Clinical trial NCT02905006
Conditions: Chronic Plaque Psoriasis
Keywords: Psoriasis Chronic Plaque Psoriasis Bimekizumab
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2016-08-01; Completion date: 2017-07-01
Enrollment: 250 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose ranging study to investigate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of Bimekizumab compared with placebo in adult subjects with moderate to severe chronic plaque psoriasis in order to guide the selection of doses and clinical indices in the Phase 3 development program.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None
Interventions: intervention 1: Bimekizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects will be randomized to receive a combination of injections of Bimekizumab. intervention 2: Subjects randomized to the placebo group, will receive a combination of several injections of Placebo to maintain the blinding.

Protocol documents:
Prot_000.pdf: 
UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 1 of 103
PROTOCOL PS0010 AMENDMENT 2
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP, DOSE 
RANGING STUDY TO EVALUATE THE SAFETY, EFFICACY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS OF 
BIMEKIZUMAB IN ADULT SUBJECTS WITH MODERATE TO 
SEVERE CHRONIC PLAQUE PSORIASIS
PHASE 2B
EudraCT Number: 2016-001891-31
IND Number: 128707
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
Belgium
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
01 Jun 2016
Not applicable
Protocol Amendment 1
08 Jul 2016
Substantial
Protocol Amendment 2
18 Jul 2016
Nonsubstantial
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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B Bio
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 2 of 103
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL, Allée de la Recherche 60, B-1070 Brussels, Belgium
Sponsor Study Physician
Name:
Address:
UCB BioPharma SPRL, Allée de la Recherche, 60, Brussels,
Belgium, B-1070
Phone:
Fax:
Clinical Project Manager
Name:
Address:
UCB BioPharma SPRL, Allée de la Recherche, 60, Brussels,
Belgium, B-1070
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
UCB Biosciences, 8010 Arco Corporation Drive, Raleigh, NC 
27617
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International (IRL) Limited-Ireland
Address:
Ireland Limited at 70 Sir John Rogerson’s Quay, Dublin 2, 
Ireland
Phone:
+353 (1) 477 3171
Fax:
+353 (1) 477 3308
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 3 of 103
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA: +1 800 880 6949
or +1 866 890 3175
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com 
REDACTED COPY 
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 4 of 103
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................10
1
SUMMARY.....................................................................................................................13
2
INTRODUCTION ...........................................................................................................14
2.1 Psoriasis ...........................................................................................................................14
2.1.1
Global epidemiology of psoriasis ........................................................................15
2.1.2
Current treatments for psoriasis...........................................................................15
2.2 Bimekizumab ...................................................................................................................16
2.2.1
Clinical.................................................................................................................16
2.2.2
Nonclinical...........................................................................................................18
3
STUDY OBJECTIVES....................................................................................................18
3.1 Primary objective.............................................................................................................18
3.2 Secondary objectives .......................................................................................................18
3.3 Other objectives ...............................................................................................................19
4
STUDY VARIABLES.....................................................................................................19
4.1 Efficacy variables.............................................................................................................19
4.1.1
Primary efficacy variables ...................................................................................19
4.1.2
Secondary efficacy variable.................................................................................19
4.1.3
Other efficacy variables.......................................................................................19
4.2 Pharmacokinetic, pharmacodynamic, and pharmacogenomic variables .........................20
4.2.1
Pharmacokinetic variables...................................................................................20
4.2.2
Pharmacodynamic variable..................................................................................20
4.2.3
Pharmacogenomic variables ................................................................................21
4.2.3.1
Genomic, genetic, and metabolite variables..............................................21
4.3 Immunological variable ...................................................................................................21
4.4 Safety variables................................................................................................................21
5
STUDY DESIGN.............................................................................................................21
5.1 Study description .............................................................................................................21
5.1.1
Study Periods.......................................................................................................21
5.1.2
Study duration per subject ...................................................................................22
5.1.3
Planned number of subjects and sites ..................................................................23
5.1.4
Anticipated regions and countries .......................................................................23
5.2 Schedule of study assessments.........................................................................................23
5.3 Schematic diagram...........................................................................................................26
5.4 Rationale for study design and selection of dose.............................................................26
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................27
6.1 Inclusion criteria ..............................................................................................................27
6.2 Exclusion criteria .............................................................................................................28
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
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Page 5 of 103
6.3 Withdrawal criteria ..........................................................................................................31
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................33
7
STUDY TREATMENT(S) ..............................................................................................34
7.1 Description of investigational medicinal product(s)........................................................34
7.2 Treatments to be administered.........................................................................................34
7.3 Packaging.........................................................................................................................34
7.4 Labeling ...........................................................................................................................34
7.5 Handling and storage requirements..................................................................................34
7.6 Drug accountability..........................................................................................................35
7.7 Procedures for monitoring subject compliance................................................................35
7.8 Concomitant medication(s)/treatment(s)..........................................................................36
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................36
7.8.2
Prohibited concomitant treatments (medications and therapies).........................36
7.9 Blinding............................................................................................................................38
7.9.1
Procedures for maintaining and breaking the treatment blind.............................38
7.9.1.1
Maintenance of study treatment blind.......................................................38
7.9.1.2
Breaking the treatment blind in an emergency situation...........................38
7.10 Randomization and numbering of subjects......................................................................38
8
STUDY PROCEDURES BY VISIT ...............................................................................39
8.1 Screening Visit.................................................................................................................39
8.2 Baseline Visit...................................................................................................................40
8.3 Week 1 (+/-3 days)...........................................................................................................42
8.4 Week 2 (+/- 3 days)..........................................................................................................42
8.5 Week 4 (+/- 3 days)..........................................................................................................43
8.6 Week 6 (+/- 3 days)..........................................................................................................44
8.7 Week 8 (+/- 3 days)..........................................................................................................45
8.8 Week 12 (+/- 3 days) Study Exit/Early Withdrawal........................................................46
8.9 Safety Follow-Up Visit (20 weeks after the last dose) ....................................................47
8.10 Early Withdrawal Visit ....................................................................................................48
8.11 Unscheduled Visit............................................................................................................48
9
ASSESSMENT OF EFFICACY......................................................................................48
9.1 Psoriasis Area and Severity Index ...................................................................................48
9.2 BSA affected by psoriasis................................................................................................49
9.3 Investigator’s Global Assessment....................................................................................49
9.4 Dermatology Life Quality Index......................................................................................50
9.5 Hospital Anxiety and Depression Scale...........................................................................50
9.6 Modified Nail Psoriasis Severity Index Score.................................................................50
9.7 Patient’s Global Assessment of Disease Activity for the arthritis visual analog scale....51
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
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Page 6 of 103
9.8 Patient Global Impression of Change ..............................................................................51
9.9 Patient Global Impression of Severity.............................................................................51
9.10 Psoriasis Scalp Severity Index.........................................................................................51
9.11 Patient Symptom Diary responses ...................................................................................52
9.12 36-Item Short Form Health Survey..................................................................................53
10
ASSESSMENT OF PHARMACOKINETICS/ 
PHARMACODYNAMICS/PHARMACOGENOMICS.................................................53
10.1 Pharmacokinetic and pharmacodynamic variables..........................................................53
10.2 Pharmacogenomic variables ............................................................................................53
10.2.1
Genomics, genetics, and proteomics variables....................................................53
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................54
11.1 Assessment of immunogenicity.......................................................................................54
11.2 Assessment of immunological variables..........................................................................54
12
ASSESSMENT OF SAFETY..........................................................................................54
12.1 Adverse events.................................................................................................................54
12.1.1
Definition of adverse event..................................................................................54
12.1.2
Adverse events of special interest........................................................................55
12.1.3
Adverse events for special monitoring ................................................................55
12.1.4
Procedures for reporting and recording adverse events.......................................55
12.1.5
Description of adverse events..............................................................................55
12.1.6
Follow up of adverse events ................................................................................56
12.1.7
Rule for repetition of an adverse event................................................................56
12.1.8
Pregnancy ............................................................................................................56
12.1.9
Suspected transmission of an infectious agent via a medicinal product..............57
12.1.10
Overdose of investigational medicinal product ...................................................57
12.1.11
Safety signal detection.........................................................................................57
12.2 Serious adverse events .....................................................................................................58
12.2.1
Definition of serious adverse event .....................................................................58
12.2.2
Procedures for reporting serious adverse events .................................................59
12.2.3
Follow up of serious adverse events....................................................................59
12.3 Immediate reporting of adverse events............................................................................59
12.4 Anticipated serious adverse events ..................................................................................60
12.5 Laboratory measurements................................................................................................60
12.5.1
Evaluation of PDILI ............................................................................................61
12.5.1.1
Consultation with Medical Monitor and local hepatologist ......................66
12.5.1.2
Immediate action: determination of IMP discontinuation.........................66
12.5.1.3
IMP restart/rechallenge .............................................................................66
12.5.1.4
Testing: identification/exclusion of alternative etiology...........................66
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Bimekizumab
PS0010
Confidential
Page 7 of 103
12.5.1.5
Follow-up evaluation.................................................................................68
12.6 Other safety measurements..............................................................................................68
12.6.1
Assessment and management of TB and TB risk factors....................................68
12.6.1.1
Tuberculosis assessment by IGRA............................................................70
12.6.1.2
Chest x-ray for tuberculosis ......................................................................71
12.6.1.3
Tuberculosis questionnaire........................................................................71
12.6.1.4
Tuberculosis management.........................................................................71
12.6.2
Pregnancy testing.................................................................................................72
12.6.3
Vital signs ............................................................................................................72
12.6.4
12-lead electrocardiograms..................................................................................72
12.6.5
Physical examination...........................................................................................72
12.6.6
Height and body weight.......................................................................................73
12.6.7
Assessment of suicidal ideation and behavior.....................................................73
12.7 Other study measurements...............................................................................................73
12.7.1
Demographic information....................................................................................73
12.7.2
Medical History ...................................................................................................73
12.7.3
Psoriasis History..................................................................................................73
12.7.4
Data Monitoring Committee................................................................................73
13
STUDY MANAGEMENT AND ADMINISTRATION.................................................74
13.1 Adherence to protocol......................................................................................................74
13.2 Monitoring .......................................................................................................................74
13.2.1
Definition of source data .....................................................................................74
13.2.2
Source data verification .......................................................................................75
13.3 Data handling...................................................................................................................75
13.3.1
Case Report Form completion.............................................................................75
13.3.2
Database entry and reconciliation........................................................................75
13.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............76
13.4 Termination of the study..................................................................................................76
13.5 Archiving and data retention............................................................................................76
13.6 Audit and inspection ........................................................................................................77
13.7 Good Clinical Practice .....................................................................................................77
14
STATISTICS ...................................................................................................................77
14.1 Definition of analysis sets................................................................................................77
14.2 General statistical considerations.....................................................................................78
14.3 Planned efficacy analyses ................................................................................................78
14.3.1
Analysis of the primary efficacy variable............................................................78
14.3.1.1
Sensitivity analyses ...................................................................................79
14.3.2
Other efficacy analyses........................................................................................79
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Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 8 of 103
14.3.2.1
Analysis of the secondary efficacy variables ............................................79
14.3.2.2
Analysis of the other efficacy variables ....................................................79
14.3.3
Subgroup analyses ...............................................................................................80
14.4 Planned safety and other analyses....................................................................................80
14.4.1
Safety analyses.....................................................................................................80
14.4.2
Pharmacokinetics/pharmacodynamics analyses ..................................................80
14.5 Handling of protocol deviations.......................................................................................81
14.6 Handling of dropouts or missing data..............................................................................81
14.7 Planned interim analysis and data monitoring.................................................................82
14.8 Determination of sample size...........................................................................................82
15
ETHICS AND REGULATORY REQUIREMENTS......................................................83
15.1 Informed consent .............................................................................................................83
15.2 Subject identification cards..............................................................................................83
15.3 Institutional Review Boards and Independent Ethics Committees..................................84
15.4 Subject privacy.................................................................................................................84
15.5 Protocol amendments.......................................................................................................85
16
FINANCE, INSURANCE, AND PUBLICATION.........................................................85
17
REFERENCES ................................................................................................................85
18
APPENDICES .................................................................................................................88
18.1 Protocol Amendment 1 ....................................................................................................88
18.2 Protocol Amendment 2 ....................................................................................................97
19
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................102
20
SPONSOR DECLARATION ........................................................................................103
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................23
Table 7‒1:
Prohibited psoriasis medications......................................................................37
Table 9‒1:
Body areas for calculation of percent BSA for PASI ......................................49
Table 9‒2:
Five-point Investigator’s Global Assessment..................................................50
Table 9‒3:
Parameters assessed for the PSSI.....................................................................52
Table 12‒1:
Anticipated serious adverse events for the population of subjects with 
moderate to severe chronic plaque psoriasis....................................................60
Table 12‒2:
Laboratory measurements................................................................................60
Table 12‒3:
Required investigations and follow up for PDILI............................................63
Table 12‒4:
PDILI laboratory measurements......................................................................67
Table 12‒5:
PDILI information to be collected...................................................................68
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Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 9 of 103
LIST OF FIGURES
Figure 5‒1:
Schematic diagram of PS0010.........................................................................26
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 10 of 103
LIST OF ABBREVIATIONS
AE
adverse event
AESI
adverse events of special interest
AESM
adverse events for special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BSA
body surface area (affected by psoriasis) 
cAMP
cyclic adenosine monophosphate
CAT
Computed Axial Tomography
CDMS
clinical data management system
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRF
Case Report Form
CRP
C-reactive protein
eCRF
electronic Case Report Form
CRO
Contract Research Organization
eC-SSRS
electronic Columbia Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
DAP
data analysis plan
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
ECG
electrocardiogram
EDC
Electronic Data Capture
ES
Enrolled Set
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FACS
Fluorescence-activated cell sorting
FAS
Full Analysis Set
GCP
Good Clinical Practice
GI
gastrointestinal
GMP
Good Manufacturing Practice
HADS
Hospital Anxiety and Depression Scale
HBV
hepatitis B virus
HBcAb
anti-hepatitis B core antibody
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 11 of 103
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IgG1
immunoglobulin G1
IGRA
interferon-gamma release assay  
IL
interleukin
IMP
investigational medicinal product
IND
Investigational New Drug
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
iv
intravenous
IXRS
interactive voice or web response system (IVRS or IWRS)
IWRS
interactive web response system
kg
kilogram
LOCF
last observation carried forward
LTB
latent TB
mAb
monoclonal antibody
MCS
Mental Component Summary
MCID
minimal clinically important difference
MID
minimally important difference
MedDRA
Medical Dictionary for Regulatory Activities
mNAPSI
modified nail psoriasis severity index
NOAEL
no adverse effect level
NRI
non-responder imputation
NSAID
non-steroidal anti-inflammatory drug
PASI
Psoriasis Area and Severity Index
PBO
placebo
PCS
Physical Component Summary 
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Bimekizumab
PS0010
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Page 12 of 103
PD
pharmacodynamics 
PDE4
phosphodiesterase 4
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamics Per-Protocol Set 
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetics
PK-PPS
Pharmacokinetics Per-Protocol Set
PPS
Per-Protocol Set
PRO
Patient-reported outcome
PS
Patient Safety
PSO
psoriasis
PSSI
Psoriasis Scalp Severity Index
PGADA
Patient’s Global Assessment of Disease Activity
RS
Randomized Set
SAE
serious adverse event
SAP
statistical analysis plan
sc
subcutaneous
SF-36
36-Item Short Form Health Survey
SFU
Safety Follow-Up
SOC
System Organ Class
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TNF
tumor necrosis factor
ToPAS
Toronto Psoriatic Arthritis Screening questionnaire
ULN
upper limit of normal
VAS
visual analog scale
WD
withdrawal
Q4W
every 4 weeks
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 13 of 103
1
SUMMARY
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to investigate the safety, efficacy, pharmacokinetics (PK), and 
pharmacodynamics (PD) of bimekizumab (also known as UCB4940) compared with placebo in 
adult subjects with moderate to severe chronic plaque psoriasis in order to guide the selection of 
doses and clinical indices in the Phase 3 development program.
The study population consists of adult subjects (≥18 years of age) with a diagnosis of moderate 
to severe chronic plaque psoriasis (Baseline Psoriasis Area and Severity Index [PASI] ≥12 and 
body surface area [BSA] affected by psoriasis ≥10% and Investigator’s Global Assessment 
[IGA] score ≥3 [on a 5-point scale]) who are a candidate for systemic psoriasis therapy and/or 
phototherapy and/or chemophototherapy.
Approximately 320 subjects will be screened in order to have 240 subjects randomized in the 
study. There will be approximately 40 subjects per treatment arm. For each subject, the study 
will last a maximum of 32 weeks and will consist of 3 periods, a Screening Period (2 to 
4 weeks), a Treatment Period (12 weeks), and a Safety Follow-Up (SFU) Period (20 weeks after 
the last dose of study medication). After the 12-week Treatment Period, eligible subjects will be 
allowed to enroll in an extension study. 
During the Treatment Period eligible subjects will be randomized 1:1:1:1:1:1 to receive the 
following blinded study treatment regimens:
!
Bimekizumab 64mg administered subcutaneously (sc) every 4 weeks (Q4W)
!
Bimekizumab 160mg administered sc Q4W
!
Bimekizumab 320mg loading dose administered sc at Baseline followed by 160mg dose 
administered sc Q4W.
!
Bimekizumab 320mg administered sc Q4W
!
Bimekizumab 480mg administered sc Q4W
!
Placebo administered sc Q4W
Approximately 40 subjects will be randomized to each treatment arm and study medication will 
be administered in the clinic at Baseline, Week 4, and Week 8. Additional nondosing study visits 
will occur at Week 1, Week 2, and Week 6. At Week 12, all subjects enrolling in the extension 
study will undergo the Week 12 study assessments before receiving their first extension study
dose of study treatment. All subjects not enrolling in the extension study will have the Week 12 
study assessments and will enter the SFU Period.
Subjects withdrawing early from the study will undergo the Early Withdrawal Visit assessments 
and will enter the SFU Period. Subjects who withdraw early from study treatment will be asked 
to return for study assessments 12 weeks after the first dose (ie, the Week 12 Visit) and for the 
SFU Visit.
The primary objective of the study is to evaluate the dose response of bimekizumab administered 
sc every 4 weeks for 12 weeks in the treatment of subjects with moderate to severe chronic 
plaque psoriasis.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 14 of 103
The secondary objectives of the study are to assess the efficacy of individual dose regimens of 
bimekizumab compared to placebo, the PK, safety, tolerability, and immunogenicity of 
bimekizumab, and to assess the exposure response relationship of bimekizumab as it relates to 
efficacy and safety.
The other objectives of the study are to demonstrate the effects of bimekizumab on improvement 
of general health-related quality of life (QOL), skin-related QOL, and psoriatic disease in nails 
and scalp (in subjects with nail and scalp disease at Baseline). Analyses of genomic, genetic, and 
proteomic biomarkers may also be performed.
The primary efficacy variable is the PASI90 response defined as a subject that achieves 90% 
reduction in the PASI score at Week 12. The secondary efficacy variables are IGA response at 
Week 12 and Week 8, PASI90 response at Week 8, PASI75 response at Week 12, and PASI100 
response at Week 12. The other efficacy variables are listed in Section 4.1.3. 
Pharmacokinetic and PD variables are listed in Section 4.2.1 and Section 4.2.2, respectively,
immunological variables are listed in Section 4.3, and pharmacogenomics variables are listed in
Section 4.2.3.
Pharmacokinetic, PD, genomic, genetic, proteomic, and immunological variables will be 
evaluated to assess their relationship to treatment response.
Safety variables to be assessed are adverse events (AEs), vital signs, electrocardiograms (ECGs), 
physical examination, and measurements of laboratory parameters.
2
INTRODUCTION
2.1
Psoriasis 
Psoriasis is a common, chronic inflammatory disease characterized by a series of linked cellular 
changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and 
infiltration of T lymphocytes, neutrophils, and other types of leukocytes in affected skin. Though 
the pathophysiology of psoriasis is not fully understood, the importance of T-cells and 
inflammatory cytokines has been demonstrated by the clinical benefit provided by therapies 
directed at these targets (Kreuger and Ellis, 2005). 
There are a variety of forms including plaque, guttate, inverse, pustular, and erythrodermic. 
Plaque psoriasis is the most common, comprising approximately 80% to 90% of all cases. 
Approximately 17% of those with psoriasis have moderate to severe disease (Kurd et al, 2008).
In addition to the impact on skin, psoriasis has a multitude of psychosocial and emotional effects 
on patients, including increased self-consciousness, frustration, fatigue, depression, and suicidal 
ideation. As a result, patients frequently report sleeping problems, difficulties at work, problems 
interacting with family members, disrupted leisure activities, and sexual difficulties 
(Dowlatshahi et al, 2014; Gottlieb, 2005; Mukhtar et al, 2004; Ortonne, 2004; Krueger et al, 
2001). 
A number of comorbidities have been associated with psoriasis, especially with more severe 
psoriasis. Psoriatic arthritis, cardiovascular disease, metabolic syndrome, chronic pulmonary 
disease, peptic ulcer disease, renal disease, and diabetes have all been demonstrated to have an 
increased prevalence in psoriasis patients (Yeung et al, 2013; Christophers et al, 2010; Gisondi et 
al, 2007; Gelfand et al, 2006).
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 15 of 103
2.1.1
Global epidemiology of psoriasis
Psoriasis affects approximately 3% of the adult US population (Rachakonda et al, 2014; Kurd 
and Gelfand, 2009) and its onset can begin at any age (Augustin et al, 2010; Icen et al, 2009). 
The reported worldwide incidence and prevalence of psoriasis varies greatly depending on age, 
gender, ethnicity, and geography primarily due to genetic and environmental factors. Estimates 
of incidence and prevalence include all types of psoriasis. Plaques psoriasis is the most common 
form of psoriasis therefore reported estimates of the magnitude of this condition are likely 
weighted heavily by this subtype. Both the incidence and prevalence of psoriasis are higher 
among Caucasians and those living in higher latitudes. Psoriasis affects approximately 2% to 4% 
of the population of western countries. Geographical differences are also influenced by case 
definition, study design, and the definition of prevalence (Parisi et al, 2013; Langley et al, 2005; 
Raychaudhuri and Gross, 2000).
2.1.2
Current treatments for psoriasis
Therapy for patients with psoriasis varies according to the severity of disease. Limited or mild 
disease is often treated with topical therapies such as corticosteroids and vitamin D analogs. 
Patients with more severe disease are often treated with chemophototherapy, methotrexate, the 
oral phosphodiesterase 4 (PDE4) inhibitor (apremilast), or biologic agents, such as tumor 
necrosis factor (TNF) antagonists, interleukin (IL) 12/23 inhibitors, and IL-17A inhibitors. The 
effectiveness of TNF inhibitors in the treatment of psoriasis has been demonstrated in many 
Phase 3 clinical studies and has led to the approval of multiple TNF inhibitors for use in patients 
with moderate to severe psoriasis. Interleukin inhibitors include secukinumab and ixekizumab, 
IL-17A inhibitors approved for treatment of moderate to severe psoriasis. Ustekinumab is an IL-
12/23 antagonist approved for use in patients with moderate to severe psoriasis, and brodalumab, 
an IL-17 receptor antagonist, has completed pivotal Phase 3 studies in psoriasis. Standard 
therapies for psoriasis are listed below:
!
Topical steroids (eg, triamcinolone, mometasone, clobetasol, betamethasone, hydrocortisone) 
are generally used as first-line treatment of psoriasis. High-strength steroids are typically 
reserved for use on the arms and legs. Areas such as the face and skin folds (axillary, 
inguinal regions, etc) are usually treated with a low potency steroid. Chronic use of topical 
steroids can lead to corticosteroid-related side effects and is generally discouraged.
!
Vitamin D analogs (eg, calcipotriol and tacalcitol) are commonly used to treat mild to 
moderate psoriasis, and work best within the mild patients. They are safe but lack efficacy 
for many moderate to severe patients.
!
Chemophototherapy is a frequent option for moderate to severe patients, but the 
inconvenience of multiple treatment visits and varying efficacy limits its use in the market. 
!
Methotrexate is a systemic immunosuppressant and is used in moderate to severe patients. 
Toxicity concerns, particularly in older patients, are a major drawback.
!
Apremilast is an oral small-molecule inhibitor of PDE4 that is also approved for treatment of 
adults with moderate to severe plaque psoriasis. PDE4 inhibitors work intracellularly to 
modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic 
adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory 
cells. PDE4 inhibition elevates intracellular cAMP levels, which in turn down-regulates the 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 16 of 103
inflammatory response by modulating the expression of TNFα, IL-23, IL-17, and other 
inflammatory cytokines.
!
Biologics, including TNFα inhibitors (adalimumab, etanercept, and infliximab), 
IL-12/23 inhibitors (ustekinumab), and IL-17A inhibitors are the treatment options of choice 
for patients with moderate to severe plaques psoriasis who are candidates for systemic 
therapy or phototherapy. These products are injected sc or delivered via intravenous (iv) 
infusion and while effective, TNFα inhibitors come with boxed warnings including the risk 
of serious infections and reports of lymphoma and malignancy in children and adolescent 
patients. The efficacy of TNFα inhibitors in treating psoriasis has been attributed to their 
inhibition of Th17-T cells. Different from the traditional systemic drugs that impact the entire 
immune system, biologics target specific parts of the immune system and offer reduced 
multi-organ toxicity and adverse effects associated with traditional treatments.
Secukinumab has been approved in the US and the EU for the treatment of moderate to 
severe plaque psoriasis in adult patients who are candidates for systemic therapy or 
phototherapy. Secukinumab is a monoclonal antibody (mAb) that inhibits the activity of the 
IL-17A isoform and is the first approved drug in its class. Clinical study results have shown 
that secukinumab achieves higher efficacy response levels than other drugs historically, 
demonstrating that IL-17 is a very effective target for the development of drugs for the 
treatment of psoriasis. 
2.2
Bimekizumab
Bimekizumab is an engineered, humanized, full-length immunoglobulin G1 (IgG1) mAb, with 
high affinity for human IL-17A and IL-17F, important proinflammatory cytokines of the IL-17 
family believed to play important roles in autoimmune and inflammatory diseases. Interleukin-
17A has been shown to have a role in pathogenesis of several autoimmune disorders and IL-17F 
has been increasingly recognized to contribute to the pathogenesis of a number of inflammatory 
diseases, including psoriasis, ulcerative colitis, asthma, ankylosing spondylitis, psoriatic arthritis, 
and rheumatoid arthritis. While anti-IL-17A antibodies have demonstrated efficacy in patients 
with psoriasis, psoriatic arthritis and ankylosing spondylitis, as yet, no therapeutic approach is 
available that fully inhibits the activity of IL-17F. Bimekizumab selectively and potently inhibits 
the activity of both IL-17A and IL-17F isoforms in vitro. Therefore, it permits an evaluation of 
the potential for additional efficacy, that may be conferred by dual inhibition of both cytokines, 
in patients suffering from diseases in which both cytokines are active.
2.2.1
Clinical
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, and PA0007 in 53 subjects with 
psoriatic arthritis. Two studies (RA0123 and UP0031) are ongoing in subjects with moderate to 
severe rheumatoid arthritis and in healthy subjects, respectively.
UP0008 was a Phase 1, single ascending dose study in adults with mild to moderate psoriasis 
affecting ≤5% BSA. In this blinded study, single doses of up to 640mg (approximately 8mg/kg 
in an 80kg adult) were evaluated without any safety concerns. A total of 26 subjects with 
psoriasis with less than 5% of body surface involvement were treated with a range of single iv 
doses from 8 to 640mg. There were no clinically relevant safety findings identified at any dose 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 17 of 103
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 PK of bimekizumab was linear in the tested dose range and 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 160mg iv, respectively). 
Bimekizumab has also been investigated in a Phase 1b, proof of concept, randomized,
placebo-controlled, multiple dose study (PA0007). The primary objective of PA0007 was to 
assess the safety and PK of multiple dose administration of iv bimekizumab in subjects with 
psoriatic arthritis. Four active doses and a placebo were tested. Drug was administered as a 
loading dose at Week 0, and 2 additional doses were administered at Week 3 and Week 6. In 
each treatment group, subjects received a total of 3 doses of bimekizumab, administered every 3 
weeks as shown below:
!
80mg loading dose followed by 40mg at Weeks 3 and 6
!
160mg loading dose followed by 80mg at Weeks 3 and 6
!
240mg loading dose followed by 160 mg at Weeks 3 and 6
!
560mg loading dose followed by 320mg at Weeks 3 and 6
The results of this study demonstrated that all doses of bimekizumab were well tolerated and 
there were no unexpected clinically relevant safety findings.
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 (oropharhyngitis and vulvovaginitis, respectively) that were non-serious 
and resolved with topical therapy. There was a potential reduction in mean neutrophil count in 
the active treatment group, although this drop was not clinically relevant and a clear relationship 
with dose or time was not evident. Some increases in liver function tests were reported, but none 
had a convincing relationship to exposure to study medication. The exploratory analysis showed 
clinically relevant improvement in activity of psoriatic arthritis and in skin involvement in those 
subjects with concomitant active psoriatic lesions.
Two additional studies of bimekizumab are ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy 
of multiple doses of bimekizumab administered as add-on therapy to stable certolizumab pegol 
therapy in subjects with moderate to severe rheumatoid arthritis. UP0031 is a Phase 1 open-label, 
parallel-group, single-dose study to evaluate the relative bioavailability and tolerability of 
bimekizumab 160mg sc in healthy subjects.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 18 of 103
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
2.2.2
Nonclinical
Parallel inhibition of IL-17A and IL-17F has been shown to be efficacious 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 revealed. 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 is considered the 
consequence of a change in local mucosal immunity. To date, similar findings have not been 
seen in studies in humans.
Additional information on the nonclinical data for bimekizumab is available in the current 
version of the IB.
3
STUDY OBJECTIVES
3.1
Primary objective
The primary objective of the study is to evaluate the dose response of bimekizumab administered 
sc every 4 weeks for 12 weeks in the treatment of subjects with moderate to severe chronic 
plaque psoriasis.
3.2
Secondary objectives
The secondary objectives of the study are to:
!
Evaluate the efficacy of individual dose regimens of bimekizumab compared to placebo after 
12 weeks of treatment for subjects with moderate to severe chronic plaque psoriasis
!
Compare the efficacy of the bimekizumab 160mg treatment group versus the bimekizumab
160mg treatment group with a 320mg loading dose
!
Assess the PK of bimekizumab following sc dosing Q4W
!
Assess the safety, immunogenicity, and tolerability of bimekizumab
!
Assess the exposure response relationship of bimekizumab as it relates to efficacy and safety
!
Characterize the population PK of bimekizumab in the moderate to severe psoriatic 
population following repeat dose administration
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 19 of 103
3.3
Other objectives
The other objectives of the study are to:
!
Assess the improvement of skin-related QOL
!
Assess the improvement of general health-related QOL
!
Assess psoriatic nail disease in subjects with nail disease at Baseline
!
Assess psoriatic scalp disease in subjects with scalp psoriasis at Baseline
!
Assess the effect of bimekizumab on gene and protein expression, and explore the 
relationship between genomic, genetic, and proteomic biomarkers and disease biology, drug 
treatment and inflammatory and immune responses.
4
STUDY VARIABLES
4.1
Efficacy variables
4.1.1
Primary efficacy variables
The primary efficacy variable is the PASI90 response defined as a subject that achieves 90% 
reduction from Baseline in the PASI score at Week 12.
4.1.2
Secondary efficacy variable
The secondary efficacy variables are:
!
IGA response (Clear or Almost Clear with at least 2 category improvement from Baseline) at 
Week 12
!
IGA response (Clear or Almost Clear with at least 2 category improvement from Baseline) at 
Week 8
!
PASI90 response at Week 8
!
PASI75 response at Week 12
!
PASI100 response at Week 12
4.1.3
Other efficacy variables
The other efficacy variables are listed below and will be evaluated at all scheduled visits in 
accordance with the Schedule of Assessments in Table 5‒1. This excludes the primary and 
secondary variables as specified in Section 4.1.1 and Section 4.1.2. 
!
PASI50, PASI75, PASI90, and PASI100 response
!
IGA response (Clear or Almost Clear with at least 2 category improvement from Baseline) 
!
Absolute and percent change from Baseline in PASI score 
!
Shift from Baseline in IGA score
!
Change from Baseline in Dermatology Life Quality Index (DLQI)
!
Percentage of subjects achieving a DLQI score of 0 or 1
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 20 of 103
!
Percentage of subjects achieving a minimal clinically important difference (MCID) 
(improvement from Baseline of 5 or more) in the DLQI
!
Time to PASI50 response
!
Time to PASI75 response
!
Time to PASI90 response
!
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!
Absolute and percent change from Baseline in the BSA affected by psoriasis 
!
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subgroup of subjects with psoriatic nail disease at Baseline)
!
Change from Baseline in the Patient's Global Assessment of Disease Activity (PGADA) for 
the arthritis visual analog scale (VAS) 
!
Change from Baseline in the Psoriasis Scalp Severity Index (PSSI) (in the subgroup of 
subjects with scalp psoriasis at Baseline)
!
Change from Baseline in Short Form 36 item Health Survey (SF-36) Physical Component 
Summary (PCS) score, and Mental Component Summary (MCS) score, and individual 
domains
!
Change from Baseline in the Patient Symptom Diary responses (for subjects at sites in
selected countries) 
!
Patient Global Impression of Change (PGIC)
!
Change from Baseline in Patient Global Impression of Severity (PGIS)
!
Change from Baseline in Hospital Anxiety and Depression Scale (HADS) HADS-A and 
HADS-D scores 
!
Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
4.2
Pharmacokinetic, pharmacodynamic, and pharmacogenomic 
variables
4.2.1
Pharmacokinetic variables
The PK variables are listed below:
!
Plasma concentration of bimekizumab and population PK (CL/F, V/F)
!
Dose-exposure response characterizing the relationship between PASI score and 
bimekizumab concentration and dose, including EC50/ED50 and Emax to support dose 
selection for subsequent Phase 3 studies
4.2.2
Pharmacodynamic variable
The PD variable is to determine the plasma concentrations of cytokines of relevance to IL17-A/F 
signaling pathway and psoriasis biology, including but not limited to serum complement 
concentrations, mononuclear cell subtypes, and cytokines and other candidate biomarkers.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 21 of 103
4.2.3
Pharmacogenomic variables
4.2.3.1
Genomic, genetic, 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, and proteomic biomarkers relevant to the 
inflammatory and immune response processes. The nature and format of these tentative analyses 
will be determined when the results of the main study are made available.
4.3
Immunological variable
The immunological variable is anti-bimekizumab antibody detection prior to and following study 
treatment. 
4.4
Safety variables
Safety variables to be assessed are:
!
Severity and frequency of AEs
!
Change from Baseline in clinical laboratory values (chemistry, hematology, and urinalysis) 
!
Change from Baseline in vital signs
!
Change from Baseline in physical examination
!
ECG results
5
STUDY DESIGN
5.1
Study description
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to evaluate the safety, efficacy, PK, and PD of bimekizumab administered sc 
to subjects with psoriasis. To be eligible to participate in this study, subjects must be adults with 
a diagnosis of moderate to severe psoriasis (Baseline PASI ≥12 and BSA affected by psoriasis 
≥10% and IGA score ≥3 [on a 5-point scale]) who are a candidate for systemic psoriasis therapy 
and/or phototherapy and/or chemophototherapy.
5.1.1
Study Periods
This study will include 3 periods, a Screening Period (2 to 4 weeks), a Treatment Period 
(12 weeks), and a SFU Period (20 weeks after the last dose of study medication). After the 
12-week Treatment Period, eligible subjects will be allowed to enroll in an extension study
(PS0011). 
Screening Period
The Screening Period will last 2 weeks, but can be extended up to a total of 4 weeks in the event 
that applicable laboratory screening tests require retesting if the initial results are in error, 
borderline, or indeterminate. During this time, laboratory data (hematology, urine, and 
biochemistry tests) will be obtained, the doses of non-steroidal anti-inflammatory drug 
(NSAIDs) (if used to treat psoriatic arthritis), will be verified as stable. 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 22 of 103
Treatment Period
During the Treatment Period subjects will be randomized 1:1:1:1:1:1 to receive the following 
blinded study treatment regimens:
!
Bimekizumab 64mg administered sc Q4W
!
Bimekizumab 160mg administered sc Q4W
!
Bimekizumab 320mg loading dose administered sc at Baseline followed by 160mg dose 
administered sc Q4W
!
Bimekizumab 320mg administered sc Q4W
!
Bimekizumab 480mg administered sc Q4W
!
Placebo administered sc Q4W
Approximately 320 subjects will be screened in order to have 240 subjects randomized in the 
study. There will be approximately 40 subjects per treatment arm and study medication will be 
administered in the clinic at Baseline, Week 4, and Week 8. Additional nondosing study visits 
will occur at Week 1, Week 2, and Week 6.
At Week 12, all subjects enrolling in the extension study (PS0011) will undergo the Week 12 
study assessments and then receive their first extension study dose of study treatment. All 
subjects not enrolling in the extension study will have the Week 12 study assessments and will 
enter the SFU Period.
Subjects who withdraw early from study treatment will be asked to return for study assessments 
12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit. 
Subjects withdrawing early from the study will undergo the early Withdrawal Visit assessments 
and will enter the SFU Period.
The assessments at each Treatment Period Visit are presented in Table 5‒1.
Safety Follow-Up Period
All subjects not continuing in the extension study, 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.
5.1.2
Study duration per subject
For each subject, the study will last a maximum of up to 32 weeks. This includes the following 
study period durations:
!
Screening Period: 2 to 4 weeks 
!
Double-blind, placebo-controlled Treatment Period: 12 weeks
!
Safety Follow-Up Period: a SFU Visit is planned 20 weeks after the last dose of study 
medication
After the 12-week Treatment Period, subjects will be allowed to enroll in an extension study. 
The SFU Visit will not be conducted in PS0010 for subjects who enroll in the extension study.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 23 of 103
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.3
Planned number of subjects and sites
Approximately 320 subjects will be screened in order to have 240 subjects randomized in the 
study. There will be approximately 40 subjects per treatment arm. The planned number of study 
sites is approximately 40.
5.1.4
Anticipated regions and countries
The regions planned for study conduct are Europe, Canada, and the US, with possible extension 
to other regions and countries. 
5.2
Schedule of study assessments
A schedule of study assessments is provided in Table 5‒1.
Table 5‒1:
Schedule of study assessments
  
Visita/ Week
Protocol activity
Screening
Baseline (first 
dose)
Double-blind Treatment Period
(Time after the first dose)
1
2
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6
8
12/WD
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X
Xd
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X
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Toronto Psoriatic arthritis screening 
questionnaire
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concomitant diseases
X
Xe
Physical examf
X
X
X
Height
X
Body Weight
X
X
X
X
Vital signsg
X
X
X
X
X
X
X
X
X
HADS
X
X
X
X
X
X
eC-SSRS
X
X
X
X
X
X
X
X
X
Hematology/biochemistry/urinalysis
X
X
X
X
X
X
X
X
X
Central ECG
X
X
X
X
X
X
X
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X
X
X
X
X
X
X
X
X
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X
HIV testing
X
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X
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 24 of 103
Table 5‒1:
Schedule of study assessments
  
Visita/ Week
Protocol activity
Screening
Baseline (first 
dose)
Double-blind Treatment Period
(Time after the first dose)
1
2
4
6
8
12/WD
SFUb
IGRA tuberculosis testk
X
X
Tuberculosis questionnaire
X
X
X
Blood sample for bimekizumab 
plasma concentrationsl
X
X
X
X
X
X
X
Blood sample for anti-bimekizumab 
antibodiesl
X
X
X
X
X
Blood sample for cytokines, 
complement, candidate biomarker 
analysis, and flow cytometryl
X
X
X
X
X
Blood sample genomic, 
genetic/epigenetic proteomic, and 
metabolomics analysesc l
X
X
X
X
PASI 
X
X
X
X
X
X
X
X
X
IGA 
X
X
X
X
X
X
X
X
X
BSA affected by psoriasis
X
X
X
X
X
X
mNAPSI 
X
X
X
X
DLQI
X
X
X
X
X
X
X
PGADA 
X
X
Psoriasis Scalp Severity Index
X
X
X
X
X
Patient Symptom Diary responses (for 
subjects at sites in selected countries)
X
X
X
X
X
X
X
PGIS
X
X
X
X
X
X
X
PGIC
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
Xm
IXRSn
X
X
X
X
X
X
X
X
X
Bimekizumab or placebo 
administrationo
X
X
X
BSA=body surface area; eC-SSRS=electronic Columbia Suicide Severity Rating Scale; DLQI=Dermatology Life 
Quality Index; ECG=electrocardiogram; HADS=Hospital Anxiety and Depression Scale; HIV=human 
immunodeficiency virus; IGA=Investigator’s Global Assessment; IGRA=interferon gamma release assay; 
IXRS=interactive voice or web response system; mNAPSI=modified Nail Psoriasis Severity Index; PASI=Psoriasis 
Area and Severity Index; PGADA=Patient’s Global Assessment of Disease Activity; PGIC=Patient Global 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 25 of 103
Impression of Change; PGIS=Patient Global Impression of Severity; SF-36=36-Item Short Form Health Survey; 
SFU=Safety Follow-Up; TB=tuberculosis; WD=withdrawal
a Visit windows of +/- 3 days from the first dose at all visits except SFU. SFU Visit window is -3 and +7 days from 
last dose.
b The SFU Visit will occur 20 weeks after the last dose.
c A separate Informed Consent Form will be required for subjects who decide to participate in the genomics, 
genetics, and proteomics substudy. The Informed Consent Form must be signed prior to collecting any samples for 
the substudy. 
d A separate Informed Consent Form is required to be completed for the extension study (PS0011) at Week 8 or 
Week 12. The sites are encouraged to begin the PS0011 consent process at Week 8.
e Ensure no significant changes in medical history.
f Includes evaluation of signs and symptoms of active TB and risk for exposure to TB.
g Vital signs (blood pressures, pulse rate, and temperature) are to be measured prior to blood sampling, and prior to 
dosing, where applicable. 
h Pregnancy testing will be serum testing at Screening and SFU. The pregnancy test will be urine at all other visits.
i Subjects who have evidence of or test positive for hepatitis B by any of the following criteria: 1) positive for 
hepatitis B surface antigen (HBsAg+); or, 2) positive for anti-hepatitis B core antibody (HBcAb+) are excluded; a 
positive test for HCV is defined as: 1) positive for hepatitis C antibody (anti-HCV Ab), and 2) positive via a 
confirmatory test for HCV (for example, HCV polymerase chain reaction) are also excluded. Subjects will also be 
tested for anti-hepatitis B surface antibody.
j A chest x-ray must be performed at Screening or must occur within 3 months prior to Screening and results must 
be available at Baseline.
k It is recommended that the QuantiFERON TB GOLD test be performed.
l All blood samples taken prior to dosing.
m Including assessment for the development of different forms of psoriasis at the SFU visit.
n Drug administration is based on randomization.
o The time between doses should be no less than 24 days and no more than 32 days.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 27 of 103
!
Bimekizumab 160mg administered sc Q4W
!
Bimekizumab 320mg loading dose administered sc at Baseline followed by 160mg dose 
administered sc Q4W
!
Bimekizumab 320mg administered sc Q4W
!
Bimekizumab 480mg administered sc Q4W
!
Placebo administered sc Q4W
These doses were chosen based on the efficacy and safety data from the 3 completed clinical 
studies of bimekizumab (UP0008, RA0124, and PA0007). These doses support the maximum 
likelihood of confirmation of efficacy for bimekizumab in subjects with moderate to severe
chronic plaque psoriasis while presenting a high likelihood of an acceptable safety profile. 
The study duration of 12 weeks is considered appropriate to show the separation between the 
doses studied to assess dose-response relationship. Twelve weeks is an appropriate duration to 
determine the induction of efficacy in patients with plaque psoriasis who are starting a biologic 
therapy.
The study is double-blind in order to avoid subjective bias in the reporting and assessment of the 
efficacy, safety, and tolerability effects of bimekizumab. Placebo will be administered as a 
control in order to provide a comparison of inactive treatment to bimekizumab and to establish 
the frequency and/or magnitude of changes in clinical endpoints that may occur in the absence of 
active treatment.
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 at Screening 
and be re-confirmed at the Baseline Visit:
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent Form is signed and dated by the subject. 
2a. Subject 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. Male or female at least 18 years of age.
4. Chronic plaque psoriasis for at least 6 months prior to Screening.
5. PASI ≥12 and BSA ≥10% and IGA score ≥3 on a 5-point scale.
6. Candidates for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy.
7. 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, must be willing to use a highly effective method of contraception up till 20 weeks 
after last administration of study drug, and have a negative pregnancy test at Visit 1 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 28 of 103
(Screening) and immediately prior to first dose. The following methods are considered highly 
effective when used consistently and correctly.
∀
combined (estrogen and progestogen) hormonal contraception associated with inhibition 
of ovulation (oral, intravaginal or transdermal) 
∀
progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable)
∀
intrauterine device (IUD) 
∀
intrauterine hormone-releasing system (IUS) 
∀
bilateral tubal occlusion
∀
vasectomized partner (where postvasectomy testing had demonstrated sperm clearance).
∀
sexual abstinence if it is in accordance with a subject’s preferred and common lifestyle. 
Subjects who use abstinence as a form of birth control must agree to abstain from 
heterosexual intercourse until 20 weeks after the last dose of study medication. 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 study medication (anticipated
5 half-lives).
1. Patient agrees to not increase their usual sun exposure during the course of the study and to 
use ultraviolet A/ultraviolet B (UVA/UVB) sunscreens.
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 study drug. 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.
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, or is 
currently participating in another study of a medication or medical device under 
investigation. 
4. Subjects with a known hypersensitivity to any excipients of bimekizumab.
5a. Subjects with erythrodermic, guttate, pustular form of psoriasis, or drug-induced psoriasis.
6. 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, prior prosthetic joint 
infection at any time, subjects who are permanently bedridden or wheelchair assisted).
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 29 of 103
7. Subject has any current sign or symptom that may indicate an active infection (except for 
common cold), or has had an infection requiring systemic antibiotics within 2 weeks of 
baseline.
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: 1) 
positive for hepatitis B surface antigen (HBsAg+); or, 2) positive for anti-hepatitis B core 
antibody (HBcAb+). A positive test for the hepatitis C virus (HCV) is defined as: 1) positive 
for hepatitis C antibody (anti-HCV Ab), and 2) positive via a confirmatory test for HCV (for 
example, HCV polymerase chain reaction).
9. Subjects with known history of or current clinically active infection with Histoplasma, 
Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, 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 study drug.
11. Subjects receiving Bacillus Calmette-Guerin (BCG) vaccinations within 1 year prior to study
drug administration.
12. Subjects with a history of a lymphoproliferative disorder including lymphoma or current 
signs and symptoms suggestive of lymphoproliferative disease.
13. Subjects with primary immunosuppressive conditions, including subjects who are taking 
immunosuppressive therapy following an 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 12.6.1 for details 
on determining full TB exclusion criteria).
15. Subjects who have had a splenectomy.
16. Subjects with concurrent malignancy or 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 month after entering the study.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 30 of 103
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. Subject has a history of uncompensated heart failure, fluid overload, or myocardial 
infarction, or evidence of new onset ischemic heart disease or in the opinion of the 
Investigator other serious cardiac disease, within 12 weeks prior to Baseline.
20a. 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%).
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.
21. Subjects with clinically significant laboratory abnormalities (eg, creatinine >1.5xULN, 
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.
22. Subjects with any other condition which, in the Investigator's judgement, would make the 
subject unsuitable for inclusion in the study.
23. Subjects have been exposed to more than 1 biological response modifier (limited to anti-TNF 
or IL-12/-23) for psoriatic arthritis or psoriasis prior to the Baseline Visit. The list of 
prohibited medications is presented in Section 7.8.2.
24. Subjects have received previous treatment with any anti-IL-17 therapy for the treatment of 
psoriasis or psoriatic arthritis.
25. Subjects with a diagnosis of inflammatory conditions other than psoriasis or psoriatic 
arthritis, including but not limited to rheumatoid arthritis, sarcoidosis, or systemic lupus 
erythematosus. Subjects with a diagnosis of Crohn’s disease or ulcerative colitis are allowed 
as long as they have no active symptomatic disease at Screening or Baseline.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 31 of 103
26. Subjects taking psoriatic arthritis medications other than nonsteroidal anti-inflammatory 
drugs (NSAIDs) or analgesics. Subjects are allowed to take stable doses of NSAIDs to treat 
their psoriatic arthritis symptoms during the study. Subjects are allowed to use 
acetaminophen/paracetamol and mild opioids, as needed.
27. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
28. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review (eg, QT corrected for heart rate [QTc] using Fridericia’s correction [QTcF] >450ms, 
bundle branch block, evidence of myocardial ischemia).
29a. Presence of significant uncontrolled neuropsychiatric disorder, active suicidal ideation, or 
positive suicide behavior using the “Baseline” version of the eC-SSRS and the 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 score >10 or Anxiety score ≥15
30. Subjects are Investigator site personnel directly affiliated with this study and/or their 
immediate families. Immediate family is defined as a spouse, parent, child, or sibling, 
whether biological or legally adopted.
31. Subjects are UCB employees or are employees 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 and encouraged to come for the SFU visit (20
weeks after the last received dose) if any of the following events occur:
1. Subject withdraws his/her consent.
2. The Sponsor or a regulatory agency requests withdrawal of the subject.
Subjects should be withdrawn from all study treatment and will be asked to return for the study 
assessments 12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit (20 weeks 
after the last received dose) if any of the following events occur:
1. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
2a. 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. 
3a. Subject develops erythrodermic, guttate, or pustular form of psoriasis.
4. Subject considered as having either a suspected new LTB infection or who develop active TB 
or nontuberculosis mycobacterium (NTMB) infection during the study (including but not 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 32 of 103
limited to, conversion demonstrated by interferon-gamma release assay [IGRA] or other 
diagnostic means) must be immediately discontinued from study medication, an Early 
Withdrawal Visit must be scheduled as soon as possible, but not later than the next regular 
visit.
Confirmed active TB is a serious adverse event (SAE) and must be captured on an SAE 
Report Form and provided to the Sponsor in accordance with SAE reporting requirements. 
As with all SAEs, periodic follow-up reports should be completed as per protocol 
requirements until such time as the TB infection resolves. 
Additional information on TB policies are provided in Section 12.6.1.
5. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
6. Subject uses prohibited concomitant medications, with the exception of topicals, 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/or the Medical Monitor.
8. 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 
electronic Columbia Suicide Severity Rating Scale (eC-SSRS). The subject should be 
referred immediately to a Mental Healthcare Professional and must be withdrawn from the 
study.
9a. 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.
10. Subject experiences an AE as described below: 
∀
Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 and above AE 
that is assessed as related to study drug in the opinion of the Investigator 
◦
If the event is deemed to be not related to study drug by the Investigator, the subject 
may remain in the study after approval by the medical monitor. 
∀
Any CTCAE Grade 2 event that is evaluated as related to study drug in the opinion of the 
Investigator, is persistent, and falls into any of the following System Organ Classes 
(SOCs): “Blood and lymphatic disorders,” “Cardiac disorders,” or “Vascular disorders.” 
◦
Persistent is defined as lasting 28 days or more, which spans at least 2 scheduled 
injections.
11. Subject has a clinical laboratory value meeting the following criteria:
∀
CTCAE Grade 3 and above: subjects must be withdrawn regardless of relationship to 
study drug or duration of event.
∀
CTCAE Grade 2
◦
Subjects may remain in the study if the event is transient. If a subject has a Grade 2 
laboratory abnormality, a retest is required within 1 to 2 weeks at a scheduled or 
unscheduled visit. If the repeat value is below Grade 2, the subject may receive the 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 33 of 103
next scheduled study treatment. If the value on the repeat is still Grade 2 or above, a 
second repeat test must be performed and results made available prior to the next 
scheduled study treatment. If this second repeat value is still Grade 2 or above, the 
subject must be withdrawn. 
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 Case Report Form (CRF) 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.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 35 of 103
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access.
Appropriate storage conditions must be ensured by controlled temperature and by completion of 
a temperature log in accordance with local requirements on a regular basis per study manuals, 
showing minimum and maximum temperatures reached over the time interval.
Study drug 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 study drug documentation (eg, shipping receipts, drug 
accountability logs, 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. 
Blinded study staff may be delegated the responsibility to receive, inventory, and destroy the 
used kits. The packaging identifies each kit by a unique number that does not correlate to the 
contents and therefore, does not unblind study site staff. Unblinded study staff will be 
responsible for preparation (breaking tamper proof sticker on kit, etc) of the clinical trial 
material, including recording the administration information on source document.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee.
The Investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers) and unused IMP containers must be reconciled and returned to UCB (or designee), 
preferably in their original package. Onsite destruction of used kits only may be allowed with 
prior approval from the Sponsor or designee after reconciliation. Investigational medicinal 
product intended for the study cannot be used for any other purpose than that described in this 
protocol.
7.7
Procedures for monitoring subject compliance
During the treatment period of this study, study medication 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.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
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Page 36 of 103
7.8
Concomitant medication(s)/treatment(s)
All concomitant medications, including over the counter products, herbal, traditional remedies, 
vitamin/mineral supplements, other dietary supplements, “nutraceuticals,” and hormones must be 
recorded in the subject’s source documentation (eg, clinical chart) and on the electronic Case 
Report Form (eCRF). This record should include the name of the drug, the dose, the route and 
date(s) of administration, and the indication for use.
The Investigator should examine the acceptability of all concomitant procedures, medications, 
topical preparations and dietary supplements not explicitly prohibited in this study, and if 
necessary, discuss with the Medical Monitor. 
In order to ensure that appropriate concomitant therapy is administered, subjects will be 
instructed to consult with the Investigator prior to taking any medication (either 
self-administered non-prescription drugs or prescription therapy prescribed by another 
physician).
7.8.1
Permitted concomitant treatments (medications and therapies)
Topical medications
Subjects may continue to use topical moisturizers or emollients, bath oils, or oatmeal bath 
preparations for skin conditions during the study, as needed. Over-the-counter shampoos for the 
treatment of psoriasis of the scalp are also permitted. 
Subjects who use prohibited topical medications will be allowed to stay in the study but will be 
counseled to not use them further. No other topical preparations are allowed in the 2 weeks 
before randomization or during the study unless medically required to treat an AE.
Other medications
Subjects who are already receiving an established NSAID regimen (at least 8 weeks prior to 
Baseline) and have been on a stable dose for at least 4 weeks prior to Baseline may continue their 
use during the study. However, initiation of, or increase in dosage of, NSAIDs during the study 
(especially in subjects with a history of GI intolerance to NSAIDs or a history of GI ulceration) 
should be done with caution. Intra-articular steroid injections for arthritis of the knee are 
allowed.
Subjects who are already receiving an established anti-depressant regimen should be on a stable 
dose of anti-depressant for 12 weeks prior to Baseline.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The list of prohibited concomitant medications is provided Table 7‒1.
Subjects who use prohibited medications, with the exception of topicals, will be withdrawn from 
study treatment but followed until the SFU. 
As noted above, subjects who use prohibited topical medications will be allowed to stay in the 
study but will be counseled to not take them further.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 37 of 103
Table 7‒1:
Prohibited psoriasis medications
Drug
Exclusion criteria relative to 
Baseline Visit
Systemic retinoids
12 weeks 
Systemic treatment (non-biological):
systemic immunosuppressant agents (eg, methotrexate, 
cyclosporine, azathioprine, thioguanine)
systemic fumarate
systemic corticosteroids
phototherapy or chemophototherapy
8 weeks for methotrexate, 
azathioprine, and cyclosporine
4 weeks for everything other than 
methotrexate, azathioprine, and 
cyclosporine
Anti-TNFs:
infliximab (including biosimilar), golimumab
etanercept (including biosimilar)
certolizumab pegol
adalimumab (including biosimilar)
4 weeks for etanercept
12 weeks for everything other 
than etanercept 
Other biologics and other systemic therapies:
apremilast
ustekinumab
12 weeks for apremilast
24 weeks for ustekinumab
Anti-IL-17 therapy:
Any previous exposure excluded
Any other antipsoriatic agent (systemic) under investigation (or 
approved after the protocol is approved)
24 weeks 
Topical corticosteroids for dermatological use
Vitamin D analogues and topical retinoids
Keratolytic and coal tar
2 weeks 
Any other antipsoriatic agent (topical) under investigation
4 weeks 
IL-17=interleukin 17; TNF=tumor necrosis factor
Subjects who take prohibited medications, except topical therapies, may be withdrawn from 
study treatment but followed until the Safety Follow-Up. The decision to withdraw a subject for 
taking prohibited medications should be made in consultation with the Medical Monitor. As 
noted above, subjects that use prohibited topical medications will be allowed to stay in the study 
but will be counseled to not use them further.
Vaccines
Administration of live (including attenuated) vaccines is not allowed during the conduct of the 
study or for 20 weeks after the last dose of study drug (see Exclusion Criterion #0, Section 6.2). 
Administration of inactivated vaccines is allowed during the study at the discretion of the 
Investigator.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 38 of 103
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. 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 
administering the drug to the subjects.
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.
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 voice or 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 Clinical Project Manager (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 
Research Organization (CRO) who is otherwise not involved in this study. Subject treatment 
assignment will be stratified by region and prior biologic exposure (yes/no). The IXRS will 
generate individual assignments for subject kits of IMP, as appropriate, according to the visit 
schedule. Efforts should be made to limit the enrollment of subjects with prior biologic exposure 
to approximately 30% of the total study population. 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 39 of 103
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, a subject will be randomized into the study. The Investigator or designee 
will use the IXRS for randomization. The IXRS will automatically inform the Investigator or 
designee of the subject’s ID number. The IXRS will allocate kit numbers to the subject based on 
the subject number during the course of the study.
Subject numbers and kit numbers will be tracked via the IXRS.
8
STUDY PROCEDURES BY VISIT 
Table 5‒1 (schedule of study assessments) provides a general overview of study assessments. A 
list of procedures to be completed at each visit is described below. 
!
Visit windows of +/-3 days on either side of the scheduled dosing are permitted; 
however, the Investigator should try to keep the subjects on the original dosing schedule. 
The window of +/-3 days is relative to Baseline and applicable for all subsequent visits. 
Changes to the dosing schedule outside of the 3-day window must be discussed with the 
Medical Monitor.
!
The minimum of time between doses should be no less than 24 days and no more than 
32 days.
!
For the Safety Follow-Up 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)
8.1
Screening Visit
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.
Where local regulations permit, subjects will also be given the option to participate in the 
genomics, genetics, and proteomics substudy. Subjects agreeing to participate in the substudy 
will be required to complete a separate Informed Consent Form. The Informed Consent Form 
must be signed prior to collecting any samples for the substudy. The substudy will only be 
conducted where ethically accepted and authorized by the regulatory agencies. Refusal to 
participate in the substudy will not affect a subject’s ability to participate in the main PS0010 
study. 
Subjects may also be asked about their willingness to participate in a study exit interview near 
the end of the study. Subjects may decide to participate in the genomic, genetic and proteomic 
substudy, or the interview, or neither.
The following procedures or assessments will be performed at the Screening Visit:
!
Obtain written informed consent
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 40 of 103
!
Assessment of inclusion/exclusion criteria
!
Demographic data
!
Significant medical and procedure history and concomitant disease, including psoriasis 
disease history
!
Concomitant medications
!
Body height and weight
!
Physical examination
!
Vital signs (blood pressure, pulse rate, and temperature)
!
HADS
!
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
!
Record 12-lead ECG 
!
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is available)
!
TB questionnaire
!
Toronto Psoriatic Arthritis Screening questionnaire
!
PASI
!
IGA
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BSA
!
Obtain blood sample(s) for:
∀
TB test (interferon gamma release assay; IGRA; It is recommended that the 
QuantiFERON TB GOLD test be performed)
∀
Serum pregnancy test for women of childbearing potential 
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Hepatitis B and C testing
∀
HIV
!
Obtain urine sample for standard safety laboratory tests
!
Record AEs
!
Contact the IXRS
Individual screening tests for which the results are borderline for inclusion in the study may be 
repeated if necessary without complete rescreening of all tests.
8.2
Baseline Visit
The following procedures or assessments will be performed/recorded prior to administration of 
study drug:
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 41 of 103
!
Confirm inclusion/exclusion criteria 
!
Ensure no significant changes in medical procedure history and concomitant disease
!
Vital signs (blood pressure, pulse rate, and temperature)
!
Body weight
!
Record 12-lead ECG 
!
TB questionnaire
!
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PASI
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SF-36
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Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
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Bimekizumab plasma concentration
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Anti-bimekizumab antibodies
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Cytokines, complement, candidate biomarker analysis, and flow cytometry (serum and 
plasma) 
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Genomic, genetic/epigenetic, proteomic, and metabolomics analyses (for subjects in the 
substudy)
!
Obtain urine sample for:
∀
standard safety laboratory tests 
∀
urine pregnancy test for women of childbearing potential
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Concomitant medications
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Record AEs
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 42 of 103
!
Contact the IXRS
!
Study medication administration (after all other visit assessments completed)
8.3
Week 1 (+/-3 days)
The following procedures or assessments will be performed/recorded:
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
PASI
!
IGA
!
DLQI
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
!
Obtain urine sample for:
∀
standard safety laboratory tests 
∀
urine pregnancy test for women of childbearing potential
!
Concomitant medications
!
Record AEs
!
Contact the IXRS
8.4
Week 2 (+/- 3 days)
The following procedures or assessments will be performed/recorded:
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
Record 12-lead ECG 
!
PASI
!
IGA
!
DLQI
!
PSSI
!
SF-36
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 43 of 103
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
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Cytokines, complement, candidate biomarker analysis, and flow cytometry (serum and 
plasma) 
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Genomic, genetic/epigenetic, proteomic, and metabolomics analyses (for subjects in the 
substudy) 
!
Obtain urine sample for:
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Urine pregnancy test for women of childbearing potential
!
Concomitant medications
!
Record AEs
!
Contact the IXRS
8.5
Week 4 (+/- 3 days)
The following procedures or assessments will be performed/recorded prior to administration of 
study drug:
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
HADS
!
Record 12-lead ECG 
!
PASI
!
IGA
!
BSA
!
DLQI
!
mNAPSI
!
PSSI 
!
SF-36
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 44 of 103
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
∀
Anti-bimekizumab antibodies
!
Obtain urine sample for:
∀
standard safety laboratory tests 
∀
urine pregnancy test for women of childbearing potential
!
Concomitant medications
!
Record AEs
!
Contact the IXRS
!
Study medication administration (after all other visit assessments completed)
8.6
Week 6 (+/- 3 days)
The following procedures or assessments will be performed/recorded:
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
Record 12-lead ECG 
!
PASI
!
IGA
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Cytokines, complement, candidate biomarker analysis, and flow cytometry (serum and 
plasma) 
∀
Genomic, genetic/epigenetic, proteomic, and metabolomics analyses (for subjects in the 
substudy) 
!
Obtain urine sample for:
∀
standard safety laboratory tests 
∀
urine pregnancy test for women of childbearing potential
!
Concomitant medications
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 45 of 103
!
Record AEs
!
Contact the IXRS
8.7
Week 8 (+/- 3 days)
The following procedures or assessments will be performed/recorded prior to administration of 
study drug:
!
Obtain written informed consent for subjects planning to enter the extension study (PS0011). 
The sites are encouraged to begin the PS0011 consent process at Week 8.
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
HADS
!
PASI
!
IGA
!
BSA
!
DLQI
!
mNAPSI
!
PSSI
!
SF-36
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
TB test (interferon gamma release assay; IGRA)
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
∀
Anti-bimekizumab antibodies
∀
Cytokines, complement, candidate biomarker analysis, and flow cytometry (serum and 
plasma) 
!
Obtain urine sample for:
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standard safety laboratory tests
∀
urine pregnancy test for women of childbearing potential
!
Concomitant medications
!
Record AEs
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 46 of 103
!
Contact the IXRS
!
Study medication administration (after all other visit assessments completed)
8.8
Week 12 (+/- 3 days) Study Exit/Early Withdrawal
The following procedures or assessments will be performed:
!
Obtain written informed consent for subjects planning to enter the extension study (PS0011) 
if not obtained at Week 8. The sites are encouraged to begin the PS0011 consent process at 
Week 8.
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
HADS
!
Body weight
!
Physical examination
!
Record 12-lead ECG 
!
TB questionnaire
!
PASI
!
IGA
!
BSA
!
DLQI
!
mNAPSI
!
PGADA
!
PSSI
!
SF-36
!
Patient Symptom Diary responses (for subjects at sites in selected countries)
!
PGIC (for subjects at sites in selected countries)
!
PGIS (for subjects at sites in selected countries)
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
∀
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∀
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 47 of 103
∀
Genomic, genetic/epigenetic, proteomic, and metabolomics analyses (for subjects in the 
substudy) 
!
Obtain urine sample for:
∀
standard safety laboratory tests 
∀
urine pregnancy test for women of childbearing potential
!
Concomitant medications
!
Record AEs
!
Contact the IXRS
8.9
Safety Follow-Up Visit (20 weeks after the last dose)
All subjects not continuing in the extension study, including those withdrawn from study 
treatment, will have a SFU Visit at 20 weeks after their last dose of study medication.
The Safety Follow-up 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 following procedures or assessments will be performed at the SFU Visit:
!
Vital signs (blood pressure, pulse rate, and temperature)
!
eC-SSRS
!
HADS
!
Body weight
!
Physical examination
!
Record 12-lead ECG 
!
PASI
!
IGA
!
BSA
!
DLQI
!
Obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology and biochemistry)
∀
Bimekizumab plasma concentration
∀
Anti-bimekizumab antibodies
∀
Serum pregnancy test for women of childbearing potential 
!
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!
Concomitant medications
!
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 48 of 103
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Contact the IXRS
8.10
Early Withdrawal Visit
Subjects withdrawing early from the study (see Section 6.3) will undergo the same assessments 
as the Week 12 Visit (see Section 8.8) and will enter the SFU Period.
Subjects that withdrawal from study treatment early will be asked to return for the study 
assessments 12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit (20 weeks 
after the last received dose).
8.11
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:
!
Vital signs 
!
eC-SSRS
!
Physical examination
!
Record 12-lead ECG 
!
If medically indicated, obtain blood sample(s) for:
∀
Standard safety laboratory tests (hematology, serum chemistry) 
∀
The blood sample may also be used for PK/PD assessments, if needed.
!
Obtain urine sample for standard safety laboratory tests (including urine pregnancy test)
!
Record concomitant medication
!
Record AEs
9
ASSESSMENT OF EFFICACY
9.1
Psoriasis Area and Severity Index
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 9‒1). 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 49 of 103
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. 
Table 9‒1:
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 PASI50, PASI75, PASI90, and PASI100 responses are based on at least 50%, 75%, 90%, 
and 100% improvement in the PASI score.
The PASI will be completed at the visits specified in Table 5‒1.
9.2
BSA affected by psoriasis
The BSA palm method will be used for the evaluation of BSA as follows:
Body surface area estimation uses the palm (subject’s flat hand and thumb together, fingers 
included) as representing around 1% of the total BSA.
!
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%
Evaluation of BSA will be completed at the visits specified in Table 5‒1.
9.3
Investigator’s Global Assessment
A static IGA for psoriasis will be used to assess disease severity in all subjects during the study. 
The IGA will be completed at the visits specified in Table 5‒1. 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 50 of 103
The Investigator will assess the overall severity of psoriasis using the following 5-point scale 
presented in Table 9‒2.
Table 9‒2:
Five-point Investigator’s Global Assessment
Score
Short Descriptor
Detailed Descriptor
0
Clear
No signs of psoriasis; post-inflammatory hyperpigmentation may be present
1
Almost clear
No thickening; normal to pink coloration; no to minimal focal scaling
2
Mild
Just detectable to mild thickening; pink to light red coloration; 
predominately fine scaling
3
Moderate
Clearly distinguishable to moderate thickening; dull to bright red, clearly 
distinguishable to moderate thickening; moderate scaling
4
Severe
Severe thickening with hard edges; bright to deep dark red coloration; 
severe/coarse scaling covering almost all or all lesions
9.4
Dermatology Life Quality Index
The DLQI is a questionnaire designed for use in adult subjects with psoriasis. The DLQI is a skin 
disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect 
patients’ health related QOL. This instrument asks subjects about symptoms and feelings, daily 
activities, leisure, work and school, personal relationships and treatment. It has been shown to be 
valid and reproducible in psoriasis patients. The DLQI score ranges from 0 to 30 with higher 
scores indicating lower health related QOL. A 5-point change in the DLQI score (DLQI 
response) has been reported to be meaningful for the patient (within-patient minimal important 
difference); while a DLQI absolute score of 0 or 1 indicates no or small impact of the disease on 
health related QOL. Subjects will be asked to complete the DLQI as outlined in the Schedule of 
Study Assessments (Table 5‒1). Study site personnel should ensure that each subject completes 
the instrument prior to leaving the study site. 
9.5
Hospital Anxiety and Depression Scale
The HADS was chosen for its well-established psychometric properties and its use in clinical 
research on biological therapy in subjects with chronic plaque psoriasis (Dauden et al, 2009; 
Langley et al, 2010). 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 wheras a score 
of 15 and above is considered severe (Snaith and Zigmond, 1994).
9.6
Modified Nail Psoriasis Severity Index Score
Psoriatic nail disease will be evaluated at the Baseline Visit using the modified Nail Psoriasis 
Severity Index (mNAPSI). All affected nails 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 hemorrhages 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. The total mNAPSI score is the sum of the scores for each individual nail. If a nail is 
unaffected, it will be recorded as such and will not contribute to the total mNAPSI score. 
Subjects with nail disease at Baseline are defined as those with an mNAPSI score >0 at Baseline.
The mNAPSI will be assessed at the visits specified in Table 5‒1. 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 51 of 103
9.7
Patient’s Global Assessment of Disease Activity for the arthritis 
visual analog scale
The PGADA for the arthritis visual analog scale (VAS) will be used to provide an overall 
evaluation of arthritis disease symptoms. Subjects will respond to the question, “Considering all 
the ways your arthritis affects you, please mark a vertical line on the scale below to show how 
you are feeling today”, using a VAS where 0 is “very good, no symptoms” and 100 is “very 
poor, severe symptoms.
Each subject will complete the PGADA at the visits specified in Table 5‒1.
9.8
Patient Global Impression of Change
The PGIC will be assessed at Baseline and on a weekly basis following the completion of all the 
patient symptom diary items. Only patients in selected countries who participate in the 
completion of the patient symptom diary will participate in the completion of the PGIC. 
The PGIC is a 5-item instrument that will ask the participants to think about their 
psoriasis-related symptoms (including itching, pain, scaling, and sleep loss) since they started 
this study. Each item has 7 response categories ranging from “Very much improved,” “Much 
improved,” “Minimally improved,” “No change,” “Minimally worse,”  “Much worse,” to “Very 
much worse.”
9.9
Patient Global Impression of Severity
The PGIS will be completed at Baseline and on a weekly basis following the completion of all 
patient symptom diary items. Only patients in selected countries who participate in the 
completion of the patient symptom diary will participate in the completion of the PGIS. 
The PGIS is a 5-item instrument that will ask the participants to think about their 
psoriasis-related symptoms (including itching, pain, scaling, and sleep loss) over the past week 
and an additional 5 items asking about the same set of symptoms at the current point in time. 
Each item has 5 response categories ranging from “No (symptoms),” “Mild (symptoms),” 
“Moderate (symptoms),” “Severe (symptoms),” to “Very severe (symptoms).”
Both PGIC and PGIS will be used to evaluate participants overall sense of the status and 
perceived improvement in relevant symptoms and to aid the interpretation of the changes in the 
patient symptom diary.
9.10
Psoriasis Scalp Severity Index
The PSSI considers both the extent of the area of involvement and the severity based on the 
scoring scales outlined in Table 9‒3. The assessment considers erythema, induration and 
desquamation on the scalp. For each of these 3 elements, the scores of the area and severity are 
multiplied. Then, the score from each element is totaled to obtain the PSSI score. As with the 
PASI, the PSSI score ranges from 0 to 72 with a higher score indicating increased scalp disease 
severity.
The PSSI will be assessed at the visits specified in Table 5‒1. 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 52 of 103
Table 9‒3:
Parameters assessed for the PSSI
Assessment of extent of scalp psoriasis
Score
Definition
1
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2
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3
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4
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PSSI= Psoriasis Scalp Severity Index
9.11
Patient Symptom Diary responses
UCB is developing a new PRO measure that will be used to assess key symptoms relevant to 
patients with moderate to severe chronic plaque psoriasis. PS0010 will use the draft PRO 
measure in selected countries to enable psychometric validation of the PRO. Site staff will train 
the participating subjects on the use of the electronic PRO (ePRO) diary at the Screening Visit, 
following which the device will be dispensed to the subject for home use until the Week 12 Visit. 
The ePRO diary will be administered on a daily basis from Screening to the Week 12 Visit.
Item content of the ePRO diary will be finalized prior to study initiation and will include a 
variety of psoriasis-related characteristics, reported as relevant by patients in the published 
literature and planned concept elicitation interviews. The ePRO diary will also administer 
appropriate anchor items (eg, patient global impression of change, and patient global impression 
of concept) at the end of every study week. The ePRO diary software will be programmed such 
that the subjects will be given a window of opportunity to complete the ePRO diary each 
evening. The data collected on the ePRO diary will be uploaded to a central server database and 
will be 21 CFR Part 11 compliant. Appropriate GCP procedures (including subject/site training 
and testing) will be performed at the study sites
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 53 of 103
9.12
36-Item Short Form Health Survey
The SF-36 (Version 2, standard recall) is a 36-item generic health related QOL instrument that 
uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical 
Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items),
Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 
items), and 1 item for perceived stability or change in health (Health Transition) during the last 
year. The concepts represented by these domains contribute to physical, mental, and social 
aspects of health-related QOL. In addition to domain scores, the PCS and MCS 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 domains and the 2 component summary scores are 
standardized with a mean of 50 and a standard deviation (SD) of 10 in the general USA 
population. The minimally important differences (MIDs), in terms of T-score points, for SF-36 
domains and component summaries are the following: PCS, 2; MCS, 3; Physical Functioning, 3; 
Role-Physical, 3; Bodily Pain, 3; General Health, 2; Vitality, 2; Social Functioning, 3; 
Role-Emotional, 4; and Mental Health, 3.
The SF-36 will be completed by the subject the visits specified in Table 5‒1. 
10
ASSESSMENT OF PHARMACOKINETICS/ 
PHARMACODYNAMICS/PHARMACOGENOMICS
10.1
Pharmacokinetic and pharmacodynamic variables
Blood samples for measurement of PK and PD variables (Section 4.2) will be collected at the 
time points specified in the schedule of study assessments (Table 5‒1). 
Flow cytometry by fluorescence-activated cell sorting (FACS) analysis will include, but is not 
limited to: CD3, CD19, CD4, CD8, and CD69.
Candidate biomarkers will include, but are not limited to: IL-17A/IL17-F pathway signaling and 
psoriasis biology (eg, IL-17A, IL-17F, IL-23, IL-6, TNF, DC-STAMP, and circulating osteoclast 
precursors). 
At dosing visits, blood samples will be drawn prior to dosing, and will be drawn at the same time 
of the sampling for clinical laboratory tests. The time and date of collection will be recorded in 
the eCRF. 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. Detailed information on sample analysis will be 
provided in a bioanalytical report.
10.2
Pharmacogenomic variables
10.2.1
Genomics, genetics, and proteomics variables
For individuals consenting to the biomarker substudy, blood samples will be drawn for 
exploratory genetic/epigenetic, genomic, proteomic and metabolomics analysis at the time points 
specified in the schedule of study assessments (Table 5‒1). Collection of these samples will 
enable evaluation of biomarkers relative to disease biology and progression, drug treatment and 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 54 of 103
inflammatory and immune response processes. The nature and format of these tentative analyses 
will be determined when the results of the main study are made available. 
A separate Informed Consent Form will be required for those subjects who agree to participate in 
the genomics, genetics, and proteomics substudy. The substudy will only be conducted where 
ethically accepted and authorized by the regulatory agencies. Refusal to participate in the 
substudy will not affect a subject’s ability to participate in the main study. 
The samples will be stored at -80°C at the central biorepository for up to 20 years.
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES
11.1
Assessment of immunogenicity
Blood samples for measurement of antibodies to bimekizumab will be collected at the visits 
specified in Table 5‒1. The threshold for antibody positivity will be defined prior to analysis.
At dosing visits, blood samples will be drawn prior to dosing, and will be drawn at the same time 
of the sampling for clinical laboratory tests. The time and date of collection will be recorded in 
the eCRF. 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. 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.
11.2
Assessment of immunological variables
Blood samples for measurement of immunological variables will be collected at the time points 
specified in the schedule of study assessments (Table 5‒1). 
At dosing visits, blood samples will be drawn prior to dosing, and will be drawn at the same time 
of the sampling for clinical laboratory tests. The time and date of collection will 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.
12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definition of adverse event
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent Form), including any pretreatment and posttreatment 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 55 of 103
periods required by the protocol, must be reported in the CRF even if no IMP was taken but 
specific study procedures were conducted. This includes all AEs not present prior to the initial 
visit and all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
12.1.2
Adverse events of special interest
An AE of special interest (AESI) is any AE that a regulatory authority has mandated be reported 
on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AESI (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should then be reported if an 
alternative etiology is identified during investigation and monitoring of the subject.
12.1.3
Adverse events for special monitoring
UCB has identified AEs for special monitoring (AESM). An AESM is an AE or safety topic for 
which special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB), are considered appropriate. Identified AESM can be of particular 
interest 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 12.6.1), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the eC-SSRS), depression-and anxiety (assessed using the 
HADS, see Section 9.5), 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 CRF and 
source documents should be consistent. Any discrepancies between the subject’s own words on 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 56 of 103
his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the severity of an AE in the CRF (ie, mild, moderate, or severe), the Investigator 
must refer to the CTCAE Version 4 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm). Details for 
completion of the Adverse Event CRF (including judgment of severity and relationship to IMP) 
are described in the CRF 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. 
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 Patient Safety (PS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see SAE reporting 
information at the beginning of this protocol). The subject should be withdrawn from the study 
as soon as pregnancy is known (by positive pregnancy test), and the following should be 
completed:
!
The subject should return for an early Withdrawal Visit.
!
The subject should immediately stop the intake of the IMP 
!
A SFU Visit should be scheduled 20 weeks after the subject has discontinued her IMP.
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 57 of 103
the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s PS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/contract research organization (CRO) contract monitor for the 
study. The Investigator will complete the Pregnancy Report and Outcome form and send it to 
UCB’s PS department (for contact details see SAE reporting information at the beginning of this 
protocol) only after the partner has agreed that additional information can be captured and has 
provided the signed Partner Pregnancy Consent form. UCB’s PS department is also the primary 
contact for any questions related to the data collection for the partner pregnancy, eventual birth, 
and follow up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective for 
a medical indication or spontaneous), unintended pregnancy after hormonal contraceptive failure 
(if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal demise, or any 
congenital anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report Form.
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.
In addition, an independent Data Monitoring Committee (DMC) will periodically review and 
monitor the safety data from this study and advise UCB. Details are provided in the DMC
Charter. A cardiovascular (CV) Adjudication Committee will also periodically review and 
monitor the safety data from this study and advise UCB. Details are provided in the CV 
Adjudication Committee Charter.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 58 of 103
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.
12.2
Serious adverse events
12.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
!
Death
!
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)
!
Significant or persistent disability/incapacity
!
Congenital anomaly/birth defect (including that occurring in a fetus)
!
Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include but are not limited to, potential Hy’s Law (see 
Section 12.1.2), allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.)
!
Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 59 of 103
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 Serious Adverse Event Reporting 
section at the front of the protocol). The Investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE Report Form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE Report Form will be provided to the Investigator. The Investigator SAE 
Report Form must be completed in English. 
It is important for the Investigator, when completing the SAE Report Form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE Report Form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE Report Form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the IB.
12.2.3
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. 
Information on SAEs obtained after clinical database lock will be captured through the Drug 
Safety 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
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 60 of 103
!
AEs of special interest as defined in Section 12.1.2
12.4
Anticipated serious adverse events
The following list of Anticipated SAEs 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 moderate to severe chronic plaque psoriasis
MedDRA® system order class
MedDRA preferred term
Skin and subcutaneous tissue disorders
Any psoriatic condition HLT
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy
HLT=high level term; MedDRA=Medical Dictionary for Regulatory Activities; SAE=serious adverse event
Note: Exception: Listed events will not be regarded as anticipated SAEs if they are life threatening or if they result 
in the death of the study subject.
12.5
Laboratory measurements
Clinical laboratory assessments consist of serum chemistry, hematology, and urinalysis. 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 #7, 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.
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
CRP
Crystals
Atypical lymphocytes
Magnesium
Glucose
Monocytes
Potassium
pH
Neutrophils
Sodium
RBC
Hematocrit
Glucose
WBC
Hemoglobin
BUN
Urine dipstick for pregnancy testinga
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 61 of 103
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
MCH
Creatinine
MCHC
ALP
MCV
AST
Platelet count
ALT
RBC count
GGT
WBC count
Total bilirubin
LDH
Total cholesterol
Serum pregnancy testinga
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; LDH=lactate dehydrogenase; MCH=mean 
corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; 
RBC=red blood cell; WBC=white blood cell
a Pregnancy testing will consist of serum testing at the Screening and SFU Visits. The pregnancy test will be urine 
at all other visits.
Assessments of immunological variables are described in Section 11. Assessments of PK and PD 
variables are described in Section 10.
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 AESI (see Section 12.1.2), and, if applicable, also reported as an SAE (see 
Section 12.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.5.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 12.5.1.5). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 62 of 103
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.
REDACTED COPY 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 63 of 103
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 values.d
≥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
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 64 of 103
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 
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baseline) 
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<5xULN 
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baseline)
<2xULN
No
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Medical Monitor 
required.
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow 
up requirements).c
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 12.5.1.2).
IMP discontinuation 
required if any of the 
following occur:
! Subject cannot 
comply with 
monitoring 
schedule. 
! Liver chemistry 
values continue to 
increase 
! Liver chemistry 
values remain 
≥3xULN (and 
≥2x baseline) after 
2 weeks of 
monitoring without 
evidence of 
resolution
Essential: Every 
attempt must be 
made to have repeat 
liver chemistry 
values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.5.1.4).
Monitoring of liver 
chemistry values at least 
twice per week for 2 
weeks.d
!
Immediate IMP 
discontinuation 
required if liver 
chemistry values 
continue to increase.
After 2 weeks of 
monitoring liver 
chemistry values:
!
Discontinue IMP if 
levels remain 
≥3xULN (and ≥2x 
baseline) without 
evidence of 
resolutiond
Continue to monitor until 
values normalize, 
stabilize, or return to 
within baseline values.d
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 65 of 103
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.
REDACTED COPY 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 66 of 103
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, may be 
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:
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 67 of 103
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/or
quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screen
a
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/INRb
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
The following additional information is to be collected:
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 68 of 103
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
Assessment and management of TB and TB risk factors
All subjects will be assessed for tuberculosis (TB) at Screening and at the timepoints specified in 
the Schedule of Assessments (Table 5‒1) through physical examination for signs and symptoms 
of TB, chest x-ray (Section 12.6.1.2), laboratory testing (Section 12.6.1.1), and subject
questionnaire (Section 12.6.1.3). 
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 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 69 of 103
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, or latent TB infection 
are excluded. 
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
b. High risk of acquiring TB infection is defined as:
∀
Known exposure to another person with active TB infection within the 3 months prior to 
Screening
∀
Time spent in a healthcare delivery setting or institution where individuals infected with 
TB are housed and where the risk of transmission of infection is high
c.
Latent TB infection is defined as:
∀
The absence of signs, symptoms (ie, evidence of organ-specific involvement), or physical 
findings suggestive of TB infection with a positive IGRA test (or 2 indeterminate IGRA 
test results) and a chest x-ray (or other imaging) without evidence of TB infection. If the 
result of the IGRA test is indeterminate, the particular IGRA test previously performed 
may be repeated once; if positive or indeterminate on retest, the subject may not be 
randomized to study medication. The retest must be done during the protocol-defined 
Screening window (2 to 4 weeks).
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 nontuberculous mycobacterial (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 is common 
compared to normal population.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 70 of 103
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.
LTBI 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. 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 (2 to 4 weeks). Laboratory diagnosis should 
be undertaken via mycobacteria culture media (or if available by preferred nucleic acid 
amplification test such as the Xpert MTB RIF test) and result must be negative for TB inducing 
pathogens.
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 study drug 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 Drug Safety function.
Latent TB
In case the evaluation by the appropriate specialist indicates a new LTBI during the study, a 
prophylactic TB treatment should be initiated and the subject must be withdrawn from the study. 
Every related action should be discussed in advance with the Medical Monitor. 
Once withdrawn from study treatment, subjects should return for the Week 12/WD Visit, 
complete all Early Withdrawal Visit assessments, and complete a SFU Visit (20 weeks after the 
last dose of study medication).
Active TB or nontuberculosis mycobacterium 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 Early 
Withdrawal 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. 
12.6.1.1
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 8/Early 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 72 of 103
Subjects diagnosed with active TB or LTB infection should be withdrawn from the study and 
receive appropriate TB or prophylaxis therapy. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Confirmed active 
TB must be reported as an SAE. The Investigator is to complete and submit the TB follow up 
form provided.
The subject should be transferred to the care of his/her physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the Week 12/WD Visit as soon as possible 
but no later than the next scheduled study visit and complete all Week 12/WD 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.
12.6.2
Pregnancy testing
Pregnancy testing will consist of serum testing at the Screening and SFU Visits. The pregnancy 
test will be urine at all other visits. 
The Screening Visit serum pregnancy testing results must be negative and received and reviewed 
prior to randomization. A negative urine pregnancy test result should be obtained immediately 
prior to each administration of study drug and at all subsequent post-dosing visits. Pregnancy 
tests should be administered to all female subjects of childbearing potential, regardless of their 
use of birth control.
12.6.3
Vital signs
Vital signs will be collected at every visit and will include systolic and diastolic BP, pulse rate, 
and body temperature (oral, axillary, or otic). Subjects should be sitting for 5 minutes before and 
during vital signs assessments. 
Vital signs are to be measured prior to blood sampling, and prior to dosing, where applicable. 
12.6.4
12-lead electrocardiograms
Twelve-lead standard ECGs will be recorded at the visits specified in Table 5‒1, and read by a 
central ECG laboratory. 
Full details of ECG recording will be provided in the ECG Manual. 
12.6.5
Physical examination
The physical examination will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; GI; musculoskeletal; hepatic; neurological (including limb 
reflexes); and mental status. Physical examination will be performed at Screening, the 
Week 12/WD Visit, and the SFU Visit. Findings considered clinically significant changes since 
the physical examination at the Screening Visit will be recorded as AEs.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 73 of 103
12.6.6
Height and body weight
Height will be measured at Screening, only.
Body weight will be measured at Screening, Baseline, the Week 12/WD Visit, and at the 
SFU Visit.
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 (Mundt et al, 2010; Posner et al, 2011). 
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.
12.7
Other study measurements
12.7.1
Demographic information
Demographic information will be collected in all subjects and 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.
12.7.2
Medical History
A complete medical history will be collected as part of the Screening assessment and include all 
clinically relevant past or coexisting medical conditions and surgeries. Findings will be recorded 
in the eCRF. 
12.7.3
Psoriasis History
A detailed history of each subject’s psoriasis history will be collected and include the date of 
onset and past treatments for psoriasis. 
12.7.4
Data Monitoring Committee 
The DMC membership includes experienced clinicians and a statistician, all of whom have 
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 PS0010. The DMC may also be asked to provide a 
review of final study results, as deemed appropriate.
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.
The DMC procedures will ensure that data remain blind to the study team and Investigators at all 
times throughout the conduct of the study.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 74 of 103
A cardiovascular (CV) Adjudication Committee will also periodically review the safety data 
from this study. Details will be described in a separate charter document.
13
STUDY MANAGEMENT AND ADMINISTRATION 
13.1
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.
13.2
Monitoring
UCB (or designee) will monitor the study to meet the Sponsor’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 eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
13.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. Source documentation 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 eCRFs are not considered 
acceptable source documents. Source documents are original records in which raw data are first 
recorded. These may include hospital/clinic/general practitioner records, charts, diaries, x-rays, 
laboratory results, printouts, pharmacy records, care records, ECG or other printouts, completed 
scales, or quality of 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 FDA Part 11 requirements and document appropriately. Source 
documents that are computer generated and stored electronically that are not FDA Part 11 
compliant, must be printed for review by the monitor (eg, ECG reports). Once printed, these 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 75 of 103
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, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by the Sponsor or designee. 
Patient Reported Outcome (PRO) measures (eg, DLQI, SF-36, and PGADA) will be completed 
by each subject utilizing electronic data capture.
The ePRO diary data will be entered into an electronic diary by the subject. The data collection 
and database management system will be supplied by a vendor and will be compliant with the 
FDA Part 11. The data collected on the ePRO diary will be uploaded to a central server database 
and will be sent electronically to UCB (or a designated CRO).
13.2.2
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 13.2.1.
13.3
Data handling
13.3.1
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 use an electronic device to capture patient reported outcomes (see 
Section 13.2.1).
Serious adverse event reporting will be done using the SAE 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 EDCwill 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.
13.3.2
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 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 76 of 103
the data. This study is performed using EDC: the data are entered into the eCRFs once and are 
subsequently verified.
An electronic audit trail system will be maintained 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.
13.3.3
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.
13.4
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.
13.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
study master file.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 77 of 103
13.6
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).
13.7
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.
14
STATISTICS
A description of statistical methods is presented below and will be described in more detail in the 
statistical analysis plan (SAP).
14.1
Definition of analysis sets
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
The Randomized Set (RS) will consist of all randomized subjects. 
The Safety Set (SS) will consist of all subjects who received at least 1 dose of the study
medication.
The Full Analysis Set (FAS) will consist of all randomized subjects who received at least 1 dose 
of the study medication and have a valid measurement of the primary efficacy variable at 
Baseline.
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who had no important protocol 
deviation affecting the primary efficacy variable. The subjects with important protocol deviations 
will be pre-defined and evaluated during a data evaluation meeting prior to unblinding of the 
data.
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of all randomized subjects who 
took at least 1 dose of the study medication and provided at least 1 quantifiable plasma 
concentration post-dose. 
The Pharmacodynamics Per-Protocol Set (PD-PPS) will consist of all randomized subjects who 
took at least 1 dose of the study medication and provided at least 1 PD measurement post-dose 
without important protocol deviations affecting the measurement.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 78 of 103
14.2
General statistical considerations
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, summary statistics will consist of the number of available observations, arithmetic 
mean, standard deviation, median, minimum, and maximum unless stated otherwise.
All statistical tests will be performed based on a 2-sided significance level of 5% unless stated 
otherwise.
14.3
Planned efficacy analyses
14.3.1
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 PASI90 response will be assessed using a 
logistic regression model which will include fixed effects for treatment, region, and prior 
biologic exposure (yes/no). This will be evaluated using a linear contrast in which equal spacing 
between each of the doses is assumed. The coefficients for this linear contrast will be -2, -1, 0, 1, 
and 2 for placebo, bimekizumab 64mg Q4W, bimekizumab 160 Q4W, bimekizumab 320mg 
Q4W, and bimekizumab 480mg Q4W, respectively. While the bimekizumab 320mg loading 
dose followed by bimekizumab 160mg Q4W has been left out of the linear contrast for 
evaluating dose response, it will remain a part of the logistic regression model and will be 
compared to the bimekizumab 160mg Q4W dose. Prior biologic exposure was selected as a fixed 
effect in the logistic regression model as it is a stratification variable for randomization and 
because it may have an impact on efficacy. The use of region as a fixed effect in the model is 
also based on its use as a stratification variable in randomization and is intended to combine 
study centers into similar geographic regions. The geographic regions to be used will be defined 
in the IXRS and in the SAP. If the logistic regression model is unable to converge, then prior 
biologic exposure may be dropped from the model to facilitate convergence. The linear contrast 
from the logistic regression model will be evaluated at a 2-sided 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, the same logistic regression model 
described above will be used to assess the effect of each individual dose vs placebo on PASI90 
response. Comparisons will be made for each dose vs placebo at a 2-sided significance level of 
α=0.05. For each dose, the odds ratio vs placebo, the 95% confidence interval, and the 
corresponding p-value will be calculated. 
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a 2-sided significance 
level of α=0.05. This procedure will control the overall Type I error rate. A pairwise comparison 
will also be made for the bimekizumab 160mg Q4W group versus the bimekizumab 320mg 
loading dose followed by bimekizumab 160mg Q4W group, but this evaluation will not be part 
of the sequential testing procedure described above (ie, the p-value will be nominal).
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 79 of 103
Non-responder imputation (NRI) will be used to account for missing data in the primary 
analysis. That is, subjects with a missing PASI score at Week 12 or who discontinued study 
treatment prior to the Week 12 Visit will be considered non-responders for the primary analysis.
14.3.1.1
Sensitivity analyses
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.
An ordered categorical analysis using a non-parametric correlation statistic of Mantel and 
Haenszel (1959) and modified ridit scores will be performed as a sensitivity analysis to the 
primary dose-response evaluation based on the logistic regression model. This analysis will 
include region and prior biologic exposure as stratification factors to adjust for potential 
differences in the dose response based on these variables, and will be evaluated at a 2-sided 
significance level of α=0.05.
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 greater detail in 
Section 14.6.
14.3.2
Other efficacy analyses
14.3.2.1
Analysis of the secondary efficacy variables
The secondary efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables (ie, PASI75/90/100 response, IGA response [clear, almost clear]) will 
be analyzed for treatment effects using pairwise comparisons based on the same method as that 
described for the primary efficacy variable.
Dose and exposure response will be assessed using a non-linear model assessing the relationship 
between dose/exposure and PASI score. The model will include fixed effects for dose/exposure 
and test the clinical and statistical relevance of covariate effects. Further details will be given in a 
separate data analysis plan (DAP) and reported in a separate document.
14.3.2.2
Analysis of the other efficacy variables
All other efficacy variables will be analyzed for all subjects in the FAS.
All categorical variables will be summarized using frequency tables by treatment group for each 
visit.
All continuous variables will be summarized using descriptive statistics by treatment group for 
each visit.
Time to PASI50, PASI75, PASI90, and PASI100 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 
the given response will be censored at the date of the Week 12 Visit. The median time to
response, including the 2-sided 95% confidence interval, will be calculated for each treatment.
Between group differences (each bimekizumab dose vs placebo) will be analyzed with the log-
rank statistic.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 80 of 103
All other efficacy variables will be summarized based on imputed data (NRI and last observation 
carried forward [LOCF] for binary and continuous variables, respectively) and observed case 
data (ie, subjects with missing data or who have prematurely discontinued study treatment are 
treated as missing).
14.3.3
Subgroup analyses
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: age, gender, disease duration, region, 
body weight, BMI, prior systemic phototherapy or chemophototherapy, prior nonbiologic 
systemic therapy, prior biologic systemic exposure, any prior systemic therapy, and antibody 
positivity. These summaries will be based on imputed data (NRI) and will include descriptive 
statistics only.
14.4
Planned safety and other analyses
14.4.1
Safety analyses
All safety variables will be analyzed for all subjects in the SS. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®). Treatment-emergent adverse events (TEAEs) will be summarized descriptively by 
treatment group, primary system organ class, high level term, and preferred term. Additional 
tables will summarize TEAEs by intensity and relationship to study drug, TEAEs leading to 
withdrawal from the study, treatment-emergent SAEs, and deaths.
TEAEs will be defined as events that have a start date on or following the first administration of 
study treatment through the final administration of study treatment +140 days (covering the 
20-week SFU period). To allow for a fair comparison across all subjects, exposure at risk for 
defining treatment-emergence during the 12-week treatment period will be cut off at the Week 
12 visit (for subjects who complete through the Week 12 visit) or at 12 weeks (84 days) after the 
first administration of study treatment (for subjects who discontinue prior to the Week 12 visit). 
Adverse events that emerge following the 12-week treatment period will be summarized 
separately.
Laboratory values, urinary values, ECGs, vital signs, and extent of exposure will be presented 
descriptively by treatment group.
14.4.2
Pharmacokinetics/pharmacodynamics analyses
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS. Pharmacodynamic 
variables will be analyzed for all subjects in the PD-PPS. 
Pharmacokinetic and PD analyses will be detailed in a separate DAP and reported in a separate 
document.
An analysis will be performed based on data through Week 8 to confirm the dose selection for 
Phase 3. Details will be described in the DAP and linked with the Operational Plan and SAP.
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit.
Anti-bimekizumab antibody data will be summarized for each treatment at each scheduled visit.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 81 of 103
IL-17A, IL-17F, IL-6, and IL-23 data will be summarized for each treatment at each scheduled 
visit.
14.5
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.
14.6
Handling of dropouts or missing data
For the primary efficacy analysis based on evaluating dose response, missing data will be 
imputed using NRI. That is, subjects with missing data at Week 12 or who discontinue double-
blind study treatment prior to Week 12 will be counted as non-responders for the analysis. Two 
sensitivity analyses will be performed for the primary analysis:
1. An analysis will be performed in which all available data at Week 12 will be considered. 
This analysis will be based on the logistic regression model 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 non-responders. 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 treated as missing. 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 PASI90 at Week 12. The following sensitivity analysis will be 
conducted:
1. Missing data will be addressed by using multiple imputation (MI) based on the Markov-
Chain Monte Carlo (MCMC) method for intermittent missing data, followed by monotone 
regression for monotone missing data. The actual PASI scores will be imputed and then 
dichotomized to obtain the PASI90 response status. The multiply imputed data sets will be 
analyzed using a logistic regression model with factors of treatment group, prior biologic 
exposure (yes/no), and region. Finally, SAS PROC MIANALYZE will be used to combine 
the results into a single inference. This procedure assumes a missing at random (MAR) 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 82 of 103
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, 
2012). This is an estimand of efficacy to evaluate the de jure hypothesis.
2. The logistic regression model will be applied where all available data at Week 12 will be 
considered, as described in sensitivity analysis #1 for the primary dose-response efficacy 
analysis.
3. The logistic regression model will be applied where only observed data for subjects still on 
the initially randomized treatment at Week 12 will be considered, as described in sensitivity 
analysis #2 for the primary dose-response efficacy analysis.
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model.
Other categorical efficacy variables will be imputed using NRI.
Other continuous efficacy variables will be imputed using LOCF where the last observed value 
of a variable is used to impute the missing data.
14.7
Planned interim analysis and data monitoring
After all enrolled subjects have completed 8 weeks of treatment, an interim analysis will be 
performed to analyze the dose-exposure response for PASI, including the PASI90 response, in 
each dose group to determine the optimal therapeutic dose(s) for subsequent studies. Decisions 
related to the conduct of the PS0010 study will not be impacted by these analyses as they will be 
conducted by individuals that are not part of the clinical study team, and they will not be shared 
with any clinical study team members until after the lock of Week 12 data, at which point the 
study will be unblinded. Further details related to this interim analysis will be outlined in a 
separate DAP.
14.8
Determination of sample size
A total of 240 subjects (40 in each treatment group) are planned to be randomized in this study. 
The primary efficacy analysis will be based on the FAS. While some randomized subjects may 
not be in the FAS, it is expected that this number will not impact the following calculations.
The sample size is calculated based on published PASI90 response data from the secukinumab 
psoriasis program (ERASURE and FIXTURE studies) and from a Phase 2 bimekizumab study in 
subjects with psoriatic arthritis (PA0007). As an IL-17A inhibitor, the secukinumab data are 
important in the estimation of the response of bimekizumab, an IL-17A/F inhibitor. In the 
ERASURE and FIXTURE studies, PASI90 responses at Week 12 were reported to be 59.2% and 
54.2% for the 300mg treatment group and 39.1% and 41.9% for the 150mg treatment group 
versus 1.2% and 1.5% in the placebo group, respectively (Langley et al, 2014). Limited data 
from a subset of subjects with psoriasis BSA >3% in the PA0007 study indicate a PASI90 
response of 86.7% after 8 weeks of treatment for the combined top 3 doses versus no response in 
the placebo group.  
For the sample size calculation, responder rates of 60%, 50%, and 2% at the end of a 12-week 
Treatment Period for bimekizumab 480mg Q4W, bimekizumab 320mg Q4W, and placebo have 
been assumed, respectively. These assumptions are similar to the results observed in the 
ERASURE and FIXTURE studies and conservative relative to the PA0007 study in order to 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 83 of 103
account for uncertainty in the estimates. The PASI90 responder rates for the 160mg Q4W, and 
64mg Q4W doses are assumed to decrease, using estimates of 40% and 20%, respectively. Note 
that the bimekizumab 320mg loading dose followed by bimekizumab 160mg Q4W has been left 
out of this sample size calculation as it will not be included in the test for dose response, but will 
rather be compared separately to the bimekizumab 160mg Q4W dose.
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 
significance level of 0.05. With 40 subjects in each treatment group, the test for detecting the 
overall dose response based on PASI90 response is powered at >99%.
The sample size calculations were performed using the software nQuery Advisor® 7.0.
15
ETHICS AND REGULATORY REQUIREMENTS
15.1
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.
A separate Informed Consent Form will be required for subjects participating in the substudy for 
genomics, genetics, and proteomics blood sampling.
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 and by the person who conducted the informed consent 
discussion (Investigator or designee). The subject must receive a copy of the signed and dated 
Informed Consent Form. As part of the consent process, each subject must consent to direct 
access to his/her medical records for study-related monitoring, auditing, IRB/IEC review, and 
regulatory inspection.
If the Informed Consent Form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent Form by the IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form.
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.
15.2
Subject identification cards
Upon signing the Informed Consent, the subject will be provided with a subject identification 
card in the language of the subject. The Investigator will fill in the subject identifying 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 84 of 103
information and medical emergency contact information. The Investigator will instruct the 
subject to keep the card with him/her at all times.
15.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, Informed 
Consent Form, IB, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), 
and all other subject-related documents to be used for the study to the IRB/IEC for its review and 
approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
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.
15.4
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 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 85 of 103
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).
15.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
16
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.
17
REFERENCES
Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schäfer I. Epidemiology and 
comorbidity of psoriasis in children. Br J Dermatol. 2010;162:633-6.
Christophers E, Barker JN, Griffiths CE, Daudén E, Milligan G, Molta C, et al. The risk of 
psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in 
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 86 of 103
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Krueger G, Ellis CN. Psoriasis–recent advances in understanding its pathogenesis and treatment. 
J Am Acad Dermatol. 2005;53(1 Suppl 1):S94-100.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 87 of 103
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 88 of 103
18
APPENDICES
18.1
Protocol Amendment 1
Rationale for the amendment
The purpose of this amendment is the following:
!
Extend the timing of the SFU Visit to 20 weeks after the last dose of study medication
!
Remove references to legal representatives being able to provide consent on behalf of 
subjects. Subjects who lack the capacity to consent will not be included in the study.
!
Clarify the exclusion criterion regarding laboratory values
!
Clarify that subjects with any pustular PSO (ie, localized or generalized) are ineligible for 
study participation and that development of any form of pustular PSO (ie, localized or 
generalized) during the study will result in withdrawal from the study
!
Clarify the HADS thresholds for study eligibility in the Exclusion Criteria and for 
withdrawal of a subject in the Withdrawal Criteria
!
Provide more detail in the Withdrawal Criterion regarding subjects that develop illnesses that 
would interfere with study participation
!
Provide more detail in the Withdrawal Criteria regarding the withdrawal of subjects due to 
adverse events and clinical laboratory values
!
Clarify the timing of the optional study exit interview
!
Clarify the adverse events for special monitoring
!
Provide additional detail and a reference for recording the severity of AEs
!
Remove the requirement to test for alcohol in the PDILI urine toxicology screen
!
Clarify the subgroup analyses that will be performed
Modifications and changes
Global changes
The following changes were made throughout the protocol:
!
Section 2 Introduction was revised with updated information
!
The timing of the Safety Follow-Up Visit was changed from 17 weeks after the last dose of 
study medication to 20 weeks after the last dose of study medication.
!
The maximum study duration for enrolled subjects was changed from 29 weeks to 32 weeks.
!
The List of Abbreviations was revised
!
The term “photochemotherapy” was changed to “chemophototherapy” throughout for 
consistency
!
Minor editorial revisions were made
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 89 of 103
Specific changes
Change #1
Section 2.1.2 Current treatments for psoriasis
Therapy for patients with psoriasis varies according to the severity of disease. Limited or mild 
disease is often treated with topical therapies such as corticosteroids and vitamin D analogs. 
Patients with more severe disease are often treated with photochemotherapy, methotrexate, the 
oral phosphodiesterase 4 (PDE4) inhibitor (apremilast), or biologic agents, such as tumor 
necrosis factor (TNF) antagonists, interleukin (IL) 12/23 inhibitors, and IL-17A inhibitors. The 
effectiveness of TNF inhibitors in the treatment of psoriasis has been demonstrated in many 
Phase 3 clinical studies and has led to the approval of multiple TNF inhibitors for use in patients 
with moderate to severe psoriasis. Interleukin inhibitors include secukinumab, an IL-17A 
inhibitor approved for treatment of moderate to severe psoriasis; and ixekizumab, an IL-17A 
inhibitor currently under regulatory review. Ustekinumab is an IL-12/23 antagonist approved for 
use in patients with moderate to severe psoriasis, and brodalumab, an IL-17 receptor antagonist, 
has completed pivotal Phase 3 studies in psoriasis. Standard therapies for psoriasis are listed 
below:
Has been changed to
Therapy for patients with psoriasis varies according to the severity of disease. Limited or mild 
disease is often treated with topical therapies such as corticosteroids and vitamin D analogs. 
Patients with more severe disease are often treated with photochemophototherapy, 
methotrexate, the oral phosphodiesterase 4 (PDE4) inhibitor (apremilast), or biologic agents, 
such as tumor necrosis factor (TNF) antagonists, interleukin (IL) 12/23 inhibitors, and IL-17A 
inhibitors. The effectiveness of TNF inhibitors in the treatment of psoriasis has been 
demonstrated in many Phase 3 clinical studies and has led to the approval of multiple TNF 
inhibitors for use in patients with moderate to severe psoriasis. Interleukin inhibitors include 
secukinumab and ixekizumab, an IL-17A inhibitors approved for treatment of moderate to 
severe psoriasis; and ixekizumab, an IL 17A inhibitor currently under regulatory review. 
Ustekinumab is an IL-12/23 antagonist approved for use in patients with moderate to severe 
psoriasis, and brodalumab, an IL-17 receptor antagonist, has completed pivotal Phase 3 studies in 
psoriasis. Standard therapies for psoriasis are listed below:
Change #2
Section 2.2.1 Clinical
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, PA0007 in 53 subjects with 
psoriatic arthritis. A fourth study in subjects with moderate to severe rheumatoid arthritis is 
ongoing (RA0123).
Has been changed to
Three clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque psoriasis, RA0124 in 30 healthy volunteers, and PA0007 in 53 subjects with 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 90 of 103
psoriatic arthritis. Two studies (RA0123 and UP0031) are ongoing in subjects with moderate 
to severe rheumatoid arthritis and in healthy subjects, respectively. A fourth study in 
subjects with moderate to severe rheumatoid arthritis is ongoing (RA0123).
Change #3
Section 2.2.1 Clinical
A fourth study of bimekizumab is ongoing. RA0123 is a Phase 2a, double-blind, randomized, 
placebo-controlled, multiple dose study to evaluate the safety, PK, PD, and efficacy of multiple 
doses of bimekizumab administered as add-on therapy to stable certolizumab pegol therapy in 
subjects with moderate to severe rheumatoid arthritis.
Has been changed to
Two additional studies of bimekizumab are ongoing A fourth study of bimekizumab is 
ongoing. RA0123 is a Phase 2a, double-blind, randomized, placebo-controlled, multiple dose 
study to evaluate the safety, PK, PD, and efficacy of multiple doses of bimekizumab
administered as add-on therapy to stable certolizumab pegol therapy in subjects with moderate to 
severe rheumatoid arthritis. UP0031 is a Phase 1 open-label, parallel-group, single-dose study 
to evaluate the relative bioavailability and tolerability of bimekizumab 160mg sc in healthy 
subjects.
Change #4
Section 6.1 Inclusion criteria
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.
Has been changed to
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent Form is signed and dated by the subject or legal representative.
Change #5
Section 6.1 Inclusion criteria
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.
Has been changed to
2a. 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.
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 91 of 103
Change #6
Section 6.2 Exclusion criteria
5. Subjects with erythrodermic, guttate, generalized pustular form of psoriasis, or drug-induced 
psoriasis.
Has been changed to
5a. Subjects with erythrodermic, guttate, generalized pustular form of psoriasis, or drug-induced 
psoriasis.
Change #7
Section 6.2 Exclusion criteria
20. 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 2x ULN and <3x ULN 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.
Has been changed to
20a. 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 2x ULN and <3x ULN 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. 
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18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 92 of 103
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.
Change #8
Section 6.2 Exclusion criteria
29. Presence of significant uncontrolled neuropsychiatric disorder, active suicidal ideation, or 
positive suicide behavior using the “Baseline” version of the eC-SSRS and the 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 score ≥10 and Anxiety score ≥15
Has been changed to
29a.Presence of significant uncontrolled neuropsychiatric disorder, active suicidal ideation, or 
positive suicide behavior using the “Baseline” version of the eC-SSRS and the 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 Qquestion 4 or Qquestion 5 of the 
“Screening/Baseline” version of the eC-SSRS at screening. 
∀
HADS Depression score >10 or Anxiety score ≥15
Change #9
Section 6.3 Withdrawal criteria
2. Subject develops an illness that would interfere with his/her continued participation.
Has been changed to
2a. 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.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 93 of 103
Change #10
Section 6.3 Withdrawal criteria
3. Subject develops erythrodermic, guttate, or generalized pustular form of psoriasis.
Has been changed to
3a. Subject develops erythrodermic, guttate, or generalized pustular form of psoriasis.
Change #11
Section 6.3 Withdrawal criteria
The following withdrawal criterion has been deleted
7. Subject develops total bilirubin >2xULN (except Gilbert’s); neutropenia <1.0x109/L; 
lymphopenia <0.5x109/L or other laboratory abnormalities consistent with rheumatology 
Common Terminology Criteria (CTC) Grade 3 or higher if clinically relevant.
Change #12
Section 6.3 Withdrawal criteria
9. Subjects with a HADS-D score ≥15 must be withdrawn. Any subject who has a HADS-D 
score of ≥10 should be referred immediately to a Mental Healthcare Professional for further 
evaluation and potential withdrawal by the Investigator.
Has been changed to
9a. Subjects with a HADS-D score ≥15 must be withdrawn. Any subject who has 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.
Change #13
Section 6.3 Withdrawal criteria
The following withdrawal criteria have been added
10.
Subject experiences an AE as described below: 
∀
Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 and above AE 
that is assessed as related to study drug in the opinion of the Investigator 
◦
If the event is deemed to be not related to study drug by the Investigator, the subject 
may remain in the study after approval by the medical monitor. 
∀
Any CTCAE Grade 2 event that is evaluated as related to study drug in the opinion of the 
Investigator, is persistent, and falls into any of the following System Organ Classes 
(SOCs): “Blood and lymphatic disorders,” “Cardiac disorders,” or “Vascular disorders.” 
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 94 of 103
◦
Persistent is defined as lasting 28 days or more, which spans at least 2 scheduled 
injections.
11. 
Subject has a clinical laboratory value meeting the following criteria:
∀
CTCAE Grade 3 and above: subjects must be withdrawn regardless of relationship to 
study drug or duration of event.
∀
CTCAE Grade 2
◦
Subjects may remain in the study if the event is transient. If a subject has a Grade 2 
laboratory abnormality, a retest is required within 1 to 2 weeks at a scheduled or 
unscheduled visit. If the repeat value is below Grade 2, the subject may receive the 
next scheduled study treatment. If the value on the repeat is still Grade 2 or above, a 
second repeat test must be performed and results made available prior to the next 
scheduled study treatment. If this second repeat value is still Grade 2 or above, the 
subject must be withdrawn.
Change #14
Section 8.1 Screening Visit
Subjects will also be asked about their willingness to participate in a post-study interview 
process. Subjects may decide to participate in the genomic, genetic and proteomic substudy, or 
the interview, or neither.
Has been changed to
Subjects may will also be asked about their willingness to participate in a post study exit
interview near the end of the study process. Subjects may decide to participate in the genomic, 
genetic and proteomic substudy, or the interview, or neither.
Change #15
Section 12.1.3 Adverse events for special monitoring
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 12.6.1), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the eC-SSRS), depression-and anxiety (assessed using the 
HADS, see Section 9.5), major cardiac events and liver function test changes/enzyme elevations 
(ALT, AST, and bilirubin; see Section 12.5.1), malignancies, and inflammatory bowel diseases.
Has been changed to
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 12.6.1), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the eC-SSRS), depression-and anxiety (assessed using the 
HADS, see Section 9.5), major cardiac cardiovascular events and liver function test 
changes/enzyme elevations (ALT, AST, and bilirubin; see Section 12.5.1), malignancies, and 
inflammatory bowel diseases.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 95 of 103
Change #16
Section 12.1.5 Description of adverse events
Details for completion of the Adverse Event CRF (including judgment of relationship to IMP) 
are described in the CRF Completion Guidelines.
Has been changed to
When recording the severity of an AE in the CRF (ie, mild, moderate, or severe), the 
Investigator must refer to the CTCAE Version 4 
(http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm). Details for 
completion of the Adverse Event CRF (including judgment of severity and relationship to IMP) 
are described in the CRF Completion Guidelines.
Change #17
Table 12-4 PDILI laboratory measurements
a
For detecting substances (ie, alcohol, 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.
Has been changed to
a
For detecting substances (ie, alcohol, 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.
Change #18
Section 14.3.3 Subgroup analyses
Subgroup analyses will be performed on the primary and secondary efficacy variables. The 
following variables for subgroup analyses will be defined: age, gender, disease duration, region, 
body weight, BMI, prior systemic chemotherapy or chemophototherapy, prior biologic exposure, 
and antibody positivity. These summaries will be based on imputed data (NRI) and will include 
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 will be defined: age, gender, disease duration, region, 
body weight, BMI, prior systemic phototherapy or chemotherapy or chemophototherapy, 
prior nonbiologic systemic therapy, prior biologic systemic exposure, any prior systemic 
therapy, and antibody positivity. These summaries will be based on imputed data (NRI) and will 
include descriptive statistics only.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 96 of 103
Change #19
Section 15.1 Informed consent
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.
Has been changed to
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.
Change #20
Section 15.2 Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), 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.
Has been changed to
Upon signing the Informed Consent and Assent form (as applicable), 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.
Change #21
Section 17 References
The following reference was added:
Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. National Institutes of 
Health, National Cancer Institute, Division of Cancer Treatment and Diagnosis. 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Updated 03 Mar 
2016.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 97 of 103
18.2
Protocol Amendment 2
Rationale for the amendment
The purpose of this amendment is the following:
!
To revise the references to PS0011 as an “open-label extension study.” Because of 
changes to the study design of PS0011, the PS0011 study is no longer planned to be an 
“open-label” study. 
!
Clarify that the SFU Visit will not be conducted in PS0010 for subjects who enroll in the 
extension study.
!
Clarify and correct text regarding the analyses of safety.
Modifications and changes
Global changes
The reference to PS0011 as an “open-label extension study” was changed throughout the
document. “Open-label” was deleted and, instead, the PS0011 study is being referred to as an 
“extension study.”
Specific changes
Change #1
Section 1 Summary
Approximately 40 subjects will be randomized to each treatment arm and study medication will 
be administered in the clinic at Baseline, Week 4, and Week 8. Additional nondosing study visits 
will occur at Week 1, Week 2, and Week 6. At Week 12, all subjects enrolling in the open-label 
extension study will undergo the Week 12 study assessments before receiving their first 
open-label dose of bimekizumab. All subjects not enrolling in the open-label extension study will 
have the Week 12 study assessments and will enter the SFU Period.
Has been changed to
Approximately 40 subjects will be randomized to each treatment arm and study medication will 
be administered in the clinic at Baseline, Week 4, and Week 8. Additional nondosing study visits 
will occur at Week 1, Week 2, and Week 6. At Week 12, all subjects enrolling in the open label
extension study will undergo the Week 12 study assessments before receiving their first 
extension studyopen label dose of bimekizumabstudy treatment. All subjects not enrolling in 
the open label extension study will have the Week 12 study assessments and will enter the SFU 
Period.
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 98 of 103
Change #2
Section 5.1.1 Study Periods
At Week 12, all subjects enrolling in the open-label extension study (PS0011) will undergo the 
Week 12 study assessments and then receive their first open-label dose of bimekizumab. All 
subjects not enrolling in the open-label extension study will have the Week 12 study assessments 
and will enter the SFU Period.
Has been changed to
At Week 12, all subjects enrolling in the open label extension study (PS0011) will undergo the 
Week 12 study assessments and then receive their first extension studyopen label dose of 
bimekizumabstudy treatment. All subjects not enrolling in the open label extension study will 
have the Week 12 study assessments and will enter the SFU Period.
Change #3
Section 5.1.2 Study duration per subject
After the 12-week Treatment Period, subjects will be allowed to enroll in an extension study. 
The SFU Visit will not be required for subjects who enroll in the extension study.
Has been changed to
After the 12-week Treatment Period, subjects will be allowed to enroll in an extension study. 
The SFU Visit will not be requiredconducted in PS0010 for subjects who enroll in the 
extension study.
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REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 101 of 103
treatment (for subjects who discontinue prior to the Week 12 visit). Adverse events that emerge following 
the 12-week treatment period will be summarized separately.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 102 of 103
19
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
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UCB
18 Jul 2016
Clinical Study Protocol
Bimekizumab
PS0010
Confidential
Page 103 of 103
20
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. 


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

SAP_001.pdf: 
UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 1 of 63
STATISTICAL ANALYSIS PLAN 
Study: PS0010
Product: BIMEKIZUMAB
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP, DOSE RANGING STUDY TO EVALUATE THE SAFETY, 
EFFICACY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF BIMEKIZUMAB 
IN ADULT SUBJECTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS
SAP/Amendment Number
Date
Final SAP
13 Oct 2016
Amendment 1
13 June 2017
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.
17
17
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CONT
CON
TE TH
E TH
MICS O
ICS 
ONI
NIC 
C
ocumen
cume
us
ca


UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 2 of 63
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................6
1
INTRODUCTION .............................................................................................................8
2
PROTOCOL SUMMARY.................................................................................................8
2.1 Study objectives.................................................................................................................8
2.1.1
Primary objective...................................................................................................8
2.1.2
Secondary objectives .............................................................................................8
2.1.3
Other objectives.....................................................................................................8
2.2 Study variables...................................................................................................................8
2.2.1
Efficacy variables ..................................................................................................8
2.2.1.1
Primary efficacy variable ............................................................................8
2.2.1.2
Secondary efficacy variables.......................................................................9
2.2.1.3
Other efficacy variables...............................................................................9
2.2.2
Pharmacokinetic/pharmacodynamic variables ....................................................10
2.2.2.1
Pharmacokinetic variables.........................................................................10
2.2.2.2
Pharmacodynamic variable .......................................................................10
2.2.3
Pharmacogenomic variables ................................................................................10
2.2.3.1
Genomic, genetic, and metabolite variables..............................................10
2.2.4
Immunological variable.......................................................................................10
2.2.5
Safety variables....................................................................................................10
2.3 Study design and conduct ................................................................................................11
2.3.1
Study description .................................................................................................11
2.3.2
Study periods .......................................................................................................11
2.3.3
Study duration per subject ...................................................................................12
2.4 Determination of sample size...........................................................................................12
3
DATA ANALYSIS CONSIDERATIONS......................................................................13
3.1 General presentation of summaries and analyses ............................................................13
3.2 Definition of Baseline values...........................................................................................14
3.3 Mapping of assessments performed at early study withdrawal visit ...............................14
3.4 Protocol deviations...........................................................................................................14
3.5 Analysis sets.....................................................................................................................14
3.5.1
Enrolled Set .........................................................................................................14
3.5.2
Randomized Set...................................................................................................15
3.5.3
Safety Set.............................................................................................................15
3.5.4
Full Analysis Set..................................................................................................15
3.5.5
Per Protocol Set ...................................................................................................15
3.5.6
Other analysis sets ...............................................................................................15
3.5.6.1
Pharmacokinetics Per-Protocol Set ...........................................................15
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 3 of 63
3.5.6.2
Pharmacodynamics Per-Protocol Set ........................................................15
3.6 Treatment assignment and treatment groups ...................................................................15
3.7 Center pooling strategy....................................................................................................16
3.8 Coding dictionaries ..........................................................................................................16
3.9 Analysis time points.........................................................................................................16
3.9.1
Pre-treatment period ............................................................................................16
3.9.2
Double-blind treatment period.............................................................................16
3.9.3
Follow-up period .................................................................................................16
3.10 Relative day .....................................................................................................................17
3.11 Changes to protocol-defined analyses..............................................................................17
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................17
4.1 Adjustments for covariates...............................................................................................17
4.2 Handling of dropouts or missing data..............................................................................18
4.2.1
Handling missing data for the primary efficacy variable ....................................18
4.2.2
Handling missing data for the secondary analysis of the primary efficacy
variable ................................................................................................................18
4.2.3
Handling missing data for other efficacy variables .............................................18
4.2.4
Safety variables....................................................................................................19
4.3 Interim analyses and data monitoring..............................................................................20
4.4 Multicenter studies...........................................................................................................21
4.5 Multiple comparisons/multiplicity...................................................................................21
4.6 Use of an efficacy subset of subjects ...............................................................................21
4.7 Active-control studies intended to show equivalence......................................................21
4.8 Examination of subgroups ...............................................................................................21
5
STUDY POPULATION CHARACTERISTICS.............................................................22
5.1 Subject disposition...........................................................................................................22
5.2 Protocol deviations...........................................................................................................22
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................22
6.1 Demographics ..................................................................................................................22
6.2 Other Baseline characteristics..........................................................................................23
6.3 Medical history and concomitant diseases.......................................................................24
6.4 Prior and concomitant medications..................................................................................24
7
MEASUREMENTS OF TREATMENT COMPLICANCE............................................25
8
EFFICACY ANALYSES ................................................................................................25
8.1 Statistical analysis of the primary efficacy variable ........................................................25
8.1.1
Derivations of PASI score and response .............................................................25
8.1.2
Primary analysis of the primary efficacy variable...............................................26
8.1.3
Secondary analyses of the primary efficacy variable ..........................................27
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 4 of 63
8.1.4
Supportive and sensitivity analyses of the primary efficacy variable .................28
8.1.4.1
Sensitivity analyses ...................................................................................28
8.1.4.2
Supportive analysis....................................................................................29
8.1.4.3
Multiple imputation analysis.....................................................................29
8.2 Statistical analysis of the secondary efficacy variables ...................................................31
8.2.1
Derivation of IGA response.................................................................................31
8.2.2
Analysis of Investigator’s Global Assessment ....................................................31
8.2.3
Analyses of secondary PASI responder variables ...............................................32
8.2.3.1
PASI90 at Week 8 .....................................................................................32
8.2.3.2
PASI75 at Week 12 ...................................................................................32
8.2.3.3
PASI100 at Week 12 .................................................................................32
8.3 Analysis of other efficacy variables.................................................................................32
8.3.1
Further analysis of  Investigator’s Global Assessment........................................33
8.3.2
Further analysis of  PASI.....................................................................................33
8.3.3
Analysis of BSA ..................................................................................................33
8.3.4
Derivation of DLQI score and response ..............................................................33
8.3.5
Analysis of DLQI ................................................................................................34
8.3.6
Derivation of mNAPSI score...............................................................................34
8.3.7
Analysis of mNAPSI ...........................................................................................35
8.3.8
Derivation of PGADA for the arthritis VAS .......................................................35
8.3.9
Analysis of PGADA for the arthritis VAS ..........................................................35
8.3.10
Derivation of PSSI...............................................................................................35
8.3.11
Analysis of PSSI..................................................................................................36
8.3.12
Derivation of SF-36 .............................................................................................36
8.3.13
Analysis of SF-36 ................................................................................................36
8.3.14
Definition of Time to PASI Response.................................................................37
8.3.15
Analysis of Time to PASI Response ...................................................................37
8.3.16
Definition of Subject Symptom Diary responses ................................................37
8.3.17
Analysis of Subject Symptom Diary responses...................................................38
8.3.18
Definition of HADS.............................................................................................38
8.3.19
Analysis of HADS ...............................................................................................38
8.3.20
Definition of PGIC ..............................................................................................38
8.3.21
Analysis of PGIC.................................................................................................38
8.3.22
Definition of PGIS...............................................................................................38
8.3.23
Analysis of PGIS .................................................................................................38
9
PHARMACOKINETICS AND PHARMACODYNAMICS..........................................39
9.1 Pharmacokinetics .............................................................................................................39
9.2 Pharmacodynamics ..........................................................................................................39
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 5 of 63
9.3 Immunogenicity...............................................................................................................39
9.3.1
Anti-bimekizumab antibodies..............................................................................39
10
SAFETY ANALYSES.....................................................................................................39
10.1 Extent of exposure ...........................................................................................................40
10.1.1
Duration of exposure ...........................................................................................40
10.1.2
Number of doses received ...................................................................................40
10.1.3
Exposure days at risk...........................................................................................40
10.2 Adverse events.................................................................................................................40
10.2.1
Treatment-emergent adverse events ....................................................................40
10.2.2
Deaths, serious adverse events, and other significant adverse events .................45
10.3 Clinical laboratory evaluations ........................................................................................46
10.4 Vital signs, physical findings, and other observations related to safety..........................50
10.4.1
Vital signs ............................................................................................................50
10.4.2
Electrocardiograms..............................................................................................50
10.4.3
Other safety variables ..........................................................................................51
10.4.3.1
Assessment and management of TB and TB risk factors..........................51
10.4.3.2
Electronic Columbia Suicide Severity Rating Scale .................................51
10.4.3.3
Physical examination.................................................................................51
11
REFERENCES ................................................................................................................52
12
APPENDICES .................................................................................................................53
12.1 Classification of the SF-36v2 questionnaire....................................................................53
12.2 AESM Opportunistic infections.......................................................................................54
12.3 MedDRA algorithmic approach to anaphylaxis ..............................................................54
13
AMENDMENT TO THE STATISTICAL ANALYSIS PLAN......................................57
13.1 Amendment 1...................................................................................................................57
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................63
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 6 of 63
LIST OF ABBREVIATIONS
AB
antibody
AbAb
anti-bimekizumab antibody
ADR
adverse drug reaction
AE
adverse event
AESM
adverse  events of special monitoring
ATC
Anatomical Therapeutic Chemical
BLQ
below level of quantification
BSA
body surface area
CMH
Cochran-Mantel-Haenszel
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DAP
Data Analysis Plan
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
EAER
exposure adjusted event rate
EAIR
exposure adjusted incidence rate
ES
Enrolled Set
ECG
electrocardiogram
eCRF
electronic Case Report Form
FAS
Full Analysis Set
Full MSE
Full Missing Score Estimation
HADS
Hospital Anxiety and Depression Scale
HLGT
Higher level group term
IGA
Investigator’s Global Assessment
LLOQ
lower level of quantification
LOCF
last observation carried forward
MAR
missing at random
MCID
minimal clinically important difference
MCMC
Markov Chain Monte Carlo
MCS
Mental Component Summary
MI
multiple imputation
MMRM
mixed-effects model of repeated measures
mNAPSI
modified Nail Psoriasis Severity Index
NRI
non-responder imputation
NSAID(s)
non-steroidal anti-inflammatory drug(s)
PASI 
Psoriasis Area and Severity Index
PCS
Physical Component Summary
PD
pharmacodynamics
PDILI
Potential drug-induced liver injury
PGADA
Patient's Global Assessment of Disease Activity
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetics
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 7 of 63
PPS
Per Protocol Set
PSSI
Psoriasis Scalp Severity Index
PT
preferred term
Q4W
every four weeks
QOL
quality of life
RS
Randomized Set
sc
subcutaneously
SD
standard deviation
SAP
statistical analysis plan
SF-36
Short Form 36 item Health Survey
SFU
Safety Follow-Up
SMQ
Standard MedDRA query
SOC
system organ class
SS
Safety Set
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ToPAS
Toronto Psoriatic Arthritis Screening questionnaire
VAS
visual analog scale
WHO
World Health Organization
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 8 of 63
1
INTRODUCTION
This statistical analysis plan (SAP) defines the summary tables, figures, and listings (TFLs) to be 
generated for the clinical study report (CSR) and is based on the final protocol (01 Jun 2016), 
protocol amendment 1 (08 Jul 2016), and protocol amendment 2 (18 Jul 2016).
2
PROTOCOL SUMMARY
2.1
Study objectives
2.1.1
Primary objective
The primary objective of the study is to evaluate the dose response of bimekizumab administered 
subcutaneously (sc) every four weeks (Q4W) for 12 weeks in the treatment of subjects with 
moderate to severe chronic plaque psoriasis.
2.1.2
Secondary objectives
The secondary objectives of the study are to:
•
Evaluate the efficacy of individual dose regimens of bimekizumab compared to placebo after 
12 weeks of treatment for subjects with moderate to severe chronic plaque psoriasis
•
Compare the efficacy of the bimekizumab 160mg treatment group versus the bimekizumab 
160mg treatment group with a loading dose
•
Assess the pharmacokinetics (PK) of bimekizumab following sc dosing Q4W
•
Assess the safety, immunogenicity, and tolerability of bimekizumab
•
Assess the exposure response relationship of bimekizumab as it relates to efficacy and safety
•
Characterize the population PK of bimekizumab in the moderate to severe psoriatic 
population following repeat dose administration.
2.1.3
Other objectives
The other objectives of the study are to:
•
Assess the improvement of skin-related quality of life (QOL)
•
Assess the improvement of general health-related QOL
•
Assess psoriatic nail disease in subjects with nail disease at Baseline
•
Assess psoriatic scalp disease in subjects with scalp psoriasis at Baseline
•
Assess the effect of bimekizumab on gene and protein expression, and explore the 
relationship between genomic, genetic, and proteomic biomarkers and disease biology, drug 
treatment and inflammatory and immune responses.
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variable
The primary efficacy variable is the Psoriasis Area and Severity Index (PASI)90 response 
defined as a subject that achieves 90% reduction from Baseline in the PASI score at Week 12.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 9 of 63
2.2.1.2
Secondary efficacy variables
The secondary efficacy variables are:
•
Investigator’s Global Assessment (IGA) response (Clear or Almost Clear with at least two 
category improvement from Baseline) at Week 12
•
IGA response (Clear or Almost Clear with at least two category improvement from Baseline) 
at Week 8
•
PASI90 response at Week 8
•
PASI75 response at Week 12
•
PASI100 response at Week 12
2.2.1.3
Other efficacy variables
The other efficacy variables detailed below will be evaluated at all scheduled visits in accordance 
with the Schedule of Assessments (see study protocol Table 5-1).  This excludes the primary and 
secondary variables as specified in Section 2.2.1.1 and Section 2.2.1.2.
The other efficacy variables are:
•
PASI50, PASI75, PASI90, and PASI100 response
•
IGA response (Clear or Almost Clear with at least 2 category improvement from Baseline)
•
Absolute and percent change from Baseline in PASI score
•
Shift from Baseline in IGA score
•
Change from Baseline in Dermatology Life Quality Index (DLQI)
•
Percentage of subjects achieving a DLQI score of 0 or 1
•
Percentage of subjects achieving a minimal clinically important difference (MCID) 
(improvement from Baseline of four or more) in the DLQI
•
Time to PASI50 response
•
Time to PASI75 response
•
Time to PASI90 response
•
Time to PASI100 response
•
Absolute and percent change from Baseline in the body surface area (BSA) affected by 
psoriasis
•
Change from Baseline in modified Nail Psoriasis Severity Index (mNAPSI) score (in the 
subgroup of subjects with psoriatic nail disease at Baseline)
•
Change from Baseline in the Subject's Global Assessment of Disease Activity (PGADA) for 
the arthritis visual analog scale (VAS)
•
Change from Baseline in the Psoriasis Scalp Severity Index (PSSI) (in the subgroup of 
subjects with scalp psoriasis at Baseline)
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 10 of 63
•
Change from Baseline in Short Form 36 item Health Survey (SF-36) Physical Component 
Summary (PCS) score, and Mental Component Summary (MCS) score, and individual 
domains
•
Change from Baseline in the Subject Symptom Diary responses (for subjects at sites in 
selected countries)
•
Patient Global Impression of Change (PGIC)
•
Change from Baseline in Patient Global Impression of Severity (PGIS)
•
Change from Baseline in Hospital Anxiety and Depression Scale (HADS) HADS-A and 
HADS-D scores
•
Percentage of subjects with scores below eight in HADS-A and HADS-D (subjects with 
normal scores)
2.2.2
Pharmacokinetic/pharmacodynamic variables
2.2.2.1
Pharmacokinetic variables
The PK variables are:
•
Plasma concentration of bimekizumab and population PK
•
Dose-exposure response characterizing the relationship between PASI score and 
bimekizumab concentration and dose, including EC50/ED50 and Emax to support dose 
selection for subsequent Phase 3 studies
2.2.2.2
Pharmacodynamic variable
The pharmacodynamic (PD) variable is to determine the plasma concentrations of cytokines of 
relevance to IL17-A/F signaling pathway and psoriasis biology, including but not limited to 
serum complement concentrations, mononuclear cell subtypes, and cytokines and other candidate 
biomarkers.
2.2.3
Pharmacogenomic variables
2.2.3.1
Genomic, genetic, 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, and proteomic biomarkers relevant to the 
inflammatory and immune response processes. The nature and format of these tentative analyses 
will be determined when the results of the main study are made available.
2.2.4
Immunological variable
The immunological variable is anti-bimekizumab antibody (AbAb) detection prior to and 
following study treatment.
2.2.5
Safety variables
Safety variables to be assessed are:
•
Severity and frequency of adverse events (AEs) (including serious AEs)
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 11 of 63
•
Change from Baseline in clinical laboratory values (chemistry, hematology, and urinalysis)
•
Change from Baseline in vital signs
•
Change from Baseline in physical examination
•
Electrocardiogram (ECG) results
2.3
Study design and conduct
2.3.1
Study description
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
dose-ranging study to evaluate the safety, efficacy, PK, and PD of bimekizumab administered sc
to subjects with chronic plaque psoriasis. To be eligible to participate in this study, subjects must 
be adults with a diagnosis of moderate to severe psoriasis (Baseline PASI ≥12 and BSA affected 
by psoriasis ≥10% and IGA score ≥3 [on a 5-point scale]) who are a candidate for systemic 
psoriasis therapy and/or phototherapy and/or chemophototherapy.
2.3.2
Study periods
This study will include three periods which are:
•
Screening Period (2 to 4 weeks)
•
Treatment Period (12 weeks)
•
Safety Follow-Up (SFU) Period (20 weeks after the last dose of study medication for subjects 
not entering the extension study)
After the 12-week Treatment Period, eligible subjects will be allowed to enroll in an extension 
study (PS0011).
Screening Period
The Screening Period will last two weeks, but can be extended up to a total of four weeks in the 
event that applicable laboratory screening tests require retesting if the initial results are in error, 
borderline, or indeterminate. During this time, laboratory data (hematology, urine, and 
biochemistry tests) will be obtained, the doses of non-steroidal anti-inflammatory drug 
(NSAIDs) (if used to treat psoriatic arthritis), will be verified as stable.
Treatment Period
During the Treatment Period subjects will be randomized 1:1:1:1:1:1 to receive the following 
blinded study treatment regimens:
•
bimekizumab 64mg administered sc Q4W
•
bimekizumab 160mg administered sc Q4W
•
bimekizumab 320mg loading dose administered sc at Baseline followed by 160mg dose 
administered sc Q4W
•
bimekizumab 320mg administered sc Q4W
•
bimekizumab 480mg administered sc Q4W
•
Placebo administered sc Q4W
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 12 of 63
Approximately 320 subjects will be screened in order to have 240 subjects randomized in the 
study. There will be approximately 40 subjects per treatment group and study medication will be 
administered in the clinic at Baseline, Week 4, and Week 8. Additional non-dosing study visits 
will occur at Week 1, Week 2, and Week 6. 
At Week 12, all subjects enrolling in the extension study (PS0011) will undergo the Week 12 
study assessments and then receive their extension study dose of study treatment. All subjects 
not enrolling in the extension study will have the Week 12 study assessments and will enter the 
SFU Period.
Subjects who withdraw early from study treatment will be asked to return for study assessments 
12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit.
Subjects withdrawing early from the study who are unable to return for the Week 12 Visit will 
undergo the early Withdrawal Visit assessments and will enter the SFU Period.
Safety Follow-Up Period
All subjects not continuing in the extension study, including those withdrawn from study 
treatment, will have a SFU Visit 20 weeks after their last dose of study medication.
2.3.3
Study duration per subject
For each subject, the study will last for a maximum of up to 29 weeks. This includes the 
following study period durations:
•
Screening Period: 2 to 4 weeks
•
Double-blind, placebo-controlled Treatment Period: 12 weeks
•
SFU Period: a SFU Visit is planned 20 weeks after the last dose of study medication
After the 12-week Treatment Period, subjects will be allowed to enroll in an extension study. 
The SFU Visit will not be required for subjects who enroll in the extension study.
The end of the study is defined as the date of the last visit of the last subject in the study.
2.4
Determination of sample size
A total of 240 subjects (40 in each treatment group) are planned to be randomized in this study. 
The primary efficacy analysis will be based on the full analysis set (FAS). While some 
randomized subjects may not be in the FAS, it is expected that this number will not impact the 
following calculations.
The sample size is calculated based on published PASI90 response data from the secukinumab 
psoriasis program (ERASURE and FIXTURE studies) and from a Phase 2 bimekizumab study in 
subjects with psoriatic arthritis (PA0007). As an IL-17A inhibitor, the secukinumab data are 
important in the estimation of the response of bimekizumab, an IL-17A/F inhibitor. In the 
ERASURE and FIXTURE studies, PASI90 responses at Week 12 were reported to be 59.2% and 
54.2% for the 300mg treatment group and 39.1% and 41.9% for the 150mg treatment group 
versus 1.2% and 1.5% in the placebo group, respectively (Langley et al, 2014). Limited data 
from a subset of subjects with psoriasis BSA >3% in the PA0007 study indicate a PASI90 
response of 86.7% after eight weeks of treatment for the combined top three doses versus no 
response in the placebo group.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 13 of 63
For the sample size calculation, responder rates of 60%, 50%, and 2% at the end of a 12-week 
Treatment Period for bimekizumab 480mg Q4W, bimekizumab 320mg Q4W, and placebo have 
been assumed, respectively. These assumptions are similar to the results observed in the 
ERASURE and FIXTURE studies and conservative relative to the PA0007 study in order to 
account for uncertainty in the estimates. The PASI90 responder rates for the 160mg Q4W and 
64mg Q4W doses are assumed to decrease, using estimates of 40% and 20%, respectively. Note 
that the bimekizumab 320mg loading dose followed by bimekizumab 160mg Q4W has been left 
out of this sample size calculation as it will not be included in the test for dose response, but will 
rather be compared separately to the bimekizumab 160mg Q4W dose.
The sample size for the primary objective of evaluating the dose response relationship was 
calculated using a two-sided test for detecting a linear trend across proportions at a significance 
level of 0.05. With 40 subjects in each treatment group, the test for detecting the overall dose 
response based on PASI90 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
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be performed using SAS Version 9.3 or higher. All tables and listings will use Courier New 
font size 9. 
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. 
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, standard deviation (SD), median, minimum, and maximum. For 
bimekizumab PK concentrations, summary statistics will include geometric mean, geometric 
coefficient of variation (CV), 95% confidence intervals for geometric mean, arithmetic mean, 
SD, median, minimum, and maximum. All summaries of PK variables will be based on the 
observed values. No imputation will be used.
Decimal places for descriptive statistics will always apply the following rules:
•
“n” will be an integer
•
Mean, SD, and median will use one additional decimal place compared to the original data
•
CV[%] will be presented with one decimal place
•
Minimum and maximum will have the same number of decimal places as the original value.
Derived variables in general will display the mean, SD and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics.
Statistical tests of efficacy variables will be presented as two-sided p-values rounded to three 
decimal places. P-values less than 0.001 will be presented as “<0.001” and p-values greater than 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 14 of 63
0.999 will be presented as “>0.999.” Statistical comparisons will be two-sided and will be 
performed at the 0.05 level of significance.
A complete set of data listings containing all documented data as well as calculated data (eg, 
change from Baseline) will be generated.
3.2
Definition of Baseline values
Unless otherwise specified, the last valid measurement before study medication administration in 
the double-blind period will be used as the Baseline value. The same Baseline definition will be 
used for the follow-up period. If a Baseline visit measurement is missing, and a Screening visit 
measurement is available, the Screening value will be utilized as Baseline. 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.
3.3
Mapping of assessments performed at early study withdrawal 
visit
Study assessments at an early study withdrawal 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 withdrawal 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. The only exception to this rule is for anti-bimekizumab antibody (AbAb) assessments 
where all premature withdrawal visit assessments will be assigned to the next scheduled visit at 
which AbAb are assessed. All by-visit summaries will contain nominal visits only. Unscheduled 
visits will not be mapped to scheduled visits. For subjects who discontinue study treatment early 
and return for the Week 12 visit as per the protocol, the assessments collected at that visit are 
summarized as Week 12 assessments in observed case summaries. For summaries based on 
imputed data, the Week 12 value will be treated as missing and imputed according to the rules 
for the given variable.
3.4
Protocol deviations 
Important protocol deviations are defined as those deviations from the protocol likely to have a 
meaningful impact on the efficacy, 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. All protocol deviations will be reviewed as part of the ongoing data 
cleaning process and all important deviations will be identified and documented in a separate 
Protocol Deviation Tracker prior to unblinding to confirm exclusion from analysis sets.
3.5
Analysis sets
The primary efficacy variable will be summarized using the FAS and also the Per Protocol Set 
(PPS) as a supportive analysis. All other efficacy analyses will be based on the FAS. Safety 
variables will be summarized using the Safety Set (SS).
3.5.1
Enrolled Set
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 15 of 63
3.5.2
Randomized Set
The Randomized Set (RS) will consist of all randomized subjects.
3.5.3
Safety Set
The SS will consist of all subjects who received at least one dose of the study medication.
3.5.4
Full Analysis Set
The FAS will consist of all randomized subjects who received at least one dose of the study 
medication and have a valid measurement of the primary efficacy variable at Baseline.
3.5.5
Per Protocol Set
The PPS will consist of all subjects in the FAS who had no important protocol deviation 
affecting the primary efficacy variable. The subjects with important protocol deviations will be 
pre-defined and evaluated during a data evaluation meeting prior to unblinding of the data.
3.5.6
Other analysis sets
3.5.6.1
Pharmacokinetics Per-Protocol Set
The PK-PPS will consist of all randomized subjects who took at least one dose of the study 
medication and provided at least one quantifiable plasma concentration post-dose and had no 
important protocol deviations affecting the pharmacokinetic variables, as confirmed during 
ongoing data cleaning meetings prior to database lock.
3.5.6.2
Pharmacodynamics Per-Protocol Set
The PD-PPS will consist of all randomized subjects who took at least one dose of the study 
medication and provided at least one PD measurement post-dose with no important protocol 
deviations affecting the measurement.
3.6
Treatment assignment and treatment groups
At Baseline, eligible subjects will be randomly assigned as described in Section 2.3.2. Treatment 
assignment for the FAS and PPS will be according to randomization and not actual treatment 
received. 
It is expected that subjects will receive treatment as randomized. Hence, safety analyses should 
be based on randomized treatment for the SS. However, if it is determined after unblinding that 
subjects randomized to placebo received bimekizumab at any time, then these subjects will be 
reallocated to the appropriate bimekizumab group and will be summarized accordingly from the 
time point at which the misallocation occurred. If a subject receives different doses of 
bimekizumab at different time points (not including bimekizumab 160mg subjects who have a 
320mg loading dose at Baseline), then the subject will be allocated to the highest dose received. 
If the highest dose was received earlier than the other(s), then all safety data will be summarized 
under that dose. If the highest dose was received later than the other(s), then safety data will be 
summarized under that dose starting from the time point at which it was first received. Since the 
period of exposure at risk (140 days) is longer than the treatment period (84 days), no 
consideration is given to the time at which exposure to misallocated doses can be considered 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 16 of 63
Subjects randomized to a bimekizumab group will only be reallocated to the placebo treatment 
group if they never received bimekizumab.
3.7
Center pooling strategy
Centers will be pooled into regions for analysis purposes. Due to the small number of subject in 
the Asia region, this will be combined with Europe. Centers will be grouped in the following 
regions: North America, Europe & Asia. These regions include the following countries:
•
North America: Canada, USA
•
Europe & Asia: Czech Republic, Hungary, Poland, Japan
3.8
Coding dictionaries
All prior and concomitant medications other than study drug will be classified by WHO 
Anatomical Therapeutic Chemical (ATC) Classification, presenting Anatomical Main Group 
(ATC Level 1), Pharmacological Subgroup (ATC level 3), and preferred term, using version 
SEP/2015 of the World Health Organization Drug Dictionary (WHO-DD), according to UCB 
standard operating procedures (SOP).
All AEs will be classified by primary system organ class (SOC), high level term (HLT) and 
preferred term (PT) using version 19.0 of MedDRA® according to UCB Standard Operating 
Procedures (SOP). Previous and ongoing medical history will be classified by MedDRA® SOC 
and PT.
3.9
Analysis time points
3.9.1
Pre-treatment period
The pre-treatment period (Screening period) of the study is the period prior to a subject’s first 
dose of study medication intake. This period starts at the Screening visit (2 to 4 weeks prior to 
first dose) and ends at the Baseline visit (Week 0) up to the time of first study medication 
administration (exclusive). Unless specific time information is available to indicate that a 
Baseline visit assessment was performed after a subject’s first study medication administration, 
all assessments performed at the baseline visit will be attributed to the pre-treatment period.
3.9.2
Double-blind treatment period
The double-blind treatment period begins at the Baseline visit (Week 0) at the time of first study 
medication administration (inclusive) and ends at the Week 12/WD Visit.
Premature withdrawal visit assessments will be assigned to the next scheduled visit following the 
last visit where assessments are available. All visit measurements, even violating the visit 
window, will be utilized for the respective visit as long as they are in the proper sequence. 
Subjects will be classified as completing the study if they complete the Week 12 Visit without 
early withdrawal from the study. This is regardless of whether they attend the Follow-up visit 
and regardless of whether they consent to the extension study.
3.9.3
Follow-up period
For the subjects who do not consent to the extension study the SFU visit will take place 20 weeks 
after the last dose of study medication. 
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 17 of 63
AEs that occur during the follow-up period will be reported separately. In addition AEs that 
occur in subjects who have entered the extension study will be captured within the extension 
study.
3.10
Relative day
The relative day will be included in different listings and will be calculated as follows:
•
If the start (stop) date occurred on or after the first dose, but prior to the double-blind drug 
stop date, relative day is calculated as start (stop) date minus first dose date + 1
•
If the start (stop) date occurred after the last dose of double-blind drug, the relative day to the 
most recent dose is calculated as start (stop) date minus most recent dose date. The relative 
day in this situation should be preceded by a ‘+’
•
If the start (stop) date occurred before the first dose, the relative day is calculated as start 
(stop) date minus first dose date. The relative day in this situation should be preceded by a
‘-‘.
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. Relative day will only be 
computed for fully completed dates and will be missing for partial dates.
3.11
Changes to protocol-defined analyses
Section 14.6 of the protocol (Handling of dropouts or missing data) describes the sensitivity 
analysis to be used in this study. More specifically, the protocol describes a sensitivity analysis 
using multiple imputation as the method for handling missing data and states that the MCMC 
method will be used for intermittent missing data and that monotone regression will be used for 
monotone missing data. This SAP has been modified such that the MCMC method will be used 
for all missing data whether intermittent or monotone.
Section 14.6 of the protocol also notes that the missing data for all continuous efficacy variables 
that have not been specifically described elsewhere will be imputed using the last observation 
carried forward (LOCF) approach. This has been updated in this SAP so that these continuous 
variables will in fact be imputed using the multiple imputation method. However, in the event 
that multiple imputation is not possible (eg, Due to small group sizes or insufficient missing 
data) then the LOCF method will be used. 
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
The primary efficacy analyses and selected secondary analyses will be adjusted for the following 
covariates:
•
Prior biologic exposure
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 18 of 63
4.2
Handling of dropouts or missing data
Based on previous studies of biologics in subjects with moderate to severe chronic plaque 
psoriasis, it is expected that the number of subjects who discontinue prior to Week 12 will be 
low. For the small percentage of subjects for whom primary endpoint data are unavailable at 
Week 12, this lack of data is suggestive of an ineffective study treatment, thereby supporting the 
imputation of nonresponse. Achieving the clinical response and making it through 12 weeks of 
study treatment are both critical components of the primary outcome. Therefore, nonresponder 
imputation (NRI) will be used as the method for handling missing data in the primary analysis. 
However, to account for other possible mechanisms of missing data other sensitivity analyses 
will be performed as described in Section 8.1.4.1.
4.2.1
Handling missing data for the primary efficacy variable
For the primary efficacy analysis based on evaluating dose response, missing data will be 
imputed using NRI. That is, subjects with missing data at Week 12 or who discontinue double 
blind study treatment prior to Week 12 will be counted as non-responders for the analysis.
In addition, sensitivity analyses will be performed which will assess the impact of different 
methods of handling missing data. These methods are described in Section 8.1.4.1. 
4.2.2
Handling missing data for the secondary analysis of the primary 
efficacy variable
For the key secondary analysis of the primary efficacy variable based on performing pairwise 
comparisons of bimekizumab doses versus placebo, missing data will be imputed using NRI as 
described in Section 4.2.1.
In addition there will be 4 sensitivity analyses to assess the impact of missing data. These are 
further described in Section 8.1.4.1.
4.2.3
Handling missing data for other efficacy variables
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model. However, the dose/exposure response model is 
outside of the scope of this SAP and is described in greater detail in a separate data analysis plan 
(DAP).
Other categorical efficacy variables will be imputed using NRI (ie. Missing data or subjects who 
prematurely discontinue study treatment prior to Week 12 will be counted as non-responders) or 
summarized as observed cases. One exception to this rule is the imputation of missing data when 
summarizing HADS-A and HADS-D scores below 8 (ie. Normal HADS scores). In these 
summaries, LOCF will be used. That is, the last available HADS-A/HADS-D score while the 
subject was on study treatment will be carried forward to the missing time points to determine 
whether or not the subject had normal HADS scores.
Continuous efficacy variables will be imputed using multiple imputation (MI) via the Markov-
Chain Monte Carlo (MCMC) method. Summaries based on observed case data will also be 
prepared.
The MI procedure for continuous efficacy variables (based on MCMC) will be applied as follows
using a starting “seed” value of 17402:
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 19 of 63
1. Create a dataset, one for each treatment group, of subjects with observed values and those 
needing estimation by multiple imputation. The missing values in each dataset will be 
filled in using the MCMC method with a total of 100 sets of imputations being 
performed. Biologic exposure, geographic region and values at baseline and at each post-
baseline visit (in chronological order) will be included in the imputation model. If 
required, in order to facilitate the imputation model, variables can be omitted in the order 
of biologic exposure and geographical region. Cut-off values will be applied to the 
imputed data, as appropriate, to ensure that imputed values do not exceed the range of 
plausible values for the variable being imputed. The resulting datasets for each treatment 
arm will be combined into one complete dataset based on each of the 100 imputations
2. The relevant change from Baseline (or percent change from Baseline) values will then be 
derived based on the datasets which include observed and imputed values for the variable 
being considered
3. The results from each of the 100 imputed datasets will be combined for the calculation of 
means and standard errors using Rubin’s rules, which account for the uncertainty 
associated with the imputed values (Rubin, 1987). This will be done using SAS PROC 
MIANALYZE. For calculation of other descriptive statistics such as the median, min and 
max, Rubin's rules do not apply. Multiple imputation estimates will be computed by
simply averaging the estimates from the ݉ൌ1, … , ܯindependent repetitions of the 
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subgroups), in such situations the LOCF approach will instead be used to impute the missing 
data.  If LOCF is used instead of multiple imputation for this reason, this will be clearly specified 
in the corresponding table summary. Should there be no missing data for a study variable then 
only observed case data will be produced.
Summaries for all variables based on observed case data will also be prepared.
4.2.4
Safety variables
For analyses of AEs and concomitant medication usage, a complete date must be established in
order to correctly identify the AE or medication as occurring during treatment or not. For
purposes of imputing missing components of partially-reported start and stop dates for AEs and
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed
values will be displayed in data listings).
Partial AE and concomitant medication start dates will be imputed as follows:
Imputation of Partial Start Dates
•
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, then use the 1st of the month
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 20 of 63
•
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
•
If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use the 1st of January of the year of the start date
•
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
•
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.
Imputation of Partial Stop Dates
•
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•
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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 a 
medication was concomitant or an adverse event was treatment emergent, the medication will be 
considered as concomitant or the adverse event will be considered treatment emergent.
4.3
Interim analyses and data monitoring
After all enrolled subjects have completed the Week 8 visit, an interim analysis will be 
performed to analyze the dose-exposure response for PASI, including the PASI90 response, in 
each dose group to aid in determining the optimal therapeutic dose(s) for subsequent studies. The 
purpose of performing this analysis at this time is so as to be able to develop a dose-response 
model in advance of the Week 12 database lock.  The final model will include all data up to and 
including Week 12 and the model will be revised/updated accordingly (if required). The details 
of this model are outside of the scope of this SAP and are described in a separate DAP.
Decisions related to the conduct of the PS0010 study will not be impacted by these analyses as 
they will be conducted by individuals that are not part of the clinical study team, and they will 
not be shared with any clinical study team members until after the database lock, at which point 
the PS0010 study team will be unblinded.
The database lock to support the development of the PS0010 interim CSR will occur before all 
subjects have completed the PS0010 study. Specifically, subjects who do not enter the extension 
study (PS0011) will need to complete the SFU Visit, which occurs 20 weeks after the last dose of 
study treatment. The Week 12 interim database lock will be performed based on the last subject 
completing the Week 12 visit. It is anticipated that there will be some subjects still awaiting the 
SFU at that time. The number of subjects in that position is expected to be low, and the minimal 
data to be collected from their SFU visits is not considered mandatory to evaluating the key 
efficacy and safety objectives of the study, therefore it is considered acceptable to proceed with
the PS0010 data analysis and interim CSR development in the absence of these data. Once all 
SFU data have been collected and the full PS0010 study database has been locked, all TLFs will 
be re-run to include the SFU data that have been added to the database following the Week 12 
interim database lick. A final CSR will subsequently be prepared based on this final set of TLFs. 
Other than the additional data from the pending SFU visits, it is expected that this final CSR will 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 21 of 63
include biomarker and flow cytometry data summaries that will not be available in the interim 
CSR. In addition, an independent Data Monitoring Committee (DMC) will periodically review 
and monitor the safety data from this study and advise UCB.
Details will be provided in the DMC Charter and further details related to this DMC will be 
outlined in a separate analysis plan.
4.4
Multicenter studies
Not applicable.
4.5
Multiple comparisons/multiplicity
In order to control for the study-wise Type I error rate, the secondary analysis of pairwise 
comparisons of bimekizumab will be formally evaluated for statistical significance only if the 
primary efficacy analysis is statistically significant at the 5% 2-sided 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 5% 2-sided level.  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 using the PPS as 
a supportive analysis.
4.7
Active-control studies intended to show equivalence
Not applicable.
4.8
Examination of subgroups
Subgroup analyses will be performed on the primary and secondary efficacy variables.
The following variables for subgroup analyses will be used:
•
Age (<65 years, ≥65 years)
•
Gender (male, female)
•
Disease duration (<median, ≥median)
•
Region (North America [Canada, USA], Europe & Asia [Czech Republic, Hungary, Poland, 
Japan]
•
Body weight (<100 kg, ≥100 kg)
•
BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2)
•
Prior systemic phototherapy or chemophototherapy (yes, no)
•
Prior nonbiologic systemic therapy (yes, no)
•
Prior biologic therapy (yes, no)
•
Prior anti-TNF therapy (yes,no)
•
Any prior systemic therapy (yes, no)
•
IGA score at baseline (3 vs 4)
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 22 of 63
•
PASI score at baseline (<20, ≥20)
•
Psoriasis BSA at baseline (<20%, ≥20%)
These summaries will be based on imputed data (NRI) and will include descriptive statistics 
only.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
Summaries of reasons for screen failures (for all subjects screened), disposition of subjects (for 
all subjects screened) as well as the subjects who discontinued due to AEs (for the RS) will be 
produced. The disposition of subjects for all subjects screened will include the number of 
subjects included in each analysis set (ES, RS, FAS, PPS, SS, PK-PPS, and PD-PPS) overall and 
by site.
In addition, the number and percentage of subjects who discontinued treatment and who 
discontinued the study, including a breakdown of the main reason for discontinuation will be 
presented for subjects in the RS.
5.2
Protocol deviations
A summary, using the RS, of the number and percentage of subjects with an important protocol 
deviation (including a summary of subjects excluded from the PPS due to important protocol 
deviations) by treatment group and overall and by type of deviation will be provided.
A by-subject listing of important protocol deviations will be provided.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
Unless specified otherwise all summaries detailed in this section 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.
6.1
Demographics
Demographic variables will be summarized by treatment group and overall.
The following continuous variables will be summarized using descriptive statistics (number of 
subjects, mean, SD, minimum, median and maximum).
•
Age at the time of study entry (years)
The following categorical variables will be summarized using frequency counts and percentages.
•
Age group (≤18, 19-<65, ≥65 years)
•
Age group (18-<65, 65-<85, ≥85 years)
•
Age group (<40, 40-<65, ≥65 years)
•
Gender
•
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 23 of 63
•
Ethnicity
•
Height (cm)
•
Weight (kg)
•
BMI (kg/m2) 
By-subject listings of demographics will be provided.
6.2
Other Baseline characteristics
Baseline characteristics (including Baseline clinical measures) will be summarized by treatment 
group and overall.
•
The following continuous variables will be summarized using descriptive statistics (number 
of subjects, mean, SD, minimum, median and maximum).Psoriasis BSA (%)
•
Duration of disease (in years)
•
PASI score
•
mNAPSI total score
•
PGADA VAS score
•
PSSI score
•
DLQI total score
•
HADS-A score
•
HADS-D score
BMI (kg/m2) will be calculated as:
ܤܯܫൌ Weight ሺkgሻ
ሺHeight ሺmሻሻଶ
(1)
Duration of disease (years) will be calculated as:
ܦ݅ݏ݁ܽݏ݁ܦݑݎܽݐ݅݋݊ൌ
ሺDate of randomization െܦܽݐ݁ ݋݂ ݋݊ݏ݁ݐ ݋݂ ݈ܲܽݍݑ݁ ܲݏ݋ݎ݅ܽݏ݅ݏଵሻ
365.25
(2)
1 If the date of onset of plaque psoriasis 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).
Should the date of randomization be missing then the duration of disease will be derived using
the date of screening.
The following categorical variables will be summarized using frequency counts and percentages.
•
Age (<40 years, 40 to <65 years, ≥65 years)
•
Region (North America [Canada, USA], Europe & Asia [Czech Republic, Hungary, Poland, 
Japan]
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 24 of 63
•
Country
•
BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2)
•
Duration of disease (<median, ≥median)
•
IGA score
•
Body weight (<100 kg, ≥100 kg)
•
Prior biologic therapy (yes, no)
•
Prior anti-TNF therapy (yes, no)
•
Prior phototherapy or chemophototherapy (yes, no)
•
Prior nonbiologic systemic therapy (yes, no)
•
Any prior systemic therapy (yes, no)
•
HADS-A score (<8, 8 to 10, 11 to 14, >14)
•
HADS-D score (<8, 8 to 10, 11 to 14, >14)
•
Tobacco use (never, current, former)
By-subject listings of Baseline characteristics will be provided.
6.3
Medical history and concomitant diseases
All medical history will be listed and the number and percentage of subjects with any medical 
history will be summarized by treatment group, system organ class (SOC) and preferred term 
(PT).
6.4
Prior and concomitant medications
Medication start and stop dates will be compared to the date of first dose of treatment to allow 
medications to be classified as either Prior or Concomitant.
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.
Details of imputation methods for missing or partial dates are described in Section 4.2.4.
The number and percentage of subjects taking Prior medications (excluding past psoriasis 
medications) will be summarized by treatment group, overall and by ATC class, presenting 
Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC level 3), and 
preferred term.
The number and percentage of subjects taking Concomitant medications will be summarized 
similarly.
Past psoriasis treatment will be captured separately and will also be summarized by treatment 
group.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 25 of 63
A by-subject listing of all Prior and Concomitant medications and of past psoriasis treatment will 
be provided.
7
MEASUREMENTS OF TREATMENT COMPLICANCE
All summaries detailed in this section will be performed on the SS.
Due to the method of administration of the treatments, compliance will be examined in terms of 
completed doses, where one dose will be considered as one complete treatment administration 
(ie, three injections).
Treatment compliance will be calculated as:
ݐ݋ݐ݈ܽ ݊ݑܾ݉݁ݎ ݋݂ ܿ݋݉݌݈݁ݐ݁݀ ݀݋ݏ݁ݏ
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(3)
where the total number of expected doses is derived relative to when the subject finishes 
treatment. If a subject completes treatment nine doses are expected (three each at Baseline, Week 
4 and Week 8). If a subject discontinues early, then the number of expected injections is based 
on the time of early discontinuation relative to the dosing visits.
A summary of percent treatment compliance categorized as ≤75% and >75% will be provided by 
treatment group.
A by-subject listing of treatment compliance will be provided.
8
EFFICACY ANALYSES
8.1
Statistical analysis of the primary efficacy variable
8.1.1
Derivations of PASI score and response
PASI scoring of psoriatic plaques is based on three criteria: redness (R), thickness (T), and 
scaliness (S). Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 
4 for very marked involvement). The body is divided into four areas comprising the head (h), 
upper extremities (u), trunk (t), and lower extremities (l). In each of these areas, the fraction of 
total surface area affected is graded on a 0-6 scale (0 for no involvement; up to 6 for 90% - 100% 
involvement).
The various body regions are weighted to reflect their respective proportion of BSA. The 
composite PASI score is then calculated by multiplying the sum of the individual-severity scores 
for each area by the weighted area-of-involvement score for that respective area, and then 
summing the four resulting quantities as follows (note for R, T, and S scores are as follows: 0 = 
none, 1 = slight, 2 = moderate, 3 = marked, and 4 = very marked): 
ܲܣܵܫൌሺ0.1 ൈሺܴ௛൅ܶ௛൅ܵ௛ሻൈܣ௛ሻ൅ሺ0.2 ൈሺܴ௨൅ܶ௨൅ܵ௨ሻൈܣ௨ሻ
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(4)
where 
Rh, Ru, Rt, Rl = redness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively; 
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 26 of 63
Th, Tu, Tt, Tl = thickness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively; 
Sh, Su, St, Sl = scaliness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively; 
Ah, Au, At, Al = numerical value translation of % area of psoriatic involvement score for the 
head, upper extremities, trunk, and lower extremities, respectively (where 0 = 0% [clear], 1 = 
>0% to <10%, 2 = 10% to <30%, 3 = 30% to <50%, 4 = 50% to <70%, 5 = 70% to <90%, and 6 
= 90% to 100%).
The highest potential PASI score is 72 for severe disease; the lowest is 0 for no psoriasis lesion. 
PASI scores are treated as a continuous score, with 0.1 increments within these values. The 
percent improvement in PASI scores from Baseline will be computed as: 
Percent improvement from Baseline ൌ100 ൈBaseline PASI െPost Baseline PASI
Baseline PASI
(5)
If a subject has experienced an improvement, this measure will be positive. If a subject has 
experienced a worsening in their condition, this measure will be negative. 
If a subject is missing 1 or 2 severity measurements for a certain region, the average of the 
remaining severity measurement(s) within that region will be utilized to substitute for the 
missing severity measurement(s) in that region. If the area of affected skin and/or all severity 
measurements for up to 2 regions are missing, then the missing (R+T+S) x A for a region will be 
substituted by the average of the available (R+T+S) x A. Otherwise, the PASI will be set to 
missing.
A categorical variable, PASI90, is defined to be equal to 1 if the percentage improvement from 
Baseline in the PASI scores is 90% or greater and 0 if the percentage improvement from baseline 
is less than 90%. This definition is introduced for the purpose of identifying subjects who 
respond to the treatment (1 = responder, 0 = non-responder). Similarly, the categorical secondary 
efficacy variables PASI50, PASI75, and PASI100 response are equal to 1 for subjects with 
improvements of 50% or greater, 75% or greater and 100% from Baseline in PASI score,
respectively (and equal to 0 otherwise),
8.1.2
Primary analysis of the primary efficacy variable
The primary efficacy variable will be analyzed for all subjects in the FAS.
The number and percentage of subjects achieving a PASI90 response (as defined in 
Section 8.1.1) at Week 12 will be presented by treatment group. 
The dose-response relationship between treatment and PASI90 response will be assessed to test 
the following hypotheses:
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where 1 = placebo, 2 = bimekizumab 64mg Q4W, 3 = bimekizumab 160mg Q4W, 4 = 
bimekizumab 320mg Q4W, and 5 = bimekizumab 480mg Q4W.
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 27 of 63
This will be done by using a logistic regression model which will include fixed effects for 
treatment, region (see Section 4.8), and prior biologic exposure (yes/no). This will be evaluated 
using a linear contrast in which equal spacing between each of the doses is assumed. 
The coefficients for this linear contrast will be -2, -1, 0, 1 and 2 for placebo, bimekizumab 64mg 
Q4W, bimekizumab 160mg Q4W, bimekizumab 320mg Q4W, and bimekizumab 480mg Q4W, 
respectively. While the bimekizumab 320mg loading dose followed by bimekizumab 160mg 
Q4W has been left out of the linear contrast for evaluating dose response, it will remain a part of 
the logistic regression model and will be compared to the bimekizumab 160mg Q4W dose as a 
secondary analysis of the primary efficacy variable.
If the logistic regression model is unable to converge, then prior biologic exposure will be 
dropped from the model to facilitate convergence. If convergence is not obtained after dropping 
prior biologic exposure, then region may be dropped from the model. The linear contrast from 
the logistic regression model will be evaluated at a two-sided significance level of α=0.05. 
NRI will be used to account for missing data; ie, subjects with a missing PASI score at Week 12 
or who discontinued study treatment prior to the Week 12 Visit will be considered non-
responders for the primary analysis.
The results produced in the SAS modelling process for the primary endpoint will be provided as 
a supportive output.
8.1.3
Secondary analyses of the primary efficacy variable
As a supportive analysis for the primary efficacy variable, the same logistic regression model 
described in Section 8.1.2 will be used to assess the effect of each individual dose vs placebo on 
PASI90 response. Comparisons will be made for each dose vs placebo at a two-sided 
significance level of α=0.05. For each dose, the odds ratio vs placebo, the 95% confidence 
interval, and the corresponding p-value will be calculated. 
The pairwise comparisons of bimekizumab versus placebo will be formally evaluated for 
statistical significance only if the primary dose response efficacy analysis is statistically 
significant. Once the dose response has been established, pairwise testing of each bimekizumab 
dose versus placebo will account for multiplicity by using a fixed sequence testing procedure 
with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. 
Each test will only be conducted if the previous test reaches significance at a two-sided 
significance level of α=0.05. This procedure will control the overall Type I error rate. While 
formal evaluation of statistical significance will only proceed as described above, the p-values 
for all pairwise tests vs placebo will be provided, regardless of whether or not the testing 
procedure was completed for all bimekizumab doses.
A pairwise comparison will also be made for the bimekizumab 160mg Q4W group versus the 
bimekizumab 320mg loading dose followed by bimekizumab 160mg Q4W group, but this 
evaluation will not be part of the sequential testing procedure described above (ie, the p-value 
will be nominal).
The results produced in the SAS modelling process for the secondary analyses of the primary 
efficacy variable will be provided as a supportive output.
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 28 of 63
8.1.4
Supportive and sensitivity analyses of the primary efficacy variable
8.1.4.1
Sensitivity analyses
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. 
An ordered categorical analysis using a non-parametric correlation statistic of Mantel and 
Haenszel and modified ridit scores will be performed as a sensitivity analysis to the primary 
dose-response evaluation based on the logistic regression model. This analysis will include 
region and prior biologic exposure as stratification factors to adjust for potential differences in 
the dose response based on these variables, and will be evaluated at a 2-sided significance level 
of α=0.05.
Sensitivity analyses for the primary dose response analysis of the primary efficacy variable, 
designed to evaluate the assumptions related to the handling of missing data are as follows:
1. An analysis will be performed in which all available data at Week 12 will be considered. 
This analysis will be based on the logistic regression model to evaluate dose-response as 
specified in the primary analysis (see Section 8.1.2). 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, NRI will be used for these subjects. For the purposes of 
analyses these will be referred to as “Week 12 de facto analysis”. 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. The treatment by region interaction will be investigated by including the interaction term in 
the primary model, should this interaction be statistically significant at the 10% level this 
term will be included into the main model.
The following sensitivity analyses will be performed for the secondary pairwise comparison 
analysis of the primary efficacy variable in order to assess the missing data assumptions:
1. Missing data will be addressed by using MI based on the Markov-Chain Monte Carlo 
(MCMC) method for missing data. The actual PASI scores will be imputed and then 
dichotomized to obtain the PASI90 response status. The multiple imputed data sets will be 
analyzed using a logistic regression model with factors of treatment group, prior biologic 
exposure, and region. Finally, SAS PROC MIANALYZE will be used to combine the results 
into a single inference (see Section 8.1.4.3). 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, 2012).
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
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Page 29 of 63
2. The logistic regression model will be applied where all available data at Week 12 will be 
considered, as described in #1 in the sensitivity analysis for the primary dose response in 
Section 8.1.4.1.
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 #2 in the 
sensitivity analysis for the primary dose response in Section 8.1.4.1.
8.1.4.2
Supportive analysis
A supporting analysis will be performed 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 treated as missing. For the purposes of analysis 
these will be referred to as “Observed Values for Randomized Treatment Completers”. The same 
statistical method described for the primary efficacy analysis of dose response will be used.
An additional supportive analysis will be performed to take into account the data for subjects that 
are withdrawn due to CTCAE Grade 3 and/or repeated CTCAE Grade 2 lab abnormalities 
highlighted in Withdrawal Criterion #11. These subjects will be identified programmatically as 
those with a reason for discontinuation of “Other” where the specific description  provided in the 
free text field refers to ”Withdrawal Criterion #11”. This sensitivity analysis will use LOCF for 
these subjects where the last observed value of a variable prior to discontinuation (including 
Baseline) is used to impute the missing data.  For all other subjects with missing data or who 
discontinued study treatment prior to Week 12, NRI will be used.
8.1.4.3
Multiple imputation analysis
The multiple imputation analysis is a sensitivity analysis for the secondary analysis of the 
primary variable (see Section 8.1.4.1).
Investigators will be given discretion to discontinue study treatment for subjects not responding 
in order to provide them with alternative therapy to treat the condition. Therefore, in many cases, 
missing efficacy data due to study treatment discontinuation should be dependent on the 
observed efficacy scores, but independent of unobserved data. This would be consistent with a 
missing at random (MAR) pattern of missingness. In order to investigate the efficacy results 
under the assumption of data being MAR, a multiple imputation method will be applied as 
follows:
1. Create a data set, one for each treatment group, of subjects with observed values and those 
needing estimation by multiple imputation. The missing PASI values in each data set will be 
filled in using the MCMC method with a total of 100 sets of imputations being performed. 
Biologic exposure, geographic region and values at baseline and at each post-baseline visit 
(in chronological order) will be included in the imputation model. Note that PASI scores at 
earlier visits will also be used as predictors for the model of PASI at later visits. The resulting 
data sets for each treatment arm will be combined into one complete data set based on each 
of the 100 imputations.
Note: The imputation model based on the MCMC method will only allow continuous 
variables in the imputation model. Therefore, prior biologic exposure and region will be re-
coded as indicator variables (with values of 0 or 1 for each level of the variable). In order to 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 30 of 63
achieve model convergence prior biologic exposure may be dropped from the model, if 
convergence is still not obtained then region may be also be dropped from the model. 
2. For each complete imputed data set, the dichotomous responder rate based on the PASI 
scores will be computed. Each complete imputed data set will then be analyzed based on a 
logistic regression model with factors of treatment group, region, and prior biologic 
exposure.
Note: For derivation of PASI90 response, the PASI value at Week 12 in the imputed data sets 
will be compared directly to the observed Baseline PASI value to determine whether or not a 
reduction of at least 90% was achieved. If values outside of the pre-defined range of values 
for PASI (0-72) are imputed, they will be cut off as appropriate after the multiple imputation 
procedure but before deriving the responder variable. For example, an imputed PASI value of 
-0.5 would be changed to 0 before deriving the PASI90 responder variable.
3. The Week 12 results from the logistic regression analysis of each of the 100 imputed data 
sets will be combined for overall inference using Rubin’s rules, which account for the 
uncertainty associated with the imputed values (Rubin, 1987). This will be done using SAS 
PROC MIANALYZE.
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below:
As the estimates of the odds ratios from the logistic regression model in step 3 follow a log-
normal distribution, a log transformation is needed to normalize these estimates since the 
procedures for combining results from multiple imputed datasets are based on the assumption 
that the statistics estimated from each imputed dataset are normally distributed. Therefore, the 
log of the odds ratio estimates from the logistic regression model are used when combining into a 
single inference (the use of PROC MIANALYZE in step 3). Additionally, the standard errors 
(SE) for the odds ratios are transformed as follows:
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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:
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 31 of 63
will be done such that odds ratios and corresponding confidence intervals are calculated for the 
odds ratio of each bimekizumab dose versus placebo. Note that the p-values presented in the 
tables will be the ones provided initially by PROC MIANALYZE and are not impacted by the 
transformations described above.
8.2
Statistical analysis of the secondary efficacy variables
All secondary efficacy variables will be summarized for subjects in the FAS.
Unless specified otherwise, both NRI (or MI for continuous variables) and Observed Case 
analyses will be performed (see Section 8.1.4). No other sensitivity or supportive analyses will 
be presented for the secondary efficacy variables.
Also, in addition to any endpoint tabulations, summary tables of each endpoint by visit and 
treatment will be provided.
All p-values presented for secondary efficacy variables will be nominal.
8.2.1
Derivation of IGA response
A static IGA for psoriasis will be used to assess disease severity in all subjects during the study.
The Investigator will assess the overall severity of psoriasis using the following five-point scale 
(see Table 8‒1):
Table 8‒1:
Five-point Investigator's Global Assessment
Score
Short Descriptor
Detailed Descriptor
0
Clear
No signs of psoriasis; post-inflammatory hyperpigmentation 
may be present
1
Almost clear
No thickening; normal to pink coloration; no to minimal focal 
scaling
2
Mild
Just detectable to mild thickening; pink to light red coloration;
predominately fine scaling
3
Moderate
Clearly distinguishable to moderate thickening; dull to bright 
red, clearly distinguishable to moderate thickening; moderate 
scaling
4
Severe
Severe thickening with hard edges; bright to deep dark red 
coloration; severe/coarse scaling covering almost all or all 
lesions
IGA response is defined as clear [0] or almost clear [1] with at least a two category improvement 
from Baseline.
8.2.2
Analysis of Investigator’s Global Assessment
The number and percentage of subjects achieving an IGA response (defined as clear [0] or 
almost clear [1] with at least two category improvement from Baseline) at Week 12 will be 
presented by treatment group. 
The same logistic model as described for the secondary analysis of the primary efficacy variable 
(see Section 8.1.3) will be used to analyze IGA response at Week 12, performing pairwise 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 32 of 63
comparisons versus placebo and presenting the odds ratio vs placebo, 95% confidence interval 
and corresponding p-value for each dose. 
Similarly the number and percentage of subjects achieving an IGA response at Week 8 will also 
be presented by treatment group and will be analyzed in the same way as the Week 12 IGA 
response.
A line plot of the IGA responder rate over time, by treatment group will be produced.
8.2.3
Analyses of secondary PASI responder variables
8.2.3.1
PASI90 at Week 8
The number and percentage of subjects achieving a PASI90 response (as defined in
Section 8.1.1) at Week 8 will be presented by treatment group.
The same logistic regression model as described in Section 8.1.3 will be used to analyze PASI90 
at Week 8, performing pairwise comparisons of each bimekizumab dose versus placebo and
presenting the odds ratio vs placebo, 95% confidence interval and corresponding p-value for 
each dose.
A line plot of the PASI90 responder rate over time, by treatment group will be produced.
8.2.3.2
PASI75 at Week 12
The number and percentage of subjects achieving a PASI75 response (as defined in 
Section 8.1.1) at Week 12 will be presented by treatment group.
The same logistic regression model as described in Section 8.1.3 will be used to analyze PASI75 
at Week 12, performing pairwise comparisons of each bimekizumab dose versus placebo and 
presenting the odds ratio vs placebo, 95% confidence interval and corresponding p-value for 
each dose.
A line plot of the PASI75 responder rate over time, by treatment group will be produced.
8.2.3.3
PASI100 at Week 12
The number and percentage of subjects achieving a PASI100 response (as defined in 
Section 8.1.1) at Week 12 will be presented by treatment group.
The same logistic regression model as described in Section 8.1.3 will be used to analyze 
PASI100 at Week 12, performing pairwise comparisons of each bimekizumab dose versus 
placebo and presenting the odds ratio vs placebo, 95% confidence interval and corresponding p-
value for each dose.
A line plot of the PASI100 responder rate over time, by treatment group will be produced.
8.3
Analysis of other efficacy variables
All other efficacy variables will be summarized for subjects in the FAS.
All other efficacy variables will be summarized based on imputed data (NRI and MI for binary 
and continuous variables, respectively) and observed case data (ie, subjects with missing data or 
who have prematurely discontinued study treatment are treated as missing) unless otherwise 
specified.
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 33 of 63
8.3.1
Further analysis of  Investigator’s Global Assessment
The distribution of the IGA score will be summarized in a shift table comparing the change from 
Baseline versus post-Baseline by treatment group for the FAS. Cross-tabulations of the Baseline 
vs post-Baseline IGA score will be reported for each time point, including the number of subjects 
with missing data.
In addition, the IGA responses as described in Section 8.2.1 will be summarized by treatment 
group across all visits.
8.3.2
Further analysis of  PASI
Absolute value, change from baseline, and percentage change from Baseline in PASI score will 
be summarized by treatment group and visit.
In addition summaries of the PASI50 response, PASI75 response, PASI90 response and 
PASI100 response will be summarized by treatment group and visit.
A line plot of the percentage change from Baseline in PASI score over time, by treatment group 
will be produced.
8.3.3
Analysis of BSA
Absolute value, change from baseline, and percentage change from Baseline in BSA affected by 
psoriasis will be summarized by treatment group and visit.
8.3.4
Derivation of DLQI score and response
The DLQI questionnaire is used for patients with psoriasis and consists of 10 questions. Question 
7 consists of a sub-question which is only to be answered following a “No” response to the main 
question. The questions are scored as shown below in Table 8‒2, and the DLQI score is 
categorized as shown in Table 8‒3.
Table 8‒2:
DLQI Scoring
Question Number
0 points
1 point
2 points
3 points
1,2
Not at all
A little
A lot
Very Much
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A lot
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 34 of 63
Table 8‒3:
DLQI - Categorization
In the case of one missing value the result imputed for that question will be 0 and the DLQI 
score created as normal. Should two or more questions be unanswered then the DLQI score will 
be set to missing. For question 7, if “Not relevant” is selected the score for the question will be 0, 
if the question is answered “No” but the second half of the question is incomplete then the 
question will still be scored as 0.
A four-point change in the DLQI score has been reported to be meaningful for the subject 
(within-Subject MCID); while a DLQI absolute score of 0 or 1 indicates no or small impact of 
the disease on health related QOL.
A line plot of the percentage changes from baseline in DLQI score over time, by treatment group 
will be produced.
8.3.5
Analysis of DLQI
Absolute value, change from Baseline, and percentage change from Baseline value for DLQI 
will be summarized by treatment group and visit.
The number and percentage of subjects achieving a DLQI score of 0 or 1 at each visit will be 
presented by treatment group.
The number and percentage of subjects achieving DLQI MCID (as defined in Section 8.3.4) at 
each visit will be presented by treatment group.
8.3.6
Derivation of mNAPSI score
Psoriatic nail disease will be evaluated at the Baseline visit using the mNAPSI. All affected nails 
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. The total mNAPSI score is the sum of 
the scores for each individual nail. If a nail is unaffected, it will be recorded as such and will not 
contribute to the total mNAPSI score. 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.
Category
Score Range
No Effect
0-1
Small Effect
2-5
Moderate Effect
6-10
Very Large Effect
11-20
Extremely Large Effect
21-30
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 35 of 63
8.3.7
Analysis of mNAPSI
The change from Baseline in mNAPSI scores will be summarized at each visit by treatment 
group for the subset of subjects with psoriatic nail disease at Baseline.
8.3.8
Derivation of PGADA for the arthritis VAS
The PGADA for the arthritis VAS will be used to provide an overall evaluation of arthritis 
disease symptoms. Subjects will respond to the question, “Considering all the ways your arthritis 
affects you, please mark a vertical line on the scale below to show how you are feeling today”, 
using a VAS where 0 is “very good, no symptoms” and 100 is “very poor, severe symptoms”.
8.3.9
Analysis of PGADA for the arthritis VAS
The actual and change from Baseline in PGADA VAS scores will be summarized at each visit by 
treatment group.
Subjects who have psoriatic arthritis as defined by the Toronto Psoriatic Arthritis Screening 
questionnaire (ToPAS) questionnaire results at the baseline assessment will also have the 
PGADA VAS scores summarized separately.
8.3.10
Derivation of PSSI
The PSSI considers both the extent of the scalp area of involvement and the severity based on the 
scoring scales outlined in Table 8‒4 and Table 8‒5.
The assessment considers erythema, induration and desquamation on the scalp. For each of these 
three elements, the scores of the area and severity are multiplied. Then, the score from each 
element is totaled to obtain the PSSI score. As with the PASI, the PSSI score ranges from 0 to 72 
with a higher score indicating increased scalp disease severity.
If a subject is missing 1 severity measurement, the average of the remaining severity 
measurements will be utilized to substitute for the missing severity measurement. If the area of 
affected skin is missing or if 2 or more severity measurements are missing, then the PSSI score 
will be set to missing.
Table 8‒4:
PSSI assessment of extent of scalp psoriasis
Score
Definition
1
<10%
2
10-29%
3
30-49%
4
50-69%
5
70-89%
6
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 36 of 63
Table 8‒5:
PSSI assessment of clinical symptoms
8.3.11
Analysis of PSSI
The analysis of PSSI score will be conducted for subjects who have scalp psoriasis, defined as 
PSSI>0 at Baseline.
The change from Baseline will be summarized at each visit by treatment group.
8.3.12
Derivation of SF-36
The SF-36v2, standard recall, 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 classification of the 
questionnaire items to the health domains is shown in Section 12.1.
The SF-36 Physical and Mental Component Summary scores (PCS and MCS, respectively) 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 8 health 
domain scales are used to score both components summary measures.
One additional item asks respondents about health change over the past year.
The SF-36 will be used using QualityMetric’s Health Outcomes™Scoring Software. The 
software uses updates 2009 U.S. population norms and applies a Full Missing Score Estimation 
(Full MSE) method as follows:
•
A health domain score (except the PF domain) will be estimated provided that at least one 
non-missing response is available within that domain
•
For the PF domain item response theory will be used to develop a model for estimates of the 
missing score
•
Regression methods are then applied to estimate the PCS and the MCS on the basis of the 
available domains.
8.3.13
Analysis of SF-36
The change from Baseline in the SF-36 PCS and MCS scores as well as for the individual 
domain scores will be summarized at each visit by treatment group.
Score
Definition
0
Absent
1
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2
Moderate
3
Severe
4
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13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 37 of 63
As a sensitivity analysis the SF-36 PCS, MCS and individual domain scores will be also 
summarized at each visit and by treatment group for the complete cases, where any missing data 
will result in the affected domains and component scores for that visit also being set to missing. 
8.3.14
Definition of Time to PASI Response
Time to PASI50, PASI75, PASI90, and PASI100 response (in days) will each be calculated as:
Date of first PASIx response – Date of Baseline visit +1
(9)
8.3.15
Analysis of Time to PASI Response
Time to PASI50, PASI75, PASI90, and PASI100 response will each be estimated and presented 
using the Kaplan-Meier product-limit method for each treatment group. 
Kaplan-Meier plots of time to PASI50, PASI75, PASI90, and PASI100 response will be 
presented by treatment group.  
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 
the given response will be censored at the date of the Week 12 Visit. 
The median time to response, including the two-sided 95% confidence interval, will be 
calculated for each treatment. Comparisons of each bimekizumab dose vs placebo will be 
analyzed using a log-rank test stratified by region and prior biologic exposure. In addition 
between group differences for bimekizumab 320mg loading dose + 160mg Q4W vs 
bimekizumab 160mg Q4W and bimekizumab 320mg loading dose + 160mg Q4W vs 
bimekizumab 320mg Q4W will be analyzed using the log-rank test stratified by region and prior 
biologic exposure.
8.3.16
Definition of Subject Symptom Diary responses
UCB is developing a new PRO measure that will be used to assess key symptoms relevant to 
subjects with moderate to severe chronic plaque psoriasis. 
PS0010 will use the draft PRO measure in selected countries to enable psychometric validation 
of the PRO. Site staff will train the participating subjects on the use of the electronic PRO 
(ePRO) diary at the Screening visit, following which the device will be dispensed to the subject 
for home use until the Week 12 Visit.
The ePRO diary will be administered on a daily basis from Baseline to the Week 12 Visit. Item 
content of the ePRO diary will be finalized prior to study initiation and will include a variety of 
psoriasis-related characteristics, reported as relevant by subjects in the published literature and 
planned concept elicitation interviews. 
The ePRO diary will also administer appropriate anchor items (eg, subject global impression of 
change, and subject global impression of concept) at the end of every study week.
The weekly score is the sum of the individual scores within the week. A maximum of 3 missed 
days are permitted (irrespective of whether these are consecutive or not) for the derivation of the 
weekly score and will be included in the analysis. The missing days will be counted as missing 
data for the purposes of the weekly score.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 38 of 63
8.3.17
Analysis of Subject Symptom Diary responses
The mean responses for each question on the subject symptom diary will be summarized by 
treatment group and week, in terms of absolute values and changes from baseline.
8.3.18
Definition of 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 (Snaith et al, 1994). 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, a score between 8 and 10 is considered 
mild, scores between 11 and 14 are considered moderate and a score of 15 and above is 
considered severe (Langley et al, 2009).
8.3.19
Analysis of HADS
Change from Baseline in HADS-A and HADS-D will be summarized at each visit by treatment 
group. 
In addition the percentage of subjects with scores below 8, between 8 and 10, between 11 and 14 
and greater than 14 in HADS-A and HADS-D will be summarized by visit and treatment group.
8.3.20
Definition of PGIC
The PGIC will be assessed at Baseline and on a weekly basis following the completion of all the 
patient symptom diary items. Only subjects in selected countries who participate in the 
completion of the patient symptom diary will participate in the completion of the PGIC. 
The PGIC is a five-item instrument that will ask the participants to think about their psoriasis 
related symptoms (including itching, pain, scaling, and sleep loss) since they started this study. 
Each item has seven response categories ranging from “Very much improved,” “Much 
improved,” “Minimally improved,” “No change,” “Minimally worse,”  “Much worse,” to “Very 
much worse.”
8.3.21
Analysis of PGIC
The response category for each item of the PGIC will be summarized by treatment group and 
week.
8.3.22
Definition of PGIS
The PGIS will be completed at Baseline and on a weekly basis following the completion of all 
patient symptom diary items. Only subjects in selected countries who participate in the 
completion of the patient symptom diary will participate in the completion of the PGIS. 
The PGIS is a five-item instrument that will ask the participants to think about their psoriasis 
related symptoms (including itching, pain, scaling, and sleep loss) over the past week and an 
additional five items asking about the same set of symptoms at the current point in time. Each 
item has five response categories ranging from “No (symptoms),” “Mild (symptoms),” 
“Moderate (symptoms),” “Severe (symptoms),” to “Very severe (symptoms).”
8.3.23
Analysis of PGIS
The shift from Baseline in response category to each relevant visit will be summarized by 
question, treatment group and week.
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Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 39 of 63
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
All PK and antibody (AB) data will be listed together.
9.1
Pharmacokinetics
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit as described in Section 3.1 using the PK-PPS analysis set.
If bimekizumab plasma concentration measurements are deemed to be below the level of 
quantification (BLQ), then for calculation of the derived statistics this sample result will be set to 
half the LLOQ.  The subjects with at least 1 result that is defined as BLQ will also be listed 
within the respective analysis table. Descriptive statistics will be calculated if at least 2/3 of the 
values are above the LLOQ. If this is not the case, only median, minimum, and maximum will be 
presented.
In addition geometric mean bimekizumab plasma concentration time curves will be plotted by 
treatment group, and by cumulative antibody status for subjects randomized to bimekizumab.
The bimekizumab concentrations will also be listed.
Additional PK analyses will be described in the DAP.
9.2
Pharmacodynamics
IL-17A, IL-17F, IL-6, and IL-23 data will be summarized for each treatment at each scheduled 
visit using the PD-PPS analysis set.
Additional PD analyses will be described in the DAP.
9.3
Immunogenicity
9.3.1
Anti-bimekizumab antibodies
The AbAb status will be determined for each visit where samples are taken for drug 
concentration means. The cut point for determining whether the anti-bimekizumab antibody level 
is sufficiently high to be considered AbAb positive is not yet known.  However, this will be 
determined prior to the database lock of the PK and AbAb data.
The number and percentage of subjects with AbAb levels above the specified cut point will be 
reported as:
•
Number and percentage of subjects with AbAb level above the specified cut point at the time 
of each visit
•
Number and percentage of subjects with AbAb level above the specified cut point at any visit 
during the treatment period.
In addition the timepoint of the first occurrence of AbAb positivity during the treatment 
period (excluding baseline and pre-treatment) will be summarized for each treatment group.
All individual subject-level AbAb results will be listed.
10
SAFETY ANALYSES
All safety summaries and listings will be performed using all subjects in the SS.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 40 of 63
10.1
Extent of exposure
A by-subject listing of treatment administration (including exposure duration and total dose) will 
be provided.
10.1.1
Duration of exposure
The duration of exposure (in days) will be calculated as:
Date of last injection െDate of first injection ൅28
(10)
Should the date of the last injection plus 28 days equate to a date that is beyond the Week 12 
visit date then the exposure will be calculated as:
Week 12 visit date െDate of first injection
(11)
For subjects who have died the exposure will be as follows:
Date of Death - Date of first injection ൅1
(12)
The duration of exposure will be summarized by treatment group using descriptive statistics.
10.1.2
Number of doses received
The number of injections received will be summarized by treatment group over the 12 week 
administration period. There is anticipated to be 3 injections per dosing visit.
10.1.3
Exposure days at risk
For subjects who complete the Week 12 Visit and continue to the extension study, exposure days 
at risk will be calculated as:
ܦܽݐ݁ ݋݂ ܹ݁݁݇ 12 ܸ݅ݏ݅ݐଵെDate of first administration of study medication൅1
(13)
1 and the extension study administration of study medication.
For subjects who discontinue on or prior to the Week 12 Visit for reasons other than death, 
exposure days at risk will be fixed as 84 days (which is equivalent to the intended 12-week initial 
period). This method is used to provide balance for the comparison of the exposure denominator 
for the initial period.
For subjects who die prior to the Week 12 Visit, exposure days at risk will be calculated as:
Date of death െDate of first administration of study medication൅1
(14)
10.2
Adverse events
10.2.1
Treatment-emergent adverse events
An AE is any untoward medical occurrence in a subject 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 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 41 of 63
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
Treatment-emergent AEs (TEAEs) are defined as those AEs that have a start date on or 
following the first administration of study treatment through the final administration of study 
treatment + 140 days (covering the 20-week SFU period). If it is not possible (due to partial 
dates) to determine whether or not an AE is treatment-emergent then it will be assumed to be a 
TEAE.
To allow for a fair comparison across all subjects, exposure at risk for defining 
treatment-emergence will be cut off at the Week 12 Visit. Subjects who discontinue prior to the 
Week 12 Visit will also have their treatment-emergence cut off at Week 12 (84 days). All events 
that occur on the date of the Week 12 visit, with the exception of those with a HLT of injection-
site reactions or any event that meets the criteria for anaphylactic reaction as defined in the AEs 
of Special Monitoring, will be considered treatment emergent and will be captured as part of the 
PS0011 study.
An overview of TEAEs that emerge following the 12-week treatment period (Post-Treatment 
Period) but within <140 days of the last dose (while sill in he PS0010 study) will be summarized 
separately. However, subjects who consent to the PS0011 extension study will have any Post-
Treatment Period AEs reported only within the extension study to prevent duplicate reporting.
Adverse drug reactions (ADRs) are defined as a response to a drug which is noxious and 
unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or 
therapy of disease or for modification of physiological function. Any AE that is considered 
“Related” to study treatment will be classed as an ADR.
If 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.
Subject time at risk represents the time a subject was at risk for having an AE. The definitions 
for subject time at risk (in days) are outlined in Section 10.1.3. These definitions will be used for 
exposure-adjusted AE summaries.
Selected AE summaries will include the exposure adjusted incidence rate (EAIR) with associated 
95% confidence interval and the 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:
ܧܣܫܴൌ100 ൈ݊/ ෍൫ܶா௫௣ሺ௜ሻ൯
ே
௜ୀଵ
(15)
If a subject has multiple events, the time of exposure is calculated to the first occurrence of the 
AE being considered. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997):
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 42 of 63
(16)
(17)
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:
ܧܣܧܴൌ100 ൈܰ஺ா/ ෍൫ܶோ௜௦௞ሺ௜ሻ൯
ே
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where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Subject time at risk represents the time a subject was at risk for having an AE as described in 
Section 10.1.3.
The following summaries will be provided by treatment group and for the ‘All bimekizumab’ 
group. In addition all summaries of TEAEs ‘per 100 subject years’ will display EAIR and 
EAER:
•
Incidence of TEAEs During Treatment Period – Overview
•
Incidence of TEAEs During Post-Treatment Period – Overview (subjects not entering the 
extension study only)
•
Incidence of TEAEs per 100 subject years During Treatment Period by SOC, HLT, and PT
•
Incidence of TEAEs per 100 subject years During Post-Treatment Period by SOC, HLT, and 
PT (subjects not entering the extension study only)
•
Incidence of TEAEs per 100 subject years During Treatment Period by SOC, HLT, and PT 
and by Time of Onset Relative to Anti-bimekizumab Antibody Status
•
Incidence of TEAEs During Treatment Period by SOC, HLT and PT
•
Incidence of TEAEs During Treatment Period by Relationship by SOC, HLT, and PT
•
Incidence of TEAEs During Treatment Period by decreasing frequency of PT
•
Incidence of TEAEs During Treatment Period by Severity, SOC, HLT, and PT
•
Incidence of TEAEs Above Reporting Threshold of 5% During Treatment Period by SOC,
and PT
•
Incidence of Non-Serious TEAEs During Treatment Period by SOC, HLT, and PT
•
Incidence of Non-Serious TEAEs During Treatment Period by Relationship SOC, HLT, and 
PT
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 43 of 63
•
Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% During Treatment 
Period by SOC and PT
•
Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% During Treatment 
Period by Relationship SOC and PT
•
Incidence of Adverse Drug Reactions During Treatment Period by SOC, HLT, and PT
•
Incidence of Adverse Drug Reactions Above Reporting Threshold of 5% During Treatment 
Period by PT
All AE summaries will be ordered alphabetically for SOC and HLT within SOC and in terms of 
decreasing frequency for PT within HLT, in the “All bimekizumab” treatment group. 
For each subject and each AE, the worst severity recorded will be attributed and used in the 
by-severity summaries. Similarly, the worst causality (most related to treatment) will be 
attributed and used in the by-causality summaries. If severity or causality is missing, the worst 
case will be assumed. 
The following are AEs of special monitoring (AESM) that require special statistical analyses:
1. Serious infections, including TB and opportunistic infections
Serious infections will be identified based on MedDRA classification (SOC “Infections and 
infestations”) using the “Any SAE” table. A separate table does not need to be produced to 
summarize these events.
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 infections (including tuberculosis) 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 12.2.
These events will be presented in two stand-alone tables which include EAIR and EAER:
2. Malignancies, including lymphoma.    
These events will be presented in two stand-alone tables which include EAIR and EAER:
•
One table will be based on the criteria SMQ = “Malignant or unspecified tumours (SMQ)” 
•
One 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 included all 
TEAEs which code to a PT included in the Scope=Narrow group within each SMQ.
The output tables will include 2 different overall incidence rows:
•
The first overall incidence row will summarize “Any malignancies (including unspecified)” 
or “Any malignancies” (depending on the table) and this row will summarize the incidence of 
all AEs flagged for inclusion in the table, regardless of the High Level Term (HLT) it codes 
to. 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 44 of 63
The second overall incidence row will summarize “Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)” or “Any malignancy (excluding non-melanomic skin 
cancers)” (depending on the table) and this row will summarize the incidence of AEs flagged for 
inclusion in the table, excluding those which code to an HLT of “skin neoplasms malignant and 
unspecified (excl melanoma)”.
3. Major cardiovascular events 
Major cardiovascular events will be presented in a stand-alone table which includes EAIR and 
EAER. The table will include TEAEs that are identified using the following UCB-defined search 
criteria:
•
All serious TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow
groups of the following SMQs:
−
Haemorrhagic central nervous system vascular conditions (SMQ)
−
Ischaemic central nervous system vascular conditions (SMQ)
•
All serious TEAEs which code to a PT included in the HLT “Ischaemic coronary artery 
disorders” except events coding to PT “Chest Pain” or “Chest discomfort”
•
All serious TEAEs which code to a PT of “Cardiac failure congestive”.
4. 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.
5. Neuropsychiatric events (in particular depression and suicide)
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.
6. 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”.
7. Anaphylactic reaction
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.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 45 of 63
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 follows:
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 12.3 will be included in the summary 
table.
8. Hepatic events and DILI
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.
Hy’s Law cases are to be reported separately in the liver function test summary table (with 
adjudication for “Potential drug-induced liver injury (PDILI)” cases).
By-subject listings of all AEs, all TEAEs during the treatment period, all TEAEs that occurred 
within 140 days of the last dose during the post treatment period and within the TEAE window 
and all non-TEAEs will be provided. A by-subject listing of all ADRs will also be provided. In 
addition listings will be produced for AESM.
10.2.2
Deaths, serious adverse events, and other significant adverse events
The following summaries will be provided:
•
Incidence of Serious TEAEs per 100 subject years During Treatment Period by SOC, HLT,
and PT
•
Incidence of Serious TEAEs per 100 subject years During Post-Treatment Period by SOC, 
HLT and PT (subjects not entering the extension study only)
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 46 of 63
•
Incidence of Serious TEAEs During Treatment Period by SOC, HLT, and PT
•
Incidence of Serious TEAEs During Treatment Period by Relationship SOC, HLT, and PT
•
Incidence of TEAEs Leading to Discontinuation During Treatment Period by SOC, HLT, and 
PT
•
Incidence of TEAEs Leading to Death During Treatment Period by SOC, HLT, and PT
•
Incidence of TEAEs Leading to Death by Relationship by SOC, HLT, and PT
•
Incidence of Serious Adverse Drug Reactions During Treatment Period by SOC, HLT, and 
PT
The following listings will be provided:
•
A by-subject listing of all serious AEs
•
A by-subject listing of all AEs leading to discontinuation of study treatment
•
A by-subject listing of all death data
10.3
Clinical laboratory evaluations
All laboratory data recorded in the electronic case report form (eCRF) will be summarized. If 
any additional analytes to those in Table 10‒1 are also recorded then these will be listed only.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 47 of 63
Table 10‒1: Laboratory measurements
Hematology
Chemistry
Urinalysis
Basophils
Calcium
Albumin
Eosinophils
Chloride
Bacteria
Lymphocytes
C-reactive protein
Crystals
Atypical lymphocytes
Magnesium
Glucose
Monocytes
Potassium
pH
Neutrophils
Sodium
Red blood cell
Hematocrit
Glucose
White blood cell
Hemoglobin
Blood urea nitrogen
Urine dipstick for pregnancy 
testing1
Mean corpuscular hemoglobin
Creatinine
Mean corpuscular hemoglobin 
concentration
Alkaline phosphatase
Mean corpuscular volume
Aspartate aminotransferase
(AST)
Platelet count
Alanine aminotransferase
(ALT)
Red blood cell count
Gamma glutamyltransferase
(GGT)
White blood cell count
Total bilirubin
Lactate dehydrogenase
Total cholesterol
Serum pregnancy testing1
1 Pregnancy testing will consist of serum testing at the Screening and SFU visits. The pregnancy 
test will be urine at all other visits.
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. For tables where multiple measurements 
over a period of time are considered (as in shift tables), unscheduled and repeat visits will be 
considered as long as they were collected in the period being summarized. All summaries will be 
presented in SI units and will be based on observed case values. 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. The following 
summaries will be provided:
•
A summary of the absolute and change from Baseline values in each laboratory variable by 
treatment group and visit
•
A summary of the number and percentage of subjects experiencing markedly abnormal 
values by laboratory variable, treatment group and visit
•
A shift table of the number and percentage of subjects experiencing low, normal or high 
values at Baseline to maximum post-Baseline value (ie, low, normal, high), by laboratory 
variable and treatment group
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 48 of 63
•
A Shift table of the number and percentage of subjects experiencing low, normal or high 
values at Baseline to minimum post-Baseline value (ie, low, normal, high), by laboratory 
variable and treatment group
•
A Shift table of the number and percentage of subjects experiencing low, normal or high 
values at Baseline to the End of Treatment1 value (ie, low, normal, high), by laboratory 
variable and treatment group.
1The End of Treatment value refers to the value from the last observed non-missing post baseline visit prior to the 
end of treatment. 
A by-subject listing of all laboratory data will be provided. This listing will be presented by 
treatment group and will include: center, subject identifier, age, sex, race, weight, visit, 
laboratory variable, result (with abnormal values flagged as “L” or “H” accordingly) and unit.
A summary table highlighting the potential cases of Hy’s Law, within each treatment group will 
be presented. Hy’s Law is defined as. 
•
AST >3xULN or ALT >3xULN and
•
Total Bilirubin >2xULN
Markedly abnormal values are defined as those with a severity of Grade 3 and above based on 
the common terminology criteria for adverse events (CTCAE) criteria (U.S. Department of 
Heath and Human Services 2010). Definitions of markedly abnormal values using the Grade 3 
cutpoints are given in the tables below for age ranges of ≥17 years (Table 10‒2 for markedly 
abnormal liver function tests values, Error! Reference source not found. for markedly 
abnormal hematology values and Table 10‒4 for markedly abnormal biochemistry values). The 
laboratory results classified as Grade 3 or Grade 4 will be listed separately.
Table 10‒2: Definitions of Marked Abnormal Liver Function Tests
Parameter name
Conventional
Standard
Unit
Criteria
Unit
Criteria
Abnormal 
Designation
Alkaline Phosphatase
>5.0 x ULN
>5.0 x ULN
AH
ALT
U/L
>5.0 x ULN
U/L
>5.0 x ULN
AH
AST
U/L
>5.0 x ULN
U/L
>5.0 x ULN
AH
Total Bilirubin
mg/dL
>3.0 x ULN
umol/L
>3.0 x ULN
AH
GGT
U/L
>5.0 x ULN
U/L
>5.0 x ULN
AH
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 49 of 63
Table 10‒3: Definitions of Marked Abnormal Clinical Chemistry Values
Parameter name
Conventional
Standard
Unit
Criteria
Unit
Criteria
Abnormal 
Designation
Creatinine
mg/dL
>3.0 x ULN
mmol/L
>3.0 x ULN
AH
Glucose
mg/dL
<30
>250
mmol/L
<1.7
>13.9
AL
AH
Calcium
mg/dL
>12.5
<7.0
mmol/L
>3.1
<1.75
AH
AL
Magnesium
mg/dL
>3.0
<0.9
mmol/L
>1.23
<0.4
AH
AL
Potassium
mmol/L
>6.0
<3.0
mmol/L
>6.0
<3.0
AH
AL
Sodium
mmol/L
>155
<130
mmol/L
>155
<130
AH
AL
Total Cholesterol
mg/dL
>400
mmol/L
>10.34
AH
Table 10‒4: Definitions of Marked Abnormal Hematology Values
Parameter name
Conventional
Standard
Unit
Criteria
Unit
Criteria
Abnormal 
Designation
Hemoglobin
g/dL
<8.0
>4.0 above 
ULN
g/L
<80
>40 above 
ULN
AL
AH
Lymphocytes Absolute
109/L
<0.5
>20.0
109/L
<0.5
>20.0
AL
AH
Neutrophils Absolute
109/L
<1.0
109/L
<1.0
AL
Platelets
109/L
<50
109/L
<50
AL
WBC/Leukocytes
109/L
<2.0
>100
109/L
<2.0
>100
AL
AH
Abbreviations: AH=abnormal high; AL=abnormal low; ALT= alanine aminotransferase; AST = 
aspartate aminotransferase; dL = deciliter; GGT: gamma-glutamyltransferase; L = liter; mg = 
milligram; mmol = millimoles; μg = microgram; ULN = upper limit of normal.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 50 of 63
10.4
Vital signs, physical findings, and other observations related to 
safety
10.4.1
Vital signs
The following vital signs variables will be summarized: systolic blood pressure (mmHg), 
diastolic blood pressure (mmHg), body temperature (°C) and heart rate (beats/min). The 
following summaries will be provided:
•
A summary of the absolute and change from Baseline value for each vital sign variable by 
treatment group and visit
•
A summary of the number and percentage of subjects experiencing at least one markedly 
abnormal value for a vital sign variable as defined in Table 10‒5, by treatment group and 
visit.
Table 10‒5: Definitions of markedly abnormal blood pressure values
Parameter (unit)
Markedly Abnormal Low
Markedly Abnormal High
Systolic blood pressure (mmHg)
<90 and a decrease from 
Baseline of ≥20
<90
>180 and an increase from 
Baseline of ≥20
>140
Diastolic blood pressure (mmHg)
<50 and a decrease from 
Baseline of ≥15
<60
>105 and an increase from 
Baseline of ≥15
>90
A by-subject listing of all vital signs data will be provided. This listing will be presented by 
treatment group and will include: center, subject identifier, age, sex, race, weight, visit, vital sign 
variable and result (with abnormal values flagged as “L” or “H” accordingly).
10.4.2
Electrocardiograms
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.
The following ECG variables will be summarized (absolute values and change from baseline) by 
visit: QTcF, RR, PR, QRS and QT.
QTc outliers are defined as QTcF values following dosing that are greater than 450 ms or are 
increases from baseline greater than 30 ms.  QTcF outliers will be highlighted in the data listings 
and summarized using the following categories:
•
Values >450 ms, >480 ms, >500 ms
•
Increase from baseline of >30 ms, Increase from baseline of >60 ms, Increase from baseline 
of >90 ms
•
Values >450 ms and increases of >30 ms.  Values >500 ms and increases of >60 ms
The number and percentage of subjects who meet the ECG outlier criteria at any assessment 
post-date of first dose will be summarized.
A by-subject listing of all 12-lead ECG data will be provided.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 51 of 63
10.4.3
Other safety variables
10.4.3.1
Assessment and management of TB and TB risk factors
A by-subject listing of all of the “Evaluation of signs and symptoms of tuberculosis” 
questionnaire data will be provided.
10.4.3.2
Electronic Columbia Suicide Severity Rating Scale
The results of the Columbia Suicide Severity Rating Scale (CSSRS) will be summarized using 
the number of subject and percentage with (i) events in suicide behavior, (ii) suicidal ideation, 
(iii) suicidal behavior and ideation, and (iv) self-injurious behavior without suicidal intent.
Suicidal ideation is defined as an event in any of the following 4 categories:
•
•
•
•
Q3 is not supplied for this study.
Suicidal behavior is defined as an event in any of the following 4 categories:
•
Actual attempt
•
Interrupted attempt
•
Aborted attempt
•
Preparatory acts or behavior
Self-injurious behavior without suicidal intent is defined as an event in the category non-suicidal 
self-injurious injuries.
The incidence of subjects with suicidal intent, suicidal behavior and self-injurious behavior will 
be summarized by treatment group.  
A by-subject listing of the electronic Columbia Suicide Severity Rating Scale questionnaire data 
will be provided.
10.4.3.3
Physical examination
A summary of the number and percentage of subjects experiencing abnormalities including 
clinically significant abnormalities by treatment group and visit will be presented.
A by-subject listing of all physical examination data will be provided.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 52 of 63
11
REFERENCES
Basra, M. K., Fenech, R., Gatt, R. M., Salek, M. S., & Finlay, A. Y., The Dermatology Life 
Quality Index 1994-2007: a comprehensive review of validation data and clinical results. Br J 
Dermatol., 2008; 159, 997-1035.
Daudén, E., Griffiths, C. E., Ortonne, J. P., Kragballe, K., Molta, C. T., 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
Langley, R. G., Feldman, S. R., Han, C., Schenkel, B., Szapary, P., Hsu, M. C., 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.
Maruish, M. E., User’s manual for the SF-36v2 Health Survey (3rd ed.). Lincoln, RI: Quality 
Metric Incorporated, 2011.
Mosteller, R. D., Simplified calculation of body-surface area. The New England Journal of 
Medicine, 1987, October 22; 317(17), 1098.
Ratitch, B., Lipkovich, I., O’Kelly, M., Combining Analysis Results from Multiply Imputed 
Categorical Data. PharmaSUG, 2013.
Rubin D.B. 1987. Multiple Imputation for Nonresponse in Surveys. New York: John Wiley and 
Sons.
Snaith, R. P., & Zigmond, A. S., 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(12), 373-375
U.S. Department of Health and Human Services, Common Terminology Criteria for Adverse 
Events (CTCAE), Version 4.0, June 2010.
Ware, J. E., Kosinski, M., Bjorner, J. B., Turner-Bowker, D. M., Gandek, B., & Maruish, M. E., 
User's Manual for the SF-36v2TM Health Survey (2nd Ed). Lincoln, RI: QualityMetric 
Incorporated, 2007.
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 53 of 63
12
APPENDICES
12.1
Classification of the SF-36v2 questionnaire
Items
Scales
Physical Functioning
Role-Physical
Bodily Pain
General Health
Vitality
Social Functioning
Role-Emotional
Mental Health
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 54 of 63
12.2
AESM Opportunistic infections
Opportunistic infections are identified in two steps:
Step 1: Refer to column B of the spreadsheet which identifies the Preferred Terms (PTs) to be 
classified as opportunistic infections using either a single ‘x’ or a double ‘xx’.
•
TEAEs which code to a PT flagged with a single ‘x’ need to also be serious in order to be 
considered an opportunistic infection
•
All TEAEs which code to a PT flagged with a double ‘xx’ are considered to be an 
opportunistic infection, regardless of seriousness. 
All serious TEAEs in the study database which code to a PT flagged with a single ‘x’ and all 
TEAEs in the study database which code to a PT flagged with a double ‘xx’ will be summarized 
as an opportunistic infection in the stand-alone table.
Step 2: Refer to column C of the spreadsheet which identifies the PTs that need to be evaluated 
on a case-by-case basis by the study physician in order to determine whether it is a true 
opportunistic infection or not. The process for physician review is as follows:
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 (HLT), Lower Level Term (LLT), 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.
12.3
MedDRA algorithmic approach to anaphylaxis
The SMQ Anaphylactic reaction consists of three parts:
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 55 of 63
•
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 
•
A broad search: If a subject reports any TEAE which codes to a PT included in Category B 
AND reports any TEAE which codes to a PT included in Category C, and both TEAEs 
have the same start date, then both events will be flagged as anaphylactic reactions and 
summarized as such in the table.
−
Category B 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 56 of 63
−
Category C
−
Category D
•
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
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 57 of 63
13
AMENDMENT TO THE STATISTICAL ANALYSIS PLAN
13.1
Amendment 1
Rationale for the amendment
The purpose of this amendment is to apply modifications as a result of conclusions made at Data 
Evaluation Meeting 2 including changing LOCF methods to MI methods.
Global changes
Various spelling and formatting amendments were made.
Due to the small population size in the Asia region, Asia was combined with Europe in all cases.
Specific changes
Change #1
Page 10, Section 2.2.2.1 Pharmacokinetic variables, removed “CL/F” and “V/F” from the PK 
variables collected.
Change #2
Page 13, Section 3.1 General Presentation of Summaries and Analyses, added “Derived variables 
in general will display the mean, SD and median to 1 more decimal place than the variables used 
in the derivation. If the number of decimal places reported in the raw data is varied then use 
either the maximum raw number of reported decimal places or 3, whichever is the lowest, as a 
guide for the descriptive statistics.”.
Change #3
Page 14, Section 3.3. Mapping of assessments performed at early stage study withdrawal visit, 
added in the following two sections of text.
“The only exception to this rule is for anti-bimekizumab antibody (AbAb) assessments where all 
premature withdrawal visit assessments will be assigned to the next scheduled visit at which 
AbAb are assessed. All by-visit summaries will contain nominal visits only. Unscheduled visits 
will not be mapped to scheduled visits.”
“in observed case summaries. For summaries based on imputed data, the Week 12 value will be 
treated as missing and imputed according to the rules for the given variable.”
Change #4
Page 15, Section 3.5.6.1 Pharmacokinetic Per Protocol Set, added the following to the end of the 
sentence “and had no important protocol deviations affecting the pharmacokinetic variables, as 
confirmed during ongoing data cleaning meetings prior to database lock.”.
Change #5
Page 17, Section 3.11 Changes to protocol-defined analyses, added the following text into this 
section.
“Section 14.6 of the protocol (Handling of dropouts or missing data) describes the sensitivity 
analysis to be used in this study. More specifically, the protocol describes a sensitivity analysis 
using multiple imputation as the method for handling missing data and states that the MCMC 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 58 of 63
method will be used for intermittent missing data and that monotone regression will be used for 
monotone missing data. This SAP has been modified such that the MCMC method will be used 
for all missing data whether intermittent or monotone.
Section 14.6 of the protocol also notes that the missing data for all continuous efficacy variables
that have not been specifically described elsewhere will be imputed using the LOCF approach. 
This has been updated in this SAP so that these continuous variables will in fact be imputed 
using the multiple imputation method. However, in the event that multiple imputation is not 
possible (eg, Due to small group sizes or insufficient missing data) then the LOCF method will 
be used. ”
Change #6
Page 18, Section 4.2.3 Handling missing data for other efficacy variables, the text was changed.
From
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model. 
Other categorical efficacy variables will be imputed using NRI and observed cases. 
To
For the dose/exposure response model, missing data will not be imputed. If a subject drops out, 
this will be used as a covariate in the model. However, the dose/exposure response model is 
outside of the scope of this SAP and is described in greater detail in a separate data analysis plan 
(DAP).
Other categorical efficacy variables will be imputed using NRI (ie. Missing data or subjects who 
prematurely discontinue study treatment prior to Week 12 will be counted as non-responders) 
and summarized as observed cases. One exception to this rule is the imputation of missing data 
when summarizing HADS-A and HADS-D scores below 8 (ie. Normal HADS scores). In these 
summaries, LOCF will be used. That is, the last available HADS-A/HADS-D score while the 
subject was on study treatment will be carried forward to the missing time points to determine 
whether or not the subject had normal HADS scores.
From 
Other continuous efficacy variables will be imputed using last observation carried forward 
(LOCF) where the last observed value of a variable prior to discontinuation (including Baseline) 
is used to impute the missing data. Summaries based on observed case data will also be prepared.
To
Continuous efficacy variables will be imputed using multiple imputation (MI) via the Markov-
Chain Monte Carlo (MCMC) method. Summaries based on observed case data will also be 
prepared.
The MI procedure for continuous efficacy variables (based on MCMC) will be applied as 
follows:
1. Create a dataset, one for each treatment group, of subjects with observed values and those 
needing estimation by multiple imputation. The missing values in each dataset will be 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 59 of 63
filled in using the MCMC method with a total of 100 sets of imputations being 
performed. Biologic exposure, geographic region and values at baseline and at each post-
baseline visit (in chronological order) will be included in the implementation model, if 
required, in order to facilitate the imputation model, variables can be omitted in the order 
of biologic exposure and geographical region. Cut-off values will be applied to the 
imputed data, as appropriate, to ensure that imputed values do not exceed the range of 
plausible values for the variable being imputed. The resulting datasets for each treatment 
arm will be combined into one complete dataset based on each of the 100 imputations
2. The relevant change from Baseline (or percent change from Baseline) values will then be 
derived based on the datasets which include observed and imputed values for the variable 
being considered
3. The results from each of the 100 imputed datasets will be combined for the calculation of 
means and standard errors using Rubin’s rules, which account for the uncertainty 
associated with the imputed values (Rubin, 1987). This will be done using SAS PROC 
MIANALYZE. For calculation of other descriptive statistics such as the median, min and 
max, Rubin's rules do not apply. Multiple imputation estimates will be computed by 
simply averaging the estimates from the ݉ൌ1, … , ܯindependent repetitions of the 
imputation algorithm:
ߠ̅ ൌ1
ܯ෍ߠ෠௠
ெ
௠ୀଵ
where ߠ෡݉= estimate of ߠfrom the completed dataset ݉ൌ1, … , ܯ.
There may be cases where the multiple imputation model fails to converge (eg, sparse 
subgroups), in such situations the LOCF approach will instead be used to impute the missing 
data.  If LOCF is used instead of multiple imputation for this reason, this will be clearly specified 
in the corresponding table summary. Should there be no missing data for a study variable then 
only observed case data will be produced.
Summaries for all variables based on observed case data will also be prepared.
Change #7
Page 20, Section 4.3 Interim analyses and data monitoring, added the following paragraph.
The database lock to support the development of the PS0010 interim CSR will occur before all 
subjects have completed the PS0010 study. Specifically, subjects who do not enter the extension 
study (PS0011) will need to complete the SFU Visit, which occurs 20 weeks after the last dose of 
study treatment. The Week 12 interim database lock will be performed based on the last subject 
completing the Week 12 visit. It is anticipated that there will be some subjects still awaiting the 
SFU at that time. The number of subjects in that position is expected to be low, and the minimal 
data to be collected from their SFU visits is not considered mandatory to evaluating the key 
efficacy and safety objectives of the study, therefore it is considered acceptable to proceed with 
the PS0010 data analysis and interim CSR development in the absence of these data. Once all 
SFU data have been collected and the full PS0010 study database has been locked, all TLFs will 
be re-run to include the SFU data that have been added to the database following the Week 12 
interim database lick. A final CSR will subsequently be prepared based on this final set of TLFs. 
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 60 of 63
Other than the additional data from the pending SFU visits, it is expected that this final CSR will 
include biomarker and flow cytometry data summaries that will not be available in the interim 
CSR..
Change #8
Page 21, Section 4.8 Examination of subgroups, removed the subgroup “Anti-bimekizumab 
antibody positivity at Baseline (Yes, No)”.
Change #9
Page 22, Section 6.1 Demographics, amended the first age category by changing “≥65-<85, ≥85” 
to “≥65” in order to match exactly EudraCT age categorizations.
Change #10
Page 23, Section 6.2 Other Baseline Characteristics, removed “SF-36 Total score” and “Anti-
bimekizumab antibody positivity at Baseline (Yes, No)” from the list of variables to be 
summarized. In addition height, weight and BMI have been moved to Section 6.1 Demographics.
Change #11
Page 26, Section 8.1.2 Primary analysis of the primary efficacy variable, added in the 320mg 
loading dose followed by 160mg Q4W into the primary model with a linear contrast coefficient 
of 0. In addition, added the following text to the end of the section “The results produced in the 
SAS modelling process for the primary endpoint will be provided as a supportive output.”
Change #12
Page 27, Section 8.1.3 Secondary analyses of the primary efficacy variable, added the following 
text to the end of the section “The results produced in the SAS modelling process for the 
secondary analyses of the primary efficacy variable will be provided as a supportive output.”.
Change #13
Page 29, Section 8.1.4.2 Supportive Analysis, included an additional sensitivity analysis to be 
based on LOCF for the subjects that were withdrawn due to withdrawal criterion #11.
Change #14
Page 40, Section 10.1.1 Duration of exposure – Equation 13, removed “Date of last injection” 
from the equation.
Change #15
Page 40, Section 10.1.3 Exposure days at risk – Equations 14 and 15 added a “+1” to the 
deviation.
Change #16
Page 41, Section 10.2.1 Treatment-emergent Averse Events, added to the exclusion criteria for 
considering AEs that occur on the date of the Week 12 Visit to be treatment emergent to include 
any AE that met the criteria for anaphylactic reaction
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 61 of 63
Change #17
Page 43, Section 10.2.1 Treatment-emergent Averse Events, changed the reporting level from 
10% to 5% in all cases. 
Change #18
Page 47, Section 10.3 Clinical laboratory evaluations Table 10-2 – Definitions of Marked 
Abnormal Liver Function Tests, the abnormal ranges were amended from ≥5 and ≥3 to >5 and 
>3 respectively.
Change #19
Page 49, Section 10.3 Clinical laboratory evaluations Table 10-3 – Definitions of Marked 
Abnormal Clinical Chemistry Tests, the standard units for the chemistry parameters have been 
changed from umol/L to mmol/L.  In addition the abnormal high for calcium was corrected from 
>12.5 to >3.1.  In addition Albumin was removed from the table.
Change #20
Page 50, Section 10.4.1 Vital signs Table 10-5 – Definitions of markedly abnormal blood 
pressure values. Added in the additional lower and upper limits for systolic blood pressure and 
diastolic blood pressure.
Change #21
Page 51, Section 10.4.3.2 Electronic Columbia Suicide Severity Rating Scale, section has been 
re-written to contain more detail.
From 
The incidence of subjects with suicidal ideation, behavior and injuries will be summarized by
treatment group and visit
To
The results of the Columbia Suicide Severity Rating Scale (CSSRS) will be summarized using 
the number of subject and percentage with (i) events in suicide behavior, (ii) suicidal ideation, 
(iii) suicidal behavior and ideation, and (iv) self-injurious behavior without suicidal intent.
Suicidal ideation is defined as an event in any of the following 4 categories:
•
•
•
•
Q3 is not supplied for this study.
Suicidal behavior is defined as an event in any of the following 4 categories:
•
Actual attempt
•
Interrupted attempt
•
Aborted attempt
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 62 of 63
•
Preparatory acts or behavior.
Self-injurious behavior without suicidal intent is defined as an event in the category non-suicidal 
self-injurious injuries.
The incidence of subjects with suicidal intent, suicidal behavior and self-injurious behavior will 
be summarized by treatment group.  
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UCB
13 June 2017
Statistical Analysis Plan
BIMEKIZUMAB
PS0010
Confidential
Page 63 of 63
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
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