Clinical trial NCT03230292
Conditions: Chronic Plaque Psoriasis
Keywords: Psoriasis Chronic Plaque Psoriasis Bimekizumab
Sponsor: UCB Biopharma SRL
Start date: 2017-07-03; Completion date: 2019-03-06
Enrollment: 43 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a study to assess the long-term safety, tolerability, and efficacy of bimekizumab.

Detailed description:

Arms: arm 1: Subjects in this cohort will receive dose 1 every four weeks (Q4W) subcutaneously (sc) during the 48-week open-label Treatment Period. There will be an option to increase the dose to dose 2 Q4W at the discretion of the Investigator if the subject's Psoriasis Area and Severity Index (PASI) response is \>=50% to \<75% reduction from the Baseline of PS0016 at Week 12 or later. If the subject's disease is adequately controlled on dose 2 Q4W, they may return to dose 1 Q4W at the discretion of the Investigator.
Interventions: intervention 1: Bimekizumab
Intervention descriptions: intervention 1: Bimekizumab will be administered subcutaneously in 2 different doses.

Protocol documents:
Prot_000.pdf: 
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PROTOCOL PS0018 AMENDMENT 3
A MULTICENTER, 48-WEEK, OPEN-LABEL EXTENSION 
STUDY TO ASSESS THE LONG-TERM SAFETY, 
TOLERABILITY, AND EFFICACY OF BIMEKIZUMAB IN ADULT 
SUBJECTS WITH MODERATE TO SEVERE CHRONIC
PLAQUE PSORIASIS
PHASE 2
EudraCT Number: 2016-002934-57
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 Aug 2016
Not applicable
Protocol Amendment 1
06 Sep 2016
Nonsubstantial
Protocol Amendment 2
23 Sep 2016
Not applicable
Protocol Amendment 3
16 Feb 2018
Substantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL, Allée de la Recherche 60, B-1070 Brussels, Belgium
Sponsor Study Physician
Name:
Address:
UCB, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Clinical Project Manager
Name:
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
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
Address:
One Kilmainham Square; Inchicore Road; Kilmainham; 
Dublin 8; Ireland
Phone:
+35 314739500
Fax:
+35 314739501
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SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA and Canada: +1 800 880 6949
or +1 866 890 3175
Email
Global: DS_ICT@ucb.com 
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................9
1
SUMMARY.....................................................................................................................11
2
INTRODUCTION ...........................................................................................................11
2.1 Psoriasis ...........................................................................................................................11
2.1.1
Global epidemiology of psoriasis ........................................................................12
2.1.2
Current treatments for psoriasis...........................................................................12
2.2 Bimekizumab ...................................................................................................................13
2.2.1
Clinical.................................................................................................................14
2.2.2
Nonclinical...........................................................................................................15
3
STUDY OBJECTIVES....................................................................................................16
3.1 Primary objective.............................................................................................................16
3.2 Secondary objectives .......................................................................................................16
4
STUDY VARIABLES.....................................................................................................16
4.1 Safety variables................................................................................................................16
4.1.1
Primary safety variable........................................................................................16
4.1.2
Other safety variables ..........................................................................................16
4.2 Pharmacokinetic variables ...............................................................................................16
4.3 Immunological variables..................................................................................................17
4.4 Efficacy variables.............................................................................................................17
5
STUDY DESIGN.............................................................................................................17
5.1 Study description .............................................................................................................17
5.1.1
Study duration per subject ...................................................................................18
5.1.2
Planned number of subjects and sites ..................................................................18
5.1.3
Anticipated regions and countries .......................................................................18
5.2 Schedule of study assessments.........................................................................................18
5.3 Schematic diagram...........................................................................................................21
5.4 Rationale for study design and selection of dose.............................................................23
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................23
6.1 Inclusion criteria ..............................................................................................................23
6.2 Exclusion criteria .............................................................................................................24
6.3 Withdrawal criteria ..........................................................................................................25
6.3.1
PDILI IMP discontinuation criteria.....................................................................27
6.4 Study stopping rules.........................................................................................................27
7
STUDY TREATMENT...................................................................................................28
7.1 Description of investigational medicinal product............................................................28
7.2 Treatments to be administered.........................................................................................28
7.3 Packaging.........................................................................................................................28
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7.4 Labeling ...........................................................................................................................29
7.5 Handling and storage requirements..................................................................................29
7.6 Drug accountability..........................................................................................................29
7.7 Procedures for monitoring subject compliance................................................................29
7.8 Concomitant medication(s)/treatment(s)..........................................................................30
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................30
7.8.2
Prohibited concomitant treatments (medications and therapies).........................30
7.9 Blinding............................................................................................................................31
7.10 Randomization and numbering of subjects......................................................................31
8
STUDY PROCEDURES BY VISIT ...............................................................................32
8.1 Baseline Visit...................................................................................................................32
8.2 Week 4 (±3 days); and Week 28 (±3 days)......................................................................33
8.3 Week 8 (±3 days); Week 16 (±3 days); and Week 40 (±3 days).....................................33
8.4 Week 12 (±3 days)...........................................................................................................34
8.5 Week 20 (±3 days); and Week 44 (±3 days)....................................................................35
8.6 Week 24 (±3 days)...........................................................................................................35
8.7 Week 32 (±3 days)...........................................................................................................36
8.8 Week 36 (±3 days)...........................................................................................................36
8.9 Week 48 (±3 days) Study Exit/Early Withdrawal ...........................................................37
8.10 SFU Visit (20 weeks after the last dose; -3/+7 days).......................................................37
8.11 Early Withdrawal Visit ....................................................................................................38
8.12 Unscheduled Visit............................................................................................................38
9
ASSESSMENT OF SAFETY..........................................................................................39
9.1 Adverse events.................................................................................................................39
9.1.1
Definition of AE ..................................................................................................39
9.1.2
Procedures for reporting and recording AEs .......................................................39
9.1.3
Description of AEs ..............................................................................................39
9.1.4
Follow up of AEs.................................................................................................40
9.1.5
Rule for repetition of an AE ................................................................................40
9.1.6
Pregnancy ............................................................................................................40
9.1.7
Suspected transmission of an infectious agent via a medicinal product..............41
9.1.8
Overdose of investigational medicinal product ...................................................41
9.1.9
Safety signal detection.........................................................................................41
9.2 Serious adverse events .....................................................................................................42
9.2.1
Definition of SAE................................................................................................42
9.2.2
Procedures for reporting SAEs ............................................................................42
9.2.3
Follow up of SAEs...............................................................................................43
9.3 Immediate reporting of AEs.............................................................................................43
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9.4 Anticipated SAEs.............................................................................................................43
9.5 Adverse events of special interest....................................................................................44
9.6 Adverse events for special monitoring ............................................................................44
9.7 Laboratory measurements................................................................................................44
9.7.1
Evaluation of PDILI ............................................................................................45
9.7.1.1
Consultation with Medical Monitor and local hepatologist ......................49
9.7.1.2
Immediate action: determination of IMP discontinuation.........................49
9.7.1.3
Testing: identification/exclusion of alternative etiology...........................49
9.7.1.4
Follow-up evaluation.................................................................................51
9.8 Other safety measurements..............................................................................................51
9.8.1
Assessment and management of TB and TB risk factors....................................51
9.8.1.1
TB assessment by IGRA ...........................................................................53
9.8.1.2
Chest x-ray for TB.....................................................................................54
9.8.1.3
TB questionnaire .......................................................................................54
9.8.1.4
TB management ........................................................................................54
9.8.2
Pregnancy testing.................................................................................................55
9.8.3
Vital signs ............................................................................................................55
9.8.4
12-lead ECGs.......................................................................................................55
9.8.5
Physical examination...........................................................................................55
9.8.6
Assessment of suicidal ideation and behavior.....................................................55
9.8.7
Data Monitoring Committee................................................................................56
10
ASSESSMENT OF PHARMACOKINETIC VARIABLES...........................................56
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................56
12
ASSESSMENT OF EFFICACY......................................................................................56
12.1 Psoriasis Area and Severity Index ...................................................................................56
12.2 Investigator’s Global Assessment....................................................................................57
12.3 BSA affected by psoriasis................................................................................................58
12.4 Hospital Anxiety and Depression Scale...........................................................................58
13
STUDY MANAGEMENT AND ADMINISTRATION.................................................58
13.1 Adherence to protocol......................................................................................................58
13.2 Monitoring .......................................................................................................................58
13.2.1
Definition of source data .....................................................................................59
13.2.2
Source data verification .......................................................................................59
13.3 Data handling...................................................................................................................59
13.3.1
eCRF completion.................................................................................................59
13.3.2
Database entry and reconciliation........................................................................60
13.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............60
13.4 Termination of the study..................................................................................................60
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13.5 Archiving and data retention............................................................................................60
13.6 Audit and inspection ........................................................................................................61
13.7 Good Clinical Practices....................................................................................................61
14
STATISTICS ...................................................................................................................61
14.1 Definition of analysis sets................................................................................................61
14.2 Planned safety analyses....................................................................................................61
14.2.1
Primary safety analysis........................................................................................62
14.2.2
Other safety analyses ...........................................................................................62
14.3 Planned PK analyses........................................................................................................63
14.4 Planned immunological analyses.....................................................................................63
14.5 Planned efficacy analyses ................................................................................................63
14.6 Planned interim analysis and data monitoring.................................................................64
14.7 Determination of sample size...........................................................................................64
15
ETHICS AND REGULATORY REQUIREMENTS......................................................64
15.1 Informed consent .............................................................................................................64
15.2 Subject identification cards..............................................................................................65
15.3 IRBs and IECs..................................................................................................................65
15.4 Subject privacy.................................................................................................................66
15.5 Protocol amendments.......................................................................................................66
16
FINANCE, INSURANCE, AND PUBLICATION.........................................................66
17
REFERENCES ................................................................................................................66
18
APPENDICES .................................................................................................................69
18.1 Protocol Amendment 1 ....................................................................................................69
18.2 Protocol Amendment 2 ....................................................................................................71
18.3 Protocol Amendment 3 ....................................................................................................75
19
DECLARATION AND SIGNATURE OF INVESTIGATOR .......................................77
20
SPONSOR DECLARATION ..........................................................................................78
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................19
Table 7‒1:
Prohibited psoriasis medications during PS0018.............................................31
Table 9‒1:
Anticipated SAEs for the population of subjects with moderate to severe 
chronic plaque psoriasis...................................................................................44
Table 9‒2:
Laboratory measurements................................................................................45
Table 9-3:
Required investigations and follow-up for PDILI ...........................................47
Table 9-4:
PDILI laboratory measurements......................................................................50
Table 9-5:
PDILI information to be collected...................................................................51
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Table 12‒1:
Body areas for calculation of percent BSA for PASI ......................................57
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................22
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LIST OF ABBREVIATIONS
AE
adverse event
AESM
adverse event for special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BSA
body surface area (affected by psoriasis) 
cAMP
cyclic adenosine monophosphate
CRO
Contract Research Organization
C-SSRS
Columbia-Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
DMC
Data Monitoring Committee
EAER
exposure adjusted event rate
EAIR
exposure adjusted incidence rate
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GI
gastrointestinal
GMP
Good Manufacturing Practice
HADS
Hospital Anxiety and Depression Scale
HADS-A
Hospital Anxiety and Depression Scale-Anxiety
HADS-D
Hospital Anxiety and Depression Scale-Depression
HLT
high level term
IB
Investigator’s Brochure
IBD
Inflammatory Bowel Disease
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IGRA
interferon gamma release assay  
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IL
interleukin
IMP
investigational medicinal product
IRB
Institutional Review Board
iv
intravenous
IXRS
interactive voice or web response system
LTB
latent tuberculosis
mAb
monoclonal antibody
NSAID
nonsteroidal anti-inflammatory drug
NTMB
nontuberculous mycobacterium
PASI
Psoriasis Area and Severity Index
PDE4
phosphodiesterase 4
PDILI
potential drug-induced liver injury
PK
pharmacokinetics
PK-PPS
Pharmacokinetics Per-Protocol Set
PS
Patient Safety
PT
preferred term
Q4W
every 4 weeks
QOL
quality of life
SAE
serious adverse event
SAP
statistical analysis plan
sc
subcutaneous(ly)
SFU
Safety Follow-Up
SOC
system organ class
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
ULN
upper limit of normal
VAS
visual analog scale
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1
SUMMARY
PS0018 is a multicenter, 48-week, open-label extension study to assess the long-term safety, 
tolerability, and efficacy of bimekizumab in eligible adult subjects with moderate to severe 
chronic plaque psoriasis who participated in PS0016. 
During the Open-Label Treatment Period, subjects will attend study visits at the site every 
4 weeks (Q4W) for study assessments and administration of bimekizumab (if applicable) by 
study site staff through Week 48. Following completion or early withdrawal from the 48-week 
Open-Label Treatment Period, subjects will return for a Safety Follow-Up (SFU) Visit at 
20 weeks after their last dose of bimekizumab. Subjects withdrawing early from the study will 
undergo the Early Withdrawal Visit assessments and will enter the SFU Period.
Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during
the 48-week Open-Label Treatment Period. There will be an option to increase the dose to 
320mg Q4W at the discretion of the Investigator if the subject’s Psoriasis Area and Severity 
Index (PASI) response is ≥50% to <75% reduction from the Baseline of PS0016 at Week 12 or 
later. If the subject’s disease is adequately controlled on the 320mg Q4W dose, they may return 
to 160mg Q4W at the discretion of the Investigator. The decision to return to 160mg Q4W
dosing should be based upon treatment response, tolerability, and Investigator discretion, with 
the aim to use the dosing regimen that achieves the optimal benefit-risk for each subject. If a 
subject does not achieve a PASI50 at Week 12 or later then they will be withdrawn from the 
study.
Up to 45 subjects are anticipated to enroll in PS0018 at approximately 15 sites in Europe and 
North America, with possible extension to other regions and countries as required in PS0016.
The primary objective of the study is to assess the long-term safety and tolerability of 
bimekizumab. Secondary objectives of the study are to assess the safety and tolerability of 
increasing the dose of bimekizumab from 160mg Q4W to 320mg Q4W; to assess the 
pharmacokinetics (PK) of bimekizumab; to assess the immunogenicity of bimekizumab; and to 
assess the efficacy of open-label bimekizumab 160mg Q4W administered over 48 weeks.
The primary safety variable is the incidence of treatment-emergent adverse events (TEAEs) 
adjusted by duration of subject exposure to treatment. The secondary safety variables are severity 
and frequency of TEAEs and change from Baseline of PS0016 in clinical laboratory values 
(chemistry, hematology, and urinalysis), vital signs, physical examination, and 12-lead 
electrocardiogram (ECG) results.
Pharmacokinetic variables are plasma concentrations of bimekizumab. The immunological 
variable is anti-bimekizumab antibody levels prior to and following study treatment. The 
efficacy assessments are PASI, Investigator’s Global Assessment (IGA), body surface area 
(BSA) affected by psoriasis, and the Hospital Anxiety and Depression Scale (HADS); a detailed 
list of efficacy variables is presented in Section 4.4.
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 
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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).
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. Plaque 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:
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
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. Phosphodiesterase 4 inhibitors work 
intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. 
Phosphodiesterase 4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the 
dominant PDE in inflammatory cells. Phosphodiesterase 4 inhibition elevates intracellular 
cAMP levels, which in turn down-regulates the 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 (also known as UCB4940) is an engineered, humanized, full-length 
immunoglobulin G1 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 
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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 
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
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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 nonserious 
and resolved with topical therapy. There was a reduction in mean neutrophil count in the active 
treatment group, although this drop was not clinically relevant and a clear relationship with dose 
or time was not evident. 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, 
pharmacodynamics, 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.
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
The current study, PS0018, is a 48-week open-label extension study for eligible subjects who
participated in PS0016 (including subjects who relapse at Week 16 through 28 in PS0016), a 
Phase 2a, randomized, subject-blind, Investigator-blind study in adult subjects with moderate to 
severe chronic plaque psoriasis. In PS0016, subjects will be randomized 2:1 to receive the 
following study treatment regimens:

Treatment arm A: Bimekizumab 320mg administered sc at Baseline and Week 4, followed 
by placebo administration at Week 16

Treatment arm B: Bimekizumab 320mg administered sc at Baseline and Weeks 4 and 16
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 observed adverse effect level 
of 200mg/kg/week. The findings of note in toxicity studies were diarrhea related to infectious 
enteritis (observed in the single dose study) and asymptomatic mild colonic ulceration in a 
proportion of animals (in the repeat dose study); this latter finding was not associated with 
hematology abnormalities. Data suggest that bimekizumab has induced primary lesions to the 
mucosa-associated lymphoid tissue via a pharmacologically-related mechanism. In a second 
repeat-dose study, none of the minor apoptosis/necrosis findings observed in gut associated 
lymph nodes were 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 
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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 assess the long-term safety and tolerability of 
bimekizumab.
3.2
Secondary objectives
Secondary objectives of the study are:

To assess the safety and tolerability of increasing the dose of bimekizumab from 160mg 
Q4W to 320mg Q4W for subjects with an inadequate response at Week 12

To assess PK of bimekizumab

To assess the immunogenicity of bimekizumab

To assess the efficacy of open-label bimekizumab 160mg Q4W administered over 48 weeks 
4
STUDY VARIABLES
4.1
Safety variables
4.1.1
Primary safety variable
The primary safety variable is the incidence of TEAEs adjusted by duration of subject exposure 
to treatment.
4.1.2
Other safety variables
Change from Baseline variables will be defined relative to the Baseline measurement from 
PS0016. 
The other safety variables are:

Severity and frequency of TEAEs 

Change from Baseline in clinical laboratory values (chemistry, hematology, and urinalysis) 

Change from Baseline in vital signs

Change from Baseline in physical examination

Change from Baseline in 12-lead ECG results
4.2
Pharmacokinetic variables
The PK variables are:

Plasma concentrations of bimekizumab
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4.3
Immunological variables
The immunological variable is anti-bimekizumab antibody levels prior to and following study 
treatment.
4.4
Efficacy variables
Change from Baseline variables will be defined relative to the Baseline measurement from 
PS0016.
The efficacy variables are listed below and will be evaluated at all scheduled visits in accordance 
with the schedule of assessments in Table 5‒1. 

PASI50, PASI75, PASI90, and PASI100 response

IGA response (Clear or Almost Clear with at least a 2 category improvement from Baseline
on a 5-point scale)

Absolute and percent change from Baseline in PASI score

Shift from Baseline in IGA score

Absolute and percent change from Baseline in the BSA affected by psoriasis

Change from Baseline in the HADS Anxiety (HADS-A) and Depression (HADS-D) scores

Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores)
5
STUDY DESIGN
5.1
Study description
PS0018 is a multicenter, 48-week, open-label extension study to assess the long-term safety, 
tolerability, and efficacy of bimekizumab in eligible adult subjects with moderate to severe 
chronic plaque psoriasis who participated in PS0016. 
During the Open-Label Treatment Period, subjects will attend study visits at the site Q4W for 
study assessments and administration of bimekizumab by study site staff through Week 48. 
Following completion or early withdrawal from the 48-week Open-Label Treatment Period, 
subjects will return for a SFU Visit 20 weeks after their last dose of bimekizumab. Subjects 
withdrawing early from the study will undergo the Early Withdrawal Visit assessments and will 
enter the SFU Period.
Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during 
the 48 week Open Label Treatment Period. There will be an option to increase the dose to 320mg 
Q4W at the discretion of the Investigator if the subject’s PASI response is ≥50% to <75% 
reduction from the Baseline of PS0016 at Week 12 or later. If the subject’s disease is adequately 
controlled on the 320mg Q4W dose, they may return to 160mg Q4W at the discretion of the 
Investigator. The decision to return to 160mg Q4W dosing should be based upon treatment 
response, tolerability, and Investigator discretion, with the aim to use the dosing regimen that 
achieves the optimal benefit-risk for each subject. If a subject does not achieve a PASI50 at 
Week 12 or later then they will be withdrawn from the study.
A schedule of study assessments in presented in Table 5‒1.
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A study schematic diagram of PS0018 is presented in Figure 5‒1.
5.1.1
Study duration per subject
The study duration for each subject is estimated to be up to a maximum of 64 weeks:

Open-Label Treatment Period: up to 48 weeks

SFU Visit: 20 weeks after the last dose of bimekizumab
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.2
Planned number of subjects and sites
Up to 45 subjects are anticipated to enroll in PS0018 at approximately 15 sites.
5.1.3
Anticipated regions and countries
The regions planned for study conduct are Europe and North America, with possible extension to 
other regions and countries as required in PS0016.
5.2
Schedule of study assessments
A schedule of study assessments is presented in Table 5‒1.
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Table 5‒1:
Schedule of study assessments
Visit Week a
Protocol activity
PS0018
Baseline
Open-Label Treatment Period
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 48/ 
WD
SFU b
Informed consent
X c
Inclusion/exclusion
X d
Physical exam e
X f
X
X
Body weight
X f
X
X
Vital signs g
X f
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology/biochemistry/urinalysish
X f
X
X
X
X
X
X
X
12-lead ECG
X f
X
X
X
Pregnancy testing i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C-SSRS
X f
X
X
X
X
X
X
X
X
X
X
X
X
X
IGRA TB test j
Xf
X
X
TB questionnaire
X f
X
X
X
X
Blood sample for bimekizumab plasma 
concentrations k
X f
X
X
X
X
X
X
X
X
Blood sample for anti-bimekizumab
antibodies k
X f
X
X
X
X
X
X
X
X
PASI
X f
X
X
X
X
X
X
X
X
X
X
X
X
X
IGA
X f
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X f
X
X
X
X
X
X
X
X
X
X
X
X
HADS
X f
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X l
IXRS 
X
X
X
X
X
X
X
X
X
X
X
X
Bimekizumab administration m, n
X
X
X
X m
X m
X m
X m
X m
X m
X m
X m
X m
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Table 5‒1:
Schedule of study assessments
Visit Week a
Protocol activity
PS0018
Baseline
Open-Label Treatment Period
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 48/ 
WD
SFU b
BSA=body surface area; C-SSRS=Columbia-Suicide Severity Rating Scale;ECG=electrocardiogram;  HADS=Hospital Anxiety and Depression Scale; 
IGA=Investigator’s Global Assessment; IGRA=interferon gamma release assay; IXRS=interactive voice or web response system; PASI=Psoriasis Area and 
Severity Index; Q4W=every 4 weeks; SFU=Safety Follow-Up; TB=tuberculosis; WD= withdrawal; Wk=week
a Visit windows of ±3 days from the first dose (Baseline) at all visits except SFU, which has a window of -3 and +7 days from scheduled visit date.
b The SFU Visit will occur 20 weeks after the last dose.
c Ensure that the informed consent for PS0018 was completed by the subject (must be done before any study assessments are performed for PS0018).
d To be performed prior to the first dose of open-label bimekizumab.
e Includes evaluation of signs and symptoms of active TB and risk for exposure to TB.
f The noted PS0018 Baseline assessments will be obtained at the final visit of PS0016 and do not need to be recorded on the case report form for this study.
g Vital signs (blood pressure, pulse rate, and temperature) are to be measured prior to blood sampling and prior to dosing, where applicable.
h  The FSH test should only be performed on postmenopausal females who have been postmenopausal for ≥1 year and last menstrual cycle occurred <2 year sago.
i Pregnancy testing will be urine testing at all visits except SFU, which will be a serum test.
j It is recommended that the QuantiFERON TB GOLD test be performed.
k All blood samples are to be taken prior to dosing.
l Including assessment for the development of different forms of psoriasis at the SFU visit.
m Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during the 48 week Open Label Treatment Period. There will be an 
option to increase the dose to 320mg Q4W at the discretion of the Investigator if the subject’s PASI response is ≥50% to <75% reduction from the Baseline of 
PS0016 at Week 12 or later. If the subject’s disease is adequately controlled on the 320mg Q4W dose, they may return to 160mg Q4W at the discretion of the 
Investigator. The decision to return to 160mg Q4W dosing should be based upon treatment response, tolerability, and Investigator discretion, with the aim to 
use the dosing regimen that achieves the optimal benefit-risk for each subject. If a subject does not achieve a PASI50 at Week 12 or later then they will be 
withdrawn from the study.
n Subjects should not receive their first dose in PS0018 until at least 4 weeks (+/-3 days) after their last dose in PS0016.
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5.3
Schematic diagram
A study schematic diagram of PS0018 is presented in Figure 5‒1.
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Figure 5‒1: Schematic diagram
BL=Baseline; PASI=Psoriasis Area and Severity Index; Q4W=every 4 weeks; sc=subcutaneously
a Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during the 48 week Open Label Treatment Period. There will be an 
option to increase the dose to 320mg Q4W at the discretion of the Investigator if the subject’s PASI response is ≥50% to <75% reduction from the Baseline of 
PS0016 at Week 12 or later. If the subject’s disease is adequately controlled on the 320mg Q4W dose, they may return to 160mg Q4W at the discretion of the 
Investigator. The decision to return to 160mg Q4W dosing should be based upon treatment response, tolerability, and Investigator discretion, with the aim to 
use the dosing regimen that achieves the optimal benefit-risk for each subject. If a subject does not achieve a PASI50 at Week 12 or later then they will be 
withdrawn from the study.
48-Week Open-Label 
Treatment Period
Eligible 
subjects 
who 
participated 
in PS0016
Week
PS0018
BL
4
24
8
12
16
20
Safety Follow-Up 
Visit
28
32
36
40
48
Bimekizumab 320mg Q4W sc
20 weeks after 
the last dose of 
bimekizumab
Dose increase to 320mg Q4W if ≥50% to
<PASI75 from PS0016 BL and at the 
Investigator’s discretion 
a
64 
Bimekizumab 160mg Q4W sc
44
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5.4
Rationale for study design and selection of dose
PS0018 is a 48-week open-label extension study for eligible subjects who participated in 
PS0016, a Phase 2a, randomized, subject-blind, Investigator-blind study in adult subjects with 
moderate to severe chronic plaque psoriasis. This study will allow the collection of further data 
on the long-term safety, tolerability, and efficacy of bimekizumab in this subject population and
will provide continued access to bimekizumab.
Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during 
the 48 week Open Label Treatment Period. There will be an option to increase the dose to 320mg 
Q4W at the discretion of the Investigator if the subject’s PASI response is ≥50% to <75% 
reduction from the Baseline of PS0016 at Week 12 or later. If the subject’s disease is adequately 
controlled on the 320mg Q4W dose, they may return to 160mg Q4W at the discretion of the 
Investigator. The decision to return to 160mg Q4W dosing should be based upon treatment 
response, tolerability, and Investigator discretion, with the aim to use the dosing regimen that 
achieves the optimal benefit-risk for each subject. If a subject does not achieve a PASI50 at 
Week 12 or later then they will be withdrawn from the study.
The rationale for the selection of the 160mg Q4W dose for this study is based on the following: 

The optimal therapeutic dose of bimekizumab will not yet be known at the time subjects 
begin entering PS0018 from PS0016.

The 160mg Q4W dose is within the range of doses that have already been explored by iv
administration. This dose was selected based on modeling using the currently available data 
and may be modified, if appropriate, as further data are collected on the optimal dose of 
bimekizumab.

The 160mg Q4W starting dose in PS0018 will provide data to evaluate the safety and 
efficacy of a dose reduction.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject. 
2. Subject is considered reliable and capable of adhering to the protocol and visit schedule 
according to the judgment of the Investigator.
3. Subject completes all dosing requirements in PS0016 without meeting any withdrawal 
criteria.
4. Female subjects must be postmenopausal (at least 1 year; to be confirmed hormonally at the 
PS0018 Baseline Visit, 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 until 20 weeks 
after last administration of study medication (anticipated 5 half-lives), and have a negative 
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pregnancy test at Visit 1 (Baseline) 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, or implantable)

intrauterine device 

intrauterine hormone-releasing system 

bilateral tubal occlusion

vasectomized partner 

sexual abstinence if it is in accordance with a subject’s preferred and common lifestyle. 
Subjects who use abstinence as a form of birth control must agree to abstain from 
heterosexual intercourse until 20 weeks after the last dose of 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).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria are met:
1. Subject has previously participated in this study.
2. Female subjects who plan to become pregnant during the study or within 20 weeks following 
last dose of study medication. Male subjects who are planning a partner pregnancy during the 
study or within 20 weeks following the last dose.
3. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the subject’s ability to participate in this study. Note: 
For any subject with an ongoing serious adverse event (SAE), or a history of serious 
infections (including herpes zoster or hospitalizations) in PS0016, the Medical Monitor must 
be consulted prior to the subject’s entry into PS0018.
4. Subject has any current sign or symptom that may indicate a medically significant infection.
5. Subject has current clinically active infection with Histoplasma, Coccidiodes, 
Paracoccidioides, Pneumocystis, tuberculosis (TB), nontuberculous mycobacteria (NTMB), 
Blastomyces, Aspergillus, or Candidiasis (systemic). Any subject diagnosed with 
Histoplasmosis, Coccidiodes, Paracoccidiodes, Pneumocystis, TB, NTMB, Blastomyces, 
Aspergillus, or Candidiasis (systemic) during PS0016 is excluded from PS0018 even if 
treatment has been completed.
6. Any subject who meets any withdrawal criteria in the feeder study (PS0016) is excluded 
from participating in the open-label extension study (PS0018).
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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 will be asked to complete the Early 
Withdrawal Visit and SFU Visit (20 weeks after the last received dose) if any of the following 
events occur:
1. Subject withdraws his/her consent.
2. There is confirmation of a pregnancy in a female subject during the study, as evidenced by a 
positive pregnancy test.
3. The Sponsor or a regulatory agency requests withdrawal of the subject.
4. Subject develops an illness that in the opinion of the Investigator would interfere with his/her 
continued participation if the risk of continuing participation outweighs the potential benefit. 
5. Subject develops erythrodermic, guttate, or pustular form of psoriasis.
6. Subjects considered to have either a suspected new latent tuberculosis (LTB) infection or 
who develop an active TB or NTMB infection during the study (including but not limited to, 
conversion demonstrated by interferon-gamma release assay [IGRA] or other diagnostic 
means) must be immediately discontinued from study medication; an Early Withdrawal Visit 
must be scheduled as soon as possible, but not later than the next regular visit.
Confirmed active TB is an 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. 
7. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
8. Subject uses prohibited concomitant medications that may present a risk to the safety of the 
subject in the opinion of the Investigator and/or the Medical Monitor.
9. 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.
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10. 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.
11. 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 
Columbia-Suicide Severity Rating Scale (C-SSRS). The subject should be referred 
immediately to a Mental Healthcare Professional and must be withdrawn from the study.
12. 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.
13. Subject does not achieve a PASI50 at Week 12 or later following open-label treatment in 
PS0018.
14. Subjects with newly diagnosed Inflammatory Bowel Disease (IBD) or with IBD flares during 
the study must:
-
Be referred, as appropriate, to a healthcare professional treating IBD, such as a 
gastroenterologist
-
Discontinue the IMP and be followed-up until resolution of active IBD symptoms
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact 
the Medical Monitor and UCB study physician to confirm the subject's suitability for 
continued participation in the study.
Investigators should attempt to obtain information on subjects in the case of withdrawal. For 
subjects considered as lost to follow-up, the Investigator should make an effort (at least 1 phone 
call and 1 written message to the subject), and document his/her effort (date and summary of the 
phone call and copy of the written message in the source documents), to complete the final 
evaluation. All results of these evaluations and observations, together with a narrative description 
of the reason(s) for removing the subject, must be recorded in the source documents. The eCRF 
must document the primary reason for withdrawal.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
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6.3.1
PDILI IMP discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if 
investigational medicinal product (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 9.7.1. 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 eCRF must document the primary 
reason for IMP discontinuation.
6.4
Study stopping rules
During the study, planned dosing and procedures may be discontinued or suspended for all 
subjects in any part of the study and appropriate follow up procedures established. Where it is 
possible to do so without threatening the safety of subjects, such discontinuation/suspension 
should be discussed with the UCB Study Physician prior to its implementation.
Possible reasons for discontinuation or suspension of the study include (but are not limited to):

A pattern of AEs occurs that contraindicates the further dosing of enrolled / additional 
subjects, including (but not limited to):

More than 1 subject meets any individual Withdrawal Criteria 6, 9, 10, 11 or 12 (as 
provided in Section 6.3), regardless of whether they met the same or different criteria.

Once a second subject meets any of those criteria, referral to the DMC may not be 
delayed while awaiting the outcome of either case.
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If the above criteria are reached, the DMC will meet as soon as possible to determine 
whether discontinuation or suspension of the study should occur, and to determine what 
investigations, analyses, procedural amendments, or other actions should occur, before 
making any recommendation regarding the possibility of recommencing the study.  Further 
details on the role of the DMC are provided in Section 9.8.7. 

If the Sponsor or its designees judges it necessary for medical, safety, regulatory, or any 
other reasons consistent with applicable laws, regulations, and GCP.
7
STUDY TREATMENT
7.1
Description of investigational medicinal product
The IMP used in this study is bimekizumab. 
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative free solution in 2mL Type I, colorless glass vials (1.0mL extractable volume) closed 
with a rubber stopper and sealed with an aluminum cap overseal. Each single-use dose vial 
contains 160mg/mL bimekizumab in 55mM sodium acetate, 220mM glycine and 0.04% (w/v) 
polysorbate 80 at pH 5.0.
Further details of the study medication and specifications are provided in the IMP Handling 
Manual.
7.2
Treatments to be administered
During the Treatment Period, all subjects will receive bimekizumab 160mg Q4W sc 
administered for up to 48 weeks in an open-label manner. Subjects should not receive their first 
dose in PS0018 until at least 4 weeks (+/-3 days) after their last dose in PS0016. At the discretion 
of the Investigator, and if the subject does not achieve a PASI75 response (75% reduction in the 
PASI score from the Baseline of PS0016) at Week 12, the bimekizumab dose in PS0018 may be 
increased to 320mg Q4W sc. If the subject’s disease is adequately controlled on the 320mg Q4W 
dose, they may return to 160mg Q4W. The decision to return to 160mg Q4W dosing should be 
based upon treatment response, tolerability, and Investigator discretion, with the aim to use the 
dosing regimen that achieves the optimal benefit-risk for each subject.
The study medication is to be administered in the clinic by study site staff as 1 sc injection for 
the 160mg dose or 2 sc injections for the 320mg dose. Suitable areas for sc injections are the 
lateral abdominal wall and upper outer thigh. Injection sites should be rotated and injections 
should not be given into areas where the skin is tender, bruised, red, or hard. 
The minimum time between doses should be no less than 24 days and no more than 32 days for 
Q4W dosing.
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing.
7.3
Packaging
Bimekizumab will be packaged and labeled according to Good Manufacturing Practice (GMP) 
guidelines and applicable laws or regulations. It will be suitably packaged in such a way as to 
protect the product from deterioration during transport and storage. Further information 
regarding storage and transport conditions are provided in the IMP Handling Manual.
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7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and GMP and will include any 
locally required statements. If necessary, labels will be translated into the local language.
7.5
Handling and storage requirements
The IMP must be stored under refrigerated conditions (2ºC to 8ºC) and protected from light. The 
study drug must not be frozen. 
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access according to the storage conditions mentioned on the label.
Appropriate storage conditions must be ensured by controlling the temperature (eg, room, 
refrigeration unit) and by completion of a temperature log in accordance with local requirements 
on a regular basis per study manuals, showing actual and minimum/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, as per 
instructions contained in the IMP Handling Manual. 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, damaged (due to breakage or wastage), not used, partially used, disposed of at the 
study site, or returned to the Sponsor or designee must also be recorded on the appropriate forms. 
All supplies and pharmacy documentation must be made available throughout the study for UCB 
(or designee) to review.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee.
The Investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers), partially used, unused, damaged, and/or expired IMP must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB SOPs or returned to UCB (or 
designee). 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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7.8
Concomitant medication(s)/treatment(s)
All concomitant medications, including over the counter products, herbal, traditional remedies, 
vitamin/mineral supplements, other dietary supplements, “nutraceuticals,” and hormones must be 
recorded in the subject’s source documentation (eg, clinical chart) and on the eCRF. This record 
should include the name of the drug, the dose, the route and date(s) of administration, and the 
indication for use.
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 nonprescription 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 will be allowed to use topical medications (corticosteroids, retinoids, Vitamin D analogs 
coal tar, etc) as needed during this open-label extension. 
Other medications
Subjects who were already receiving an established nonsteroidal anti-inflammatory drug 
(NSAID) regimen during PS0016 may continue their use during this study. However, initiation 
of, or increase in dosage of, NSAIDs during the study (especially in subjects with a history of 
gastrointestinal [GI] intolerance to NSAIDs or a history of GI ulceration) should be done with 
caution. Intra-articular injections for arthritis of the knee are allowed.
Subjects who were already receiving an established anti-depressant regimen during PS0016 may 
continue their use during this study.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The list of prohibited concomitant medications is provided Table 7‒1.
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Table 7‒1:
Prohibited psoriasis medications during PS0018
Drug
Systemic retinoids
Systemic treatment (non-biological):
systemic immunosuppressant agents (eg, methotrexate, cyclosporine, azathioprine, thioguanine)
systemic fumarate
systemic corticosteroids
phototherapy or chemophototherapy
Anti-TNFs:
infliximab (including biosimilar), golimumab
etanercept (including biosimilar)
certolizumab pegol
adalimumab (including biosimilar)
Other biologics and other systemic therapies:
apremilast
ustekinumab
Anti-IL-17 therapy
Any other antipsoriatic agent (systemic)
Any other antipsoriatic agent (topical) under investigation
IL=interleukin; TNF=tumor necrosis factor
Subjects who take prohibited medications may be withdrawn from study treatment but followed 
until the SFU Visit. The decision to withdraw a subject for taking prohibited medications should 
be made in consultation with the Medical Monitor. 
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. Administration of inactivated vaccines is 
allowed during the study at the discretion of the Investigator.
7.9
Blinding
This is an open-label extension study and no blinding will be performed. All subjects’ treatment 
assignments during PS0016 will remain blinded until database lock of PS0016.
7.10
Randomization and numbering of subjects
This is an open-label extension study and no randomization will be performed. All subjects will 
receive bimekizumab 160mg Q4W sc with an option to increase the dose to 320mg Q4W at the 
discretion of the Investigator (see Section 7.2 for further details).
Subjects will continue with the 5-digit subject numbers assigned by the interactive voice or web 
response system (IXRS) in the preceding study.
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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 provided in the sections that follow. 

Visit windows of ±3 days on either side of the scheduled dosing are permitted for all visits 
other than the SFU Visit (see below); however, the Investigator should try to keep the 
subjects on the original dosing schedule. The window of ±3 days is relative to the first dose 
(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 time between doses should be no less than 24 days and no more than 32 days 
for Q4W dosing.

For the SFU Visit (20 weeks after the last dose), the visit should occur no more than 3 days
prior to the scheduled visit date and within 7 days after the scheduled visit date 
(-3 days/+7 days).
8.1
Baseline Visit
The Baseline assessments noted with an * will be obtained at the final visit of PS0016 and do not 
need to be recorded on the eCRF for this study.
All procedures or assessments will be performed prior to administration of study drug, unless 
otherwise noted. The following procedures or assessments will be performed:

Ensure that a separate Informed Consent Form was completed by the subject for PS0018
(must be done prior to any PS0018 study procedures)

Confirm that a TB test (IGRA) was performed at the final visit of PS0016 and the results 
were negative

Assessment of inclusion/exclusion criteria

Vital signs (blood pressure, pulse rate, and temperature)*

Body weight*

Physical examination*

Record 12-lead ECG*

C-SSRS*

TB questionnaire*

PASI*

IGA*

BSA*

HADS*

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)*
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
Bimekizumab plasma concentration*

Anti-bimekizumab antibodies*

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)*

Urine pregnancy test for women of childbearing potential*

Concomitant medications

Record adverse events (AEs)

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.2
Week 4 (±3 days); and Week 28 (±3 days)
All procedures or assessments will be performed prior to administration of study drug, unless 
otherwise noted. The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

PASI

IGA

BSA

Obtain blood samples for:

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for: 

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.3
Week 8 (±3 days); Week 16 (±3 days); and Week 40 (±3 days)
All procedures or assessments will be performed prior to administration of study drug (if 
applicable), unless otherwise noted. The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

PASI
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
IGA

BSA

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.4
Week 12 (±3 days)
The following procedures or assessments will be performed prior to administration of study drug
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain blood samples for:

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for: 

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS
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
Study medication administration (after all other visit assessments are completed)
8.5
Week 20 (±3 days); and Week 44 (±3 days)
The following procedures or assessments will be performed prior to administration of study drug 
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

PASI

IGA

BSA

Obtain urine sample for: 

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.6
Week 24 (±3 days)
The following procedures or assessments will be performed prior to administration of study drug 
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Obtain urine samples for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications
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
Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.7
Week 32 (±3 days)
All procedures or assessments will be performed prior to administration of study drug (if 
applicable), unless otherwise noted. The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

PASI

IGA

BSA

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.8
Week 36 (±3 days)
The following procedures or assessments will be performed prior to administration of study drug 
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain urine sample for: 

Urine pregnancy test for women of childbearing potential
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
Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
8.9
Week 48 (±3 days) Study Exit/Early Withdrawal
The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

Body weight

Physical examination

Record 12-lead ECG

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain blood samples for:

TB test (IGRA; QuantiFERON TB GOLD test is recommended)

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs
8.10
SFU Visit (20 weeks after the last dose; -3/+7 days)
The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

Body weight

Physical examination
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
C-SSRS

Record 12-lead ECG

PASI

IGA

Obtain blood samples for:

TB test (IGRA; QuantiFERON TB GOLD test is recommended)

Standard safety laboratory tests (hematology and biochemistry)

Serum pregnancy test for women of childbearing potential

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)

Concomitant medications

Record AEs (including assessment for development of other forms of psoriasis)
8.11
Early Withdrawal Visit
Subjects withdrawing early from the study (see Section 6.3) will undergo the same assessments 
as the Week 48 Visit (see Section 8.9) and will enter the SFU Period.
8.12
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 additional visit (or unscheduled visit) is conducted due to safety or efficacy reasons, a 
C-SSRS assessment will be performed with the subject during the visit. If an additional visit (or 
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), a C-SSRS will not be required at these visits.
At this visit, any of the following assessments may be performed, depending on the reason for 
the visit:

Vital signs

Physical examination

Record 12-lead ECG 

C-SSRS

If medically indicated, obtain blood sample(s) for:

Standard safety laboratory tests (hematology and biochemistry) 

The blood sample may also be used for PK assessments, if needed
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
Obtain urine sample for standard safety laboratory tests (urinalysis; including urine 
pregnancy test)

Concomitant medications

Record AEs
9
ASSESSMENT OF SAFETY
9.1
Adverse events
9.1.1
Definition of AE
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
9.1.2
Procedures for reporting and recording AEs
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 employed in the 
study.
9.1.3
Description of AEs
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records 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 AE eCRF (including judgment of severity and relationship to IMP) are 
described in the eCRF Completion Guidelines.
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9.1.4
Follow up of AEs
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. Further 
details regarding follow up of PDILI events are provided in Section 9.7.1.4.
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
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.
9.1.5
Rule for repetition of an AE
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
9.1.6
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 
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 
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be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/Contract Research Organization (CRO) contract monitor for 
the study. The Investigator will complete the Pregnancy Report and Outcome form and send it to 
UCB’s PS department (for contact details see SAE reporting information at the beginning of this 
protocol) only after the partner has agreed that additional information can be captured and has 
provided the signed Partner Pregnancy Consent form. UCB’s PS department is also the primary 
contact for any questions related to the data collection for the partner pregnancy, eventual birth, 
and follow up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective or 
spontaneous), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report form.
9.1.7
Suspected transmission of an infectious agent via a medicinal 
product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
9.1.8
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).
9.1.9
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 Adjudication Committee will also periodically review and monitor the 
safety data from this study and advise UCB. Details are provided in the Cardiovascular
Adjudication Committee Charter.
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.
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9.2
Serious adverse events
9.2.1
Definition of SAE
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 9.5], allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
Note: Confirmed active TB is always to be considered as an SAE and must be captured on an 
SAE Report Form and provided to the Sponsor in accordance with SAE reporting requirements.
9.2.2
Procedures for reporting SAEs
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the SAE Reporting section at the 
front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
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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.
9.2.3
Follow up of SAEs
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. Further 
details regarding follow up of PDILI events is provided in Section 9.7.1.4.
Information on SAEs obtained after clinical database lock will be captured through the PS
database without limitation of time.
9.3
Immediate reporting of AEs
The following AEs must be reported immediately:

SAE: AE that the Investigator classifies as serious by the definitions in Section 9.2.1
regardless of causality

Suspected transmission of an infectious agent via a medicinal product

AEs of special interest as defined in Section 9.5
9.4
Anticipated SAEs
The following Anticipated SAEs (Table 9‒1) are anticipated to occur in the population studied in 
this protocol at some frequency that is independent of drug exposure. This original list will 
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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 9.2.2.
Table 9‒1:
Anticipated SAEs 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.
9.5
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AE of special interest (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.
9.6
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 9.8.1), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the C-SSRS; see Section 9.8.6), depression and anxiety 
(assessed using the HADS; see Section 12.4), major cardiovascular events, and liver function test 
changes/enzyme elevations (ALT, AST, bilirubin; see Section 9.7.1), malignancies, and 
inflammatory bowel diseases.
9.7
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 
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laboratory testing should also be collected using the central laboratory. Laboratory parameters to 
be measured are listed in Table 9‒2. 
Specific details regarding the handling and processing of serum chemistry, hematology, and 
urinalysis samples are provided in the study laboratory manuals.
Table 9‒2:
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
MCH
Creatinine
MCHC
ALP
MCV
AST
Platelet count
ALT
RBC count
GGT
WBC count
Total bilirubin
LDH
Total cholesterol
Serum pregnancy testing a
Serum FSHb (Screening)
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; FSH=follicle stimulating hormone; 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 SFU Visit. The pregnancy test will be urine at all other visits 
and will be performed locally.
b The FSH test should only be performed on postmenopausal females who have been postmenopausal for ≥1 year 
and last menstrual cycle occurred <2 year sago.
Assessments of PK variables are described in Section 10. Assessments of immunological
variables are described in Section 11.
9.7.1
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 
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must be reported as an AE and reported to the study site and Sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AE of special interest (see Section 9.5), and, if applicable, also reported as an SAE 
(see Section 9.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 9-3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 9.7.1.1). 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 9.7.1.4). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
When IMP is stopped due to PDILI (as described in Section 6.3.1), IMP must be permanently 
discontinued even if a subsequent alternative diagnosis fully explains the hepatic findings. 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Table 9-3 summarizes the approach to investigate PDILI.
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Table 9-3:
Required investigations and follow-up for PDILI
Laboratory value
Symptoms a of 
hepatitis or 
hypersensitivity
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULN b
NA
Hepatology consult.c
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 9.7.1.3); 
recommended to 
occur at the site 
with HCP.
Monitoring of liver 
chemistry values at least 
twice per week until values 
normalize, stabilize, or 
return to within baseline 
values. 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.
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Table 9-3:
Required investigations and follow-up for PDILI
Laboratory value
Symptoms a of 
hepatitis or 
hypersensitivity
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN 
(and ≥2x 
baseline) 
and 
<5xULN
(and ≥2x 
baseline)
<2xULN
No
Discussion with 
Medical Monitor 
required.
Consider need for 
hepatology consult if 
there is no evidence 
of resolution (see 
Follow up 
requirements). c
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 9.7.1.2).
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 9.7.1.3).
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 resolution d
Continue to monitor until 
values normalize, 
stabilize, or return to 
within baseline values. d
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 alkaline phosphatase, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
.c Details provided in Section 9.7.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of potential 
hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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9.7.1.1
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 9.7.1.3) and SAE report (if applicable).
9.7.1.2
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 9-3 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.
9.7.1.3
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP include, but are not 
limited to, those listed in Table 9-4 (laboratory measurements) and Table 9-5 (additional 
information). Results of the laboratory measurements and information collected are to be 
submitted to the Sponsor on the corresponding eCRF. If the medical history of the subject 
indicates a requirement for other assessments not included below, these additional assessments 
should be completed and submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The laboratory measurements to be assessed are presented in Table 9-4.
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Table 9-4:
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 screena
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
Additional
Prothrombin time/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).
Additional information to be collected is presented in Table 9-5.
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Table 9-5:
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
9.7.1.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 9-3. 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.
9.8
Other safety measurements
9.8.1
Assessment and management of TB and TB risk factors
All subjects will be assessed for TB through physical examination for signs and symptoms of 
TB, laboratory testing (Section 9.8.1.1), and subject questionnaire (Section 9.8.1.3). A chest 
x-ray can be performed in PS0018, if warranted, to confirm or exclude TB (Section 9.8.1.2).
At the Baseline Visit of PS0018, all subjects will undergo physical examination for signs and 
symptoms of TB and must be confirmed to have undergone an IGRA test (QuantiFERON TB 
GOLD is recommended) in PS0016 with negative results. In addition, each subject will complete 
a TB questionnaire with questions directed at symptoms of TB and potential exposure to TB. 
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Exclusion criteria at Baseline of PS0018
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 
enrollment

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 
enrolled in the study. The retest must be done prior to entry in PS0018.
Note: If available, respiratory or other specimens must also be smear and culture 
negative for TB (Centers for Disease Control diagnosis of LTB infection 
http://www.cdc.gov/TB/topic /testing/default.htm)
d. Current or history of NTMB infection
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 GI system, 
bone/joints, lymph glands and meninges, etc. However, in immune compromised patients and/or 
patients treated with TNF inhibitors, extrapulmonary manifestations of TB are common 
compared to the normal population.
Some common symptoms that the subject may present are dependent on the primary focus of 
infection and may include cough, blood in sputum, night sweats, lymphadenitis, joint 
pain/swelling, spinal deformity, headache/confusion, abdominal pain (mimicking inflammatory 
bowel disease), etc. Unusual presentations should always be considered.
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Latent TB infection is defined in the “Exclusion Criteria” above. If the result of the IGRA is 
indeterminate, the particular IGRA previously performed may be repeated once; if positive or 
indeterminate on retest, the subject may not be enrolled in the study without further evaluation 
by a TB specialist. In the event of an indeterminate test result, the retest must be done prior to the 
next visit. If LTB infection or active TB is identified, subject must undergo appropriate study 
specified withdrawal procedures. 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 the 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 LTB infection, active TB, or NTMB then, per UCB TB working 
instructions, TB test conversion (confirmed) should be classified adequately, either as due to 
LTB infection, active TB infection, or NTMB, respectively. Additional assessments (eg, blood 
tests or IGRA, chest x-rays, or other imaging) should be performed where medically relevant and 
documented. Such conversions should be reported to the UCB PS function.
LTB
In case the evaluation by the appropriate specialist indicates a new LTB infection 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 48/Withdrawal Visit, 
complete all Early Withdrawal Visit assessments, and complete a SFU Visit (20 weeks after the 
last dose of study medication).
Active TB or NTMB infection 
Subjects who develop active TB or NTMB infection during the study must be withdrawn from 
the study. The subject must be immediately discontinued from study medication and an 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. 
9.8.1.1
TB assessment by IGRA
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD is 
recommended) will be performed at the final visit of PS0016 and should be repeated at 
Week 48/Early Withdrawal Visit and the SFU visit for all subjects. The test results will be 
reported as positive, negative, or indeterminate. UCB also recommends that a TB specialist be 
consulted where TB (latent or active) is suspected or if there are doubts regarding test results. If 
latent or active TB is identified, the subject must undergo appropriate study-specified withdrawal 
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procedures. In the event of an indeterminate test result, the retest must be done prior to the next 
visit.
9.8.1.2
Chest x-ray for TB
Chest x-ray will be performed in PS0018 only when required to confirm or exclude TB. Any 
new clinically significant findings on chest x-ray must be documented in the source documents 
and the eCRF as an AE.
9.8.1.3
TB questionnaire 
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will be completed at the Baseline Visit of PS0018, and at 
the Week 12, Week 24, Week 36, and Week 48/Withdrawal Visit. The questionnaire will assist 
with the identification of subjects who may require therapy for TB. A subject who answers 
“Yes” to the question
 
 or to any of the other questions within 
the questionnaire at any visit should trigger further careful assessment to determine if subject has 
LTB or active TB. 
Subjects with a latent or active TB infection must be withdrawn from the study.
9.8.1.4
TB management
LTB infection and active TB identified during study
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of study medication and will be referred to an 
appropriate TB specialist (pulmonologist or infectious disease specialist) for further evaluation. 
Evidence of LTB infection is defined as the subject’s IGRA test converts to positive or 
indeterminate (and confirmed indeterminate on repeat), or the subject’s questionnaire or history 
and physical indicates that TB infection or exposure may have occurred. Evidence of active TB 
includes, in addition to the aforementioned tests, signs and symptoms of organ involvement. In 
either situation, the subject should be carefully assessed by a TB specialist for active TB. 
Subjects diagnosed with active TB or LTB infection should be withdrawn from the study and 
receive appropriate TB or prophylaxis therapy. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Confirmed active 
TB must be reported as an SAE. The Investigator is to complete and submit the TB follow up 
form provided.
The subject should be transferred to the care of his/her physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the Week 48/Withdrawal Visit as soon as 
possible, but no later than the next scheduled study visit, and complete all Week 48/Withdrawal 
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.
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9.8.2
Pregnancy testing
Pregnancy testing will consist of serum testing at the SFU Visit and urine testing at all other 
visits. 
The Baseline Visit urine pregnancy test result must be negative prior to enrollment of the subject. 
A negative urine pregnancy test result should be obtained immediately prior to each 
administration of study drug and at all subsequent visits. Pregnancy tests should be administered 
to all female subjects of childbearing potential, regardless of their use of birth control.
9.8.3
Vital signs
Vital signs will be collected at every visit and will include systolic and diastolic blood pressure, 
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. 
Body weight will be measured at the time points specified in the schedule of study assessments 
(Table 5‒1).
9.8.4
12-lead ECGs
Standard 12-lead ECG will be recorded after 10 minutes of rest in the supine or semirecumbent 
position. The following ECG variables will be recorded: heart rate, PR interval, QRS duration, 
QT interval, Fridericia’s  QTc interval (QTcF), and the Investigator’s interpretation of the ECG 
profile.
9.8.5
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 the time points specified 
in the schedule of study assessments (Table 5‒1). Findings considered clinically significant 
changes since the physical examination at the Screening Visit of PS0016 will be recorded as 
AEs.
9.8.6
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed by trained study personnel using the C-SSRS. 
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the C-SSRS assessments will be performed are specified in the schedule of 
study assessments (Table 5‒1).
The C-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Mundt et al, 2010; Posner et al, 2011). 
Subjects respond to standardized clinical questions that are presented in a uniform fashion. The 
C-SSRS defines five subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The C-SSRS takes approximately 3 to 10 minutes to complete.
Refer to Section 6.3 for C-SSRS-related withdrawal criteria.
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9.8.7
Data Monitoring Committee
The DMC membership includes clinicians knowledgeable about the disease or the treatment. The 
DMC will include a statistician, and at a minimum, specialists in dermatology and infectious 
disease. All members have experience and expertise in clinical trials. Board members may not 
participate in the study as principal or co-Investigators, or as study subject care physicians. The 
duration of membership for the DMC will be inclusive of planned analyses for PS0018. 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.
A Cardiovascular Adjudication Committee will also periodically review the safety data from this 
study. Details will be described in a separate charter document.
10
ASSESSMENT OF PHARMACOKINETIC VARIABLES
Blood samples for measurement of PK (Section 4.2) 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.
11
ASSESSMENT OF IMMUNOLOGICAL VARIABLES
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.
12
ASSESSMENT OF EFFICACY
12.1
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. 
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The degree of involvement is estimated across 4 body areas; head, upper limbs, trunk, and lower 
limbs and then transferred into a grade (Table 12‒1). 
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 12‒1: Body areas for calculation of percent BSA for PASI
Body area
Details of area
BSA
Degree of involvement of 
body area a
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 improvement will be based on changes from the 
PASI score at the Baseline of PS0016.
The PASI will be completed at the visits specified in Table 5‒1.
12.2
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. 
The Investigator will assess the overall severity of psoriasis using the following 5-point scale:
5 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
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12.3
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.
12.4
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 
(Snaith and Zigmond, 1994).
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 Clinical Project Manager 
of the Sponsor within 24 hours and follow any local regulatory requirements.
13.2
Monitoring
The CRO will monitor the study using their own monitoring Standard Operating Procedures
(SOPs), in line with ICH GCP guidelines and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
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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 QOL questionnaires, for example. Source documents should be kept in a secure, 
limited access area.
The Sponsor or designee will review to ensure that computerized source documents produced by 
the site are compliant with Food and Drug Administration (FDA) Part 11 requirements and 
document appropriately. Source documents that are computer generated and stored electronically 
that are not FDA Part 11 compliant, must be printed for review by the monitor (eg, ECG reports). 
Once printed, these copies should be signed and dated by the Investigator and become a 
permanent part of the subject’s source documents. The Investigator will facilitate the process for 
enabling the monitor to compare the content of the printout and the data stored in the computer 
to ensure all data are consistent.
Electronic data records, such as PASI data, must be saved and stored as instructed by the 
Sponsor or designee. 
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
eCRF 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.
Serious AE reporting will be done using the SAE Form (see Section 9.2.2) while also entering 
the event in the appropriate eCRF section. The safety database and the clinical database will be 
reconciled during the study and discrepancies will be corrected as needed.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Access to the EDC will be given after training has been received. A training certificate will be 
provided and filed.
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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. Computerized data cleaning checks will be 
used in addition to manual review to check for discrepancies and to ensure consistency of the 
data. This study is performed using EDC: the data are entered into the eCRFs once and are 
subsequently verified.
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 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 
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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 (Committee for Proprietary Medicinal Products [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.
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 Practices
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 for PS0018.
The Safety Set (SS) will consist of all subjects who receive at least 1 dose of the study 
medication in PS0018.
The Full Analysis Set (FAS) will consist of all enrolled subjects who receive at least 1 dose of 
the study medication and have a valid efficacy measurement for PASI at Baseline of PS0018. 
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of all enrolled subjects who 
receive at least 1 dose of the study medication and provide at least 1 quantifiable plasma 
concentration postdose in PS0018.
14.2
Planned safety analyses
Safety variables will be analyzed for all subjects in the SS.
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Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®). Treatment-emergent AEs will be defined as events that have a start date on or 
following the first administration of study treatment in PS0018 through the final administration 
of study treatment +140 days (covering the 20-week SFU Period). Treatment-emergent AEs will 
be categorized to treatment group based on the dose being received at the time of onset of the 
event. Tables will include columns for bimekizumab 320mg Q4W, bimekizumab 160mg Q4W, 
and All bimekizumab (ie, either dose of bimekizumab). 
Change from Baseline safety variables will be defined relative to the Baseline measurement from 
PS0016.
14.2.1
Primary safety analysis
All TEAEs will be summarized descriptively by treatment group, primary system organ class 
(SOC), high level term (HLT), and preferred term (PT). This summary will include the exposure 
adjusted incidence rate (EAIR) with associated 95% confidence interval and the exposure 
adjusted event rate (EAER). 
For EAIR, the numerator will be the total number of subjects experiencing the AE. The
denominator will be 100 subject-years; that is, the total summation of individual subject-years at 
risk up to the first occurrence of the AE for subjects with that AE, and the total subject-years at 
risk for those subjects not experiencing that AE, divided by 100. Exposure adjusted incidence 
rates will be presented with a 95% exact confidence interval based upon the Chi-Square 
distribution (Ulm, 1990). 
For EAERs, the numerator will be the number of AEs including repeat occurrences in individual 
subjects; the denominator will be 100 subject-years. That is, the total summation of individual 
subject-years at risk divided by 100. No confidence interval will be computed for EAER. 
Subject exposure at risk in days will be defined as date of last administration of study medication 
– date of first administration of study medication +140 days (ie, the duration of the SFU Period). 
If a subject dies, patient exposure at risk is censored at the date of death. The sum of these 
exposure days at risk across subjects is converted to years for the EAIR and EAER calculations 
described above.
14.2.2
Other safety analyses
Additional tables will summarize TEAEs by intensity and relationship to study medication, 
TEAEs leading to withdrawal from the study, treatment-emergent SAEs, and deaths. 
In order to evaluate if there is any difference in the TEAE profile of subjects who have dose 
adjustments, additional summaries will be generated and are described further here. With respect 
to dose adjustments, subjects will be classified into 1 of the following 3 groups:

Nonadjusters – This group consists of subjects who do not experience a dose adjustment 
during the study.

Single adjusters – This group consists of subjects who experience just one dose adjustment 
during the study. Per the protocol, if just a single adjustment occurs, then that adjustment 
must be to go from bimekizumab 160mg Q4W to 320mg Q4W.

Multiple adjusters – This group consists of subjects who experience more than 1 dose 
adjustment during the study. This means that the subjects in this group dose adjust from 
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bimekizumab 160mg Q4W to 320mg Q4W and then adjust back to 160mg Q4W (with 
further dose adjustments possible).
Summaries based on these 3 groups will be done by PS0016 randomized treatment group for the 
TEAE overview, incidence of TEAEs (by SOC, HLT, and PT), and incidence of treatment-
emergent SAEs.
Extent of exposure to study medication in PS0018 will be summarized using descriptive 
statistics. As with the primary summaries of TEAEs, extent of exposure will be presented with 
columns for bimekizumab 160mg Q4W, bimekizumab 320mg Q4W, and All bimekizumab. 
Change from Baseline in laboratory values, ECGs, and vital signs will be presented using 
descriptive statistics by PS0016 randomized treatment group and overall. As these variables are 
summarized over time and the initial values can be impacted by the randomized treatment in 
PS0016, the presentation by PS0016 randomized treatment group is intended to provide 
perspective on the change in these values starting with the initial PS0016 randomization through 
the 48-week Open-Label Treatment Period of PS0018. The table presentations will display 
descriptive statistics for the PS0016 Baseline and the observed and change from PS0016
Baseline results by scheduled visit for PS0018.
14.3
Planned PK analyses
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS. 
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit.
14.4
Planned immunological analyses
Immunological variables will be analyzed for all subjects in the PK-PPS. 
Anti-bimekizumab antibody data will be summarized for each treatment at each scheduled visit.
14.5
Planned efficacy analyses
Efficacy variables will be summarized based on the FAS. The summaries described in this 
section will provide data on maintenance of effect of open-label bimekizumab over 48 weeks. 
Additionally, it will allow an assessment of the impact of dose adjustments on efficacy results.
Responder efficacy variables (PASI50, PASI75, PASI90, PASI100, IGA score of 0 or 1, and 
HADS normal scores) will be summarized descriptively using counts and percentages by 
scheduled visit and PS0016 randomized treatment group and overall. The PASI responder 
variables are derived relative to the PS0016 Baseline. Missing data will be handled by using 
nonresponder imputation (NRI), meaning that subjects that discontinue early or who have 
missing data at a given time point are imputed as though they did not achieve the given response. 
Supportive summaries will be based on observed case data.
Continuous efficacy variables based on the change from Baseline (PASI, BSA, and HADS) will 
be summarized using descriptive statistics by scheduled visit and PS0016 randomized treatment 
group and overall. The table presentations will display descriptive statistics for the PS0016
Baseline and the observed and change from PS0016 Baseline results by scheduled visit for 
PS0018. Figures for selected variables will also be generated in order to demonstrate the kinetics 
of response over time. Missing data will be handled by using multiple imputation (MI) via the 
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Markov-Chain Monte Carlo (MCMC) method. Supportive summaries will be based on observed 
case data.
In addition to the summaries described above, the impact of dose adjustment on efficacy will be 
considered. This will be done primarily by summarizing efficacy variables by the 3 adjuster 
groups as defined in Section 14.2.2. Furthermore, a supportive analysis specifically for single 
adjusters will be performed in which PASI score will be summarized by visit, where Baseline is 
recalibrated for each individual subject and defined as the visit where the bimekizumab 
320mg Q4W dose is initiated. The visits summarized will be in weeks relative to when the 
320mg Q4W dose was started as opposed to the scheduled week of the PS0018 assessment.
These summaries will be based on observed data only.
14.6
Planned interim analysis and data monitoring
A DMC will review the safety data on a recurring basis as outlined in the DMC charter.
14.7
Determination of sample size
Up to 45 subjects are anticipated to enroll in PS0018. This number is based on the fact that 
45 subjects are planned to be randomized in the feeder study, PS0016. The calculations to reach 
that sample size are outlined in the PS0016 protocol. As the primary objective of this study is to 
assess the long-term safety and tolerability of bimekizumab 160mg Q4W, the number of subjects 
anticipated is based on the number of subjects completing PS0016 and meeting eligibility 
requirements for PS0018.
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.
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.
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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 
information and medical emergency contact information. The Investigator will instruct the 
subject to keep the card with him/her at all times.
15.3
IRBs and IECs
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.
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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 
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 
European dermatology clinics. J Eur Acad Dermatol Venereol. 2010;24:548-54.
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.
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
Dauden E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or 
paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol 
Venereol. 2009;23(12):1374-82.
Dowlatshahi EA, Wakkee M, Arends LR, Nijsten T. The prevalence and odds of depressive 
symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. 
J Invest Dermatol. 2014;134:1542-51.
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Feldman SR. A quantitative definition of severe psoriasis for use in clinical trials. J Dermatolog 
Treat. 2004;15(1):27-9.
Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial 
infarction in patients with psoriasis. JAMA. 2006;296:1735-41.
Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S, Peserico A, et al. Prevalence of 
metabolic syndrome in patients with psoriasis: a hospital-based case-control study. 
Br J Dermatol. 2007;157:68-73.
Gottlieb AB. Psoriasis: Emerging therapeutic strategies. Nat Rev Drug Discov. 2005;4:19-34.
Icen M, Crowson CS, McEvoy MT, Dann FJ, Gabriel SE, Maradit Kremers H. Trends in 
incidence of adult-onset psoriasis over three decades: a population-based study. 
J Am Acad Dermatol. 2009;60:394-401.
Krueger G, Ellis CN. Psoriasis–recent advances in understanding its pathogenesis and treatment. 
J Am Acad Dermatol. 2005;53(1 Suppl 1):S94-100.
Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T. The impact of psoriasis on 
quality of Life. Results of a 1998 National Psoriasis Foundation patient-membership survey. 
Arch Dermatol. 2001;137:280-4. 
Kurd SK, Smith N, VanVoorhees A, Troxel AB, Badmaev V, Seykora JT, et al. Oral curcumin 
in the treatment of moderate to severe psoriasis vulgaris: a prospective clinical trial. J Am Acad 
Dermatol. 2008;58:625-31.
Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US 
adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009;60:218-24.
Langley RG, Krueger GG, Griffiths CEM. Psoriasis: epidemiology, clinical features, and quality 
of life. Ann Rheum Dis. 2005;64(Suppl II):ii18–ii23.
Langley RG, Feldman SR, Han C, Schenkel B, Szapary P, Hsu MC, et al. Ustekinumab 
significantly improves symptoms of anxiety, depression, and skin-related quality of life in 
patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, 
placebo-controlled phase III trial. J Am Acad Dermatol. 2010;63(3):457-65.
Mukhtar R, Choi J, Koo JY. Quality of life issues in psoriasis. Dermatol Clin. 2004;22:389-95. 
Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Model JG. Feasibility and 
validation of a computer-automated Columbia-Suicide Severity Rating Scale using Interactive 
Voice Response Technology. J Psychiatric Res. 2010;44:1224-1228.
Ortonne JP. Redefining clinical response in psoriasis: targeting the pathological basis of disease. 
J Drugs Dermatol. 2004;3:13-20.
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Identification and Management of Psoriasis 
and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: A 
systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377–385.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-
Suicide Severity Rating Scale: Initial validity and internal consistency findings from three 
multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266-1277.
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Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United 
States. J Am Acad Dermatol. 2014;70:512-6. 
Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset 
psoriasis. Pediatric Dermatology. 2000;17(3):174–178.
Snaith RP, Zigmond AS. The Hospital Anxiety and Depression Scale Manual. NFER: Nelson, 
Windsor; 1994.
Ulm K. A simple method to calculate the confidence interval of a standardized mortality ratio. 
Am J Epidemiol. 1990;131(2):373-375.
Yeung H, Takeshita J, Mehta NN, Kimmel SE, Ogdie A, Margolis DJ, et al. Psoriasis severity 
and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 
2013;149:1173-9.
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18
APPENDICES
18.1
Protocol Amendment 1
Rationale for the amendment
The purpose of this amendment is to revise the following: 

Serious adverse event reporting contact information included the wrong fax number for 
Canada and this was corrected

The PtGADA assessment was removed from the protocol, as this assessment is not relevant 
for the study population of patients with psoriasis
Specific changes
Change #1 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 
Has been changed to
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA and Canada: +1 800 880 6949
or +1 866 890 3175
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com 
Change #2 List of Abbreviations
The table row with PtGADA and its definition was deleted
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Change #3 Section 1 Summary
Original text:
Pharmacokinetic variables are plasma concentrations of bimekizumab. The immunological 
variable is anti-bimekizumab antibody levels prior to and following study treatment. The 
efficacy assessments are PASI, Investigator’s Global Assessment (IGA), body surface area 
(BSA) affected by psoriasis, Patient’s Global Assessment of Disease Activity (PtGADA), and 
the Hospital Anxiety and Depression Scale (HADS); a detailed list of efficacy variables is 
presented in Section 4.4.
Has been changed to: 
Pharmacokinetic variables are plasma concentrations of bimekizumab. The immunological 
variable is anti-bimekizumab antibody levels prior to and following study treatment. The 
efficacy assessments are PASI, Investigator’s Global Assessment (IGA), body surface area 
(BSA) affected by psoriasis, Patient’s Global Assessment of Disease Activity (PtGADA), and 
the Hospital Anxiety and Depression Scale (HADS); a detailed list of efficacy variables is 
presented in Section 4.4.
Change #4 Section 4.4 Efficacy variables
The variable “Change from Baseline in the PtGADA for the arthritis visual analog scale (VAS)” 
was deleted.
Change #5 Table 5-1 Schedule of study assessments
The table row for the PtGADA assessment was deleted. 
The footnote with PtGADA abbreviation definition was deleted.
Change #6 Section 8.1 Baseline Visit
PtGADA assessment was deleted.
Change #7 Section 8.4 Week 12 (±3 days)
PtGADA assessment was deleted.
Change #8 Section 8.6 Week 24 (±3 days)
PtGADA assessment was deleted.
Change #9 Section 8.7 Week 36 (±3 days)
PtGADA assessment was deleted.
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Change #10 Section 8.8 Week 48 (±3 days)
PtGADA assessment was deleted.
Change #11 Section 12 Assessment of Efficacy
The subsection discussing the PtGADA (Section 12.4 PtGADA for the arthritis VAS) was 
deleted.
Change #12 Section 14.5 Planned efficacy analyses
Original text:
Continuous efficacy variables based on the change from Baseline (PASI, BSA, PtGADA, and 
HADS) will be summarized using descriptive statistics by scheduled visit and PS0016 
randomized treatment group and overall.
Has been changed to:
Continuous efficacy variables based on the change from Baseline (PASI, BSA, PtGADA, and 
HADS) will be summarized using descriptive statistics by scheduled visit and PS0016 
randomized treatment group and overall.
18.2
Protocol Amendment 2
Rationale for the amendment
The purpose of this amendment is the following:

Revise the timepoints for the blood sample for anti-bimekizumab antibodies assessment and 
blood sample for bimekizumab plasma concentrations assessment

Specify the study stopping rules
Specific changes
Change #1
Table 5-1 Schedule of study assessments
For the Blood sample for bimekizumab plasma concentrations assessment, the “X” in the Wk 24 
column and the “X” in the Wk 32 column were deleted. An “X” was added to the Wk 28 
column.
Change #2
Table 5-1 Schedule of study assessments
For the Blood sample for anti-bimekizumab antibodies assessment, the “X” in the Wk 24 column 
and the “X” in the Wk 32 column were deleted. An “X” was added to the Wk 28 column.
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Change #3
Section 6.4 Study stopping rules was added
6.4
Study stopping rules
During the study, planned dosing and procedures may be discontinued or suspended for all 
subjects in any part of the study and appropriate follow up procedures established. Where it is 
possible to do so without threatening the safety of subjects, such discontinuation/suspension 
should be discussed with the UCB Study Physician prior to its implementation.
Possible reasons for discontinuation or suspension of the study include (but are not limited to):

A pattern of AEs occurs that contraindicates the further dosing of enrolled / additional 
subjects, including (but not limited to):

More than 1 subject meets any individual Withdrawal Criteria 6, 9, 10, 11 or 12 (as 
provided in Section 6.3), regardless of whether they met the same or different criteria.

Once a second subject meets any of those criteria, referral to the DMC may not be 
delayed while awaiting the outcome of either case.
If the above criteria are reached, the DMC will meet as soon as possible to determine 
whether discontinuation or suspension of the study should occur, and to determine what 
investigations, analyses, procedural amendments, or other actions should occur, before 
making any recommendation regarding the possibility of recommencing the study.  Further 
details on the role of the DMC are provided in Section 9.8.7. 

If the Sponsor or its designees judges it necessary for medical, safety, regulatory, or any 
other reasons consistent with applicable laws, regulations, and GCP.
Change #4
The section heading
8.2
Week 4 (±3 days)
was changed to 
8.2
Week 4 (±3 days); and Week 28 (±3 days)
Change #5
The section heading
8.3
Week 8 (±3 days); Week 16 (±3 days); Week 32 (±3 days); and Week 40 
(±3 days)
was changed to 
8.3
Week 8 (±3 days); Week 16 (±3 days); and Week 40 (±3 days)
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Change #6
The section heading
8.5
Week 20 (±3 days); Week 28 (±3 days); and Week 44 (±3 days)
was changed to
8.5
Week 20 (±3 days); and Week 44 (±3 days)
Change #7
Section 8.6 Week 24 (±3 days)
The following procedures or assessments will be performed prior to administration of study drug
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine samples for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
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was changed to
The following procedures or assessments will be performed prior to administration of study drug 
(if applicable):

Vital signs (blood pressure, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

PASI

IGA

BSA

HADS

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine samples for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
Change #8
Section 8.7 Week 32 (±3 days) was added:
8.7
Week 32 (±3 days)
All procedures or assessments will be performed prior to administration of study drug (if 
applicable), unless otherwise noted. The following procedures or assessments will be performed:

Vital signs (blood pressure, pulse rate, and temperature)

C-SSRS

PASI

IGA
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
BSA

Obtain blood samples for:

Standard safety laboratory tests (hematology and biochemistry)

Obtain urine sample for: 

Standard safety laboratory tests (urinalysis)

Urine pregnancy test for women of childbearing potential

Concomitant medications

Record AEs

Contact the IXRS

Study medication administration (after all other visit assessments are completed)
18.3
Protocol Amendment 3
Rationale for the amendment
The purpose of this amendment is to revise the withdrawal criteria to provide instructions for the 
management of subjects with newly diagnosed IBD or with IBD flares during the study. In 
addition, the study contact information was updated.
Modifications and changes
Specific changes
Change #1
Sponsor Study Physician
Name:
 MD, PhD, PharmMed
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Was Changed to:
Name:
, MD
Address:
UCB, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Change #2
Clinical Trial Biostatistician
Name:
Address:
UCB Biosciences, 8010 Arco Corporation Drive, Raleigh, NC 
27617
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Phone:
Fax:
Was changed to:
Name:
Address:
UCB Biosciences, 8010 Arco Corporation Drive, Raleigh, NC 
27617
Phone:
Fax:
Change #3
List of Abbreviations
Inflammatory Bowel Disease (IBD) was added to the list  
Change #4
Section 6.3 Withdrawal criteria
The following was added to the withdrawal criteria:
14. Subjects with newly diagnosed Inflammatory Bowel Disease (IBD) or with IBD flares during 
the study must:

Be referred, as appropriate, to a healthcare professional treating IBD, such as a 
gastroenterologist

Discontinue the IMP and be followed-up until resolution of active IBD symptoms
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact 
the Medical Monitor and UCB study physician to confirm the subject's suitability for 
continued participation in the study.
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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
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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.
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ELECTRONIC SIGNATURES 
 
Signed by 
Meaning of Signature 
Server Approval Date 
(dd-mon-yyyy 
(HH:mm)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PS0018 Protocol Amendment 3 - Phase 2, open-label extension
Clinical Approval
26-Feb-2018 23:02 GMT+01
Clinical Approval
27-Feb-2018 09:06 GMT+01
Clinical Approval
27-Feb-2018 13:33 GMT+01
Clinical Approval
01-Mar-2018 10:00 GMT+01
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SAP_001.pdf: 
UCB 
 
29 October 2018 
Statistical Analysis Plan 
Bimekizumab 
PS0018 
 
 
 
Confidential 
Page 1 of 57 
STATISTICAL ANALYSIS PLAN AMENDMENT 1 
Study: PS0018 
Product: Bimekizumab (UCB4940) 
A MULTICENTER, 48-WEEK, OPEN-LABEL EXTENSION STUDY TO ASSESS THE 
LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF BIMEKIZUMAB IN 
ADULT SUBJECTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS 
PHASE 2 
SAP/Amendment Number Date 
Final SAP 
14 September 2017 
SAP Amendment 1 
29 October 2018 
Confidentiality Statement 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, reproduced, 
published, or otherwise used without the express permission of UCB. 
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Statistical Analysis Plan 
Bimekizumab 
PS0018 
 
 
 
Confidential 
Page 2 of 57 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 6 
1 
INTRODUCTION ............................................................................................................. 9 
2 
PROTOCOL SUMMARY ................................................................................................. 9 
2.1 
Study objectives ............................................................................................................. 9 
2.1.1 
Primary objective ................................................................................................... 9 
2.1.2 
Secondary objectives ............................................................................................. 9 
2.2 
Study variables ............................................................................................................. 10 
2.2.1 
Safety variables .................................................................................................... 10 
2.2.1.1 
Primary safety variable .............................................................................. 10 
2.2.1.2 
Secondary safety variables ........................................................................ 10 
2.2.2 
Pharmacokinetic variables ................................................................................... 10 
2.2.3 
Immunogenicity variable ..................................................................................... 10 
2.2.4 
Efficacy variable .................................................................................................. 10 
2.3 
Study design and conduct ............................................................................................ 11 
2.4 
Determination of sample size ....................................................................................... 11 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 11 
3.1 
General presentation of summaries and analyses ........................................................ 11 
3.2 
General study level definitions .................................................................................... 13 
3.2.1 
Analysis time points ............................................................................................ 13 
3.2.1.1 
Relative day ............................................................................................... 13 
3.2.1.2 
Study periods ............................................................................................. 13 
3.2.2 
Daylight saving dates ........................................................................................... 13 
3.3 
Definition of Baseline values ....................................................................................... 13 
3.4 
Protocol deviations....................................................................................................... 14 
3.5 
Analysis sets................................................................................................................. 15 
3.5.1 
Enrolled Set ......................................................................................................... 15 
3.5.2 
Safety Set ............................................................................................................. 15 
3.5.3 
Full Analysis Set .................................................................................................. 15 
3.5.4 
Pharmacokinetic-Per Protocol Set ....................................................................... 15 
3.6 
Treatment assignment and treatment groups ............................................................... 15 
3.7 
Center pooling strategy ................................................................................................ 18 
3.8 
Coding dictionaries ...................................................................................................... 18 
3.9 
Changes to protocol-defined analyses ......................................................................... 18 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 18 
4.1 
Adjustments for covariates .......................................................................................... 18 
4.2 
Handling of dropouts or missing data .......................................................................... 18 
4.2.1 
Efficacy data ........................................................................................................ 19 
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4.2.1.1 
Psoriasis Area and Severity Index ............................................................. 19 
4.2.1.2 
Body surface area ...................................................................................... 19 
4.2.1.3 
Investigator’s Global Assessment ............................................................. 19 
4.2.1.4 
Hospital Anxiety and Depression Scale .................................................... 19 
4.2.2 
Safety laboratory data .......................................................................................... 19 
4.2.3 
Bimekizumab concentration data......................................................................... 19 
4.2.4 
Dates and times .................................................................................................... 19 
4.3 
Handling of repeated and unscheduled measurements ................................................ 21 
4.4 
Handling of measurements obtained at the withdrawal visit ....................................... 21 
4.5 
Interim analyses and data monitoring .......................................................................... 22 
4.6 
Multicenter studies ....................................................................................................... 23 
4.7 
Multiple comparisons/multiplicity ............................................................................... 23 
4.8 
Use of an efficacy subset of subjects ........................................................................... 23 
4.9 
Active-control studies intended to show equivalence .................................................. 23 
4.10 
Examination of subgroups ........................................................................................... 23 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 23 
5.1 
Subject disposition ....................................................................................................... 23 
5.2 
Protocol deviations....................................................................................................... 24 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 24 
6.1 
Derivation of variables ................................................................................................. 24 
6.1.1 
Calculation of body mass index ........................................................................... 24 
6.1.2 
Classification of age categories ........................................................................... 25 
6.2 
Demographics .............................................................................................................. 25 
6.3 
Other Baseline characteristics ...................................................................................... 25 
6.4 
Medical history and concomitant diseases ................................................................... 26 
6.5 
Prior and concomitant medications .............................................................................. 26 
6.5.1 
Prior medication definition .................................................................................. 26 
6.5.2 
Concomitant medication definition ..................................................................... 26 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 26 
8 
EFFICACY ANALYSES ................................................................................................ 27 
8.1 
Derivations of efficacy variables ................................................................................. 27 
8.1.1 
Psoriasis Area and Severity Index ....................................................................... 27 
8.1.2 
Investigator’s Global Assessment Response ....................................................... 28 
8.1.3 
Hospital Anxiety and Depression Scale .............................................................. 29 
8.2 
Statistical analysis of the primary efficacy variables ................................................... 30 
8.2.1 
Psoriasis Area and Severity Index ....................................................................... 30 
8.2.2 
Change in body surface area affected by psoriasis .............................................. 31 
8.2.4 
Hospital Anxiety and Depression Scale .............................................................. 32 
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9 
PHARMACOKINETICS ................................................................................................. 33 
10 IMMUNOLOGY ............................................................................................................. 33 
11 SAFETY ANALYSES ..................................................................................................... 35 
11.1 
Extent of exposure ....................................................................................................... 35 
11.1.1 
Drug administration ............................................................................................. 35 
11.1.2 
Subject time at risk .............................................................................................. 35 
11.2 
Adverse events ............................................................................................................. 36 
11.2.1 
Definitions and classification of adverse events .................................................. 36 
11.2.2 
Calculation of exposure adjusted incidence and event rates................................ 37 
11.2.3 
Presentation of adverse events ............................................................................. 38 
11.3 
Clinical laboratory evaluations .................................................................................... 40 
11.4 
Vital signs, physical findings, and other observations related to safety ...................... 41 
11.4.1 
Vital signs ............................................................................................................ 41 
11.4.2 
Body weight ......................................................................................................... 42 
11.4.3 
12-Lead Electrocardiograms ................................................................................ 42 
11.4.4 
Other safety variables .......................................................................................... 43 
11.4.4.1 
Physical examination ................................................................................. 43 
11.4.4.3 
Columbia-Suicide Severity Rating Scale .................................................. 43 
12 OTHER ANALYSES ...................................................................................................... 43 
13 REFERENCES ................................................................................................................ 44 
14 APPENDICES ................................................................................................................. 45 
14.1 
Classification of markedly abnormal laboratory values based on CTCAE grades ...... 45 
14.2 
Treatment-emergent abnormal liver values ................................................................. 46 
14.3 
Adverse events of special monitoring .......................................................................... 47 
14.3.1 
Major cardiovascular events ................................................................................ 47 
14.3.2 
Serious infections, including opportunistic infections and tuberculosis ............. 47 
14.3.2.1 
Serious infections ...................................................................................... 47 
14.3.3 
Malignancies including lymphoma ...................................................................... 48 
14.3.5 
Neuropsychiatric events ....................................................................................... 49 
14.3.6 
Inflammatory bowel disease ................................................................................ 49 
14.3.7 
Anaphylactic reaction .......................................................................................... 49 
14.3.7.1 
Anaphylactic reaction algorithm ............................................................... 50 
14.3.8 
Hepatic events and drug-induced liver injury ...................................................... 53 
14.4 
Treatment-emergent markedly abnormal vital signs values ........................................ 53 
15 AMENDMENTS TO THE SAP ...................................................................................... 55 
15.1 
Amendment 1 ............................................................................................................... 55 
15.1.1 
Rationale for the amendment ............................................................................... 55 
15.1.2 
List of changes ..................................................................................................... 55 
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Bimekizumab 
PS0018 
 
 
 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 57 
LIST OF TABLES 
Table 3‒1: 
Definition of Baseline ...................................................................................... 14 
Table 3‒1: 
Treatment group assignment for the TFLs....................................................... 17 
Table 4‒1: 
Calculation rules for duration of adverse events .............................................. 20 
Table 8‒1: 
Body regions for calculation of percent BSA for PASI ................................... 27 
Table 8‒2: 
Investigator's Global Assessment .................................................................... 29 
Table 8‒3: 
Hospital Anxiety and Depression Scale ........................................................... 29 
Table 11‒1: 
Clinical laboratory measurements.................................................................... 40 
Table 14‒2: 
Criteria for markedly abnormal laboratory tests .............................................. 45 
Table 14‒3: 
Definition of treatment emergent liver function values ................................... 46 
Table 14‒4: 
TEMA/PCS criteria for vital signs ................................................................... 54 
 
 
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LIST OF ABBREVIATIONS 
ACP 
above cut point 
ADA 
anti-drug (bimekizumab) antibody 
AE(s) 
adverse event(s) 
AESM 
adverse events of special monitoring 
ALC 
absolute lymphocyte count 
ALP 
alkaline phosphatase 
ALQ 
above the limit of quantification 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
BCP 
below cut point 
BKZ 
bimekizumab 
BLQ 
below the limit of quantification 
BMI 
body mass index 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CIs 
confidence interval(s) 
CP 
confirmed positive 
CRP 
C-reactive protein 
CSR 
clinical study report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
DEM 
data evaluation meeting 
DMC 
Data Monitoring Committee 
EAER 
exposure adjusted event rate 
EAIR 
exposure adjusted incidence rate 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
ES 
Enrolled Set 
EudraCT 
European Union Drug Regulating Authorities 
Clinical Trials 
FAS 
Full Analysis Set 
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FSH 
follicle stimulating hormone 
geoCV 
geometric CV  
GGT 
gamma glutamyltransferase 
HADS 
Hospital Anxiety and Depression Scale 
HADS-A 
Hospital Anxiety and Depression Scale -Anxiety 
HADS-D 
Hospital Anxiety and Depression Scale -Depression 
HLT 
high level term 
IGA 
Investigator’s Global Assessment 
IMP 
investigational medicinal product 
LCL 
lower confidence limit 
LDH 
lactate dehydrogenase 
LLOQ 
lower limit of quantification  
LOCF 
last observation carried forward 
MCHC 
mean corpuscular hemoglobin concentration 
MCMC 
Markov Chain Monte Carlo 
MCV 
mean corpuscular volume 
MedDRA® 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
NCP 
not confirmed positive 
NRI 
non responder imputation 
PASI  
Psoriasis Area and Severity Index 
PBO 
placebo 
PCS 
potentially clinically significant 
PK 
pharmacokinetics 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
PT 
preferred term 
Q4W 
every four weeks 
QTcF 
QT corrected for heart rate using Fridericia’s 
formula 
RBC 
red blood cell 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
sc 
subcutaneous 
SD 
standard deviation 
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SFU 
Safety Follow-Up 
SIB 
suicidal ideation and behavior 
SMQ 
standard Medical Dictionary for Regulatory Activities query 
SOC 
system organ class 
SS 
Safety Set 
TB 
tuberculosis 
TEAE(s) 
treatment-emergent adverse event(s) 
TEMA 
treatment-emergent markedly abnormal 
TFLs 
tables, figures and listings 
ULN 
upper limit of normal 
WBC 
white blood cell 
WD 
withdrawal 
WHODD 
World Health Organization Drug Dictionary 
 
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Statistical Analysis Plan 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the required statistical analysis of study PS0018. It also defines the summary tables, 
figures and listings (TFLs) to be included in the final clinical study report (CSR) according to the 
protocol. 
This SAP is based on, and assumes familiarity, with the following documents: 
 Final protocol dated 01 August 2016 
 Protocol amendment 1 dated 06 September 2016 
 Protocol amendment 2 dated 23 September 2016 
 Protocol amendment 3 dated 16 February 2018 
Unless specified in the sections below, the study will be analyzed as described in the most recent 
version of the protocol. If a future protocol amendment necessitates a substantial change to the 
statistical analysis of the study data, this SAP will be amended accordingly. In addition, if 
analysis definitions have to be modified or updated prior to database lock, a SAP amendment 
will be required. If, after database lock, additional analyses are required to supplement the 
planned analyses described in this SAP, these changes will be described in the CSR together with 
the associated rationale. 
The content of this SAP is compatible with the International Council for Harmonisation /Food 
and Drug Administration E9 Guidance documents. 
UCB is the Sponsor and PAREXEL is the Contract Research Organization for this study. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective of the study is to assess the long term safety and tolerability of 
bimekizumab. 
2.1.2 
Secondary objectives 
Secondary objectives of the study are: 
 To assess the safety and tolerability of increasing the dose of bimekizumab from 160mg 
every four weeks (Q4W) to 320mg Q4W for subjects with an inadequate response at Week 
12 
 To assess pharmacokinetics (PK) of bimekizumab 
 To assess the immunogenicity of bimekizumab 
 To assess the efficacy of open label bimekizumab 160mg Q4W administered over 48 weeks 
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2.2 
Study variables 
2.2.1 
Safety variables 
2.2.1.1 
Primary safety variable 
The primary safety variable is the incidence of treatment emergent adverse events (TEAEs) 
adjusted by duration of subject exposure to treatment. 
2.2.1.2 
Secondary safety variables 
Change from Baseline variables will be defined relative to the Baseline measurement from 
PS0016. 
The other safety variables are: 
 Severity and frequency of TEAEs 
 Change from Baseline in clinical laboratory values (chemistry, hematology, and urinalysis) 
 Change from Baseline in vital signs 
 Change from Baseline in physical examination 
 Change from Baseline in 12 lead electrocardiogram (ECG) results 
2.2.2 
Pharmacokinetic variables 
The PK variables are: 
 Plasma concentrations of bimekizumab 
2.2.3 
Immunogenicity variable 
The immunological variable is anti-drug (bimekizumab) antibody (ADA) levels prior to and 
following study treatment. 
2.2.4 
Efficacy variable 
Change from Baseline variables will be defined relative to the Baseline measurement from 
PS0016. 
The efficacy variables are listed below and will be evaluated at all scheduled visits in accordance 
with the schedule of assessments in Table 5‒1 of the clinical study protocol. 
 Psoriasis Area and Severity Index (PASI)50, PASI75, PASI90, and PASI100 response 
 Investigator’s Global Assessment (IGA) response (Clear or Almost Clear with at least a 2 
category improvement from Baseline on a 5-point scale) 
 Absolute and percent change from Baseline in PASI score 
 Shift from Baseline in IGA score 
 Absolute and percent change from Baseline in the body surface area (BSA) affected by 
psoriasis 
 Change from Baseline in the Hospital Anxiety and Depression Scale (HADS) Anxiety 
(HADS-A) and Depression (HADS-D) scores 
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 Percentage of subjects with scores below 8 in HADS-A and HADS-D (subjects with normal 
scores) 
2.3 
Study design and conduct 
PS0018 is a multicenter, 48-week, open-label extension study to assess the long-term safety, 
tolerability, and efficacy of bimekizumab in eligible adult subjects with moderate to severe 
chronic plaque psoriasis who participated in PS0016. 
During the Open-Label Treatment Period, subjects will attend study visits at the site Q4W for 
study assessments and administration of bimekizumab by study site staff through Week 48. 
Following completion or Withdrawal (WD) from the 48-week Open-Label Treatment Period, 
subjects will return for a Safety Follow-Up (SFU) Visit 20 weeks after their last dose of 
bimekizumab. Subjects withdrawing early from the study will also undergo the WD assessments 
and will enter the SFU Visit. 
Bimekizumab will initially be administered at a dose of 160mg Q4W subcutaneously (sc) during 
the 48 week Open-Label Treatment Period. There will be an option to increase the dose to 
320mg Q4W at the discretion of the Investigator if the subject’s PASI reduction is ≥50% to 
<75% from the PS0016 Baseline at Week 12 or later in the PS0018 study. If the subject’s disease 
is adequately controlled on the 320mg Q4W dose, they may return to 160mg Q4W at the 
discretion of the Investigator. The decision to return to 160mg Q4W dosing should be based 
upon treatment response, tolerability, and Investigator discretion, with the aim to use the dosing 
regimen that achieves the optimal benefit-risk for each subject. If a subject does not achieve a 
PASI50 at Week 12 or later during the PS0018 study based on change from PS0016 Baseline 
then they will be withdrawn from the study. 
2.4 
Determination of sample size 
Up to 45 subjects are anticipated to enroll in PS0018. This number is based on the fact that 45 
subjects are planned to be randomized in the feeder study, PS0016. The calculations to reach that 
sample size are outlined in the PS0016 protocol. As the primary objective of the PS0018 study is 
to assess the long-term safety and tolerability of bimekizumab 160mg Q4W, the number of 
subjects anticipated is based on the number of subjects completing PS0016 and meeting 
eligibility requirements for PS0018. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical evaluation will be performed by PAREXEL. The datasets will follow the UCB 
analysis data model (ADaM) data specifications. 
All analyses will be performed using SAS version 9.3 or higher (SAS Institute, Cary, North 
Carolina, United States). 
Continuous variables will be summarized by PS0016 randomized treatment group, visit and 
timepoint (where applicable) including number of subjects (n), mean, standard deviation (SD), 
median, minimum, maximum and confidence intervals (CI) where stated in the SAP. Categorical 
variables will be summarized by PS0016 randomized treatment group, visit and timepoint (where 
applicable) with frequency counts and percentages. Coefficient of variation (CV), geometric 
mean and 95% CI for the geometric mean will also be presented in the descriptive statistics for 
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the PK concentration data. In all outputs the confidence limits will be restricted to the possible 
values that the variable can take. 
When reporting relative frequencies or other percentage values, the following rules apply: 
 For values where all subjects fulfill certain criteria, the percentage value will be displayed as 
100 
 For values where the absolute frequency is zero, there will be no percentage displayed at all 
 All other percentage displays will use 1 decimal place 
 Percentages displayed based on continuous data (eg percentage changes from baseline) will 
be displayed to 1 decimal place. Unless otherwise stated, the denominator for the percentages 
will be based on the number of subjects in the respective analysis. 
 When reporting descriptive statistics, the following rules will apply in general (with the 
exception of PK concentration data, for which additional rules are stated below): 
 n will be an integer 
 Mean (arithmetic and geometric), SD and median will use 1 decimal place more than the 
original data 
 CV will be reported as a percentage to 1 decimal place 
 Minimum and maximum will be reported using the same number of decimal places as the 
original value 
 If no subjects have data at a given timepoint, for example, then only n=0 will be presented. If 
n<3, then only the n, minimum and maximum will be presented. If n=3, then only n, median, 
minimum and maximum will be presented. The other descriptive statistics will be left blank 
When reporting individual values and descriptive statistics for PK concentration data, the 
following rules will apply with regard to rounding and precision: 
 Individual values for PK concentration data will be reported to the same level of precision as 
received from the bioanalytical laboratory 
 Descriptive statistics for PK concentration data will be reported to the same level of precision 
as the individual data for the minimum and maximum, and to 1 additional significant figure 
for the mean (arithmetic and geometric), median, SD and 95% CI for the geometric mean 
 Geometric CV (geoCV) will be reported as a percentage to 1 decimal place 
All tabulations will be presented by treatment group, visit and timepoint (where applicable). In 
the tabulations, the order the treatment groups will be displayed is detailed in Section 3.6. 
Data listings containing all documented data and all derived data will be generated.  Data listings 
will highlight the dose switching; all timepoints on or after the dose increases to 320mg Q4W 
will be flagged, up to the time point the dose switches back to 160mg Q4W. 
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3.2 
General study level definitions 
3.2.1 
Analysis time points 
3.2.1.1 
Relative day 
Relative day for an event will be derived with the date of the first sc injection of investigational 
medicinal product (IMP) in PS0018 as reference. 
Relative days for an event of measurement occurring before the date of first sc injection are 
calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦= 𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛 𝑖𝑛 𝑃𝑆0018 
[1] 
The relative day for an event or measurement occurring on or after the reference date to the date 
of the last injection is calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦= (𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒−𝐷𝑎𝑡𝑒 𝑜𝑓𝐹𝑖𝑟𝑠𝑡 𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛 𝑖𝑛 𝑃𝑆0018) + 1 
[2] 
For events or measurements occurring after the date of the last injection, relative day will be 
prefixed with ‘+’ in the data listings and will be calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦= 𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐼𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛 𝑖𝑛 𝑃𝑆0018 
[3] 
There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a subject data listing. In such cases, relative day should be presented as ‘-‘in the 
subject data listings. 
For AE listings only, relative day will, in addition, be calculated with respect to the first sc 
injection in PS0016. 
3.2.1.2 
Study periods 
For each subject, the study duration is estimated to be up to a maximum of 64 weeks: 
 Open-Label Treatment Period: 48 weeks 
 SFU Visit: 20 weeks after the last dose of study medication scheduled at Week 44 
The end of the study is defined as the date of the last visit of the last subject in the study. 
3.2.2 
Daylight saving dates 
Daylight saving dates will be considered in the calculation of the absolute scheduled and actual 
times and in the duration when this is based on times. Therefore, if any daylight saving change 
occurs during the study development, this will impact the description of the blood sample 
collections, the calculation of the PK parameters, and any AE duration in case the time is 
included in the calculation of the duration. 
3.3 
Definition of Baseline values 
Baseline is defined as the last available value prior to the first injection of study medication in 
the PS0016 study. 
All changes from Baseline refer to changes from PS0016 Baseline, unless stated otherwise. 
Scheduled or unscheduled measurements can be used as the Baseline value in either case. 
Measurement specific Baseline timepoints are presented in Table 3‒1. 
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Table 3‒1: 
Definition of Baseline 
 Category 
Measurement or analysis 
Definition of 
Baseline 
Safety 
Clinical laboratory values (chemistry, 
hematology, and urinalysis) 
Vital signs 
12-lead ECG results 
PS0016 Baseline Visit 
 or if missing the PS0016 Screening 
results. 
Safety 
C-SSRS 
The ‘Baseline’ version of the 
questionnaire will be completed at 
PS0016 Screening and the ‘Since Last 
Visit’ version will be completed at all 
subsequent visits. 
Efficacy 
PASI score 
IGA score 
BSA affected by psoriasis 
HADS  
PS0016 Baseline Visit 
or if missing the PS0016 Screening 
results 
Immunological  
ADA 
PS0016 Baseline 
ADA=anti-drug (bimekizumab) antibody; BSA=body surface area; C-SSRS = Columbia-Suicide Severity Rating 
Scale; ECG=electrocardiogram; HADS=Hospital Anxiety and Depression Scale; IGA=Investigator’s Global 
Assessment; PASI=Psoriasis Area and Severity Index. 
If a measurement is repeated at the defined Baseline and is obtained prior to receiving the first 
dose of study medication, then the last available measurement will be used as the Baseline value. 
The rollover visit from PS0016 will be the entry visit into PS0018. The day of first dose will be 
labelled as PS0018 Week 0 in the tabulations, and will be included in any change from PS0016 
Baseline summaries. 
3.4 
Protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the key safety, efficacy or PK outcomes for an 
individual subject. The criteria for identifying such protocol deviations will be defined within the 
protocol deviation specifications document which is part of the data cleaning plan. Important 
protocol deviations will include the following categories: 
 Inclusion criteria deviation 
 Exclusion criteria deviation 
 Withdrawal criteria deviation 
 Prohibited concomitant medication use 
 Incorrect treatment or dose 
 Treatment non-compliance 
 Procedural non-compliance 
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Important protocol deviations will be reviewed as part of the ongoing data cleaning process and 
data evaluation. 
After all data have been verified/coded/entered into the database, the final data evaluation 
meeting (DEM) will be performed. The purpose of this DEM will be to review all protocol 
deviations, define the analysis sets and check the quality of the data prior to database lock. The 
review will also help decide how to manage problems in the subjects’ data (eg missing values 
and withdrawals). 
After the pre-analysis review, resolution of all issues, and documentation of all decisions, the 
database will be locked. 
3.5 
Analysis sets 
3.5.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all subjects who have given informed consent for PS0018. 
This is equivalent to All Subjects Screened. 
3.5.2 
Safety Set 
The Safety Set (SS) will consist of all subjects who received at least 1 dose of the study 
medication in PS0018. 
Safety variables will be summarized on the SS. 
3.5.3 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all enrolled subjects who received at least 1 dose of 
the study medication and have a valid efficacy measurement for PASI at PS0018 Week 0. 
Efficacy variables will be summarized based on the FAS. 
3.5.4 
Pharmacokinetic-Per Protocol Set 
The Pharmacokinetic-Per Protocol Set (PK-PPS) will consist of all enrolled subjects who 
received at least one dose of the study medication, provide at least one quantifiable plasma 
concentration postdose in PS0018, and have no important protocol deviations that impact the 
pharmacokinetics. 
Pharmacokinetic and immunology variables will be summarized on the PK-PPS. 
3.6 
Treatment assignment and treatment groups 
Treatment assignment for the SS and PK-PPS will be according to the actual treatment received 
in PS0018, unless stated otherwise in Table 3‒1.  Analyses of efficacy data (based on the FAS) 
will be conducted according to the PS0016 randomized treatment group. 
Subjects receiving the incorrect treatment (for example due to a dosing error) at a particular visit 
will be excluded from the PK-PPS as this would be considered as an important protocol 
deviation. Subjects may be excluded from the analysis at a particular visit (or visits) only, 
following discussion at the DEM. 
Listings will be presented by subjects as randomized in PS0016. Summaries will be presented by 
treatment group and overall where applicable.  See Table 3‒1 for the treatment assignment of the 
3 different sets of treatment groups. 
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In the TFLs the treatment groups based on the PS0016 randomized treatment group will be 
displayed as follows, where BKZ refers to bimekizumab and PBO refers to placebo: 
 BKZ 320mg + PBO 
 BKZ 320mg 
 All Subjects 
In the TFLs the treatment groups based on the actual PS0018 treatment received (ie PS0018 dose 
at onset of event or measurement) will be displayed as follows: 
 BKZ 160mg Q4W 
 BKZ 320mg Q4W 
 All BKZ 
Lastly there will be the grouping based on dose adjustment in PS0018 defined as follows: 
 Nonadjusters – This group consists of subjects who do not experience a dose adjustment 
during the study. 
 Single adjusters – This group consists of subjects who experience just one dose adjustment 
during the study. Per the protocol, if just a single adjustment occurs, then that adjustment 
must go from bimekizumab 160mg Q4W to 320mg Q4W. 
 Multiple adjusters – This group consists of subjects who experience more than 1 dose 
adjustment during the study. This means that the subjects in this group dose adjust from 
bimekizumab 160mg Q4W to 320mg Q4W and then adjust back to 160mg Q4W (with 
further dose adjustments possible). 
For summary purposes, the single and multiple adjuster groupings will be combined.
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The treatment group labels and tabulation requirements for each data type are displayed in Table 3‒1  Error! Reference source not 
found.. 
Table 3‒1: 
Treatment group assignment for the TFLs 
 
PS0016 
randomized treatment group 
PS0018  
dose at onset 
Dose adjustment 
group 
TFL group 
BKZ 
320mg + 
PBO 
BKZ 320mg 
All 
Subjects 
BKZ 160mg 
Q4W 
BKZ 320mg 
Q4W 
All 
BKZ 
Non-
adjuster 
Adjuster 
Subject disposition 
X 
X 
X 
 
 
 
 
 
Protocol deviations 
X 
X 
X 
 
 
 
 
 
Demographics 
X 
X 
X 
 
 
 
 
 
Medical history 
X 
X 
X 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
 
 
 
 
 
Compliance 
X 
X 
X 
 
 
 
 
 
Exposure 
 
 
 
X 
X 
X 
 
 
AEs a 
X 
X 
X 
X 
X 
X 
X 
X 
Safety data (including 
vital signs, ECGs and 
laboratory tests) 
X 
X 
 
 
 
 
 
 
Efficacy (except PASI) 
X 
X 
X 
 
 
 
 
 
 PASI 
X 
X 
X 
 
 
 
X 
X 
Pharmacokinetic data 
X 
X 
 
 
 
 
 
 
ADA 
X 
X 
 
 
 
 
 
 
ADA= anti-bimekizumab drug antibody; AE=adverse events; ECG= electrocardiogram; IMP= investigational medicinal product; Q4W= every 
four weeks; TFL= tables, figures, and listings. 
a Select tables presenting TEAEs by PS0016 randomized treatment group and Dose adjustment group, as defined in Section 11.2.3. 
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3.7 
Center pooling strategy 
The data from different sites will be pooled for all analyses. There will be no stratification by site 
or country performed. 
3.8 
Coding dictionaries 
Adverse events (AEs) and medical history will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA®), Version 19.0. 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD [September 2015]). Medical procedures will not be coded 
3.9 
Changes to protocol-defined analyses 
Change from Baseline in physical examination is listed as a secondary safety variable, in 
Section 2.2.1.2. Only whether the physical examination was performed and the date it was 
performed is recorded on the CRF. Thus no summaries for the change from Baseline in physical 
examination will be provided.” 
For the continuous efficacy variables based on the change from Baseline (PASI, BSA, and 
HADS), imputation for missing values in the protocol is based on multiple imputation (MI) via 
the Markov Chain Monte Carlo (MCMC) method.  However, due to the smaller sample size in 
PS0018 this may cause problems in the algorithm.  For this reason and for consistency with the 
PS0016 SAP, imputation in PS0018 will instead be based on last observation carried forward 
(LOCF). 
For the dose adjustment groupings, the single and multiple dose adjuster groupings will be 
combined for summary purposes, unless stated otherwise. 
 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
There will be no adjustments for covariates. 
4.2 
Handling of dropouts or missing data 
If a subject does not achieve a PASI50 at Week 12 or later during the open-label treatment 
period then they will be withdrawn from the study, in order to provide the subjects with 
alternative therapy to treat the condition.  Therefore, in many cases, missing data due to study 
treatment discontinuation will occur.  For missing continuous data single imputation by means of 
LOCF will be applied.  
Missing data for the binary response variables will be imputed using non responder imputation 
(NRI), ie subjects with a missing score at a specific visit will be considered as non-responders 
for the summaries. This will include visits after the point of withdrawal. 
Supportive summaries will be based on observed case data and will be repeated for all analyses 
presented with imputation. 
Missing data will be handled as described in the sections below for efficacy, safety and PK 
results. No other imputations will be performed. 
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4.2.1 
Efficacy data 
4.2.1.1 
Psoriasis Area and Severity Index 
Missing data for the individual items of the PASI score will be imputed as described in 
Section 8.1.1 in order to calculate the PASI score at each visit.  
For the summaries of the observed, change and percentage change from PS0016 Baseline in 
PASI score, LOCF will be applied to address the issue of missing scores as described in 
Section 4.2. There will be no imputation of missing individual item scores in the summaries for 
the PASI; LOCF will apply to the overall PASI score only.  
Missing data for the binary response variables (PASI50, PASI75, PASI90 and PASI100) will be 
imputed using NRI for the summaries. This will include visits after the point of withdrawal.  
4.2.1.2 
Body surface area 
Missing body surface area (BSA) data will be handled using LOCF as described in Section 4.2. 
4.2.1.3 
Investigator’s Global Assessment 
There will be no imputation of missing individual data for the IGA score. For the responder 
analysis, missing data will be imputed using NRI, ie subjects with missing data at a specific visit 
will be considered as non-responders for the analysis. This will include visits after the point of 
withdrawal if applicable. 
4.2.1.4 
Hospital Anxiety and Depression Scale 
Missing data for the individual items of the HADS will be imputed as described in Section 8.1.3 
in order to calculate the HADS-A and HADS-D scores at each visit. Missing HADS-A and 
HADS-D domain scores will be handled using LOCF as described in Section 4.2. 
4.2.2 
Safety laboratory data 
Measurements below the limit of quantification (BLQ) will be imputed with half of the lower 
limit of quantification (LLOQ) for the purpose of calculating change from PS0016 Baseline and 
for descriptive statistics. Measurements above the limit of quantification (ALQ), if applicable, 
will be imputed to the upper quantification limit. 
These rules will be applied to all numeric safety laboratory data including clinical chemistry, 
hematology and urinalysis variables. 
4.2.3 
Bimekizumab concentration data 
Measurements that are BLQ will be imputed with LLOQ/2 for the purpose of calculating the 
geometric mean and its 95% CI, the geoCV, the arithmetic mean, and SD for summaries and 
figures. 
For the individual figures, any concentrations that are BLQ will be imputed with LLOQ/2.  
Additional rules for PK data summaries are provided in Section 9. 
4.2.4 
Dates and times 
Partial dates may be imputed for the following reasons: 
 Classification of AEs as treatment-emergent 
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 Classification of medications as prior or concomitant 
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the 
database.  
The following rules will be applied for partial start dates with respect to the first dosing in 
PS0018: 
 If only the month and year are specified and the month and year of first dosing is not the 
same as the month and year of the start date then use the 1st of the month. If time is missing 
this will be imputed as 00:00 h 
 If only the month and year are specified and the month and year of first dosing is the same as 
the month and year of the start date, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use the 1st of the month. If the 
imputed date is the date of first dosing then time will be imputed with the time of first dosing 
(ie event will be regarded as treatment-emergent) 
 If only the year is specified, and the year of dosing is not the same as the year of the start date 
then use January 01 of the year of the start date. If time is missing this will be imputed as 
00:00 h 
 If only the year is specified, and the year of dosing is the same as the year of the start date, 
then use the date of first dosing in the given year. If this results in an imputed start date that 
is after the specified end date, then use January 01 of the year of start date. If the imputed 
date is the date of first dosing then time will be imputed with the time of first dosing (ie event 
will be regarded as treatment-emergent) 
 If the start date is completely unknown, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use January 01 of the year of the 
end date. If the imputed date is the date of first dosing then time will be imputed as the start 
time of first dosing (ie event will be regarded as treatment-emergent) 
The following rules will be applied for partial stop dates: 
 If only the month and year are specified, then use the last day of the month 
 If only the year is specified, then use December 31 of the known year 
 If the stop date is completely unknown, do not impute the stop date 
Missing or partially missing date and/or times will be imputed as described in Table 4‒1 for the 
calculation of duration of each AE. Adverse event duration is computed in and reported in day 
and time format: xx d hh:mm. 
Table 4‒1: 
Calculation rules for duration of adverse events 
Data availability 
Onset 
date/time 
Outcome 
date/time 
Calculation rules 
Complete data 
D1/T1 
D2/T2 
Duration = [(D2 – D1)*24 + (T2 – T1)]/24 d 
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Table 4‒1: 
Calculation rules for duration of adverse events 
Data availability 
Onset 
date/time 
Outcome 
date/time 
Calculation rules 
End time missing 
D1/T1 
D2/-- 
End time is substituted by time 23:59h (=23.98 in 
decimal format) 
Duration = <[(D2 – D1)*24 + (23.98 – T1)]/24 d 
Start time missing 
D1/-- 
D2/T2 
Onset time is substituted by time 00:00h. Duration = 
<[(D2 – D1)*24 + T2]/24 d 
Start and end time 
missing 
D1/-- 
D2/-- 
Duration = <D2 – D1 + 1 
Start day and time 
missing 
--/-- 
D2/T2 
Duration = <[(D2 – D0)*24 + (T2 – T0)]/24 d For a 
subject in the SS, D0 and T0 are the date and time of 
first administration of PS0018 study medication and for 
PS0018 screen failures, duration will not be calculated. 
End day and time 
missing 
D1/T1 
--/-- 
If the stop date is missing, duration will not be 
calculated. 
Start and end date 
missing 
--/-- 
--/-- 
If the stop date is missing, duration will not be 
calculated. 
IMP=investigational medicinal product; SS=Safety Set. 
4.3 
Handling of repeated and unscheduled measurements 
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements: 
 For repeated or unscheduled measurements obtained prior to the first dose of study 
medication, the latest value (which may be scheduled or unscheduled) prior to the first dose 
will be used in the calculation of descriptive statistics at each visit; 
 For repeated or unscheduled measurements obtained at the designated Baseline visit, the 
latest value (which may be scheduled or unscheduled) will be defined as the Baseline 
provided that this occurred prior to the first dose of study medication; 
 For repeated or unscheduled measurements obtained at any timepoint after the first dose of 
study medication, the first value will be used in the calculation of changes from Baseline and 
for the descriptive statistics (ie in summaries by timepoint). Unscheduled and repeated 
measurements will not be included in the summaries by timepoint, for all timepoints after the 
first dose of study medication. 
4.4 
Handling of measurements obtained at the withdrawal visit 
Subjects who withdraw from the PS0018 study prematurely will be encouraged to return for the 
early WD visit and the SFU Visit, the latter at 20 weeks following the final dose of study 
medication. 
The following rules will apply with regard to the inclusion of the results obtained at the early 
WD visit in the descriptive summaries: 
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 Any efficacy, PK, immunological and safety measurements conducted at the early WD visit 
should be included in the summaries for the respective scheduled visit, if the early WD visit 
occurs at the time of the next scheduled visit (within the tolerance window specified in the 
protocol). For example, if the early WD visit occurs on Day 28, the results would be 
summarized together with the Week 4 results. 
 If the early WD visit does not correspond to the day of a scheduled visit, all assessments of 
the early WD visit should be mapped to the nearest scheduled visit, relative to the PS0018 
Week 0 visit date, following the last scheduled visit where assessments are available. 
 If the date of the early WD visit is equidistant between 2 scheduled visits at which no 
scheduled assessments were performed, the assessments from the early WD visit will be 
mapped to the earlier of these visits. 
 If an EW visit mapping results in data being mapped to a visit where the specific assessment 
is not actually collected per the protocol schedule of assessments, these data will not be 
included in the summary statistics and will be listed only. 
 The only exception to the above rule is for ADA (for both BKZ and CZP) assessments, in 
which all early withdrawal visit assessments will be assigned to the next scheduled visit at 
which ADA are assessed. The rationale for this is that ADA positivity is summarized over a 
given study period. As part of that summary, a table indicating the first visit at which ADA 
positivity is observed will be presented. In order to match the number of subjects who were 
ADA positive at specific visits with the overall positivity for the period, it is necessary to 
ensure that ADA positivity is attributed to a visit where ADA antibody assessments were 
performed. 
Assessments from the EW visit will be displayed as the mapped visit and will be flagged in the 
by-visit data listings. 
For example, vital sign assessments are performed at PS0018 Weeks 0, 4, 8, 12, 16, 20, 24, 28, 
32, 36, 40 and 44. If a subject discontinues on Day 37, and the previous vital sign assessment 
was done at Week 4 (Day 28), the nearest scheduled assessment (following the last visit at which 
assessments were available) would be Week 8 (Day 56). Therefore, the early WD visit 
assessment should be re-assigned to the Week 8 visit. 
However, if a subject discontinues at Day 37, and the previous vital sign assessment was done at 
PS0018 Week 0, the early WD visit assessments would be re-assigned to the Week 4 (Day 28) 
visit, which would be the nearest scheduled visit relative to the PS0018 Week 0 visit date. 
Different domains (eg vital signs, ECG, safety laboratory tests, PASI, IGA) from the same early 
WD visit may be re-assigned to different study visits depending on the study schedule of 
assessments, ie measurements obtained at the early WD visit can only be mapped to a scheduled 
visit at which the respective assessment was intended to be measured. Assessments from the 
early WD visit that are mapped to scheduled visits will be flagged in the data listings. 
 
4.5 
Interim analyses and data monitoring 
There will be no interim analysis. 
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An independent Data Monitoring Committee (DMC) will be convened to periodically review and 
monitor safety data and to advise UCB accordingly. A separate cardiovascular adjudication 
committee and neuropsychiatric adjudication committee will also review the relevant data for 
assessment of cardiovascular and potential suicide events respectively, and will provide 
additional advice to UCB. 
The detailed role, scope, responsibilities and complete procedures as well as the identity of the 
DMC members will be described in a separate DMC Charter. The details regarding the outputs to 
be produced and the analyses to be performed for the DMC review will be provided in a separate 
DMC SAP. 
A separate Charter will be written for each of the cardiovascular and neuropsychiatric 
adjudication committees. 
4.6 
Multicenter studies 
Individual center results will not be displayed. 
4.7 
Multiple comparisons/multiplicity 
Not applicable. 
4.8 
Use of an efficacy subset of subjects 
Not applicable. 
4.9 
Active-control studies intended to show equivalence 
Not applicable. 
4.10 
Examination of subgroups 
Not applicable. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The number and percentage of subjects who were enrolled into the PS0018 study, subjects who 
completed or prematurely discontinued the PS0018 study, as well as the reason for 
discontinuation will be presented by PS0016 randomized treatment group and for all subjects, 
based on the SS. Subjects withdrawn from the study due to not achieving PASI50 at week 12 or 
later will be presented in the summary under primary reason for discontinuation in the category 
‘Lack of efficacy’.  
The number and percentage of subjects who discontinued due to AEs will be separately 
summarized by PS0016 randomized treatment group for all subjects, based on the SS.  
The number and percentage of subjects included into each of the analysis sets will be 
summarized by PS0016 randomized treatment group and for all subjects based on the ES (all 
subjects screened). Percentages will be based on the SS for the purpose of this summary. 
Finally, screen failure reasons will be listed, including glossary and summarized, based on the 
ES.  
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A subject who completed the study is defined as a subject having completed the 48 weeks of 
Open-Label Treatment Period. 
In addition, the following listings will be presented by PS0016 randomized treatment group: 
 Subject disposition (all subjects screened [ES]) 
 Study discontinuation (SS) 
 Visit dates (SS) 
 Subject analysis sets (all subjects screened [ES]) 
The listing of subject disposition will include the date of informed consent, date and time of first 
and last dose of study medication in PS0018, date of premature termination (and primary reason) 
and date of final contact.  
The listing of study discontinuation will include the reason for discontinuation and the total days 
on study medication relative to first dose in PS0018. 
A summary of the dose adjustment grouping (nonadjuster, single adjuster, and multiple adjuster) 
will be presented by the FAS and SS, respectively.  
The number of days on PS0018 study medication will be calculated as follows: 
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝐷𝑎𝑦𝑠 𝑜𝑛 𝑆𝑡𝑢𝑑𝑦 𝑀𝑒𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐷𝑜𝑠𝑒 𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑−
𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒 𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑) +  1 
[4] 
5.2 
Protocol deviations 
Important protocol deviations will be identified and classified by the deviation types listed in the 
protocol deviation specification document. A listing of all important protocol deviations will be 
presented for all subjects by PS0016 randomized treatment group and will include the deviation 
type and description. The number and percentage of subjects with important protocol deviations 
will be summarized by PS0016 randomized treatment group and for all subjects for each 
deviation type, based on the SS. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Derivation of variables 
Demographic and baseline characteristics are based on data recorded at the PS0016 Baseline 
visit. 
6.1.1 
Calculation of body mass index 
The body mass index (BMI) in kg/m2 is calculated based on the height (in m) and the weight (in 
kg) using the following formula: 
𝐵𝑀𝐼= 𝑊𝑒𝑖𝑔ℎ𝑡/(𝐻𝑒𝑖𝑔ℎ𝑡)2 
[5] 
The BMI will be reported to 1 decimal place. 
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6.1.2 
Classification of age categories 
Age will be classified into categories based on requirements for European Union Drug 
Regulating Authorities Clinical Trials (EudraCT) and clinicaltrials.gov reporting. 
For the EudraCT reporting, the categories will include: 
 18 to <65 years 
 65 to <85 years 
 ≥85 years 
For the clinicaltrials.gov reporting, the categories will include: 
 ≤18 years 
 19 to <65 years 
 ≥65 years 
6.2 
Demographics 
A by-subject listing of Baseline demographic characteristics will be presented by PS0016 
randomized treatment group based on all subjects screened, ie ES. This will include the year of 
birth (if available), age (in years), sex, race, ethnicity, height (in cm), weight at PS0016 
Screening (in kg) and BMI for all subjects enrolled into PS0018. The age will be directly entered 
into the study database and will not be re-calculated for the statistical analysis. 
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by PS0016 randomized treatment group and for all subjects based on the SS. The 
summary of age will include descriptive statistics and categorical summaries, the latter based on 
requirements for EudraCT and clinicaltrials.gov reporting. 
The tabulation will be repeated for the FAS, only if the SS differs from the FAS. 
6.3 
Other Baseline characteristics 
The following Baseline characteristics will be presented in a by-subject listing for the SS: 
 *Percentage BSA involvement 
 *PASI total score 
 IGA score 
 *HADS-A and HADS-D scores 
Baseline for each variable (where applicable) is defined in Table 3‒1. 
The Baseline characteristics listed above will be summarized using descriptive statistics (for 
continuous variables only*). The IGA score will be summarized including the number and 
percentage of subjects with each specific IGA score.  
The tabulation will be presented by PS0016 randomized treatment group and for all subjects 
based on the FAS. 
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6.4 
Medical history and concomitant diseases 
Medical history not reported in PS0016 will be listed for the SS by PS0016 randomized 
treatment group. The reported term will be included in the listing as well as whether the 
condition is related to psoriasis (yes/no). A glossary of all medical history conditions will be 
presented for the SS including the system organ class (SOC), preferred term (PT) and reported 
term. 
Concomitant medical procedures performed during the study will be listed for the SS. 
6.5 
Prior and concomitant medications 
Prior and concomitant medications will be listed for the SS by PS0016 randomized treatment 
group and subject and summarized for the SS by WHODD Anatomical Main Group (Level 1), 
Pharmacological Subgroup (Level 3) and PT. Tabulations will be presented by PS0016 
randomized treatment group and for all subjects, with separate tabulations for prior (and 
concomitant categories. 
All tabulations will be sorted alphabetically by Level 1 term, alphabetical Level 3 term within 
Level 1 and decreasing frequency of PT in the ‘All Subjects’ column. 
A glossary of all prior and concomitant medications will be presented for the SS including the 
Anatomical Main Group (Level 1), Pharmacological Subgroup (Level 3), PT and reported term. 
6.5.1 
Prior medication definition 
Prior medications include any medications that started prior to the date of administration of the 
first dose of PS0018 study medication.  
6.5.2 
Concomitant medication definition 
Concomitant medications are medications taken on or after the start of PS0018 study medication 
and up to and including 28 days after last dose, ie during the Open-Label Treatment Period. 
Any medication that started prior to PS0018 dosing and continued after dosing will therefore be 
classified as both prior and concomitant. Such medications will therefore be counted in 
tabulations for both prior and concomitant categories.  
Any medications with missing dates and/or times will be handled as described in Section 4.2.4 in 
order to classify them as prior or concomitant. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
During the Open-Label treatment period of this study, study medication will be administered in 
the clinic and compliance will be determined at the visit by study personnel. 
Due to the method of administration of the treatments, compliance will be examined in terms of 
completed number of injections. One dose of 160 mg requires one injection, one dose adjustment 
of 320 mg requires two injections. A dose reduction from 320 mg back down to 160 mg is 
allowed. 
Treatment compliance will be calculated as: 
Overall compliance (%)   =   total number of completed injections     x 100 
 
 
 
 [6] 
 total number of expected injections    
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where the total number of expected injections is derived relative to when the subject finishes 
treatment.  If a subject discontinues early, then the number of expected completed injections is 
based on the date of early discontinuation relative to the dosing visits. The planned dose recorded 
at a given visit will indicate if one injection for bimekizumab 160 mg Q4W, or two injections for 
bimekizumab 320mg Q4W are expected to be given.  If a subject completes treatment with no 
dose adjustment, 12 injections are expected (one each at Weeks 0, 4, 8, 12, etc. through to Week 
44). 
The calculated overall compliance will be listed by PS0016 randomized treatment group and 
subject, and summarized by PS0016 randomized treatment group, based on the SS. The summary 
will include both descriptive statistics for overall compliance (n, mean, SD, median, minimum 
and maximum) and the number and percentage of subjects based on the following classifications: 
 Compliance ≤80.0% 
 Compliance >80.0% 
8 
EFFICACY ANALYSES 
All efficacy listings will be based on the FAS and be summarized based on this population. 
Changes and improvements from Baseline are relative to PS0016 Baseline. 
Supportive summaries based on observed case data will be included for all analysis based on 
imputations, see Section 4.2. 
8.1 
Derivations of efficacy variables 
8.1.1 
Psoriasis Area and Severity Index 
The PASI is the most commonly used assessment for grading the severity of psoriasis in clinical 
studies and quantifies the severity and extent of the disease and weighs these with the percentage 
of BSA involvement. The body is divided into four regions comprising the head (h), upper 
extremities (ue), trunk (t), and lower extremities (le). In each of these regions, the total surface 
area of involvement (A) is graded on a scale of 0 to 6 (0 for no involvement up to 6 for 90% - 
100% involvement). The body regions and associated BSA are presented in Table 8‒1. 
Table 8‒1: 
Body regions for calculation of percent BSA for PASI 
Body region 
Details of region 
BSA 
Area-of involvement of 
body region (A) a 
Head (h) 
Face, back of head 
10% 
0 to 6 
Upper limbs (ue) 
Left, right, upper lower, flexor surface, 
extensor surface 
20% 
0 to 6 
Trunk (t) 
Front, back, groin 
30% 
0 to 6 
Lower limbs (le) 
Left, right, upper lower, flexor surface, 
extensor surface, including buttocks 
40% 
0 to 6 
Total 
 
100% 
 
A=area of involvement score; 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. 
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Scoring of psoriatic plaques for the PASI is based on 3 criteria: redness (R), thickness (T), and 
scaliness (S). Severity is rated for each index (R, T, S) on a scale of 0 to 4 (0=none, 1=slight, 
2=moderate, 3=marked, and 4=very marked). 
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 
(R, T and S) for each region by the weighted area of involvement score (A) for that respective 
region, and then summing the 4 resulting quantities as follows: 
PASI = 0.1 × [(Rh + Th + Sh) × Ah] + 0.2 × [(Rue + Tue + Sue) × Aue 
+0.3[(Rt + Tt + St) × At] + 0.4 × [(Rle + Tle + Sle) × Ale] 
[7] 
The following rules will be applied in the calculation of the PASI score in case of missing data: 
 If 1 or 2 severity measurements are missing for a certain region (eg head), the average of the 
remaining measurements within that region will be utilized to substitute the missing values 
 If the area of affected skin and/or all severity measurements for 1 or 2 regions are missing, 
then the missing (R+T+S)×A for a region will be substituted by the average of the available 
(R+T+S)×A across the remaining regions 
 If the PASI assessment has more missing data than indicated above, at a given visit, then the 
PASI will be set to missing for that visit 
The highest potential PASI score is 72 for severe disease; the lowest score is 0 which indicates 
no psoriatic lesions are present. The PASI scores are considered as a continuous variable and will 
be calculated and presented to 1 decimal place in the listings. The percentage change in PASI 
score from PS0016 Baseline will be calculated as follows: 
𝑃𝑒𝑟𝑐𝑒𝑛𝑡𝑎𝑔𝑒 𝑐ℎ𝑎𝑛𝑔𝑒 𝑓𝑟𝑜𝑚 𝑃𝑆0016 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒= 
100 × [(𝑃𝑆0018 𝑃𝐴𝑆𝐼−𝑃𝑆0016 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑃𝐴𝑆𝐼)/PS0016 Baseline PASI] 
[8] 
Thus, for subjects with an improvement in the PASI score, the percentage will be negative. For 
subjects with a worsening in the PASI score, the percentage will be positive. 
A categorical response variable, such as PASI90, is defined to be equal to 1 if the percentage 
improvement from PS0016 Baseline in the PASI scores is 90% or greater and 0 if the percentage 
improvement from PS0016 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 
PS0016 Baseline in PASI score, respectively (and equal to 0 otherwise). 
If a subject does not achieve PASI50 at Week 12 or reverts below PASI50 later during the 
PS0018 study based on a change from PS0016 Baseline then they will be withdrawn from the 
study. 
8.1.2 
Investigator’s Global Assessment Response 
A static IGA for psoriasis will be used to assess disease severity in all subjects during the study. 
The Investigator will assess the severity of psoriasis using a 5-point scale Table 8‒2. 
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A clinical response with regard to the IGA is defined as Clear (0) or Almost Clear (1) with at 
least a 2 category improvement from PS0016 Baseline on a 5-point scale. 
Table 8‒2: 
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 
For the handling of missing data see Section 4.2.1.3. 
8.1.3 
Hospital Anxiety and Depression Scale 
The scores for each item range from 0 to 3, with higher scores indicating more severe anxiety or 
depression Table 8‒3. The total score for each domain ranges from 0 to 21. A score of <8 for a 
given domain is considered as normal. 
In case of missing individual data, the following rules will be applied: 
 If a maximum of 1 item is missing in a given domain, the missing item will be imputed with 
the mean score from the remaining completed items within the same domain 
 If more than 1 item is missing in a given domain, the domain subscore will not be calculated 
For the handling of missing domain data see Section 4.2.1.4. 
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8.2 
Statistical analysis of the primary efficacy variables 
In addition to the summaries described below, the impact of dose adjustment on efficacy will be 
considered. This will be done primarily by using descriptive statistics to summarize PASI score 
for each visit by PS0016 randomized treatment group and the dose adjustment categories as 
defined in Section 4.10 along with the All Subjects (ie All BKZ) group. This will be based on 
observed data only. 
8.2.1 
Psoriasis Area and Severity Index 
The individual scores for the PASI for each body region (redness, thickness and scaliness 
severity scores and area of involvement score [A]), and the derived total PASI score (from 0 to 
72) will be listed for each subject by PS0016 randomized treatment group and visit. The listing 
will include the change from PS0016 Baseline and percentage change from Baseline for the total 
score only. Subjects achieving a PASI50, PASI75, PASI90 and PASI100 response at each visit 
will be flagged in the listing. Missing data will not be imputed for the listings. 
Descriptive statistics (including 95% CI) will be presented by PS0016 randomized treatment 
group and overall and by Dose adjustment, and by visit for absolute values, changes from 
PS0016 Baseline and percentage change from PS0016 Baseline (based on the total PASI score 
only). For the purpose of the tabulations the lower and upper 95% confidence limits will be 
truncated as follows: 
 For the absolute values the lower 95% confidence limit will be truncated at 0 and the upper 
95% confidence limit will be truncated at 72 
 For the changes from Baseline the lower 95% confidence limit will be truncated at -72 and 
the upper 95% confidence limit will be truncated at +72 
 For the percentage change from Baseline the lower 95% confidence limit will be truncated at 
-100%, there will be no truncation of the upper 95% confidence limit 
The following figures will be presented: 
 Combined individual (spaghetti) plots displaying percentage change from Baseline in PASI 
score versus time (visit) by PS0016 randomized treatment group (all subjects will be overlaid 
on the same plot with separate plots for each PS0016 randomized treatment group) 
 Mean (with 95% CI) percentage change from Baseline in PASI score versus time (visit) by 
PS0016 randomized treatment group (both treatment groups will be overlaid on the same 
plot) 
All tabulations and both individual and mean figures will be presented using the FAS with 
imputation and observed cases. All listings will be presented using the SS. 
For subjects that discontinue the study, missing data will be imputed using LOCF as described in 
Section 4.2 for the tabulations and mean figures.  
Missing data will not be imputed for the individual figures. 
Furthermore, a supportive analysis specifically for adjusters will be performed in which PASI 
score will be summarized by visit, where Baseline is recalibrated for each individual subject and 
defined as the visit where the bimekizumab 320mg Q4W dose is initiated. The visits summarized 
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will be in weeks relative to when the bimekizumab 320mg Q4W dose was started as opposed to 
the scheduled week of the PS0018 assessment. These summaries will be based on observed data 
only. 
The PASI50, PASI75, PASI90, and PASI100 responses are based on at least 50%, 75%, 90%, 
and 100% improvement from Baseline in the PASI score. Thus, the following will apply: 
 If the percentage improvement is ≥50% then the subject is a PASI50 responder 
 If the percentage improvement is ≥75% then the subject is a PASI75 responder (and is a 
PASI50 responder also) 
 If the percentage improvement is ≥90% then the subject is a PASI90 responder (and is a 
PASI50 and PASI75 responder also) 
 If the percentage improvement is 100% then the subject is a PASI100 responder (and is a 
PASI50, PASI75 and PASI90 responder also) 
The number and percentage of subjects achieving a PASI50, PASI75, PASI90, and PASI100 
response will be tabulated by visit and overall and by PS0016 randomized treatment group and 
by Dose adjustment. The 95% CI for the percentage of responders will be calculated using a 
Wilson approximation and be included in the tabulation.  
In addition, the percentage of responders (including 95% CI) will be plotted at each PS0018 visit 
for each response variable. Separate plots will be presented for each of PASI50, PASI75, 
PASI90 and PASI100 with both treatment groups overlaid on the same plot. These plots will be 
presented by PS0016 randomized treatment and by Dose adjustment separately. 
For the purpose of the tabulation the lower and upper 95% confidence limits for the percentage 
of responders will be truncated at 0 and 100% respectively. 
Missing data will be imputed using NRI as described in Section 4.2.1.1. Subjects with missing 
data will be regarded as non-responders for the PASI50, PASI75, PASI90, and PASI100 
variables. 
The tabulation will also be repeated using observed cases for both treatment assignments that 
will include a category for missing data. Those who discontinue will be counted in the missing 
category for this tabulation where applicable. For this tabulation based on observed cases, the 
denominator for the percentage of responders and non-responders, will be the number of subjects 
with nonmissing data at the visit. 
8.2.2 
Change in body surface area affected by psoriasis 
The percentage BSA (0 to 100%) affected by psoriasis will be listed by PS0016 randomized 
treatment, by subject and visit including the percentage change from PS0016 Baseline. Missing 
data will not be imputed for the listing. 
Descriptive statistics will be presented by PS0016 randomized treatment group and overall, by 
visit for both absolute values and percentage changes from Baseline. 
Missing data for the tabulations will be imputed as described in Section 4.2.1.2. Tabulations 
(absolute values and percentage change from PS0016 Baseline) will be repeated using observed 
cases for both treatment assignments and will include the category missing. 
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8.2.3 
Investigator’s Global Assessment  
The results of the IGA will be listed by PS0016 randomized treatment group, subject and visit. A 
clinical response with regard to the IGA is defined as clear (0) or almost clear (1) with at least a 
2 category improvement from Baseline. Subjects achieving a clinical response will be flagged in 
the listing at relevant visit timepoints. Missing data will not be imputed for the listing. 
The number and percentage of subjects achieving an IGA response at each PS0018 visit will be 
summarized by PS0016 randomized treatment group and overall. The 95% CI for the percentage 
of responders will be included, calculated using a Wilson approximation. For the purpose of the 
tabulation the lower and upper 95% confidence limits for the percentage of responders will be 
truncated at 0 and 100% respectively. 
Missing data will be imputed using NRI as described in Section 4.2.1.3. The tabulation will also 
be repeated using observed cases for both treatment assignments and will include a category for 
missing data; those who discontinue will be counted in the missing category for this tabulation 
where applicable. For the tabulation based on observed cases, the denominator for the percentage 
of responders and non-responders, will be the number of subjects with nonmissing data at the 
visit.  
Shift tables will be presented for the IGA score, by PS0016 randomized treatment group and 
overall, at each PS0018 visit, compared to the PS0016 Baseline score. 
In addition, a frequency table will be presented showing the number and percentage of subjects 
with each specific IGA score at each visit by PS0016 randomized treatment group. Both 
tabulations will include a category for missing data. The denominator for the percentages will be 
the number of subjects in the FAS, for each PS0016 randomized treatment group. No imputation 
for missing values will be done for these analyses. 
8.2.4 
Hospital Anxiety and Depression Scale 
The HADS scores for anxiety HADS-A and depression HADS-D each range from 0 to 21with 
higher scores indicating worse state. A score below 8 is considered to be normal whereas a score 
of 15 and above is considered severe (Snaith and Zigmond, 1994). The individual items, 
associated item scores and calculation rules for the anxiety and depression domains are provided 
in Section 8.1.3. 
The results of the HADS will be listed by PS0016 randomized treatment group, subject and visit 
including the individual item responses and the derived domain scores for HADS-A and 
HADS-D. Changes from Baseline will be calculated based on the domain scores only, and will 
be included in the listing. A Glossary will also be included. 
Descriptive statistics will be presented by PS0016 randomized treatment group and overall, ,  by 
visit for both absolute values and changes from Baseline, separately for each domain HADS-A 
and HADS-D. Missing data will be imputed as defined in Section 4.2.1.3 and supportive 
summaries of observed cases will also be included for both treatment assignments. 
The number and percentage of subjects with scores categories <8, ≥8 to <11, ≥15 and missing for 
the HADS-A and HADS-D will be summarized by PS0016 randomized treatment group and 
overall at each visit based on observed cases. The percentages will be based on the number of 
available observations at each visit. 
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9 
PHARMACOKINETICS 
There will be no calculation of PK parameters for this study. The analysis of PK data for this 
study will focus on the concentrations of bimekizumab only. 
Individual blood sampling times and concentrations of bimekizumab will be listed by PS0016 
randomized treatment group for the SS and will include the actual sampling time in weeks 
relative to the first PS0018 dose. 
Individual concentrations will be summarized by PS0016 randomized treatment group at each 
scheduled visit based on the PK-PPS, using n, mean, median, SD, minimum, maximum, 
geometric mean, 95% CI for the geometric mean and geoCV (assuming log-normally distributed 
data). 
Individual concentration versus time (week) profiles will be presented graphically in linear and 
semi-logarithmic scale with all subjects overlaid on the same plot (spaghetti plots) and separate 
plots for each treatment group. Geometric mean profiles of bimekizumab will also be presented 
on both linear and semi-logarithmic scale respectively with and without the corresponding lower 
and upper limit of the 95% CI for linear and semi-logarithmic plots respectively.  Both treatment 
groups (PS0016 randomized treatment groups) will be overlaid on the same plot.  All figures will 
include the LLOQ on the semi logarithmic plots. 
The following rules will apply for PK data listings and summaries: 
 Values below the LLOQ will be reported as BLQ 
 Descriptive statistics of concentrations will be calculated if at most ⅓ of the individual data 
points are missing or are not quantifiable ie LLOQ. Values that are BLQ will be replaced by 
the numerical values of the LLOQ/2 in this instance. However, if n≤3 or more than ⅓ of the 
individual data points are missing or are not quantifiable, then only n, minimum and 
maximum will be presented. The other descriptive statistics will be left blank. 
 The 95% CI for the geometric mean should be left blank if the SD (or equivalently, the 
geoCV) is 0 
 The geoCV will be calculated using the following formula where SD is the standard 
deviation from the log-transformed data 
𝑔𝑒𝑜𝐶𝑉= [100 × √(𝑒𝑆𝐷2 −1)]  
[9] 
Additional rules for handling values that are BLQ are described in Section 4.2.3. 
10 
IMMUNOLOGY 
The results for the anti-drug (bimekizumab) antibody (ADA) measurements will be listed by 
PS0016 randomized treatment group and timepoint based on the SS, including the screening 
assay, confirmatory assay and titer (if applicable).  
A cut point will be determined by the bioanalytical laboratory that will be used to determine the 
status of ADA as above the cut point (ACP) or below the cut point (BCP). For any ADA levels 
that are ACP, a further confirmatory assay will be performed, the results of which will be 
determined as either ‘confirmed positive’ (CP) or ‘not confirmed positive’ (NCP). For samples 
that are CP, a further titer assay will be performed and the ADA titer will be reported. 
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The following definitions will be applied 2 ways: firstly including the PS0018 SFU visit, and 
then excluding the PS0018 SFU visit: 
 An ADA status of positive will be concluded for any subject with an ADA level that is ACP 
and CP at any timepoint (PS0016 Baseline, Week 4 and Week 8, and all PS0018 visits) 
 An ADA status of negative will be concluded for any subject with an ADA level that is either 
BCP or ACP and NCP at any timepoint (PS0016 Baseline, Week 4 and Week 8, and all 
PS0018 visits) 
 A subject will be classified as having ADA positivity at PS0016 Baseline if the PS0016 
Day 1, predose result is ACP and CP 
 A subject will be classified as having treatment-induced ADA positivity when meeting one 
of the following criteria: 
 The PS0016 Baseline result is either BCP or ACP and NCP, and at least one PS0018 
timepoint is ACP and CP 
 The PS0016 Baseline result is positive (ACP and CP) and at least one PS0018 
measurement shows a pre-defined fold increase in titer from the Baseline value (the fold 
increase from PS0016 Baseline required to meet this criteria will be defined with the 
development of the assay and will be included in the TFLs) 
 A subject will be classified as overall positive if at least one PS0018 measurement is ACP 
and CP (this includes subjects who have negative results at Baseline) 
 A subject will be classified as overall negative if at all PS0018 visits the ADA status is 
negative (this includes subjects who have positive [ACP and CP] results at Baseline) 
All listings, summaries and figures will include the PS0016 visits Baseline, Week 4 and Week 8 
and all PS0018 visits. 
The ADA status (positive/negative) will be summarized as a categorical endpoint (number and 
percentage of subjects) by PS0016 randomized treatment group for all timepoints and overall, 
based on the SS.  
In addition, the first occurrence of treatment-induced ADA positivity (based on the definitions 
above) will be summarized (number and percentage of subjects) by PS0016 randomized 
treatment group at the visits PS0016 Baseline and Week 4 and Week 8 of PS0016 and 
additionally at each PS0018 visit, based on the SS. This tabulation will count the number of 
subjects at each PS0018 visit who fulfill at least one of the above defined criteria for 
treatment-induced positivity; subjects will be counted in the numerator based on the earliest visit 
at which one of these criteria is fulfilled. At other visits, subjects will be counted in the 
denominator (assuming a measurement is available). For all tabulations, percentages will be 
based on the number of observations at each visit. 
A separate listing will be presented (based on the SS) showing the bimekizumab concentrations 
and ADA measurements in the same output in adjacent columns. The listing will include the 
bimekizumab concentration, ADA status (ACP or BCP) and confirmatory assay results if 
applicable (NCP or CP), together with the titer for results that are CP. In addition, the time since 
the previous administration of study medication will be reported (in days).  
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Finally, individual subject plots will be presented displaying the PASI total score, ADA titer and 
bimekizumab concentrations overlaid on the same figure. The figure will also show the timing 
and dose of each administration of bimekizumab received during the study. The ADA data will 
be plotted using a semi-logarithmic scale. 
The rules for handling values that are BLQ in the bimekizumab concentration data are described 
in Section 4.2.3. For the ADA data, any negative results for which there are no titers available at 
a specific visit will be substituted with 0.001 for the purpose of the figure. 
11 
SAFETY ANALYSES 
All analysis of safety variables will be performed using the SS, unless otherwise stated. Changes 
from Baseline for all safety variables are changes from PS0016 Baseline. 
11.1 
Extent of exposure 
11.1.1 
Drug administration 
All drug administration details (including date, time of injection, location, side of body and 
volume delivered) will be listed by subject and visit. The study medication will be given as 1 or 
2 sc injections depending on dose, at each planned dosing visit (PS0018 Week 0, Weeks 4, 8, 12, 
16, 20, 24, 28, 32, 40 and Week 44). 
The duration of exposure (in days) will be calculated as: 
Date of last dose in PS0018 −Date of first dose in PS0018 + 28                       [10] 
Should the date of the last dose plus 28 days equate to a date that is beyond the Week 48 visit 
date then the exposure will be calculated as: 
Week 48 visit date −Date of first dose in PS0018 + 1                                   [11] 
For subjects who have died the exposure will be as follows: 
Date of death −Date of first dose in PS0018 + 1                                     [12] 
For subjects who switched dose during PS0018, the duration of dose within each dose interval 
(except the last dose interval) will be calculated as: 
Date of last dose in PS0018 −Date of first dose in PS0018 + 1                       [13] 
The dose taken in the last dose interval will be calculated as: 
Date of last dose in PS0018 −Date of first dose in PS0018 + 28                       [14] 
In this case duration of exposure will be calculated as the sum of the dose intervals for 
bimekizumab 160mg Q4W and 320mg Q4W, respectively.  
Extent of exposure in PS0018 will be summarized using descriptive statistics and presented by 
bimekizumab 160mg Q4W, 320mg Q4W, respectively and All bimekizumab. 
11.1.2 
Subject time at risk 
The subject time at risk represents the time a subject was at risk for having an AE and will be 
used to calculate the exposure adjusted incidence rate (EAIR) and exposure adjusted event rate 
(EAER) as described in Section 11.2.2. 
The subject time at risk (days) will be calculated as follows: 
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𝑇𝑖𝑚𝑒 𝑎𝑡 𝑟𝑖𝑠𝑘= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝑃𝑆0018 𝐼𝑀𝑃−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝑃𝑆0018 𝐼𝑀𝑃) + 140 
[15] 
This includes the duration of the SFU Period. 
For subjects who switch dose during PS0018, time at risk will be derived in each dose interval 
and calculated as per equation [13] above, and equation [15] will be applied for the dose in the 
final dose interval. 
In cases where the last clinical contact or last visit occurs prior to completion of the SFU period, 
the subject time at risk is calculated as follows: 
𝑇𝑖𝑚𝑒 𝑎𝑡 𝑅𝑖𝑠𝑘= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐶𝑜𝑛𝑡𝑎𝑐𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝑃𝑆0018 𝐼𝑀𝑃) + 1 
[16] 
This will apply for the following: 
 For subjects that discontinue prematurely (ie, and no SFU data are available), the date of 
final contact refers to the date of the latest contact with the subject during the study PS0018 
after which no further information or data are available. This will be reported on the study 
termination page of the electronic Case Report Form (eCRF). 
 For subjects that have died during the study the date of last contact refers to the date of death 
The sum of these exposure days at risk across subjects in the relevant PS0018 dose group is 
converted to years for the EAIR and EAER calculations described in Section 11.2.2. 
Subject-years at risk is defined as the subject time (in days) at risk divided by 365.25. The days 
at risk and subject years at risk will be listed and summed by PS0018 dose at onset, together with 
the drug administration information (Section 11.1.1). 
11.2 
Adverse events 
11.2.1 
Definitions and classification of adverse events 
All AEs will be recorded in the CRF from informed consent until study completion or 
termination. 
Adverse events will be coded according to MedDRA® version 19.0. Treatment-emergent 
adverse events (TEAEs) will be defined as events that have a start date on or after the first 
administration of study treatment in PS0018 until the last received dose of study medication 
+140 days (which covers the 20-week SFU Period). Adverse events occurring after this date will 
not be classified as TEAEs and will therefore be excluded from the summary tables. TEAEs will 
be categorized according to the PS0018 dose at onset, ie, the last dose being received at the time 
of onset of the event. If a TEAE occurs on the same day as a change in dosage and it cannot be 
clearly established whether or not the TEAE started before or after dosing, because for example 
the time of the AE is missing, then the TEAE will be attributed to the treatment dose that the 
subject has just completed, unless the adverse event is related to the injection (ie higher level 
term (HLT) of “injection site reactions”) or an anaphylactic reaction (Section 14.3.7.1), in which 
case the TEAE will be assigned to the treatment dose administered on that day. Tables will 
include columns for BKZ 160mg Q4W, BKZ 320mg Q4W, and All BKZ. 
Any adverse events considered ongoing from PS0016 which do not worsen in severity during 
PS0018, or starting prior to first PS0018 dose will not be considered treatment emergent in 
PS0018 and will be tabulated separately. 
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In order to evaluate if there is any difference in the TEAE profile of subjects who have dose 
adjustments, additional summaries will be generated based on Dose adjustment described in 
Section 3.6 for select tables as given in Section 11.2.3. 
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent, 
unless there is clear evidence to suggest that the AE started prior to PS0018 dosing. Handling of 
missing dates/times for classification of AEs as TEAEs is described in Section 4.2.4. 
All AEs will be coded and categorized by intensity (mild/moderate/severe) and relationship to 
study medication (related/not related). 
In summaries including relationship to study medication, the following relationship categories 
will be included: 
 Related 
 Not related 
Subjects who experience the same event multiple times will be included in the most related 
category for tabulations by maximum relationship. Events with missing relationship will be 
considered as ‘Related’ for summary purposes but shown as missing in the data listings. 
In summaries including intensity, the following categories will be summarized: 
 Mild 
 Moderate 
 Severe 
Subjects who experience the same event multiple times will be included in the most severe 
category for tabulations by maximum intensity. Events with missing intensity will be considered 
as severe for summary purposes but shown as missing in the data listings.  
All AE data will be presented as recorded in the database for the listings. 
11.2.2 
Calculation of exposure adjusted incidence and event rates 
The EAIR is defined as the number of subjects (n) with a specific TEAE adjusted for the 
exposure and will be scaled to 100 subject years: 
𝐸𝐴𝐼𝑅= 100 ×
𝑛
∑
𝑇𝐸𝑥𝑝,𝑖
𝑁
𝑖=1
 
[17] 
In the above equation, N is the total number of subjects at risk (in each PS0018 dose group) and 
TExp,i is the time at risk for subject i, expressed in years. Subject time at risk represents the time 
a subject was at risk for having a TEAE calculated as follows: 
 For subjects experiencing the specific TEAE the time at risk (TExp,i) is calculated from the 
time of the first PS0018 dose to the onset of the TEAE. If a subject has multiple events, the 
time at risk is calculated relative to the first occurrence of the TEAE being considered. 
 For subjects who do not experience the specific TEAE the total time at risk (TExp,i) is 
calculated as described in Section 11.1.2. 
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Exact Poisson 95% CIs (lower confidence limit [LCL], upper confidence limit [UCL]) for the 
EAIR will be calculated using the relationship between the Poisson and the chi-square 
distribution (Ulm, 1990; Fay and Feuer, 1997): 
𝐿𝐶𝐿=
𝜒2𝑛,𝛼
2
2
2   , 𝑈𝐶𝐿=
𝜒2(𝑛+1),1−𝛼
2
2
2
   
[18] 
where n is the number of subjects with the specific TEAE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile. The LCL and 
UCL calculated above will be scaled to the number of subject years by dividing these by the total 
exposure at risk for each treatment group (∑
TExp, i
𝑁
𝑖=1
 ). 
The EAER is defined as the total number of TEAEs (including repeat occurrences in individual 
subjects) divided by the total time at risk scaled to 100 subject years: 
𝐸𝐴𝐸𝑅= 100 ×
𝑛𝐴𝐸 
∑
TRisk,i
𝑁
𝑖=1
 
[19] 
where nAE is the total number of TEAEs and TRisk,i is the time at risk for subject i, expressed in 
years (calculated as described in Section 11.1.2). 
No CIs will be computed for EAER. 
11.2.3 
Presentation of adverse events 
An overview of the number and percentage of subjects who experience TEAEs will be presented 
based on the SS. This tabulation will include the number and percentage of subjects with any 
TEAEs, serious TEAEs, related TEAEs, discontinuation due to TEAEs, severe TEAEs, AEs 
leading to death and TEAEs leading to death; event counts will also be included.  
 The tabulation will be presented by PS0018 dose at onset. 
 This tabulation will be repeated by Dose adjustment and PS0016 randomized treatment 
group.  
In addition, the following summaries will be presented by PS0018 dose at onset, SOC, high level 
term (HLT) and PT, based on the SS:  
 Incidence of TEAEs by PS0018 dose at onset, including the EAIR and EAER calculated as 
described in Section 11.2.2 for the ‘Any TEAE’ category only 
 Incidence of TEAEs by PS0018 dose at onset, including the EAIR and EAER calculated as 
described in Section 11.2.2 for the ‘Any TEAE’ category only by overall ADA status 
(positive/negative) 
 Incidence of TEAEs by Dose adjustment and PS0016 randomized treatment group 
 Incidence of serious TEAEs by PS0018 dose at onset and Dose adjustment 
 Incidence of TEAEs by relationship and PS0018 dose at onset  
 Incidence of TEAEs by maximum relationship and PS0018 dose at onset  
 Incidence of TEAEs by maximum intensity and PS0018 dose at onset  
 Incidence of fatal TEAEs by relationship and PS0018 dose at onset  
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 Incidence of serious TEAEs by relationship and PS0018 dose at onset  
 Incidence of non-serious TEAEs above threshold of 5% of subjects by PS0018 dose at onset  
 Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship and 
PS0018 dose at onset 
 Incidence of ongoing AEs from PS0016  
 Incidence of ongoing AEs from PS0016 which do not worsen in severity, or AEs started prior 
to PS0018 dose, by PS0016 randomized treatment group  
In addition, separate AE summaries by PS0018 dose at onset, SOC, HLT and PT will be 
included for the following AEs of special monitoring (AESM) further defined in Section 14.3. 
 Major cardiovascular events  
 Serious infections, including opportunistic infections and tuberculosis (TB) 
 Malignancies including lymphoma 
 Cytopenias 
 Neuropsychiatric events (in particular, depression and suicide) 
 Inflammatory bowel disease 
 Anaphylactic reaction (hypersensitivity and anaphylactic reactions) 
 Hepatic events and drug-induced liver injury  
All summary tables (including those for AESM) will contain the number and percentage of 
subjects and the number of events where applicable. A subject who has multiple events in the 
same SOC, HLT and PT will be counted only once in the subject counts but all events will be 
included. In addition, for all tabulations of AESM, the EAER and EAIR will be reported only for 
the categories ‘Any TEAE’. 
The criteria for identifying AESM and additional criteria for reporting AESM are provided in 
Section 14.3. 
Adverse event summaries will be ordered by alphabetical SOC, alphabetical HLT within SOC 
and decreasing frequency of PT in the ‘BKZ 320mg’ column for the PS0016 randomized 
treatment group. In the PS0018 dose at onset tables, the summaries will be presented in a similar 
manner in decreasing frequency of PT in the ‘All BKZ’ column.  
For tables including only number and percentage of subjects, summaries will be ordered by 
alphabetical SOC, alphabetical HLT within SOC and decreasing incidence of PT within HLT 
and SOC in the ‘All BKZ’ column. 
Any adverse events considered ongoing from PS0016 which do not worsen in severity during 
PS0018 dosing, or starting prior to first PS0018 dose will not be considered treatment emergent 
in PS0018 and will be tabulated separately.  
The AEs will be listed by PS0016 randomized treatment group and include all subjects screened 
in the ES. The listing will include the onset date/time and outcome date/time of the event 
(including relative days), the AE duration (derived), dose at onset, days since first dose of study 
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medication, days since most recent dose of study medication, pattern of event, intensity, 
relationship, action taken and outcome. In addition the listing will flag AEs that led to 
discontinuation, TEAEs, AESM, AEs of special interest (as reported on the eCRF) and SAEs. 
A glossary of all TEAE terms will be provided including the SOC, HLT, PT and reported term. 
11.3 
Clinical laboratory evaluations 
Laboratory data (clinical chemistry, hematology, and urinalysis) and changes from Baseline (if 
applicable) for numeric variables will be listed by PS0016 randomized treatment group and visit. 
Any laboratory variables with values that are BLQ or ALQ will be handled as described in 
Section 4.2.2 for calculation of changes from Baseline and for summary tables. Values outside 
the reference range for the numeric variables will be flagged in the listings. 
Clinical chemistry and hematology variables will be summarized by PS0016 randomized 
treatment group at each visit, for both absolute values and changes from PS0016 Baseline. 
Laboratory variables will be grouped according to the laboratory function panel and categorized 
as normal, high or low, if applicable, based on the reference range supplied by the analytical 
laboratory. For selected variables that are identified in Table 11‒1, the change in category from 
Baseline will be presented in shift tables at all PS0018 visits. 
The number and percentage of subjects with treatment-emergent markedly abnormal (TEMA) 
laboratory results will be tabulated by PS0016 randomized treatment group and visit. Markedly 
abnormal laboratory values will be defined as those categorized as Grade 3 and above based on 
the ranges defined as per the Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03 (2016). These are provided in Table 14‒2. The tabulation will include a category 
for the incidence of TEMA results over all visits which will also count unscheduled 
measurements. 
Laboratory measurements meeting the criteria for TEMA will be listed separately for 
hematology and chemistry. The listings will include all measurements for any variable with at 
least one TEMA result for each subject. 
Any additional laboratory variables not included in the outputs described previously will be 
listed separately. These will include the following: 
 Pregnancy tests (serum and urine) 
 Follicle stimulating hormone (FSH) (only for postmenopausal women) 
Subjects with treatment-emergent liver function test abnormalities at any PS0018 visit will be 
summarized (number and percentage of subjects) by PS0016 randomized treatment group. The 
criteria for this tabulation are presented in Table 14‒3. 
Table 11‒1: Clinical laboratory measurements 
Category 
Panel 
Variable 
Hematology 
Red blood cell 
RBC count, hemoglobin, hematocrit 
 
Red blood cell indices 
MCH, MCHC, MCV 
 
Platelet 
Platelets 
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Table 11‒1: Clinical laboratory measurements 
Category 
Panel 
Variable 
 
White blood cell 
WBC count 
 
White blood cell differential 
Absolute counts: ANC, basophils, eosinophils, ALC, 
monocytes, atypical lymphocytes (if indicated) 
Percentages: neutrophils/leukocytes, 
basophils/leukocytes, eosinophils/leukocytes, 
lymphocytes/leukocytes, monocytes/leukocytes. 
Chemistry 
Electrolytes 
Sodium, chloride, potassium, calcium, magnesium 
 
Kidney function 
BUN, creatinine 
 
Liver function 
AST, ALT, GGT, ALP, LDH, total bilirubin (direct 
bilirubin, indirect bilirubin, if indicated) 
 
Lipids 
Total cholesterol 
 
Metabolic function 
Glucose 
 
Hormones 
FSHb 
 
Fertility 
Pregnancy testa 
 
Other 
CRP 
Urinalysis 
Dipstick 
pH, protein, blood, leukocyte esterase, nitrite, glucose 
 
Urine sediment (if indicated) 
WBC, RBC, epithelial cells (squamous, transitional and 
renal tubular), hyaline casts, WBC casts, RBC casts, 
waxy casts, granular casts, calcium oxalate crystals, uric 
acid crystals, triphosphate crystals, yeast, bacteria, 
amorphous urates, amorphous phosphates  
ALC=absolute lyphoctye count; ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC=absolute 
neutrophil count; AST=aspartate aminotransferase; BUN=blood urea nitrogen; CRP=C-reactive protein; 
FSH=follicle stimulating hormone; 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 SFU Visit. The pregnancy test will be urine at all other visits 
and will be performed locally. 
b The FSH test should only be performed on postmenopausal females who have been postmenopausal for ≥1 year 
and last menstrual cycle occurred <2 years ago. 
11.4 
Vital signs, physical findings, and other observations related to 
safety 
11.4.1 
Vital signs 
Vital signs will be measured at every visit and will include: 
 Systolic and diastolic blood pressure 
 Pulse rate 
 Body temperature (oral, axillary, or otic) 
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Vital signs are to be measured prior to blood sampling, and prior to dosing, where applicable. 
A by-subject listing of all vital sign measurements and changes from Baseline will be presented 
by PS0016 randomized treatment group and visit. The listing will include a flag for 
measurements identified as TEMA/potentially clinically significant (PCS) as calculated by the 
criteria outlined in Table 14‒4. 
Descriptive statistics will be reported for all vital sign measurements. Measured values and 
changes from Baseline will be summarized by vital signs variable and visit for each PS0016 
randomized treatment group. 
The number and percentage of subjects with TEMA/PCS vital sign values will be summarized by 
PS0016 randomized treatment group and variable at each visit and overall (ie across all PS0018 
visits). 
11.4.2 
Body weight 
A by-subject listing of body weight will be presented. No summary tabulations will be provided 
for this variable. 
11.4.3 
12-Lead Electrocardiograms 
Standard 12-lead ECG will be recorded after 10 minutes of rest in the supine or semi recumbent 
position. The following ECG variables will be recorded together with the Investigator’s 
interpretation of the ECG profile: 
 Heart rate 
 PR interval 
 QRS duration 
 QT interval 
 QT corrected for heart rate using Fridericia’s formula (QTcF) 
The results of all ECG variables will be reported in the by-subject listings. The listing will also 
include the change from Baseline for numeric parameters and will be presented by PS0016 
randomized treatment group and visit. 
Measured values and changes from Baseline will be summarized for each variable by PS0016 
randomized treatment group and visit. 
The following cut-points in QTcF (raw data and change from Baseline) will be summarized 
categorically by PS0016 randomized treatment group (number and percentage of subjects) and 
visit. The denominator for the percentages will be the number of subjects with a non-missing 
measurement for the variable at the specific visit. 
Raw QTcF data: 
 <450msec 
 ≥450 msec to <480msec 
 ≥480msec to <500msec 
 ≥500msec 
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Change from Baseline QTcF: 
 <30msec 
 ≥30msec to <60msec 
 ≥60msec 
Electrocardiogram findings will be listed separately. 
11.4.4 
Other safety variables 
11.4.4.1 
Physical examination 
Physical examination will not be reported as part of the CSR. 
11.4.4.2 
Tuberculosis 
Tuberculosis assessment by interferon gamma release assay 
The TB assessment by interferon gamma release assay will be performed for all subjects. The 
test results will be listed for each subject by PS0016 randomized treatment group and visit, 
reported as positive, negative, or indeterminate. 
Chest x ray for Tuberculosis 
Chest x ray will be performed in PS0018 only when required to confirm or exclude TB. Any 
clinically significant findings on chest x ray will be documented in the eCRF as an AE and will 
thus be listed and summarized together with TEAEs as described in Section 11.2.3. 
Tuberculosis questionnaire 
The TB questionnaire results will be listed for each subject by PS0016 randomized treatment 
group and visit. 
11.4.4.3 
Columbia-Suicide Severity Rating Scale 
The results of the C-SSRS will be listed for each subject by PS0016 randomized treatment group 
and visit. 
12 
OTHER ANALYSES  
A listing of comments on the SS will be presented, if applicable. 
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13 
REFERENCES 
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. 
Fay MP, Feuer EJ. Confidence intervals for directly standardized rates: a method based on the 
gamma distribution. Statistics in Medicine 1997; Vol 16: 791-801.  
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the 
irritability-depression-anxiety scale and the Leeds situational anxiety scale manual 1994. 
Ulm K. A simple method to calculate the confidence interval of a standardized mortality ratio. 
Am J Epidemiol. 1990;131(2):373-375. 
 
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14 
APPENDICES 
14.1 
Classification of markedly abnormal laboratory values based on 
CTCAE grades 
The criteria for assessing laboratory values as markedly abnormal are presented in Table 14‒2. 
Baseline in the table refers to PS0016 Baseline. 
Table 14‒2: Criteria for markedly abnormal laboratory tests 
Category 
Panel 
Variable 
Criteria (CTCAE 
Grade 3 and above) 
Hematology 
Red blood cell 
Hemoglobin (Decrease) 
<80 g/L 
 
 
Hemoglobin (Increase) 
>4 g/dL (>40 g/L) above ULN OR 
>4 g/dL (>40 g/L) above Baseline 
if Baseline is >ULN 
 
White blood cell 
WBC count (Decrease) 
<2.0 x 10^9/L 
 
 
WBC count (Increase) 
>100 x 10^9/L 
 
White blood cell 
differential 
ALC (Decrease) 
<0.5 x 10^9/L 
 
 
ALC (Increase) 
>20 x 10^9/L 
 
 
ANC 
<1.0 x 10^9/L 
 
Platelet 
Platelet 
<50 x 10^9/L 
Chemistry 
Liver function 
ALT 
>5.0 x ULN 
 
 
ALP 
>5.0 x ULN 
 
 
AST 
>5.0 x ULN 
 
 
Total bilirubin 
>3.0 x ULN 
 
 
GGT 
>5.0 x ULN 
 
Kidney function 
Creatinine 
>3.0 x Baseline value OR 
>3.0 x ULN 
 
Electrolytes 
Calcium (Decrease) 
<1.75 mmol/L 
 
 
Calcium (Increase) 
>3.1 mmol/L 
 
 
Magnesium (Increase) 
<0.4 mmol/L 
 
 
Magnesium (Increase) 
>1.23 mmol/L 
 
 
Potassium (Decrease) 
<3.0 mmol/L 
 
 
Potassium (Increase) 
>6.0 mmol/L 
 
 
Sodium (Decrease) 
<130 mmol/L 
 
 
Sodium (Increase) 
>155 mmol/L 
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Table 14‒2: Criteria for markedly abnormal laboratory tests 
Category 
Panel 
Variable 
Criteria (CTCAE 
Grade 3 and above) 
 
Lipids 
Total cholesterol 
>10.34 mmol/L 
ALC= absolute lymphocyte count; ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC= absolute 
neutrophil count; AST=aspartate aminotransferase; GGT=gamma glutamyltransferase; RBC=red blood cell; 
ULN=upper limit of normal, WBC=white blood cell: 
14.2 
Treatment-emergent abnormal liver values 
The criteria for identifying treatment-emergent liver function abnormalities are presented in 
Table 14‒3. Subjects will be counted in all applicable categories for the tabulations ie, a subject 
with ≥5 x ULN in aspartate aminotransferase (AST) will also be counted in the ≥3 x ULN in 
AST category, the ≥3 x ULN in AST or alanine aminotransferase (ALT) category and the ≥5x 
ULN in AST or ALT category. Increases from Baseline are based on PS0016 Baseline. 
Table 14‒3: Definition of treatment emergent liver function values 
Criterion 
≥3 x ULN increase for AST 
≥5 x ULN increase for AST 
≥10 x ULN increase for AST 
≥20 x ULN increase for AST 
≥3 x ULN increase for ALT 
≥5 x ULN increase for ALT 
≥10 x ULN increase for ALT 
≥20 x ULN increase for ALT 
≥3 x ULN increase for AST or ALT 
≥5 x ULN increase for AST or ALT 
≥10 x ULN increase for AST or ALT 
≥20 x ULN increase for AST or ALT 
≥1 x ULN increase for bilirubin 
≥1.5 x ULN increase for bilirubin 
≥1.5 x ULN increase for ALP 
≥1 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit) 
≥2 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit) 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of 
normal. 
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14.3 
Adverse events of special monitoring 
The following AESM are defined for bimekizumab and will be summarized separately as 
described in Section 11.2.3: 
 Major cardiovascular events  
 Serious infections, including opportunistic infections and tuberculosis (TB) 
 Malignancies including lymphoma 
 Cytopenias 
 Neuropsychiatric events (in particular, depression and suicide) 
 Inflammatory bowel disease 
 Anaphylactic reaction (hypersensitivity and anaphylactic reactions) 
 Hepatic events and drug-induced liver injury  
All AESM tabulations will be presented by Treatment at onset, SOC, HLT and PT, based on the 
SS, and will include the EAIR and EAER in the ‘Any TEAE’ categories only. 
14.3.1 
Major cardiovascular events 
Major adverse cardiac events (MACE) will be presented in a table. The classification of an event 
as MACE is determined by an external cardiovascular event adjudication committee. 
14.3.2 
Serious infections, including opportunistic infections and 
tuberculosis 
14.3.2.1 
Serious infections 
Serious infections are based on MedDRA classification using the SOC = ‘Infections and 
Infestations’. Such events will be included in the tabulations of SAEs and no separate summary 
tabulations will be presented. 
14.3.2.2 
Fungal infections 
Fungal infections will be summarized separately based on all TEAEs coding to the high level 
group term (HLGT) = ‘Fungal infectious disorders’. 
14.3.2.3 
Opportunistic infections 
Opportunistic infections (including tuberculosis) will be summarized in a stand-alone table. The 
table will include all TEAEs identified using UCB-defined search criteria (refer to Excel 
spreadsheet on “OI - MedDRA v19.0.xlsx” in “Bimekizumab-Safety-Topics-of-Interest.docx”). 
The following steps are followed for identifying opportunistic infections: 
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 to be 
considered an opportunistic infection. 
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 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 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. At quarterly Infectious Disease Committee (IDC) Meetings, outputs will be produced and 
reviewed by the study physician ahead of the IDC Meeting. The IDC will then agree on the 
final adjudication for each potential opportunistic infection. A final output for opportunistic 
infections will be produced and agreed upon between the study physician and the IDC prior 
to finalizing the database. 
4. Study programming team incorporates these decisions into the AE dataset by merging the 
final 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 in Step 2 will be summarized as such in the stand-alone table, along 
with all events identified in Step 1 of this process. 
The timing and frequency of Step 2 will be outlined 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 prior to the DMC meeting. 
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 final study physician decisions (with 
IDC agreement) on the full set of case-by-case events, will be archived at the conclusion of the 
study. 
14.3.3 
Malignancies including lymphoma 
Malignancies will be presented in 2 separate tables based on the following SMQs: 
 Malignant or unspecified tumours 
 Malignant tumours 
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Events included in the ‘Malignant tumours’ tabulation will be a subset of the events in the 
‘Malignant or unspecified tumours’ tabulation. The SMQ search should include all TEAEs 
which code to a PT included in the Scope=Narrow group within each SMQ. 
The output tables will include 2 different overall incidence rows: 
 The first overall incidence row will summarize ‘Any malignancies (including unspecified)’ 
or ‘Any malignancies’ (depending on the table) and this row will summarize the incidence of 
all AEs flagged for inclusion in the table, regardless of the HLT it codes to.  
 The second overall incidence row will summarize ‘Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)’ or ‘Any malignancy (excluding non-melanomic 
skin cancers)’ (depending on the table) and this row will summarize the incidence of AEs 
flagged for inclusion in the table, excluding those which code to an HLT of ‘skin neoplasms 
malignant and unspecified (excl melanoma)’. 
14.3.4 
Cytopenias 
Cytopenias will be tabulated separately based on the SMQ = ‘Haematopoietic cytopenias’. 
Serious and non-serious TEAEs will be included in the tabulation. The SMQ search should 
include all serious TEAEs which code to a PT included in the Scope=Broad and/or 
Scope=Narrow groups within the SMQ. 
14.3.5 
Neuropsychiatric events 
This table is based on the SMQ of “Depression and suicide/self-injury” (all TEAEs that code to a 
PT included in the Scope=Broad and/or Scope=Narrow). 
An external neuropsychiatric adjudication committee will evaluate potential neuropsychiatric 
events and determine whether any of those events were associated with suicidal ideation and 
behavior (SIB). If an event is adjudicated as SIB, further information will be provided. A 
separate listing for SIB events as determined by the adjudication committee will be included. 
14.3.6 
Inflammatory bowel disease 
Inflammatory bowel disease events will be tabulated separately, based on the HLGT = ‘Colitis 
excl infective’. 
14.3.7 
Anaphylactic reaction 
Anaphylactic reactions will be summarized together in a stand-alone table with the following 
incidence rows: 
 The first row within the body of the table will be labeled ‘Any hypersensitivity/anaphylactic 
reaction’ and will represent the overall incidence of subjects who reported at least one 
hypersensitivity reaction or at least one anaphylactic reaction. 
 The second row within the body of the table will be labeled ‘Any hypersensitivity reaction’ 
and will represent the overall incidence of subjects who reported at least one hypersensitivity 
reaction. 
 The third row within the body of the table will be labeled ‘Any anaphylactic reaction’ and 
will represent the overall incidence of subjects who reported at least one anaphylactic 
reaction. 
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Following these three overall incidence rows, all TEAEs that have been identified as either a 
hypersensitivity reaction or an anaphylactic reaction will be summarized by SOC, HLT and PT 
(these will not be presented by subcategory). 
Hypersensitivity reactions and anaphylactic reactions will be identified as follows: 
 Hypersensitivity reactions: all TEAEs with onset (start date/time) within 24 hours after any 
administration of study medication, which code to a PT which contains the term 
‘hypersensitivity’ will be considered to be a hypersensitivity reaction and included in the 
summary table 
 Anaphylactic reactions: An algorithmic approach will be used to identify TEAEs that are 
considered to be anaphylactic reactions. Preferred terms are separated into 4 distinct 
categories (A, B, C, D) prior to the algorithmic approach being applied. 
All TEAEs with onset (start date/time) within 24 hours after any administration of study 
medication, and which fulfill any of the 3 criteria described in Section 14.3.7.1 will be 
included in the summary table. 
Any TEAEs with missing start time will be assumed to have occurred at the time of or after 
dosing for this purpose, if the event date is on the same day as a dosing date. 
14.3.7.1 
Anaphylactic reaction algorithm 
The SMQ = ‘anaphylactic reaction’ consists of 3 parts: 
A narrow search containing PTs that represent core anaphylactic reaction terms. If a subject 
reports any TEAE which codes to a PT included in Category A, then the event will be flagged as 
an anaphylactic reaction and summarized as such in the table. 
 Category A 
5. Anaphylactic reaction 
6. Anaphylactic shock 
7. Anaphylactic transfusion reaction 
8. Anaphylactoid reaction 
9. Anaphylactoid shock 
10. Circulatory collapse 
11. Dialysis membrane reaction 
12. Kounis syndrome 
13. Shock 
14. Shock symptom 
15. Type I hypersensitivity 
 A broad search: If a subject reports any TEAE which codes to a PT included in Category B 
AND reports any TEAE which codes to a PT included in Category C, and both TEAEs 
have the same start date, then both events will be flagged as anaphylactic reactions and 
summarized as such in the table.  
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 Category B 
1. Acute respiratory failure 
2. Asthma 
3. Bronchial oedema 
4. Bronchospasm 
5. Cardio-respiratory distress 
6. Chest discomfort 
7. Choking 
8. Choking sensation 
9. Circumoral oedema 
10. Cough 
11. Cyanosis 
12. Dyspnoea 
13. Hyperventilation 
14. Irregular breathing 
15. Laryngeal dyspnoea 
16. Laryngeal oedema 
17. Laryngospasm 
18. Laryngotracheal oedema 
19. Mouth swelling 
20. Nasal obstruction 
21. Oedema mouth 
22. Oropharyngeal spasm 
23. Oropharyngeal swelling 
24. Respiratory arrest 
25. Respiratory distress 
26. Respiratory dyskinesia 
27. Respiratory failure 
28. Reversible airways obstruction 
29. Sensation of foreign body 
30. Sneezing 
31. Stridor 
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32. Swollen tongue 
33. Tachypnoea 
34. Throat tightness 
35. Tongue oedema 
36. Tracheal obstruction 
37. Tracheal oedema 
38. Upper airway obstruction 
39. Wheezing 
 Category C 
1. Allergic oedema 
2. Angioedema 
3. Erythema 
4. Eye oedema 
5. Eye pruritis 
6. Eye swelling 
7. Eyelid oedema 
8. Face oedema 
9. Flushing 
10. Generalised erythema 
11. Injection site urticaria 
12. Lip oedema 
13. Lip swelling 
14. Nodular rash 
15. Ocular hyperaemia 
16. Oedema 
17. Periorbital oedema 
18. Pruritis 
19. Pruritis allergic 
20. Pruritis generalised 
21. Rash 
22. Rash erythematous 
23. Rash generalized 
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24. Rash pruritic 
25. Skin swelling 
26. Swelling 
27. Swelling face 
28. Urticaria 
29. Urticaria papular 
 Category D 
1. Blood pressure decreased 
2. Blood pressure diastolic decreased 
3. Blood pressure systolic decreased 
4. Cardiac arrest 
5. Cardio-respiratory arrest 
6. Cardiovascular insufficiency 
7. Diastolic hypertension 
8. Hypotension 
An algorithmic approach: If a subject reports any TEAE which codes to a PT included in 
Category D AND reports (either a TEAE which codes to a PT included in Category B OR a 
TEAE which codes to a PT included in Category C), and both TEAEs have the same start 
date, then both events will be flagged as anaphylactic reactions and summarized as such in the 
table. 
14.3.8 
Hepatic events and drug-induced liver injury 
Hepatic events will include: 
 Events based on the SMQ = ‘Drug related hepatic disorders – comprehensive search’ 
(excluding sub-SMQs = ‘Liver neoplasms, benign [incl cysts and polyps]’ and ‘Liver 
neoplasms, malignant and unspecified’). All AEs should be included in the tabulation 
(included those considered both related and not related to the IMP) which code to a PT 
included in the Scope=Narrow group within each SMQ. 
 Hy’s Law cases will also be summarized separately in a table of liver function abnormalities 
as described in Section 14.2 (with adjudication for potential drug-induced liver injury cases). 
14.4 
Treatment-emergent markedly abnormal vital signs values 
The criteria for identifying TEMA/PCS vital signs values are provided in Table 14‒4. Decreases 
and increases from Baseline are based on PS0016 Baseline. 
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Table 14‒4: TEMA/PCS criteria for vital signs 
Variable 
Unit 
Lowa 
Higha 
Systolic blood pressure 
mmHg 
Value ≤90 and ≥20 decrease 
from Baseline 
Value ≥180 and ≥20 increase 
from Baseline 
Diastolic blood pressure 
mmHg 
Value ≤50 and ≥15 decrease 
from Baseline 
Value ≥105 and ≥15 increase 
from Baseline 
Note: the change in measurement (increase or decrease) will be calculated relative to the value obtained at Baseline. 
a Both conditions must be satisfied for a measurement to be considered TEMA/PCS. 
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15 
AMENDMENTS TO THE SAP 
15.1 
Amendment 1 
15.1.1 
Rationale for the amendment 
This SAP was amended in order to make minor corrections to the text that were noted during the 
dry run.  
15.1.2 
List of changes 
Specific changes 
Change #1: Section 1, 2nd paragraph. 
The following bullet has been added:- 
• 
Protocol amendment 3 dated 16 February 2018 
Change #2: Section 3.2.2 
The following section has been added:- 
3.2.2 Daylight saving dates 
Daylight saving dates will be considered in the calculation of the absolute scheduled and 
actual times and in the duration when this is based on times. Therefore, if any daylight saving 
change occurs during the study development, this will impact the description of the blood 
sample collections, the calculation of the PK parameters, and any AE duration in case the 
time is included in the calculation of the duration. 
Change #3: Section 3.3, final sentence 
The sentence has changed from: 
 This will be labelled as PS0018 Week 0 in the tabulations, and will be included in any 
change from PS0016 Baseline summaries. 
to 
 The day of first dose will be labelled as PS0018 Week 0 in the tabulations, and will be 
included in any change from PS0016 Baseline summaries. 
Change #4: Section 4.4 
The second bullet has changed from: 
 "If the early WD visit does not correspond to the day of a scheduled visit, all the efficacy, 
safety and other relevant assessments of the early WD visit should be mapped to the nearest 
scheduled visit, relative to the PS0018 Week 0 visit date, following the last scheduled visit 
where assessments are available." 
to: 
 "If the early WD visit does not correspond to the day of a scheduled visit, all the efficacy, 
safety and other relevant assessments of the early WD visit should be mapped to the nearest 
scheduled visit, relative to the PS0018 Week 0 visit date, following the last scheduled visit 
where assessments are available." 
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Change #5: Section 4.4 
Two further bullets, and a sentence have been added:- 
 If an EW visit mapping results in data being mapped to a visit where the specific assessment 
is not actually collected per the protocol schedule of assessments, these data will not be 
included in the summary statistics and will be listed only. 
 The only exception to the above rule is for ADA (for both BKZ and CZP) assessments, in 
which all early withdrawal visit assessments will be assigned to the next scheduled visit at 
which ADA are assessed. The rationale for this is that ADA positivity is summarized over a 
given study period. As part of that summary, a table indicating the first visit at which ADA 
positivity is observed will be presented. In order to match the number of subjects who were 
ADA positive at specific visits with the overall positivity for the period, it is necessary to 
ensure that ADA positivity is attributed to a visit where ADA antibody assessments were 
performed. 
Assessments from the EW visit will be displayed as the mapped visit and will be flagged in the 
by-visit data listings. 
Change #6: Section 11.2.3 
Two bullets have been removed:- 
 Incidence of non-serious TEAEs by PS0018 dose at onset and Dose adjustment 
 Incidence of non-serious TEAEs by relationship and PS0018 dose at onset  
Change #7: Section 11.2.3 
One bullet has been added:- 
 Incidence of ongoing AEs from PS0016  
Change #8: Section 14.3.4 
The second sentence has changed from: 
 "Only serious TEAEs will be included in the tabulation" 
to: 
 "Serious and non-serious TEAEs will be included in the tabulation"  
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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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Approval Signatures
Name:
ps0018-sap-am1
Version:
1. 0
Document Number:
CLIN-000127049
Title:
PS0018 Statistical Analysis Plan amendment 1
Approved Date:
01 Nov 2018
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 30-Oct-2018 15:08:31 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 01-Nov-2018 16:58:18 GMT+0000
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