the database for Week 12 was 
locked for ongoing subjects. All analyses for the period between Week 12 and Week 24 are only 
for those treatment groups that are not rerandomized. Following variables will be analyzed: 
ASAS40, ASAS20, ASDAS-CRP, BASDAI, PK, AbAb and TEAEs. It depends on the analysis 
how those additional time points will be presented in the interim analysis. Two summary tables 
for TEAE will be presented. The first table will include TEAEs with a relative TEAE start 
date less equal 84 (12*7) days by treatment group at Baseline. The second table will include 
TEAEs with a relative TEAE start date less equal 112 (16*7) days by the following 
treatment groups: bimekizumab 160mg and bimekizumab 320mg. The summary table for 
the other variables will present only data up to Week 12 for the Baseline treatment groups 
Placebo, bimekizumab 16mg, and bimekizumab 64mg. Data up to Week 16 will be presented for 
bimekizumab 160mg and bimekizumab 320mg. All Listings which include data up to Week 16 
will use the same approach.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will be 
allocated to the Double-Blind treatment. An exception from this general rule is made for adverse 
drug reactions (ADRs), and AE of hypersensitivity reactions and anaphylactic reactions. If those 
AEs occur on the same days as the treatment switch, the AEs will be allocated to the Dose-Blind 
treatment and will not be presented for the interim analysis.
Exposure of study medication will not be summarized but a listing will be provided including 
following information: date of first dose, date of last dose, and duration of exposure. The last 
dose for the Double-Blind Period is planned on Visit 6 (Week 8). For subject who completed the 
Double-Blind Period the Week 8 date is the date of the last dose. If a subject discontinued within 
the Double-Blind Period, the discontinuation date will be presented for the date of last dose.
For the interim analysis, the database will be locked and the treatment codes will be made 
available to UCB personnel with exception of operational staff working on the study. An interim 
report will be written. The investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48. 
Further details are available in the AS0008 blinding plan.
Safety data will be provided to an independent Data Monitoring Committee (DMC). The DMC 
will review those safety data periodically. The composition and operation of the DMC will be 
defined in the DMC charter. The presentation and analysis of data for the DMC meetings is 
described within a separate DMC SAP.
Section 4.8 Examination of subgroups
The following variables for subgroup analyses will be used:
x
Age (<45 years, ≥45 years)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 126 of 194
x
Gender (male, female)
x
Geographic region (North America, Europe)
x
Treatment-emergent AbAb status (positive, negative)
x
TNF inhibitor exposure (yes, no)
x
Synthetic disease-modifying antirheumatic drugs (DMARDs) (concomitant, non 
concomitant)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12). 
Has been changed to
The following variables for subgroup analyses will be used:
x
Age (<45 years, ≥45 years)
x
Gender (male, female)
x
Geographic region (North America, Eastern and Western Europe)
x
Treatment-emergent AbAb status (positive, negative)
x
Prior TNF inhibitor exposure (yes, no)
x
Synthetic disease modifying antirheumatic drugs (DMARDs) (concomitant, non 
concomitant)
x
Current NSAIDs at Baseline (yes, no)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12). 
Section 6.2 Other Baseline characteristics
AS history will be summarized for subjects in the FAS and SS including the time since first 
diagnosis of AS, time since first symptoms of AS, and age at first diagnosis date. The history 
will be listed for all subjects in the RS.
Time since first diagnosis of AS will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏ
ൌܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(6)
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are missing).
Time since first symptoms will be calculated as:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 127 of 194
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ
ൌܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(7)
…
Has been changed to
AS history will be summarized for subjects in the FAS and SS including the time since first 
diagnosis of AS, time since first symptoms of AS, and age at first diagnosis date. The history 
will be listed for all subjects in the RS.
Time since first diagnosis of AS will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏ
ൌܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(6)
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are missing).
Time since first symptoms will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ
ൌܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(7)
The absolute values of the formulas (6) and (7) will be used to display positive values.
Section 8.1.1 Derivations of ASAS score and response
…
For all non-missed visits, if any of the component scores are missing, then the following rules 
will be applied:
x
If all the component values are missing from Baseline through the visit being considered, the 
percent improvement from Baseline to that visit for the given component will be imputed as 
0%. The unit improvement will be imputed as 0.
x
If the component value at a given visit is missing and the Baseline value is present, the 
missing component will be replaced by the last non-missing observation (LOCF) for that 
component.
If the Baseline value of an ASAS component is 0, then for the purposes of calculating ASAS, the 
percent change from Baseline will be determined as follows (zero divisor rule):
x
If the post-Baseline component value is also 0, set the percent change equal to 0;
x
If the post-Baseline component value is >0, then calculate the percent change as though the 
Baseline value were 0.1.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 128 of 194
…
For all non-missed visits, if any of the component scores are missing, then the following rules 
will be applied:
x
If all the component values are missing from Baseline through the visit being considered, the 
percent improvement from Baseline to that visit for the given component will be imputed as 
0%. The unit improvement will be imputed as 0.
x
If the component values are missing at Baseline, the percent improvement from 
Baseline to a visit for the given component will be imputed as 0%. The unit 
improvement will be imputed as 0.
x
If the component value at a given visit is missing and the Baseline value is present, the 
missing component will be replaced by the last non-missing observation (LOCF) for that 
component.
If the Baseline value of an ASAS component is 0, then for the purposes of calculating ASAS, the 
percent change from Baseline will be determined as follows (zero divisor rule):
x
If the post-Baseline component value is also 0, set the percent change equal to 0;
x
If the post-Baseline component value is >0, then calculate the percent change as though the 
Baseline value were 0.1.
…
Section 8.1.3 Secondary analyses of the primary efficacy variable
As the secondary analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure. To 
avoid the problem of the so-called monotone likelihood resulting in infinite large confidence 
intervals (eg, if one of the cell counts in the 2x2 table is equal to zero), a penalized maximum 
likelihood approach based on the modified score procedure of Firth (eg, Heinze and Schemper, 
2002) will be used in the logistic models. If the logistic regression model is unable to converge, 
then geographic region may be dropped from the model to facilitate convergence. If the logistic 
regression model is unable to converge after dropping the geographic region, then prior TNF 
inhibitor exposure may be dropped as well. Comparisons will be made for each dose versus 
placebo at a 2-sided significance level of α=0.05. For each dose, the odds ratio versus placebo, 
the 95% confidence interval, and the corresponding p-value will be calculated.
…
Has been changed to
As the secondary analysis for the primary efficacy variable, a logistic regression model will be 
used to assess the effect of each individual dose versus placebo on ASAS40 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure. To 
avoid the problem of the so-called monotone likelihood resulting in infinite large confidence 
intervals (eg, if one of the cell counts in the 2x2 table is equal to zero), a penalized maximum 
likelihood approach based on the modified score procedure of Firth (eg, Heinze and Schemper, 
2002) will be used in the logistic models. If the logistic regression model is unable to 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 129 of 194
converge, then a 2-way categorical variable for geographic region (North America and 
Europe) will be used. Should the logistic regression model be unable to converge even with 
this restriction, then geographic region may be dropped from the model to facilitate 
convergence. If the logistic regression model is unable to converge after dropping the geographic 
region, then prior TNF inhibitor exposure may be dropped as well. Comparisons will be made 
for each dose versus placebo at a 2-sided significance level of α=0.05. For each dose, the odds 
ratio versus placebo, the 95% confidence interval, and the corresponding p-value will be 
calculated.
…
Section 8.3 Statistical analysis of other efficacy variables
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in weeks from Baseline until the first date when the response is achieved. 
Subjects who discontinue study treatment prior to achieving a response will be censored at the 
date of study treatment discontinuation. Subjects who reach the Week 12 visit without achieving 
a response will be censored at the date of the Week 12 visit. Missing response data will be 
imputed with NRI.
Has been changed to
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in weeks from Baseline until the first date when the response is achieved. 
Following derivation will be used: Days from Baseline until the first date divided by 7. 
There will be no rounding for the Kaplan Meier estimates. Subjects who discontinue study 
treatment prior to achieving a response will be censored at the date of study treatment 
discontinuation. Subjects who reach the Week 12 visit without achieving a response will be 
censored at the date of the Week 12 visit. Missing response data will be imputed with NRI.
Section 8.4 Subgroup analysis
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: 
x
Age (<45 years, ≥45 years)
x
Gender (male, female)
x
Geographic region (North America, Europe)
x
Treatment-emergent AbAb status (positive, negative)
x
TNF inhibitor exposure (yes, no)
x
Synthetic DMARDs (concomitant, non concomitant)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 130 of 194
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
Has been changed to
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses are defined in Section 4.8. be defined:
x
Age (<45 years, ≥45 years)
x
Gender (male, female)
x
Geographic region (North America, Eastern and Western Europe)
x
Treatment emergent AbAb status (positive, negative)
x
Prior TNF inhibitor exposure (yes, no)
x
Synthetic DMARDs (concomitant, non concomitant)
x
Current NSAIDs at Baseline (yes, no)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12).
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
Section 10.1 Extent of exposure
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(14)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 131 of 194
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(15)
where 140 days refers to 5*half-life of bimekizumab.
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
Has been changed to
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(14)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(15)
where 140 days refers to 5*half-life of bimekizumab.
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ࡰࢇ࢙࢟࢕࢔࢚࢘ࢋࢇ࢚࢓ࢋ࢔࢚
ൌࡰࢇ࢚ࢋ࢕ࢌ࢒ࢇ࢙࢚Ȁ࢒ࢇ࢚ࢋ࢙࢚ࢊ࢕࢙ࢋ
െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘࢖࢒ࢇࢉࢋ࢈࢕࢕࢘࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈ࢊ࢕࢙ࢋ൅૚
(16)
ࡰࢇ࢙࢟࢕࢔࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈࢚࢘ࢋࢇ࢚࢓ࢋ࢔࢚
ൌࡰࢇ࢚ࢋ࢕ࢌ࢒ࢇ࢙࢚Ȁ࢒ࢇ࢚ࢋ࢙࢚ࢊ࢕࢙ࢋ
െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈ࢊ࢕࢙ࢋ൅૚
(17)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 132 of 194
Section 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(16)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(17)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(18)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (17 and 18) will be used but the date of first bimekizumab dose will be 
used instead of the date of first dose. The time to first dose and time to first bimekizumab dose 
differs only for those subjects who receive placebo at Baseline.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(19)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(20)
Has been changed to
The duration of each AE will be calculated as follows:
ܣܧܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(18)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 133 of 194
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(19)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(20)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (17 and 18) will be used but the date of first bimekizumab dose will be 
used instead of the date of first dose. The time to first dose and time to first bimekizumab dose 
differs only for those subjects who receive placebo at Baseline.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
ܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(19)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(20)
Section 10.2.2 Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER)
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊
෌
ܶா௫௣ǡ௜
௡
௜ୀଵ
(21)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest.
If a subject has multiple events, the time of exposure is calculated to the first occurrence of the 
AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 134 of 194
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(22)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(23)
where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෌
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(24)
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Has been changed to
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊
෌
ܶா௫௣ǡ௜
௡
௜ୀଵ
(21)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest
(equation [18] in years) at the level of coding evaluated.
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (15) is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(22)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(23)
where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 135 of 194
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෌
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(24)
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Section 10.2.3 AE of Special Monitoring
…
Inflammatory bowel disease
These events will be presented in a stand-alone table which includes EAIR and EAER. The table 
will include all TEAEs which code into the HLGT of “Colitis excl infective”.
…
Has been changed to
…
Inflammatory bowel disease
These events will be presented in a stand-alone table which includes EAIR and EAER. The table 
will include all TEAEs which code into the HLGT of “Colitis excl infective”.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 136 of 194
13.3
Amendment 3
13.3.1
Rationale for the amendment
The SAP has been amended to:
x
Add Section with changes from interim analysis to SAP-defined analyses
x
Change definition of AE of special monitoring for final analysis
x
Analyze the MASES Score on a subset of the FAS 
x
Change the missing item rule for ASQoL
x
Add limit of quantification for CRP and hs-CRP
x
Update AE section to apply the interim rules to the final analysis
x
Update markedly abnormal laboratory units and add the RCTC reference
x
Update AbAb Section to clarify the overall AbAb status and the first occurrence of AbAb 
positivity
x
Change subgroup analysis sections to change the definitions of treatment-emergent AbAb 
status
x
Remove rounding information for BMI, hs-CRP, and CRP
x
Update prohibited medication section to remove the rule that efficacy results should be set to 
missing after receiving prohibited medication
x
Update pharmacokinetics section to be aligned with TFLs shells
13.3.2
Modifications and changes
List of abbreviation
Has been changed to
…
BUN
Blood urea nitrogen
CP
Confirmed positive
…
RBC
Red blood cell
RNA
Ribonucleic acid
…
…
BUN
Blood urea nitrogen
CDISC
Clinical Data Interchange Standards 
Consortium
remov
remo
dicatio
icatio
to be a
to be 
ch
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 137 of 194
Section 4.3.1 has been added
Section 4.3.1 Changes from interim analysis to SAP-defined analyses
For TEAE two summary tables were presented as described in previous section with one 
modification: the first table was displaying all TEAE during the Double-Blind Period 
instead of limiting it TEAE with a relative TEAE start date less equal 84 days. 
The definitions of AE of special monitoring were updated with the third SAP Amendment 
after the interim analysis. The interim analysis used the previous definition which is 
displayed in Section 4.3.1.2. The interim analysis only displayed the overall number of AE 
of special monitoring by treatment group.
The definitions of time since first diagnosis of AS and time since first symptoms were 
updated with the third SAP Amendment after the interim analysis. In the previous 
definitions the date of informed consent was subtracted from the date of diagnosis or first 
symptoms which results in negative values. For the interim analysis following calculations 
were used:
ࢀ࢏࢓ࢋ࢙࢏࢔ࢉࢋࢌ࢏࢙࢚࢘ࢊ࢏ࢇࢍ࢔࢕࢙࢏࢙ሺ࢟ࢋࢇ࢙࢘ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌࡵ࢔ࢌ࢕࢘࢓ࢋࢊ࡯࢕࢔࢙ࢋ࢔࢚െࡰࢇ࢚ࢋ࢕ࢌࢊ࢏ࢇࢍ࢔࢕࢙࢏࢙
૜૟૞Ǥ ૛૞
ࢀ࢏࢓ࢋ࢙࢏࢔ࢉࢋࢌ࢏࢙࢚࢙࢘࢟࢓࢖࢚࢕࢓࢙ሺ࢟ࢋࢇ࢙࢘ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌࡵ࢔ࢌ࢕࢘࢓ࢋࢊ࡯࢕࢔࢙ࢋ࢔࢚െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢙࢘࢟࢓࢖࢚࢕࢓࢙
૜૟૞Ǥ ૛૞
Section 4.3.2 has been added
Section 4.3.2 Search and selection criteria for AE of special monitoring for interim analysis
Following AEs are defined as TEAEs of special monitoring: 
x
Fungal infectious disorder 
x
Opportunistic infection (including TB) 
x
Malignant or unspecified tumor
x
Malignant tumor 
x
Major cardiovascular event
CP
Confirmed positive
…
RBC
Red blood cell
RCTC
Rheumatology Common Toxicity Criteria
RNA
Ribonucleic acid
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 138 of 194
x
Haematopoietic cytopenias
x
Neuropsychiatric events 
x
Inflammatory bowel disease
x
Hypersensitivity and anaphylactic reaction
x
Hepatic events 
Fungal Infectious disorder
All TEAEs which code into the High Level Group Term (HLGT) of “Fungal infectious 
disorders”.
Opportunistic infection
All TEAEs identified using UCB-defined search criteria as described in Section 12.13.
Malignant or unspecified tumor
The search criteria is based on the criteria Standardized MedDRA Query (SMQ) = 
“Malignant or unspecified tumours (SMQ)”. 
Malignant tumor
The search criteria is based on the criteria SMQ=”Malignant tumours (SMQ)”.
Major cardiovascular events
The major cardiovascular events are identified using the following UCB-defined search 
criteria:
x
All serious TEAEs which code to a PT included in the Scope=Broad and/or 
Scope=Narrow groups of the following SMQs:

Haemorrhagic central nervous system vascular conditions (SMQ)

Ischaemic central nervous system vascular conditions (SMQ)
x
All serious TEAEs which code to a PT included in the HLT “Ischaemic coronary artery 
disorders” except events coding to PT “Chest Pain” or “Chest discomfort”
x
All serious TEAEs which code to a PT included in any of the following HLTs: “Heart 
Failures NEC”, “Left Ventricular Failures”, or “Right Ventricular Failures” and which 
also code to the SOC of “Cardiac Disorders” as Primary SOC.
Haematopoietic cytopenias
The search criteria is based on the SMQ = “Haematopoietic cytopenias”. 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.
Neuropsychiatric events
The search criteria is based on the SMQ = “Depression and suicide/self-injury (SMQ)”. 
The SMQ search will 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
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 139 of 194
Inflammatory bowel disease
All TEAEs which code into the HLT of “Colitis (excl infective)”.
Hypersensitivity reactions and anaphylactic reactions
Hypersensitivity reactions and anaphylactic reactions will be identified as follow:
c) Hypersensitivity reactions: All TEAEs that either emerged on the same day as when 
a study medication injection reaction was received, or that emerged one day after a 
study medication injection was received, which code to a PT which contains the 
term “hypersensitivity” will be considered to be a hypersensitivity reaction and 
included in the summary table as such.
d) Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs 
that are considered to be anaphylactic reactions. PTs are separated into the 4 
distinct categories (A, B, C, D) prior to the algorithmic approach being applied.
All TEAEs that either emerged on the same day as when a study medication injection 
reaction was received, or that emerged one day after a study medication injection was 
received, and which fulfill any of the 3 criteria described in Section 12.14 will be included 
in the summary table.
Hepatic events
The search criteria is based on all TEAEs in the SMQ “Drug related hepatic disorders -
comprehensive search (SMQ)”. Note that the following two sub-SMQs are to be excluded: 
“Liver neoplasms, benign (incl cysts and polyps)” and “Liver neoplasms, malignant and 
unspecified (SMQ)”.
The SMQ search should include all TEAEs (regardless of whether they have been judged 
as related to study medication or not) which code to a PT included in the Scope=Narrow 
group within each SMQ.
Section 4.8 Examination of subgroups
…
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12). 
Has been changed to
…
Subjects will be counted to have a positive treatment-emergent AbAb status in case the first 
AbAb positivity occurred up to between the first dose and Visit 7 (Week 12). The definition of 
first AbAb occurrence is described in Section 9.2.
Section 6.1 Demographics
…
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the formula:
For adults:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 140 of 194
ܤܯܫൌܹ݄݁݅݃ݐ
ܪ݄݁݅݃ݐଶ
(5)
Even if they are available in the database, these variables are calculated during analysis (if 
applicable). These calculated values are used in the statistical analysis since they are considered 
more accurate. BMI is rounded to 1 decimal.
…
Has been changed to
…
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the formula:
For adults:
ܤܯܫൌܹ݄݁݅݃ݐ
ܪ݄݁݅݃ݐଶ
(5)
Even if they are available in the database, these variables are calculated during analysis (if 
applicable). These calculated values are used in the statistical analysis since they are considered 
more accurate. BMI is rounded to 1 decimal.
…
Section 6.2 Other Baseline characteristics
…
Time since first diagnosis of AS will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏ
ൌܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(6)
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are missing).
Time since first symptoms will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ
ൌܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏെܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
(7)
Age at first diagnosis will be calculated as:
ܣ݃݁ܽݐ݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏൌܦܽݐ݁݋݂݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܾ݅ݎݐ݄
͵͸ͷǤʹͷ
(8)
The absolute values of the formulas (6) and (7) will be used to display positive values.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 141 of 194
Has been changed to
…
Time since first diagnosis of AS will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺ࢟ࢋࢇ࢙࢘ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌࡵ࢔ࢌ࢕࢘࢓ࢋࢊ࡯࢕࢔࢙ࢋ࢔࢚െࡰࢇ࢚ࢋ࢕ࢌࢊ࢏ࢇࢍ࢔࢕࢙࢏࢙൅૚
૜૟૞Ǥ ૛૞
(6)
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are missing).
Time since first symptoms will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏሺ࢟ࢋࢇ࢙࢘ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌࡵ࢔ࢌ࢕࢘࢓ࢋࢊ࡯࢕࢔࢙ࢋ࢔࢚െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢙࢘࢟࢓࢖࢚࢕࢓࢙൅૚
૜૟૞Ǥ ૛૞
(7)
Age at first diagnosis will be calculated as:
ܣ݃݁ܽݐ݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏൌܦܽݐ݁݋݂݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܾ݅ݎݐ݄
͵͸ͷǤʹͷ
(8)
The absolute values of the formulas (6) and (7) will be used to display positive values.
…
Section 6.5 Prohibited medication and rescue medication
Prohibited medications are defined in the protocol (Section 7.8.2). All efficacy data collected at 
assessments after the use of prohibited medications should be treated as missing. Prohibited 
medication use and date of first usage should be determined and documented during the data 
evaluation meeting (DEM) prior to the database lock. 
…
Has been changed to
Prohibited medications are defined in the protocol (Section 7.8.2). All efficacy data collected at 
assessments after the use of prohibited medications should be treated as missing. Prohibited 
medication use and date of first usage should be determined and documented during the data 
evaluation meeting (DEM) prior to the database lock. 
…
Section 8.3 Statistical analysis of other efficacy variables
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 142 of 194
All categorical variables will be presented using frequency tables by each visit. All continuous 
variables will be summarized using descriptive statistics by each visit.
The Hospital Anxiety and Depression Scale (HADS) will be analyzed separately for HADS-A
and HADS-D. The summary statistics for HADS-A and HADS-D will be presented in two 
different tables.
Times series plots will be provided for the response rate or change from Baseline for the primary 
and secondary efficacy variables. The plots will show the weekly response rate over the first 12 
weeks.
The MRI of the spine and sacroiliac joints will be performed in a substudy with subjects who 
were classified as MRI-positive at Baseline as per ASAS-Outcome Measures in Rheumatology 
Clinical Trials (OMERACT) criteria.
…
Has been changed to
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
All categorical variables will be presented using frequency tables by each visit. All continuous 
variables will be summarized using descriptive statistics by each visit.
The Hospital Anxiety and Depression Scale (HADS) will be analyzed separately for HADS-A
and HADS-D. The summary statistics for HADS-A and HADS-D will be presented in two 
different tables.
Times series plots will be provided for the response rate or change from Baseline for the primary 
and secondary efficacy variables. The plots will show the weekly response rate over the first 12 
weeks.
The MRI of the spine and sacroiliac joints will be performed in a substudy with subjects who 
were classified as MRI-positive at Baseline as per ASAS-Outcome Measures in Rheumatology 
Clinical Trials (OMERACT) criteria.
A subset of the FAS will be used for the analyses of MASES. The MASES Score will only 
be analyzed for subjects with enthesitis at Baseline (MASES > 0).
…
Section 8.3.5 Ankylosing Spondylitis Quality of Life (ASQoL)
The ASQoL consists of 18 items, each with a score of 0 = no or 1 = yes, so that the sum score 
ranges from 0 to 18, with higher scores indicating worse quality of life. The questionnaire is 
available in Section 12.11.
If 6 or fewer items are missing, the missing responses will be imputed with the mean of the 
available responses from that visit to calculate a total score. If more than 6 items are missing, the 
total score will be left missing.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 143 of 194
Has been changed to
The ASQoL consists of 18 items, each with a score of 0 = no or 1 = yes, so that the sum score 
ranges from 0 to 18, with higher scores indicating worse quality of life. The questionnaire is 
available in Section 12.11.
If 63 or fewer items are missing, the missing responses will be imputed with the mean of the 
available responses from that visit to calculate a total score. If more than 63 items are missing, 
the total score will be left missing
Section 8.3.9 C-reactive protein (CRP) and high-sensitivity C-reactive protein (CRP)
…
The values of hs-CRP and CRP will be rounded to integers prior to calculating ratio to Baseline 
and values below the limit of quantification should be set to should be set to half the limit of 
quantification for the calculations. 
Has been changed to
…
The values of hs CRP and CRP will be rounded to integers prior to calculating ratio to Baseline 
and hs-CRP and CRP values below the limit of quantification should be set to should be set to
half the limit of quantification for the calculations. The limit of quantification for hs-CRP is 
0.16 mg/L and 0.4 mg/dL = 4.00 mg/L for CRP.
Section 8.4 Subgroup analysis
…
Subjects will be counted to have a positive treatment-emergent AbAb status in case the positivity 
occurred between the first dose and Visit 7 (Week 12).
…
Has been changed to
…
Subjects will be counted to have a positive treatment-emergent AbAb status in case the first 
AbAb positivity occurred up to between the first dose and Visit 7 (Week 12). The definition of 
first AbAb occurrence is described in Section 9.2.
…
Section 9.1 Pharmacokinetics
…
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group, and by cumulative antibody status (ie, positive, negative) for subjects 
randomized to bimekizumab as well as individual time curves of DAS28(CRP), bimekizumab 
concentration, and AbAb.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 144 of 194
Has been changed to
…
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group, and by cumulative antibody status (ie, positive, negative) for subjects 
randomized to bimekizumab as well as individual time curves of DAS28(CRP), bimekizumab 
concentration, and AbAb.
…
Section 9.2 Pharmacodynamics and Immunogenicity
…
In addition, overall AbAb status should be determined:
x
Subject AbAb positivity is defined as having with AbAb+ at any time in the treatment 
period. This does not include Baseline/pre-treatment
x
Subject AbAb negativity is defined with AbAb- at any time in the treatment period. This 
does also include AbAb+ at Baseline/pre-treatment
x
Treatment-emergent AbAb positivity is defined when a subject is AbAb+ for the first time 
during treatment period excluding Baseline/pre-treatment. If there is AbAb+ at 
Baseline/pretreatment and there is a pre-defined fold increase in titre at least at one visit 
during the treatment period, then the subject has also a treatment-emergent AbAb positivity 
status.
Note: The fold increase from Baseline required will be defined with the development of the 
assay prior to database lock.
…
Has been changed to
…
In addition, overall AbAb status should be determined:
x
Subject AbAb positivity is defined as having with AbAb+ at any time in the treatment 
period. This does not include Baseline/pre-treatment
x
Subject AbAb negativity is defined with AbAb- at any time in the treatment period. This 
does also include AbAb+ at Baseline/pre-treatment
x
Treatment emergent AbAb positivity is defined when a subject is AbAb+ for the first time 
during treatment period excluding Baseline/pre treatment. If there is AbAb+ at 
Baseline/pretreatment and there is a pre defined 4-fold increase in titre at least at one visit 
during the treatment period, then the subject has also an treatment emergent overall AbAb 
positivity status.
Note: The fold increase from Baseline required will be defined with the development of the 
assay prior to database lock.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 145 of 194
The visit of the first occurrence of AbAb positivity is defined as the visit when a subject is 
AbAb+ for the first time during treatment period excluding Baseline/pre-treatment. If 
there is AbAb+ at Baseline/pre-treatment and there is a 4-fold increase in titre at least at 
one visit during the treatment period, then the subject’s first occurrence visit is the 
Baseline Visit.
…
Section 10.2 Adverse events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
AEs (including serious AEs) are characterized as either non-treatment or treatment emergent 
according to the following criteria:
x
Non-treatment emergent are the events with onset date and time prior to the very first 
administration of study medication (bimekizumab or placebo) or after a 140-day period after 
the final drug administration.
x
Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment emergent (eg, in the case of 
premature discontinuation or during the SFU period).
All AEs occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the eCRF. For each AE the following information will be recorded in the eCRF: 
AE term (verbatim term), date of onset, whether or not the AE was classified as a SAE, as an AE 
of special interest, intensity, relationship to study medication, action taken with study 
medication, other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation.
The following code lists will be used for AE recording:
x
Pattern of event: intermittent or continuous
x
Intensity of event: mild, moderate or severe
x
Relationship: related or not related
x
Action taken with IMP: dose not changed, dose reduced, dose increased, drug temporarily, 
interrupted, drug permanently withdrawn or not applicable
x
Outcome: resolving, not resolved, resolved, resolved with sequelae, worsened, fatal or 
unknown
For all TEAEs the following variables will be calculated:
x
Duration
x
Time since first dose
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 146 of 194
Adverse drug reactions (ADRs) are defined as a response to a drug which is noxious and 
unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or 
therapy of disease or for modification of physiological function. Any AE that is considered 
“Related” to study treatment will be classed as an ADR.
…
Has been changed to
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
AEs (including serious AEs) are characterized as either non-treatment or treatment emergent 
according to the following criteria:
x
Non-treatment emergent are the events with onset date and time prior to the very first 
administration of study medication (bimekizumab or placebo) or after a 140-day period after 
the final drug administration.
x
Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment emergent (eg, in the case of 
premature discontinuation or during the SFU period).
All AEs occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the eCRF. For each AE the following information will be recorded in the eCRF: 
AE term (verbatim term), date of onset, whether or not the AE was classified as a SAE, as an AE 
of special interest, intensity, relationship to study medication, action taken with study 
medication, other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation.
The following code lists will be used for AE recording:
x
Pattern of event: intermittent or continuous
x
Intensity of event: mild, moderate or severe
x
Relationship: related or not related
x
Action taken with IMP: dose not changed, dose reduced, dose increased, drug temporarily, 
interrupted, drug permanently withdrawn or not applicable
x
Outcome: resolving, not resolved, resolved, resolved with sequelae, worsened, fatal or 
unknown
For all TEAEs the following variables will be calculated:
x
Duration
x
Time since first dose
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 147 of 194
Adverse drug reactions (ADRs) are defined as a response to a drug which is noxious and 
unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or 
therapy of disease or for modification of physiological function. Any AE that is considered 
“Related” to study treatment will be classed as an ADR.
If an AE occurs on the same day as the treatment switch (Visit 7, Week 12) then the AE will 
be allocated to the Double-Blind treatment. An exception from this general rule is made for 
ADRs, and AE of hypersensitivity reactions and anaphylactic reactions. If those AEs occur 
on the same days as the treatment switch, the AEs will be allocated to the Dose-Blind 
treatment.
Section 10.2.3AE of Special Interest and AE of Special Monitoring
AE of special interest is any AE which meets the Hy’s Law criteria, defined as ≥3x upper limit 
of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with 
coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with 
no alternative explanation for the biochemical abnormality.
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and TB), cytopenias, hypersensitivities, suicide ideation or behavior (assessed using 
the electronic Columbia-Suicide Severity Rating Scale [eC-SSRS]), depression and anxiety 
(assessed using the HADS), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin), malignancies, and inflammatory bowel diseases.
The incidence of TEAEs of special monitoring will be summarized by MedDRA system organ 
class, high level term, and PT. EAIR with associated 95% CI, and the EAER will be included in 
the summary tables for following TEAEs of special monitoring:
•
Fungal infectious disorder 
•
Opportunistic infection (including TB) 
•
Malignant or unspecified tumor
•
Malignant tumor 
•
Major cardiovascular event
•
Haematopoietic cytopenias
•
Neuropsychiatric events 
•
Inflammatory bowel disease
•
Hypersensitivity and anaphylactic reaction
•
Hepatic events 
Fungal Infectious disorder
Fungal infections will be summarized in a stand-alone table which presents EAIR and EAER. 
The table will include all TEAEs which code into the High Level Group Term (HLGT) of 
“Fungal infectious disorders”.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 148 of 194
Opportunistic infections (including TB) will be summarized in a stand-alone table which 
presents EAIR and EAER. The table will include all TEAEs identified using UCB-defined 
search criteria as described in Section 12.13.
Malignant or unspecified tumor
These events will be presented in one stand-alone table which will include EAIR and EAER. The 
table will be based on the criteria Standardized MedDRA Query (SMQ) = “Malignant or 
unspecified tumours (SMQ)”. 
The output table will include 2 different overall incidence rows:
1. The first overall incidence row will summarize “Any malignancies (including unspecified)” 
and this row will summarize the incidence of all AEs flagged for inclusion in the table,
regardless of the High Level Term (HLT) it codes to. 
2. The second overall incidence row will summarize “Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)” 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)”.
Malignant tumor
These events will be presented in one stand-alone table which will include EAIR and EAER. The 
table will be based on the criteria SMQ=”Malignant tumours (SMQ)”.
Note that the events included in the “Malignant tumours” table will be a subset of the events 
included in the “Malignant or unspecified tumours” table. The SMQ search should include all 
TEAEs which code to a PT included in the Scope=Narrow group within each SMQ.
The output table will include 2 different overall incidence rows:
1. The first overall incidence row will summarize “Any malignancies” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table, regardless of the High 
HLT it codes to. 
2. The second overall incidence row will summarize “Any malignancy (excluding non-
melanomic skin cancers)” 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)”.
Major cardiovascular events
The major cardiovascular events are 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 SMQs:

Haemorrhagic central nervous system vascular conditions (SMQ)

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disorders” except events coding to PT “Chest Pain” or “Chest discomfort”
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 149 of 194
•
All serious TEAEs which code to a PT included in any of the following HLTs: “Heart 
Failures NEC”, “Left Ventricular Failures”, or “Right Ventricular Failures” and which also code 
to the SOC of “Cardiac Disorders” as Primary SOC.
Haematopoietic cytopenias 
These events will be presented in a stand-alone table that is based on the SMQ = 
“Haematopoietic cytopenias”. 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.
Neuropsychiatric events
These events will be presented in a stand-alone table including EAIR and EAER. The table will 
be based on the SMQ = “Depression and suicide/self-injury (SMQ)”. The SMQ search will 
include all TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow 
groups within the SMQ.
Inflammatory bowel disease
These events will be presented in a stand-alone table which includes EAIR and EAER. The table 
will include all TEAEs which code into the HLT of “Colitis excl infective”.
Hypersensitivity reactions and anaphylactic reactions
Anaphylactic reactions will be summarized together in a stand-alone table.
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 (together – not broken 
out by type) by SOC, HLT and PT.
Hypersensitivity reactions and anaphylactic reactions will be identified as follow:
c) Hypersensitivity reactions: All TEAEs that either emerged on the same day as when a study 
medication injection reaction was received, or that emerged one day after a study medication 
injection was received, which code to a PT which contains the term “hypersensitivity” will be 
considered to be a hypersensitivity reaction and included in the summary table as such.
d) Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs that are 
considered to be anaphylactic reactions. PTs are separated into the 4 distinct categories (A, B, C, 
D) prior to the algorithmic approach being applied.
All TEAEs that either emerged on the same day as when a study medication injection reaction 
was received, or that emerged one day after a study medication injection was received, and 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 150 of 194
which fulfill any of the 3 criteria described in Section 12.14 will be included in the summary 
table.
Hepatic events
Although not officially considered to be AEs of special monitoring but hepatic events are 
nonetheless considered to be interesting enough to be summarized in stand-alone tables.
Hepatic events will be summarized in a stand-alone table that includes all TEAEs in the SMQ 
“Drug related hepatic disorders - comprehensive search (SMQ)”. Note that the following two 
sub-SMQs are to be excluded: “Liver neoplasms, benign (incl cysts and polyps)” and “Liver 
neoplasms, malignant and unspecified (SMQ)”.
The SMQ search should include all TEAEs (regardless of whether they have been judged as 
related to study medication or not) which code to a PT included in the Scope=Narrow group 
within each SMQ.
Has been changed to
AE of special interest is any AE which meets the Hy’s Law criteria, defined as ≥3x upper limit 
of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with 
coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with 
no alternative explanation for the biochemical abnormality.
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and TB), cytopenias, hypersensitivities, suicide ideation or behavior (assessed using 
the electronic Columbia Suicide Severity Rating Scale [eC SSRS]), depression and anxiety 
(assessed using the HADS), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin), malignancies, and inflammatory bowel diseases.
AE of special monitoring for this study include: 
x
Infections (serious, opportunistic, fungal and TB) 
x
Malignancies, including lymphoma
x
Major cardiovascular events
x
Neutropenia
x
Neuropsychiatric events (in particular depression and suicide)
x
Inflammatory bowel disease
x
Anaphylactic reaction
x
Hepatic events 
For the definitions of AE of special monitoring the Bimekizumab Safety Topics of Interest 
(Version date 19Feb2018) will be used.
The incidence of TEAEs of special monitoring will be summarized by MedDRA system organ 
class, high level term, and PT. EAIR with associated 95% CI, and the EAER will be included in 
the summary tables. Serious infections are also classified as AE of special monitoring but no 
separate table will be produced.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 151 of 194
The output table for the search criteria Standardized MedDRA Query (SMQ) = 
“Malignant or unspecified tumours (SMQ)” will include two different overall rows:
x
The first overall incidence row will summarize “Any malignancies (including 
unspecified)” and this row will summarize the incidence of all AEs flagged for inclusion 
in the table, regardless of the High Level Term (HLT) it codes to. 
x
The second overall incidence row will summarize “Any malignancy (including 
unspecified, excluding non-melanomic skin cancers)” 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)”.
The output table for the search criteria SMQ=”Malignant tumours (SMQ)” will include 
two different overall rows:
x
The first overall incidence row will summarize “Any malignancies” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table, regardless of the 
High Level Term (HLT) it codes to. 
x
The second overall incidence row will summarize “Any malignancy (excluding non-
melanomic skin cancers)” 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)”.
The output table for Anaphylactic reaction will include three different overall rows: 
x
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.
x
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.
•
Fungal infectious disorder 
•
Opportunistic infection (including TB) 
•
Malignant or unspecified tumor
•
Malignant tumor 
•
Major cardiovascular event
•
Haematopoietic cytopenias
•
Neuropsychiatric events 
•
Inflammatory bowel disease
•
Hypersensitivity and anaphylactic reaction
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 152 of 194
•
Hepatic events
Fungal Infectious disorder
Fungal infections will be summarized in a stand alone table which presents EAIR and EAER. 
The table will include all TEAEs which code into the High Level Group Term (HLGT) of 
“Fungal infectious disorders”.
Opportunistic infection
Opportunistic infections (including TB) will be summarized in a stand alone table which 
presents EAIR and EAER. The table will include all TEAEs identified using UCB defined 
search criteria as described in Section 12.13.
Malignant or unspecified tumor
These events will be presented in one stand alone table which will include EAIR and EAER. The 
table will be based on the criteria Standardized MedDRA Query (SMQ) = “Malignant or 
unspecified tumours (SMQ)”. 
The output table will include 2 different overall incidence rows:
1. The first overall incidence row will summarize “Any malignancies (including unspecified)” 
and this row will summarize the incidence of all AEs flagged for inclusion in the table, 
regardless of the High Level Term (HLT) it codes to.
2. The second overall incidence row will summarize “Any malignancy (including unspecified, 
excluding non melanomic skin cancers)” 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)”.
Malignant tumor
These events will be presented in one stand alone table which will include EAIR and EAER. The 
table will be based on the criteria SMQ=”Malignant tumours (SMQ)”.
Note that the events included in the “Malignant tumours” table will be a subset of the events 
included in the “Malignant or unspecified tumours” table. The SMQ search should include all 
TEAEs which code to a PT included in the Scope=Narrow group within each SMQ.
The output table will include 2 different overall incidence rows:
1. The first overall incidence row will summarize “Any malignancies” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table, regardless of the High 
HLT it codes to.
2. The second overall incidence row will summarize “Any malignancy (excluding non
melanomic skin cancers)” 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)”.
Major cardiovascular events
The major cardiovascular events are identified using the following UCB defined search criteria:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 153 of 194
•
All serious TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow 
groups of the following SMQs:
Haemorrhagic central nervous system vascular conditions (SMQ)
Ischaemic central nervous system vascular conditions (SMQ)
•
All serious TEAEs which code to a PT included in the HLT “Ischaemic coronary artery 
disorders” except events coding to PT “Chest Pain” or “Chest discomfort”
•
All serious TEAEs which code to a PT included in any of the following HLTs: “Heart 
Failures NEC”, “Left Ventricular Failures”, or “Right Ventricular Failures” and which also code 
to the SOC of “Cardiac Disorders” as Primary SOC.
Haematopoietic cytopenias 
These events will be presented in a stand alone table that is based on the SMQ = 
“Haematopoietic cytopenias”. 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.
Neuropsychiatric events
These events will be presented in a stand alone table including EAIR and EAER. The table will 
be based on the SMQ = “Depression and suicide/self injury (SMQ)”. The SMQ search will 
include all TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow 
groups within the SMQ.
Inflammatory bowel disease
These events will be presented in a stand alone table which includes EAIR and EAER. The table 
will include all TEAEs which code into the HLT of “Colitis excl infective”.
Hypersensitivity reactions and anaphylactic reactions
Anaphylactic reactions will be summarized together in a stand alone table.
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 (together not broken 
out by type) by SOC, HLT and PT.
Hypersensitivity reactions and anaphylactic reactions will be identified as follow:
c) Hypersensitivity reactions: All TEAEs that either emerged on the same day as when a study 
medication injection reaction was received, or that emerged one day after a study medication 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 154 of 194
injection was received, which code to a PT which contains the term “hypersensitivity” will be 
considered to be a hypersensitivity reaction and included in the summary table as such.
d) Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs that are 
considered to be anaphylactic reactions. PTs are separated into the 4 distinct categories (A, B, C, 
D) prior to the algorithmic approach being applied.
All TEAEs that either emerged on the same day as when a study medication injection reaction 
was received, or that emerged one day after a study medication injection was received, and 
which fulfill any of the 3 criteria described in Section 12.14 will be included in the summary 
table.
Hepatic events
Although not officially considered to be AEs of special monitoring but hepatic events are 
nonetheless considered to be interesting enough to be summarized in stand alone tables.
Hepatic events will be summarized in a stand alone table that includes all TEAEs in the SMQ 
“Drug related hepatic disorders comprehensive search (SMQ)”. Note that the following two 
sub SMQs are to be excluded: “Liver neoplasms, benign (incl cysts and polyps)” and “Liver 
neoplasms, malignant and unspecified (SMQ)”.
The SMQ search should include all TEAEs (regardless of whether they have been judged as 
related to study medication or not) which code to a PT included in the Scope=Narrow group 
within each SMQ.
Section 10.3 Clinical laboratory evaluations
…
Markedly abnormal values for biochemistry and hematology are defined in Table 10‒2 and 
Table 10‒3.The markedly abnormal laboratory results will be listed separately.
Values that are below the lower limit of the reference range will be flagged as “L” (low) and 
values that are above the upper limit of the reference range will be flagged as “H” (high) and 
listed as well. 
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. In the case where laboratory values are 
below the lower limit of quantification, then these will be set to the midpoint between 0 and the 
lower limit of quantification for the purpose of summarizing the data.
Table 13‒5:
Definitions of Markedly Abnormal Biochemistry Values
Variable (Standard international 
units)
Markedly abnormal definition
Low
High
ALP
N/A
>3 x ULN
ALT
N/A
>3 x ULN
AST
N/A
>3 x ULN
Calcium (mg/dL)
<7.0
>12.5
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 155 of 194
Table 13‒5:
Definitions of Markedly Abnormal Biochemistry Values
Variable (Standard international 
units)
Markedly abnormal definition
Low
High
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
ALP=alkaline phosphatase; AST=aspartate aminotransferase; N/A=Not applicable; ULN=upper limit of normal.
Table 13‒6:
Definitions of Markedly Abnormal Hematology Values
Variable (Standard international 
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.
Has been changed to
…
Markedly abnormal values for biochemistry and hematology will be defined as laboratory 
values graded 3 or 4 according to the Rheumatology Common Toxicity Criteria (RCTC). 
Definitions of the markedly abnormal values are given in Table 10‒2 and Table 10‒3 and 
are based on the RCTC units. All units in the tables below will be converted to the 
standard units based on Clinical Data Interchange Standards Consortium (CDISC)
standards. The markedly abnormal laboratory results will be listed separately.
Values that are below the lower limit of the reference range will be flagged as “L” (low) and 
values that are above the upper limit of the reference range will be flagged as “H” (high) and 
listed as well. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 156 of 194
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. In the case where laboratory values are 
below the lower limit of quantification, then these will be set to the midpoint between 0 and the 
lower limit of quantification for the purpose of summarizing the data.
Table 13‒7:
Definitions of Markedly Abnormal Biochemistry Values
Variable (Standard international 
RCTC units)
Markedly abnormal definition
Low
High
ALP
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
ALP=alkaline phosphatase; AST=aspartate aminotransferase; N/A=Not applicable; RCTC= Rheumatology 
Common Toxicity Criteria; ULN=upper limit of normal.
Table 13‒8:
Definitions of Markedly Abnormal Hematology Values
Variable (Standard international
RCTC units)
Markedly abnormal definition
Low
High
Hemoglobin (g/dL)
<LLN
AND
>2.0 decrease from Baseline
N/A
Hemoglobin (g/dL)
<8.0
N/A
Leukocytes (total x 1000)
<2.0
N/A
Lymphocytes (x 1000)
<0.5
N/A
Neutrophils (x 1000)
<1.0
N/A
Platelets (x 1000)
<50
N/A
LLN=lower limit of normal; N/A = not applicable; RCTC= Rheumatology Common Toxicity Criteria.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 157 of 194
13.4
Amendment 4
13.4.1
Rationale for the amendment
The main objectives of this SAP amendment are to describe an additional interim analysis Week 
48 and correct small errors. 
13.4.2
Modifications and changes
Section 2.2.1.3 Other efficacy variables
…
x
ASAS5/6 response (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
…
Has been changed to
…
x
ASAS5/6 response (Week 1, 2, 4, 8, 12, 16, 24, 36, 48)
…
Section 3.1 General presentation of summaries and analyses
…
All original and derived variables will be listed and described using summary statistics (number 
of observations [n], mean, standard deviation [SD], median, minimum and maximum, unless 
otherwise stated) or frequency counts (number of subjects [N] and percentages). 
…
Statistical tests of efficacy variables will be presented as 2-sided p-values rounded 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”. Statistical comparisons will be performed by two-sided
statistical tests at the 0.0500 level of significance.
…
In the Double-Blind Period the order of treatment groups to be presented in tables from left to 
right will be placebo, bimekizumab 16mg, bimekizumab 64mg, bimekizumab 160 mg, and 
bimekizumab 320 mg. The general principle is to go from the lowest to highest dose when 
moving from left to right. Tables may also include columns for all subjects or all subjects on 
bimekizumab. An overview of the treatment group assignment is available in Table 12‒2.
Selected tables which are specified in the TFL shells will only use data from the Dose-Blind 
Period. For listings and the selected tables, the label and order of treatment groups will be 
presented as follows: placebo to bimekizumab 160mg at Week 12, bimekizumab 16mg to 
bimekizumab 160mg at Week 12, bimekizumab 64mg to bimekizumab 160mg at Week 12, 
bimekizumab 160mg, placebo to bimekizumab 320mg at Week 12, bimekizumab 16mg to 
bimekizumab 320mg at Week 12, bimekizumab 64mg to bimekizumab 320mg at Week 12, and 
bimekizumab 320mg. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 158 of 194
The abbreviation for bimekizumab is BKZ and will be used in tables and listings headers. All 
subjects on bimekizumab will be labeled as “All BKZ“ in the TFLs.
…
Has been changed to
…
All original and derived variables will be listed and described using summary statistics (number 
of observations [n], mean, standard deviation [SD], median, minimum and maximum, unless 
otherwise stated) or frequency counts (number of subjects [N] and percentages). For multiple 
post-Baseline assessments at a specific visit, the first non-missing measurement will be used 
for summary statistics or frequency counts. 
…
Statistical tests of efficacy variables will be presented as 2-sided p-values rounded to 34 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”. Statistical comparisons will be performed by two-sided
statistical tests at the 0.0500 level of significance.
…
In the Double-Blind Period the order of treatment groups to be presented in tables from left to 
right will be placebo, bimekizumab 16mg, bimekizumab 64mg, bimekizumab 160 mg, and 
bimekizumab 320 mg. Placebo, BKZ16mg, BKZ64mg, BKZ160mg, and BKZ320mg, where 
BKZ is the abbreviation for bimekizumab. The general principle is to go from the lowest to 
highest dose when moving from left to right. Tables may also include columns for all subjects or 
all subjects on bimekizumab. An overview of the treatment group assignment is available in 
Table 12‒2.
Selected tables which are specified in the TFL shells will only use data from the Dose-Blind 
Period. For listings and the selected tables, the label and order of treatment groups will be 
presented as follows: placebo to bimekizumab 160mg at Week 12, bimekizumab 16mg to 
bimekizumab 160mg at Week 12, bimekizumab 64mg to bimekizumab 160mg at Week 12, 
bimekizumab 160mg, placebo to bimekizumab 320mg at Week 12, bimekizumab 16mg to 
bimekizumab 320mg at Week 12, bimekizumab 64mg to bimekizumab 320mg at Week 12, and 
bimekizumab 320mg. Placebo-BKZ160mg, Placebo-BKZ320mg, BKZ16mg-BKZ160mg, 
BKZ16mg-BKZ320mg, BKZ64mg-BKZ160mg, BKZ64mg-BKZ320mg, BKZ160mg-
BKZ160mg, and BKZ320mg-BKZ320mg.
The abbreviation for bimekizumab is BKZ and will be used in tables and listings headers. All
subjects on bimekizumab will be labeled as “All BKZ“ in the TFLs.
…
Section 3.2.2 Study Periods
The following study periods are defined for the classification by study period:
x
Pre-treatment period (Screening period): up to 28 days, ends with the first dose of 
bimekizumab.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 159 of 194
x
Double-Blind treatment period: starts with the first dose of study medication (Visit 2), ends 
at Week 12 prior to the treatment re-randomization.
x
Dose-Blind treatment period: starts at the Week 12 visit after the treatment re-randomization, 
ends at Week 48.
x
Post-treatment period: The post-treatment period (Follow-up period) is the period after the 
last dose of bimekizumab administration. 
Has been changed to
The following study periods are defined for the classification by study period:
x
Pre-treatment period (Screening period): up to 28 days, ends with the visit date of the first 
dose of study medication (Visit 2) first dose of bimekizumab.
x
Double-Blind treatment period: starts with the visit date of the first dose of study medication 
(Visit 2), ends at Week 12 visit date prior to the treatment re randomization.
x
Dose-Blind treatment period: starts at the Week 12 visit after the treatment re randomization,
ends at Week 48 visit.
x
Post-treatment period: the post-treatment period (Follow-up period) is the period after the 
Week 48 visitlast dose of bimekizumab administration.
Section 3.3 Definition of Baseline values
Unless otherwise specified, the last valid measurement before first dose of study drug (Visit 2) 
will be used as the Baseline value. The same Baseline definition will be used for the follow-up
period. However, for some variables, assessments may be scheduled for Screening only and not 
for Baseline. In this case the Screening value will be utilized as Baseline value. If a Baseline 
measurement is missing, and a Screening value available, the Screening value will be utilized as 
Baseline instead.
If a scheduled Baseline assessment is taken on the same day as first administration of study 
medication and no time is collected, it will be assumed to have been taken prior to study 
medication.
Has been changed to
Unless otherwise specified, tThe last valid measurement before first dose of study drug (Visit 2) 
will be used as the Baseline value. If a scheduled Baseline assessment is taken on the same 
day and after the first administration of study medication, it will be analyzed as the first 
post-Baseline assessment. If a scheduled Baseline assessment is taken on the same day as 
first administration of study medication and no time is collected, it will be assumed to have 
been taken prior to study medication. 
The exception of the above rule are the questionnaires collected from the vendor ERT. For 
those measurement, the last valid measurement at the same day as Visit 2 will be used as 
the Baseline value. 
The same Baseline definition will be used for the follow up period. However, for some variables, 
assessments may be scheduled for Screening only and not for Baseline. In this case the Screening 
easure
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 160 of 194
value will be utilized as Baseline value. If a Baseline measurement is missing, and a Screening 
value available, the Screening value will be utilized as Baseline instead.
If a scheduled Baseline assessment is taken on the same day as first administration of study 
medication and no time is collected, it will be assumed to have been taken prior to study 
medication.
Section 3.7 Treatment assignment and treatment groups
…
For AE tables and listings, AEs for each subject will be summarized based on the treatment 
actually received at the onset of each particular AE. It should be noted that this could result in 
one subject being summarized in two different treatment groups within one output if they were 
on a treatment regimen that involved treatment switching and experienced AEs under both 
treatment allocations.
Efficacy analyses will be performed according to randomization and not actual treatment 
received.
Has been changed to
…
For AE tables and listings, AEs for each subject will be summarized based on the treatment 
actually received at the onset of each particular AE. It should be noted that this could result in 
one subject being summarized in two different treatment groups within one output if they were 
on a treatment regimen that involved treatment switching and experienced AEs under both 
treatment allocations.
Efficacy analyses will be performed according to randomization and not actual treatment 
received.
Depending on the analysis sets, subjects will be summarized and listed based on the actual 
received treatment or according to the randomization which will be considered as planned 
treatment:
x
All subjects screened/ES: planned treatment
x
RS: planned treatment
x
SS: actual treatment
x
FAS: planned treatment
x
PPS: planned treatment
x
PK-PPS: actual treatment 
x
PD-PPS: actual treatment 
x
DBS: actual treatment 
x
ESS: planned treatment
x
DBRS: planned treatment 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 161 of 194
Section 4.2.3 Handling of missing data for prior and concomitant medication
…
Imputation of Partial Start Dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the month and year are specified and the subject did switch treatment during that 
month and year, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
If only the year is specified, and the year of first dose is the same as the year the subject did 
switch treatment, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is the same as the year of the start date 
and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
x
If the start date is completely unknown and the stop date is prior to the date of first dose, then 
set the start date to the 1st of January of the year of the end date.
If the date of first study medication or switch treatment is partial, then the above imputation 
approach will be applied:
x
If only the day of first study medication or switch treatment administration is unknown, then 
this will be set to either the first of the month, or the day of first treatment allocation visit 
(excluding placebo run-in), whichever is later.
x
If both the day and month of first study medication or switch treatment are unknown, then 
this date will be imputed to be the date of first treatment allocation visit.
…
Has been changed to 
…
Imputation of Partial Start Dates:
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date and the subject did not switch treatment during that 
month and year, then use the 1st of the month.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 162 of 194
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the month and year are specified and the subject did switch treatment during that 
month and year, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date and the subject did not switch treatment during that year, then use the 1st of January of 
the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
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switch treatment, then use the date of first switch treatment.
x
If only the year is specified, and the year of first dose is the same as the year of the start date 
and the same as the year the subject did switch treatment, then use the date of first dose. 
x
If only the year is specified and the end date is before date of first dose, then set the 
start date to the 1st of January of the year of the start date.
x
If only the year and day are specified and month is missing, then only the year will be 
considered and the month and day will be imputed with the rules above
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
x
If the start date is completely unknown and the stop date is prior to the date of first dose, then 
set the start date to the 1st of January of the year of the end date.
If the date of first study medication or switch treatment is partial, then the below above
imputation approach will be applied:
x
If only the day of first study medication or switch treatment administration is unknown, then
this will be set to either the first of the month, or the day of first treatment allocation visit 
(excluding placebo run-in), whichever is later.
x
If both the day and month of first study medication or switch treatment are unknown, then 
this date will be imputed to be the date of first treatment allocation visit.
…
Section 4.3 Interim analyses and data monitoring
…
Exposure of study medication will not be summarized but a listing will be provided including 
following information: date of first dose, date of last dose, and duration of exposure. The last 
dose for the Double-Blind Period is planned on Visit 6 (Week 8). For subject who completed the 
Double-Blind Period the Week 8 date is the date of the last dose. If a subject discontinued within 
the Double-Blind Period, the discontinuation date will be presented for the date of last dose.
…
Section 4.3.1 Changes from interim analysis to SAP-defined analyses
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 163 of 194
For TEAE two summary tables were presented as described in previous section with one 
modification: the first table was displaying all TEAE during the Double-Blind Period instead of 
limiting it TEAE with a relative TEAE start date less equal 84 days. 
The definitions of AE of special monitoring were updated with the third SAP Amendment after 
the interim analysis. The interim analysis used the previous definition which is displayed in 
Section 4.3.1.2. The interim analysis only displayed the overall number of AE of special 
monitoring by treatment group.
The definitions of time since first diagnosis of AS and time since first symptoms were updated 
with the third SAP Amendment after the interim analysis. In the previous definitions the date of 
informed consent was subtracted from the date of diagnosis or first symptoms which results in 
negative values. For the interim analysis following calculations were used:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ
͵͸ͷǤʹͷ
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ
͵͸ͷǤʹͷ
Section 4.3.2 Search and selection criteria for AE of special monitoring for interim analysis
…
Has been changed to
Section 4.3 Interim analyses and data monitoring
Two interim analyses are planned for the study after the subjects have completed 12 and 48 
weeks.
Section 4.3.1 Interim analysis Week 12
….
Exposure of study medication will not be summarized but a listing will be provided including 
following information: date of first dose, date of last dose, and duration of exposure. The last 
dose for the Double-Blind Period is planned on Visit 6 (Week 8). For subject who completed the 
Double Blind Period the Week 8 date is the date of the last dose. If a subject discontinued within 
the Double Blind Period, the discontinuation date will be presented for the date of last dose.
…
Section 4.3.1.1 Changes from interim analysis Week 12 to SAP-defined analyses
For TEAE two summary tables were presented as described in previous section with one 
modification: the first table was displaying all TEAE during the Double-Blind Period instead of 
limiting it TEAE with a relative TEAE start date less equal 84 days. 
The definitions of AE of special monitoring were updated with the third SAP Amendment after 
the interim analysis. The interim analysis used the previous definition which is displayed in 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 164 of 194
Section 4.3.1.2. The interim analysis only displayed the overall number of AE of special 
monitoring by treatment group.
The definitions of time since first diagnosis of AS and time since first symptoms were updated 
with the third SAP Amendment after the interim analysis. In the previous definitions the date of 
informed consent was subtracted from the date of diagnosis or first symptoms which results in 
negative values. For the interim analysis following calculations were used:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ
͵͸ͷǤʹͷ
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐݏݕ݉݌ݐ݋݉ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐ
ܦܽݐ݁݋݂݂݅ݎݏݐݏݕ݉݌ݐ݋݉ݏ
͵͸ͷǤʹͷ
Section 4.3.1.2 Search and selection criteria for AE of special monitoring for interim 
analysis Week 12
…
Section 4.3.2 Interim analysis Week 48
After all enrolled subjects have completed the Week 48 or Early termination visit, a second 
interim analysis will be performed to analyze the key efficacy and safety data for the whole 
treatment period.
No separate SAP for that interim analysis will be provided. The interim analysis is a subset 
of the final analysis and will focus on the primary and secondary efficacy analysis. The 
TFL shells for the final analysis will be used.
The snapshot for the AS0008 interim analysis Week 48 will occur before all subjects have 
completed the AS0008 study. Specifically, subjects who do not enter the extension study 
will need to complete the SFU Visit, which occurs 20 weeks after the last dose of study 
treatment. The Week 48 interim database lock will be performed based on the last subject 
completing the Week 48 visit. It is anticipated that there will be some subjects still awaiting 
the SFU at that time. The number of subjects in that position is expected to be low, and the 
minimal data to be collected from their SFU visits is not considered mandatory to 
evaluation of the key efficacy and safety objectives of the study. 
Section 6.4 Prior and concomitant medications
Prior medications include any medications that started prior to the start date of study medication. 
Past medications are a subset of prior medications, and include prior medications with a stop date 
before the date of first study medication administration. Concomitant medications are 
medications taken at least one day in common with the study medication dosing period. For 
bimekizumab, the dosing period is typically from the date of first dose up to (but not including) 
one dosing interval post last dose. Thus, a concomitant medication is any medication whose start 
date is on or after the date of first study medication and prior to the date of last study medication 
administration + 28 days (1 dosing interval), and whose stop date is either missing, or on or after 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 165 of 194
the date of first study medication administration. Medications may be both prior and 
concomitant.
In the case of missing data, the classification of medications as prior or concomitant will be 
performed as described in Section 4.2.3. Imputations of missing data will be performed before 
calculation of relative study days. 
…
Has been changed to
Prior medications include any medications that started and ended prior to the start date of study 
medication. Past medications are a subset of prior medications, and include prior medications 
with a stop date before the date of first study medication administration. Concomitant 
medications are medications taken at least one day in common with the study medication dosing 
period. For bimekizumab, the dosing period is typically from the date of first dose up to (but not 
including) one dosing interval post last dose. Thus, a concomitant medication is any medication 
whose start date is on or after the date of first study medication and prior to the date of last study 
medication administration + 28 days (1 dosing interval), and whose stop date is either missing, or 
on or after the date of first study medication administration. Medications may be both prior and 
concomitant.
In the case of missing data, the classification of medications as prior or concomitant will be 
performed as described in Section 4.2.3. Imputations of missing data will be performed before 
calculation of relative study days. 
…
Section 7 Measurements of treatment compliance
…
where the total number of expected doses is derived relative to when the subject finishes 
treatment. If a subject completes treatment 12 doses are expected (Baseline and every 4th week 
afterwards until Week 48). If a subject discontinues early, then the number of expected doses is 
based on the time of early discontinuation relative to the dosing visits.
A summary of percent treatment compliance categorized as ≤80% and >80% will be provided by 
treatment group.
…
Has been changed to
…
where the total number of expected doses is derived relative to when the subject finishes 
treatment. If a subject completes treatment 12 doses are expected (Baseline and every 4th week 
afterwards until Week 448). If a subject discontinues early, then the number of expected doses is 
based on the time of early discontinuation relative to the dosing visits. If a dose is not 
completely given at a specific visit (eg, subject only received one injection instead of the two 
planned injections), then the subject will be considered to have no compliance for the visit. 
In the formula above it will be counted as no dose received at this visit.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 166 of 194
A summary of percent treatment compliance categorized as ≤80% and >80% will be provided by 
treatment group for the overall treatment period as well as for double-blind treatment 
period.
…
Section 8.3 Statistical analysis of other efficacy variables
…
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in weeks from Baseline until the first date when the response is achieved. 
Following derivation will be used: Days from Baseline until the first date divided by 7. There 
will be no rounding for the Kaplan Meier estimates. Subjects who discontinue study treatment 
prior to achieving a response will be censored at the date of study treatment discontinuation. 
Subjects who reach the Week 12 visit without achieving a response will be censored at the date 
of the Week 12 visit. Missing response data will be imputed with NRI.
…
Has been changed to
…
Time to onset of ASAS20 response and ASAS40 response will be estimated and presented using 
the Kaplan-Meier product-limit method for each treatment. Time to a given response will be 
defined as the length in weeks from Baseline until the first date when the response is achieved. 
Following derivation will be used: Days from Baseline until the first date divided by 7. There 
will be no rounding for the Kaplan Meier estimates. Subjects who discontinue study treatment
prior to achieving a response will be censored at the date of study treatment discontinuation. 
Subjects who reach the Week 12 visit without achieving a response will be censored at the date 
of the Week 12 visit. Missing response data will be imputed with NRI.
…
Section 10.1 Extent of exposure
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 167 of 194
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(14)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(15)
where 140 days refers to 5*half-life of bimekizumab.
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(16)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(17)
Has been changed to
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. If a change of treatment occurs prior to 
completion of the dosing interval, duration of exposure to study medication will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂ݐݎ݁ܽݐ݉݁݊ݐ݄ܿܽ݊݃݁െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊
(13)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(1314)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 168 of 194
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(1415)
where 140 days refers to 5*half-life of bimekizumab.
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(1516)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(1617)
Section 10.2.1Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(18)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(19)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(20)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (17 and 18) will be used but the date of first bimekizumab dose will be 
used instead of the date of first dose. The time to first dose and time to first bimekizumab dose 
differs only for those subjects who receive placebo at Baseline.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 169 of 194
Has been changed to
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(1718)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2 and Table 12‒1: Calculation rules for duration of adverse events.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(1819)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(1920)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (1817 and 1918) will be used but the date of first bimekizumab dose will 
be used instead of the date of first dose. The time to first dose and time to first bimekizumab 
dose differs only for those subjects who receive placebo at Baseline.
Section 10.2.2 Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER)
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊
෌
ܶா௫௣ǡ௜
௡
௜ୀଵ
(21)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [18] in years) at the level of coding evaluated. 
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (15) is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(22)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 170 of 194
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(23)
where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෌
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(24)
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Has been changed to
The EAIR is defined as the number of subjects (nAE) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊஺ா
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(2021)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [18] in years) at the level of coding evaluated, nnoAE the number of subjects without 
the specific AE and ࢀࡾ࢏࢙࢑ǡ࢐the total time at risk scaled to 100 patient-years (equation [14] in 
years).
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (1415) in years is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 171 of 194
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
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where nAE is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2, ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of 
interest (equation [18] in years) at the level of coding evaluated, nnoAE the number of subjects 
without the specific AE and ࢀࡾ࢏࢙࢑ǡ࢐the total time at risk scaled to 100 patient-years 
(equation [14] in years).
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
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where NAE is the total number of AEs, ࢀࡾ࢏࢙࢑ǡ࢐is a subject’s total time at risk in years and nAll
the number of subjects.
No confidence interval will be computed for EAER.
Section 10.3 Clinical laboratory evaluations
The routine clinical laboratory evaluations specified in Table 10‒1 and will be summarized. If 
any additional analytes are also recorded then these will be listed only.
Different summary tables for hematology and biochemistry variables will be provided: observed 
values and change from Baseline, from Baseline to maximum post-Baseline value, from Baseline 
to minimum post-baseline value, shift from Baseline to end of treatment, shift from Baseline to 
end of double-blind treatment, and markedly abnormal laboratory data. 
…
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Basophils 
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 172 of 194
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
a A serum pregnancy test will be performed at Screening for all women of childbearing potential. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles and 
women during menopause. Natural menopause is recognized to have occurred after 12 consecutive months of 
amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause 
Society, 2015). A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A urine 
pregnancy test will also be performed at any study visit where there has been a delay in menses. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. 
Pregnancy test results must be negative prior to administering IMP.
b Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
…
Has been changed to
The routine clinical laboratory evaluations specified in Table 10‒1 and will be summarized. If 
any additional analytes are also recorded then these will be listed only.
Different summary tables for hematology and biochemistry variables will be provided, based on 
data from scheduled visits: observed values and change from Baseline, from Baseline to 
maximum post-Baseline value, from Baseline to minimum post-baseline value, shift from 
Baseline to end of treatment, shift from Baseline to end of double blind treatment, and markedly 
abnormal laboratory data. 
End of treatment will be defined as the Week 48 visit or the early termination assessment 
depending if the subject discontinued early or not.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 173 of 194
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Basophils 
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testinga
MCH
AST
MCHC
ALT
MCV
ALP
Platelet count
GGT
RBC count
Total bilirubin
WBC count
LDH
Uric acid
Total cholesterol
Albumin
Serum pregnancy testinga
CRPb
hs-CRPb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity C-reactive protein; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood 
cell
a A serum pregnancy test will be performed at Screening for all women of childbearing potential. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles and 
women during menopause. Natural menopause is recognized to have occurred after 12 consecutive months of 
amenorrhea, for which there is no other obvious pathological or physiological cause (International Menopause 
Society, 2015). A urine pregnancy test is also required at the Baseline, Week 48, ET, and at SFU visits. A urine 
pregnancy test will also be performed at any study visit where there has been a delay in menses. This 
recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. 
Pregnancy test results must be negative prior to administering IMP.
b Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
…
Section 12.1 Calculation rules for duration of adverse events
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 174 of 194
The calculation rules for duration of AEs are presented in Table 12‒1. AE duration is computed 
and reported in day.
Table 13‒1: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Complete data
D1
D2
Duration = D2 – D1 + 1
Start date missing
-
D2
Duration = < D2 – D0
Where, for a subject in the FAS, D0 is the date of the 
first intake of IMP, and for screen failures, D0 is the 
date of the Screening visit day 
End date missing
D1
-
Duration = > Discharge day – D1
For resolved and ongoing AE Duration
Where discharge refers to the date of Visit 16 (Week
48) or date of discontinuation
Start and end date 
missing
-
-
Duration = > Discharge day – D0
For resolved and ongoing AE Duration 
Where, for a subjects in the FAS, D0 is the
date of the first intake of IMP, and for screen
failures, D0 is the date of the Screening visit day,
Discharge refers to the date of Visit 16 (Week 48) or
date of discontinuation.
Has been changed to
The calculation rules for duration of AEs are presented in Table 12‒1. AE duration is computed 
and reported in day.
Table 13‒1: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Complete data
D1
D2
Duration = D2 – D1 + 1
Start date missing
-
D2
Duration = < D2 – D0 + 1
Where, for a subject in the SSFAS, D0 is the date of the 
first intake of IMP, and for screen failures, D0 is the 
date of the Screening visit day 
End date missing
D1
-
Duration = > Final contact dateDischarge day – D1 +1 
For resolved and ongoing AE Duration
Where discharge refers to the date of Visit 16 (Week
48) or date of discontinuation
date
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 175 of 194
Table 13‒1: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Start and end date 
missing
-
-
Duration = > Final contact dateDischarge day – D0 +
1
For resolved and ongoing AE Duration 
Where, for subjects in the SSFAS, D0 is the date of the 
first intake of IMP, and for screen failures, D0 is the 
date of the Screening visit day,
Discharge refers to the date of Visit 16 (Week 48) or
date of discontinuation.
REDACTED COPY 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 176 of 194
13.5
Amendment 5
13.5.1
Rationale for the amendment
The main objectives are to describe the different presentation of the safety assessments and to
define the additional two analysis sets for efficacy analyses.
13.5.2
Modifications and changes
Section 1 Introduction
The purpose of this statistical analysis plan (SAP) is to provide all necessary information to 
perform the required interim and final statistical analysis for study AS0008. It also defines the 
summary tables, figures, and listings (TFLs) to be generated in the clinical study report 
according to the final protocol (29 Jul 2016) and Protocol Amendment 1 (15 Mar 2017). 
…
Has been changed to
The purpose of this statistical analysis plan (SAP) is to provide all necessary information to 
perform the required interim and final statistical analysis for study AS0008. It also defines the 
summary tables, figures, and listings (TFLs) to be generated in the clinical study report 
according to the final protocol (29 Jul 2016), and Protocol Amendment 1 (15 Mar 2017), and 
Protocol Amendment 2 (09 Mar 2018).
…
Section 3.3 Definition of Baseline values
…
The exception of the above rule are the questionnaires collected from the vendor ERT. For those 
measurement, the last valid measurement at the same day as Visit 2 will be used as the Baseline 
value. 
…
Has been changed to
…
The exception of the above rule are the questionnaires collected from the vendor ERT and 
measurements for C-reactive protein (CRP) and high sensitivity C-reactive protein (hs-
CRP). For those measurement, the last valid measurement at the same day as Visit 2 will be used 
as the Baseline value. 
…
Section 3.6 Analysis sets
The primary efficacy variable will be analyzed for all subjects in the FAS. The supportive 
analysis for the primary efficacy variables will be performed for Randomized Set (RS), PPS, and
FAS. All other efficacy variables will be based on the FAS. Demographics tables will be 
performed for FAS as well as Safety Set (SS). Safety variables will be summarized using the SS. 
In addition, safety analyses during the Dose-Blind Period will be conducted on all subjects in the 
Dose-Blind Set (DBS). PK variables will be analyzed for all subjects in the Pharmacokinetics 
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 177 of 194
Per-Protocol Set (PK-PPS). PD variables will be analyzed for all subjects in the 
Pharmacodynamics Per-Protocol Set (PD-PPS).
…
Section 3.6.9 Escape Subject Set (ESS)
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved at 
least a 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
Section 3.6.10 Dose-Blind Responder Set (DBRS)
The Dose-Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved at least a 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. 
Has been changed to
The primary efficacy variable will be analyzed for all subjects in the FAS. The supportive 
analysis for the primary efficacy variables will be performed for Randomized Set (RS), PPS, and 
FAS. All other efficacy variables will be based on the FAS. Demographics tables will be 
performed for FAS, as well as Safety Set (SS), and Dose-Blind Set (DBS). Safety variables will 
be summarized using the SS. In addition, safety analyses during the Dose-Blind Period will be 
conducted on all subjects in the Dose Blind Set (DBS). PK variables will be analyzed for all 
subjects in the Pharmacokinetics Per-Protocol Set (PK-PPS). PD variables will be analyzed for 
all subjects in the Pharmacodynamics Per-Protocol Set (PD-PPS).
At the time of the Week 48 interim it was discovered that the Dose-Blind Responder Set
(DBRS) and Escape Subject Set (ESS) were defined incorrectly from the original intent. 
The original intent of the ESS analysis set was to have only those subjects that were eligible 
to receive rescue therapy, that went on to actually receive rescue therapy, with all other 
subjects remaining in the DBRS. As such, two extra sets, the Corrected Dose-Blind 
Responder Set (cDBRS) and Corrected Escape Subject Set (cESS) have been added. These 
analysis sets will correctly select out those subjects that were eligible and received rescue
medication. All outputs created on the DBRS and ESS will also be produced on the cDBRS 
and cESS to give full transparency of the difference. Further all outputs using the DBRS 
and ESS will be repeated on the DBS and this analysis will be used as the main analysis of 
the Dose-Blind as this analysis set is the most unbiased set.
…
Section 3.6.9 Escape Subject Set (ESS)
The Escape Subject Set (ESS) consists of all subjects starting the Dose-Blind Period and who 
received at least 1 dose of the IMP during the Dose-Blind Period and who have not achieved at 
least a 10% reduction from Baseline in PGADA and total and nocturnal spinal pain at either 
Week 16, Week 24, or Week 36.
Section 3.6.10 Dose-Blind Responder Set (DBRS)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 178 of 194
The Dose Blind Responder Set (DBRS) consists of all subjects starting the Dose-Blind Period
and who received at least 1 dose of the IMP during the Dose-Blind Period and who have 
achieved at least a 10% reduction from Baseline in PGADA and total and nocturnal spinal pain 
at Week 16, Week 24, and Week 36. 
3.6.11 Corrected Escape Subject Set (cESS)
The cESS is a corrected version of the ESS, which was incorrectly defined previously. The 
cESS consists of subjects that have shown less than a 10% improvement in SJC and TJC at 
either Week 16, Week 24, or Week 36 and received rescue therapy.
3.6.12 Corrected Dose-Blind Responder Set (cDBRS)
The cDBRS is a corrected version of the DBRS, which was incorrectly defined previously. 
The cDBRS consists of subjects that have shown at least a 10% improvement in SJC or 
TJC at Week 16, Week 24 and Week 36. Subjects that would be in the cESS, including 
subjects that discontinue, that did not receive rescue therapy will be in the cDBRS.
Section 3.7
…
Depending on the analysis sets, subjects will be summarized and listed based on the actual 
received treatment or according to the randomization which will be considered as planned 
treatment:
x
All subjects screened/ES: planned treatment
x
RS: planned treatment
x
SS: actual treatment
x
FAS: planned treatment
x
PPS: planned treatment
x
PK-PPS: actual treatment 
x
PD-PPS: actual treatment 
x
DBS: actual treatment 
x
ESS: planned treatment
x
DBRS: planned treatment
Has been changed to
…
Depending on the analysis sets, subjects will be summarized and listed based on the actual 
received treatment or according to the randomization which will be considered as planned 
treatment:
x
All subjects screened/ES: planned treatment
x
RS: planned treatment
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 179 of 194
x
SS: actual treatment
x
FAS: planned treatment
x
PPS: planned treatment
x
PK-PPS: actual treatment
x
PD-PPS: actual treatment
x
DBS: planned treatment (demographics, baseline characteristics, and efficacy analyses)
or actual treatment
x
ESS: planned treatment
x
DBRS: planned treatment
Text added for Section 4.2.1 Handling of missing data for efficacy analysis
The imputation model will be applied for each treatment group separately. However, in the 
event there are computational challenges with the imputation model (eg, due to a standard 
deviation of 0 for responses of a given imputation), it is acceptable to modify the imputation 
model to include treatment as a variable in the model rather than running a separate 
model for each treatment group. It should be noted that doing so assumes that treatment 
does not interact with any of the other variables in the imputation model.
Section 4.2.3 Handling of missing data for prior and concomitant medication
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days.
…
Has been changed to
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days.
…
Section 4.3.1.1 added
Section 4.3.1.1 Changes from interim analysis Week 12 to SAP-defined analyses
The baseline definition for CRP and hs-CRP measurements were updated with the fifth 
SAP Amendment after the interim analysis. The interim analysis used the previous 
definition: The last valid measurement before first dose of study drug (Visit 2) will be used 
as the Baseline value.
Section 4.3.2 Interim analysis Week 48
…
The snapshot for the AS0008 interim analysis Week 48 will occur before all subjects have 
completed the AS0008 study. Specifically, subjects who do not enter the extension study will 
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 180 of 194
need to complete the SFU Visit, which occurs 20 weeks after the last dose of study treatment. 
The Week 48 interim database lock will be performed based on the last subject completing the 
Week 48 visit. It is anticipated that there will be some subjects still awaiting the SFU at that 
time. The number of subjects in that position is expected to be low, and the minimal data to be 
collected from their SFU visits is not considered mandatory to evaluation of the key efficacy and 
safety objectives of the study. 
Has been changed to
…
The snapshot for the AS0008 interim analysis Week 48 will occur before all subjects have 
completed the AS0008 study. Specifically, subjects who do not enter the extension study will 
need to complete the SFU Visit, which occurs 20 weeks after the last dose of study treatment. 
The Week 48 interim database lock will be performed based on the last subject completing the 
Week 48 visit. It is anticipated that there will be some subjects still awaiting the SFU at that 
time. The number of subjects in that position the SFU period is expected to be low, and the 
minimal data to be collected from their SFU visits is not considered mandatory to evaluation of 
the key efficacy and safety objectives of the study. 
Section 4.3.2.1 and Section 4.3.2.2 added
Section 4.3.2.1 Changes from interim analysis to SAP-defined analyses
The baseline definition for CRP and hs-CRP measurements were updated with the fifth 
SAP Amendment after the interim analysis. The interim analysis used the previous 
definition: The last valid measurement before first dose of study drug (Visit 2) will be used 
as the Baseline vale.
Section 4.3.2.2 Changes during interim analysis to SAP-defined analyses
At the time of the Week 48 interim it was discovered that the DBRS and ESS were defined 
incorrectly from the original intent. The original intent of the ESS analysis set was to have 
only those subjects that were eligible to receive rescue therapy, that went on to actually 
receive rescue therapy, with all other subjects remaining in the DBRS. As such, two extra 
sets, the cDBRS and cESS have been added. These analysis sets will correctly select out 
those subjects that were eligible and received rescue medication. For the final analysis, all 
outputs created on the DBRS and ESS will also be produced on the cDBRS and cESS to 
give full transparency of the difference. Further all outputs using the DBRS and ESS will 
be repeated on the DBS and this analysis will be used as the main analysis of the Dose-
Blind as this analysis set is the most unbiased set.
Section 6.1 Demographics
…
The summary tables will be performed on the SS and repeated using the FAS. If the SS and FAS 
analysis sets are identical the summaries will not be repeated. The Listing will be provided for all 
subjects screened, except the Lifestyle listing will use the RS.
Has been changed to
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 181 of 194
The summary tables will be performed on the SS and repeated using the FAS, and the DBS. If 
the SS and FAS analysis sets are identical the summaries will not be repeated. The Listing will 
be provided for all subjects screened, except the Lifestyle listing will use the RS.
Section 6.2 Other Baseline characteristics
…
Baseline characteristics (including scores relevant for inclusion and exclusion criteria) will be 
summarized by treatment group and overall for FAS and SS. Following variables will be 
summarized:
…
Has been changed to
…
Baseline characteristics (including scores relevant for inclusion and exclusion criteria) will be 
summarized by treatment group and overall for FAS, and SS, and DBS. Following variables will 
be summarized:
…
Section 6.4 Prior and concomitant medications
Prior medications include any medications that started and ended prior to the start date of study 
medication. Concomitant medications are medications taken at least one day in common with the 
study medication dosing period. For bimekizumab, the dosing period is typically from the date of 
first dose up to (but not including) one dosing interval post last dose. Thus, a concomitant 
medication is any medication whose start date is on or after the date of first study medication and 
prior to the date of last study medication administration + 28 days (1 dosing interval), and whose 
stop date is either missing, or on or after the date of first study medication administration. 
Medications may be both prior and concomitant.
…
Has been changed to
Prior medications include any medications that started and ended prior to the start date of study 
medication. Concomitant medications are medications taken at least one day in common with the 
study medication dosing period. For bimekizumab, the dosing period is typically from the date of 
first dose up to (but not including) one dosing interval post last dose. Thus, a concomitant 
medication is any medication whose start date is on or after the date of first study medication and 
prior to the date of last study medication administration + 28 days (1 dosing interval), or whose 
stop date is either missing, or on or after the date of first study medication administration. 
Medications may be both prior and concomitant.
…
Section 7 Measurements of treatment compliance
…
A summary of percent treatment compliance categorized as ≤80% and >80% will be provided by 
treatment group for the overall treatment period as well as for Double-Blind treatment period.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 182 of 194
A by-subject listing of treatment compliance will be provided.
Has been changed to
…
A summary of percent treatment compliance categorized as ≤80% and >80% will be provided by 
treatment group for the overall treatment period as well as for Double-Blind treatment period.
For the Double-Blind treatment period compliance will refer to the first 12 weeks and will 
be presented by treatment received at baseline. For the overall treatment period, the 
compliance will be calculated for the following three groups: bimekizumab 160mg, 
bimekizumab 320mg, and all bimekizumab. Treatment compliance for the bimekizumab 
160mg and 320mg group will be calculated for the time the subject receives 160mg or 
320mg, eg for a subject who switches from Placebo or bimekizumab 16mg to bimekizumab 
160mg at Week 12, the compliance will only be calculated for the time the subject receives 
bimekizumab 160mg. The all bimekizumab group will consist of all the doses of 
bimekizumab including bimekizumab 16mg, and will only exclude the time subjects receive 
Placebo.
A by-subject listing of treatment compliance will be provided, presenting percent compliance 
and numbers of expected and received doses for the Double-Blind Period and for treatment 
with any dose of bimekizumab.
Section 8.3 Statistical analysis of other efficacy variables
All other efficacy variables in the Double-Blind Period will be analyzed for all subjects in the 
FAS. For the Dose-Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
…
Has been changed to
All other efficacy variables in the Double Blind Period will be analyzed for all subjects in the 
FAS. For the Dose Blind Period, other efficacy variables will be analyzed for all subjects in the 
DBRS, and ESS.
Other efficacy variables will be analyzed for all subjects in the FAS, DBRS, ESS, cDBRS,
cESS, and DBS.
…
Section 9.1 Pharmacokinetics
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit using the PK-PPS analysis set. 
…
Has been changed to
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit using the PK-PPS, analysis set and using a subset of the DBS which includes subjects 
that belong to both analysis sets, the DBS and the PK-PPS.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 183 of 194
Section 9.2 Pharmacodynamics and Immunogenicity
The biomarker data will be separated between LGC assays, mulitplex proinflammatory cytokine 
and chemokine analysis, flow cytometry - TBNK panel, and flow cytometry -
Th1/Th2/Th17/Th22 panel. Biomarker variables will be summarized and listed for each 
treatment at each scheduled visit using the PD-PPS analysis set.
…
In addition the time point of the first occurrence of AbAb positivity during the treatment period 
(excluding Baseline and pre-treatment) will be summarized for each treatment group.
…
Has been changed to
The biomarker data will be separated between LGC assays, mulitplex proinflammatory cytokine 
and chemokine analysis, flow cytometry - TBNK panel, and flow cytometry -
Th1/Th2/Th17/Th22 panel. Biomarker variables will be summarized and listed for each 
treatment at each scheduled visit using the PD-PPS, analysis set and using a subset of the DBS 
which includes subjects that belong to both analysis sets, the DBS and the PK-PPS.
…
In addition, the time point of the first occurrence of AbAb positivity during the Double-Blind 
Period, and the entire treatment period (excluding Baseline and pre-treatment) will be 
summarized for each treatment group.
…
Section 10.1 Extent of exposure
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. 
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(13)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose and the duration of exposure will be performed.
Time at risk (in days) is defined as:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(14)
where 140 days refers to 5*half-life of bimekizumab.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 184 of 194
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(15)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(16)
Has been changed to
The duration of exposure and time at risk will be summarized for the Double-Blind Period
and the entire treatment period. For the entire treatment period the duration of exposure 
and time at risk will be calculated for bimekizumab 160mg, bimekizumab 320mg, and all 
bimekizumab. The calculation of exposure duration and time at risk for the all 
bimekizumab group is different from that of the other two groups. For all bimekizumab 
the duration of exposure and time at risk will include the time a subject received any dose 
of bimekizumab (including 16mg or 64mg) while for the other two treatment groups only 
the time a subject received 160mg, or 320mg will be included into the calculation. 
Duration of exposure Double-Blind Period
The duration of exposure (in days) during the Double-Blind Period will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ʹͺ
(12)
28 days refer to one half-life of bimekizumab. 
Note: If the date of last injection (Double-Blind Period) + 28 extends to a date beyond the 
date of first injection (Dose-Blind Period), then this calculation reverts to
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(13)
For subjects who die during the Double-Blind Period, then this calculation reverts to:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 185 of 194
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀ܲ݁ݎ݅݋݀ሻ൅ͳ
(14)
Duration of exposure entire treatment period
For subjects who do not switch study treatments, or who receive bimekizumab 16mg or 
64mg will be summarized under all bimekizumab group:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(15)
Note: If the date of last injection +28 extends to a date beyond the final visit date (not 
including SFU), then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(16)
For subjects who die, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(17)
For subjects who receive Placebo or bimekizumab 16mg or 64mg in the Double-Blind 
Period and will be summarized under their Dose-Blind treatment in the overall table group 
bimekizumab 160mg or 320mg, or subjects who received Placebo and will be summarized 
in the overall table under their Dose-Blind treatment:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ʹͺ
(18)
Note: If the date of last dose +28 extends to a date beyond the final visit date (not including 
SFU), then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(19)
For subjects who die during the Dose-Blind Period, then this calculation reverts to:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 186 of 194
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(20)
The sum over all duration of exposure (in years) will be calculated for the total subject-years of 
duration of exposure.
The duration of exposure will be summarized by treatment group using descriptive statistics. A 
by-subject listing of date of first and last dose in Double-Blind Period, the date of first and 
last dose in Dose-Blind Period and the duration of exposure during Double-Blind Period and 
under bimekizumab treatment (any dose of bimekizumab) will be performed.
Time at risk Double-Blind Period
For subjects who complete the final visit of the Double-Blind Period and continue to the 
Dose-Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(21)
For subjects who discontinue on or prior to the final visit of the Double-Blind Period, use 
the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳͶͲ
(22)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(23)
ܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(24)
where 140 days refers to 5*half-life of bimekizumab.
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(25)
Time at risk entire treatment period
For subjects who do not switch study treatments, or who receive bimekizumab 16mg or 
64mg and will be summarized under all bimekizumab group:
For subjects who complete the Dose-Blind Period and enter the extension study:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂ܸ݅ݏ݅ݐͳ͸ ሺܹ݁݁݇Ͷͺሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(26)
For subjects who die prior to the final visit:
െܾ݈݅݊
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 187 of 194
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(27)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(28)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(29)
For subjects who receive Placebo or bimekizumab 16mg or 64mg in the Double-Blind 
Period and will be summarized under their Dose-Blind treatment in the overall table group 
bimekizumab 160mg or 320mg, or subjects who received Placebo and will be summarized 
in the overall table under their Dose-Blind treatment:
For subjects who complete the Dose-Blind Period and enter the extension study:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂ܸ݅ݏ݅ݐͳ͸ ሺܹ݁݁݇Ͷͺሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(30)
For subjects who die during the Dose-Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(31)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳͶͲ
(32)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(33)
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(34)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(35)
Section 10.2 Adverse events (AEs)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 188 of 194
…
The incidence of TEAEs will be summarized by MedDRA system organ class, high level term, 
and PT. Tables with incidences of classified TEAEs by maximum intensity, by relationship, and 
by subject number will be provided. The incidence of non-serious TEAEs above the reporting 
threshold of 5% of subjects and relationship will be summarized. Furthermore the incidence of 
all TEAEs, serious TEAEs, non-serious TEAEs, and TEAEs leading to study discontinuation 
and/or permanent withdrawal of study medication will be summarized. In addition an overall 
summary table will be provided. 
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER) will be 
calculated for following tables in the final analysis: all TEAEs, serious TEAEs, TEAEs leading 
to study discontinuation and/or permanent withdrawal, ADRs, fungal infectious disorder TEAEs, 
opportunistic infection (including tuberculosis) TEAEs, malignant or unspecified tumor TEAEs, 
malignant tumor TEAEs, major cardiovascular event TEAEs, haematopoietic cytopenias TEAEs,
neuropsychiatric events TEAEs, inflammatory bowel disease TEAEs, hypersensitivity and 
anaphylactic Reaction TEAEs, hepatic events TEAEs, and TEAEs by timing of onset relative to 
AbAb Status.
Has been changed to
…
The incidence of TEAEs will be summarized by MedDRA SOC, high level term, and PT. 
Tables with incidences of classified TEAEs by maximum intensity, by relationship, and by 
subject number will be provided. The incidence of non TEAEs, non-serious TEAEs above 
the reporting threshold of 5% of subjects and relationship will be summarized. 
Furthermore the incidence of all TEAEs, serious TEAEs, non-serious TEAEs, and TEAEs 
leading to study discontinuation and/or permanent withdrawal of study medication, 
adverse drug reactions, fungal infectious disorder TEAEs, opportunistic infection 
(including tuberculosis) TEAEs, malignant or unspecified tumor TEAEs, malignant tumor 
TEAEs, major cardiovascular event TEAEs, haematopoietic cytopenias TEAEs, 
neuropsychiatric events TEAEs, inflammatory bowel disease TEAEs, hypersensitivity and 
anaphylactic Reaction TEAEs, hepatic events TEAEs, and TEAEs by timing of onset 
relative to AbAb Status will be summarized. In addition, an overall summary table will be 
provided.
The tables will be split into the Double-Blind Period and the complete treatment period 
(exception non TEAE table and TEAEs by timing of onset relative to AbAb Status). 
Presentations for the Double-Blind Period will summarize AEs that start prior to or at 
Visit 7 (see details given above) by treatment group as randomized for the Double-Blind 
Period. Presentations for the complete treatment period will only summarize AEs that 
occur under treatment with bimekizumab, irrespective of the treatment period. For 
summaries of the bimekizumab 160mg, and bimekizumab 320mg treatment groups, 
patients randomized to Placebo, bimekizumab 16mg or 64mg at Baseline will only be 
included with AEs that start in the Dose-Blind Period. The all bimekizumab treatment 
group will also present AEs occurring under bimekizumab 16mg or 64mg treatment in the 
Double-Blind Period. AEs for each subject will be summarized based on the treatment 
actually received at the onset of each particular AE.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 189 of 194
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER) will 
only be calculated for the complete treatment period for following tables in the final 
analysis: all TEAEs, serious TEAEs, TEAEs leading to study discontinuation and/or 
permanent withdrawal, adverse drug reactions, fungal infectious disorder TEAEs, 
opportunistic infection (including tuberculosis) TEAEs, malignant or unspecified tumor 
TEAEs, malignant tumor TEAEs, major cardiovascular event TEAEs, haematopoietic 
cytopenias TEAEs, neuropsychiatric events TEAEs, inflammatory bowel disease TEAEs, 
hypersensitivity and anaphylactic Reaction TEAEs, hepatic events TEAEs, and TEAEs by 
timing of onset relative to AbAb Status.
Section 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(17)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2 and Table 12‒1.
The time to first dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(18)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(19)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (18 and 19) will be used but the date of first bimekizumab dose will be 
used instead of the date of first dose. The time to first dose and time to first bimekizumab dose 
differs only for those subjects who receive placebo at Baseline.
Has been changed to
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ൅ͳ
(3617)
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.2 and Table 12‒1.
The time to first dose for each AE will be calculated as follows for all TEAEs:
REDACTED 
will b
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 190 of 194
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐെ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(3718)
The time to most recent dose for each AE will be calculated as follows for all TEAEs:
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(3819)
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs.
For the calculation of time to first bimekizumab and time to most recent bimekizumab dose the 
same formulas as above (3718 and 3819) will be used but the date of first bimekizumab dose will 
be used instead of the date of first dose. The time to first dose and time to first bimekizumab 
dose differs only for those subjects who receive placebo at Baseline.
Section 10.2.2 Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER)
The EAIR is defined as the number of subjects (nAE) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊஺ா
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(20)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [18] in years) at the level of coding evaluated, nnoAE the number of subjects without the 
specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years (equation [14] in years). 
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (14) in years is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ಲಶǡఈ
ଶ
ଶ
ʹ
(21)
ܷܥܮൌ
߯ଶሺ௡ಲಶାଵሻǡଵିఈȀଶ
ଶ
ʹ
(22)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 191 of 194
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
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ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(23)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(24)
where nAE is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2, ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of
interest (equation [18] in years) at the level of coding evaluated, nnoAE the number of subjects 
without the specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years (equation 
[14] in years).
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
ܧܣܧܴൌͳͲͲ כ
ܰ஺ா
෍
ܶோ௜௦௞ǡ௝
௡ಲ೗೗
௝ୀଵ
(25)
where NAE is the total number of AEs, ܶோ௜௦௞ǡ௝is a subject’s total time at risk in years and nAll the
number of subjects.
No confidence interval will be computed for EAER.
Has been changed to
The EAIR is defined as the number of subjects (nAE) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
ܧܣܫܴൌͳͲͲ כ
݊஺ா
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(3920)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [3618] in years) at the level of coding evaluated, nnoAE the number of subjects without 
the specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years (Section 10.1
equation [14] in years).
If a subject has multiple events at the level of coding evaluated, the time of exposure is 
calculated to the first occurrence of the AE of interest. If a subject has no events, the total time at 
risk (Section 10.1 14) in years is used. As indicated above, exposure-adjusted incidence rates 
will only be calculated for the overall treatment period. These presentations do not include 
AEs that occur under Placebo treatment. Therefore, a subject’s exposure time will only 
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 192 of 194
start at the first dose of bimekizumab in the Dose-Blind Period for subjects randomized to 
Placebo at Baseline. Also, for subject’s randomized to bimekizumab 16mg or 64mg at 
Baseline, exposure time will only be considered from the start of Dose-Blind Period, when 
presenting AEs for the bimekizumab 160mg, or bimekizumab 320mg groups. All exposure 
time on any bimekizumab dose is considered for the all bimekizumab column.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ಲಶǡఈ
ଶ
ଶ
ʹ
(4021)
ܷܥܮൌ
߯ଶሺ௡ಲಶାଵሻǡଵିఈȀଶ
ଶ
ʹ
(4122)
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(4223)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(4324)
where nAE is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2, ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of 
interest (equation [3618] in years) at the level of coding evaluated, nnoAE the number of subjects 
without the specific AE and ܶோ௜௦௞ǡ௝the total time at risk scaled to 100 patient-years (Section 10.1
equation [14] in years).
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
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where NAE is the total number of AEs, ܶோ௜௦௞ǡ௝is a subject’s total time at risk in years and nAll the
number of subjects.
No confidence interval will be computed for EAER.
Section 10.3 Clinical laboratory evaluations
…
Different summary tables for hematology and biochemistry variables will be provided, based on 
data from scheduled visits: observed values and change from Baseline, from Baseline to 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 193 of 194
maximum post-Baseline value, from Baseline to minimum post-baseline value, shift from 
Baseline to end of treatment, and markedly abnormal laboratory data. 
End of treatment will be defined as the Week 48 visit or the early termination assessment 
depending if the subject discontinued early or not.
…
Has been changed to
…
Different summary tables for hematology and biochemistry variables will be provided, based on 
data from scheduled visits: observed values and change from Baseline, shift from Baseline to 
maximum post-Baseline value (in Double-Blind Period), shift from Baseline to maximum 
post-Baseline value (in Dose-Blind Period), shift from Baseline to minimum post-Baseline 
value (in Double-Blind Period), shift from Baseline to minimum post-Baseline value (in 
Dose-Blind Period), shift from Baseline to end of treatment (in Double-Blind Period), shift 
from Baseline to end of treatment (in Dose-Blind Period), and markedly abnormal laboratory 
data. 
End of treatment (in Double-Blind Period) will be defined as the last visit in the Double-
Blind Period or the early termination assessment depending if the subject discontinued in 
the Double-Blind Period.
End of treatment (in Dose-Blind Period) will be defined as the Week 48 visit or the early 
termination assessment depending if the subject discontinued early or not.
…
Table 10-5 updated to align with Table 12-4 from the Protocol Amendment 2.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
AS0008
Confidential
Page 194 of 194
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.
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


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