Clinical trial NCT02969525
Conditions: Psoriatic Arthritis
Keywords: Psoriatic Arthritis PsA Bimekizumab
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2016-10-01; Completion date: 2018-07-01
Enrollment: 206 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study to evaluate the dose response based on the efficacy, safety and tolerability of bimekizumab in subjects with active psoriatic arthritis.

Detailed description:

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

Protocol documents:
Prot_000.pdf: 
UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 1 of 131
PROTOCOL PA0008 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 ACTIVE 
PSORIATIC ARTHRITIS
PHASE 2B
EudraCT Number: 2016-001103-23
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
16 Dec 2016
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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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 3 of 131
Clinical Monitoring Contract Research Organization
Name:
PRA Health Sciences
Address:
4130 Park Lake Avenue, Suite 400
Raleigh, NC 27612
UNITED STATES
Phone:
+1-919-786-8200
Fax:
+1-919-786-8201
REDACTED COPY 
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or r variations 
v
thereof. 


UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 4 of 131
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com
REDACTED COPY 
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or variations 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 5 of 131
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................16
2
INTRODUCTION ...........................................................................................................18
2.1.1
Clinical.................................................................................................................19
2.1.2
Nonclinical...........................................................................................................20
3
STUDY OBJECTIVES....................................................................................................21
3.1 Primary objective.............................................................................................................21
3.2 Secondary objectives .......................................................................................................21
3.3 Other objectives ...............................................................................................................21
4
STUDY VARIABLES.....................................................................................................21
4.1 Efficacy variables.............................................................................................................21
4.1.1
Primary efficacy variable.....................................................................................21
4.1.2
Secondary efficacy variables ...............................................................................22
4.1.3
Other efficacy variables.......................................................................................22
4.2 PK and PD variables ........................................................................................................23
4.2.1
PK variables.........................................................................................................23
4.2.2
PD variables.........................................................................................................23
4.3 Pharmacogenomic variables ............................................................................................23
4.3.1
Genomic, proteomic, and metabolite variables ...................................................23
4.4 Immunological variables..................................................................................................23
4.5 Safety variables................................................................................................................24
5
STUDY DESIGN.............................................................................................................24
5.1 Study description .............................................................................................................24
5.1.1
Screening Period/Baseline...................................................................................25
5.1.2
Double-Blind Period............................................................................................25
5.1.3
Dose-Blind Period ...............................................................................................25
5.1.4
Rescue therapy.....................................................................................................26
5.1.5
Safety Follow-Up Visit........................................................................................27
5.1.6
Safety monitoring strategy...................................................................................27
5.1.7
Study duration per subject ...................................................................................27
5.1.8
Planned number of subjects and site(s) ...............................................................28
5.1.9
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.............................................................36
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................37
6.1 Inclusion criteria ..............................................................................................................37
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
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6.2 Exclusion criteria .............................................................................................................38
6.3 Withdrawal criteria ..........................................................................................................42
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................44
7
STUDY TREATMENTS.................................................................................................44
7.1 Description of investigational medicinal products ..........................................................44
7.2 Treatments to be administered.........................................................................................45
7.3 Packaging.........................................................................................................................45
7.4 Labeling ...........................................................................................................................45
7.5 Handling and storage requirements..................................................................................45
7.6 Drug accountability..........................................................................................................46
7.7 Procedures for monitoring subject compliance................................................................46
7.8 Concomitant medication(s)/treatment(s)..........................................................................46
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................47
7.8.2
Prohibited concomitant treatments (medications and therapies).........................48
7.9 Blinding............................................................................................................................49
7.9.1
Procedures for maintaining and breaking the treatment blind.............................50
7.9.1.1
Maintenance of study treatment blind.......................................................50
7.9.1.2
Breaking the treatment blind in an emergency situation...........................50
7.10 Randomization and numbering of subjects......................................................................50
8
STUDY PROCEDURES BY VISIT ...............................................................................51
8.1 Screening..........................................................................................................................51
8.2 Baseline (Day 1) ..............................................................................................................53
8.3 Double-Blind Period (Week 1 to Week 12).....................................................................54
8.3.1
Week 1 (+/-3 days) ..............................................................................................54
8.3.2
Week 2 (+/-3 days) ..............................................................................................55
8.3.3
Week 4 (+/-3 days) ..............................................................................................55
8.3.4
Week 8 (+/-3 days) ..............................................................................................56
8.3.5
Week 12 (+/-3 days) ............................................................................................57
8.4 Dose-Blind Period (Week 16 to Week 48) ......................................................................58
8.4.1
Week 16 (+/-4 days) ............................................................................................58
8.4.2
Week 20 (+/-4 days) ............................................................................................59
8.4.3
Week 24 (+/-4 days) ............................................................................................60
8.4.4
Week 28 (+/-4 days) ............................................................................................61
8.4.5
Week 32 (+/-4 days) ............................................................................................61
8.4.6
Week 36 (+/-4 days) ............................................................................................62
8.4.7
Week 40 (+/-4 days) ............................................................................................63
8.4.8
Week 44 (+/-4 days) ............................................................................................63
8.4.9
Week 48 (+/-4 days) ............................................................................................64
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 7 of 131
8.5 Early Termination Visit ...................................................................................................65
8.6 Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final dose)......................66
8.7 Unscheduled Visit............................................................................................................67
9
ASSESSMENT OF EFFICACY......................................................................................68
9.1 TJC and SJC.....................................................................................................................68
9.1.1
78/76 joint evaluation for ACR response and verification of Inclusion Criterion 
5
68
9.1.2
28 joint evaluation for determination of DAS28(CRP).......................................68
9.2 Patient’s Global Assessment of Disease Activity............................................................69
9.3 Physician’s Global Assessment of Disease Activity .......................................................69
9.4 Patient’s Assessment of Arthritis Pain.............................................................................69
9.5 Health Assessment Questionnaire-Disability Index score...............................................69
9.6 CRP levels (hs-CRP/CRP)...............................................................................................69
9.7 ACR20, ACR50, and ACR70 response ...........................................................................70
9.8 BSA-PSO .........................................................................................................................70
9.9 Psoriasis Area and Severity Index (PASI).......................................................................70
9.10 MDA 71
9.11 DAS28(CRP) ...................................................................................................................72
9.12 BASDAI...........................................................................................................................72
9.13 mNAPSI...........................................................................................................................72
9.14 MASES ............................................................................................................................72
9.15 LDI
72
9.16 PsAID-9 ...........................................................................................................................72
9.17 PsAQoL............................................................................................................................73
9.18 SF-3673
9.19 Hospital Anxiety and Depression Scale...........................................................................73
10
ASSESSMENT OF PHARMACOKINETIC, PHARMACODYNAMIC, 
PHARMACOGENOMIC, AND PROTEOMIC VARIABLES......................................73
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................74
12
ASSESSMENT OF SAFETY..........................................................................................74
12.1 Adverse events.................................................................................................................74
12.1.1
Definition of adverse event..................................................................................74
12.1.2
Adverse events of special interest........................................................................75
12.1.3
Adverse events for special monitoring ................................................................75
12.1.4
Procedures for reporting and recording adverse events.......................................75
12.1.5
Description of adverse events..............................................................................75
12.1.6
Follow-up of adverse events................................................................................76
12.1.7
Rule for repetition of an adverse event................................................................76
12.1.8
Pregnancy ............................................................................................................76
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 8 of 131
12.1.9
Suspected transmission of an infectious agent via a medicinal product..............77
12.1.10
Overdose of investigational medicinal product ...................................................77
12.1.11
Safety signal detection.........................................................................................77
12.2 Serious adverse events .....................................................................................................78
12.2.1
Definition of serious adverse event .....................................................................78
12.2.2
Procedures for reporting serious adverse events .................................................79
12.2.3
Follow-up of serious adverse events....................................................................80
12.3 Immediate reporting of adverse events............................................................................80
12.4 Anticipated serious adverse events ..................................................................................80
12.5 Laboratory measurements................................................................................................81
12.5.1
Evaluation of PDILI ............................................................................................82
12.5.1.1
Consultation with Medical Monitor and local hepatologist ......................86
12.5.1.2
Immediate action: determination of IMP discontinuation.........................86
12.5.1.3
IMP restart/rechallenge .............................................................................86
12.5.1.4
Testing: identification/exclusion of alternative etiology...........................86
12.5.1.5
Follow-up evaluation.................................................................................88
12.6 Other safety measurements..............................................................................................88
12.6.1
Vital signs ............................................................................................................88
12.6.2
Body weight and height.......................................................................................89
12.6.3
Physical examination...........................................................................................89
12.6.4
12-lead electrocardiogram ...................................................................................89
12.6.5
Tuberculosis and TB risk factor assessment and management ...........................89
12.6.5.1
Tuberculosis assessment by IGRA............................................................91
12.6.5.2
Chest x-ray for tuberculosis ......................................................................91
12.6.5.3
Tuberculosis questionnaire........................................................................92
12.6.5.4
Tuberculosis management.........................................................................92
12.6.6
Pregnancy testing.................................................................................................93
12.6.7
Assessment of suicidal ideation and behavior.....................................................93
13
OTHER STUDY MEASUREMENTS ............................................................................93
13.1 Medical history ................................................................................................................93
13.2 Psoriatic arthritis history..................................................................................................93
13.3 Demography.....................................................................................................................94
13.4 Prior and concomitant medications..................................................................................94
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................94
14.1 Adherence to protocol......................................................................................................94
14.2 Monitoring .......................................................................................................................94
14.2.1
Definition of source data .....................................................................................94
14.2.2
Source data verification .......................................................................................95
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Clinical Study Protocol
Bimekizumab
PA0008
Confidential
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14.3 Data handling...................................................................................................................95
14.3.1
Case Report Form completion.............................................................................95
14.3.2
Database entry and reconciliation........................................................................95
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............96
14.4 Termination of the study..................................................................................................96
14.5 Archiving and data retention............................................................................................96
14.6 Audit and inspection ........................................................................................................97
14.7 Good Clinical Practice .....................................................................................................97
15
STATISTICS ...................................................................................................................97
15.1 Definition of analysis sets................................................................................................97
15.2 General statistical considerations.....................................................................................98
15.3 Planned efficacy analyses ................................................................................................98
15.3.1
Analysis of the primary efficacy variable............................................................98
15.3.1.1
Supportive analyses...................................................................................99
15.3.2
Other efficacy analyses........................................................................................99
15.3.2.1
Analysis of the secondary efficacy variables ............................................99
15.3.2.2
Analysis of the other efficacy variables ..................................................100
15.4 Subgroup analyses .........................................................................................................100
15.5 Planned safety and other analyses..................................................................................101
15.5.1
Safety analyses...................................................................................................101
15.5.2
Other analyses....................................................................................................101
15.6 Handling of protocol deviations.....................................................................................101
15.7 Handling of dropouts or missing data............................................................................101
15.8 Planned interim analysis and data monitoring...............................................................103
15.9 Determination of sample size.........................................................................................103
16
ETHICS AND REGULATORY REQUIREMENTS....................................................104
16.1 Informed consent ...........................................................................................................104
16.2 Subject identification cards............................................................................................104
16.3 Institutional Review Boards and Independent Ethics Committees................................104
16.4 Subject privacy...............................................................................................................105
16.5 Protocol amendments.....................................................................................................105
17
FINANCE, INSURANCE, AND PUBLICATION.......................................................106
18
REFERENCES ..............................................................................................................106
19
APPENDICES ...............................................................................................................110
19.1 CASPAR criteria............................................................................................................110
19.2 Markedly abnormal laboratory values ...........................................................................111
19.3 Protocol Amendment 1 ..................................................................................................112
19.4 Protocol Amendment 2 ..................................................................................................123
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
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Page 10 of 131
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................130
21
SPONSOR DECLARATION ........................................................................................131
LIST OF TABLES
Table 5‒1:
Schedule of assessments ..................................................................................29
Table 7-1
Prohibited or restricted medications and required wash-out periods prior 
to Baseline........................................................................................................48
Table 7-2
Additional prohibited psoriasis treatments ......................................................49
Table 7‒3:
Preparation of placebo and bimekizumab injections .......................................50
Table 9-1
Swelling and tenderness grading .....................................................................68
Table 9‒2:
Body areas for calculation of percent BSA for PASI ......................................71
Table 9‒3:
Minimal disease activity (MDA) criteria in psoriatic arthritis.........................71
Table 12‒1:
Anticipated serious adverse events for the population of subjects with 
psoriatic arthritis ..............................................................................................80
Table 12‒2:
Laboratory measurements................................................................................82
Table 12‒3:
Required investigations and follow-up for PDILI ...........................................84
Table 12‒4:
PDILI laboratory measurements......................................................................87
Table 12‒5:
PDILI information to be collected...................................................................88
Table 19‒1:
CASPAR Criteria...........................................................................................110
Table 19-2
Definitions of markedly abnormal hematology values..................................111
Table 19‒3:
Definitions of markedly abnormal biochemistry values................................111
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................35
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 11 of 131
LIST OF ABBREVIATIONS
ACR
American College of Rheumatology
ACR20, 50, 70
American College of Rheumatology 20, 50, 70% response criteria
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
AST
aspartate aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BP
blood pressure
BSA
body surface area
CASPAR
Classification Criteria for Psoriatic Arthritis
CCP
cyclic citrullinated peptide
CD
cluster of differentiation
CDC
Centers for Disease Control
CDMS
clinical data management system
CI
confidence interval
CL/F
total body clearance
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRF/eCRF
Case Report Form/electronic CRF
CRO
Contract Research Organization
CRP
C-reactive protein
C-SSRS/eC-SSRS
Columbia-Suicide Severity Rating Scale/electronic C-SSRS
CZP
certolizumab pegol
DAS28(CRP)
Disease Activity Score-28 joint count C-reactive protein
DBS
Dose-Blind Set
DBRS
Dose-Blind Responder Set
DIP
distal interphalangeals
DMARD
disease-modifying antirheumatic drug
tion
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 12 of 131
DMC
Data Monitoring Committee
ECG
electrocardiogram
EDC
electronic data capture
ES
Enrolled Set
ESS
Escape Subject Set
ET
Early Termination
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 
HAQ-DI
Health Assessment Questionnaire – Disability Index
HBV
hepatitis B virus
HbsAg
hepatitis B surface antigen
HbcAB
hepatitis B core antibody
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRQoL
Health-Related Quality of Life
hs
high sensitivity
IB
Investigator’s Brochure
IBD
Inflammatory Bowel Disease
ICH
International Council on Harmonisation
IEC
independent ethics committee
IGRA
interferon-gamma release assay
IIV
interindividual variability
IP
interphalangeal
IL
interleukin
im
intramuscular
IMP
investigational medicinal product
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 13 of 131
IMS
International Menopause Society
IRB
institutional review board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
iv
intravenous
IXRS
interactive voice or web response system 
LDI
Leeds Dactylitis Index
LEF
leflunomide
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
MCP
metacarpophalangeal
MCS
mental component summary
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MMR
measles-mumps-rubella
mNAPSI
modified Nail Psoriasis Severity Index
MTB
mycobacterium tuberculosis
MTP
metatarsophalangeal
MTX
methotrexate
NOAEL
no adverse effect level
NRI
nonresponder imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
NTMB
nontuberculous mycobacteria
OPV
oral polio vaccine
PASI
Psoriasis Area and Severity Index
PASI75, PASI90, 
PASI100
Psoriasis Area and Severity Index 75%, 90%, 100%
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 14 of 131
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
PIP
proximal interphalangeal
PK
pharmacokinetics
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per-Protocol Set
PS
Patient Safety
PSO
psoriasis
PsA
psoriatic arthritis
PsAID-9
Psoriatic Arthritis Impact of Disease-9
PsAQoL
Psoriatic Arthritis Quality of Life
PtAAP
Patient’s Assessment of Arthritis Pain
PUVA
psoralen plus ultraviolet A light therapy
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
receptor A
RCTC
Rheumatology Common Toxicity Criteria
RF
rheumatoid factor
RIF
rifampin
RS
Randomized Set
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
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 15 of 131
SJC
swollen joint count
SOC
standard of care
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
Th17
T helper 17
TJC
tender joint count
TNF
tumor necrosis factor
TNFα
tumor necrosis factor-alpha
ULN
upper limit of normal
UVA
ultraviolet A
VAS
visual analog scale
V/F
volume of distribution
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 16 of 131
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 psoriatic arthritis (PsA) in order to guide the selection of doses and 
clinical indices in the Phase 3 development program.
The study population will consist of adult subjects (≥18 years of age) fulfilling the Classification 
Criteria for Psoriatic Arthritis (CASPAR) criteria and having active disease with tender joint 
count (TJC) ≥3 out of 78 and swollen joint count (SJC) ≥3 out of 76. Subjects must be 
rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative and have active 
psoriatic lesion(s) and/or a documented history of PSO. 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) every 4 weeks (Q4W) for 12 weeks in the treatment of subjects 
with active PsA. The primary efficacy variable is the American College of Rheumatology 50% 
(ACR50) response at Week 12, with a responder defined as a subject with an improvement from 
Baseline of ≥50% in the swollen and tender joint counts and at least 3 of the other 5 components 
of the core set of American College of Rheumatology (ACR) response measures. 
The secondary objectives are to assess efficacy of the individual dose regimens of bimekizumab
compared to placebo, skin and nail psoriasis in the subgroup of affected subjects at Baseline, 
safety and tolerability, PK, PD, immunogenicity, and the exposure:response relationship of 
bimekizumab as it relates to efficacy and safety. The secondary efficacy variables are American 
College of Rheumatology 20% (ACR20) response, American College of Rheumatology 70% 
(ACR70) response, Psoriasis Area and Severity Index 90% (PASI90) response, and Psoriasis 
Area and Severity Index 75% (PASI75) response, 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 of treatment on patient-reported quality of life, axial 
disease and biological pathways relating to disease biology, progression, and response to therapy 
via biomarker analysis, as well as to enable genomic and related approaches for analysis of 
subject samples and evaluation of the potential for subject stratification approaches. 
An estimated 70 sites in Europe and North America will randomize 200 subjects. Enrollment of 
TNF inhibitor experienced subjects will be limited to 30% of the total study population.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 17 of 131
The study consists of a Screening Period (14 to 28 days), Double-Blind Period (12 weeks), 
Dose-Blind Period (36 weeks) and Safety Follow-up Period (20 weeks after last dose; 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 last 14 to 28 days. During the Screening Period, the Investigator will 
obtain laboratory data and verify that the doses of methotrexate (MTX), leflunomide (LEF),
nonsteroidal anti-inflammatory drugs (NSAIDs), or corticosteroids, if used, are stable. The 
Screening Period will also enable washout of any medications not permitted for use during the 
study.
Double-Blind Period
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:
!
Placebo
!
Bimekizumab 16mg administered sc Q4W
!
Bimekizumab 160mg administered sc Q4W
!
Bimekizumab 320mg administered sc Q4W
!
Bimekizumab 320mg loading dose followed by 160mg administered sc starting at Week 4 
and Q4W thereafter
Enrollment of TNF inhibitor experienced subjects will be limited to approximately 30% of the 
total study population. Therefore, each arm will have approximately 12 TNF inhibitor
experienced subjects in a total of 40 subjects per arm.
Investigational medicinal product (IMP) will be administered sc in the clinic at Baseline/Day 1, 
Week 4, Week 8, and Week 12. Additional nondosing study visits in the Double-Blind Period 
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. 
Dose-Blind Period
Subjects will be allocated to bimekizumab treatment regimens as follows: 
!
Subjects in the placebo group will be rerandomized 1:1 to bimekizumab 160mg or 
bimekizumab 320mg Q4W
!
Subjects in the bimekizumab 16mg dose group will be rerandomized 1:1 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
!
Subjects in the bimekizumab 320mg (loading)/160mg dose group will continue to receive 
bimekizumab 160mg Q4W
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 18 of 131
During the 36-week Dose-Blind Period, subjects will be evaluated for inadequate response to 
treatment at defined time points. Subjects who do not show an improvement in tender and 
swollen joint count will be eligible to receive rescue therapy as defined in Section 5.1.4. 
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 
Safety Follow-up (SFU) Visit at 20 weeks after their last dose of study medication. 
2
INTRODUCTION
Psoriatic arthritis, a chronic inflammatory musculoskeletal disorder, occurs in approximately 6 to 
41% of people affected by PSO (Ogdie and Weiss, 2015). A substantial proportion of subjects 
have polyarthritis (McHugh et al, 2003). Disease-modifying antirheumatic drugs and biological 
agents targeting TNFα, interleukin (IL)-17, and IL-12/23 are effective in PsA (Kavanaugh et al, 
2012; Kavanaugh et al, 2009; Gottlieb et al, 2009; Gladman et al, 2007; Genovese et al, 2007; 
Kavanaugh et al, 2006; Antoni et al, 2005a; Antoni et al, 2005b; Mease et al, 2005; Mease et al, 
2004, McInnes et al, 2015; Mease et al, 2015). However, some subjects are not responsive to 
these treatments, do not maintain a clinical response (defined as achieving ACR20 response 
criteria), or have contraindications or intolerance to these agents.
Recent work has implicated various isoforms comprising the IL-17 cytokine family in the 
pathophysiology of psoriasis (PsO) and of PsA (Raychaudhuri et al, 2012; Fujishima et al, 2010; 
Watanabe et al, 2009; Harper et al, 2009; Johansen et al, 2009). Numbers of IL-17A positive 
cells are increased and localized in psoriatic skin lesions (Fujishima et al, 2010; Watanabe et al, 
2009; Harper et al, 2009; Johansen et al, 2009), and IL-17A and IL-17F are overexpressed in the 
serum and skin lesions of subjects with PSO (Johansen et al, 2009), while IL-17F in particular is 
a key inflammatory cytokine contributing to PSO pathology (Fujishima et al, 2010; Watanabe et 
al, 2009). Cluster of differentiation (CD) 4 + T helper 17 (Th17) cells, IL-17A, and IL-17 
receptor A (IL-17-RA) have recently been shown to play a role in PsA (Raychaudhuri et al, 
2012). Anti-IL-17 antibodies have been shown to be effective treatments for PSO (Papp et al, 
2012; Leonardi et al, 2012; Hueber et al, 2010) and have also shown activity in subjects with 
rheumatoid arthritis, PsA, and ankylosing spondylitis (McInnes et al, 2014; Mease et al, 2015; 
Hueber et al, 2010; Genovese et al, 2010). Taken together these data suggest that inhibition of 
both IL-17A and IL-17F could be therapeutically effective in subjects with PSO and PsA, as well 
as spondyloarthritis disease, including axial spondylitis (axSpA).
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. 
Therefore, it 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. As a consequence, a Phase 2b dose-ranging study (PA0008) was designed 
to investigate the efficacy and safety of various bimekizumab dose regimens in subjects with 
active PsA. Furthermore, a proof-of-concept study with bimekizumab in patients with 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 19 of 131
moderate-to-severe PsA demonstrated an efficacy signal that warrants further exploration of 
bimekizumab in this indication. 
2.1.1
Clinical
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque PSO, RA0124 in 30 healthy volunteers, and PA0007 in 53 subjects with PsA. 
UP0008 was a Phase 1, single ascending dose study in adults with mild to moderate PSO
affecting ≤5% body surface area (BSA). In this blinded study, single doses of up to 640mg 
(approximately 8mg/kg in an 80kg adult) were evaluated. A total of 26 subjects with PSO with 
less than 5% of body surface involvement were treated with a range of single intravenous (iv) 
doses from 8 to 640mg. The PK of bimekizumab was linear in the tested dose range. There were 
no clinically relevant safety findings identified at any dose and all doses were well tolerated. The 
pre-specified exploratory assessment of disease activity showed clinically relevant and 
statistically significant improvements at the higher doses studied.
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 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 t1/2 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 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, respectively. In each treatment group, subjects received a total of 
3 doses of bimekizumab, administered every 3 weeks. In this study, 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 (versus 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 (versus 0% [95% CI: 0.0, 43.4] in the placebo group).  
Infections (mostly nasopharyngitis) were the most commonly reported events in both the active 
treatment and the placebo group. 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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 20 of 131
treatment group, although this drop was not clinically relevant and a clear relationship with dose 
or time was not evident. Some increases in liver function tests were reported, but none had a 
convincing relationship to exposure to study medication. 
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 
symptoms of co-existing Crohn’s disease in patients with psoriasis and ankylosing spondylitis 
(Baeten et al 2015).
Two additional studies 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 rheumatoid arthritis. 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.
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
2.1.2
Nonclinical
Parallel inhibition of IL-17A and IL-17F have 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 (NOAEL) 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 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 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 21 of 131
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 active PsA.
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 PsA.
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 skin and nail psoriasis in the subgroup of affected subjects at Baseline
!
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
Other objectives of the study are as follows: 
!
To assess the impact on patient-reported quality of life
!
To assess the impact of bimekizumab treatment on axial disease
!
To assess the impact of bimekizumab on dactylitis and 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
4
STUDY VARIABLES
4.1
Efficacy variables
4.1.1
Primary efficacy variable
The primary efficacy variable for this study is as follows:
!
ACR50 response at Week 12
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or variations thereof. 


UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 22 of 131
4.1.2
Secondary efficacy variables
The secondary efficacy variables for this study are as follows:
!
ACR20 response at Week 12 
!
ACR70 response at Week 12 
!
PASI90 response at Week 12 in the subgroup of subjects with psoriasis involving at least 3% 
of body surface area at Baseline/Day 1
!
PASI75 response at Week 12 in the subgroup of subjects with psoriasis involving at least 3% 
of body surface area at Baseline/Day 1
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 4.1.2 are exploratory):
!
Time to ACR20 and ACR50 response  
!
Psoriasis Area and Severity Index 100% (PASI100) response in the subgroup of subjects 
with psoriasis involving at least 3% of body surface area at Baseline/Day 1
!
ACR20, ACR50, and ACR70 response
!
Composite endpoint comprised of ACR50 and PASI90 response in the subgroup of subjects
with PSO involving at least 3% of body surface area at Baseline/Day 1
!
Minimal Disease Activity (MDA), as defined in Table 9‒3. 
!
Change from Baseline in the Disease Activity Score-28 based on CRP (DAS28 [CRP]) 
!
Change from Baseline in all individual ACR core components:
∀
SJC
∀
TJC
∀
Health Assessment Questionnaire—Disability Index (HAQ-DI)
∀
Patient’s Assessment of Arthritis Pain (PtAAP)
∀
Physician’s Global Assessment of Disease Activity (PhGADA)
∀
Patient’s Global Assessment of Disease Activity (PGADA)
∀
CRP
!
Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
!
Change from Baseline in the modified Nail Psoriasis Severity Index (mNAPSI) 
!
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
!
Change from Baseline in the Leeds Dactylitis Index (LDI)
!
Psoriatic Arthritis Impact of Disease (PsAID)-9
!
Psoriatic Arthritis Quality of Life (PsAQoL)
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 23 of 131
!
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 Hospital Anxiety and Depression Scale (HADS) 
HADS-Anxiety (A) and HADS-Depression (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 IL 17A/F signaling pathway 
and PsA 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 metabolite 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). 
!
Cytokines and other exploratory markers  
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 24 of 131
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 [BP] and 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)
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 
PsA. To be eligible to participate in this study, subjects must meet the following key inclusion 
criteria: 
!
Subject has a documented diagnosis of adult-onset PsA classified by CASPAR criteria with 
symptoms for at least 6 months prior to Screening with active PsA and must have at Baseline 
TJC ≥3 out of 78 and SJC ≥3 out of 76 (dactylitis of a digit counts as 1 joint each).
!
Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies 
negative.
!
Subject must have active psoriatic lesion(s) and/or a documented history of PSO.
!
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
Two hundred subjects will be randomized to 1 of 5 treatment arms (Section 5.1.2). Subjects in 
any treatment group who complete the 12-week Double-Blind Period will enter the 36-week 
Dose-Blind Period (Section 5.1.3). Treatment during the Dose-Blind Period will start at Week 12 
and be administered Q4W thereafter through Week 44 (for subjects who will not enter the 
extension study or Week 48 (for subjects who enter the extension study). 
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.
A schematic diagram of the study design is presented in Figure 5‒1. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 25 of 131
5.1.1
Screening Period/Baseline
The Screening Period will last 14 to 28 days. During the Screening Period, the Investigator will 
obtain laboratory data and verify that the doses of MTX (for those taking MTX), LEF (for those 
taking LEF), NSAIDs (if used), and corticosteroids are stable. The Screening Period will also 
enable washout of medications not permitted for use during the study (Section 7.8.2). The 
assessments at the Screening Period Visit are presented in Table 5‒1.
5.1.2
Double-Blind Period
During the Double-Blind Period, subjects will be randomized 1:1:1:1:1 (stratified by region and 
prior TNF inhibitor exposure) to receive the following blinded study treatment regimens:
!
Placebo
!
Bimekizumab 16mg administered sc Q4W
!
Bimekizumab 160mg administered sc Q4W
!
Bimekizumab 320mg administered sc Q4W
!
Bimekizumab 320mg loading dose followed by 160mg administered sc starting at Week 4 
and Q4W thereafter
Enrollment of TNF inhibitor experienced subjects will be limited to approximately 30% of the 
total study population. Therefore, each arm will have approximately 12 TNF inhibitor
experienced subjects in a total of 40 subjects per arm.
The Double-Blind Period is 12 weeks in duration. Study medication will be administered sc in 
the clinic at Baseline, Week 4, Week 8, and Week 12. 
Additional study visits (without dosing) will occur at Week 1 and Week 2.
Subjects withdrawing early from the study will undergo the Early Termination (ET) Visit 
assessments and will enter the SFU Period.
The assessments at each Double-Blind Period Visit are presented in Table 5‒1.
At 12 weeks, subjects will transition from the double-blind placebo-controlled treatment into the 
36-week Dose-Blind Period as discussed in Section 5.1.3.
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 will be rerandomized 1:1 to bimekizumab 160mg or 
bimekizumab 320mg Q4W
!
Subjects in the bimekizumab 16mg dose group will be rerandomized 1:1 to 
bimekizumab 160mg or bimekizumab 320mg Q4W
!
Subjects in the bimekizumab 160mg dose group will continue to receive 
bimekizumab 160mg Q4W
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 26 of 131
!
Subjects in the bimekizumab 320mg dose group will continue to receive 
bimekizumab 320mg Q4W
!
Subjects in the bimekizumab 320mg (loading)/160mg dose group will continue to receive 
bimekizumab 160mg Q4W
The assessments at each Dose-Blind Period Visit are presented in Table 5‒1. 
During the 36-week Dose-Blind Period, subjects will be evaluated for inadequate response to 
treatment at defined time points. Subjects who do not show an improvement in tender and 
swollen joint count will be eligible to receive rescue therapy as defined in Section 5.1.4.
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, 
provided they do not qualify for rescue therapy as outlined in Section 5.1.4.
5.1.4
Rescue therapy
At Week 16, Week 24, and Week 36 of the Dose-blind Period, subjects will be evaluated for 
their response to treatment to determine eligibility for rescue therapy.
Subjects who have shown <10% improvement from Baseline in TJC and SJC will be eligible for 
rescue therapy. Rescue therapy for eligible subjects will be at the Investigator’s discretion, with 
the following options: 
!
Nonsteroidal anti-inflammatory drugs, DMARDs (MTX, sulfasalazine, LEF, apremilast), 
and/or joint injections may be given as rescue therapy if deemed appropriate by the 
Investigator as outlined below. Subjects may receive these add-on therapies while continuing 
to receive their randomized dose of bimekizumab.
∀
For subjects taking NSAID/COX-2 inhibitors at Baseline or at Week 16, Week 24, or 
Week 36, a change can be made to a different NSAID/COX-2. Changes from an NSAID 
to a COX-2 or from a COX-2 to an NSAID are permitted up to the maximum approved 
or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 may be taken at a given 
time.
∀
For subjects not taking NSAID/COX-2 inhibitors at Baseline, Week 16, Week 24, or 
Week 36, either a NSAID or COX-2 inhibitor can be initiated, up to the maximum 
approved or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 may be taken at a 
given time.
∀
Methotrexate may be added or increased to a maximum dose of 25mg/week, or the 
maximum tolerated dose, whichever is lower. The route of administration may be 
changed from oral to sc. 
∀
Sulfasalazine may be given up to a maximum dose of 3g/day, or the maximum tolerated 
dose, whichever is lower. 
∀
Leflunomide may be given at a maximum dose of 20mg/day (or an average of 20mg/day 
if not dosed daily), or the maximum tolerated dose, whichever is lower. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 27 of 131
∀
Apremilast may be given at a maximum dose of 30mg twice daily, or the maximum 
tolerated dose, whichever is lower.
∀
Combination DMARDs are allowed except that LEF and MTX may not be given 
together.
∀
One joint may be injected at or after the Week 16, Week 24, and Week 36 Visit; 
however, the same joint should not be injected more than once during the study.
!
A decrease in dose or dosing frequency of any agent for the treatment of PsA is permitted for 
reasons of intolerance/AEs/side-effects at any time.
!
If, in the judgment of the Investigator, the options outlined above are not considered 
appropriate for the subject, or the subject does not achieve sufficient response to these 
options, biologics may be considered. Subjects must discontinue treatment with 
bimekizumab prior to use of another biologic therapy and follow the withdrawal criteria and 
follow-up as outlined in Section 6.3. 
!
Rescue therapy will be determined by the Investigator taking into account the half-life of 
bimekizumab (27.8 days).
No other medication changes or additions are permitted for rescue therapy.
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 
early, including those withdrawn from study treatment, will have a SFU Visit 20 weeks after 
their last dose of study medication.
The assessments for the SFU Visit are presented in Table 5‒1.
5.1.6
Safety monitoring strategy
An independent Data Monitoring Committee (DMC) will be reviewing 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.
5.1.7
Study duration per subject
For each subject, the study will last a maximum of 68weeks, as follows:
!
2 to 4 weeks of Screening
!
12 weeks in the Double-Blind Period
!
36 weeks in the Dose-Blind Period
!
A SFU Visit 20 weeks after the last dose of study medication (for subjects not entering the 
extension study or who discontinue 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 28 of 131
5.1.8
Planned number of subjects and site(s)
The planned number of randomized subjects in PA0008 is 200; there will be 40 subjects per 
treatment arm. The planned number of study sites is approximately 70.
5.1.9
Anticipated regions and countries
The planned study sites will be located in Europe and North America.
5.2
Schedule of study assessments
The schedule of study assessments in presented in Table 5‒1. 
REDACTED COPY 
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
PA0008
Confidential
Page 29 of 131
Table 5‒1:
Schedule of assessments
Visita/
Week
Protocol activity
Screening
(V1) (14-28 
days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
3/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
20
10/
24
11/
28
12/
32
13/
36
14/
40
15/
44
16/
48
Written Informed consent
X
Demographic data
X
PsA 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
PsAQoL
X
X
X
X
X
X
X
X
X
X
BASDAI
X
X
X
X
X
X
X
X
X
X
X
X
HAQ-DI
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
PGADA
X
X
X
X
X
X
X
X
X
X
X
X
X
PtAAP
X
X
X
X
X
X
X
X
X
X
X
X
X
PsAID-9
X
X
X
X
X
X
X
X
X
X
Tuberculosis questionnaire
X
X
X
X
X
X
X
X
Height
X
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 30 of 131
Table 5‒1:
Schedule of assessments
Visita/
Week
Protocol activity
Screening
(V1) (14-28 
days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
3/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
20
10/
24
11/
28
12/
32
13/
36
14/
40
15/
44
16/
48
Vital signs (pulse, temperature, BP)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
Physical examinatione
X
X
X
X
X
X
SJC and TJC
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA affected by PSO (BSA palm 
method)
X
X
X
X
X
X
PASIf
X
X
X
X
X
X
X
X
X
X
mNAPSI
X
X
X
X
X
X
MASES
X
X
X
X
X
X
X
X
X
X
LDI
X
X
X
X
X
X
X
X
X
X
PhGADA
X
X
X
X
X
X
X
X
X
X
X
X
ECG
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
hs-CRPg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CRPg
X
X
X
X
Pregnancy testingh
X
X
X
X
X
Hepatitis B and C testing
X
HIV testing
X
RF, anti-CCP antibodies
X
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 31 of 131
Table 5‒1:
Schedule of assessments
Visita/
Week
Protocol activity
Screening
(V1) (14-28 
days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
3/
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8/
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9/
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10/
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11/
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12/
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13/
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14/
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15/
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16/
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Blood sample for bimekizumab
plasma concentrationsi
X
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab antibody detectioni
X
X
X
X
X
X
X
X
X
X
X
Blood samples for cytokines, 
complement, and biomarker analysisi
X
X
X
X
X
X
X
Blood samples for genomic, 
proteomic/metabolomics analysesi,j
X
X
X
X
X
X
X
For participating centers: 
Blood samples for flow cytometryi
X
X
X
X
X
X
X
Blood samples for genetic/epigenetic 
analysisi,j
X
X
X
X
IGRA Tuberculosis testk
X
X
X
X
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X
X
X
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X
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X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab or placebo 
administrationp,q
X
X
X
X
X
X
X
X
X
X
X
X
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BP=blood pressure; BSA=body surface area; CCP= cyclic citrullinated peptide; CRP=C-reactive 
protein; eCRF=electronic Case Report Form; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; ET=Early Termination; 
HADS=Hospital Anxiety and Depression Scale; HAQ-DI=Health Assessment Questionnaire—Disability Index; HIV=human immunodeficiency virus; 
hs-CRP=high sensitivity CRP; IGRA=interferon gamma release assay; IMP=investigational medicinal product; IXRS=interactive voice or web response 
system; mNAPSI=modified Nail Psoriasis Severity Index; LDI=Leeds Dactylitis Index; PASI=psoriasis area severity index; PGADA=Patient’s Global 
Assessment of Disease Activity; PhGADA=Physician’s Global Assessment of Disease Activity; PsA=psoriatic arthritis; PsAID=Psoriatic Arthritis Impact of 
Disease; PsAQoL=Psoriatic Arthritis Quality of Life; PSO=psoriasis; PtAAP=Patient’s Assessment of Arthritis Pain; RF=rheumatoid factor; SF-36=short 
form-36; SFU=Safety Follow-Up; SJC=swollen joint count; TB=tuberculosis; TJC=tender joint count
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 32 of 131
Table 5‒1:
Schedule of assessments
Visita/
Week
Protocol activity
Screening
(V1) (14-28 
days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
3/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
20
10/
24
11/
28
12/
32
13/
36
14/
40
15/
44
16/
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 Safety Follow-up 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, 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 and risk for exposure to TB.
f PASI will be assessed in all subjects with Baseline/Day 1 BSA affected by PSO ≥3% as determined by the BSA palm method (Section 9.8). 
g High sensitivity-CRP is performed at Screening, Baseline, and all other study visits as marked with an X. CRP will be performed at Baseline, Week 4, 
Week 12, and Week 24 only. After Screening, the 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 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. 
j  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.
k It is recommended that Quantiferon TB GOLD test be performed. 
l  At Weeks 16, 24, and 36, subjects will be evaluated for inadequate response to treatment. Subjects who do not show an improvement in tender and swollen 
joint counts as defined in Section 5.1.4 will be eligible to receive rescue therapy.
m 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.  
n Hand and foot x-rays are not required if the subject has hand and/or foot x-rays (only hand OR foot is required) that are no more than 2 years from the date of 
Screening, and are available for submission within the Screening Period to the central radiology reader and whose reading is consistent with CASPAR Criteria 
#5 showing ill-defined ossification near joint margin (but excluding osteophyte formation). For those subjects without prior x-rays that meet this Criterion and 
those whose submitted films are not read with changes consistent with CASPAR, hand and foot x-rays may be done during the Screening Period.
o IXRS is used to register the Subject at Screening, randomize the Subject at Baseline/Day 1, rerandomize the Subject at Week 12 (Subjects in the placebo or 
bimekizumab 16mg treatment groups), and to register all visits.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 33 of 131
Table 5‒1:
Schedule of assessments
Visita/
Week
Protocol activity
Screening
(V1) (14-28 
days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first dose)
Dose-Blind Period
(weeks after first dose)
ET
SFUb
3/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
20
10/
24
11/
28
12/
32
13/
36
14/
40
15/
44
16/
48
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
PA0008
Confidential
Page 34 of 131
5.3
Schematic diagram
The study schematic diagram for PA0008 is presented in Figure 5‒1.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
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
PA0008
Confidential
Page 36 of 131
5.4
Rationale for study design and selection of dose
The following doses of bimekizumab are proposed in the Phase 2b study: 16mg, 160mg, and 
320mg administered sc Q4W, as well as another dosing arm in which bimekizumab 320mg 
loading dose will be administered sc at Week 1 followed by bimekizumab 160mg Q4W. The 
proposed dose range has been selected considering the predicted therapeutic dose range of 
bimekizumab in PsA based on the available clinical data. The clinical data generated for 
bimekizumab to date were used to define the exposure:response relationship between the plasma 
concentration of bimekizumab and ACR and PASI response (REP-1-UCB-4940-PMX-1). 
Simulations were performed using the model to predict the dose response of ACR50 and PASI90 
responder rates at Week 12 and indicated that increasing doses above 320mg may not provide 
additional benefit in terms of efficacy in either ACR50 or PASI90 responder rates. Therefore, 
bimekizumab 320mg has been selected as the maximum dose in the current study. Two 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 ACR50 responder rate close to the placebo, 
while still delivering some benefit to patients. The bimekizumab 160mg Q4W was selected in 
order to precisely characterize the dose-exposure response curves.  
The rationale for the additional arm with the bimekizumab 320mg loading dose is as follows: the 
model was used to simulate the effect of loading dose on maximum response or time to 
maximum response, which indicated that loading dose had minimal benefit on the onset of action 
or maximum ACR50 response. This inclusion of a fourth arm in which bimekizumab 320mg will 
be administered at Baseline/Day 1 followed by 160mg Q4W allows a direct comparison with the 
160mg unit dose arm to see the effect of loading dose on maximum response as well as time to 
maximum response. 
Doses greater than 320mg have previously been 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 of sc administration, bimekizumab exposure is expected to be lower with sc 
administration compared with iv administration , therefore, the dose regimens are expected to be 
safe. 
The proposed doses will provide adequate information to study the dose-exposure response of 
bimekizumab in PsA. This information will be used to determine the right dose and dosage 
regimen for future studies of bimekizumab in this indication.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 37 of 131
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/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), at least 18 years of age.
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 a documented diagnosis of adult-onset PsA classified by CASPAR criteria 
(Table 19‒1), with symptoms for at least 6 months prior to Screening, with active PsA at 
Baseline/Day 1, and must have at Baseline TJC ≥3 out of 78 and SJC ≥3 out of 76 (dactylitis 
of a digit counts as 1 joint each).
6. Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies 
negative.
8. Subject must have active psoriatic lesion(s) and/or a documented history of PSO.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 38 of 131
9. Subjects who are regularly taking NSAIDs/COX-2 inhibitors as part of their PsA therapy are 
required to be on a stable dose/dose regimen for at least 14 days before Baseline and should 
remain on a stable dose through the Week 16 visit.
10. 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 through 
the Week 16 visit.
11. 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 sc) should remain stable up to 
Week 16 visit. It is strongly recommended that subjects taking MTX are also taking folic 
acid supplementation.
12. Subjects taking LEF (≤20mg/day or an average of 20mg/day if not dosed daily) are allowed 
to continue their medication if started at least 3 months 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.
13. 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
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is 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 trial 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 3 months or at least 5 half-lives, whichever is greater. 
4. Subjects with a known hypersensitivity to any excipients of bimekizumab.
5. Subjects with use of any medication listed in Table 7-1 and Table 7-2 meeting the 
exclusionary criteria for the specific medication(s) including wash-out described in the table. 
6. 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
PA0008
Confidential
Page 39 of 131
7. 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, or 
subjects who are permanently bedridden or wheelchair assisted, etc). 
8.
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)
9. 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).
10. 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
11. Subjects receiving Bacillus Calmette-Guerin (BCG) vaccinations within 1 year prior to IMP
administration.
12. 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
PA0008
Confidential
Page 40 of 131
13. Subjects with primary immunosuppressive conditions, including subjects who are taking 
immunosuppressive therapy following organ transplants.
14. 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.
15. Subjects who have had a splenectomy.
16. 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
17. 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.
18. 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.
19. 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.
20. 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 <100 x109/L). Individual screening tests for which the results are in 
error, borderline, or indeterminate for inclusion in the study, can be repeated once for 
confirmation during the Screening period if they are within 25% of the exclusion limit. Upon 
retesting, subjects whose results remain outside this threshold should not be randomized.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 41 of 131
21. Subject has >2x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)*, or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If subject has 
elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to 
identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
*An isolated elevation between 2xULN and <3xULN of ALP is acceptable in the absence of 
an identified exclusionary medical condition.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation during the screening period. Upon retesting, subjects whose ALT, 
AST, or ALP remain above the thresholds defined above, should not be randomized.
For randomized subjects with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, 
a baseline diagnosis and/or the cause of any clinically meaningful elevation must be 
understood and recorded in the Case Report form (CRF).
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.
22. Subjects with any other condition which, in the Investigator's judgment, would make the 
subject unsuitable for inclusion in the study.
23. Subjects with erythrodermic, guttate, pustular form of PSO or drug-induced PSO.
24. Subjects with a diagnosis of inflammatory conditions other than psoriasis or psoriatic 
arthritis, including but not limited to rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, 
or systemic lupus erythematosus. Subjects with a diagnosis of Crohn’s disease or ulcerative 
colitis are allowed provided they have no active and/or symptomatic disease at Screening and 
Baseline.
25. Subjects with fibromyalgia or osteoarthritis symptoms that in the Investigator’s opinion 
would have potential to interfere with efficacy assessments.
26. Subjects with a diagnosis of arthritis mutilans.
27. Subjects taking PsA medications other than MTX, LEF, NSAIDs/COX-2 inhibitors, and 
corticosteroids as outlined in the Inclusion criteria (Section 6.1). Stable doses/regimens of 
analgesics are also permitted.
28. Subject has a history of chronic alcohol or drug abuse within the previous year.
29. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review by the Investigator or designee.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 42 of 131
30. 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. 
∀
HADS Depression (HADS-D) Score >10 or Anxiety (HADS-A) score ≥15.
31. 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.
32. Subject is a UCB employee or is an employee of third-party organizations 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 in the opinion of the Investigator would interfere with his/her 
continued participation, if the risk of continuing participation outweighs the potential benefit. 
5. Subject considered as having either a suspected new LTBI or who develop 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 study medication, 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 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 is provided in Section 12.6.5.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 43 of 131
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.
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; or 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 inflammatory bowel disease (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 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 44 of 131
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 electronic Case Report Form (eCRF) must document the primary reason for 
withdrawal or discontinuation.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
The PDILI criteria below require immediate and permanent discontinuation of IMP:
!
Subjects with either of the following:
∀
ALT or AST ≥5xULN
∀
ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
∀
Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without 
clear alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator. 
!
Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis 
(eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness).
Evaluation of PDILI must be initiated as described in Section 12.5.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The CRF must document the primary 
reason for IMP discontinuation.
7
STUDY TREATMENTS
7.1
Description of investigational medicinal products
The IMPs used in this study are bimekizumab and placebo. 
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative‑free solution in 2mL Type I, colorless glass vials (1.0mL extractable volume) 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 46 of 131
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. 
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, 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 in the 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 in the electronic 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
PA0008
Confidential
Page 47 of 131
7.8.1
Permitted concomitant treatments (medications and therapies)
No medication increases or additions are permitted for medications taken for PsA until after the 
Week 16 visit assessments. However, a decrease in dose or dosing frequency of any agent is 
permitted for reasons of intolerance/AEs/side-effects at any time.
At Week 16, Week 24, and Week 36 of the Dose-blind Period, subjects will be evaluated for 
their response to treatment to determine eligibility for rescue therapy.
Subjects who have shown <10% improvement from Baseline in TJC and SJC will be eligible for 
rescue therapy. Rescue therapy for eligible subjects will be at the Investigator’s discretion, with 
the following options: 
!
Nonsteroidal anti-inflammatory drugs, DMARDs (MTX, sulfasalazine, LEF, apremilast), 
and/or joint injections may be given as rescue therapy if deemed appropriate by the 
Investigator as outlined below. Subjects may receive these add-on therapies while continuing 
to receive their randomized dose of bimekizumab.
∀
For subjects taking NSAID/COX-2 inhibitors at Baseline or at Week 16, Week 24, or 
Week 36, a change can be made to a different NSAID/COX-2. Changes from an NSAID 
to a COX-2 or from a COX-2 to an NSAID are permitted up to the maximum approved 
or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 may be taken at a given 
time.
∀
For subjects not taking NSAID/COX-2 inhibitors at Baseline, Week 16, Week 24, or 
Week 36, either a NSAID or COX-2 inhibitor can be initiated, up to the maximum 
approved or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 may be taken at a 
given time.
∀
Methotrexate may be added or increased to a maximum dose of 25mg/week, or the 
maximum tolerated dose, whichever is lower. The route of administration may be 
changed from oral to sc. 
∀
Sulfasalazine may be given up to a maximum dose of 3g/day, or the maximum tolerated 
dose, whichever is lower. 
∀
Leflunomide may be given at a maximum dose of 20mg/day (or an average of 20mg/day 
if not dosed daily), or the maximum tolerated dose, whichever is lower. 
∀
Apremilast may be given at a maximum dose of 30mg twice daily, or the maximum 
tolerated dose, whichever is lower.
∀
Combination DMARDs are allowed except that LEF and MTX may not be given 
together.
∀
One joint may be injected at or after the Week 16, Week 24, and Week 36 Visit; 
however, the same joint should not be injected more than once during the study.
Subjects are allowed to use acetaminophen/paracetamol and mild opioids as needed.
Subjects who are already receiving an established antidepressant regimen should be on a stable 
dose of the antidepressant for 12 weeks prior to Baseline.
Psoriasis treatments
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 48 of 131
For treatment of PSO, subjects may continue to use topical moisturizers, emollients, salicylic 
acid preparations, bath oils, and oatmeal bath preparations for skin conditions during the study, 
as needed. Over-the-counter shampoos for the treatment of PSO of the scalp are also permitted. 
Additionally, mild topical steroids are permitted for use limited to the face, axillae, and/or 
genitalia, as needed. Subjects who use prohibited topical medications will be allowed to stay in 
the study but will counseled to not use them further. No other topical preparations are allowed in 
the 2 weeks prior to randomization or during the study unless medically required to treat an AE.
See Table 7-2 for prohibited PSO medications.
After the Week 16 Visit, the addition of topical retinoids, vitamin D analogues, coal tar 
preparations, and more potent topical steroids may be used as medically required to treat a flare, 
but are not permitted to be used within 24 hours prior to a study visit. Use of psoralen and 
ultraviolet A light (PUVA/UVA) therapy for the treatment of PSO is not permitted for the first 
16 weeks of the study and is discouraged through the duration of the study.
7.8.2
Prohibited concomitant treatments (medications and therapies)
Prohibited and/or restricted medications are summarized in Table 7-1 and Table 7-2.
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 28 days prior to 
the Baseline Visit.
Intramuscular/intravenous 
/intra-articular corticosteroids 
Any dose 
Use in the 28 days prior to the Baseline Visit.
Intra-articular hyaluronic acid 
Any dose 
Use in the 6 months prior to the Baseline Visit.
DMARDs:
-hydroxychloroquine, 
-azathioprine, 
-cyclosporine, 
-cyclophosphamide, 
-mycophenolic acid
-mycophenolate mofetil
-sulfasalazine (SSZ)a
-any other small molecule 
DMARDs (eg, tofacitinib, 
apremilasta)
Any dose
Use within 12 weeks prior to the Baseline Visit.
-methotrexate (MTX)
Any dose regimen
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
PA0008
Confidential
Page 49 of 131
Table 7-1
Prohibited or restricted medications and required wash-out periods 
prior to Baseline
Drug class
Dose
Exclusion criteria
-leflunomide (LEF)
Any dose
Use in the 6 months prior to the Baseline Visit, unless 
(1) a cholestyramine washout has been performed, in 
which case, use up to 28 days prior to the Baseline Visit 
is acceptable, or (2) Inclusion Criterion #12 is met.
TNF inhibitorb:
-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 inhibitor
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; IFX=infliximab; LEF=leflunomide; 
MTX=methotrexate; SSZ=sulfasalazine; TNF=tumor necrosis factor
a SSZ and apremilast are permitted as per Rescue Therapy (Section 5.1.4)
b Subjects must not have been exposed to more than 1 TNF inhibitor prior to the Baseline Visit.
Table 7-2
Additional prohibited psoriasis treatments
Drug class
Dose
Exclusion criteria
Phototherapy
Any dose
Use within the 28 days prior to the 
Baseline Visit.
Topical corticosteroids for dermatological use
except as detailed in Section 7.8.1, vitamin D 
analogues, topical retinoids, keratolytics, coal 
tar, and fumaric acid esters
Any dose
Use within 14 days prior to the Baseline 
Visit.
Systemic retinoids
Any dose
Use within 3 months prior to the Baseline 
Visit
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 7‒3. The unblinded personnel 
will not be involved in the study in any way other than assuring the medication is taken from the 
correct kit and prepared according to the pharmacy manual instructions and administering the 
drug to the subjects. 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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 50 of 131
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 7‒3:
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 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 
interactive web response system (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.
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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 51 of 131
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 identification 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 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. 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
The Screening Period will last 14 to 28 days. 
Prior to any study specific activities, subjects will be asked to read, sign, and date an ICF that has 
been approved by the Sponsor and an IEC/IRB, and that complies with regulatory requirements. 
Subjects will be given adequate time to consider any information concerning the study given to 
them by the Investigator or designee. As part of the informed consent procedure, subjects will be 
given the opportunity to ask the Investigator any questions regarding potential risks and benefits 
of participation in the study.
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.
The following procedures or assessments will be performed at the Screening Visit: 
!
Obtain written informed consent for main study. 
!
Determine subject’s interest in participation in genomic, genetic/epigenetic, and proteomic 
substudy. Obtain written informed consent for this, if subject wishes to partipate. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 52 of 131
!
Collect demographic data.
!
Collect PsA 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 TJC/SJC.
!
Perform an ECG. 
!
Collect samples for hematology/biochemistry/urinalysis.
!
Collect blood sample for hs-CRP. 
!
Perform a serum 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 samples for Hepatitis B and C tests. 
!
Collect samples for an HIV test.
!
Collect sample for rheumatoid factor (RF) test. 
!
Collect sample for anti-CCP antibody test
!
Perform an IGRA tuberculosis test.
!
Obtain a chest radiograph, unless one has been obtained 3 months prior to the Screening 
Visit.
!
Obtain radiographs of the hand and/or foot, unless subject has hand and/or foot x-rays (only 
hand OR foot is required) that are no more than 2 years from the date of Screening, and are 
available for submission within the Screening Period to the central radiology reader and 
whose reading is consistent with CASPAR Criteria #5 showing ill-defined ossification near 
joint margin (but excluding osteophyte formation). For those subjects without prior x-rays 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 53 of 131
that meet this Criterion and those whose submitted films are not read with changes consistent 
with CASPAR, hand and foot x-rays may be done during the Screening Period.
!
Register the subject using IXRS. 
8.2
Baseline (Day 1)
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 PsAQoL.
!
Determine the BASDAI. 
!
Administer the HAQ-DI. 
!
Administer the SF-36.
!
Administer the PGADA. 
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
Administer the tuberculosis questionnaire.
!
Measure temperature, pulse, and BP. 
!
Measure weight.
!
Perform TJC/SJC.
!
Determine BSA affected by PSO using the BSA palm method. 
!
If the BSA affected by PSO is ≥3%, determine the PASI. 
!
Determine the mNAPSI
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Collect samples for hematology/biochemistry/urinalysis. 
!
Collect blood sample for hs-CRP and CRP. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 54 of 131
!
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.  
!
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 genetics/epigenetics analysis.
!
For participating centers, collect blood sample for flow cytometry.
!
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 at 30 minutes and 1 hour after dosing.
8.3
Double-Blind Period (Week 1 to Week 12)
8.3.1
Week 1 (+/-3 days)
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
Determine the BASDAI.
!
Administer the PGADA
!
Administer the PtAAP.
!
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.
!
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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 55 of 131
!
Record visit in the IXRS.
8.3.2
Week 2 (+/-3 days)
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Measure temperature, pulse, and BP. 
!
Perform TJC/SJC.
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Perform 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 blood sample for bimekizumab plasma concentrations.
!
Record visit in the IXRS.
8.3.3
Week 4 (+/-3 days)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA. 
!
Administer the PtAAP.
!
Administer the PsAID-9.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 56 of 131
!
Measure temperature, pulse, and BP. 
!
Perform TJC/SJC.
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Collect samples for hematology/biochemistry/urinalysis.
!
Collect blood sample for hs-CRP and 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) 
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the PGADA.
!
Administer the PtAAP.
!
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!
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!
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 57 of 131
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the MASES.
!
Administer the LDI.
!
Perform 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) 
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
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.
!
Perform TJC/SJC.
!
Determine BSA affected by PSO using the BSA palm method. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 58 of 131
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the mNAPSI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Perform an ECG. 
!
Collect samples for hematology/biochemistry/urinalysis.
!
Collect blood sample for hs-CRP and 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.
!
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
Dose-Blind Period (Week 16 to Week 48)
8.4.1
Week 16 (+/-4 days)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 59 of 131
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
Measure temperature, pulse, and BP. 
!
Perform TJC/SJC.
!
Determine the MASES.
!
Determine the LDI.
!
Perform 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)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the HAQ-DI.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Measure temperature, pulse, and BP. 
!
Perform TJC/SJC.
!
Perform 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 60 of 131
!
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)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
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.
!
Perform TJC/SJC.
!
Determine BSA affected by PSO using the BSA palm method. 
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the mNAPSI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Collect samples for hematology/biochemistry/urinalysis.
!
Collect blood sample for hs-CRP and CRP.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 61 of 131
!
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).
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)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
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) 
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Measure temperature, pulse, and BP. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 62 of 131
!
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.
8.4.6
Week 36 (+/-4 days) 
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
Administer the tuberculosis questionnaire.
!
Measure temperature, pulse, and BP. 
!
Measure weight.
!
Perform TJC/SJC.
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the mNAPSI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 63 of 131
!
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)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
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)
The following procedures of assessments will be completed prior to administration of IMP:
!
Record concomitant medications.
!
Record AEs.
!
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. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 64 of 131
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)
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
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.
!
Perform TJC/SJC.
!
Determine BSA affected by PSO using the BSA palm method. 
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the mNAPSI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Perform an ECG.
!
Collect samples for hematology/biochemistry/urinalysis.
!
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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 65 of 131
!
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.
!
Record visit in the IXRS.
8.5
Early Termination Visit
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
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.
!
Perform TJC/SJC.
!
Determine BSA affected by PSO using the BSA palm method. 
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the mNAPSI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Perform an ECG.
!
Collect samples for hematology/biochemistry/urinalysis.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 66 of 131
!
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.
!
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.
8.6
Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final 
dose)
!
Record concomitant medications.
!
Record AEs.
!
eC-SSRS
!
HADS
!
Administer the PsAQoL.
!
Determine the BASDAI.
!
Administer the HAQ-DI.
!
Administer the SF-36.
!
Administer the PGADA.
!
Administer the PtAAP.
!
Administer the PsAID-9.
!
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. 
!
Perform TJC/SJC.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 67 of 131
!
Determine BSA affected by PSO using the BSA palm method. 
!
If the BSA affected by PSO was ≥3% at Baseline/Day 1, determine the PASI.
!
Determine the MASES.
!
Determine the LDI.
!
Perform the PhGADA.
!
Perform an ECG.
!
Collect samples for hematology/biochemistry/urinalysis.
!
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.
!
Collect a blood sample for bimekizumab plasma concentrations and anti-bimekizumab
antibody detection.
!
Perform an IGRA tuberculosis test.
!
Record visit in the IXRS.
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
!
Measure temperature, pulse, and BP. 
!
Physical examination
!
Record 12-lead ECG 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 68 of 131
!
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 ACR50 response at Week 12 is the primary efficacy variable. In addition the ACR20 and 
ACR70 responses are secondary or other efficacy variables. Several assessments must be 
completed in order to determine the ACR response. These include the TJC and SJC based on 78 
and 76 joints, respectively, PGADA, PhGADA, PtAAP, HAQ-DI, and CRP. The methods for the 
component measures will be described first, followed by ACR response and assessments used in 
secondary and other efficacy variables. 
The timing for all assessments is specified in the Schedule of Assessments (Table 5‒1). 
9.1
TJC and SJC
9.1.1
78/76 joint evaluation for ACR response and verification of Inclusion 
Criterion 5
The Principal Investigator, another delegated physician, or an appropriately qualified medical 
professional (based on local requirements) who has had documented training on how to perform 
these assessments correctly assesses the following joints for tenderness: the distal 
interphalangeal, proximal interphalangeal and metacarpophalangeal joints of the hands, and 
metatarsophalangeal joints of the feet, the carpometacarpal and wrist joints (counted separately), 
the elbows, shoulders, acromioclavicular, sternoclavicular, hip, knee, talo-tibial, and 
midtarsaljoints. All of these except for the hips are assessed for swelling.
Artificial and ankylosed joints, as well as missing joints (ie, amputated joints), are excluded from 
both tenderness and swelling assessments.
One dactylitic digit is to be counted as 1 swollen joint (instead of counting as 3 in the finger or 
2 in the toe).
Table 9-1 summarizes the swelling and tenderness grading criteria.
Table 9-1
Swelling and tenderness grading
9.1.2
28 joint evaluation for determination of DAS28(CRP)
The following 28 joints will be used for calculation of the DAS28(CRP).
!
Upper extremity (26)-bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal and 
carpometacarpal bones considered as a single unit), MCP I, II, III, IV, and V, thumb 
interphalangeals (IP), PIP II, III, IV, and V 
!
Lower extremity (2)-knees
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 69 of 131
9.2
Patient’s Global Assessment of Disease Activity
Subjects will score their Global Assessment of Disease Activity using a visual analog scale 
(VAS) where 0 is “very good, no symptoms” and 100 is “very poor, severe symptoms”.
The subject should be asked to consider both joint and skin components in their response to this 
question.
9.3
Physician’s Global Assessment of Disease Activity
The Investigator will assess the overall status of the subject with respect to their PsA signs and 
symptoms and functional capacity (considering both joint and skin components) using a VAS 
where 0 is “very good, asymptomatic and no limitation of normal activities” and 100 is “very 
poor, very severe symptoms which are intolerable and inability to carry out all normal activities”.
This assessment by the Investigator should be made blind to the PGADA.
9.4
Patient’s Assessment of Arthritis Pain 
The Patient’s Assessment of Arthritis Pain VAS or ‘Pain VAS’ is part of the ACR core set of 
measures in arthritis (Felson et al, 1993). Subjects will assess their arthritis pain using a VAS
where 0 is “no pain” and 100 is “most severe pain”.
9.5
Health Assessment Questionnaire-Disability Index score 
The HAQ-DI contains 20 items divided into 8 domains that measure: dressing and grooming, 
arising, eating, walking, hygiene, reach, grip, and common daily activities. Subjects are required 
to indicate 
 on a 
4-point scale that ranges from 0 (without difficulty) to 3 (unable to do). Any individual score of 
less than 2 is adjusted to 2 
 
. The highest score in each category is then summed (0 to 24) and divided by 
the number of categories scored to give a score that ranges from 0 to 3. 
9.6
CRP levels (hs-CRP/CRP)
C-reactive protein (CRP) levels will be analyzed by the central laboratory.
High sensitivity-CRP is performed at Screening, Baseline, and all other study visits as marked 
with an X in the Schedule of Study Assessments (Table 5‒1). CRP will be performed at 
Baseline, Week 4, Week 12, and Week 24 only. 
After Screening, the hs-CRP and CRP data will not be sent to the Investigator to protect the 
blinded nature of the treatment assignments.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 70 of 131
9.7
ACR20, ACR50, and ACR70 response
The ACR20, ACR50, and ACR70 response rates are based on a 20%, 50%, and 70% or greater 
improvement relative to Baseline in the following measures:
!
TJC based on 78 joints
!
SJC based on 76 joints
!
3 of the 5 remaining core set measures:
∀
PGADA
∀
PhGADA
∀
PtAAP
∀
HAQ-DI
∀
CRP
9.8
BSA-PSO
The BSA palm method will be used for the evaluation of BSA affected by PSO as follows:
The subject’s hand, including the palm, fingers and thumb, is used as the reference point for 
measuring how much of their skin is affected by psoriasis, representing roughly 1% of the body’s 
surface. 
!
Subject’s palm=1%
!
Head and neck=10% (10 palms)
!
Upper extremities=20 % (20 palms)
!
Trunk=30% (30 palms)
!
Lower extremities=40 % (40 palms) 
Total BSA=100%
9.9
Psoriasis Area and Severity Index (PASI)
PASI will be assessed in all subjects with Baseline/Day 1 BSA affected by PSO ≥3% determined 
by the method described in Section 9.8 (ie, the BSA palm method). 
The PASI is the most commonly used and validated assessment for grading the severity of 
psoriasis in clinical studies (Feldman, 2004). The PASI quantifies the severity and extent of the 
disease and weighs these with the percentage of BSA involvement. 
The percent area of involvement (BSA%) is estimated across 4 body areas; head, upper limbs, 
trunk, and lower limbs and then transferred into a grade (Table 9‒2). 
The Investigator assesses the average redness, thickness, and scaliness of lesions in each body
area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. 
The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 71 of 131
Table 9‒2:
Body areas for calculation of percent BSA for PASI
Body area
Details of area
BSA
Degree of 
involvement of 
body areaa
Head
Face, back of head
10% 
0 to 6
Upper limbs 
Left, right, upper lower, flexor 
surface, extensor surface
20% 
0 to 6
Trunk
Front, back, groin
30% 
0 to 6
Lower limbs 
Left, right, upper lower, flexor 
surface, extensor surface, including 
buttocks
40% 
0 to 6
Total
100% 
BSA=body surface area; PASI=Psoriasis Area and Severity Index
a Where 0=none; 1=1% to <10% affected, 2=10% to <30% affected, 3=30% to <50% affected, 4=50% to <70% 
affected, 5=70% to <90% affected, 6=90% to 100% affected
The PASI75, PASI90, and PASI100 responses are based on at least 75%, 90%, and 100% 
improvement in the PASI score. PASI will be assessed at Screening and at Baseline/Day 1. 
Thereafter PASI will be assessed for the purposes of determining response only in subjects with 
psoriasis involving at least 3% of body surface area at Baseline/Day 1. 
9.10
MDA
Minimal Disease Activity is a state of disease activity deemed a useful target of treatment by 
both the patient and physician, given current treatment possibilities and limitations. Criteria 
shown in Table 9‒3 covering all of the domains of the disease have been developed to determine 
whether or not patient has reached MDA based on key outcome measures in PsA. A subject is 
considered as having MDA if 5 or more of the following 7 criteria in Table 9‒3 are fulfilled:
Table 9‒3:
Minimal disease activity (MDA) criteria in psoriatic arthritis
A subject is classified as in MDA when they meet 5 of 7 of the following criteria: 
Tender joint count ≤1
Swollen joint count ≤1
PASI ≤1 or BSA ≤3
Patient pain VAS ≤15
Patient global activity VAS ≤20
HAQ ≤0.5
Tender enthesial points ≤1
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Data sources: Mease, 2011; Coates et al, 2010
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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
PA0008
Confidential
Page 73 of 131
activities, functional capacity, discomfort, sleep disturbance, coping, and 
anxiety/fear/uncertainty. Each domain is assessed with a single question using a 0 to 10 
numerical rating scale. Each domain score is multiplied by a weighting factor and the results are 
then summed to provide the total score. The total score ranges from 0 to 10, with higher scores 
indicating a worse status. The PsAID-9 demonstrated satisfactory psychometric properties in an 
international validation study; however, further validation is needed (Gossec et al, 2014). A score 
below 4 out of 10 is considered a patient-acceptable status. A change of 3 or more points is 
considered relevant absolute change. 
9.17
PsAQoL
The use of the PsAQoL is recommended by the health regulatory authorities as one of the disease 
specific Health-Related Quality of Life (HRQoL) measures in PsA (CHMP/EWP/438/04). The 
PsAQoL comprises 20 items so that the score ranges from 0 to 20 with higher scores indicating 
worse HRQoL.
9.18
SF-36
The SF-36 (Version 2, standard recall) is a 36 item generic 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 
. 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. 
9.19
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 ACR and PASI) are the PK variables. 
The PD variables are the concentrations of cytokines of relevance to IL-17A/F signaling pathway 
and PsA 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
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 74 of 131
biomarkers relevant to 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 
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.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 75 of 131
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 
ideation or behavior (assessed using the eC-SSRS), depression and anxiety (assessed using the 
HADS, see Section 9.19), 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.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 76 of 131
When recording the intensity of an AE in the CRF (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 consequence
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 is 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.
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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 77 of 131
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 
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 CRF, 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 78 of 131
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 PA0008. 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.
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.)
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Initial inpatient hospitalization or prolongation of hospitalization
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 79 of 131
(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 
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.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 80 of 131
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 is 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.
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 psoriatic arthritis
MedDRA system organ class
MedDRA preferred term
Eye disorders
Uveitis
Cardiac disorders
Myocardial infarction
Atrial fibrillation
Gastrointestinal disorders
Crohn's disease
Hepatobiliary disorders
Non-alcoholic steatohepatitis
Metabolism and Nutrition disorders
Metabolic syndrome
Diabetes mellitus
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy
Neoplasms benign, malignant and unspecified (incl 
cysts and polyps)
Basal cell carcinoma
Squamous cell carcinoma
Nervous system disorders
Embolic Stroke
Ischaemic Stroke
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 81 of 131
MedDRA system organ class
MedDRA preferred term
Psychiatric disorders
Anxiety
Depression
Skin and subcutaneous tissue disorders
Psoriasis
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 #8, 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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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 82 of 131
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 testingb
MCH
hs-CRP/CRPa
MCHC
AST
MCV
ALT
Platelet count
GGT
RBC count
ALP
WBC count
Total bilirubin
LDH
Total cholesterol
Uric acid
Serum pregnancy testingb
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; hs-CRP=high sensitivity-CRP; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; SFU=Safety Follow-up; RBC=red blood cell; WBC=white blood 
cell
a  Both hs-CRP and CRP will be tested at specified study visits per Table 5‒1.
b 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.
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 
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). 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 83 of 131
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 CRF 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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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 84 of 131
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 
Further investigation 
– immediate IMP 
discontinuation not 
required (see
Section 12.5.1.2).
IMP discontinuation 
required if any of the 
Essential: Every 
attempt must be 
made to have repeat 
liver chemistry 
values and 
additional testing 
completed within 
48 hours at the site 
Monitoring of liver 
chemistry values at least 
twice per week for 2 
weeks.d
!
Immediate IMP 
discontinuation 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 85 of 131
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 
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chemistry values 
continue to increase.
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!
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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
PA0008
Confidential
Page 86 of 131
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 CRF. 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
PA0008
Confidential
Page 87 of 131
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 
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
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
PA0008
Confidential
Page 88 of 131
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 1, collect pulse and BP prior to drug administration and then at 30 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 89 of 131
minutes and 1 hour after dosing. At all other visits collect pulse and BP prior to drug 
administration and once after dosing (any time). 
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.
a.
Known TB infection whether present or past is defined as:
∀
Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra-pulmonary)
∀
History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection, unless adequately treated and proven to be fully 
recovered upon consult with a TB specialist.
∀
Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject’s medical history
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 90 of 131
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 study medication 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 study medication 
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
PA0008
Confidential
Page 91 of 131
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 study medication 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 Week 48/ET Visit, 
complete all Early Termination Visit assessments, and complete a SFU Visit (20 weeks after the 
last dose of study medication).
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 study medication 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
PA0008
Confidential
Page 93 of 131
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 study 
medication).
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
Medical history
The Investigator or designee will obtain a complete medical history as part of the screening 
assessment and include all clinically relevant past or coexisting medical conditions, responses to 
PsA treatment as available, and surgeries. Findings will be recorded in the eCRF.
13.2
Psoriatic arthritis history
The Investigator or designee will obtain a detailed history of PsA, including the date of onset and 
past treatments for PsA and PsA subtype. Specific information related to PsA history, including 
family history, will be recorded in the eCRF.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 94 of 131
13.3
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.
13.4
Prior and concomitant medications
As part of the medical history, the Investigator or designee will obtain the 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 CRFs 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 CRFs, 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
PA0008
Confidential
Page 95 of 131
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 
(see Section 14.2.1).
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
PA0008
Confidential
Page 96 of 131
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
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 CRFs, 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.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 97 of 131
14.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and 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 Enrolled Set (ES) will consist of all subjects who have given informed consent.
The Randomized Set (RS) consists of all randomized subjects. 
The Safety Set (SS) consists of all randomized subjects who received at least 1 dose of the IMP.
The Full Analysis Set (FAS) consists of all randomized subjects who received at least 1 dose of 
the IMP and have valid measurement of the primary efficacy variable at Baseline.
The Per-Protocol Set (PPS) consists 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 PD-PPS consists of all randomized subjects who took at least one dose of the IMP and 
provided at least 1 PD measurement post-dose that is without important protocol deviation 
affecting that time point.
The Dose-Blind Set (DBS) consists of all subjects who started the Dose-Blind Period and who 
received at least 1 dose of IMP during the Dose-Blind Period.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 98 of 131
The Escape Subject Set (ESS) consists of all subjects who started 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 SJC and TJC at Week 16, Week 24, or 
Week 36.
The Dose-Blind Responder Set (DBRS) consists of all subjects who started 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 SJC and TJC 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.
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 ACR50 response will be assessed with an 
ordered categorical analysis using a nonparametric 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 a stratification factor as it may have an impact on efficacy. The 
use of region as a 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 ACR50 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 ACR50 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 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. In addition, a comparison will be 
made for the bimekizumab 320mg loading dose followed by bimekizumab 160mg Q4W versus 
bimekizumab 160mg Q4W using the same logistic model described above.
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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 99 of 131
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 (NRI) will be used to account for missing data in the primary analysis.
That is, subjects with a missing ACR score at Week 12 or who discontinued study treatment 
prior to the Week 12 visit will be considered nonresponders for the primary analysis.
15.3.1.1
Supportive analyses
The following supportive analyses 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 ACR50 response to explore the effect of the signs and 
symptoms of the individual components on the composite endpoint. Since all ACR 
components are continuous variables (eg, change from Baseline in TJC), an 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, ACR20/70 response and PASI75/90 response) will be analyzed for 
treatment effects using pairwise comparisons using the same logistic model as described in 
Section 15.3.1. 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 ACR and PASI responses. 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 ACR and PASI depend on drug exposure. The stochastic part of the model is 
further divided into the interindividual variability (IIV) and the residual unexplained variability 
(RUV). The IIV describes how individual specific parameters differ from the typical individual.
The RUV describes the differences between the observations and the predictions from the model. 
Further details will be given in a separate data analysis plan and reported in a separate document.
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 100 of 131
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 ACR20/50 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 two-sided 95% confidence interval (CI) will be 
calculated for each treatment. Between group differences (each bimekizumab dose versus
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 for categorical/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: 
!
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All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 101 of 131
15.5
Planned safety and other analyses
15.5.1
Safety analyses
Safety variables will be analyzed for all subjects in the SS. In addition, safety analyses during the 
Dose-Blind Period will be analyzed for all subjects in the DBS.
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.
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. Pharmadynamic 
variables will be analyzed for all subjects in the PD-PPS. 
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 ACR or PASI 
responder rates will be used as the PK and PD response. If data merits, 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.
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 primary analysis for the 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 
treatment prior to Week 12, will be counted as a nonresponder.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 102 of 131
Two sensitivity analyses will be performed for the primary dose-response analysis and for 
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.
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.
Sensitivity analyses will also be performed for the pairwise comparisons of bimekizumab doses 
versus placebo based on ACR50 response at Week 12. The following sensitivity analyses will be 
conducted:
1.
Missing data will be imputed using multiple imputation (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 ACR components will be imputed 
individually and then the ACR 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 missing at random (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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 103 of 131
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.
For 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.
All continuous efficacy variables will be imputed using MI as described above assuming that 
missingness is MAR.
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 ACR and 
PASI 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 200 subjects (40 in each treatment group) are planned to be randomized in this study.
The sample size is calculated based on the ACR50 response data from the Phase 2 bimekizumab
study in subjects with PsA (PA0007). The ACR50 responses at Weeks 12 were reported to be 
80.0% (95% CI: 37.6%; 96.4%), 52.6% (95% CI: 31.7%; 72.7%), and 33.3% (95% CI: 9.7%; 
70.0%) for the bimekizumab 560/320mg, bimekizumab 240/160mg, and bimekizumab 80/40mg 
doses, respectively. Placebo ACR50 response at Week 12 is based on the PA0007 study (0%), 
the FUTURE 1 study (8.0%; Mease et al, 2015) and FUTURE 2 study (6.0%; 
McInnes et al, 2015). 
Since the uncertainty of ACR50 responder rates of PA0007 is high due to the small number of 
subjects, the midpoint of the point estimate and the lower 95% CI was used for the sample size 
calculation of all active dose groups as a conservative assumption. For the bimekizumab 16mg 
dose, the midpoint of the 80/40mg dose was reduced by 6.5%.
Hence, ACR50 responder rates of 58.5%, 42.2%, 15.0%, and 8% at the end of a 12-week 
treatment period for bimekizumab 320mg, bimekizumab 160mg, bimekizumab 16mg, and 
placebo have been assumed, respectively. Since those ACR50 responder rates are based on a 
study population of TNF inhibitor naïve subjects, an adjustment was made for a reduction in 
ACR50 response of 25% by a maximum of 30% of subjects with TNF inhibitor experience (ie, 
12 subjects per group).
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 104 of 131
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. With 40 subjects in each treatment group, the test for detecting 
the overall dose response based on ACR50 response is powered at >99%.
The sample size calculations were performed using the software nQuery Advisor® 7.0.
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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 105 of 131
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, Informed 
Consent form, IB, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), 
and all other subject-related documents to be used for the study to the IRB/IEC for its review and 
approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 106 of 131
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
17
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
18
REFERENCES
Antoni CE, Kavanaugh A, Kirkham B, Tutuncu Z, Burmester GR, Schneider U, et al. Sustained 
benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: 
results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis 
Rheum. 2005a;52:1227–36.
Antoni C, Krueger GG, de Vlam K, Birbara C, Beutler A, Guzzo C, et al. Infliximab improves 
signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 107 of 131
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 108 of 131
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 109 of 131
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 110 of 131
19
APPENDICES
19.1
CASPAR criteria
Inflammatory articular disease (joint, spine, or entheseal) AND at least 3 points of the following 
5 categories:
Table 19‒1: CASPAR Criteria
Category
Definition
Points
1) Evidence of psoriasis: 
(Score for 1 of the followinga)
Current psoriasis
Psoriatic skin or scalp disease present today as 
judged by a dermatologist or rheumatologist
2 points
Personal history of psoriasis
A history of psoriasis that may be obtained from the 
subject, family physician, dermatologist, 
rheumatologist, or other qualified health care 
provider
1 point
Family history of psoriasis
A history of psoriasis in a first- or second-degree 
relative according to subject report
1 point
2) Psoriatic nail dystrophy
Typical psoriatic nail dystrophy, including 
onycholysis, pitting, and hyperkeratosis, observed on 
current physical examination
1 point
3) A negative test for rheumatoid 
factor
By any method except latex, but preferably by 
enzyme-linked immunosorbent assay (ELISA) or 
nephelometry, according to the local laboratory 
reference range
1 point
4) Dactylitis: 
(Score for 1 of the following)
Current dactylitis
Swelling of an entire digit
1 point
History of dactylitis
A history of dactylitis recorded by a rheumatologist
1 point
5) Radiologic evidence of 
juxta-articular new bone 
formation
Ill-defined ossification near joint margins (but 
excluding osteophyte formation) on plain radiographs 
of the hand or foot
1 point
CASPAR=Classification Criteria for Psoriatic Arthritis 
a “Score for 1 of the following” means that only 1 of the 3 criteria is applicable (either current psoriasis [scores 2 
points], personal history [scores 1 point], or family history [scores 1 point]).
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 111 of 131
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)
<1.0a
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
Data source: modified from Appendix Rheumatology Common Toxicity Criteria v.2.0 presented in 
Woodworth et al, 2007
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 112 of 131
19.3
Protocol Amendment 1
Rationale for the amendment
The purpose of this protocol amendment is the following: 
!
The SAE reporting fax number 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 and dactylitis.
!
The inclusion criterion #7 that permitted inclusion of subjects with an hs-CRP ≥ULN and one 
retesting during the Screening Period, was removed to allow subject enrollment independent 
of the hs-CRP level. 
!
Since the inclusion criterion on CRP was removed from the protocol, a subgroup analysis on 
CRP was added to study the impact of CRP levels on the efficacy of bimekizumab.
!
Criteria for the definition of AE intensity were added in response to a regulatory agency 
request. 
In addition, minor typographical errors were corrected.
Modifications and changes
Global changes
a.
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.
b. The following appendices and respective references have been removed from the protocol.
!
Section 19.3: Health Assessment Questionnaire Disability Index
!
Section 19.4: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
!
Section 19.5: PsAID-9
!
Section 19.6: Psoriatic Arthritis Quality of Life
!
Section 19.7: Short-Form (SF36) Questionnaire
!
Section 19.8: Tuberculosis Questionnaire
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 113 of 131
Specific changes
Change #1
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
Change #2
List of abbreviations
Original text: 
BASDAI
Bath Ankylosing Spondylitis Disease Index
Has been changed to:
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
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09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 114 of 131
Change #3
Section 1 Summary
Original text: 
The study population will consist of adult subjects (≥18 years of age) fulfilling the Classification 
Criteria for Psoriatic Arthritis (CASPAR) criteria and having active disease with tender joint 
count (TJC) ≥3 out of 78 and swollen joint count (SJC) ≥3 out of 76. Subjects must be 
rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative, have a high 
sensitivity (hs)-C-reactive protein (CRP) ≥upper limit of normal (ULN) (with no other reason for 
elevated CRP such as infection), and have active psoriatic lesion(s) and/or a documented history 
of PSO. 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:
Has been changed to: 
The study population will consist of adult subjects (≥18 years of age) fulfilling the Classification 
Criteria for Psoriatic Arthritis (CASPAR) criteria and having active disease with tender joint 
count (TJC) ≥3 out of 78 and swollen joint count (SJC) ≥3 out of 76. Subjects must be 
rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative, have a high 
sensitivity (hs) C reactive protein (CRP) ≥upper limit of normal (ULN) (with no other reason for 
elevated CRP such as infection), and have active psoriatic lesion(s) and/or a documented history
of PSO. 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:
Change #4
Section 3.3 Other objectives
Original text: 
To assess the impact of bimekizumab on extra-articular disease manifestations (dactylitis, 
enthesitis, uveitis, inflammatory bowel disease, and psoriasis)
Has been changed to: 
To assess the impact of bimekizumab on extra articular disease manifestations (dactylitis, 
enthesitis, uveitis, inflammatory bowel disease, and psoriasis) dactylitis and enthesitis
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 115 of 131
Change #5
Section 4.1.3 Other efficacy variables
Original text: 
!
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
Has been deleted.
Change #6
Section 4.1.3 Other efficacy variables
Original text:
!
Change from Baseline in the Bath Ankylosing Spondylitis Disease Index (BASDAI) 
Has been changed to:
!
Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
Change #7
Section 5.1 Study description
Original text:
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 
PsA. To be eligible to participate in this study, subjects must meet the following key inclusion 
criteria: 
!
Subject has a documented diagnosis of adult-onset PsA classified by CASPAR criteria with 
symptoms for at least 6 months prior to Screening with active PsA and must have at Baseline 
TJC ≥3 out of 78 and SJC ≥3 out of 76 (dactylitis of a digit counts as 1 joint each).
!
Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies 
negative.
!
Subject must have an hs-CRP ≥ULN (with no other reason for elevated CRP such as 
infection) One retesting of CRP during the Screening Period is permitted.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 116 of 131
Has been changed to:
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 
PsA. To be eligible to participate in this study, subjects must meet the following key inclusion 
criteria: 
!
Subject has a documented diagnosis of adult-onset PsA classified by CASPAR criteria with 
symptoms for at least 6 months prior to Screening with active PsA and must have at Baseline 
TJC ≥3 out of 78 and SJC ≥3 out of 76 (dactylitis of a digit counts as 1 joint each).
!
Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies 
negative.
!
Subject must have an hs CRP ≥ULN (with no other reason for elevated CRP such as 
infection) One retesting of CRP during the Screening Period is permitted.
Change #8
Table 5-1 Schedule of assessments (footnotes)
Original text:
BASDAI=Bath Ankylosing Spondylitis Index
Has been changed to:
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index
Change #9
Table 5-1 Schedule of assessments (footnotes)
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 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 117 of 131
Change #10
Section 6.1, Inclusion criteria
Original text:
7. Subject must have an hs-CRP ≥ULN (with no other reason for elevated CRP such as 
infection) One retesting of CRP during the Screening Period is permitted.
Has been deleted.
Change #11
Section 6.2, Exclusion criteria
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:
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).
Change #12
Section 6.3 Withdrawal criteria
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; or 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 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
PA0008
Confidential
Page 118 of 131
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; or 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].)
Change #13
Section 7.8.2 Prohibited concomitant treatments (medications and therapies), 
Table 7-2
Original table:
Drug class
Dose
Exclusion criteria
Phototherapy
Any dose
Use within the 28 days prior to the 
Baseline Visit.
Topical corticosteroids for dermatological use 
except as detailed in Section 7.8.1, vitamin D 
analogues, topical retinoids, keratolytics, coal 
tar
Any dose
Use within 14 days prior to the Baseline 
Visit.
Systemic retinoids
Any dose
Use within 3 months prior to the Baseline 
Visit
Has been changed to: 
Drug class
Dose
Exclusion criteria
Phototherapy
Any dose
Use within the 28 days prior to the 
Baseline Visit.
Topical corticosteroids for dermatological use 
except as detailed in Section 7.8.1, vitamin D 
analogues, topical retinoids, keratolytics, coal 
tar, and fumaric acid esters
Any dose
Use within 14 days prior to the Baseline 
Visit.
Systemic retinoids
Any dose
Use within 3 months prior to the Baseline 
Visit
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 119 of 131
Change #14
Original section and text:
Section 9.19 Extra-articular manifestations
Information regarding uveitis, enthesitis, dactylitis, inflammatory bowel disease, and psoriasis 
disease activity will be captured. Enthesitis is assessed via MASES. Dactylitis is assessed via 
LDI.
Has been removed.
Change #15
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 CRF (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 consequence
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
PA0008
Confidential
Page 120 of 131
Change #16
Section 12.5 Laboratory measurements, Table 12-2
Original table:
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
hs-CRP/CRPa
MCHC
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ALT
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GGT
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ALP
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LDH
Total cholesterol
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 121 of 131
Has been changed to:
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
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Sodium
pH
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RBC
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BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy testingb
MCH
hs-CRP/CRPa
MCHC
AST
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ALT
Platelet count
GGT
RBC count
ALP
WBC count
Total bilirubin
LDH
Total cholesterol
Uric acid
Serum pregnancy testingb
Change #17
Section 13.1 Demography
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.
Has been moved.
13.3 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.
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 122 of 131
Change #18
Section 15.1 Definition of analysis sets
Original text:
The PK-PPS consists of all randomized subjects who took at least one dose of the IMP and 
provided at least 1 quantifiable plasma concentration post-dose.
Has been changed.
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.
Change #19
Section 15.4 Subgroup analyses
Original text 
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: 
!
Age
!
Gender
!
Region
!
BASDAI >4
!
TNF inhibitor exposure
!
Anti-bimekizumab antibody status
!
Extent of PSO involvement >3%
Has been changed to:
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: 
!
Age
!
Gender
!
Region
!
BASDAI >4
!
TNF inhibitor exposure
!
Anti-bimekizumab antibody status
!
Extent of PSO involvement >3%
!
CRP level
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 123 of 131
19.4
Protocol Amendment 2
The purpose of this substantial protocol amendment is as follows:
!
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.
!
Add new details for the IMP packaging.
!
To revise and clarify the SAE criteria for pregnancy for consistency.
!
Amend the table for identification/exclusion of alternative etiology to include AST and ALT. 
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 abbreviations and definitions were added: 
IBD
Inflammatory bowel disease
Change #2
STUDY CONTACT INFORMATION
Original table: 
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
 (office)
 (mobile)
Has been changed to: 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 125 of 131
Change #4
Section 5.2 Schedule of study assessments, Table 5-1
Original text: 
Table footer:
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: 
p 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 #5
Section 6.3 Withdrawal Criteria
The following was added to the withdrawal criteria:
11. Subjects with newly diagnosed inflammatory bowel disease (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.
Change #6
Section 7.2 Treatments to be administered, paragraph 2
Original text: 
Study medication (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: 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 126 of 131
Study medication (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 #7
Section 7.3 Packaging
The following was added: 
The IMPs are manufactured, packaged, and labeled according to Good Manufacturing 
Practice guidelines and applicable laws or regulations. Investigational medicinal products 
will be suitably packaged in such a way as to protect the IMPs from deterioration during 
transport and storage.
Change #8
Section 8 STUDY PROCEDURES BY VISIT
Original text: 
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 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. Changes to the dosing schedule outside of the allowed windows must be discussed with the 
Medical Monitor and may result in subject withdrawal.
Has been changed to: 
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 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. Changes to the dosing schedule outside of the allowed windows must be discussed with the 
Medical Monitor and may result in subject withdrawal.
Change #9
Section 12.1.8 Pregnancy
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 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 127 of 131
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 #10
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
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
Additional
Prothrombin time/INR
b
Serum pregnancy test
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 128 of 131
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
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; 
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 129 of 131
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 #11
Section 19.2 Markedly abnormal laboratory values, Tables 19-1 (Definitions of 
markedly abnormal hematology values) and 19-2 (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 (RCTCSI units)
Markedly Abnormal Definition
Low
High
Change #12
Section 19.2 Markedly abnormal laboratory values, Table 19-1 (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 #13
Section 19.2 Markedly abnormal laboratory values, Table 19-2 (Definitions of 
markedly abnormal biochemistry values)
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable;
SI=standard international; ULN=upper limit of normal
Has been changed to:
LLN=lower limit of normal; N/A = Not Applicable; SI=standard international RCTC=
Rheumatology Common Toxicity Criteria
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UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 130 of 131
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
Date/S
Date/S
PY 
PY
This document cannot be used to support any marketing authorization
Signa
ign
app
natu
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pplication 
pp
and any extensions
be 
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or
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variations thereof. 


UCB
09 Mar 2018
Clinical Study Protocol
Bimekizumab
PA0008
Confidential
Page 131 of 131
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
PA0008
Confidential
Page 1 of 183
STATISTICAL ANALYSIS PLAN AMENDMENT 5
Study: PA0008
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 ACTIVE 
PSORIATIC ARTHRITIS
SAP/Amendment Number
Date
Final SAP
12 May 2017
SAP Amendment 1
11 Aug 2017
SAP Amendment 2
7 Nov 2017
SAP Amendment 3
02 Mar 2018
SAP Amendment 4
09 Aug 2018
SAP 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
THR
THR
May 2
May 2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ZED, 
ZED, 
OLLED
LLED
Y TO 
Y TO
IZUM
IZUM
ITIS
TIS
2017
2017
ug
ug 201
20
Nov
ov 20
2
02 Ma
02 M
09


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 2 of 183
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................7 
1 
INTRODUCTION ...........................................................................................................13 
2 
PROTOCOL SUMMARY...............................................................................................13 
2.1 
Study objectives...........................................................................................................13 
2.1.1 
Primary objective.................................................................................................13 
2.1.2 
Secondary objectives ...........................................................................................13 
2.1.3 
Other objectives...................................................................................................14 
2.2 
Study variables.............................................................................................................14 
2.2.1 
Efficacy variables ................................................................................................14 
2.2.1.1 
Primary efficacy variable ..........................................................................14 
2.2.1.2 
Secondary efficacy variable(s) ..................................................................14 
2.2.1.3 
Other efficacy variables.............................................................................14 
2.2.2 
Pharmacokinetic/pharmacodynamic variables ....................................................15 
2.2.2.1 
Pharmacokinetic variable ..........................................................................15 
2.2.2.2 
Pharmacodynamic variables......................................................................16 
2.2.3 
Pharmacogenomic variables ................................................................................16 
2.2.4 
Immunological variables .....................................................................................16 
2.2.5 
Safety variables....................................................................................................16 
2.3 
Study design and conduct ............................................................................................16 
2.4 
Determination of sample size.......................................................................................25 
3 
DATA ANALYSIS CONSIDERATIONS......................................................................25 
3.1 
General presentation of summaries and analyses ........................................................25 
3.2 
General study level definitions ....................................................................................27 
3.2.1 
Relative day .........................................................................................................27 
3.2.2 
Study Periods.......................................................................................................27 
3.3 
Definition of Baseline values.......................................................................................27 
3.4 
Protocol deviations.......................................................................................................28 
3.5 
Mapping of assessments performed at early termination visit.....................................28 
3.6 
Analysis sets.................................................................................................................28 
3.6.1 
Enrolled Set (ES) .................................................................................................29 
3.6.2 
Randomized Set (RS) ..........................................................................................29 
3.6.3 
Safety Set (SS).....................................................................................................29 
3.6.4 
Full Analysis Set (FAS).......................................................................................29 
3.6.5 
Per-Protocol Set (PPS).........................................................................................29 
3.6.6 
Pharmacokinetics Per-Protocol Set (PK-PPS).....................................................29 
3.6.7 
Pharmacodynamics Per-Protocol Set (PD-PPS)..................................................29 
3.6.8 
Dose-Blind Set (DBS) .........................................................................................29 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 3 of 183
3.6.9 
Escape Subject Set (ESS) ....................................................................................29 
3.6.10 
Dose-Blind Responder Set (DBRS).....................................................................30 
3.6.11 
Corrected Escape Subject Set (cESS)..................................................................30 
3.6.12 
Corrected Dose-Blind Responder Set (cDBRS)..................................................30 
3.7 
Treatment assignment and treatment groups ...............................................................30 
3.8 
Center pooling strategy................................................................................................31 
3.9 
Coding dictionaries ......................................................................................................31 
3.10 
Changes to protocol-defined analyses .........................................................................31 
4 
STATISTICAL/ANALYTICAL ISSUES.......................................................................31 
4.1 
Adjustments for covariates ..........................................................................................31 
4.2 
Handling of dropouts or missing data..........................................................................31 
4.2.1 
Handling of missing data for efficacy analysis....................................................31 
4.2.2 
Handling of missing data for AE.........................................................................34 
4.2.3 
Handling of missing data for prior and concomitant medication ........................35 
4.3 
Interim analysis and data monitoring...........................................................................36 
4.3.1 
Interim analysis Week 12 ....................................................................................36 
4.3.1.1 
Changes from interim analysis to SAP-defined analyses..........................38 
4.3.1.2 
Search and selection criteria for AE of special monitoring for interim 
analysis ......................................................................................................38 
4.3.2 
Interim analysis Week 48 ....................................................................................40 
4.3.2.1 
Changes from interim analysis to SAP-defined analyses..........................40 
4.3.2.2 
Changes during interim analysis to SAP-defined analyses.......................41 
4.4 
Multicenter studies.......................................................................................................41 
4.5 
Multiple comparisons/multiplicity...............................................................................41 
4.6 
Use of an efficacy subset of subjects ...........................................................................41 
4.7 
Active-control studies intended to show equivalence..................................................41 
4.8 
Examination of subgroups ...........................................................................................41 
5 
STUDY POPULATION CHARACTERISTICS.............................................................42 
5.1 
Subject disposition.......................................................................................................42 
5.2 
Protocol deviations.......................................................................................................42 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................43 
6.1 
Demographics ..............................................................................................................43 
6.2 
Other Baseline characteristics......................................................................................43 
6.3 
Medical history and concomitant diseases...................................................................45 
6.4 
Prior and concomitant medications..............................................................................45 
6.5 
Prohibited medication and rescue medication .............................................................45 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................45 
8 
EFFICACY ANALYSES ................................................................................................46 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 4 of 183
8.1 
Statistical analysis of the primary efficacy variable ....................................................46 
8.1.1 
Derivations of primary ACR score and response ................................................46 
8.1.1.1 
Tender joint count (TJC) and swollen joint count (SJC)...........................47 
8.1.1.2 
Patient’s Global Assessment of Disease Activity (PGADA)....................48 
8.1.1.3 
Physician’s Global Assessment of Disease Activity (PhGADA) .............48 
8.1.1.4 
Patient’s Assessment of Arthritis Pain (PtAAP) .......................................48 
8.1.1.5 
Health Assessment Questionnaire-Disability Index (HAQ-DI) score.......48 
8.1.1.6 
Body surface area (BSA)-Psoriaris ...........................................................49 
8.1.2 
Primary analysis of the primary efficacy variable...............................................49 
8.1.3 
Secondary analyses of the primary efficacy variable ..........................................50 
8.1.4 
Supportive analyses of the primary efficacy variable..........................................51 
8.1.5 
Sensitivity analyses of the primary efficacy variable..........................................51 
8.2 
Statistical analysis of the secondary efficacy variables ...............................................52 
8.2.1 
Derivation of Psoriasis Area and Severity Index (PASI), PASI75, PASI90, and 
PASI100...............................................................................................................52 
8.3 
Analysis of other efficacy variables.............................................................................54 
8.3.1 
Minimal disease activity (MDA).........................................................................55 
8.3.1.1 
Modified MDA..........................................................................................56 
8.3.2 
Disease Activity Score-28 joint count C-reactive protein (DAS28[CRP]) .........56 
8.3.3 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).......................56 
8.3.4 
Modified Nail Psoriasis Severity Index (mNAPSI).............................................57 
8.3.5 
Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index .........................57 
8.3.6 
Leeds Dactylitis Index (LDI)...............................................................................57 
8.3.7 
Psoriatic Arthritis Impact of Disease-9 (PsAID-9)..............................................58 
8.3.8 
Psoriatic Arthritis Quality of Life (PsAQoL) ......................................................59 
8.3.9 
Short Form – 36 Items Health Survey.................................................................59 
8.3.10 
Hospital Anxiety and Depression Scale (HADS)................................................59 
8.3.11 
C-reactive protein (CRP) and high-sensitivity C-reactive protein (CRP) ...........60 
8.4 
Subgroup analysis ........................................................................................................60 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS ..........................................60 
9.1 
Pharmacokinetics .........................................................................................................60 
9.2 
Pharmacodynamics and Immunogenicity....................................................................61 
10 SAFETY ANALYSES.....................................................................................................62 
10.1 
Extent of exposure .......................................................................................................62 
10.2 
Adverse events.............................................................................................................65 
10.2.1 
Exposure duration................................................................................................67 
10.2.2 
Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER) ................................................................................................................67 
10.2.3 
AE of Special Interest and AE of Special Monitoring ........................................68 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 5 of 183
10.3 
Clinical laboratory evaluations ....................................................................................70 
10.4 
Potential drug-induced liver injury (PDILI) assessment .............................................72 
10.5 
Vital signs, physical findings, and other observations related to safety......................75 
10.5.1 
Vital signs ............................................................................................................75 
10.5.2 
Electrocardiograms..............................................................................................75 
10.5.3 
Other safety variables ..........................................................................................76 
Physical Examination ....................................................................................................76 
Assessment of Tuberculosis...........................................................................................76 
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)...................................76 
11 REFERENCES ................................................................................................................78 
12 APPENDICES .................................................................................................................80 
12.1 
Classification Criteria for Psoriatic Arthritis (CASPAR) Criteria...............................80 
12.2 
Calculation rules for duration of adverse events..........................................................80 
12.3 
Treatment group assignment for tables and figures.....................................................81 
12.4 
Hematology and biochemistry variables for the interim analysis................................83 
12.5 
Health Assessment Questionnaire-Disability Index (HAQ-DI) ..................................84 
12.6 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)...............................87 
12.7 
Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) questionnaire ...........88 
12.8 
Psoriatic Arthritis Impact of Disease-9 (PsAID-9)......................................................89 
12.9 
Psoriatic Arthritis Quality of Life (PsAQoL) ..............................................................91 
12.10 Short-Form (SF-36) Questionnaire..............................................................................95 
12.11 Classification of the SF-36 questionnaire..................................................................100 
12.12 Tuberculosis Questionnaire .......................................................................................102 
12.13 Identification of Opportunistic infections..................................................................102 
12.14 MedDRA algorithmic approach to anaphylaxis ........................................................103 
13 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN...............................106 
13.1 
Amendment 1.............................................................................................................106 
13.1.1 
Rationale for the amendment.............................................................................106 
13.1.2 
Modifications and changes ................................................................................106 
13.2 
Amendment 2.............................................................................................................113 
13.2.1 
Rationale for the amendment.............................................................................113 
13.2.2 
Modifications and changes ................................................................................113 
13.3 
Amendment 3.............................................................................................................124 
13.3.1 
Rationale for the amendment.............................................................................124 
13.3.2 
Modification and changes..................................................................................124 
13.4 
Amendment 4.............................................................................................................147 
13.4.1 
Rationale for the amendment.............................................................................147 
13.4.2 
Modification and changes..................................................................................147 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 6 of 183
13.5 
Amendment 5.............................................................................................................169 
13.5.1 
Rationale for the amendment.............................................................................169 
13.5.2 
Modification and changes..................................................................................169 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE...................................................183 
REDACTED COPY 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 7 of 183
LIST OF ABBREVIATIONS
AbAb
anti-bimekizumab antibody
ACR
American College of Rheumatology
ACR20,50,70
American College of Rheumatology 20, 50, 70% 
response criteria
ACP
above the cut point
ADR
adverse drug reaction
AE
adverse event
AJ
assessed joints
ALP
alkaline phosphatase
ANCOVA
analysis of covariance
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATC
anatomical therapeutic chemical
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BCP
below the cut point
BKZ
bimekizumab
BLQ
below the level of quantification
BMI
body mass index
BSA
body surface area
BUN
blood urea nitrogen
CASPAR
Classification Criteria for Psoriatic Arthritis
CCP
cyclic citrullinated peptide
cDBRS
corrected Dose-Blind Responder Set
CDF
cumulative distribution function
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 8 of 183
CDISC
Clinical Data Interchange Standards Consortium
cESS
corrected Escape Subject Set
CI
confidence interval
CL/F
total body clearance
CP
confirmed positive
CPK
creatine phosphokinase
CRP
C-reactive protein
CV
coefficient of variance
DAP
data analysis plan
DAS28(CRP)
Disease Activity Score-28 joint count C-reactive 
protein
DBS
Dose-Blind Set
DBRS
Dose-Blind Responder Set
DEM
data evaluation meeting
DMC
Data Monitoring Committee
ECG
electrocardiogram
eCRF
electronic case report form
eC-SSRS
electronic Columbia-Suicide Severity Rating Scale
EAER
exposure adjusted event rate
AEIR
exposure adjusted incidence rate
ES
Enrolled Set
ESS
Escape Subject Set
ET
early termination
FAS
Full Analysis Set
GGT
gamma glutamyltransferase
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 9 of 183
H
high
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale—Anxiety
HADS-D
Hospital Anxiety and Depression Scale—
Depression
HAQ-DI
Health Assessment Questionnaire – Disability Index
HBcAb-IgM
Hepatitis B core antibody-IgM
HBsAg
Hepatitis B surface antigen
HIV
human immunodeficiency virus
HLGT
High-Level Group Term
HLT
High Level Term
HRQoL
Health-Related Quality of Life
hs-CRP
high sensitivity C-reactive protein
INR
international normalized ratio
ITT
Intent-to-treat
IMP
investigational medicinal product
L
low
LCL
lower confidence limit
LD
loading dose
LDH
lactate dehydrogenase
LDI
Leeds Dactylitis Index
LEF
leflunomide
IgM
immunoglobulin M
LLN
lower limit of normal
LLOQ
lower limit of quantification
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 10 of 183
LOCF
last observation carried forward
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
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MTX
methotrexate
mNAPSI
modified Nail Psoriasis Severity Index
N
number of subjects
n
number of observations
N/A
not applicable
NCP
not confirmed positive
NRI
non-responder imputation
NRS
numerical rating scale
NSAID
nonsteroidal anti-inflammatory drug
OR
odds ratio
PASI
Psoriasis Area and Severity Index
PASI75, PASI90, PASI100
Psoriasis Area and Severity Index 75%, 90%, 100%
PCS
physical component summary
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 11 of 183
PD
pharmacodynamic
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
pharmacokinetic
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per-Protocol Set
PsA
psoriatic arthritis
PsAID-9
Psoriatic Arthritis Impact of Disease-9
PsAQoL
Psoriatic Arthritis Quality of Life
PT
preferred term
PtAAP
Patient’s Assessment of Arthritis Pain
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
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous(ly)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 12 of 183
SD
standard deviation
SE
standard error
SF-36
Short-Form 36-item Health Survey
SFU
Safety Follow-up
SJC
swollen joint count
SMQ
Standard MedDRA query
SOC
system organ class
SS
Safety Set
TEAE
treatment-emergent adverse event
TJC
tender joint count
TFLs
tables, figures, and listings
TNF
tumor necrosis factor
TNFα
tumor necrosis factor-alpha
TB
tuberculosis
UCL
upper confidence limit
ULN
upper limit of normal
V/F
volume of distribution
VAS
visual analog scale
WBC
white blood cell
WHO-DD
World Health Organization Drug Dictionary
Z
critical value from the standard normal distribution
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 13 of 183
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 PA0008. 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 (16 Dec 2016), 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 psoriatic arthritis (PsA) in order to guide the selection of doses and 
clinical indices in the Phase 3 development program.
The study population will consist of adult subjects (≥18 years of age) fulfilling the Classification 
Criteria for Psoriatic Arthritis (CASPAR, Table 12‒1) criteria and having active disease with 
tender joint count (TJC) ≥3 out of 78 and swollen joint count (SJC) ≥3 out of 76. Subjects must 
be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative and have 
active psoriatic lesion(s) and/or a documented history of psoriasis. Subjects may be tumor 
necrosis factor (TNF) inhibitor naïve or may have received 1 prior TNF inhibitor.
Subjects who have been on a TNF inhibitor previously must have:
x
experienced an inadequate response to previous treatment given for at least 3 months
x
been intolerant to administration (eg, had a side-effect/adverse event (AE) that led to 
discontinuation)
x
lost access to TNF inhibitor for other reasons
An estimated 70 sites in Europe and North America will randomize 200 subjects. Enrollment of
TNF inhibitor experienced subjects will be limited to 30% of the total study population.
The study consists of a Screening Period (14 to 28 days), Double-Blind Period (12 weeks), Dose-
Blind Period (36 weeks) and Safety Follow-up Period (20 weeks after last dose; 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 PsA.
2.1.2
Secondary objectives
The secondary objectives of the study are as follows:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 14 of 183
x
To assess the efficacy of the individual dose regimens of bimekizumab compared to placebo
x
To assess skin and nail psoriasis in the subgroup of affected subjects at Baseline
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 relates to efficacy and 
safety
2.1.3
Other objectives
Other objectives of the study are as follows:
x
To assess the impact on patient-reported quality of life
x
To assess the impact of bimekizumab treatment on axial disease
x
To assess the impact of bimekizumab on dactylitis and 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
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variable
The primary efficacy variable for this study is as follows:
x
American College of Rheumatology 50% (ACR50) response at Week 12
2.2.1.2
Secondary efficacy variable(s)
The secondary efficacy variables for this study are as follows:
x
American College of Rheumatology 20% (ACR20) response at Week 12
x
American College of Rheumatology 70% (ACR70) response at Week 12
x
Psoriasis Area and Severity Index 90% (PASI90) response at Week 12 in the subgroup of 
subjects with psoriasis involving at least 3% of body surface area (BSA) at Baseline/Day 1
x
Psoriasis Area and Severity Index 75% (PASI75) response at Week 12 in the subgroup of 
subjects with psoriasis involving at least 3% of BSA at Baseline/Day 1
2.2.1.3
Other efficacy variables
Other efficacy variables will be assessed as specified in Table 2‒1:
x
Time to ACR20 and ACR50 response
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 15 of 183
x
Psoriasis Area and Severity Index 100% (PASI100) response in the subgroup of subjects 
with psoriasis involving at least 3% of BSA at Baseline/Day 1
x
ACR20, ACR50, and ACR70 response
x
Composite endpoint comprised of ACR50 and PASI90 response in the subgroup of subjects 
with psoriasis involving at least 3% of BSA at Baseline/Day 1
x
Minimal Disease Activity (MDA) and modified MDA
x
Change from Baseline in the Disease Activity Score-28 based on high sensitivity C-reactive 
protein (DAS28 [CRP])
x
Change from Baseline in all individual American College of Rheumatology (ACR) score 
components:

SJC

TJC

Health Assessment Questionnaire—Disability Index (HAQ-DI)

Patient’s Assessment of Arthritis Pain (PtAAP)

Physician’s Global Assessment of Disease Activity (PhGADA)

Patient’s Global Assessment of Disease Activity (PGADA)

high sensitivity C-reactive protein (hs-CRP)
x
Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
x
Change from Baseline in the modified Nail Psoriasis Severity Index (mNAPSI)
x
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index
x
Change from Baseline in the Leeds Dactylitis Index (LDI)
x
Psoriatic Arthritis Impact of Disease (PsAID)-9
x
Psoriatic Arthritis Quality of Life (PsAQoL)
x
Change from Baseline in Physical Component Summary (PCS) and Mental Component 
Summary (MCS) of the SF-36 (Short-Form 36-Item Health Survey)
x
Change from Baseline in Hospital Anxiety and Depression Scale (HADS) HADS-Anxiety 
(A) and HADS-Depression (D) scores
x
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
2.2.2
Pharmacokinetic/pharmacodynamic variables
2.2.2.1
Pharmacokinetic variable
The PK variable is plasma concentration of bimekizumab. The assessment schedule for plasma 
concentration is available in Table 2‒1.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 16 of 183
2.2.2.2
Pharmacodynamic variables
The PD variables are concentrations of cytokines of relevance to IL 17A/F signaling pathway 
and PsA 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 metabolite biomarkers relevant to 
disease biology and progression, response to therapy, and the inflammatory and immune 
response processes.
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 AEs and serious adverse events (SAEs)
x
Withdrawal due to AEs
x
Change from Baseline in vital signs (blood pressure and 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
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:
x
Subject has a documented diagnosis of adult-onset PsA classified by CASPAR criteria with 
symptoms for at least 6 months prior to Screening with active PsA and must have at Baseline 
TJC ≥3 out of 78 and SJC ≥3 out of 76 (dactylitis of a digit counts as 1 joint each).
x
Subject must be rheumatoid factor and anti-CCP antibodies negative.
x
Subject must have active psoriatic lesion(s) and/or a documented history of psoriasis.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 17 of 183
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 3 months

been intolerant to administration (eg, had a side-effect/AE that led to discontinuation)

lost access to TNF inhibitor for other reasons
Two hundred subjects will be randomized to 1 of 5 treatment arms. Subjects in any treatment 
group who complete the 12-week Double-Blind Period will enter the 36-week Dose-Blind 
Period. Treatment during the Dose-Blind Period will start at Week 12 and be administered Q4W 
thereafter through Week 44.
Screening Period/ Baseline
During the Screening Period, the Investigator will obtain laboratory data and verify that the 
doses of methotrexate (MTX), leflunomide (LEF), nonsteroidal anti-inflammatory drugs 
(NSAIDs), or corticosteroids, if used, are stable. The Screening Period will also enable washout 
of medications not permitted for use during the study. The Screening Period will last 14 to 28 
days.
Double-Blind Period
During the Double-Blind Period, subjects will be randomized 1:1:1:1:1 (stratified by region and
prior TNF inhibitor exposure) to receive the following blinded study treatment regimens:
x
Placebo
x
Bimekizumab 16mg administered sc Q4W
x
Bimekizumab 160mg administered sc Q4W
x
Bimekizumab 320mg administered sc Q4W
x
Bimekizumab 320mg loading dose followed by 160mg administered sc starting at Week 4
and Q4W thereafter
Enrollment of TNF inhibitor experienced subjects will be limited to approximately 30% of the
total study population. 
Investigational medicinal product (IMP) will be administered sc in the clinic at Baseline, Week 
4, and Week 8. Additional non-dosing study visits in the Double-Blind Period 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. Note that the other assessments are planned to be performed before 
the IMP administration and will be analyzed for the Double-Blind Period.
Dose-Blind Period
The first IMP for the Dose-Blind Period will be administered at Week 12. At the Week 12 Visit, 
subjects will be allocated to bimekizumab treatment regimens as follows:
x
Subjects in the placebo group will be rerandomized 1:1 to bimekizumab 160mg or 
bimekizumab 320mg Q4W
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 18 of 183
x
Subjects in the bimekizumab 16mg dose group will be rerandomized 1:1 to bimekizumab 
160mg or bimekizumab 320mg Q4W
x
Subjects in the bimekizumab 160mg dose group will continue to receive bimekizumab 
160mg Q4W
x
Subjects in the bimekizumab 320mg dose group will continue to receive bimekizumab 
320mg Q4W
x
Subjects in the bimekizumab 320mg (loading)/160mg dose group will continue to receive 
bimekizumab 160mg Q4W
All assessments for the Dose-Blind Period will be done from Week 18 to Week 48. The last IMP 
administration is on Week 44.
The total duration of treatment is 36 weeks.
During the 36-week Dose-Blind Period, subjects will be evaluated for inadequate response to
treatment at defined time points. Subjects who do not show an improvement in tender and
swollen joint count will be eligible to receive rescue therapy as defined in Section 6.5.
Safety Follow-up/Extension study
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,
provided they do not qualify for rescue therapy.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 19 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
2
0
1
0/
2
4
1
1/
2
8
1
2/
3
2
1
3/
3
6
1
4/
4
0
15/
44
16/
48
Written Informed consent
X
Demographic data
X
PsA 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
PsAQoL
X
X
X
X
X
X
X
X
X
X
BASDAI
X
X
X
X
X
X
X
X
X
X
X
X
HAQ-DI
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 20 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
2
0
1
0/
2
4
1
1/
2
8
1
2/
3
2
1
3/
3
6
1
4/
4
0
15/
44
16/
48
PGADA
X
X
X
X
X
X
X
X
X
X
X
X
X
PsAID-9
X
X
X
X
X
X
X
X
X
X
Tuberculosis questionnaire
X
X
X
X
X
X
X
X
Height
X
Vital signs (pulse, 
temperature, BP)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
Physical examinatione
X
X
X
X
X
X
SJC and TJC
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA affected by PSO 
(BSA palm method)
X
X
X
X
X
X
PASIf
X
X
X
X
X
X
X
X
X
X
mNAPSI
X
X
X
X
X
X
MASES
X
X
X
X
X
X
X
X
X
X
LDI
X
X
X
X
X
X
X
X
X
X
PhGADA
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 21 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
2
0
1
0/
2
4
1
1/
2
8
1
2/
3
2
1
3/
3
6
1
4/
4
0
15/
44
16/
48
ECG
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
hs-CRPg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CRPg
X
X
X
X
Pregnancy testingh
X
X
X
X
X
Hepatitis B and C testing
X
HIV testing
X
RF, anti-CCP antibodies
X
Blood sample for 
bimekizumab plasma 
concentrationsi
X
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab antibody 
detectioni
X
X
X
X
X
X
X
X
X
X
X
Blood samples for 
cytokines, complement, 
and biomarker analysisi
X
X
X
X
X
X
X
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 22 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
2
0
1
0/
2
4
1
1/
2
8
1
2/
3
2
1
3/
3
6
1
4/
4
0
15/
44
16/
48
Blood samples for 
genomic, 
proteomic/metabolomics 
analysesi,j 
X
X
X
X
X
X
X
For participating centers: 
Blood samples for flow 
cytometryi
X
X
X
X
X
X
X
Blood samples for 
genetic/epigenetic 
analysisi,j
X
X
X
X
IGRA Tuberculosis testk
X
X
X
X
Evaluation for rescuel
X
X
X
Chest x-raym
X
Hand and foot x-raysn
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
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BP=blood pressure; BSA=body surface area; CCP= cyclic citrullinated peptide; 
CRP=C-reactive protein; eCRF=electronic Case Report Form; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 23 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
2
0
1
0/
2
4
1
1/
2
8
1
2/
3
2
1
3/
3
6
1
4/
4
0
15/
44
16/
48
ET=Early Termination; HADS=Hospital Anxiety and Depression Scale; HAQ-DI=Health Assessment Questionnaire—Disability Index; HIV=human 
immunodeficiency virus; hs-CRP=high sensitivity CRP; IGRA=interferon gamma release assay; IMP=investigational medicinal product; IXRS=interactive 
voice or web response system; mNAPSI=modified Nail Psoriasis Severity Index; LDI=Leeds Dactylitis Index; PASI=psoriasis area severity index; 
PGADA=Patient’s Global Assessment of Disease Activity; PhGADA=Physician’s Global Assessment of Disease Activity; PsA=psoriatic arthritis; 
PsAID=Psoriatic Arthritis Impact of Disease; PsAQoL=Psoriatic Arthritis Quality of Life; PSO=psoriasis; PtAAP=Patient’s Assessment of Arthritis Pain; 
RF=rheumatoid factor; SF-36=short form-36; SFU=Safety Follow-Up; SJC=swollen joint count; TB=tuberculosis; TJC=tender joint count
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 Safety Follow-up 
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, 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 and risk for exposure to TB.
f PASI will be assessed in all subjects with Baseline/Day 1 BSA affected by PSO ≥3% as determined by the BSA palm method.
g High sensitivity-CRP is performed at Screening, Baseline, and all other study visits as marked with an X. CRP will be performed at Baseline, Week 4, 
Week 12, and Week 24 only. After Screening, the 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 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. 
j  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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 24 of 183
Table 2‒1:
Schedule of assessments
Visita/
Week
Protocol 
activity
Screening (V1) (14-
28 days)
Baseline 
(Day 1, V2)
(first dose)
Double-Blind Period
(weeks after first 
dose)
Dose-Blind Period
(weeks after first dose)
ET
SFU
b
3
/
1
4/
2
5/
4
6/
8
7/
12
8/
16
9/
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0
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3
6
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4
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16/
48
k  It is recommended that Quantiferon TB GOLD test be performed. 
l  At Weeks 16, 24, and 36, subjects will be evaluated for inadequate response to treatment. Subjects who do not show an improvement in tender and swollen 
joint counts will be eligible to receive rescue therapy.
m
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.
n Hand and foot x-rays are not required if the subject has hand and/or foot x-rays (only hand OR foot is required) that are no more than 2 years from the date 
of Screening, and are available for submission within the Screening Period to the central radiology reader and whose reading is consistent with CASPAR 
Criteria #5 showing ill-defined ossification near joint margin (but excluding osteophyte formation). For those subjects without prior x-rays that meet this 
Criterion and those whose submitted films are not read with changes consistent with CASPAR, hand and foot x-rays may be done during the Screening 
Period.
o IXRS is used to register the Subject at Screening, randomize the Subject at Baseline/Day 1, rerandomize the Subject at Week 12 (Subjects in the placebo or 
bimekizumab 16mg 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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 25 of 183
2.4
Determination of sample size
A total of 200 subjects (40 in each treatment group) are planned to be randomized in this study. 
The sample size is calculated based on the ACR50 response data from the Phase 2 bimekizumab 
study in subjects with PsA (PA0007). The ACR50 responses at Week 12 were reported to be 
80.0% (95% CI: 37.6%; 96.4%), 52.6% (95% CI: 31.7%; 72.7%), and 33.3% (95% CI: 9.7%; 
70.0%) for the bimekizumab 560/320mg, bimekizumab 240/160mg, and bimekizumab 80/40mg 
doses, respectively. Placebo ACR50 response at Week 12 is based on the PA0007 study (0%), 
the FUTURE 1 study (8.0%; Mease et al, 2015) and FUTURE 2 study (6.0%; McInnes et al, 
2015).
Since the uncertainty of ACR50 responder rates of PA0007 is high due to the small number of 
subjects, the midpoint of the point estimate and the lower 95% CI was used for the sample size 
calculation of all active dose groups as a conservative assumption. For the bimekizumab 16mg 
dose, the midpoint of the 80/40mg dose was reduced by 6.5%.
Hence, ACR50 responder rates of 58.5%, 42.2%, 15.0%, and 8% at the end of a 12-week 
treatment period for bimekizumab 320mg, bimekizumab 160mg, bimekizumab 16mg, and 
placebo have been assumed, respectively. Since those ACR50 responder rates are based on a 
study population of TNF inhibitor naïve subjects, an adjustment was made for a reduction in 
ACR50 response of 25% by a maximum of 30% of subjects with TNF inhibitor experience (ie, 
12 subjects per group).
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. With 40 subjects in each treatment group, the test for detecting 
the overall dose response based on ACR50 response is powered at >99%.
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 26 of 183
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 will be presented in tables from left to 
right will be 
x
Placebo
x
Bimekizumab 16mg
x
Bimekizumab 160mg
x
Bimekizumab 160mg with loading dose 320mg
x
Bimekizumab 320mg
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 Section 12.3.
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: 
x
Placebo to bimekizumab 160mg at Week 12
x
Placebo to bimekizumab 320mg at Week 12
x
Bimekizumab 16mg to bimekizumab 160mg at Week 12
x
Bimekizumab 16mg to bimekizumab 320mg at Week 12
x
Bimekizumab 160mg with loading dose 320mg to bimekizumab 160mg at Week 12
x
Bimekizumab 160mg
x
Bimekizumab 320mg
The abbreviation for bimekizumab is BKZ and will be used in tables and listings headers. In the 
TFLs subjects on bimekizumab 160mg with loading dose 320mg will be displayed as “BKZ 
160mg w/LD”. All subjects on bimekizumab will be labeled as “All BKZ” in the TFLs. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 27 of 183
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), variable (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 fist 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 
x
Dose-Blind treatment period: starts at the Week 12 visit, ends at Week 48 visit.
x
Post-treatment period: the post-treatment period (Follow-up period) is the period after the 
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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 28 of 183
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 CRP and 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.
3.6
Analysis sets
The primary efficacy variable will be analyzed for all subjects in the Full Analysis Set (FAS). 
The supportive analyses for the primary efficacy variables will include the Randomized Set (RS) 
and PPS. 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 PK-
PPS. PD variables will be analyzed for all subjects in the 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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 29 of 183
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.
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 consists of all randomized subjects.
3.6.3
Safety Set (SS)
The SS consists of all randomized subjects who received at least 1 dose of the IMP.
3.6.4
Full Analysis Set (FAS)
The FAS consists of all randomized subjects who received at least 1 dose of the IMP and have 
valid measurement of the primary efficacy variable at Baseline.
3.6.5
Per-Protocol Set (PPS)
The PPS consists 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.
3.6.7
Pharmacodynamics Per-Protocol Set (PD-PPS)
The PD-PPS consists of all randomized subjects who took at least one dose of the IMP and 
provided at least 1 PD measurement post-dose that is without important protocol deviation 
affecting that time point.
3.6.8
Dose-Blind Set (DBS)
The DBS consists of all subjects who started the Dose-Blind Period and who received at least 1 
dose of IMP during the Dose-Blind Period.
3.6.9
Escape Subject Set (ESS)
The ESS consists of all subjects who started 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 SJC and TJC at Week 16, Week 24, or Week 36.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 30 of 183
3.6.10
Dose-Blind Responder Set (DBRS)
The DBRS consists of all subjects who started 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 SJC and TJC 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
x
SS: actual treatment
x
FAS: planned treatment
x
PPS: planned treatment
x
PK-PPS: actual treatment 
x
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x
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actual treatment 
x
ESS: planned treatment
x
DBRS: planned treatment 
x
cESS: planned treatment
x
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 31 of 183
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.
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 (SOC) and preferred term (PT). 
All AEs will be classified by primary SOC, 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
The PK variables total body clearance (CL/F) and volume of distribution (V/F) will be analyzed 
separately. CL/F and V/F variables were removed from the PK variable list. 
Following two subgroup analyses were added: time since first diagnosis of PsA and body weight.
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. 
The other efficacy variable modified MDA was added to the analysis. The definition for the 
modified MDS is available in Section 8.3.1.
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. 
Two addition analyses were added in the section analysis of other efficacy variables. A 
frequencies table counting the number of subjects with PSAID-9 ≤ 3 as well as cumulative 
distribution function (CDF) plots of PSAID-9 change from Baseline to Week 12 and Week 12 to 
Week 48 by treatment group.
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 
who has discontinued Double-Blind study treatment prior to Week 12 will be counted as a non-
responder. 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 32 of 183
Sensitivity analysis will be performed for the secondary analysis of the primary variable (ACR50 
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 ACR 
components at each post-Baseline visit where ACR 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 ACR 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 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 
ACR components (eg, HAQ-DI [0-3]) 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.
2. The ACR50 response will be calculated using the complete datasets. That is, the values of the 
ACR components at Week 12 based on the complete datasets will be compared to their 
corresponding Baseline values to calculate an ACR50 response for each subject (as described 
in Section 8.1.1). Each complete imputed data set will then be analyzed based on a logistic
regression model with factors of treatment group, geographic region, and prior TNF inhibitor 
exposure as fixed effects.
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). 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 33 of 183
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals (CIs) 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
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where UCL and LCL are the upper and lower confidence limit, respectively, for the CI 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% CI). 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
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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 and Zα/2 is the relevant critical value from the standard normal 
distribution (1.96 for a 95% CI). These calculations will be done such that odds ratios and 
corresponding CIs 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 ACR components), and all continuous 
secondary efficacy variables will use the same MI 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.
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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
PA0008
Confidential
Page 34 of 183
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 AE
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
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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:
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
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.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 35 of 183
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,
x
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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
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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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x
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the year of the start date.
x
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x
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switch treatment, then use the date of first switch treatment.
x
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 36 of 183
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 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.
Imputation of Partial Stop Dates:
x
If only the month and year are specified, then use the last day of the month,
x
If only the year is specified, then use December 31st of that year.
x
If the stop date is completely unknown, do not impute the stop date.
There will be no imputation of any other missing data.
4.3
Interim analysis 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 ACR and PASI 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. The TFL shells for the 
interim and final analysis will be provided in two different documents. 
The interim analysis will summarize disposition, demographics, PsA history, Baseline 
characteristics, PsA 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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 37 of 183
hematology and biochemistry variables will be provided as listed in Table 12‒4. 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 analysis. In addition, summary tables for the primary and 
secondary efficacy variables, the ACR components, and MDA will be provided. Categorical 
variables will be summarized using frequency tables by each visit. 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 ACR50 response and ACR20 response will 
be summarized and plotted as described in Section 8.3.
PK and AbAb data will be analyzed in the interim analysis as described in Section 9.1 and 
Section 9.2 .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 24. 
The data up to Week 24 may include partial results up to the time the database for Week 12 was 
locked for ongoing subjects. Following variables will be analyzed: primary and secondary 
efficacy variables, ACR components, MDA, PK, AbAb, TEAEs, biochemistry and hematology 
laboratory results, and Hy’s Law. It depends on the variable how those additional time points 
will be presented in the interim analysis. 
The efficacy analyses and the plasma concentration analyses for the period between Week 12 
and Week 24 are only for those treatment groups that are not rerandomized. Two summary tables 
for each of the primary and secondary efficacy variables, the ACR components, and MDA 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 24 by the following treatment groups: bimekizumab 
160mg and bimekizumab 160mg with loading dose 320mg, and bimekizumab 320mg. The 
summary table for plasma concentration will present only data up to Week 12 for the Baseline 
treatment groups Placebo and bimekizumab 16mg. Data up to Week 24 will be presented for 
bimekizumab 160mg, bimekizumab 160mg with loading dose 320mg, and bimekizumab 320mg. 
All Listings which include data up to Week 24 will use the same approach as for plasma 
concentration tables. 
The safety analysis (TEAEs, biochemistry and hematology laboratory results, and Hy’s Law) 
will be handled as follows: Two summary tables for each of the safety analysis 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 24 and will also present subjects under their Baseline treatment 
group. For the second table any event/finding that is unique to a treatment group should only be 
presented in the “All subjects” column and the treatment columns should remain blank. 
Following rules will be applied for the TEAEs: If the relative TEAE start date is less or equal to 
84 (12*7) days, then the TEAE will be presented in the up to Week 12 table. If the relative start 
date is less or equal to 168 (24*7) days, then the TEAE will be presented in the up to Week 24 
table. 
The treatment group information will not be displayed for the interim listings.
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 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 38 of 183
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 
bimekizumab dosing regimen until the subject completes the Dose-Blind Period at Week 48.
Further details are available in the PA0008 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 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 fourth 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
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 39 of 183
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.
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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 40 of 183
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.
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. 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 PA0008 interim analysis Week 48 will occur before all subjects have 
completed the PA0008 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 fourth 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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 41 of 183
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.
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 to <65 years, ≥65 years)
x
Gender (male, female)
x
Geographic region (North America, Europe)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
x
Prior TNF inhibitor exposure (yes, no)
x
Treatment-emergent AbAb status (positive, negative)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 42 of 183
x
Extent of psoriasis involvement (<3%, ≥3% to <10%, ≥10%)
x
hs-CRP level (<= upper limit normal, > upper limit normal)
x
Time since first diagnosis of PsA (< 2 years, ≥ 2 years)
x
Body weight (<100 kg, ≥100 kg)
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.
The derivation of time since first diagnosis of PsA is described in Section 6.2.
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 and DBS. 
The table using RS will analyze subjects for the complete study as well as the Double-Blind 
Period. Completed study is defined as completed the 12-week Double-Blind Period and the 36-
week Dose-Blind Period including the safety follow-up visit. Subjects will be allocated to the 
treatment group at Baseline. The table using DBS will only summarize subjects in the Dose-
Blind Period. 
Study eligibility criteria will be listed and a separate listing of subjects who did not meet the 
eligibility criteria will be presented.
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 and Baseline 
treatment groups.
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 43 of 183
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, body mass 
index (BMI), country, and geographic region. Age and BMI will be summarized as a continuous 
variable and as categorical variables. Age will be combined based on the following categories: 
≤18, 19-<65, ≥65 years (clinicaltrials.gov requirement), 18-<65, 65-<85, ≥85 years (EudraCT 
requirement), and 18-<45, ≥45-<65, ≥65 years. BMI will be summarized based on the following 
categories: <25, 25-<30, ≥30 kg/m2.
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the formula:
For adults:
ܤܯܫൌܹ݄݁݅݃ݐ
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(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.
A frequency table for Lifestyle will be presented as well as a corresponding listing. Data 
collected in the CRF for subject’s childbearing potential and birth control 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
PsA history will be summarized for subjects in the FAS and SS including the time since first 
diagnosis of PsA, age at first diagnosis date, and PsA subtype (polyarticular – symmetric 
arthritis, oligoarticular – asymmetric arthritis, distal interphalangeal, joint predominant, 
spondylitis predominant, arthritis mutilans). Time since first diagnosis will be summarized as a 
continuous variable and as categorical variables based on following categories: <2, ≥2 years. The 
history will be listed for all subjects in the RS.
Time since first diagnosis of PsA will be calculated as:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܫ݂݊݋ݎ݉݁݀ܥ݋݊ݏ݁݊ݐെܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ൅ͳ
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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).
Age at first diagnosis will be calculated as:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 44 of 183
ܣ݃݁ܽݐ݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏൌܦܽݐ݁݋݂݂݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏെܦܽݐ݁݋݂ܾ݅ݎݐ݄
͵͸ͷǤʹͷ
(7)
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
TJC
x
SJC
x
hs-CRP
x
Rheumatoid factor 
x
Anti-CCP antibodies
x
Prior NSAID therapy, and prior anti-TNF therapy
x
Psoriasis BSA
x
Nail psoriasis
x
Dactylitis
x
NSAID therapy
x
Synthetic DMARDs
x
MTX
x
Sulfasalazine
x
Hydroxychloroquine
A rheumatoid factor value < 15 IU/mL is defined as negative and a value ≥ 15 IU/mL is defined 
as positive. Anti-CCP antibodies negative is a value < 5 U/mL and a value ≥ 5 U/mL is defined 
as positive.
For hs-CRP following rules will be applied: 
x
If Baseline hs-CRP values are missing, then take the Screening hs-CRP values. 
x
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The corresponding listings will be presented for the RS.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 45 of 183
6.3
Medical history and concomitant diseases
Medical history and ongoing medical conditions will be summarized by MedDRA 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. 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). 
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 both summary tables and the RS will be used for the listings.
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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 46 of 183
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 and 160mg with loading dose, 
bimekizumab 320mg, and all bimekizumab. Treatment compliance for the bimekizumab 160mg 
and 160mg with loading dose group will be calculated for the time the subject receives 160mg or 
160mg with loading dose, 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 same approach will be done for bimekizumab 320mg. 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 primary ACR score and response
ACR20/50/70 response represents at least 20%, 50%, or 70% respective improvement from 
Baseline for each of the following:
x
TJC (based on 78 joints)
x
SJC (based on 76 joints)
x
At least 3 of the 5 remaining core set measures

Disease activity as assessed by PGADA

Disease activity as assessed by PhGADA

Pain as assessed by PtAAP

Physical function as assessed by the HAQ-DI

Acute phase response as assessed by the hs-CRP
For all non-missed visits, if any of the component scores are missing, then those scores will be 
considered as not having met the criteria for improvement for the respective component. For 
component scores with a Baseline value of 0, the percentage improvement is not calculable and 
is treated as missing. However, if ACR20, ACR50, or ACR70 response is used as the primary 
endpoint in a study, consideration should be given to requiring a value >0 for each of the 
component endpoints in order to enter the study. For component scores with a Baseline value >0 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 47 of 183
and a post-Baseline value of 0, percentage improvement will be calculated as for any other non-
missing data.
Missing items for TJC, SJC, and HAQ-DI will be handled as described in Section 8.1.1.1 and 
Section 8.1.1.5.
8.1.1.1
Tender joint count (TJC) and swollen joint count (SJC)
8.1.1.1.1
78/76 joint evaluation for ACR response
The Principal Investigator, another delegated physician, or an appropriately qualified medical 
professional (based on local requirements) who has had documented training on how to perform 
these assessments correctly assesses the following joints for tenderness: the distal 
interphalangeal, proximal interphalangeal and metacarpophalangeal joints of the hands, and 
metatarsophalangeal joints of the feet, the carpometacarpal and wrist joints (counted separately), 
the elbows, shoulders, acromioclavicular, sternoclavicular, hip, knee, talo-tibial, and 
midtarsaljoints. All of these except for the hips are assessed for swelling.
Artificial and ankylosed joints, as well as missing joints (ie, amputated joints), are excluded from 
both tenderness and swelling assessments.
One dactylitic digit is to be counted as 1 swollen joint (instead of counting as 3 in the finger or 2 
in the toe).
Table 8‒1 summarizes the swelling and tenderness grading criteria.
Table 8‒1:
Swelling and tenderness grading
The tender joint counts (TJC) and swollen joint counts (SJC) are weighted joint counts. If there 
are missing observations in the tender or swollen joint assessments, then the remaining 
observations will be assessed and weighted by the number of the assessed joints (AJ): 
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where n is the number of total joints. If a joint is missing at Baseline, then that joint is set to 
missing throughout the study. If more than 50% of the tender joint assessments or 50% of the 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 48 of 183
swollen joint assessments are missing at the time of a given assessment, then no imputation will 
be done and the total TJC or SJC will be set to missing for that visit.
Injected joints will be counted as swollen and tender from the date of injection up to 52 weeks 
after injection, ie, swelling and tenderness grading is 1.
8.1.1.1.2
28 joint evaluation for determination of DAS28(CRP)
The following 28 joints will be used for calculation of the DAS28(CRP).
x
Upper extremity (26)-bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal and 
carpometacarpal bones considered as a single unit), MCP I, II, III, IV, and V, thumb 
interphalangeals (IP), PIP II, III, IV, and V
x
Lower extremity (2)-knees
Injected joints will be counted as swollen and tender from the date of injection up to 52 weeks 
after injection, ie, swelling and tenderness grading is 1.
8.1.1.2
Patient’s Global Assessment of Disease Activity (PGADA)
Subjects will score their Global Assessment of Disease Activity using a visual analog scale 
(VAS) where 0 is “very good, no symptoms” and 100 is “very poor, severe symptoms”. The 
subject should be asked to consider both joint and skin components in their response to this 
question.
8.1.1.3
Physician’s Global Assessment of Disease Activity (PhGADA)
The Investigator will assess the overall status of the subject with respect to their PsA signs and 
symptoms and functional capacity (considering both joint and skin components) using a 
numerical rating scale (NRS) where 0 is “very good, asymptomatic and no limitation of normal 
activities” and 100 is “very poor, very severe symptoms which are intolerable and inability to 
carry out all normal activities”.
8.1.1.4
Patient’s Assessment of Arthritis Pain (PtAAP)
The PtAAP VAS is part of the ACR core set of measures in arthritis (Felson et al, 1993). 
Subjects will assess their arthritis pain using a VAS where 0 is “no pain” and 100 is “most severe 
pain”.
8.1.1.5
Health Assessment Questionnaire-Disability Index (HAQ-DI) score
The HAQ-DI contains 20 items divided into 8 domains that measure: dressing and grooming (2
items), arising (2 items), eating (3 items), walking (2 items), hygiene (3 items), reach (2 items),
grip (3 items), and common daily activities (3 items). The questionnaire is available in the
Appendix Section 12.5. Subjects are required to indicate the degree of difficulty they have 
experienced in each domain in the past week on a 4-point scale that ranges from 0 (without 
difficulty) to 3 (unable to do). The highest score in each category is then summed (0 to 24) and 
divided by the number of categories scored to give a score that ranges from 0 to 3.
Any individual score of less than 2 is adjusted to 2 if the activity requires assistance from another 
individual or the use of an assistive device. If the category score is already a 2, and a device 
related to that category is used, or help from another person is provided for the category, the
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 49 of 183
score for that category remains 2. The following list details how each aid and device is 
associated with the category scores (Table 8‒2):
Table 8‒2:
Aid or Device associated with HAQ-DI domain
If all questions within a given category are unanswered, no score will be provided for that 
category (this rule applies even if aids and devices are non-missing). The HAQ-DI will be 
calculated by dividing the sum of the category scores by the number of categories with at least 1 
question answered. If fewer than 6 categories have responses, no disability score will be 
calculated. A lower HAQ disability score indicates an improvement in function.
8.1.1.6
Body surface area (BSA)-Psoriaris
The BSA palm method will be used for the evaluation of BSA affected by psoriasis as follows:
The subject’s hand, including the palm, fingers and thumb, is used as the reference point for 
measuring how much of their skin is affected by psoriasis, representing roughly 1% of the body’s 
surface.
x
Subject’s palm=1%
x
Head and neck=10% (10 palms)
x
Upper extremities=20 % (20 palms)
x
Trunk=30% (30 palms)
x
Lower extremities=40 % (40 palms)
Total BSA=100%.
8.1.2
Primary analysis of the primary efficacy variable
The primary efficacy variable (ACR50 at Week 12) will be analyzed for all subjects in the FAS. 
The dose-response relationship between treatment and ACR50 response will be assessed with an 
ordered categorical analysis using a nonparametric correlation statistic of Mantel and Haenszel 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 50 of 183
(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 as stratification 
factors. Prior TNF inhibitor exposure will be used as a stratification factor as it may have an 
impact on efficacy. The use of geographic region as a stratification factor is intended to combine 
study centers in similar geographic regions. The geographic regions are defined in Section 3.8.
The correlation between dose and ACR50 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.
Bimekizumab 160mg with loading dose will be excluded from the dose-response analysis. A
table will present the responder rates for placebo, BKZ 16mg, 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 in the primary analysis. That is, subjects with a 
missing ACR 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 ACR50 response. The model 
will include fixed effects for treatment, geographic region, and prior TNF inhibitor exposure 
(yes/no). 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% CI, and the corresponding p-value will be calculated. In addition, a comparison 
will be made for the bimekizumab 320mg loading dose followed by bimekizumab 160mg Q4W 
versus bimekizumab 160mg Q4W using the same logistic model described above.
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. 
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 160mg w/ LD, BKZ 
160mg, BKZ 320mg, and for each dose the odds ratios (differences to placebo), 95% CIs, and 
corresponding p-values from the logistic regression.
NRI will be used to account for missing data in the primary analysis. That is, subjects with a 
missing ACR score at Week 12 or who discontinued study treatment prior to the Week 12 visit 
will be considered non-responders for the primary analysis.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 51 of 183
8.1.4
Supportive analyses of the primary efficacy variable
The following supportive analyses 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 ACR components (ie, TJC, SJC, PGADA, PhGADA, 
PtAAP, HAQ-Di, and hs-CRP) will be analyzed using the ANCOVA with treatment group, 
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 160mg w/ LD, 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% CIs, 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 ACR50 response are not collected, the subject 
will be assumed to be a non-responder. 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. 
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 52 of 183
The following sensitivity analyses will be performed for the supportive 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 ACR components will be 
imputed individually and then the ACR 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, geographic 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, ACR20/70 response and PASI75/90 response) will be analyzed for 
treatment effects using pairwise comparisons using the same logistic model as described in the 
secondary analysis of the primary variable (Section 8.1.3).
The responder rates for placebo, BKZ 16mg, BKZ 160mg w/ LD, BKZ 160mg, BKZ 320mg, 
and for each dose the odds ratios (differences to placebo), 95% CIs, and corresponding p-values 
from the logistic regression will be provided.
The categorical efficacy variables will be analyzed using observed cases as treated and imputed 
with NRI.
8.2.1
Derivation of Psoriasis Area and Severity Index (PASI), PASI75, 
PASI90, and PASI100
PASI will be assessed in all subjects with Baseline BSA affected by psoriasis ≥3% determined 
by the method described in Section 8.1.1.6 (ie, the BSA palm method).
The PASI is the most commonly used and validated assessment for grading the severity of 
psoriasis in clinical studies (Feldman, 2004). The PASI quantifies the severity and extent of the
disease and weighs these with the percentage of BSA involvement.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 53 of 183
Table 8‒3:
Body areas for calculation of percent BSA for PASI
Body area
Details of area
BSA
Degree of involvement 
of body areaa
Head
Face, back of head
10%
0 to 6
Upper limbs
Left, right, upper lower, flexor
surface, extensor surface
20%
0 to 6
Trunk
Front, back, groin
30%
0 to 6
Lower limbs
Left, right, upper lower, flexor
surface, extensor surface, including
buttocks
40%
0 to 6
Total
100%
BSA=body surface area; PASI=Psoriasis Area and Severity Index
a Where 0=none; 1=1% to <10% affected, 2=10% to <30% affected, 3=30% to <50% affected, 4=50% to <70% 
affected, 5=70% to <90% affected, 6=90% to 100% affected
The body is divided into 4 sections (head (h) (10% of a person's skin); arms (a) (20%); trunk (t) 
(30%); legs (l) (40%), Table 8‒3). Each of these sections is scored by itself, and then the 4 scores 
are combined into the final PASI. For each section, the percent of area of skin affected (A), is 
estimated and then transformed into a grade from 0 to 6:
x
0% of involved area, grade: 0 
x
< 10% of involved area, grade: 1 
x
10-29% of involved area, grade: 2 
x
30-49% of involved area, grade: 3 
x
50-69% of involved area, grade: 4 
x
70-89% of involved area, grade: 5 
x
90-100% of involved area, grade: 6
Within each body area, the severity is estimated by three clinical signs: redness (R), thickness 
(T), and scaliness (S) (each on a 5-point scale): 0=none, 1=slight, 2=moderate, 3=marked, and 
4=very marked. The PASI is a measure of the average redness, thickness, and scaliness of the 
psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, 
and weighted by the percentage person’s skin for the respective section:
ܲܣܵܫൌͲǤͳ כ ܣ݄כ ሺܴ݄൅݄ܶ൅݄ܵሻ൅ͲǤʹ כ ܣݑכ ሺܴݑ൅ܶݑ൅ܵݑሻ൅ͲǤ͵ כ ܣݐ
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 54 of 183
Th, Tu, Tt, and Tl is the thickness score of plaques on the head, upper limbs, trunk, and lower 
limbs;
Sh, Su, St, and Sl is the scaliness score of plaques on the head, upper limbs, trunk, and lower 
limbs;
Ah, Au, At, and Al is the degree of involvement for the head, upper limbs, trunk, and lower 
limbs.
The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.
In case up to 2 severity measurements are missing for a certain region, the average of the 
remaining will be utilized to substitute the missing(s). If the area of affected skin and/or all 
severity measurements for up to 2 body areas are missing, missing (R+T+S) x A for a body area 
will be substituted by the average of the available (R+T+S) x A. Otherwise the PASI will be set
to missing.
The PASI50, PASI75, PASI90, and PASI100 responses are based on at least 50%, 75%, 90%, 
and 100% improvement from Baseline in the PASI score. 
8.3
Analysis of other efficacy variables
All other efficacy variables will be analyzed for all subjects in the FAS, DBRS, ESS, cDBRS, 
cESS, and DBS.
All binary variables will be summarized 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.
Subgroup of subjects will be used for the analyses of mNAPSI, MASES, and LDI. The MASES 
will be analyzed for subjects with enthesitis at Baseline (MASES > 0). The LDI will be 
summarized for subjects with dactylitis at Baseline (LDI > 0) and the mNAPSI will be analyzed 
on a subgroup of subjects with nail disease at Baseline (mNAPSI > 0). 
CDF plots of PSAID-9 change from Baseline to Week 12 and from Week 12 to Week 48 by 
treatment group will be presented as well as a frequency table with number of subjects with 
PSAID-9 ≤ 3.
Times series plots will be provided for the response rate for the primary and secondary efficacy 
variables. The plots will show the weekly response rate over the first 12 weeks.
Time to onset of ACR20/50 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.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 55 of 183
The median time to response including the two-sided 95% CI 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 ACR20 response and ACR50 response 
including following information: number of subjects achieving ACR20/ACR50 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 multiple imputation for categorical/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 ACR50 and PASI90 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 ACR50 and 
PASI90 responders is comparable as assessed by overlapping 95% confidence intervals, the 
potential bias is estimated to be at minimum.
8.3.1
Minimal disease activity (MDA)
MDA is a state of disease activity deemed a useful target of treatment by both the patient and 
physician, given current treatment possibilities and limitations. Criteria shown in Table 8‒4
covering all of the domains of the disease have been developed to determine whether or not 
patient has reached MDA based on key outcome measures in PsA. A subject is considered as 
having MDA if 5 or more of the following 7 criteria in Table 8‒4 are fulfilled:
Table 8‒4:
MDA criteria in PsA
A subject is classified as in MDA when they meet 5 of 7 of the following criteria:
TJC ≤1
SJC ≤1
PASI ≤1 or BSA ≤3
PtAAP ≤15
PGADA ≤20
HAQ-DI ≤0.5
Tender enthesial points ≤1
BSA=body surface area; HAQ=Health Assessment Questionnaire; MDA=minimal disease activity; PASI=Psoriasis 
Area and Severity Index; PGADA=Patient’s Global Assessment of Disease Activity; PtAAP=Patient’s Assessment 
of Arthritis Pain; SJC=swollen joint count; TJC=tender joint count
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07 Sep 2018
Statistical Analysis Plan
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PA0008
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Page 56 of 183
Following rule will be applied for subjects with BSA < 3 at Baseline due to missing post-
Baseline measurements for BASI and PASI: Subjects with BSA < 3 will always meet the criteria 
PASI ≤ 1 or BSA ≤ 3.
The MASES items will be used to check whether a subject has less or equal one tender enthesial 
point.
8.3.1.1
Modified MDA
Subjects are classified as in modified MDA when they meet the criteria PASI ≤ 1 or BSA ≤ 3 
and 4 of the following criteria: TJC ≤1, SJC ≤ 1, PtAAP ≤ 15, PGADA ≤ 20, HAQ-DI ≤ 0.5 or 
tender enthesial points ≤ 1. The difference between the MDA and the modified MDA is that the 
PASI/BSA criteria is a mandatory criteria.
8.3.2
Disease Activity Score-28 joint count C-reactive protein 
(DAS28[CRP]) 
The components for DAS28(CRP) include the TJC and SJC based on 28 joints, hs-CRP (mg/L),
and the PGADA (mm). DAS28(CRP) is calculated as follows:
ܦܣܵʹͺሺܥܴܲሻൌͲǤͷ͸ כ ඥܶܬܥ൅ͲǤʹͺ כ ඥܵܬܥ൅ͲǤͲͳͶ כ ܲܩܣܦܣ൅ͲǤ͵͸
כ ሺ݄ݏܥܴܲ൅ͳሻ൅ͲǤͻ͸
(12)
The hs-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.
8.3.3
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is the most commonly used instrument to measure the disease activity of 
ankylosing spondylitis. 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: fatigue, spinal pain, 
peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) 
over the last week. The BASDAI questionnaire is available in the Appendix Section 12.6. To
give each symptom equal weighting, the average of the 2 scores relating to morning stiffness 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:
ܤܣܵܦܣܫൌ
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07 Sep 2018
Statistical Analysis Plan
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Page 57 of 183
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.
8.3.4
Modified Nail Psoriasis Severity Index (mNAPSI)
Subjects with psoriatic nail disease will have a target nail selected at the Baseline visit for 
evaluation using the mNAPSI. The nail selected should be the most affected nail observed at 
Baseline and should be the only one assessed throughout the study. The target nail will be scored 
(0 to 3) for onycholysis/oil drop dyschromia, nail plate crumbling, and pitting and will be scored 
(0 for “no” or 1 for “yes”) for leukonychia, nail bed hyperkeratosis, splinter haemorrhages and 
red spots in the lunula. The score for an individual nail ranges from 0 to 13 with higher scores 
indicative of more severe nail disease. Subjects with nail disease at Baseline are defined as those 
with a mNAPSI score >0 at Baseline.
If 1 or 2 response items scored on the 0 to 1 scale are missing, the missing response(s) will be 
imputed by the average of the available responses. Otherwise, the total mNAPSI score will be set 
to missing.
8.3.5
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 
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 12.7.
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.
8.3.6
Leeds Dactylitis Index (LDI)
Dactylitis, the swelling of an entire digit related to articular and periarticular inflammation, is a 
characteristic of inflammatory spondyloarthropathies, including PsA. Presence of dactylitis will 
be assessed using the LDI basic which evaluates for a ≥10% difference in the circumference of 
the digit compared to the opposite digit (Healy and Helliwell, 2007; Helliwell et al, 2005). The 
percent difference between circumferences will be multiplied by a tenderness score (0 for non-
tender, 1 for tender). The digits involved and the matching contralateral digit will also be 
recorded at the same visits. The results from each digit with dactylitis will then be summed to 
produce a final score.
The following is a table of normative values, which will be used to provide the comparison, if 
matching digits are thought to be involved (Table 8‒5).
Table 8‒5:
Normative values for LDI
Digit
Men
Women
Hand
Thumb
70
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07 Sep 2018
Statistical Analysis Plan
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Table 8‒5:
Normative values for LDI
Digit
Men
Women
Index
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Middle
63
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Ring
59
50
Little
52
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Foot
Great toe
82
72
Second
52
46
Middle
50
44
Fourth
50
44
Little
52
45
The following rules will be applied for the LDI calculation in case of unclear data. If both digits 
of a given pair are recorded as affected, then each digit will be compared to the normative value. 
If both comparisons result in a difference greater than 10%, then both digits will contribute to the 
LDI score. If the circumference of the affected digit is smaller than the unaffected digit, then the 
LDI will be calculated by comparing the smaller digit to the normative value. If a digit is 
recorded as affected and the circumference of the contralateral digit is missing, the normative 
value will be used for comparison with the affected digit.
If the LDI CRF page is left empty at Baseline, it will be assumed that no digits were affected. At 
post-Baseline visits, when LDI cannot be determined, last observation carried forward (LOCF) 
imputation should be applied.
8.3.7
Psoriatic Arthritis Impact of Disease-9 (PsAID-9)
The PsAID-9 is a patient-reported outcome measure for assessing the impact of PsA in 9 
physical and psychological domains, including pain, fatigue, skin problems, work and/or leisure 
activities, functional capacity, discomfort, sleep disturbance, coping, and 
anxiety/fear/uncertainty. The questionnaire is available in the Appendix Section 12.8.
Each domain is assessed with a single question using a 0 to 10 NRS. Each domain score is 
multiplied by a weighting factor and the results are then summed to provide the total score. 
ܲݏܣܫܦൌܲܽ݅݊כ ͲǤͳ͹Ͷ ൅ܨܽݐ݅݃ݑ݁כ ͲǤͳ͵ͳ ൅ܵ݇݅݊כ ͲǤͳʹͳ
൅ܹ݋ݎ݇ܽ݊݀Ȁ݋ݎܮ݁݅ݏݑݎ݁ܣܿݐ݅ݒ݅ݐ݅݁ݏכ ͲǤͳͳͲ ൅ܨݑ݊ܿݐ݅݋݊
כ ͲǤͳͲ͹ ൅ܦ݅ݏܿ݋݂݉݋ݎݐכ ͲǤͲͻͺ ൅݈ܵ݁݁݌כ ͲǤͲͺͻ ൅ܥ݋݌݅݊݃
כ ͲǤͲͺ͹ ൅ܣ݊ݔ݅݁ݐݕכ ͲǤͲͺͷ
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The total score ranges from 0 to 10, with higher scores indicating a worse status. A score below 4 
out of 10 is considered a patient-acceptable status. A change of 3 or more points is considered 
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Statistical Analysis Plan
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If one of the 9 domains is missing, the missing value is imputed using the mean value of the 8
other (non-missing) domains. The imputed value will be used to calculate the PsAID with the 
formula above. If 2 or more of the domains are missing, the PsAID will be treated as missing.
8.3.8
Psoriatic Arthritis Quality of Life (PsAQoL)
The use of the PsAQoL is recommended by the health regulatory authorities as one of the disease 
specific Health-Related Quality of Life (HRQoL) measures in PsA (CHMP/EWP/438/04). The 
questionnaire is available in Section 12.9. The PsAQoL comprises 20 items (0 for “not true” or 1 
for “true”) so that the score ranges from 0 to 20 with higher scores indicating worse HRQoL.
If 6 or less item responses are missing, the missing responses will be imputed with the mean of 
available responses to calculate a total score. If more than 6 items responses are missing, the total 
score will be left missing.
8.3.9
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 12.10
and the classification of the questionnaire items to the health domains is shown in Section 12.11.
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 
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 calculated using QualityMetric’s Health Outcomes™ Scoring Software 4.5.
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.
8.3.10
Hospital Anxiety and Depression Scale (HADS)
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).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 60 of 183
8.3.11
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
(15)
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 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.
The derivation of time since first diagnosis of PsA is described in Section 6.2.
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
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 lower limit of quantification (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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 61 of 183
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
x
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 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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 62 of 183
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 and 160mg with loading dose, 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) while for the other two treatment groups only the time a subject 
received 160mg, 160mg with loading dose, 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
(16)
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
(17)
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀ܲ݁ݎ݅݋݀ሻ൅ͳ
(18)
Duration of exposure entire treatment period
For subjects who do not switch study treatments, who receive bimekizumab 160mg with loading 
dose at Baseline, or who receive bimekizumab 16mg and will be summarized under all 
bimekizumab group:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 63 of 183
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(19)
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
(20)
For subjects who die, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(21)
For subjects who receive Placebo or bimekizumab 16mg 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
(22)
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
(23)
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
(24)
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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 64 of 183
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(25)
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
(26)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(27)
ܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(28)
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
(29)
Time at risk entire treatment period
For subjects who do not switch study treatments, who receive bimekizumab 160mg with loading 
dose at Baseline, or who receive bimekizumab 16mg 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
(30)
For subjects who die prior to the final visit:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(31)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(32)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(33)
For subjects who receive Placebo or bimekizumab 16mg in the Double-Blind Period and will be
summarized under their Dose-Blind treatment in the overall table with bimekizumab 160mg or 
320mg, or for subjects who receive 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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 65 of 183
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂ܸ݅ݏ݅ݐͳ͸ ሺܹ݁݁݇Ͷͺሻ
െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(34)
For subjects who die during the Dose-Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(35)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳͶͲ
(36)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(37)
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
(38)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(39)
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 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 Safety Follow-up [SFU] period).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 66 of 183
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 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.
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, 160mg with loading dose and bimekizumab 320mg treatment groups, 
patients randomized to Placebo or bimekizumab 16mg 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 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 
REDACTED
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 67 of 183
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+ 1
(40)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(41)
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
(42)
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 (41 and 42) 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
݊஺ா
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௜ୀଵ
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ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(43)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [40] 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 at Baseline, exposure time will only be 
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 68 of 183
considered from the start of Dose-Blind Period, when presenting AEs for the bimekizumab 
160mg and bimekizumab160mg with loading dose, or bimekizumab 320mg groups. All exposure 
time on any bimekizumab dose is considered for the all bimekizumab column.
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):
ܮܥܮൌ
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ܥܫ௅௢௪௘௥ൌͳͲͲ כ
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ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
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ܥܫ௎௣௣௘௥ൌͳͲͲ כ
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௡೙೚ಲಶ
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(47)
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 [40] 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
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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 CI 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: 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 69 of 183
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.
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.
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 70 of 183
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 
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 the 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. C-reactive protein (CRP) 
and hs-CRP will be 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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 71 of 183
Table 10‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Hemoglobin
BUN
Urine dipstick for pregnancy 
testingb
MCH
Creatinine
MCHC
hs-CRP/CRPa
MCV
AST
Platelet count
ALT
RBC count
GGT
WBC count
ALP
Total bilirubin
LDH
Total cholesterol
Uric acid
Albumin
Serum pregnancy testingb
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 Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
b 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.
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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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 LLOQ, then these will be set to the midpoint between 0 and the LLOQ for the purpose 
of summarizing the data.
Table 10‒2: 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.
Table 10‒3: Definitions of Markedly Abnormal Biochemistry Values
Variable (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
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 
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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 (laboratory measurements) and Table 10‒5
(additional information).
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.
Table 10‒4: 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 
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
Additional
Prothrombin time/INRb
Serum pregnancy test
PK sample
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Table 10‒4: 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 
heterophile antibody or monospot testing)
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).
Table 10‒5: 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
x
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)
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
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Page 75 of 183
Table 10‒5: Additional PDILI information
New or updated information
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
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 (except temperature) 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 measurements will only be listed and not 
summarized in a table.
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)
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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 –
x
Category 4 –
x
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).
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yes/n
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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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11
REFERENCES
Berglund P, Heeringa S. Multiple imputation of missing data using SAS®. Cary, NC: SAS 
Institute Inc. 2014.
Bross I. D. J. How to use ridit analysis. Biometrics. 1958;14 (1):18-38.
CHMP/EWP/438/04. Guideline on Clinical Investigation of Medicinal Products for the 
Treatment of Psoriatic Arthritis (EMEA) Dec 2006.
Dauden E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or 
paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol 
Venereol. 2009;23(12):1374-82.
Fay MP, Feuer EJ. Confidence intervals for directly standardized rates: a method based on the 
Gamma distribution. Statistics in Medicine. 1997;16, 791-801.
Feldman SR. A quantitative definition of severe psoriasis for use in clinical trials. J Dermatolog 
Treat. 2004;15(1):27-9.
Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American 
College of Rheumatology preliminary core set of disease activity measures for rheumatoid 
arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical 
Trials. Arthritis Rheum. 1993;36(6):729-40.
Gossec L, de Wit M, Klitz U, Braun J, Kalyoncu U, Scrivo R, et al. A patient-derived and 
patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary 
validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country 
EULAR initiative. Ann Rheum Dis. 2014;73:1012-19.
Healy PJ, Helliwell PS. Measuring dactylitis in clinical trials: Which is the best instrument to 
use? J Rheumatol. 2007;34:1302-6.
Heinze, G., Schemper, M. 2002. A solution to the problem of separation in logistic regression. 
Statistics in Medicine, 21, 2109-2119.
Helliwell PS, Firth J, Ibrahim GH, Melsom RD, Shah I, Turner DE. Development of an 
assessment tool for dactylitis in patients with psoriatic arthritis. J Rheumatol. 2005;32:1745-50.
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;127-132.
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, doubleblind, placebo-
controlled phase III trial. J Am Acad Dermatol. 2010;63(3):457-65.
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.
REDACTED 
oncu U
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Mantel N, Haenszel W. Statistical aspects of the Analysis of Data From Retrospective Studies of 
Disease. J Natl Cancer Inst. 1959; 22:719-48.
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, 
a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 
2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015;386:1137-46.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh, A, Rahman, P, van der Heijde D, et al. 
Secukinumab inhibition of Interleukin-17A in patients with psoriatic arthritis. N Engl J Med 
2015;373:1329-39.
Nam, J.M. A simple approximation for calculating sample sizes for detecting linear trend in 
proportions. Biometrics 1987;43(3):701-5.
Rubin D.B. 1987. Multiple Imputation for Nonresponse in Surveys. New York: John Wiley and 
Sons.
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the irritability 
depression-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.
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12
APPENDICES
12.1
Classification Criteria for Psoriatic Arthritis (CASPAR) Criteria
A score will be derived by adding the points from each of the 5 categories. The maximum score 
will be 6. The CASPAR criteria are fulfilled, if the score is ≥3 and Inflammatory articular 
disease (joint, spine, or entheseal):
Table 12‒1: CASPAR Criteria
Category
Definition
Points
1) Evidence of psoriasis:
Current psoriasis or
Personal history of psoriasis or
Family history of psoriasis
Psoriatic skin or scalp disease present today as 
judged by a dermatologist or rheumatologist
A history of psoriasis that may be obtained from 
the subject, family physician, dermatologist, 
rheumatologist, or other qualified health care 
provider
A history of psoriasis in a first- or second-degree 
relative according to subject report
2 points
1 point
1 point 
2) Psoriatic nail dystrophy
Typical psoriatic nail dystrophy, including 
onycholysis, pitting, and hyperkeratosis, observed 
on current physical examination
1 point
3) A negative test for rheumatoid factor
By any method except latex, but preferably by 
enzyme-linked immunosorbent assay (ELISA) or 
nephelometry, according to the local laboratory 
reference range
1 point
4) Dactylitis:
Current dactylitis or
History of dactylitis
Swelling of an entire digit
A history of dactylitis recorded by a 
rheumatologist
1 point
1point
5) Radiologic evidence of juxta-articular 
new bone formation
Ill-defined ossification near joint margins (but 
excluding osteophyte formation) on plain 
radiographs of the hand or foot
1 point
CASPAR=Classification Criteria for Psoriatic Arthritis
12.2
Calculation rules for duration of adverse events
The calculation rules for duration of AEs are presented in Table 12‒2. AE duration is computed 
and reported in day.
Table 12‒2: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Complete data
D1
D2
Duration = D2 – D1 + 1
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Bimekizumab
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Table 12‒2: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
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
12.3
Treatment group assignment for tables and figures
Table 12‒3 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 12‒3: Treatment group assignment for tables and figures
Placebo
BKZ 16mg, BKZ 160mg w/LD /
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
Tuberculosis testing
X
X
X
Previous and ongoing medical 
history
X
X
X
Prior and concomitant 
medication
X
X
X
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nmen
cebo
cebo
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Statistical Analysis Plan
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Page 82 of 183
Table 12‒3: Treatment group assignment for tables and figures
Placebo
BKZ 16mg, BKZ 160mg w/LD /
BKZ 160mg/ BKZ 320mg
All 
BKZ
All 
subjects
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
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
BKZ=bimekizumab; eC-SSRS= Electronic Columbia-Suicide Severity Rating Scale; LD=loading dose.
X
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Page 83 of 183
12.4
Hematology and biochemistry variables for the interim analysis
Table 12‒4: 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.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and 
an
any 
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en
or variations 
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REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 88 of 183
12.7
Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) 
questionnaire
REDACTED COPY 
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d any 
sions 
extensi
or variations thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 89 of 183
12.8
Psoriatic Arthritis Impact of Disease-9 (PsAID-9)
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riations 
vari
thereof. 


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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 90 of 183
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or 
ions 
variatio
thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
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REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


REDACTED COPY 
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REDACTED COPY 
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07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 103 of 183
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.
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.
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 104 of 183
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
Category C
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 105 of 183
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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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 106 of 183
13
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN
13.1
Amendment 1
13.1.1
Rationale for the amendment
The main objectives of this SAP amendment are to describe and specify the extension of time 
point up to Week 24 for the interim analysis. The SAP has been amended to:
x
Add additional analyses for the time points up to Week 24 for ACR, PASI, MDA, TEAEs, 
Hy’s Law, PK, and AbAb data
x
Add the definition for rheumatoid factor and anti-CCP antibodies positivity and negativity
x
Add clarification for handling injected joints for the swollen and tender grading
x
Add assessment of potential bias of potentially unblinding at the entry of Dose-Blind phase
x
Refine the categories of the subgroup variable Psoriasis BSA
13.1.2
Modifications and changes
Change # 1:
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 ACR and PASI 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, PsA history, Baseline 
characteristics, PsA 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 12‒4.
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. 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 107 of 183
The interim efficacy analysis will focus on the primary and secondary efficacy analyses 
including supportive and sensitivity analysis. In addition, summary tables for the primary and 
secondary efficacy variables, and the ACR 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 ACR50 response and 
ACR20 response will be summarized and plotted as described in Section 8.3.
PK and PD data will not be analyzed in the interim analysis. A separate PKPD analysis based on 
a separate Data Analysis Plan (DAP) will be performed after Week 12.
…
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 ACR and PASI 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, PsA history, Baseline 
characteristics, PsA 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 12‒4. 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 analysis. In addition, summary tables for the primary and 
secondary efficacy variables, and the ACR components, and MDA 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 ACR50 response and 
ACR20 response will be summarized and plotted as described in Section 8.3.
PK and PD data AbAb data will not be analyzed in the interim analysis as described in 
Section 9.1 and Section 9.2 . A separate PKPD analysis based on a separate Data Analysis Plan 
(DAP) will be performed after Week 12. 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 
24. The data up to Week 24 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: primary and secondary efficacy variables, ACR components, 
MDA, PK, AbAb, TEAEs and Hy’s Law. It depends on the analysis how those additional 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 108 of 183
time points will be presented in the interim analysis. Two summary tables for each of the 
primary and secondary efficacy variables, the ACR components, and MDA 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 24 by following treatment groups: 
bimekizumab 160mg and bimekizumab 160mg with loading dose 320mg, and bimekizumab 
320mg. The same approach will be done for all TEAEs tables and the Hy’s Law criteria 
tables. The summary table for plasma concentration will present only data up to Week 12 
for the Baseline treatment groups Placebo and bimekizumab 16mg. Data up to Week 24 
will be presented for bimekizumab 160mg, bimekizumab 160mg with loading dose 320mg, 
and bimekizumab 320mg. All Listings which include data up to Week 24 will use the same 
approach as for plasma concentration tables.
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. 
…
Change # 2:
Section 8.1.2.1 Tender joint count (TJC) and swollen joint count (SJC)
Section 8.1.2.1.1 78/76 joint evaluation for ACR response 
The Principal Investigator, another delegated physician, or an appropriately qualified medical 
professional (based on local requirements) who has had documented training on how to perform 
these assessments correctly assesses the following joints for tenderness: the distal 
interphalangeal, proximal interphalangeal and metacarpophalangeal joints of the hands, and 
metatarsophalangeal joints of the feet, the carpometacarpal and wrist joints (counted separately), 
the elbows, shoulders, acromioclavicular, sternoclavicular, hip, knee, talo-tibial, and 
midtarsaljoints. All of these except for the hips are assessed for swelling.
Artificial and ankylosed joints, as well as missing joints (ie, amputated joints), are excluded from 
both tenderness and swelling assessments.
One dactylitic digit is to be counted as 1 swollen joint (instead of counting as 3 in the finger or 2 
in the toe).
Table 8‒1 summarizes the swelling and tenderness grading criteria.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 109 of 183
Table 13‒1: Swelling and tenderness grading
The tender joint counts (TJC) and swollen joint counts (SJC) are weighted joint counts. If there 
are missing observations in the tender or swollen joint assessments, then the remaining 
observations will be assessed and weighted by the number of the assessed joints (AJ): 
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where n is the number of total joints. If a joint is missing at Baseline, then that joint is set to 
missing throughout the study. If more than 50% of the tender joint assessments or 50% of the 
swollen joint assessments are missing at the time of a given assessment, then no imputation will
be done and the total TJC or SJC will be set to missing for that visit.
Section 8.1.2.1.2 28 joint evaluation for determination of DAS28(CRP)
The following 28 joints will be used for calculation of the DAS28(CRP).
x
Upper extremity (26)-bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal and 
carpometacarpal bones considered as a single unit), MCP I, II, III, IV, and V, thumb 
interphalangeals (IP), PIP II, III, IV, and V
x
Lower extremity (2)-knees
Has been changed to
Section 8.1.2.1 Tender joint count (TJC) and swollen joint count (SJC)
Section 8.1.2.1.1 78/76 joint evaluation for ACR response 
The Principal Investigator, another delegated physician, or an appropriately qualified medical 
professional (based on local requirements) who has had documented training on how to perform 
these assessments correctly assesses the following joints for tenderness: the distal 
interphalangeal, proximal interphalangeal and metacarpophalangeal joints of the hands, and 
metatarsophalangeal joints of the feet, the carpometacarpal and wrist joints (counted separately), 
the elbows, shoulders, acromioclavicular, sternoclavicular, hip, knee, talo-tibial, and 
midtarsaljoints. All of these except for the hips are assessed for swelling.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 110 of 183
Artificial and ankylosed joints, as well as missing joints (ie, amputated joints), are excluded from 
both tenderness and swelling assessments.
One dactylitic digit is to be counted as 1 swollen joint (instead of counting as 3 in the finger or 2 
in the toe). 
Table 8‒1 summarizes the swelling and tenderness grading criteria.
Table 13‒1: Swelling and tenderness grading
The tender joint counts (TJC) and swollen joint counts (SJC) are weighted joint counts. If there 
are missing observations in the tender or swollen joint assessments, then the remaining 
observations will be assessed and weighted by the number of the assessed joints (AJ): 
ܵܬܥൌ݊כ ෍ܵܬ
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missing throughout the study. If more than 50% of the tender joint assessments or 50% of the 
swollen joint assessments are missing at the time of a given assessment, then no imputation will 
be done and the total TJC or SJC will be set to missing for that visit.
Injected joints will be counted as swollen and tender from the date of injection up to 52 
weeks after injection, ie, swelling and tenderness grading is 1.
Section 8.1.2.1.2
28 joint evaluation for determination of DAS28(CRP)
The following 28 joints will be used for calculation of the DAS28(CRP).
x
Upper extremity (26)-bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal and 
carpometacarpal bones considered as a single unit), MCP I, II, III, IV, and V, thumb 
interphalangeals (IP), PIP II, III, IV, and V
x
Lower extremity (2)-knees
Injected joints will be counted as swollen and tender from the date of injection up to 52 
weeks after injection, ie, swelling and tenderness grading is 1.
Change # 3
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 111 of 183
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:
x
TJC
x
SJC
x
hs-CRP
x
Rheumatoid factor 
x
Anti-CCP antibodies
x
Prior NSAID therapy, and prior anti-TNF therapy
x
Psoriasis BSA
x
Nail psoriasis
x
Dactylitis
x
NSAID therapy
x
Synthetic DMARDs
x
MTX
x
Sulfasalazine
x
Hydroxychloroquine
The corresponding listings will be presented for the RS.
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. Following variables will be 
summarized:
x
TJC
x
SJC
x
hs-CRP
x
Rheumatoid factor 
x
Anti-CCP antibodies
x
Prior NSAID therapy, and prior anti-TNF therapy
x
Psoriasis BSA
x
Nail psoriasis
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 112 of 183
x
Dactylitis
x
NSAID therapy
x
Synthetic DMARDs
x
MTX
x
Sulfasalazine
x
Hydroxychloroquine
A rheumatoid factor value < 15 IU/mL is defined as negative and a value ≥ 15 IU/mL is 
defined as positive. Anti-CCP antibodies negative is a value < 5 U/mL and a value ≥ 5 
U/mL is defined as positive.
The corresponding listings will be presented for the RS.
Change # 4:
Following text has been added at the end of 
Section 8.3 Analysis of other efficacy variables
…
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 ACR50 and PASI90 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 ACR50 and 
PASI90 responders is comparable as assessed by overlapping 95% confidence intervals, the 
potential bias is estimated to be at minimum.
Change # 5:
Section 8.4 Subgroup analysis
and
Section 4.8 Examination of subgroups
…
x
Extent of psoriasis involvement >3% (yes, no)
…
Has been changed to
…
x
Extent of psoriasis involvement (<3%, ≥3% to <10%, ≥10%)
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 113 of 183
13.2
Amendment 2
13.2.1
Rationale for the amendment
The SAP has been amended to:
x
Add ‘End of Treatment’ visit for the final analysis
x
Add clarification for the different handling of additional time points in the interim analysis
x
Add rule for missing hs-CRP values 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 3.5 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.
Has been changed to
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.
A visit called ‘End of Treatment’ will be added for the TFLs in the final analysis. The visit 
will display the Week 48 assessments or the early termination assessment depending if the 
subject discontinued early or not.
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).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 114 of 183
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.
…
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
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then use the date of first dose.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 115 of 183
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 analysis and data monitoring
…
The interim analysis includes selected data up to Week 12 and in addition data up to Week 24. 
The data up to Week 24 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: 
primary and secondary efficacy variables, ACR components, MDA, modified MDA, PK, AbAb, 
TEAEs and Hy’s Law. It depends on the variable how those additional time points will be 
presented in the interim analysis. Two summary tables for each of the primary and secondary 
efficacy variables, the ACR components, MDA and modified MDA 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 24 by following treatment groups: bimekizumab 160mg and 
bimekizumab 160mg with loading dose 320mg, and bimekizumab 320mg. The same approach 
will be done for all TEAEs tables and the Hy’s Law criteria tables. The summary table for 
plasma concentration will present only data up to Week 12 for the Baseline treatment groups 
Placebo and bimekizumab 16mg. Data up to Week 24 will be presented for bimekizumab 
160mg, bimekizumab 160mg with loading dose 320mg, and bimekizumab 320mg. All Listings 
which include data up to Week 24 will use the same approach as for plasma concentration tables. 
…
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.
…
Has been changed to
…
The interim analysis includes selected data up to Week 12 and in addition data up to Week 24. 
The data up to Week 24 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. The analysis of following variables will 
include data up to Week 24Following variables will be analyzed: primary and secondary 
y
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 116 of 183
efficacy variables, ACR components, MDA, modified MDA, PK, AbAb, TEAEs, biochemistry 
and hematology laboratory results, and Hy’s Law. It depends on the variable how those 
additional time points will be presented in the interim analysis. 
The efficacy analyses and the plasma concentration analyses for the period between Week 
12 and Week 24 are only for those treatment groups that are not rerandomized. Two 
summary tables for each of the primary and secondary efficacy variables, the ACR components, 
and MDA and modified MDA 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 24 by the 
following treatment groups: bimekizumab 160mg and bimekizumab 160mg with loading dose 
320mg, and bimekizumab 320mg. The same approach will be done for all TEAEs tables and the 
Hy’s Law criteria tables. The summary table for plasma concentration will present only data up 
to Week 12 for the Baseline treatment groups Placebo and bimekizumab 16mg. Data up to Week 
24 will be presented for bimekizumab 160mg, bimekizumab 160mg with loading dose 320mg, 
and bimekizumab 320mg. All Listings which include data up to Week 24 will use the same 
approach as for plasma concentration tables. 
The safety analysis (TEAEs, biochemistry and hematology laboratory results, and Hy’s 
Law) will be handled as follows: Two summary tables for each of the safety analysis 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 24 and will also present subjects under their 
Baseline treatment group. For the second table any event/finding that is unique to a 
treatment group should only be presented in the “All subjects” column and the treatment 
columns should remain blank. Following rules will be applied for the TEAEs: If the 
relative TEAE start date is less or equal to 84 (12*7) days, then the TEAE will be presented 
in the up to Week 12 table. If the relative start date is less or equal to 168 (24*7) days, then 
the TEAE will be presented in the up to Week 24 table. 
The treatment group information will not be displayed for the interim listings.
…
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 PA0008 blinding plan.
…
Section 6.2 Other Baseline characteristics
…
Time since first diagnosis of PsA 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).
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 117 of 183
…
A rheumatoid factor value < 15 IU/mL is defined as negative and a value ≥ 15 IU/mL is defined 
as positive. Anti-CCP antibodies negative is a value < 5 U/mL and a value ≥ 5 U/mL is defined 
as positive.
The corresponding listings will be presented for the RS.
Has been changed to
…
Time since first diagnosis of PsA 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).
The absolute values of the formula (6) will be used to display positive values.
…
A rheumatoid factor value < 15 IU/mL is defined as negative and a value ≥ 15 IU/mL is defined 
as positive. Anti-CCP antibodies negative is a value < 5 U/mL and a value ≥ 5 U/mL is defined 
as positive.
For hs-CRP following rules will be applied: 
x
If Baseline hs-CRP values are missing, then take the Screening hs-CRP values. 
x
If Screening hs-CRP values are missing, then take the median hs-CRP values.
The corresponding listings will be presented for the RS.
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 to <65 years, ≥65 years)
x
Gender (male, female)
x
Geographic region (North America, Europe)
x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
x
Prior TNF inhibitor exposure (yes, no)
x
Treatment-emergent AbAb status (positive, negative)
x
Extent of psoriasis involvement (<3%, ≥3% to <10%, ≥10%)
x
hs-CRP level (<= upper limit normal, > upper limit normal)
x
Time since first diagnosis of PsA (< 2 years, ≥ 2 years)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 118 of 183
x
Body weight (<100 kg, ≥100 kg)
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).
The derivation of time since first diagnosis of PsA is described in Section 6.2.
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. will be defined:
x
Age (<45 years, ≥45 to <65 years, ≥65 years)
x
Gender (male, female)
x
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x
BASDAI (<4 [mild disease]; ≥4 to ≤7 [moderate disease]; >7 to ≤10 [severe disease])
x
Prior TNF inhibitor exposure (yes, no)
x
Treatment emergent AbAb status (positive, negative)
x
Extent of psoriasis involvement (<3%, ≥3% to <10%, ≥10%)
x
hs CRP level (<= upper limit normal, > upper limit normal)
x
Time since first diagnosis of PsA (< 2 years, ≥ 2 years)
x
Body weight (<100 kg, ≥100 kg)
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).
The derivation of time since first diagnosis of PsA is described in Section 6.2.
All subgroup analyses are based on imputed data and will be summarized using descriptive 
statistics only.
Section 8.3 Analysis of other efficacy variables
…
Time to onset of ACR20/50 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.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 119 of 183
…
Time to onset of ACR20/50 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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(15)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(16)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(17)
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
(18)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(15)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 120 of 183
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(16)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(17)
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
(18)
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൅૚
(19)
ࡰࢇ࢙࢟࢕࢔࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈࢚࢘ࢋࢇ࢚࢓ࢋ࢔࢚
ൌࡰࢇ࢚ࢋ࢕ࢌ࢒ࢇ࢙࢚Ȁ࢒ࢇ࢚ࢋ࢙࢚ࢊ࢕࢙ࢋ
െࡰࢇ࢚ࢋ࢕ࢌࢌ࢏࢙࢚࢘࢈࢏࢓ࢋ࢑࢏ࢠ࢛࢓ࢇ࢈ࢊ࢕࢙ࢋ൅૚
(20)
Section 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(19)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(20)
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
PA0008
Confidential
Page 121 of 183
ܶ݅݉݁ݏ݅݊ܿ݁݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁ሺ݀ܽݕݏሻ
ൌܦܽݐ݁݋݂ܣܧ݋݊ݏ݁ݐ
െܦܽݐ݁݋݂݉݋ݏݐݎ݁ܿ݁݊ݐ݀݋ݏ݁݌ݎ݅݋ݎݐ݋ܣܧ൅ͳ
(21)
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 (20 and 21) 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
(22)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(23)
Has been changed to
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(1921)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(220)
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
(231)
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 (20 and 21) 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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 122 of 183
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
ܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(22)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
ܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(23)
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
݊
σ
ܶா௫௣ǡ௜
௡
௜ୀଵ
(24)
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% CIs 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
(25)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(26)
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
ܰ஺ா
σ
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(27)
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௜is a subject’s total time at risk in years.
No CI 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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 123 of 183
ܧܣܫܴൌͳͲͲ כ
݊
σ
ܶா௫௣ǡ௜
௡
௜ୀଵ
(24)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [21] 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% CIs 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
(25)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(26)
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
ܰ஺ா
σ
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(27)
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௜is a subject’s total time at risk in years.
No CI 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
PA0008
Confidential
Page 124 of 183
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
Add rule for value below limit of quantification for DAS28(CRP)
x
Add Section 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
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
Modification and changes
List of abbreviation
Has been changed to
…
CDF
cumulative distribution function
CI
confidence interval
…
RBC
red blood cell
RNA
ribonucleic acid
…
…
CDF
cumulative distribution function
CDISC
Clinical Data Interchange Standards 
Consortium
CI
confidence interval
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 125 of 183
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 definition of time since first diagnosis of PsA was 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 which results in negative values. For the 
interim analysis another calculations were used:
ࢀ࢏࢓ࢋ࢙࢏࢔ࢉࢋࢌ࢏࢙࢚࢘ࢊ࢏ࢇࢍ࢔࢕࢙࢏࢙ሺ࢟ࢋࢇ࢙࢘ሻ
ൌࡰࢇ࢚ࢋ࢕ࢌࢀ࢘ࢋࢇ࢚࢓ࢋ࢔࢚ࡿ࢚ࢇ࢚࢘ࡰࢇ࢚ࢋെࡰࢇ࢚ࢋ࢕ࢌࢊ࢏ࢇࢍ࢔࢕࢙࢏࢙൅૚
૜૟૞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
x
Haematopoietic cytopenias
x
Neuropsychiatric events 
x
Inflammatory bowel disease
x
Hypersensitivity and anaphylactic reaction
x
Hepatic events 
…
RBC
Red blood cell
RCTC
Rheumatology Common Toxicity Criteria
RNA
Ribonucleic acid
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 126 of 183
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.
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:
REDACTED
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 127 of 183
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:
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 128 of 183
…
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 PsA 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).
The absolute values of the formula (6) will be used to display positive values.
…
Has been changed to
….
Time since first diagnosis of PsA 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).
The absolute values of the formula (6) will be used to display positive values.
…
Section 6.5 Prohibited medication and rescue medication
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 129 of 183
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. The number and percentage of subjects 
who used prohibited medication will be summarized and also be listed.
…
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. The number and percentage of subjects 
who used prohibited medication will be summarized and also be listed.
…
Section 8.3.2 Disease Activity Score-28 joint count C-reactive protein (DAS28[CRP])
The components for DAS28(CRP) include the TJC and SJC based on 28 joints, hs-CRP (mg/L), 
and the PGADA (mm). DAS28(CRP) is calculated as follows:
ܦܣܵʹͺሺܥܴܲሻൌͲǤͷ͸ כ ඥܶܬܥ൅ͲǤʹͺ כ ඥܵܬܥ൅ͲǤͲͳͶ כ ܲܩܣܦܣ൅ͲǤ͵͸
כ ሺ݄ݏܥܴܲ൅ͳሻ൅ͲǤͻ͸
(12)
Has been changed to
The components for DAS28(CRP) include the TJC and SJC based on 28 joints, hs-CRP (mg/L), 
and the PGADA (mm). DAS28(CRP) is calculated as follows:
ܦܣܵʹͺሺܥܴܲሻൌͲǤͷ͸ כ ඥܶܬܥ൅ͲǤʹͺ כ ඥܵܬܥ൅ͲǤͲͳͶ כ ܲܩܣܦܣ൅ͲǤ͵͸
כ ሺ݄ݏܥܴܲ൅ͳሻ൅ͲǤͻ͸
(12)
The hs-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.
Section 8.3.11 has been added
Section 8.3.11 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
(15)
with SDln – the standard deviation of the ln-transformed hs-CRP values.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 130 of 183
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.
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/pre-
treatment 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/pre-
treatment 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.
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.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 131 of 183
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 9.1Pharmacokinetics
…
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.
…
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.
…
Section 10.1 Extent of exposure
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(15)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(16)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(17)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 132 of 183
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
(18)
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
(19)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(20)
Has been changed to
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(156)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(167)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(178)
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
(189)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 133 of 183
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
(1920)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(201)
Section 10.2 Adverse events
…
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
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
…
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 134 of 183
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
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 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(19)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(20)
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
(21)
…
Has been changed to
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(1922)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 135 of 183
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(2023)
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
(2124)
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
݊
σ
ܶா௫௣ǡ௜
௡
௜ୀଵ
(24)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [21] 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% CIs 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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(26)
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
ܰ஺ா
σ
ܶோ௜௦௞ǡ௜
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 136 of 183
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௜is a subject’s total time at risk in years.
No CI 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
݊
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ܶா௫௣ǡ௜
௡
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(245)
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(equation [21] 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.
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Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
ܮܥܮൌ
߯ଶ௡ǡఈ
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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
ܰ஺ா
σ
ܶோ௜௦௞ǡ௜
௡
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(278)
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௜is a subject’s total time at risk in years.
No CI will be computed for EAER.
Section 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.
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and tuberculosis [TB]), cytopenias, hypersensitivities, suicide ideation or behavior 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 137 of 183
(assessed using the 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:
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”.
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:
4. 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.
5. 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)”.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 138 of 183
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:
6. 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 HLT 
it codes to. 
7. 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:
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 of “Cardiac failure congestive”
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 139 of 183
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:
e) 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.
f)
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.
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 140 of 183
AEs of special monitoring for this study include: serious infections (including opportunistic 
infections and tuberculosis [TB]), cytopenias, hypersensitivities, suicide ideation or behavior 
(assessed using the 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. for following TEAEs of special monitoring: 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:
•
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. 
•
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:
•
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. 
•
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)”.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 141 of 183
The output table for Anaphylactic reaction will include three different overall rows: 
•
The first row within the body of the table will be labeled “Any 
hypersensitivity/anaphylactic reaction” and will represent the overall incidence of subjects 
who reported at least one hypersensitivity reaction or at least one anaphylactic reaction.
•
The second row within the body of the table will be labeled “Any hypersensitivity 
reaction” and will represent the overall incidence of subjects who reported at least one 
hypersensitivity reaction.
•
The third row within the body of the table will be labeled “Any anaphylactic reaction” 
and will represent the overall incidence of subjects who reported at least one anaphylactic 
reaction.
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”.
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:
8. 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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 142 of 183
9. 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:
10. 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 HLT 
it codes to. 
11. 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:
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 of “Cardiac failure congestive”
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 143 of 183
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:
g) 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.
h) 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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 144 of 183
…
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 13‒2:
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
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 13‒3:
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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 145 of 183
Table 13‒2:
Definitions of Markedly Abnormal Biochemistry Values
Variable (Standard international 
units)
Markedly abnormal definition
Low
High
Platelets (x 1000)
<50
N/A
LLN=lower limit of normal; N/A = not applicable.
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…
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. 
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 13‒4:
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 146 of 183
Table 13‒4:
Definitions of Markedly Abnormal Biochemistry Values
Variable (Standard international 
RCTC units)
Markedly abnormal definition
Low
High
Table 13‒5:
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
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<0.5
N/A
Neutrophils (x 1000)
<1.0
N/A
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<50
N/A
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 147 of 183
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
Modification 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 PA0008. 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 (16 Dec 2016). 
…
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 PA0008. 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 (16 Dec 2016), and 
Protocol Amendment 2 (09 Mar 2018).
…
Section 2.3 Study design and conduct
Table 2-1 updated to align with Table 5-1 from the Protocol Amendment 2.
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.
…
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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 148 of 183
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.
…
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.
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 and after the first administration of 
study medication, it will be analyzed as the first post-Baseline assessment. If a scheduled 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 149 of 183
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 after the study medication.
Has been changed to
Unless otherwise specified, t 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 after the study medication. The same Baseline definition will be used for the 
Follow up period.
The exception of the above rule are the questionnaires collected from the vendor ERT and 
measurements for CRP and 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.
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 after the study medication.
Section 3.5 Mapping of assessments performed at early termination visit
…
A visit called ‘End of Treatment’ will be added for the TFLs in the final analysis. The visit will 
display the Week 48 assessments or the early termination assessment depending if the subject 
discontinued early or not.
Has been changed to
…
A visit called ‘End of Treatment’ will be added for the TFLs in the final analysis. The visit will 
display the Week 48 assessments or the early termination assessment depending if the subject 
discontinued early or not.
Section 3.6 Analysis sets
The primary efficacy variable will be analyzed for all subjects in the Full Analysis Set (FAS). 
The supportive analyses for the primary efficacy variables will include the Randomized Set (RS) 
and PPS. 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 PK-PPS. PD 
variables will be analyzed for all subjects in the PD-PPS.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 150 of 183
Section 3.6.9 Escape Subject Set (ESS)
The Escape Subject Set (ESS) consists of all subjects who started 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 SJC and TJC at 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 who started 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 SJC and TJC at Week 16, Week 24, and 
Week 36.
Has been changed to
The primary efficacy variable will be analyzed for all subjects in the Full Analysis Set (FAS). 
The supportive analyses for the primary efficacy variables will include the Randomized Set (RS) 
and PPS. 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 PK-PPS. PD variables will be analyzed for all subjects in the 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 who started 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 SJC and TJC at 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 who started 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 SJC and TJC at Week 16, Week 24, and 
Week 36.
3.6.11 Corrected Escape Subject Set (cESS)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 151 of 183
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 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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 152 of 183
x
DBS: planned treatment (demographics, baseline characteristics, and efficacy analyses)
or actual treatment 
x
ESS: planned treatment
x
DBRS: planned treatment 
x
cESS: planned treatment
x
cDBRS: planned treatment
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.
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 153 of 183
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..
…
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 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:
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 154 of 183
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..
…
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
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 definition of time since first diagnosis of PsA was 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 which results in negative values. For the interim analysis another 
calculations were used:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܶݎ݁ܽݐ݉݁݊ݐܵݐܽݎݐܦܽݐ݁െܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ൅ͳ
͵͸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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 155 of 183
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 
Section 4.3.1.2. The interim analysis only displayed the overall number of AE of special 
monitoring by treatment group.
The definition of time since first diagnosis of PsA was 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 which results in negative values. For the interim analysis another 
calculations were used:
ܶ݅݉݁ݏ݂݅݊ܿ݁݅ݎݏݐ݀݅ܽ݃݊݋ݏ݅ݏሺݕ݁ܽݎݏሻ
ൌܦܽݐ݁݋݂ܶݎ݁ܽݐ݉݁݊ݐܵݐܽݎݐܦܽݐ݁െܦܽݐ݁݋݂݀݅ܽ݃݊݋ݏ݅ݏ൅ͳ
͵͸ͷǤʹͷ
The baseline definition for CRP and hs-CRP measurements were updated with the fourth 
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
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 PA0008 interim analysis Week 48 will occur before all subjects have 
completed the PA0008 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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 156 of 183
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. 
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 fourth 
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
…
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:
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 157 of 183
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 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. 
…
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
Compliance will be summarized as the number of doses received relative to the number of doses 
scheduled:
ܲ݁ݎܿ݁݊ݐܿ݋݉݌݈݅ܽ݊ܿ݁ൌͳͲͲ כ    
   
(8)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 158 of 183
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. 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.
…
Has been changed to
Compliance will be summarized as the number of doses received relative to the number of doses 
scheduled:
ܲ݁ݎܿ݁݊ݐܿ݋݉݌݈݅ܽ݊ܿ݁ൌͳͲͲ כ    
   
(8)
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 4448). 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.
…
Section 8.1.1.3 Physician’s Global Assessment of Disease Activity (PhGADA)
The Investigator will assess the overall status of the subject with respect to their PsA signs and 
symptoms and functional capacity (considering both joint and skin components) using a 
numerical rating scale (NRS) where 0 is “very good, asymptomatic and no limitation of normal 
activities” and 10 is “very poor, very severe symptoms which are intolerable and inability to 
carry out all normal activities”.
Has been changed to
The Investigator will assess the overall status of the subject with respect to their PsA signs and 
symptoms and functional capacity (considering both joint and skin components) using a 
numerical rating scale (NRS) where 0 is “very good, asymptomatic and no limitation of normal 
activities” and 100 is “very poor, very severe symptoms which are intolerable and inability to 
carry out all normal activities”.
Section 8.3 Analysis of other efficacy variables
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 159 of 183
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.
…
Time to onset of ACR20/50 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
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.
…
Time to onset of ACR20/50 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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(16)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(17)
For subjects who have died the exposure will be as follows:
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 160 of 183
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(18)
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
(19)
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
(20)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(21)
Has been changed to
The duration of exposure (in days) will be calculated as:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(16)
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊
(17)
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(1718)
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:
REDACTED
݉
ܽݏݐ
ܽݏݐȀ݈ܽ
݈
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COPY
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t-year
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(19
(19
variations thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 161 of 183
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(1819)
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
(1920)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(2021)
Section 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(22)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(23)
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
(24)
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 (20 and 21) 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+ 1
(2122)
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192
variations thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 162 of 183
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(2223)
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
(2324)
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 (2220 and 2321) 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
݊
σ
ܶா௫௣ǡ௜
௡
௜ୀଵ
(25)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [21] 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% CIs 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
(26)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(27)
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.
REDACTED
ts (n)
ts (n
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This document cannot be used
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 163 of 183
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
ܰ஺ா
σ
ܶோ௜௦௞ǡ௜
௡
௜ୀଵ
(28)
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௜is a subject’s total time at risk in years.
No CI 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௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(2425)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [21] 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 [18] 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 (1815) in years 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):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(2526)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(2627)
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(27)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(28)
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, ࢀࡱ࢞࢖ǡ࢏is a subject’s exposure time in years up to the first occurrence of the 
REDACTED 
of cod
of cod
AE of 
AE of 
e ra
e ra
COPY 
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scaled
scale
OP
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ates are
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ding e
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t occur
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AE the
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 to 10
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and any extensions 
the
the e
or variations thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 164 of 183
AE of interest (equation [21] 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 [18] 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
(2928)
where NAE is the total number of AEs and ܶோ௜௦௞ǡ௝is a subject’s total time at risk in years and nAll
the number of subjects.
No CI will be computed for EAER.
Section 10.3 Clinical laboratory evaluations
…
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 
testingb
MCH
hs-CRP/CRPa
MCHC
AST
MCV
ALT
Platelet count
GGT
RBC count
ALP
REDACTED 
ments
ments
RE
COPY 
axi
ax
ne to 
ne to 
norma
orma
This document
MC
MC
nt
nt 
m
um
um
um
cannot 
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oglobi
globi
ot be 
e used 
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o support t
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s
any 
Ch
C
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an
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marketing 
chemis
chemi
g
Calcium
Calciu
rk
m
authorization
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al lab
al lab
application 
ariable
riabl
um pos
m po
nd of
nd of
and any extensions 
n years
year
or variations 
28)
a
thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 165 of 183
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
WBC count
Total bilirubin
LDH
Total cholesterol
Serum pregnancy testingb
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 Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
b 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.
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, 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.
…
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Basophils 
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
Magnesium
Crystals
Atypical lymphocytes
Potassium
Glucose
Monocytes
Sodium
pH
REDACTED 
teri
eri
olog
olog
COPY
eli
el
there 
there
ential w
ential 
ing I
ing
This documen
Eo
Eo
ent
Baso
aso
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1:
b
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on
ion
on
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ari
thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 166 of 183
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Neutrophils
Glucose
RBC
Hematocrit
BUN
WBC
Hemoglobin
Creatinine
Urine dipstick for pregnancy 
testingb
MCH
hs-CRP/CRPa
MCHC
AST
MCV
ALT
Platelet count
GGT
RBC count
ALP
WBC count
Total bilirubin
LDH
Total cholesterol
Albumin
Serum pregnancy testingb
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 Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
b 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.
…
Table 10-4 updated to align with Table 12-4 from the Protocol Amendment 2.
Table 10-5 updated to align with Table 12-5 from the Protocol Amendment 2.
Section 12.2 Calculation rules for duration of adverse events
The calculation rules for duration of AEs are presented in Table 12‒2. AE duration is computed 
and reported in day.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 167 of 183
Table 13‒2: 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 12‒2. AE duration is computed 
and reported in day.
Table 13‒3: 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
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 168 of 183
Table 13‒3: Calculation rules for duration of adverse events
Data 
Availability
Onset 
Date
Outcome 
Date
Calculation Rules
Start and end date 
missing
-
-
Duration = > Final contact date Discharge day – D0 +
1
For resolved and ongoing AE Duration 
Where, for a 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
PA0008
Confidential
Page 169 of 183
13.5
Amendment 5
13.5.1
Rationale for the amendment
The main objectives are to describe the different presentation of the safety assessments. 
13.5.2
Modification and changes
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 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. 
…
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. 
…
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.
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.
date o
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 170 of 183
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 and 
160mg with loading dose, bimekizumab 320mg, and all bimekizumab. Treatment 
compliance for the bimekizumab 160mg and 160mg with loading dose group will be 
calculated for the time the subject receives 160mg or 160mg with loading dose, 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 same approach will be done for bimekizumab 320mg. 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 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.
…
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.
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 171 of 183
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݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ʹͺ
(16)
28 days refer to one half-life of bimekizumab. 
For subjects who have died the exposure will be as follows:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂ܦ݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐܫ݆݊݁ܿݐ݅݋݊൅ͳ
(17)
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
(18)
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
(19)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(20)
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 and 160mg with loading dose, 
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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 172 of 183
received any dose of bimekizumab (including 16mg) while for the other two treatment 
groups only the time a subject received 160mg, 160mg with loading dose, 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
(16)
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
(17)
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀ܲ݁ݎ݅݋݀ሻ൅ͳ
(18)
Duration of exposure entire treatment period
For subjects who do not switch study treatments, who receive bimekizumab 160mg with 
loading dose at Baseline, or who receive bimekizumab 16mg and will be summarized under 
all bimekizumab group:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁
ൌܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ʹͺ
(19)
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
(20)
For subjects who die, then this calculation reverts to:
ܦݑݎܽݐ݅݋݊݋݂݁ݔ݌݋ݏݑݎ݁ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(21)
For subjects who receive Placebo or bimekizumab 16mg in the Double-Blind Period and 
will be summarized under their Dose-Blind treatment in the overall table group 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 173 of 183
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
(22)
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
(23)
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
(24)
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
(25)
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
(26)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(27)
ܦܽݐ݁݋݂݈ܽݏݐݒ݅ݏ݅ݐሺ݊݋ݐ݈݅݊ܿݑ݀݅݊݃ܵܨܷሻെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(28)
where 140 days refers to 5*half-life of bimekizumab.
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݆݊݁ܿݐ݅
݆݊݁ܿݐ
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ria
thereof. 


UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 174 of 183
For subjects who die during the Double-Blind Period, then this calculation reverts to:
ܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݑܾ݈݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(29)
Time at risk entire treatment period
For subjects who do not switch study treatments, who receive bimekizumab 160mg with 
loading dose at Baseline, or who receive bimekizumab 16mg 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
(30)
For subjects who die prior to the final visit:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(31)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳͶͲ
(32)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊൅ͳ
(33)
For subjects who receive Placebo or bimekizumab 16mg in the Double-Blind Period and 
will be summarized under their Dose-Blind treatment in the overall table with
bimekizumab 160mg or 320mg, or for subjects who receive 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
(34)
For subjects who die during the Dose-Blind Period:
ܶ݅݉݁ܽݐݎ݅ݏ݇ൌܦܽݐ݁݋݂݀݁ܽݐ݄െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁
െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ൅ͳ
(35)
For all other subjects, use the minimum of the following:
ܦܽݐ݁݋݂݈ܽݏݐ݆݅݊݁ܿݐ݅݋݊െܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳͶͲ
(36)
ܦܽݐ݁݋݂݂݈݅݊ܽܿ݋݊ݐܽܿݐെܦܽݐ݁݋݂݂݅ݎݏݐ݆݅݊݁ܿݐ݅݋݊ሺ݀݋ݏ݁െܾ݈݅݊݀݌݁ݎ݅݋݀ሻ
൅ͳ
(37)
The sum over all time at risk (in years) will be calculated for the total subject-years of time at 
risk.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 175 of 183
The days on treatment and days on bimekizumab treatment will be calculated as follows:
ܦܽݕݏ݋݊ݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐ݌݈ܾܽܿ݁݋݋ݎܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(38)
ܦܽݕݏ݋ܾ݊݅݉݁݇݅ݖݑܾ݉ܽݐݎ݁ܽݐ݉݁݊ݐ
ൌܦܽݐ݁݋݂݈ܽݏݐȀ݈ܽݐ݁ݏݐ݀݋ݏ݁
െܦܽݐ݁݋݂݂݅ݎݏݐܾ݅݉݁݇݅ݖݑܾ݉ܽ݀݋ݏ݁൅ͳ
(39)
Section 10.2 Adverse events
…
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-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, 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.
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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 176 of 183
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, 160mg with loading dose and bimekizumab 320mg 
treatment groups, patients randomized to Placebo or bimekizumab 16mg 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 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.
Section 10.2.1 Exposure duration
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(21)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(22)
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
(23)
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 (22 and 23) 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
PA0008
Confidential
Page 177 of 183
Has been changed to
The duration of each AE will be calculated as follows:
ܦݑݎܽݐ݅݋݊ሺ݀ܽݕݏሻൌܦܽݐ݁݋݂݋ݑݐܿ݋݉݁െܦܽݐ݁݋݂݋݊ݏ݁ݐ+ 1
(4021)
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݋݊ݏ݁ݐെܦܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁൅ͳ
(4122)
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
(4223)
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 (4122 and 4223) 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
(24)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [21] 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 [18] 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 (18) in years 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):
ܮܥܮൌ
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(25)
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 178 of 183
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(26)
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(27)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(28)
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 [21] 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 
[18] 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
(29)
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 CI 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
(4324)
where ܶா௫௣ǡ௜is a subject’s exposure time in years up to the first occurrence of the AE of interest 
(equation [4021] 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 [18] in 
yearsSection 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 (18 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 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 179 of 183
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 at Baseline, 
exposure time will only be considered from the start of Dose-Blind Period, when presenting 
AEs for the bimekizumab 160mg and bimekizumab160mg with loading dose, or 
bimekizumab 320mg groups. All exposure time on any bimekizumab dose is considered for 
the all bimekizumab column.
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):
ܮܥܮൌ
߯ଶ௡ǡఈ
ଶ
ଶ
ʹ
(4425)
ܷܥܮൌ
߯ଶሺ௡ାଵሻǡଵିఈȀଶ
ଶ
ʹ
(4526)
ܥܫ௅௢௪௘௥ൌͳͲͲ כ
ܮܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(4627)
ܥܫ௎௣௣௘௥ൌͳͲͲ כ
ܷܥܮ
෌
ܶா௫௣ǡ௜
௡ಲಶ
௜ୀଵ
൅෍
ܶோ௜௦௞ǡ௝
௡೙೚ಲಶ
௝ୀଵ
(4728)
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 [4021] 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 
[18] in 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
(4829)
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 CI will be computed for EAER.
Section 10.3 Clinical laboratory evaluations
…
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 180 of 183
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, 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.
…
Table 13‒1:
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 
testingb
MCH
Creatinine
MCHC
hs-CRP/CRPa
MCV
AST
Platelet count
ALT
RBC count
GGT
WBC count
ALP
Total bilirubin
LDH
Total cholesterol
Albumin
Serum pregnancy testingb
REDACTED 
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 181 of 183
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
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 Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
b 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.
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 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Basophils 
Calcium
Bacteria
Eosinophils
Chloride
Crystals
Lymphocytes
Magnesium
Glucose
Monocytes
Potassium
pH
Neutrophils
Sodium
RBC
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 182 of 183
Table 13‒1:
Laboratory measurements
Hematology
Biochemistry
Urinalysis
Hematocrit
Glucose
WBC
Hemoglobin
BUN
Urine dipstick for pregnancy 
testingb
MCH
Creatinine
MCHC
hs-CRP/CRPa
MCV
AST
Platelet count
ALT
RBC count
GGT
WBC count
ALP
Total bilirubin
LDH
Total cholesterol
Uric acid
Albumin
Serum pregnancy testingb
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 Both CRP and hs-CRP will be tested at specified visits per Protocol Table 5.1.
b 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.
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UCB
07 Sep 2018
Statistical Analysis Plan
Bimekizumab
PA0008
Confidential
Page 183 of 183
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.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.