Clinical trial NCT03248531
Conditions: Hidradenitis Suppurativa
Keywords: Hidradenitis Suppurativa Bimekizumab HS Moderate to Severe HS
Sponsor: UCB Biopharma SRL
Start date: 2017-09-22; Completion date: 2019-02-21
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Hidradenitis suppurativa (HS) is a painful, long-term skin condition that causes abscesses and scarring on the skin.

Detailed description:

Arms: arm 1: Subjects will receive one Bimekizumab loading dose 1 and several Bimekizumab dose 2 applications. arm 2: Subjects will receive one Adalimumab loading (dose 1) and several Adalimumab dose 2 and dose 3 applications. arm 3: Subjects will receive several placebo applications to keep the blinding.
Interventions: intervention 1: Bimekizumab intervention 2: Adalimumab intervention 3: Placebo
Intervention descriptions: intervention 1: Bimekizumab in different dosages (dose 1 and 2). intervention 2: Adalimumab in different dosages (dose 1, 2 and 3). intervention 3: Placebo will be provided matching Bimekizumab.

Protocol documents:
Prot_000.pdf: 
UCB
08 Mar 2018
Clinical Study Protocol
Bimekizumab
HS0001
Confidential
Page 1 of 100
PROTOCOL HS0001 AMENDMENT 1
A PHASE 2 MULTICENTER, INVESTIGATOR-BLIND, 
SUBJECT-BLIND, PLACEBO-CONTROLLED STUDY OF THE 
EFFICACY, SAFETY, AND PHARMACOKINETICS OF 
BIMEKIZUMAB IN SUBJECTS WITH MODERATE TO SEVERE 
HIDRADENITIS SUPPURATIVA
PHASE 2
EudraCT Number: 2017-000892-10
IND Number: 134700
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
26 May 2017
Not applicable
Protocol Amendment  0.1 (US)
28 Jul 2017
Not applicable
Protocol Amendment  0.2 (US)
28 Aug 2017
Not applicable
Protocol Amendment  0.3 (NO)
05 Oct 2017
Nonsubstantial
Protocol Amendment 0.4 (DE)
26 Oct 2017
Nonsubstantial
Protocol Amendment 1
08 Mar 2018
Substantial
Protocol Amendment 1.1 (US)
08 Mar 2018
Not applicable
Protocol Amendment 1.2 (NO)
08 Mar 2018
Substantial
Protocol Amendment 1.3 (DE)
08 Mar 2018
Substantial
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Clinical Study Protocol
Bimekizumab
HS0001
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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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Clinical Study Protocol
Bimekizumab
HS0001
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Clinical Monitoring Contract Research Organization
Name:
PAREXEL International (IRL) Limited
Address:
One Kilmainham Square; Inchicore Rd; Kilmainham; Dublin 8; 
Ireland
Phone:
+35 314739500
Fax:
+35 314739501
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Bimekizumab
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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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Bimekizumab
HS0001
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................12
1
SUMMARY.....................................................................................................................15
2
INTRODUCTION ...........................................................................................................16
2.1 Hidradenitis suppurativa ..................................................................................................16
2.1.1
Hidradenitis suppurativa disease pathology ........................................................17
2.1.2
Current treatments and unmet need .....................................................................17
2.2 Bimekizumab ...................................................................................................................18
2.2.1
Clinical.................................................................................................................19
2.2.2
Nonclinical...........................................................................................................20
3
STUDY OBJECTIVES....................................................................................................20
3.1 Primary objective.............................................................................................................20
3.2 Secondary objective.........................................................................................................21
3.3 Exploratory objective.......................................................................................................21
4
STUDY VARIABLES.....................................................................................................21
4.1 Efficacy variables.............................................................................................................21
4.1.1
Primary efficacy variable.....................................................................................21
4.1.2
Exploratory efficacy variables.............................................................................21
4.2 Pharmacokinetic, pharmacodynamic, pharmacogenomic, and pharmacogenetic variables22
4.2.1
Secondary pharmacokinetic variable...................................................................22
4.2.2
Exploratory pharmacodynamic variables ............................................................22
4.2.3
Exploratory nonhereditary pharmacogenomic variables.....................................22
4.2.4
Exploratory pharmacogenetic variables...............................................................22
4.3 Safety variables................................................................................................................22
4.3.1
Secondary safety variables ..................................................................................22
4.4 Immunological variables..................................................................................................22
4.4.1
Secondary immunological variable .....................................................................22
4.5 Imaging variables.............................................................................................................23
4.5.1
Exploratory imaging variables.............................................................................23
5
STUDY DESIGN.............................................................................................................23
5.1 Study description .............................................................................................................23
5.1.1
Study periods .......................................................................................................23
5.1.2
Study duration per subject ...................................................................................24
5.1.3
Planned number of subjects and sites ..................................................................24
5.1.4
Anticipated regions and countries .......................................................................25
5.2 Schedule of study assessments.........................................................................................25
5.3 Schematic diagram...........................................................................................................31
5.4 Rationale for study design and selection of dose.............................................................31
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Bimekizumab
HS0001
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6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................33
6.1 Inclusion criteria ..............................................................................................................33
6.2 Exclusion criteria .............................................................................................................34
6.3 Withdrawal criteria ..........................................................................................................38
6.3.1
Potential drug-induced liver injury investigational medicinal product 
discontinuation criteria ........................................................................................40
6.4 Study stopping rules.........................................................................................................40
6.4.1
Safety ...................................................................................................................40
6.4.2
Other reasons .......................................................................................................41
6.5 Retesting/rescreening.......................................................................................................41
7
STUDY TREATMENTS.................................................................................................41
7.1 Description of investigational medicinal products ..........................................................41
7.2 Treatments to be administered.........................................................................................42
7.3 Packaging.........................................................................................................................43
7.4 Labeling ...........................................................................................................................43
7.5 Handling and storage requirements..................................................................................43
7.6 Drug accountability..........................................................................................................44
7.7 Procedures for monitoring subject compliance................................................................45
7.8 Concomitant medications/treatments...............................................................................45
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................45
7.8.2
Prohibited concomitant treatments (medications and therapies).........................46
7.8.3
Rescue medication...............................................................................................46
7.9 Blinding............................................................................................................................46
7.9.1
Procedures for maintaining and breaking the treatment blind.............................47
7.9.1.1
Maintenance of study treatment blind.......................................................47
7.9.1.2
Breaking the treatment blind in an emergency situation...........................47
7.10 Randomization and numbering of subjects......................................................................47
8
STUDY PROCEDURES BY VISIT ...............................................................................48
8.1 Screening Visit (Visit 1) ..................................................................................................48
8.2 Baseline Visit (Visit 2; Day 1).........................................................................................50
8.3 Visit 3; Week 2 (±3 days) ................................................................................................51
8.4 Visit 4; Week 4 (±3 days) ................................................................................................51
8.5 Visits 5, 7, and 9; Weeks 5, 7, and 9 (±3 days)................................................................52
8.6 Visit 6; Week 6 (±3 days) ................................................................................................52
8.7 Visit 8; Week 8 (±3 days) ................................................................................................53
8.8 Visit 10; Week 10 (±3 days) ............................................................................................54
8.9 Visit 11; Week 12 (±3 days) ............................................................................................54
8.10 Safety Follow-Up Visit (Visit 12; Week 30; 20 weeks after the last dose of IMP) (-3  to 
+7 days)............................................................................................................................55
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8.11 Early Withdrawal Visit ....................................................................................................56
8.12 Unscheduled Visit............................................................................................................56
9
ASSESSMENT OF EFFICACY......................................................................................57
9.1 Hidradenitis Suppurativa Clinical Response ...................................................................57
9.2 International Hidradenitis Suppurativa Severity Score System.......................................57
9.3 Lesion count.....................................................................................................................57
9.4 Patient's Global Assessment of Skin Pain........................................................................58
9.5 Modified Sartorius score..................................................................................................58
9.6 Hidradenitis Suppurativa-Physician’s Global Assessment..............................................59
9.7 Dermatology Life Quality Index......................................................................................59
9.8 European Quality-of-Life 5 dimensions questionnaire....................................................59
9.9 Hurley Stage.....................................................................................................................59
9.10 Erythema assessment .......................................................................................................60
9.11 Hospital Anxiety and Depression Scale...........................................................................60
10
ASSESSMENT OF PHARMACOKINETICS PHARMACODYNAMIC, 
NONHEREDITARY PHARMACOGENOMICS, AND PHARMACOGENETICS .....60
10.1 Pharmacokinetic variables ...............................................................................................60
10.2 Pharmacodynamic variables ............................................................................................60
10.3 Nonhereditary pharmacogenomic variables.....................................................................61
10.4 Pharmacogenetic variables...............................................................................................61
11
ASSESSMENT OF SAFETY..........................................................................................61
11.1 Adverse events.................................................................................................................61
11.1.1
Definitions ...........................................................................................................61
11.1.1.1
Adverse Events..........................................................................................61
11.1.1.2
Serious adverse event ................................................................................62
11.1.1.3
Adverse events of special interest .............................................................63
11.1.1.4
Adverse events for special monitoring......................................................64
11.1.2
Procedures for reporting and recording adverse events.......................................64
11.1.2.1
Description of adverse events....................................................................64
11.1.2.2
Rule for repetition of an adverse event......................................................65
11.1.2.3
Additional procedures for reporting serious adverse events .....................65
11.1.2.4
Immediate reporting of adverse events......................................................65
11.1.3
Follow up of adverse events ................................................................................66
11.1.4
Pregnancy ............................................................................................................66
11.2 Laboratory measurements................................................................................................67
11.2.1
Evaluation of potential drug-induced liver injury................................................69
11.2.1.1
Consultation with Medical Monitor and local hepatologist ......................72
11.2.1.2
Immediate action: determination of investigational medicinal product 
discontinuation ..........................................................................................72
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Bimekizumab
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11.2.1.3
Investigational medicinal product restart/rechallenge...............................72
11.2.1.4
Testing: identification/exclusion of alternative etiology...........................72
11.2.1.5
Follow-up evaluation.................................................................................74
11.3 Other safety measurements..............................................................................................74
11.3.1
Assessment and management of tuberculosis and tuberculosis risk factors........74
11.3.1.1
Tuberculosis assessment by interferon-gamma release assay...................75
11.3.1.2
Chest x-ray for tuberculosis ......................................................................76
11.3.1.3
Tuberculosis questionnaire........................................................................76
11.3.1.4
Tuberculosis management.........................................................................76
11.3.2
Pregnancy testing.................................................................................................77
11.3.3
Vital signs ............................................................................................................77
11.3.4
12-lead electrocardiograms..................................................................................77
11.3.5
Physical examination...........................................................................................77
11.3.6
Body weight.........................................................................................................77
11.3.7
Assessment of suicidal ideation and behavior.....................................................78
11.4 Other study measurements...............................................................................................78
11.4.1
Demographic and Baseline information ..............................................................78
11.4.2
Medical history ....................................................................................................78
11.4.3
Hidradenitis suppurativa history..........................................................................78
11.5 Data Monitoring Committee............................................................................................78
12
ASSESSMENT OF IMMUNOLOGICAL VARIABLES...............................................78
13
ASSESSMENT OF IMAGING VARIABLES................................................................79
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................79
14.1 Adherence to protocol......................................................................................................79
14.2 Monitoring .......................................................................................................................79
14.2.1
Definition of source data .....................................................................................80
14.2.2
Source data verification .......................................................................................80
14.3 Data handling...................................................................................................................80
14.3.1
Case Report Form completion.............................................................................80
14.3.2
Database entry and reconciliation........................................................................81
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............81
14.4 Termination of the study..................................................................................................81
14.5 Archiving and data retention............................................................................................82
14.6 Audit and inspection ........................................................................................................82
14.7 Good Clinical Practice .....................................................................................................82
15
STATISTICS ...................................................................................................................82
15.1 Definition of analysis sets................................................................................................82
15.2 General statistical considerations.....................................................................................83
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Bimekizumab
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15.3 Subject disposition...........................................................................................................83
15.4 Subject characteristics......................................................................................................83
15.5 Planned efficacy analyses ................................................................................................84
15.5.1
Analysis of the primary efficacy variable............................................................84
15.5.2
Supportive analysis of the primary efficacy variable ..........................................85
15.5.3
Analysis of the exploratory efficacy variables ....................................................85
15.6 Planned pharmacokinetic analyses ..................................................................................85
15.7 Planned immunological analyses.....................................................................................85
15.8 Planned safety analyses....................................................................................................85
15.9 Handling of protocol deviations.......................................................................................86
15.10
Handling of dropouts or missing data....................................................................86
15.11
Planned interim analysis and data monitoring.......................................................86
15.12
Determination of sample size.................................................................................86
16
ETHICS AND REGULATORY REQUIREMENTS......................................................87
16.1 Informed consent .............................................................................................................87
16.2 Subject identification cards..............................................................................................88
16.3 Institutional Review Boards and Independent Ethics Committees..................................88
16.4 Subject privacy.................................................................................................................89
16.5 Protocol amendments.......................................................................................................89
17
FINANCE, INSURANCE, AND PUBLICATION.........................................................89
18
REFERENCES ................................................................................................................89
19
APPENDICES .................................................................................................................93
19.1 Protocol Amendment 1 ....................................................................................................93
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .......................................99
21
SPONSOR DECLARATION ........................................................................................100
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................26
Table 5-2:
Observed and model-predicted pharmacokinetic parameters for 
bimekizumab....................................................................................................32
Table 7‒1:
Administration of investigational medicinal product ......................................42
Table 11‒1:
Anticipated serious adverse events for the population of subjects with 
hidradenitis suppurativa...................................................................................63
Table 11-2:
Laboratory measurements................................................................................68
Table 11-3:
Required investigations and follow-up for PDILI ...........................................70
Table 11‒4:
PDILI laboratory measurements......................................................................73
Table 11‒5:
PDILI information to be collected...................................................................74
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Bimekizumab
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LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................31
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Bimekizumab
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LIST OF ABBREVIATIONS
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
AESM
adverse events for special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
APAC
Asia-Pacific
AST
aspartate aminotransferase
BA
absolute bioavailability
BMI
body mass index
BP
blood pressure
CAT
Computed Axial Tomography
CD
Crohn’s disease
CDMS
clinical data management system
CRO
Contract Research Organization
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
CXR
chest x-ray
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
ECG
electrocardiogram
eCRF
electronic Case Report form
EDC
electronic data capture
EPM
Exploratory Project Manager
EQ-5D
European Quality-of-Life 5 dimensions questionnaire
ES
Enrolled Set
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
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Bimekizumab
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GMP
Good Manufacturing Practice
HADS
Hospital Anxiety and Depression Scale
HADS-A
HADS-Anxiety
HADS-D
HADS-Depression
HBV
hepatitis B virus
HCV
hepatitis C virus
HiSCR
Hidradenitis Suppurativa Clinical Response
HIV
human immunodeficiency virus
HS
hidradenitis suppurativa
IB
Investigator’s Brochure
IBD
Inflammatory Bowel Disease
ICH
International Council for Harmonisation
ICF
Informed Consent Form
IEC
Independent Ethics Committee
IGRA
interferon-gamma release assay
IHS4
International Hidradenitis Suppurativa Severity Score System
IL
interleukin
IMP
investigational medicinal product
IRB
Institutional Review Board
IRT
Interactive Response Technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
iv
intravenous
LTB
latent tuberculosis
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed Model for Repeated Measures
NRS
numeric rating scale
NTMB
nontuberculous mycobacteria
PD
pharmacodynamics
PDILI
potential drug-induced liver injury
PGA
Patient's Global Assessment
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Bimekizumab
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PK
pharmacokinetics
PK-PPS
Pharmacokinetics Per-Protocol Set
PPS
Per-Protocol Set
PRN
as needed
PsA
psoriatic arthritis
PSO
psoriasis
PS
Patient Safety
QOL
quality-of-life
QTc
QT corrected for heart rate
QTcF
QT corrected for heart rate using Fridericia’s correction
RA
rheumatoid arthritis
RNA
ribonucleic acid
RS
Randomized Set
S100A8/9
S100 calcium-binding protein A8/9
SAE
serious adverse event
SAP
statistical analysis plan
sc
subcutaneous
SFU
Safety Follow-Up
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TEAE
treatment-emergent adverse events
Th17
IL-17-producing T helper cells
TNF-α
tumor necrosis factor-alpha
ULN
upper limit of normal
US
United States
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Bimekizumab
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1
SUMMARY
This is a Phase 2, multicenter, randomized, Investigator-blind, subject-blind, placebo-controlled, 
active-reference arm study to assess the efficacy, safety, and pharmacokinetics (PK) of 
bimekizumab (also known as UCB4940) an anti-interleukin (IL)-17A and IL-17F monoclonal 
antibody (mAb) in eligible adult subjects with moderate to severe hidradenitis suppurativa (HS).
The active reference arm for this study will be adalimumab (Humira®; a tumor necrosis factor-
alpha [TNF-α] inhibitor). 
The study population will consist of adult subjects (18 to 70 years of age, inclusive) with a 
diagnosis of moderate to severe HS for at least 1 year prior to Baseline (lesions present in at least 
2 distinct anatomic areas [1 of which must be at least Hurley Stage II or III] and a total abscess 
and inflammatory nodule count ≥3) that has been stable for at least 2 months prior to Screening 
with an inadequate response to at least a 3-month study of an oral antibiotic treatment for HS (or 
exhibited recurrence after discontinuation of, demonstrated intolerance to, or have a 
contraindication to, oral antibiotics for treatment of their HS).
A sufficient number of subjects will be screened in order to have 80 subjects randomized in the 
study. There will be approximately 40 subjects in the bimekizumab treatment group, 20 subjects 
in the placebo group, and 20 subjects in the adalimumab group. For each subject, the study will 
last a maximum of 34 weeks and will consist of 3 periods; a Screening Period (up to 4 weeks), a 
Treatment Period (up to 12 weeks), and a Safety Follow-Up (SFU) Period (up to 20 weeks after 
the last dose of investigational medicinal product [IMP]). The primary efficacy variable, as 
measured by Hidradenitis Suppurativa Clinical Response (HiSCR), will be assessed at Week 12.
During the Treatment Period, eligible subjects will be randomized 2:1:1 (bimekizumab to 
placebo to adalimumab, stratified by Baseline Hurley Stage) to receive blinded IMP (all 
administered by subcutaneous [sc] injection by unblinded study personnel). 

Subjects randomized to receive bimekizumab will receive the following:

640mg at Baseline (loading dose)

320mg at Weeks 2, 4, 6, 8, and 10

Subjects randomized to receive adalimumab will receive the following:

160mg at Baseline (loading dose)

80mg at Week 2

40mg at Weeks 4, 5, 6, 7, 8, 9, and 10

Subjects randomized to receive placebo will receive placebo at Baseline (loading dose) and 
at Weeks 2, 4, 5, 6, 7, 8, 9, and 10
Because of differences in the dosing schedule between bimekizumab and adalimumab, placebo 
injections will be administered along with active drug such that all subjects will receive the same 
number of injections at each corresponding visit. The number of placebo and active injections 
will vary by visit and treatment group, as described in Section 7.2 and Table 7‒1. 
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Subjects withdrawing early from the study will undergo the Early Withdrawal Visit assessments 
and will enter the SFU Period. Subjects who withdraw early from IMP will be asked to return for 
study assessments 12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit.
The primary objective of this study is to evaluate the efficacy of bimekizumab in subjects with 
moderate to severe HS.
The secondary objective of this study is to assess the safety, tolerability, immunogenicity, and 
PK of bimekizumab in subjects with moderate to severe HS.
The exploratory objective of the study is to further assess efficacy of bimekizumab and to
explore the effect of bimekizumab on gene and protein expression, and to explore the 
relationship between pharmacodynamics (PD), nonhereditary pharmacogenomics 
pharmacogenetic, and imaging biomarkers and HS disease biology, drug treatment, and 
inflammatory and immune responses.
The primary efficacy variable is the clinical response as measured by HiSCR (defined as at least
a 50% reduction from Baseline in the total abscess and inflammatory nodule count, with no 
increase from Baseline in abscess or draining fistula count) at Week 12. The exploratory efficacy 
variables are listed in Section 4.1.2.
Pharmacokinetic and immunological variables are listed in Section 4.2 and will be evaluated to 
assess their relationship to treatment response. Pharmacodynamic, nonhereditary 
pharmacogenomic, pharmacogenetic, and imaging variables are listing in Section 4.5 and will 
also be evaluated to assess their relationship to treatment response.
Safety variables to be assessed are the frequency and severity of adverse events (AEs) and 
serious adverse events (SAEs), withdrawal due to AEs, changes from Baseline in vital signs, 
electrocardiogram (ECG) parameters, clinical laboratory parameters, and physical examination.
2
INTRODUCTION
2.1
Hidradenitis suppurativa
Hidradenitis suppurativa or acne inversa is a chronic, inflammatory, recurrent, debilitating skin 
disease that usually presents after puberty with painful, deep-seated, inflamed lesions in the 
apocrine gland-bearing areas of the body, most commonly the axillaries, inguinal, and anogenital 
regions (Dessau definition, First International Conference on HS, 30 March to 01 April 2006, 
Dessau, Germany). The nodules are often inflamed and may rupture to form fistulas and 
subsequent scarring. Thus, many patients with HS develop permanent sequelae of past 
inflammation that are only remediable through surgical excision of the involved skin areas. 
Hidradenitis suppurativa is also associated with several complications (eg, the development of 
anal, urethral, and rectal strictures and fistulas), and the excessive scarring and fibrosis produced 
by HS lesions can lead to contractures and limitations in limb mobility (Alikhan et al, 2009;
Danby and Margesson, 2010). 
Hidradenitis suppurativa is estimated to affect about 1% of the adult European population, with a 
female to male ratio of approximately 3:1 (Revuz et al, 2008; Naldi, 2006). Recent studies have 
suggested that the prevalence of diagnosed HS in the United States (US) is lower (<0.1%), with a 
need for further research to determine the prevalence of undiagnosed HS in the US
(McMillan, 2014). Patients diagnosed with HS often experience a significant reduction in 
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quality-of-life (QOL), equivalent to severe psoriasis (PSO; Sartorius et al, 2009), due to the 
location of, and discharge from, the lesions that leads to an often persistent morbidity due to pain 
and sequelae from uncontrolled inflammation (von der Werth and Jemec, 2001; 
Wolkenstein et al, 2007). The reduction in QOL and persistent morbidity result in functional 
impairment in patients with HS similar or greater to that of heart disease, diabetes, or asthma, 
when measured by the European Quality-of-Life 5 dimensions questionnaire (EQ-5D) scale 
(Riis et al, 2016). 
There is a strong association between HS and smoking, with a majority of patients being current 
or ex-smokers, and HS is associated with a variety of concomitant and secondary diseases, such 
as obesity, metabolic syndrome, inﬂammatory bowel disease (eg, Crohn’s disease [CD]), 
spondyloarthropathy, follicular occlusion syndrome, and other hyperergic diseases 
(Sartorius et al, 2009; van der Zee, 2010; Fimmel and Zouboulis, 2010; Tzellos et al, 2015; 
Zouboulis et al, 2015b).
2.1.1
Hidradenitis suppurativa disease pathology
Neutrophilic abscess formation and influx of mainly macrophages, monocytes, and dendritic 
cells predominate in early HS lesions. In chronic disease, the infiltrate expands with increased 
frequencies of B cells and plasma cells (van der Zee et al, 2012). A large number of 
IL-17-producing T helper cells (Th17) are shown to infiltrate the dermis in chronic HS lesions. 
Interleukin-17A and IL-17F are known to stimulate the expression of key mediators that drive 
the recruitment of neutrophil expression in upregulation of IL-17A. Increased levels of Th17 
cells may be, at least in part, responsible for the excessive neutrophilic inflammation and 
purulent drainage seen in primary and secondary HS lesional skin biopsies (Schlapbach et al, 
2011). Immunohistochemistry studies performed by UCB have shown that the increased 
expression levels of IL-17A are accompanied with increased IL-17F expression.  
Keratinocytes from HS patients have been shown to be dysfunctional, leading to an excessive
tissue protective response and a chronic inflammatory response and perpetual inflammation at 
sites of infection in skin lesions (Hotz et al, 2016). Interleukin-17 is capable of upregulating 
S100 calcium-binding protein A8 (S100A8) and S100A9 in keratinocytes (Cho et al, 2012). 
Antimicrobial proteins S100A8 and S100A9, constitutively expressed at low levels in healthy 
individuals, are danger responses when upregulated and induce proinflammatory cytokine and 
chemokine expression. This induction of proinflammatory cytokine and chemokine expression 
drives infiltration of leukocytes and contributes to the amplification of inflammation. As a net 
result this leads to proliferation of keratinocytes, which is a key factor in the pathology of HS
and its most impactful effects on patients such as fistula and scar formation (Baroja-Mazo et al, 
2014; Ehrchen et al, 2009).
2.1.2
Current treatments and unmet need
Hidradenitis suppurativa is difficult and challenging to treat. Treatment depends on the stage of 
disease (eg, presence of inflammatory components and/or scarring). Most patients respond only 
partially to treatment, or the disease rapidly reoccurs after drug cessation. Historically, available 
treatment options for HS varied widely and with the exception of the recent European and 
German treatment guidelines, there were few formal treatment guidelines for this condition 
(Zouboulis et al, 2015b). Bacterial infection is believed to be a secondary event in the disease 
process (Nikolakis et al, 2015; Nikolakis et al, 2016). While antibiotics generally do not cure the 
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disease, they may relieve symptoms through either an antibacterial or an anti-inflammatory 
effect. Topical antimicrobials are generally given for mild disease (either topical antiseptics, such 
as chlorhexidine, or topical antibiotics, such as clindamycin), with modest results 
(Clemmensen, 1983). Further treatment of HS can depend on the extent and activity of the 
disease and include medical treatments (eg, systemic combination therapy with clindamycin and 
rifampicin, tetracyclines including doxycycline and minocycline, intralesional triamcinolone, 
systemic cyclosporine, anti-androgen treatment in women, systemic dapsone, systemic retinoids, 
and metformin), surgical treatments (eg, radical excision, marsupialization, and deroofing), and 
laser treatment (Naldi, 2006; Jemec, 2010; Zouboulis et al, 2015b).
Adalimumab is the only approved medicinal product for the treatment of moderate to severe HS
with an inadequate response to conventional systemic HS therapy (approved in Sep 2015). 
However, 2 randomized, double-blind, placebo-controlled studies of adalimumab in a total of 
633 adult subjects with moderate to severe HS indicated that only around 50% of subjects
achieved a clinical response at Week 12. During the second part of both studies (up to 36 week 
treatment duration), approximately 40% of subjects who initially responded to adalimumab 
weekly therapy continued to benefit from this drug (Kimball et al, 2016a). 
In summary, there is still a significant unmet medical need for additional therapies to treat this 
condition. In addition, given the significant reduction in QOL and functional impairment 
experienced by patients diagnosed with HS, there is an unmet need for medical therapies that can 
have a substantial impact on improving a patient’s QOL. 
2.2
Bimekizumab
Bimekizumab is an engineered, humanized full-length mAb of immunoglobulin  G1 subclass of 
approximately 150,000 Daltons which is expressed in a genetically engineered Chinese Hamster 
Ovary (CHO) cell line. Bimekizumab has high affinity for human IL-17A and human IL-17F and 
selectively and potently inhibits the activity of both isoforms in vitro. Interleukin-17A and 
IL-17F are key pro-inflammatory cytokines believed to play important roles in autoimmune and 
inflammatory diseases. Bimekizumab is being developed for the treatment of patients with 
inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), PSO, and axial 
spondyloarthritis. While anti-IL-17A antibodies have demonstrated efficacy in patients with 
PSO, PsA, 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.
Published data and immunohistochemistry studies performed by UCB have shown that 
expression of both IL-17A and IL-17F are present in HS lesions and there are a number of 
published reports highlighting the potential for IL-17A and IL-17F to drive HS disease pathology 
(see Section 2.1.1). This supports the hypothesis that the IL-17 cytokine family is a potential 
therapeutic target in HS. Therefore, bimekizumab is hypothesized to demonstrate a treatment 
response in HS subjects because it selectively and potently inhibits the activity of both IL-17A 
and IL-17F isoforms in vitro.
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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 groups. 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 slight 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. The exploratory analysis showed clinically relevant 
improvement in activity of PsA and in skin involvement in those subjects with concomitant 
active psoriatic lesions.
Several additional studies of bimekizumab are ongoing in various patient populations (RA, 
ulcerative colitis, PSO, ankylosing spondylitis, and PsA). 
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB).
2.2.2
Nonclinical
Parallel inhibition of IL-17A and IL-17F has shown potent effects in a variety of animal models 
of inflammatory disease. Intravenously administered bimekizumab was well tolerated in repeat 
dose toxicology studies in Cynomolgus monkeys with a no adverse effect level of 
200mg/kg/week. The findings of note in toxicity studies were diarrhea related to infectious 
enteritis (observed in the single-dose study) and asymptomatic mild colonic ulceration in a 
proportion of animals (in the repeat-dose study); this latter finding was not associated with 
hematology abnormalities. Data suggest that bimekizumab has induced primary lesions to the 
mucosa-associated lymphoid tissue via a pharmacologically-related mechanism. In a second 
repeat-dose study, none of the minor apoptosis/necrosis findings observed in gut-associated 
lymph nodes were 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, the 
gut-associated lymph node lesions observed in the first study are considered to be accidental 
and/or linked to exaggerated pharmacology and proliferation of Balantidium coli and are 
considered to be the result of a change in local mucosal immunity. 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.
The dose of bimekizumab used in this study is supported by nonclinical data and clinical data 
(see Section 5.4).
3
STUDY OBJECTIVES
3.1
Primary objective
The primary objective of this study is to evaluate the efficacy of bimekizumab in subjects with 
moderate to severe HS.
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3.2
Secondary objective
The secondary objective of this study is to assess the safety, tolerability, immunogenicity, and 
PK of bimekizumab in subjects with moderate to severe HS.
3.3
Exploratory objective
The exploratory objective of the study is to further assess the efficacy of bimekizumab and to 
explore the effect of bimekizumab on gene and protein expression, and to explore the 
relationship between PD, nonhereditary pharmacogenomics, pharmacogenetic, and imaging 
biomarkers and HS disease biology, drug treatment, and inflammatory and immune responses.
4
STUDY VARIABLES
4.1
Efficacy variables
4.1.1
Primary efficacy variable
The primary efficacy variable is the clinical response as measured by HiSCR (defined as at least 
a 50% reduction from Baseline in the total abscess and inflammatory nodule count, with no 
increase from Baseline in abscess or draining fistula count) at Week 12.
4.1.2
Exploratory efficacy variables
The exploratory efficacy variables are listed below and will be evaluated at scheduled visits in 
accordance with the schedule of assessments in Table 5‒1.

Proportion of subjects with a total abscess and inflammatory nodule count of 0, 1, or 2 at 
Week 12

Proportion of subjects with at least a 30% reduction and at least 1 unit reduction from 
Baseline in the PGA of Skin Pain (based on the subject’s worst pain over the previous 
24 hours) at Week 12 

Change from Baseline in modified Sartorius score at Week 12

Change and percentage change from Baseline in lesion count (abscess count, inflammatory 
nodule count, abscess and inflammatory nodule count, and draining fistula count) 

Change from Baseline in International Hidradenitis Suppurativa Severity Score 
System (IHS4) over time

Change from Baseline in erythema assessment

Change from Baseline in Hurley Stage 

Change and percentage change from Baseline in PGA of Skin Pain (pain at its worst and pain 
on average over the last 24 hours) 

Change from Baseline in the HS-Physician’s Global Assessment 6-point scale 

Change from Baseline in the Dermatology Life Quality Index (DLQI) 

Change from Baseline in EQ-5D (index and visual analogue scale)

Change from Baseline in Hospital Anxiety and Depression Scale (HADS) 
HADS-Anxiety (A) and HADS-Depression (D) scores
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4.2
Pharmacokinetic, pharmacodynamic, pharmacogenomic, and 
pharmacogenetic variables
4.2.1
Secondary pharmacokinetic variable
Blood samples will be collected for the measurement of plasma bimekizumab concentrations at 
scheduled visits in accordance with the schedule of assessments in Table 5‒1.
4.2.2
Exploratory pharmacodynamic variables
The PD variables assessed at time points specified in Table 5‒1 are the blood or blood derivative 
(eg, plasma) concentrations of cytokines and chemokines of relevance to IL-17A/F signaling 
pathway and HS biology. Additional variables may include, but will not be limited to, serum 
complement concentrations and mononuclear cell subtypes.
4.2.3
Exploratory nonhereditary pharmacogenomic variables
Where local regulations permit, blood, urine and tissue biopsy samples will be collected at 
specific time points specified in Table 5‒1 and stored for up to 20 years to allow for potential 
exploratory analyses of ribonucleic acid (RNA), proteins, and metabolites biomarkers relevant to 
HS and the inflammatory and immune response processes. The nature and format of these 
tentative analyses will be determined at a later stage.
4.2.4
Exploratory pharmacogenetic variables
Additional blood samples will be collected from subjects who consent to participate in the 
pharmacogenetic substudy at specific time points specified in Table 5‒1 and stored at -80°C for 
up to 20 years. Pharmacogenetic biomarkers may be measured to evaluate the relationship with 
response to treatment with bimekizumab or adalimumab, HS disease biology, and inflammatory 
and immune response processes. The nature and format of these tentative substudy analyses will 
be determined when the results of the main study are made available.
4.3
Safety variables
4.3.1
Secondary safety variables
Safety variables to be assessed are:

Frequency and severity of AEs and SAEs

Withdrawal due to AEs 

Change from Baseline in vital signs (blood pressure [BP] and pulse rate) and body weight

Changes from Baseline in ECG parameters 

Change from Baseline in clinical laboratory parameters (hematology, biochemistry, and 
urinalysis) 

Change from Baseline in physical examination
4.4
Immunological variables
4.4.1
Secondary immunological variable
Blood samples will be collected for the measurement of anti-drug antibody (ADA) at scheduled 
visits in accordance with the schedule of assessments Table 5‒1.
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4.5
Imaging variables
4.5.1
Exploratory imaging variables
Imaging biomarkers will be assessed by means of medical infrared imaging (thermography) and 
photography in specific centers with technological capabilities. Subjects who consent to 
participate in the imaging substudy at specific timepoints are specified in Table 5‒1. Imaging 
biomarkers may be measured to evaluate the relationship with response to treatment with 
bimekizumab or adalimumab, HS disease biology, and inflammatory and immune response 
processes.
5
STUDY DESIGN
5.1
Study description
HS0001 is a Phase 2 multicenter, randomized, Investigator-blind, subject-blind, 
placebo-controlled, active reference arm study to assess the efficacy, safety, and PK of 
bimekizumab in eligible adult subjects with moderate to severe HS. To be eligible to participate 
in this study, subjects must be adults with a diagnosis of moderate to severe HS for at least 1 year
prior to Screening (lesions present in at least 2 distinct anatomic areas [1 of which must be at 
least Hurley Stage II or III] and a total abscess and inflammatory nodule count ≥3) that has been 
stable for at least 2 months prior to Screening with an inadequate response to at least a 3-month 
study of an oral antibiotic treatment for HS (or exhibited recurrence after discontinuation to, or 
demonstrated intolerance to, or have a contraindication to oral antibiotics for treatment of their 
HS). 
5.1.1
Study periods
This study will include 3 periods: a Screening Period (≥2 weeks up to a maximum of 4 weeks 
prior to randomization), a Treatment Period (12 weeks), and a SFU Period (20 weeks after the 
last dose of IMP).
Screening Period
The Screening Period will last ≥2 weeks up to a maximum of 4 weeks prior to randomization
(dosing cannot occur earlier than 2 weeks after Screening due to IMP shipping timelines). 
During this time, laboratory data (hematology, urine, and biochemistry tests) will be obtained, 
and other information will be collected to confirm subject eligibility for this study.
Treatment Period
During the Treatment Period, eligible subjects will be randomized 2:1:1 (bimekizumab to 
placebo to adalimumab, stratified by Baseline Hurley Stage) to receive blinded IMP (all 
administered by sc injection by unblinded study personnel). 

Subjects randomized to receive bimekizumab will receive the following:

640mg at Baseline (loading dose)

320mg at Weeks 2, 4, 6, 8, and 10

Subjects randomized to receive adalimumab will receive the following:

160mg at Baseline (loading dose)
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
80mg at Week 2

40mg at Weeks 4, 5, 6, 7, 8, 9, and 10

Subjects randomized to receive placebo will receive placebo at Baseline (loading dose) and 
at Weeks 2, 4, 5, 6, 7, 8, 9, and 10
Because of differences in the dosing schedule between bimekizumab and adalimumab, placebo 
injections will be administered along with active drug such that all subjects will receive the same 
number of injections at each corresponding visit. The number of placebo and active injections 
will vary by visit and treatment group, as described in Section 7.2  and Table 7‒1.
A sufficient number of subjects will be screened in order to have 80 subjects randomized in the 
study. There will be approximately 40 subjects in the bimekizumab treatment group, 20 subjects 
in the placebo group, and 20 subjects in the adalimumab group. The primary efficacy variable 
will be assessed at Week 12 (Visit 11).
Subjects who withdraw early from the study for any reason, including those withdrawn from
IMP, will be asked to return for study assessments 12 weeks after the first dose (ie, the Week 12 
Visit) and for an Early Withdrawal Visit that will comprise the same assessments as planned for 
the SFU Visit (Visit 12; 20 weeks after the last dose of IMP).
A Data Monitoring Committee (DMC) will review the data on an ongoing basis, as detailed in 
Section 11.5.
The assessments at each Treatment Period Visit are presented in Table 5‒1.
Safety Follow-Up Period
All subjects, including those withdrawn from IMP, will have a SFU Visit (Visit 12; 20 weeks 
after the last dose of IMP).
The assessments for the SFU Period are presented in Table 5‒1.
5.1.2
Study duration per subject
For each subject, the study will last a maximum of 34 weeks. This includes the following study 
period durations:

Screening Period: ≥2 weeks up to a maximum of 4 weeks, from the time of informed consent 
up to randomization and administration of IMP at Baseline (Visit 2).

Treatment Period: Up to 12 weeks, from the administration of IMP at Baseline (Visit 2) to 
the assessment of the primary efficacy variable at Week 12 (Visit 11).

SFU Period: Up to 20 weeks, from the last dose of IMP at Week 10 (Visit 10) to the SFU
Visit at Week 30 (Visit 12). 
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.3
Planned number of subjects and sites
A sufficient number of subjects will be screened in order to have 80 subjects randomized in the 
study at multiple sites in North America, Europe, and Asia-Pacific (APAC) regions. 
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5.1.4
Anticipated regions and countries
The regions planned for study conduct are North America, Europe, and APAC, with possible 
extension into other regions.
5.2
Schedule of study assessments
A schedule of study assessments is provided in Table 5‒1.
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Table 5‒1:
Schedule of study assessments
Procedures 
Screening
Period
Treatment Period
SFU 
Period
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 
10
Visit 11
Visit 12/
SFU 
Visit/EW 
Visit
Scr. a
Baseline
Day 1 b
Week 
2 (±3 
days)c
Week 
4 (±3 
days)c
Week 
5 (±3 
days)c
Week 
6 (±3 
days)c
Week 
7 (±3 
days)c
Week 
8 (±3 
days)c
Week 
9 (±3 
days)c
Week 
10 (±3 
days)c
Week 
12 (±3 
days)c
Week 30
(-3 to +7 
days)c
Written informed consent
X
Demographics and 
Baseline characteristicsd
X
Inclusion/exclusion 
criteria verification
X
X
Significant past medical 
history and concomitant 
diseases
X
Xe
Hidradenitis suppurativa
history
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination f
X
X
X
X
X
X
X
X
X
Body weight
X
X
X
X
Vital signs g
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
Pregnancy test h
X
X
X
X
X
X
Urine drug screen
X
Hematology, 
biochemistry, urinalysis
X
X
X
X
X
X
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Table 5‒1:
Schedule of study assessments
Procedures 
Screening
Period
Treatment Period
SFU 
Period
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 
10
Visit 11
Visit 12/
SFU 
Visit/EW 
Visit
Scr. a
Baseline
Day 1 b
Week 
2 (±3 
days)c
Week 
4 (±3 
days)c
Week 
5 (±3 
days)c
Week 
6 (±3 
days)c
Week 
7 (±3 
days)c
Week 
8 (±3 
days)c
Week 
9 (±3 
days)c
Week 
10 (±3 
days)c
Week 
12 (±3 
days)c
Week 30
(-3 to +7 
days)c
Serology (HIV, Hepatitis 
B and C virus) i
X
Chest x-ray or CAT scan 
of chest j
X
TB questionnaire
X
X
X
X
IGRA TB test k
X
X
Blood sampling for plasma 
PK levels of 
bimekizumab l
X
X
X
X
X
X
Blood samples for PD and 
nonhereditary 
pharmacogenomic 
variables l m
X
X
X
Blood samples for 
pharmacogenetic 
variables l n
X
X
Blood samples for plasma 
levels of bimekizumab 
ADA l
X
X
X
X
X
X
Urine samples for 
biomarker research
X
X
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Table 5‒1:
Schedule of study assessments
Procedures 
Screening
Period
Treatment Period
SFU 
Period
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 
10
Visit 11
Visit 12/
SFU 
Visit/EW 
Visit
Scr. a
Baseline
Day 1 b
Week 
2 (±3 
days)c
Week 
4 (±3 
days)c
Week 
5 (±3 
days)c
Week 
6 (±3 
days)c
Week 
7 (±3 
days)c
Week 
8 (±3 
days)c
Week 
9 (±3 
days)c
Week 
10 (±3 
days)c
Week 
12 (±3 
days)c
Week 30
(-3 to +7 
days)c
Lesional and nonlesional 
skin biopsy
X
X
Photography and 
thermography o
X
X
X
X
Lesion count (including 
Hurley Stage) p
X
X
X
X
X
X
X
X
X
Modified Sartorius score
X
X
Erythema assessment
X
X
X
X
X
X
X
X
X
PGA of Skin Pain
X
X
X
X
X
X
X
X
Hidradenitis 
Suppurativa-Physician’s 
Global Assessment
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
EQ5D
X
X
X
X
X
X
X
X
HADS
X
X
X
X
X
X
X
X
X
C-SSRS
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
Subject identification 
number assigned q
X
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Table 5‒1:
Schedule of study assessments
Procedures 
Screening
Period
Treatment Period
SFU 
Period
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 
10
Visit 11
Visit 12/
SFU 
Visit/EW 
Visit
Scr. a
Baseline
Day 1 b
Week 
2 (±3 
days)c
Week 
4 (±3 
days)c
Week 
5 (±3 
days)c
Week 
6 (±3 
days)c
Week 
7 (±3 
days)c
Week 
8 (±3 
days)c
Week 
9 (±3 
days)c
Week 
10 (±3 
days)c
Week 
12 (±3 
days)c
Week 30
(-3 to +7 
days)c
Randomization r
X
IMP treatment s
X
X
X
X
X
X
X
X
X
ADA=anti-drug antibody; BMI=body mass index; CAT=Computed Axial Tomography; C-SSRS= Columbia-Suicide Severity Rating Scale; DLQI=Dermatology 
Life Quality Index; ECG=electrocardiogram; EQ-5D=European Quality-of-Life 5 dimensions questionnaire; EW=Early Withdrawal; HADS=Hospital Anxiety 
and Depression Scale; HiSCR=Hidradenitis Suppurativa Clinical Response; HIV=human immunodeficiency virus; IGRA=interferon-gamma release assay; 
IMP=investigational medicinal product; PD=pharmacodynamics; PGA=Patient's Global Assessment; PK=pharmacokinetics; RNA=ribonucleic acid; 
Scr.=Screening; SFU=Safety Follow-Up; TB=tuberculosis
Note: For subjects who prematurely terminate or complete the study, final study disposition will be recorded at the Early Withdrawal Visit. All subjects who 
prematurely terminate the study, including those withdrawn from IMP, will be asked to return for study assessments 12 weeks after the first dose (ie, the 
Week 12 Visit) and for an EW Visit that will comprise the same assessments as planned for the SFU Visit (Visit 12; 20 weeks after the last dose of IMP).
a The Screening Period will last ≥2 weeks up to a maximum of 4 weeks prior to randomization (dosing cannot occur earlier than 2 weeks after Screening due to 
IMP shipping timelines).
b Day 1 is defined as the first day of administration and Day –1 is defined as the day before Day 1. Baseline (Visit 2) will include a visit window of ±2 days for 
all assessments prior to the first dose of IMP.
c Visit windows of ±3 days from the first dose at all visits except SFU. The SFU Visit window is -3 and +7 days from last dose.
d Will include lifestyle, childbearing potential, as applicable, height, and BMI.
e Ensure no significant changes in medical history and concomitant disease.
f Will include an evaluation of signs and symptoms of active TB and risk of exposure to TB at Screening and the SFU Visit (Visit 12).
g Vital signs (blood pressure, pulse rate, and temperature) are to be measured prior to blood sampling, and prior to dosing, where applicable.
h Pregnancy testing will be serum testing at Screening and the SFU Visit (Visit 12). The pregnancy test will be urine at all other visits.
i Subjects with HIV infection or who have evidence of, or tested positive for hepatitis B or hepatitis C virus are excluded. A positive test for the hepatitis B virus 
is defined as: 1) positive for hepatitis B surface antigen; or, 2) positive for anti-hepatitis B core antibody. A positive test for the hepatitis C virus is defined as: 
1) positive for hepatitis C antibody, and 2) positive via a confirmatory test for hepatitis C virus (for example, hepatitis C virus polymerase chain reaction).
j A chest x-ray must be performed at Screening or must occur within 3 months prior to Screening and results must be available at Baseline. A CAT scan of chest 
at Screening or within 3 months prior to Screening is acceptable, if available.
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k It is recommended that the QuantiFERON TB GOLD test be performed.
l All blood samples taken prior to dosing.
m The PD variables measured include: cytokines, complement, candidate biomarker analysis, and flow cytometry. The nonhereditary pharmacogenomics 
variables include RNA, proteins, and metabolites biomarkers.
n A separate Informed Consent Form will be required for subjects who decide to participate in the pharmacogenetic substudy. The Informed Consent Form must 
be signed prior to collecting any samples for the substudy.
o At certain sites, where feasible, representative photographs of the changes in skin will be captured. Photographs will be anonymized. Thermography (as 
described in Section 13) will also be performed at the same sites as photography.
p The lesion count will be performed at every study visit and must address all relevant anatomical regions in each subject; Hurley Stage is included as an 
assessment performed during the lesion count. See Section 9.3 for more details. The data collected from the lesion count will be used for the derivation of the 
HiSCR and International Hidradenitis Suppurativa Severity Score (see Section 9.1 and Section 9.2 for more details).
q The Investigator or designee will contact the Interactive Response Technology for the subject identification number.
r Randomization to IMP will occur at Baseline (Visit 2) and an Interactive Response Technology will be used for assigning eligible subjects to a treatment 
regimen. Subjects will be randomized 2:1:1 to bimekizumab, placebo, or adalimumab (stratified by Baseline Hurley Stage).
s Subjects will receive assigned IMP as described in Section 7.2 of the protocol. Because of differences in the dosing schedule between bimekizumab and 
adalimumab, a double-dummy approach will be applied such that all subjects receive 4 injections of IMP at Baseline; 2 injections of IMP at Weeks 2, 4, 6, 8, 
and 10; and 1 injection of IMP at Weeks 5, 7, and 9. The number of placebo and active injections will vary by visit and treatment group, as shown in Table 7‒1.
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leads to increased response and it is anticipated that a dose above 480mg Q4W is unlikely to lead 
to further clinical benefit in terms of PASI90 response; therefore, 480mg Q4W has been selected 
as the maximum dose in the study. The proposed dosage regimen in this study is predicted to 
achieve median trough concentrations >40µg/ml and is greater than those achieved with the 480 
mg Q4W regimen in PSO. The 640mg dose administered at Baseline allows the predicted 
concentrations to be achieved rapidly, and 320mg Q2W is expected to maintain these 
concentrations over a period of 12 weeks.  
The proposed dose of 640mg at Baseline is predicted to achieve 6.8-fold lower Cmax (after first 
dose) compared to 640mg iv tested in mild PSO subjects due to a lower bioavailability following 
sc administration. Similarly, the predicted steady-state Cmax following the proposed multiple 
dose regimen is 2-fold lower compared to the 560mg/320 mg Q3W regimen tested in PsA 
subjects, while the AUCτ values are expected to be similar after accounting for differences in 
dosing interval. The predicted and observed PK parameters are shown in Table 5-2.
Table 5-2:
Observed and model-predicted pharmacokinetic parameters for 
bimekizumab
Parameter
640mg iv 
(UP0008)
Median (Geo CV%)
540/320mg Q3W iv
(PA0007)
Median (Geo CV%)
640/320mg Q2W sc
(Model predicted)
Median (90% PI)
Cmax (µg/mL)
260 (21.40)
--
38 (23-70)
Steady-state Cmax (µg/mL)
--
134.2 (22)
63 (37-121)
AUCτ or AUCα (µg*day/mL)
3787(39.034) a
1463 (18.9) b
823 (487-1588)
Geo CV=geometric coefficient of variation; iv=intravenous; PI=prediction interval; Q2/3W=every 2/3 weeks; 
sc=subcutaneous
a This value is for AUCα.
b This value is for AUCτ.
Current safety data from 106 subjects exposed to bimekizumab do not suggest dose dependency. 
Specifically, bimekizumab administered by iv infusion as a single ascending dose was tolerated 
at doses of up to 640mg in mild PSO subjects (UP0008). The MTD was not reached, and no 
safety issues were identified. No safety concerns were identified in PsA subjects (in PA0007),
and bimekizumab was well tolerated at multiple dose administrations up to 560mg/320mg Q3W 
in subjects with PsA. There are multiple Phase 2b studies in PSO, PsA, and axial 
spondyloarthritis that are currently being conducted and the emerging data are not signaling any 
major safety concern. See Section 2.2.1 for further details on the clinical experience of 
bimekizumab.
Bimekizumab was well tolerated in the Cynomolgus monkey when administered iv or sc at doses 
up to 200mg/kg every week for up to 26 weeks; no treatment-related changes in clinical signs, 
clinical pathology, or histopathology indicative of toxicity were noted. No changes in BP or heart 
rate and no significant effects on ECG lead II parameters (PR, RR, QT, QT corrected for heart 
rate [QTc] intervals, and QRS duration) that could be ascribed to bimekizumab were noted. The 
only findings were related to decreased muco-epidermal immunity. These findings were variable 
from 1 study to the other, affected only some animals, occurred at doses exceeding largely those 
required for full IL-17A and IL-17F neutralization and translation to human was considered 
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unlikely. Additional information on the clinical and nonclinical data for bimekizumab is 
available in the current version of the IB.
The dose of bimekizumab used in this study supports the maximum likelihood of demonstrating 
the potential efficacy for bimekizumab in subjects with moderate to severe HS with an 
acceptable safety profile. Measures have also been taken to ensure the well-being of subjects by 
applying appropriate inclusion and exclusion criteria to recruit a target population that is most 
likely to benefit from treatment, while excluding subjects with an unacceptable risk to enter the 
study (see Section 6.2). Further, during the study, measures are in place to monitor the safety of 
subjects on a weekly basis, including assessment of cardiovascular risk factors as well as the 
potential risk of suicidal ideation and behavior. An independent DMC will also review the data 
on an ongoing basis, as detailed in Section 11.5.
Adalimumab will be administered at the approved dose for HS.
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 (ICF) is signed and dated by the subject or by the legal 
representative. 
2. Subject/legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete diaries), visit schedule, and medication intake according 
to the judgment of the Investigator.
3. Adult subjects (18 to 70 years of age, inclusive) must have a diagnosis of HS for at least 
1 year prior to Baseline.
4. Hidradenitis suppurativa lesions must be present in at least 2 distinct anatomic areas, 1 of 
which must be at least Hurley Stage II or Hurley Stage III.
5. Subject must have stable HS for at least 2 months prior to Screening and also at the Baseline 
Visit as assessed by the Investigator through subject interview and review of medical history.
6. Subject must have had an inadequate response to at least a 3-month study of an oral antibiotic 
for treatment of HS (or exhibited recurrence after discontinuation to, or demonstrated 
intolerance to, or have a contraindication to oral antibiotics for treatment of their HS) as 
assessed by the Investigator through subject interview and review of medical history.
7. Subject must have a total abscess and inflammatory nodule count ≥3 at the Baseline Visit.
8. Subject must be considered, in the opinion of the Investigator, to be a suitable candidate for 
treatment with adalimumab per regional labeling. 
9. Subject must have a C-reactive protein (CRP) level >3mg/L at the Baseline Visit.
10. Subject has a negative tuberculosis (TB) Screening assessment (including an 
interferon-gamma release assay [IGRA] test using QuantiFERON-TB Gold test, or 
equivalent) and negative posterior-anterior chest x-ray (CXR) or Computed Axial 
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Tomography (CAT) scan of chest at Screening or within 3 months prior to Screening 
(nuclear magnetic resonance films are not acceptable).
11. Subject must agree to daily use (and throughout the entirety of the study) of 1 of the 
following over-the-counter topical antiseptics on their HS lesions: chlorhexidine gluconate, 
triclosan, benzoyl peroxide, or dilute bleach in bathwater.
12. Subject is assessed to have no other medical condition that would preclude their participation 
in the study, as determined by the Principal Investigator based upon the results of a medical 
history, physical examination, laboratory profile, and a 12-lead ECG performed during the 
Screening Period, and confirmed at Baseline.
13. Female subjects must be postmenopausal (at least 1 year; to be confirmed hormonally as part 
of the Screening process, if less than 2 years since last menstrual period), permanently 
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing 
potential, must be willing to use a highly effective method of contraception up till 20 weeks 
after last administration of IMP, and have a negative pregnancy test at Visit 1 (Screening) 
and immediately prior to first dose. The following methods are considered highly effective 
when used consistently and correctly.

combined (estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation (oral, intravaginal, or transdermal).

progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable).

intrauterine device (IUD).

intrauterine hormone-releasing system (IUS).

bilateral tubal occlusion.

vasectomized partner (where postvasectomy testing had demonstrated sperm 
clearance).

sexual abstinence if it is in accordance with a subject’s preferred and common 
lifestyle. Subjects who use abstinence as a form of birth control must agree to abstain 
from heterosexual intercourse until 20 weeks after the last dose of IMP. Study 
personnel must confirm the continued use of abstinence is still in accordance with the 
subject’s lifestyle at regular intervals during the study.
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up till 20 weeks after the last administration of IMP (anticipated 5 half-lives).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Prior treatment with anti-IL17s or participation in an anti-IL17 study.
2. Subjects who previously received anti-TNFs.
3. Subjects participating in another study of a medication or a medical device under 
investigation within the last 3 months or at least 5 half-lives of the investigational product, 
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whichever is greater, or is currently participating in another study of a medication or medical 
device under investigation.
4. Subject has a known hypersensitivity to any excipient(s) of bimekizumab or adalimumab.
5. Subject is using concomitant oral analgesics for HS-related or non-HS-related pain at study 
entry:

Opioid analgesics within 14 days prior to the Baseline Visit.

Non-opioid oral analgesics unless at a stable dose for at least 14 days prior to the 
Baseline Visit (PRN use is not considered a stable dose).
6. Subject requires, or is expected to require, opioid analgesics for any reason (excluding 
tramadol).
7. Subject received prescription topical therapies for the treatment of HS within 14 days prior to 
the Baseline Visit.
8. Subject received systemic non-biologic therapies for HS with potential therapeutic impact for 
HS less than 28 days prior to Baseline Visit.
9. Subject has a draining fistula count >20 at the Baseline Visit.
10. Subjects with a diagnosis of inflammatory conditions other than HS, including but not 
limited to PSO, PsA, RA, sarcoidosis, or systemic lupus erythematosus. Subjects with a 
diagnosis of CD or ulcerative colitis are allowed as long as they have no active symptomatic 
disease at Screening or Baseline.
11. Subjects with a history of chronic or recurrent infections, or a serious or life-threatening 
infection within the 6 months prior to the Baseline Visit (including herpes zoster). Subjects 
with a high risk of infection in the Investigator’s opinion (eg, subjects with leg ulcers, 
indwelling urinary catheter, persistent or recurrent chest infections, prior prosthetic joint 
infection at any time, subjects who are permanently bedridden or wheelchair assisted).
12. Subject has any current sign or symptom that may indicate an active infection (except for 
common cold), or has had an infection requiring systemic antibiotics within 2 weeks of the 
Baseline Visit.
13. Any other active skin disease or condition (eg, bacterial, fungal or viral infection) that may 
interfere with assessment of HS.
14. Subject has history of or current clinically active infection with Histoplasma, Coccidiodes, 
Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), Blastomyces, or 
Aspergillus or current active Candidiasis (local or systemic).
15. Subject has acute or chronic viral hepatitis B virus (HBV), hepatitis C virus (HCV), or 
human immunodeficiency virus (HIV) infection. Subjects who have evidence of, or tested 
positive for, hepatitis B or hepatitis C are excluded.

A positive test for the HBV is defined as: 1) positive for hepatitis B surface antigen; 
or, 2) positive for anti-hepatitis B core antibody.
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
A positive test for the HCV is defined as: 1) positive for hepatitis C antibody, and 
2) positive via a confirmatory test for HCV (for example, HCV polymerase chain 
reaction).
16. Subjects with known TB infection, at high risk of acquiring TB infection, with latent TB 
infection (LTB), or current or history of NTMB infection (refer to Section 11.3.1 for details 
on determining full TB exclusion criteria).
17. Subject has a primary immunosuppressive condition, including taking immunosuppressive 
therapy following an organ transplant, or has had a splenectomy.
18. Subjects with concurrent malignancy or history of malignancy (including surgically resected 
uterine/cervical carcinoma-in-situ) during the past 5 years will be excluded, with the 
following exceptions that may be included:
a.
≤3 excised or ablated, basal cell carcinomas of the skin.
b. One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or 
ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of 
recurrence or metastases for more than 2 years prior to Screening.
c.
Actinic keratosis(-es).
d. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 
6 months prior to Screening).
19. Subject has a history of a lymphoproliferative disorder including lymphoma or current signs 
and symptoms suggestive of lymphoproliferative disease.
20. Subject has history of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
21. Subjects with a current or recent history, as determined by the Investigator, of severe, 
progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac 
(eg, congestive heart failure, New York Heart Association Grade 3 and 4), gastrointestinal
(note: subjects with active peptic ulcer disease are excluded; subjects with a history of peptic 
ulcer disease are allowed), neurological disease, or inflammatory bowel disease.
22. Subject has a history of uncompensated heart failure, fluid overload, or myocardial 
infarction, or evidence of new onset ischemic heart disease or (in the opinion of the 
Investigator) other serious cardiac disease, within 12 weeks prior to the Baseline Visit.
23. Presence of active suicidal ideation, or positive suicide behavior using the “Baseline” version 
of the Columbia-Suicide Severity Rating Scale (C-SSRS) and the HADS with either of the 
following criteria:

Subject has a lifetime history of suicide attempt (including an actual attempt, 
interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months 
as indicated by a positive response (“Yes”) to either question 4 or question 5 of the 
“Screening/Baseline” version of the C-SSRS at Screening.

HADS-D score ≥10 and HADS-A score ≥15.
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24. Subject has >2x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), *alkaline phosphatase (ALP), or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If subject has 
elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to 
identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
*An isolated elevation between 2xULN and <3xULN of ALP is acceptable in the absence of 
an identified exclusionary medical condition.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation during the Screening Period. Upon retesting, subjects whose ALT, 
AST, or ALP remain above the thresholds defined above, should not be randomized. 
For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, 
a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be 
understood and recorded in the electronic Case Report form (eCRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at Screening, 
repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically 
relevant increase. In case of a clinically relevant increase, inclusion of the subject must be 
discussed with the Medical Monitor and/or UCB Study Physician.
25. Subjects with clinically significant laboratory abnormalities (eg, creatinine >1.5xULN, 
neutropenia <1.5x109/L, hemoglobin <8.5g/dL, lymphocytes <1.0x109/L, platelets 
<100x109/L). Individual Screening tests for which the results are in error, borderline, or 
indeterminate for inclusion in the study, can be repeated once for confirmation during the 
Screening Period if they are within 25% of the exclusion limit. Upon retesting, subjects 
whose results remain outside this threshold should not be randomized.
26. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review (eg, QTc using Fridericia’s correction [QTcF] >450ms, bundle branch block, 
evidence of myocardial ischemia).
27. Subject has received any live (includes attenuated) vaccination within the 8 weeks prior to 
the Baseline Visit (eg, inactivated influenza and pneumococcal vaccines are allowed but 
nasal influenza vaccination is not permitted). Live vaccines are not allowed during the study 
or for 20 weeks after the last dose of IMP.
28. Subject has received Bacillus Calmette-Guerin vaccination within 1 year prior to IMP
administration.
29. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
30. Subjects with any other condition which, in the Investigator's judgement, would make the 
subject unsuitable for inclusion in the study.
31. Subject has previous exposure to adalimumab.
32. Subjects are Investigator site personnel directly affiliated with this study and/or their 
immediate families. Immediate family is defined as a spouse, parent, child, or sibling, 
whether biological or legally adopted.
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33. Subjects are UCB employees or are employees of third-party organizations involved in the 
study.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects should be withdrawn from the study and encouraged to come for the SFU Visit 
(20 weeks after the last dose of IMP) if any of the following events occur:
1. Subject withdraws his/her consent.
2. The Sponsor or a regulatory agency requests withdrawal of the subject.
Subjects should be withdrawn from all IMP and will be asked to return for the study assessments 
12 weeks after the first dose (ie, the Week 12 Visit) and for the SFU Visit (20 weeks after the 
last dose of IMP) if any of the following events occur:
1. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
2. Subject develops an illness that would interfere with his/her continued participation.
3. Subject considered to have either a suspected new LTB infection or who develops active TB 
or NTMB infection during the study (including but not limited to conversion demonstrated 
by IGRA or other diagnostic means) must be immediately discontinued from IMP and an 
Early Withdrawal Visit must be conducted 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.
Additional information on TB policies are provided in Section 11.3.1.
4. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
5. Subject uses prohibited concomitant medications, with the exception of topicals, as defined 
in this protocol (Section 7.8.2), that may present a risk to the safety of the subject in the 
opinion of the Investigator and/or the Medical Monitor and/or UCB Study Physician.
6. Subject develops total bilirubin >2xULN (except Gilbert’s); neutropenia <1.0x109/L; 
lymphopenia <0.5x109/L.
7. Subject has active suicidal ideation as indicated by a positive response (“Yes”) to questions 4 
or 5 or to the suicidal behavior questions of the “Since Last Visit” version of the self-rated 
C-SSRS. The subject should be referred immediately to a Mental Healthcare Professional 
and must be withdrawn from the study.
8. Subjects with a HADS-D score ≥15 must be withdrawn. Any subject who has a HADS-D 
score of ≥10 should be referred immediately to a Mental Healthcare Professional for further 
evaluation and potential withdrawal by the Investigator.
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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 and/or UCB Study 
Physician. 

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: 
“Blood and lymphatic disorders,” “Cardiac disorders,” or “Vascular disorders.” 
◦
Persistent is defined as lasting 28 days or more, which spans at least 2 bimekizumab 
dosing visits.
10. Subject has a clinical laboratory value meeting the following criteria:

CTCAE Grade 3 and above: subject must be withdrawn regardless of relationship to 
study drug or duration of event, unless the abnormal laboratory value is a natural 
variation of a condition pre-existing before Baseline (eg, hypercholesterolemia). 

CTCAE Grade 2
◦
Subject may remain in the study if the event is transient. If a subject has a Grade 2 
laboratory abnormality that is not an expected natural variation of a condition present 
before Baseline, 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. 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 or 
discontinuation. For subjects considered as lost to follow-up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The eCRF must document the primary reason for withdrawal.
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Investigators should contact the Medical Monitor and/or UCB Study Physician, whenever 
possible, to discuss the withdrawal of a subject in advance.
6.3.1
Potential drug-induced liver injury investigational medicinal product
discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
The PDILI criteria below require immediate and permanent discontinuation of IMP: 

Subjects with either of the following:

ALT or AST ≥5xULN.

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN.

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain, or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator. 

Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis 
(eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness).
Evaluation of PDILI must be initiated as described in Section 11.2.1. 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
Reasons for suspension or discontinuation of the study can fall into 1 of the following 2 principal 
categories: safety and other reasons.
6.4.1
Safety
Should a critical safety issue or signal be identified during the study, then planned dosing and 
procedures may be discontinued or suspended for subjects in any part of the study and 
appropriate follow up procedures established. 
Where an individual Investigator believes such a safety issue or signal has been identified in one 
or more of the subjects under their care, further dosing of those subjects may be suspended, but 
this action should be discussed with the UCB Study Physician prior to its implementation, unless 
any delay incurred would materially threaten the safety of those subjects.
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Placebo will be supplied as 0.9% sodium chloride aqueous solution (physiological saline, 
preservative free) of pharmacopoeia (US Pharmacopoeia/European Pharmacopoeia) quality 
appropriate for injection.
Further details of the IMPs and their specifications are provided in the IMP Handling Manual.
7.2
Treatments to be administered
Subjects will be randomized in a 2:1:1 ratio to bimekizumab, placebo, or adalimumab (stratified 
by Baseline Hurley Stage). 

Subjects randomized to receive bimekizumab will receive the following:

640mg at Baseline (loading dose)

320mg at Weeks 2, 4, 6, 8, and 10

Subjects randomized to receive adalimumab will receive the following:

160mg at Baseline (loading dose)

80mg at Week 2

40mg at Weeks 4, 5, 6, 7, 8, 9, and 10

Subjects randomized to receive placebo will receive placebo at Baseline, and Weeks 2, 4, 5, 
6, 7, 8, 9, and 10
Because of differences in the dosing schedule between bimekizumab and adalimumab, placebo 
injections will be administered along with active drug such that all subjects will receive the same 
number of injections at each corresponding visit. The number of placebo and active injections 
will vary by visit and treatment group, as shown in Table 7‒1. 
Table 7‒1:
Administration of investigational medicinal product
Treatment group
Visit
Adalimumab a
(Total # injections, # of 
placebo injections)
Bimekizumab b
(Total # injections, # of 
placebo injections)
Placebo
Baseline
160mg 
(4 active injections, 
no placebo injections)
640mg 
(4 active injections,
no placebo injections)
4 placebo injections
Week 2
80mg 
(2 active injections, 
no placebo injections)
320mg 
(2 active injections, 
no placebo injections)
2 placebo injections
Weeks 4, 6, 8, and 10
40mg 
(1 active injection, 
1 placebo injection)
320mg 
(2 active injections, no 
placebo injections)
2 placebo injections
Weeks 5, 7, and 9
40mg 
(1 active injection, 
no placebo injection)
NA
(no active injection, 
1 placebo injection)
1 placebo injection
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Table 7‒1:
Administration of investigational medicinal product
Treatment group
Visit
Adalimumab a
(Total # injections, # of 
placebo injections)
Bimekizumab b
(Total # injections, # of 
placebo injections)
Placebo
Baseline
160mg 
(4 active injections, 
no placebo injections)
640mg 
(4 active injections,
no placebo injections)
4 placebo injections
NA=not applicable
Note: All treatments will be administered as subcutaneous injections.
a Each individual adalimumab injection will be 40mg.
b Each individual bimekizumab injection will be 160mg.
Bimekizumab will be supplied in vials, placebo will be supplied as a 0.9% sodium chloride 
aqueous solution (physiological saline, preservative free) of pharmacopoeia (US 
Pharmacopoeia/European Pharmacopoeia) quality appropriate for injection, and commercially 
available adalimumab will be supplied in prefilled syringes. Thus, in order to maintain the 
treatment blind the dosing solution will be prepared by the unblinded pharmacist and 
administered by unblinded study personnel (see Section 7.9). The unblinded study personnel will 
not have any other involvement in the study, and subject assessments will be performed by 
blinded study personnel.
Injections will be administered sc to the lateral abdominal wall or upper outer thigh. 
Investigational medicinal product will be administered by unblinded, qualified study personnel at 
the study site.
The injection should last approximately 20 seconds. The time of administration, volume, and 
injection site will be documented in the eCRF. 
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing.
7.3
Packaging
Bimekizumab, adalimumab, and placebo will be packaged and labeled according to Good 
Manufacturing Practice (GMP) guidelines and applicable laws or regulations. They will be 
suitably packaged in such a way as to protect the product from deterioration during transport and 
storage. Further information regarding storage and transport conditions are provided in the IMP 
Handling Manual.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required 
statements. If necessary, labels will be translated into the local language. If necessary, labels will 
be translated into the local language as appropriate. Details on labeling will be provided in the 
IMP Handling Manual.
7.5
Handling and storage requirements
Refer to the IMP Handling Manual for the storage conditions of the IMP.
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The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access according to the storage conditions mentioned on the label. Appropriate storage 
conditions must be ensured either by controlling the temperature (eg, room, refrigeration unit) or 
by completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a week), showing actual and minimum/maximum temperatures reached over the time 
interval. In case an out-of-range temperature is noted, it must be immediately reported as per 
instructions contained in the IMP Handling Manual.
The IMP will be shipped to the study sites in temperature controlled containers. Out-of-range 
shipping or storage conditions must be brought to the attention of the Sponsor or designee, 
immediately. Authorization to use any out-of-range IMP must be documented and received prior 
to dispensing or administering the IMP at the study site.
7.6
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the 
study site, or returned to the Sponsor or designee must also be recorded on the appropriate forms. 
All supplies and pharmacy documentation must be made available throughout the study for UCB 
(or designee) to review.
In order to maintain the blind, all IMP documentation (eg, shipping receipts, drug accountability 
logs, Interactive Response Technology [IRT] randomization materials) must be maintained and 
accessed by unblinded, trained site personnel only. 
Only unblinded study staff may be involved in the receipt, inventory, and destruction of the used, 
partially used, damaged, or unused kits since the packaging is unblinding. Unblinded study staff 
will be responsible for preparation (breaking tamper proof sticker on kit, etc) of the IMP, 
including recording the administration information on source document. Designated, unblinded 
site personnel must be appropriately trained and licensed (per country guidelines) to administer 
injections.
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 Standard Operating 
Procedures (SOPs) or returned to UCB (or designee). Investigational medicinal product intended 
for the study cannot be used for any other purpose than that described in this protocol.
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7.7
Procedures for monitoring subject compliance
During the Treatment Period of this study, IMP will be administered in the clinic and compliance 
will be determined at the visit by study personnel. Drug accountability must be recorded on the 
Drug Accountability Form.
7.8
Concomitant medications/treatments
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications/treatments are permitted during the study:

Antiseptic Therapy

Subjects are required to use a daily antiseptic wash on their HS lesions. Allowable 
antiseptic washes are limited to one of the following: chlorhexidine gluconate, 
triclosan, benzoyl peroxide, or dilute bleach in bathwater.

Wound Care

Concomitant use of wound care dressings on HS wounds is allowed; however,
options are limited to alginates, hydrocolloids, and hydrogels.

Analgesic Therapy

Most subjects will be required to washout all analgesics for 14 days prior to Baseline.
This includes analgesics for HS-related pain and other pain (non-HS-related). 
However, if a subject is on a stable dose of a non-opioid analgesic (PRN is not 
considered stable) for HS-related pain or for a non-HS medical condition (eg,
osteoarthritis), the subject may continue the analgesic, provided the dose is stable for 
14 days prior to Baseline and is anticipated to remain stable throughout study 
participation.

If a subject's pain (HS-related or non-HS-related) worsens after Baseline, they may
initiate analgesic therapy at any time as follows: For HS-related pain, permitted 
analgesics are limited to: ibuprofen (at a dose of up to 800 mg po every 6 hours) not 
to exceed 3.2 grams/per 24 hours; AND/OR acetaminophen/paracetamol as per local 
labeling. If HS-related pain is uncontrolled with ibuprofen or 
acetaminophen/paracetamol at the above dosing regimens after the Baseline Visit 
(Visit 2), subjects can be prescribed tramadol (at a dose of up to 100mg po every 4 
hours), not to exceed 400mg per 24 hours.

Antibiotic Therapy

Concomitant use of oral antibiotic therapy for treatment of HS is allowed provided 
the dosing regimen (dose and frequency) has been stable for at least 4 consecutive 
weeks (28 days) prior to Baseline. The dosing regimen must remain stable throughout 
study participation. Antibiotics taken on an "as needed" (PRN) basis are not 
considered a stable dose.

Permitted oral concomitant antibiotics include:
°
Oral: doxycycline (at a dose of up to 100 mg po bid); minocycline (at a dose 
of up to 100 mg po bid)
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°
If another Baseline oral concomitant antibiotic for HS is medically necessary, 
the UCB Study Physician must be contacted for approval. If systemic 
antibiotics are used concomitantly, the dose should remain stable and 
constant.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications are prohibited during the study:

Any other immunomodulatory therapy, including systemic steroids 

Any analgesics other than those specified in Section 7.8.1

Medications contraindicated for administration with adalimumab (per the regional approved 
labelling), including, but not limited to, abatacept, anakrina, and other TNF-blocking agents

All other biologics
7.8.3
Rescue medication
There are no absolute restrictions on the use of concomitant medications to “rescue” subjects 
whose HS deteriorates during the course of the study. While the objectives of the study should be 
protected as much as possible through observance of the restrictions detailed in Section 7.8.2, the 
well-being of the subject will always take priority, and subjects should be managed as deemed 
appropriate by the Investigator. If use of any prohibited medications is anticipated, this should be 
discussed with the Medical Monitor and/or UCB Study Physician first, whenever possible.
If a subject should require emergency treatment for an uncontrolled flare(s) (defined as a ≥25% 
increase and an absolute increase in ≥2 in total abscess and inflammatory nodule count from 
Baseline) that includes development of a painful abscess (with purulent exudate and 
inflammation) during the study, rescue treatment will be allowed. This can include some form of
analgesic for a limited period, incision and drainage of the abscess, and may also include a 
limited number of intralesional injections of triamcinolone. The need for these procedures should 
be discussed with the Medical Monitor and/or UCB Study Physician first, whenever possible.
7.9
Blinding
The IMP handling manual describes the handling of bimekizumab, adalimumab, and placebo. 
Appropriate training will be given to the site personnel to avoid the unblinding of blinded 
personnel and subjects. In case the Investigator becomes unblinded for any subject, another 
assessor will do the remaining evaluations for that subject.
Due to differences in presentation between the bimekizumab and adalimumab, unblinded study 
personnel appropriately delegated by the Investigator will be required to prepare and administer 
the IMP in order to maintain the blind. The unblinded study personnel will not have any other 
involvement in the study and will not be allowed to reveal a subject’s allocated treatment to 
study personnel or to the subject. Blinded staff will not be involved in any activities pertaining to 
the receipt, storage, handling, or administration of IMP. All IMP documentation (eg, shipping 
receipts, accountability logs, IVRS randomization materials) will be maintained by unblinded 
staff only. Designated, unblinded study personnel will be appropriately trained and licensed (per 
country guidelines) to administer injections. Each site will have a written blinding plan signed by 
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the Investigator, which details the site’s steps for ensuring that the Investigator-blind, subject-
blind nature of the study is maintained.
All Sponsor and Investigator site personnel involved in the study will be blinded to the 
randomized IMP (bimekizumab, adalimumab, or placebo) assignment with the following 
exceptions:

Sponsor clinical trial supply and qualified study personnel

Sponsor Patient Safety (PS) staff reporting SAEs to the regulatory authorities

Site pharmacist involved in IMP preparation and study personnel who administer IMP

Monitor who reviews the IMP related documentation and drug accountability

Bioanalytical staff analyzing blood samples for bimekizumab and anti-bimekizumab 
antibody determination

DMC members (unblinded safety data)

Any Sponsor staff and/or designee who is responsible for data analyses for the unblinded 
DMC and interim analyses. These individuals will be separate from the main blinded study 
team.
If necessary, the results of any planned DMC and/or interim analysis may be shared with key 
Sponsor’s personnel in order to facilitate additional Clinical Planning or Portfolio Management 
decisions. The results will include both individual and summary results, and will be presented 
unblinded. All individuals seeing unblinded data will be documented in the Trial Master File.
Further details are provided in the study manuals and site blinding plan.
7.9.1
Procedures for maintaining and breaking the treatment blind
7.9.1.1
Maintenance of study treatment blind
All subject treatment details (bimekizumab, adalimumab, or placebo) will be allocated and 
maintained by the IRT.
7.9.1.2
Breaking the treatment blind in an emergency situation
The integrity of this clinical study must be maintained by observing the treatment blind. In the 
event of an emergency for which the appropriate treatment for a subject cannot be made without 
knowing the treatment assignment, it will be possible to determine to which treatment arm the 
subject has been allocated by contacting the IRT. All sites will be provided with details of how to 
contact the system for code breaking at the start of the study. The Medical Monitor and/or UCB 
Study Physician or equivalent should be consulted prior to unblinding, whenever possible.
The Exploratory Project Manager (EPM) will be informed immediately via the IRT when a code 
is broken, but will remain blinded to specific treatment information. Any unblinding of the IMP 
performed by the Investigator must be recorded in the source documents and on the Study 
Termination eCRF page.
7.10
Randomization and numbering of subjects
An IRT will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by UCB (or 
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designee). The randomization schedule will be stratified by Baseline Hurley Stage and will be 
produced by an independent biostatistician with the Contract Research Organization (CRO) who 
is otherwise not involved in this study. The IRT will generate individual assignments for subject 
kits of IMP, as appropriate, according to the visit schedule. 
To enroll a subject at Screening (Visit 1), the Investigator or designee will contact the IRT and 
provide brief details about the subject to be enrolled. Each subject will receive a 5-digit number 
assigned at Screening that serves as the subject identifier throughout the study. The subject 
number will be required in all communication between the Investigator or designee and the IRT 
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IRT. 
To randomize a subject at Baseline (Visit 2), the Investigator or designee will contact the IRT 
and provide brief details about the subject to be randomized along with the subject’s Baseline 
Hurley Stage (stratification factor). The IRT will automatically inform the Investigator or 
designee of the subject’s randomization number. The IRT will allocate kit numbers to the subject 
based on the subject number during the course of the study. The randomization number must be 
incorporated into the eCRF.
8
STUDY PROCEDURES BY VISIT
Table 5‒1 (schedule of study assessments) provides a general overview of study assessments. A 
list of procedures to be completed at each visit is described below. 

Visit windows of ±3 days on either side of the scheduled dosing are permitted; however, the 
Investigator should try to keep the subjects on the original dosing schedule. The window of 
±3 days is relative to Baseline and applicable for all subsequent visits. Changes to the dosing 
schedule outside of the 3-day window must be discussed with the Medical Monitor and/or 
UCB Study Physician.

The minimum of time between doses should be no less than 12 days and no more than 
18 days.

For the SFU Visit (20 weeks after the last dose of IMP), the visit should occur no more than 
3 days prior to the scheduled visit date and within 7 days after the scheduled visit date 
(-3 days/+7 days).
8.1
Screening Visit (Visit 1)
The Screening Period will last ≥2 weeks up to a maximum of 4 weeks prior to randomization
(dosing cannot occur earlier than 2 weeks after the Screening Visit due to IMP shipping 
timelines).
Prior to any study specific activities, subjects will be asked to read, sign, and date an ICF that has 
been approved by the Sponsor and an IEC/IRB, and that complies with regulatory requirements. 
Subjects will be given adequate time to consider any information concerning the study given to 
them by the Investigator or designee. As part of the informed consent procedure, subjects will be 
given the opportunity to ask the Investigator any questions regarding potential risks and benefits 
of participation in the study.
Where local regulations permit, all subjects will also be given the option to participate in an 
imaging substudy (select sites) and a pharmacogenetic substudy. Subjects agreeing to participate 
in the pharmacogenomic substudy will be required to complete a separate ICF. The 
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pharmacogenomic substudy ICF must be signed prior to collecting any samples for the substudy. 
The pharmacogenomic substudy will only be conducted where ethically accepted and authorized 
by the regulatory agencies. Refusal to participate in either substudy will not affect a subject’s 
ability to participate in the main HS0001 study. 
The following procedures or assessments will be performed at the Screening Visit:

Obtain written informed consent

Contact the IRT/Subject identification number assigned

Verification of inclusion/exclusion criteria

Demographics and Baseline characteristics (will include lifestyle, childbearing potential [as 
applicable], height, weight, and body mass index [BMI])

Significant past medical history and concomitant diseases

HS history

Prior and concomitant medications

Physical examination

Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

CXR or CAT scan of chest (not necessary if performed within 3 months prior to Screening 
Visit and report is available)

TB questionnaire

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Obtain blood sample(s) for:

TB test (IGRA; it is recommended that the QuantiFERON TB GOLD test be 
performed)

Serum pregnancy test for women of childbearing potential 

Standard safety laboratory tests (hematology and biochemistry)

HBV and HCV virus testing

HIV

Obtain urine sample for:

Standard safety laboratory tests
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
Urine drug screen

Record AEs
Individual Screening tests for which the results are borderline for inclusion in the study may be 
repeated if necessary without complete rescreening of all tests.
8.2
Baseline Visit (Visit 2; Day 1)
The following procedures or assessments will be performed/recorded prior to administration of 
IMP:

Confirm inclusion/exclusion criteria 

Contact the IRT for randomization

Ensure no significant changes in medical history and concomitant disease

Physical examination

Body weight

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

Photography and thermography (for subjects participating in the substudy)

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Modified Sartorius score

Erythema assessment

Obtain blood sample(s) for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

PD and nonhereditary pharmacogenomic variables

Pharmacogenetic variables (for subjects participating in the substudy)
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
Anti-bimekizumab antibodies

Obtain urine sample for:

Standard safety laboratory tests 

Urine pregnancy test for women of childbearing potential

Biomarker research

Obtain skin biopsy samples for:

lesional and nonlesional skin biopsy

Record AEs

IMP administration (after all other visit assessments completed)
8.3
Visit 3; Week 2 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

C-SSRS

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Obtain blood sample(s) for:

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Record AEs

IMP administration (after all other visit assessments completed)
8.4
Visit 4; Week 4 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Concomitant medications
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
Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

Photography and thermography (for subjects participating in the substudy)

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Obtain blood sample(s) for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for:

Standard safety laboratory tests

Urine pregnancy test for women of childbearing potential

Record AEs

IMP administration (after all other visit assessments completed)
8.5
Visits 5, 7, and 9; Weeks 5, 7, and 9 (±3 days)
The following procedures or assessments will be performed/recorded:

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

Record AEs

IMP administration (after all other visit assessments completed)
8.6
Visit 6; Week 6 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Concomitant medications

Vital signs (BP, pulse rate, and temperature)
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
C-SSRS

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Record AEs

IMP administration (after all other visit assessments completed)
8.7
Visit 8; Week 8 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

Photography and thermography (for subjects participating in the substudy)

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Obtain blood sample(s) for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

PD and nonhereditary pharmacogenomic variables

Anti-bimekizumab antibodies
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
Obtain urine sample for:

Standard safety laboratory tests

Urine pregnancy test for women of childbearing potential

Record AEs

IMP administration (after all other visit assessments completed)
8.8
Visit 10; Week 10 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

C-SSRS

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Record AEs

IMP administration (after all other visit assessments completed)
8.9
Visit 11; Week 12 (±3 days)
The following procedures or assessments will be performed/recorded:

Physical examination

Body weight

Concomitant medications

Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

Photography and thermography (for subjects participating in the substudy)

PGA of Skin Pain
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
HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Modified Sartorius score

Erythema assessment

Obtain blood sample(s) for:

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

PD and nonhereditary pharmacogenomic variables

Pharmacogenetic variables (for subjects participating in the substudy)

Anti-bimekizumab antibodies

Obtain urine sample for:

Standard safety laboratory tests

Urine pregnancy test for women of childbearing potential

Biomarker research

Obtain skin biopsy samples for:

Lesional and nonlesional skin biopsy

Record AEs
8.10
Safety Follow-Up Visit (Visit 12; Week 30; 20 weeks after the last 
dose of IMP) (-3  to +7 days)
All subjects, including those withdrawn from IMP, will have a SFU Visit at 20 weeks after their 
last dose of IMP. 
The SFU Visit should occur no more than 3 days prior to the scheduled visit date and within 
7 days after the scheduled visit date (-3 days/+7 days).
The following procedures or assessments will be performed at the SFU Visit:

Final subject disposition determination

Physical examination

Body weight

Concomitant medications
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
Vital signs (BP, pulse rate, and temperature)

Record 12-lead ECG

C-SSRS

TB questionnaire

PGA of Skin Pain

HS-Physician’s Global Assessment

DLQI

EQ5D

HADS

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Erythema assessment

Obtain blood sample(s) for:

TB test (IGRA; it is recommended that the QuantiFERON TB GOLD test be 
performed)

Serum pregnancy test for women of childbearing potential

Standard safety laboratory tests (hematology and biochemistry)

Bimekizumab plasma concentration

Anti-bimekizumab antibodies

Obtain urine sample for:

Standard safety laboratory tests

Record AEs
8.11
Early Withdrawal Visit
Subjects who withdraw early from the study for any reason, including those withdrawn from 
IMP (see Section 6.3), will be asked to return for the study assessments 12 weeks after the first 
dose (ie, the Week 12 Visit) and will then enter the SFU Period and will undergo the same 
assessments performed at the SFU Visit (20 weeks after the last dose of IMP) (see Section 8.10). 
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 Unscheduled Visit is conducted due to safety or efficacy reasons, a C-SSRS assessment will 
be performed with the subject during the visit. If an Unscheduled Visit is conducted for reasons 
other than safety or efficacy concerns (eg, replacement of lost medication, repeated collection of 
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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 

C-SSRS

Physical examination

Lesion count (including Hurley Stage); note that data collected from the lesion count will be 
used for the derivation of the HiSCR and IHS4

Record 12-lead ECG 

If medically indicated, obtain blood sample(s) for:

Standard safety laboratory tests (hematology, biochemistry) 

The blood sample may also be used for PK assessments, if needed

Obtain urine sample for standard safety laboratory tests (including urine pregnancy test)

Record concomitant medications

Record AEs
9
ASSESSMENT OF EFFICACY
The timing for all assessments described below is specified in Table 5‒1.
9.1
Hidradenitis Suppurativa Clinical Response
The HiSCR was developed to address issues with available HS scoring systems and is a 
validated variable that is responsive to improvement in disease activity, simplifies the scoring 
process, and increases the sensitivity to detect HS-specific lesions (Kimball et al, 2014; 
Kimball et al, 2016b). 
The HiSCR is defined as at least a 50% reduction from Baseline in the total abscess and 
inflammatory nodule count, with no increase from Baseline in abscess or draining fistula count.
9.2
International Hidradenitis Suppurativa Severity Score System
The IHS4 is a validated tool to dynamically assess HS severity to be used both in real-life and 
the clinical trials setting (Zouboulis et al, in press). The determination of IHS4 requires counting 
the nodules, abscesses and draining fistulas/sinus tracts, making it straightforward to apply in 
both research and clinical practice and easy to use in conjunction with the HiSCR.
9.3
Lesion count
The lesion count is defined as a broad assessment of all the various skin “appearances” that are 
termed “lesions” in HS subjects. The lesion count must address all relevant anatomical regions in 
each subject. The lesion count will include the following:
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
Abscesses (circumscribed collection of purulent exudate frequently associated with swelling 
and other signs of inflammation, such as fluctuance, tenderness and pain)

Non-inflammatory fistulas (a fistula is a pathologic passageway connecting to the skin 
surface from dermis or sc tissue. A non-inflammatory fistula is a non-tender or minimally 
tender, non-erythematous fistula.)

Draining fistulas (fistulas that drain serous or purulent fluid, either spontaneously or by 
gentle palpation)

Fistulas/sinus tracts (a fistula with sinus tracts is a pathologic passageway that has developed 
into a channel to the skin surface)

Non-inflammatory nodules (non-tender or minimally tender, non-erythematous nodules)

Inflammatory nodules (a tender, erythematous, well-defined nodule. The lesion has no 
evidence of fluctuance. A pyogenic granuloma lesion is considered an inflammatory nodule; 
a papule or pustule is not considered an inflammatory nodule.)

Hypertrophic scars (enlargement or overgrowth of a scar so that it extends above the 
surrounding skin surface)

Hurley Stage assessment (see Section 9.9)
The longest distance between 2 relevant lesions (if only one lesion, measure diameter of lesion) 
and whether the lesions are clearly separated by normal-appearing skin (yes/no) will be 
measured.
9.4
Patient's Global Assessment of Skin Pain
The PGA of Skin Pain is a unidimensional numeric rating scale (NRS) that allows for rapid 
(often 1 item) measures of pain that can be administered multiple times with minimal 
administrative burden. The NRS consists of scores from 0 to 10 (or 0 to 100) with 0 indicating
“no skin pain” and 10 (or 100) indicating “worst skin pain imaginable”.
The PGA of Skin Pain NRS will be administered verbally. The pain will be described as “pain at
its worst during the last 24 hours” and “pain on average in the last 24 hours”.
9.5
Modified Sartorius score
The Sartorius scale was created as a more detailed and dynamic HS severity scale and was 
modified in order to further develop and simplify this assessment for the clinical setting 
(Sartorius et al, 2003; Sartorius et al, 2009; Sartorius et al, 2010). The modified Sartorius score 
was the first disease-specific instrument for dynamically measuring clinical severity.
The main parameter in the modified Sartorius score is the counting of individual nodules and 
fistulas. The modified Sartorius score includes an assessment of the anatomical regions involved, 
the numbers and scores of lesions for each region, the longest distance between 2 relevant 
regions (or size of a single lesion), and whether all lesions are separated by normal skin (yes or 
no).
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9.6
Hidradenitis Suppurativa-Physician’s Global Assessment
The HS-Physician’s Global Assessment is a validated 6-point scale that is used to measure 
improvement in inflammatory nodules, abscesses, and draining fistulas (Kimball et al, 2012; 
Zouboulis et al, 2015b). The HS-Physician’s Global Assessment scale is defined by the 
following:

Clear: No inflammatory or non-inflammatory nodules 

Minimal: Only the presence of non-inflammatory nodules

Mild: <5 inflammatory nodules or 1 abscess or draining fistula and no inflammatory nodules

Moderate: <5 inflammatory nodules or 1 abscess or draining fistula and 1 or more 
inflammatory nodules or 2 to 5 abscesses or draining fistulas and less than 10 inflammatory 
nodules

Severe: 2 to 5 abscesses or draining fistulas and 10 or more inflammatory nodules

Very severe: >5 abscesses or draining fistulas
9.7
Dermatology Life Quality Index
The DLQI is a questionnaire designed for use in adult subjects with inflammatory skin diseases
and has been used in patients with HS (Finlay, 1998; Esmann et al, 2010; Basra et al, 2012). The 
DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and 
treatment affect subjects’ health related QOL. This instrument asks subjects about symptoms and 
feelings, daily activities, leisure, work and school, personal relationships and treatment. The 
DLQI score ranges from 0 to 30 with higher scores indicating lower health related QOL. A 
4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the 
subject (within-subject minimal important difference); while a DLQI absolute score of 0 or 1 
indicates no or small impact of the disease on health related QOL.
9.8
European Quality-of-Life 5 dimensions questionnaire
The EQ-5D comprises 5 questions on mobility, self-care, pain, usual activities, and 
psychological status with 3 possible answers for each item (1=no problem, 2=moderate problem, 
3=severe problem). A summary index with a maximum score of 1 can be derived from these 
5 dimensions by conversion with a table of scores. The maximum score of 1 indicates the best 
health state, by contrast with the scores of individual questions, where higher scores indicate 
more severe or frequent problems. In addition, there is a visual analogue scale to indicate the 
general health status with 100 indicating the best health status.
9.9
Hurley Stage
The Hurley Stage is a severity classification for HS that was developed in 1989 and is widely
used for the determination of the severity of HS (Hurley, 1989). Stage I HS is the most common
(68% of patients), while Stage II occurs in about 28% of patients and Stage III only occurs in 
about 4% of patients.
The Hurley Stage is defined by the following criteria:

Stage I: Abscess formation, single or multiple, without sinus tracts and cicatrization 
(scarring).
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
Stage II: Recurrent abscesses with tract formation and cicatrization, single or multiple, 
widely separated lesions.

Stage III: Diffuse or near-diffuse involvement, or multiple interconnected tracts and 
abscesses across the entire area.
9.10
Erythema assessment
The erythema assessment is a scoring system used to assess the overall degree of erythema in the 
HS lesions. This assessment uses a 4-point ordinal scale ranging between 0 (no redness) for no 
erythema and 3 (very red or bright red coloration) for severe erythema. A score of 1 (faint but 
discernible pink coloration) or 2 (moderate red coloration) indicates a moderate degree of 
erythema.
9.11
Hospital Anxiety and Depression Scale
The HADS was chosen for its well-established psychometric properties and its use in clinical 
research on biological therapy in subjects with other inflammatory skin diseases
(Dauden et al, 2009; Langley et al, 2010). The HADS scores for anxiety and for depression range 
from 0 to 21 with higher scores indicating worse state. A score below 8 is considered to be 
normal whereas a score of 15 and above is considered severe (Snaith and Zigmond, 1994). A 
score of 11 to 14 is considered moderate.
10
ASSESSMENT OF PHARMACOKINETICS
PHARMACODYNAMIC, NONHEREDITARY 
PHARMACOGENOMICS, AND PHARMACOGENETICS
10.1
Pharmacokinetic variables
Blood samples for measurement of the PK variables (see Section 4.2.1) 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.
10.2
Pharmacodynamic variables
Blood samples for measurement of PD variables (see Section 4.2.2) will be collected at the time 
points specified in the schedule of study assessments (Table 5‒1). Flow cytometry by 
fluorescence-activated cell sorting analysis might include, but is not limited to: CD3, CD19, 
CD4, CD8, and CD69. Candidate biomarkers might include, but are not limited to: 
IL-17A/IL17-F pathway signaling and HS (eg, IL-17A, IL-17F, IL-23, IL-6, TNF, DC-STAMP, 
and circulating osteoclast precursors). At dosing visits, blood samples will be drawn prior to 
dosing, and will be drawn at the same time of the sampling for clinical laboratory tests. The time 
and date of collection will be recorded in the eCRF.
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Instructions pertaining to sample collection, processing, storage, labeling, and shipping are
provided in the laboratory manual for this study. Detailed information on sample analysis will be
provided in a bioanalytical report.
10.3
Nonhereditary pharmacogenomic variables
Where local regulations permit, blood samples will be drawn for exploratory RNA, proteins and 
metabolites biomarker analysis at the time points specified in the schedule of study assessments 
(Table 5‒1). Where local regulations permit, lesional and nonlesional skin biopsies for 
exploratory RNA, proteins, and metabolites biomarker analysis will be taken at the time points 
specified in the schedule of study assessments. Where local regulations permit, urine samples 
will be drawn for exploratory proteins and metabolites biomarker analysis at the time points 
specified in the schedule of study assessments. Collection of these samples will enable 
evaluation of biomarkers relative to disease biology and progression, drug treatment and 
inflammatory and immune response processes.
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. The nature and format of these tentative 
analyses will be determined at a later stage. The samples will be stored at the secure long-term 
storage facility selected by UCB for up to 20 years.
10.4
Pharmacogenetic variables
For individuals consenting to the pharmacogenetic substudy, blood samples will be drawn for 
exploratory genetic/epigenetic analyses at the time points specified in the schedule of study 
assessments (Table 5‒1). Collection of these samples will enable evaluation of 
genetics/epigenetics biomarkers relative to disease biology and progression, drug treatment and 
inflammatory and immune response processes. The nature and format of these tentative analyses 
will be determined when the results of the main study are made available. A separate ICF will be 
required for those subjects who agree to participate in the pharmacogenetics substudy. The 
substudy will be conducted only where ethically accepted and authorized by the regulatory 
agencies. Refusal to participate in the substudy will not affect a subject’s ability to participate in 
the main study.
The samples will be stored at -80°C at the central biorepository for up to 20 years.
11
ASSESSMENT OF SAFETY
11.1
Adverse events
11.1.1
Definitions
11.1.1.1
Adverse Events
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
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In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), 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.
11.1.1.2
Serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:

Death

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)

Significant or persistent disability/incapacity

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 11.1.1.3], allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
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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.
11.1.1.2.1
Anticipated serious adverse events
The following list of Anticipated SAEs (Table 11‒1) has been identified, as these events are 
anticipated to occur in the population studied in this protocol at some frequency that is 
independent of drug exposure. This original list will remain in effect for the duration of the 
protocol. Note that listed events will not be regarded as anticipated SAEs if they are life 
threatening or if they result in the death of the study subject.
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 11.1.2.3. 
Table 11‒1: Anticipated serious adverse events for the population of subjects 
with hidradenitis suppurativa
MedDRA system organ class
MedDRA preferred term
Gastrointestinal disorders
Crohn’s disease
Colitis ulcerative
Psychiatric disorders
Depression
Anxiety
Musculoskeletal and connective tissue disorders
Arthropathy
Skin and subcutaneous tissue disorders
Pyoderma gangrenosum
Pilonidal cyst
Acne conglobate
Hidradenitis
Neoplasms benign, malignant and unspecified (including 
cysts and polyps)
Lymphoma
Squamous cell carcinoma of skin
Infections and infestations
Cellulitis
Metabolism and nutritional disorders
Diabetes mellitus
Dyslipidaemia
Metabolic syndrome
Endocrine disorders
Thyroid disorder
Polycystic ovaries
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.
11.1.1.3
Adverse events of special interest
An adverse event of special interest (AESI) is any AE that a regulatory authority has mandated 
be reported on an expedited basis, regardless of the seriousness, expectedness, or relatedness of 
the AE to the administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
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must ALWAYS be reported to UCB as an AESI (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should then be reported if an 
alternative etiology is identified during investigation and monitoring of the subject.
11.1.1.4
Adverse events for special monitoring
UCB has identified AEs for special monitoring (AESMs). An AESM is an AE or safety topic for 
which special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB) are considered appropriate. Identified AESM can be of particular 
concern based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or comorbidities and risk factors prevalent in the 
study population.
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 11.3.1), cytopenias, hypersensitivities, suicide 
ideation or behavior (assessed using the C-SSRS), depression and anxiety (assessed using the 
HADS, see Section 9.11), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin; see Section 11.2.1), malignancies, and inflammatory bowel 
diseases.
11.1.2
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
11.1.2.1
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
When recording the intensity of an AE in the eCRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria:

Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere with 
his/her usual activities and/or is of no clinical consequence

Moderate: the AE interferes with the usual activities of the subject or it is of some clinical 
consequence

Severe: the subject is unable to work normally or to carry out his/her usual activities, or the 
AE is of definite clinical consequence
Details for completion of the AE eCRF (including judgment of intensity and relationship to IMP) 
are described in the eCRF Completion Guidelines.
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11.1.2.2
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
11.1.2.3
Additional procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the SAE Reporting section at the 
front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
completed “Investigator SAE Report Form for Development Drug” (SAE report Form) provided 
by UCB, even if the data are incomplete, or if it is obvious that more data will be needed in order 
to draw any conclusions. Information recorded on this form will be entered into the global PS 
database.
An Investigator SAE report Form will be provided to the Investigator. The Investigator SAE 
Report Form must be completed in English.
It is important for the Investigator, when completing the SAE report Form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report Form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
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.
11.1.2.4
Immediate reporting of adverse events
The following AEs must be reported immediately:

SAE: AE that the Investigator classifies as serious by the definitions in Section 11.1.1.2, 
regardless of causality

Suspected transmission of an infectious agent via a medicinal product

AESIs as defined in Section 11.1.1.3.
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
Suspected transmission of an infectious agent via a medicinal product
11.1.3
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AESIs; further details regarding follow up of 
PDILI events is provided in Section 11.2.1.5. 
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.
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time.
11.1.4
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by providing the completed 
Pregnancy Report and Outcome form (for contact details see SAE reporting information at the 
beginning of this protocol). The subject should be withdrawn from the study as soon as 
pregnancy is known (by positive pregnancy test), and the following should be completed:

The subject should return for an Early 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 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/CRO contract monitor for the study. The Investigator will 
complete the Pregnancy Report and Outcome form and send it to UCB’s PS department (for 
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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.
11.1.5
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.
11.1.6
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).
11.1.7
Safety signal detection
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory, or ECG results) for which data will be periodically reviewed during the course 
of the study.
In addition, an independent DMC will periodically review and monitor the safety data from this 
study and advise UCB. Details will be provided in the DMC Charter.
11.2
Laboratory measurements
Clinical laboratory assessments consist of biochemistry, hematology, and urinalysis. A 
centralized laboratory will be used to supply all laboratory test supplies and analyze all blood 
samples for hematology, biochemistry, and urinalysis measurements. Any unscheduled 
laboratory testing should also be collected using the central laboratory. Testing to rule out HBV, 
HCV, and HIV (see Exclusion Criteria, Section 6.2) will be performed at the Screening Visit in 
addition to those measurements listed in Table 11-2. 
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Specific details regarding the handling and processing of biochemistry, hematology, and 
urinalysis samples are provided in the study laboratory manuals.
The following laboratory parameters will be measured:
Table 11-2: Laboratory measurements
Hematology
Chemistry
Urinalysis
Serology
Basophils
Bicarbonate
Albumin
HIV
Eosinophils
Calcium
Bacteria
HLA-B27
Lymphocytes
Chloride
Crystals
Hepatitis B
Atypical lymphocytes
Creatinine
Glucose
Hepatitis C
Monocytes
hsCRP
pH
Neutrophils
Magnesium
RBC
Hematocrit
Potassium
WBC
Hemoglobin
Sodium
Urine dipstick for 
pregnancy testing a
MCH
Glucose
Urine drug screen
MCHC
BUN
MCV
ALP
Platelet count
AST
RBC count
ALT
WBC count
GGT
Total bilirubinb
Uric acid
LDH
Total cholesterol
Serum pregnancy 
testing
Serum FSH c
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; FSH=follicle-stimulating hormone; GGT=gamma glutamyltransferase; hsCRP= high sensitivity C-reactive 
protein; HLA=human leukocyte antigen; HIV=human immunodeficiency virus; 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 be done in all women of childbearing potential and will consist of serum testing at 
Screening and at the Safety Follow-Up Visit and urine testing at all other visits.
b If total bilirubin is >ULN, a direct bilirubin estimation (%) will be performed
c The serum FSH test (at Screening only) should only be performed on postmenopausal females who have been 
postmenopausal for ≥1 year and last menstrual cycle occurred <2 years ago.
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11.2.1
Evaluation of potential drug-induced liver injury
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and Sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AESI (see Section 11.1.1.3), and, if applicable, also reported as an SAE (see 
Section 11.1.1.2). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 11-3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 11.2.1.1). 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 11.2.1.5). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Table 11-3 summarizes the approach to investigate PDILI.
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Table 11-3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or 
AST
Total 
bilirubin
Symptoms a of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult c
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation.
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed ASAP 
(see Section 11.2.1.4); 
recommended to occur at 
the site with HCP.
Monitoring of liver 
chemistry values at least 
twice per week until values 
normalize, stabilize, or 
return to within Baseline 
values. d
≥3xULN
NA
Yes
≥5xULN
NA
NA
Need for hepatology 
consult to be 
discussed.(required if 
ALT or AST ≥8xULN)
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation.
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Table 11-3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow-up
ALT or 
AST
Total 
bilirubin
Symptoms a of 
hepatitis of 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN 
(and ≥2x 
Baseline) 
and 
<5xULN 
(and ≥2x 
Baseline)
<2xULN
No
Discussion with Medical 
Monitor required.
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see 
Follow-up 
requirements). c
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 11.2.1.2).
IMP discontinuation 
required if any of the 
following occur:

Subject cannot comply 
with monitoring 
schedule. 

Liver chemistry values 
continue to increase 
during 2 week 
monitoring period.

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 11.2.1.4).
Monitoring of liver 
chemistry values at least 
twice per week for 
2 weeks. d

Immediate IMP 
discontinuation required if 
liver chemistry values 
continue to increase. 
After 2 weeks of monitoring 
liver chemistry values:

Discontinue IMP if levels 
remain ≥3xULN (and 
≥2x Baseline) without 
evidence of resolution. d
Continue to monitor until 
values normalize, stabilize, 
or return to within Baseline 
values. d
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 11.2.1.1. 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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11.2.1.1
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 11.2.1.4) and SAE report (if applicable).
11.2.1.2
Immediate action: determination of investigational medicinal product 
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 11-3 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.
11.2.1.3
Investigational medicinal product restart/rechallenge
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
11.2.1.4
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are detailed in 
Table 11‒4 (laboratory measurements) and Table 11‒5 (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 measurements to be assessed are detailed in Table 11‒4.
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Table 11‒4: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screen 
a
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation
Additional
Prothrombin time/INR 
b
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
subject’s history.
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
The following additional information is to be collected (Table 11‒5).
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Table 11‒5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen/paracetamol, 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
11.2.1.5
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in
Table 11-3. 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.
11.3
Other safety measurements
11.3.1
Assessment and management of tuberculosis and tuberculosis risk 
factors
All subjects will be assessed for TB prior to administration of IMP and at the time points 
specified in the Schedule of Assessments (Table 5‒1) through physical examination for signs and 
symptoms of TB, laboratory testing (Section 11.3.1.1), CXR (Section 11.3.1.2), and subject 
questionnaire (Section 11.3.1.3).
Prior to administration of IMP, subjects will have an IGRA test (QuantiFERON TB GOLD is 
recommended), a CXR or CAT scan of chest (unless already performed within 3 months of 
Screening), and examination for signs and symptoms of TB unless an IGRA negative result is 
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available less than 4 weeks prior to the first dose of IMP. In addition, each subject will complete 
a TB questionnaire with questions directed at symptoms of TB and potential exposure to TB. 
Test Conversion
Tuberculosis test conversion is defined as a positive IGRA result for the current test when 
previous IGRA test results are negative. All subjects with TB test conversion must immediately 
stop IMP administration. In case of a TB test conversion, the subject must be considered as 
having either a suspected new latent or an active TB infection and be promptly referred to an 
appropriate specialist (eg, pulmonologist, infectious disease specialist) for further evaluation. If 
the 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, CXRs, or other imaging) should be performed where medically relevant and 
documented. Such conversions should be reported to the UCB PS function.
Latent TB
In case the evaluation by the appropriate specialist indicates a new LTB infection during the 
study, a prophylactic TB treatment should be initiated and the IMP can be continued no sooner 
than 4 weeks after start of prophylactic TB treatment, if it is deemed likely by the Investigator 
that prophylactic TB treatment is continued to completion.
If prophylaxis is not initiated, the subject must be withdrawn.
Every related action should be discussed in advance with the Medical Monitor and/or UCB 
Study Physician. 
Once withdrawn from IMP, subjects should return for the Early Withdrawal Visit and complete a 
SFU Visit (20 weeks after the last dose of IMP).
Active TB or NTMB infection 
Subjects who develop active TB or NTMB infection during the study must be withdrawn from 
the study. The subject must be immediately discontinued from IMP and an Early Withdrawal 
Visit must be scheduled as soon as possible, but no later than the next scheduled visit. The 
subject should be encouraged to attend 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. 
11.3.1.1
Tuberculosis assessment by interferon-gamma release assay
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD is 
recommended) will be performed at study entry (unless an IGRA negative result is available less 
than 4 weeks prior to the first dose of IMP). The test results will be reported as positive, 
negative, or indeterminate. UCB also recommends that a TB specialist be consulted where TB 
(latent or active) is suspected or if there are doubts regarding test results. If latent or active TB is 
identified, subject must undergo appropriate study-specified withdrawal procedures. 
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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 Early Withdrawal Visit as soon as 
possible, but no later than the next scheduled study visit and complete all Early Withdrawal Visit 
assessments. 
The subject should be encouraged to complete a SFU Visit (20 weeks after the last dose of IMP).
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed.
11.3.2
Pregnancy testing
Pregnancy testing will consist of serum testing at the Screening and SFU Visits. The pregnancy 
test will be urine at all other visits. 
The Screening Visit serum pregnancy testing results must be negative and received and reviewed 
prior to randomization. A negative urine pregnancy test result should be obtained immediately 
prior to each administration of IMP and at all subsequent post-dosing visits. Pregnancy tests 
should be administered to all female subjects of childbearing potential, regardless of their use of 
birth control.
11.3.3
Vital signs
Vital signs will be collected at the visits specified in Table 5‒1 and will include systolic and 
diastolic BP, pulse rate, and body temperature (oral, axillary, or otic). Subjects should be sitting 
for 5 minutes before and during vital signs assessments. 
Vital signs are to be measured prior to blood sampling, and prior to dosing, where applicable.
11.3.4
12-lead electrocardiograms
Twelve-lead standard ECGs will be recorded at the visits specified in Table 5‒1. 
A standard 12-lead ECG will be recorded after >10 minutes of rest in the supine position and 
prior to taking blood samples. The following ECG variables will be recorded: heart rate, PR 
interval, QRS duration, QT interval, QTcF, and the Investigator’s interpretation of the ECG 
profile.
Full details of ECG recording will be provided in the ECG Manual.
11.3.5
Physical examination
The physical examination will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; gastrointestinal; musculoskeletal; hepatic; neurological 
(including limb reflexes); and mental status. Physical examination will be performed at the visits 
specified in Table 5‒1. Findings considered clinically significant changes since the physical 
examination at the Screening Visit will be recorded as AEs.
11.3.6
Body weight
Body weight, including height and BMI, will be collected at the visits specified in Table 5‒1. 
The same scale for measuring body weight should be utilized throughout the study where 
possible.
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11.3.7
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed during the study by trained study personnel using 
the C-SSRS. 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 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The C-SSRS takes approximately 3 to 10 minutes to complete.
11.4
Other study measurements
11.4.1
Demographic and Baseline information
Demographic and Baseline information will be collected in all subjects and will include age, 
gender, race, and ethnicity along with lifestyle, childbearing potential (as applicable), height, 
weight, and BMI. Information on demographics will be collected according to local rules and 
regulations. Demographic and Baseline information will be recorded in the eCRF.
11.4.2
Medical history
A complete medical history will be collected as part of the Screening assessment (and any 
changes will be collected at Baseline [Visit 2]) and include all clinically relevant past or 
coexisting medical conditions and surgeries. Findings will be recorded in the eCRF.
11.4.3
Hidradenitis suppurativa history
Detailed information of each subject’s HS history will be collected at Screening and will include, 
but will not be limited to, the following:

The date of initial onset of HS

The date, onset, and duration of past treatments for HS

The date of any prior surgeries for HS
11.5
Data Monitoring Committee
The DMC membership includes experienced clinicians and a statistician, all of whom have 
expertise in clinical trials. Board members may not participate in the study as principal or 
co-Investigators, or as study subject care physicians. The duration of membership for the DMC 
will be inclusive of planned analyses for HS0001. 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 DMC Charter.
The DMC procedures will ensure that data remain blind to the study team and Investigators at all 
times throughout the conduct of the study.
12
ASSESSMENT OF IMMUNOLOGICAL VARIABLES
Blood samples for the measurement of ADA will be collected at the visits specified in the 
schedule of assessments (Table 5‒1). 
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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 ADA will be determined using 
a validated bioanalytical method. Detailed information on sample analysis will be provided in a 
bioanalytical report.
13
ASSESSMENT OF IMAGING VARIABLES
At certain sites, where feasible, representative imaging of the changes in skin will be captured 
through photography and thermography. 
Subjects will have full body (anterior and posterior views, below neck) photographs taken. 
Photographs will be anonymized. Study sites able to perform photography will be trained and 
receive standardized photographic equipment. 
Thermography, a non-invasive and radiation-free imaging method, has been used in research 
medicine to detect temperature changes in tissue abnormalities beneath the skin or on the skin’s 
surface in specific areas (Langemo and Spahn, 2017; Sagaidachnyi et al, 2017; Sun et al, 2017).
At the same sites, Scout (WoundVision LLC, Indianapolis, Indiana), an FDA-approved visual 
and thermal imaging device and software analysis tool, will be used for the procedure. This 
device can provide clinicians with a reliable and reproducible way to incorporate long-wave 
infrared thermography and relative temperature differential into clinical lesions assessment by 
consistently identifying control areas against which to measure lesion temperature.
14
STUDY MANAGEMENT AND ADMINISTRATION 
14.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the EPM of the Sponsor 
within 24 hours and follow any local regulatory requirements.
14.2
Monitoring
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring SOPs, ICH-GCP 
guideline, and applicable regulatory requirements, and to ensure that study initiation, conduct, 
and closure are adequate. Monitoring of the study may be delegated by UCB to a CRO or a 
contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
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The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
14.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of 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.
Sponsor or designee will review to ensure that computerized source documents produced by the 
site are compliant with FDA Part 11 requirements and document appropriately. Source 
documents that are computer generated and stored electronically that are not FDA Part 11 
compliant, must be printed for review by the monitor (eg, ECG reports). Once printed, these 
copies should be signed and dated by the Investigator and become a permanent part of the 
subject’s source documents. The Investigator will facilitate the process for enabling the monitor 
to compare the content of the printout and the data stored in the computer to ensure all data are 
consistent.
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
14.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 14.2.1.
14.3
Data handling
14.3.1
Case Report Form completion
This study will use electronic data capture (EDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the electronic eCRFs and in all required 
reports.
Serious AE reporting will be done using the SAE Form 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.
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The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Access to the EDC will be given after training has been received. A training certificate will be 
provided and filed.
Detailed instructions on the use of the EDC will be provided in the eCRF Completion 
Guidelines.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be re-approved by the Investigator. Any change or correction 
to the eCRF after saving must be accompanied by a reason for the change.
14.3.2
Database entry and reconciliation
Case Report Forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. The data will be entered into the electronic eCRFs once and will be subsequently 
verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
14.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
14.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
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14.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
Trial Master File.
14.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH-GCP, and applicable regulatory 
requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
14.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
15
STATISTICS
A description of statistical methods follows and further detail will be included in the statistical 
analysis plan (SAP). Deviations from the original SAP will be documented in the clinical study 
report (CSR).
15.1
Definition of analysis sets
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
The Randomized Set (RS) will consist of all randomized subjects.
The Safety Set (SS) will consist of all subjects who receive at least 1 dose of the IMP.
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The Full Analysis Set (FAS) will consist of all randomized subjects who receive at least 1 dose 
of the IMP and have a valid measurement of the primary efficacy variable at Baseline and at 
least one post baseline efficacy assessment. 
The Per-Protocol Set (PPS) will consist of all subjects in the FAS who have no important 
protocol deviation affecting the primary efficacy variable. The subjects with important protocol 
deviations will be predefined and evaluated during a data evaluation meeting prior to unblinding 
of the data.
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of all randomized subjects who 
received at least 1 dose of the IMP and have at least 1 quantifiable post-dose plasma 
concentration.
15.2
General statistical considerations
Statistical evaluation will be performed by PAREXEL and supervised by the Exploratory 
Statistics and Global Statistical Sciences Departments of UCB.
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, US), 
R Version 2.10.1 (R Development Core Team) or later, or OpenBUGS Version 3.0.6 or later.
Descriptive statistics will be used to provide an overview of the Baseline, efficacy, and safety 
results. For categorical parameters, the number and percentage of subjects in each category will 
be presented by treatment group. The denominator for the percentages will be based on the 
number of subjects appropriate for the purpose of analysis. Unless otherwise noted, all 
percentages will be expressed to 1 decimal place. For continuous parameters, descriptive 
statistics will include n, mean, standard deviation, median, minimum, and maximum. Two-sided 
95% confidence intervals, geometric means, and coefficient of variation will be presented for 
selected variables as appropriate.
Baseline for each assessment is defined as either the value obtained at Baseline (Visit 2) or the 
last available value obtained prior to treatment administration at Screening (Visit 1) (details to be 
specified in the SAP).
Formal statistical testing will be conducted for this study for the primary efficacy variable. 
Exploratory efficacy variables will be summarized descriptively by treatment arm. Additionally, 
exploratory analyses will be conducted as deemed appropriate and described in the SAP.
The primary treatment comparison for all formal statistical analyses of efficacy will be between 
bimekizumab and placebo.
15.3
Subject disposition
The number of subjects who were screened, subjects included in each analysis set, and subjects 
who completed/prematurely discontinued the study, as well as the primary reason for 
discontinuation, will be presented by treatment group and overall using frequency counts and 
percentages.
15.4
Subject characteristics
The following subject characteristics will summarized and listed, as appropriate:

Demographics (including gender, age, race, and ethnicity)
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
Baseline characteristics (including lifestyle, childbearing potential, height, weight, and BMI) 

Medical/procedure history

Prior and concomitant medications/medical procedures 

Baseline disease characteristics
15.5
Planned efficacy analyses
The primary efficacy analyses will be based on the PPS.
15.5.1
Analysis of the primary efficacy variable
The primary efficacy analysis will be the comparison between bimekizumab and placebo in the 
proportion of subjects achieving HiSCR at Week 12, although the model used will analyze data 
from all three treatment groups. The number and percentage of subjects who achieved HiSCR at 
Week 12 will be presented by treatment group and the statistical analysis of this variable will be 
conducted following a Bayesian paradigm utilizing an informative prior on both the placebo and 
adalimumab group response rates where these informative priors were derived from published 
summary data (Clinical Study Protocol M11-810 - PIONEER II). A vague prior will be assumed 
for the bimekizumab treatment group.
The Bayesian analysis of HiSCR at Week 12 will employ a logistic regression model including 
treatment group (placebo, adalimumab, and bimekizumab) and adjusting for Baseline Hurley 
Stage.
The posterior distributions of the treatment group response rates together with 95% credible 
intervals for all three treatment group response rates, and of the difference in response rates 
between the treatment groups will be summarized. A 95% credible interval will be presented for 
the bimekizumab versus placebo comparison and a 60% credible interval will be presented for 
the bimekizumab versus adalimumab comparison. This latter comparison of bimekizumab with 
adalimumab is an informal one to assess whether any improvements in response rate observed 
with bimekizumab (over placebo) are comparable to the current standard of care and will be used 
for internal decision making on the future development of the compound. This comparison will 
not be part of the evaluation of Proof of Concept for this study. The posterior probability that the 
difference in response rates between the placebo and bimekizumab treatment groups is greater 
than zero will also be presented.
The study will be considered a success if the posterior probability that the difference in response 
rates between the placebo and bimekizumab groups being greater than zero is at least 97.5% (ie, 
the lower bound of the 95% credible interval of the difference between bimekizumab and 
placebo in HiSCR rates is greater than or equal to zero).
If further information (independent to this study) regarding the placebo and/or adalimumab 
treatment group response rates comes to light subsequent to writing this protocol then this study 
may be updated prior to study unblinding, and details of this will be supplied in the SAP and the 
CSR. Note that the informative priors for the placebo and adalimumab treatment group response 
rates may be updated based upon any observed differences in the proportions of Baseline Hurley 
Stage II and III subjects as long as no response rate data from the current study, blinded or un-
blinded, have been taken into consideration. For example, if updated, these priors may be fitted 
by Baseline Hurley Stage if the relative proportions of Baseline Hurley Stage II and III subjects 
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within the current study differ substantially from those reported in the historical data. In this case 
the priors will still be based only on historic response data, but using the Hurley-stage specific 
information rather than the average information.
15.5.2
Supportive analysis of the primary efficacy variable
A sensitivity analysis of the choice of the prior distribution for the placebo treatment group will 
be conducted by repeating the primary efficacy analysis assuming vague priors for all parameters 
of the model. The priors will be fully documented in the SAP and in the interim analysis SAP. 
Additional sensitivity analyses will assess the primary efficacy variable for the FAS.
Further analyses of the primary efficacy variable may be performed adjusting for other Baseline 
covariates (to be defined in the SAP). Results from any additional analyses will not be used as a 
substitute for the planned analyses, but may be used as supplemental information for the CSR.
15.5.3
Analysis of the exploratory efficacy variables
The exploratory efficacy variables are listed in Section 4.1.2.
Actual values and changes (including percentage changes, where applicable) from Baseline in 
the continuous exploratory efficacy variables will be listed and summary statistics will be 
presented by treatment group and time point. Changes from Baseline in the categorical 
exploratory variables will summarized in shift tables presented by treatment group and time 
point. Any formal statistical analyses of the exploratory efficacy variables will be described in 
more detail in the SAP.
15.6
Planned pharmacokinetic analyses
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS.
Bimekizumab trough plasma concentrations will be summarized by treatment group at each time 
point using descriptive statistics. 
15.7
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 group at each scheduled 
visit, and the rate of ADA positive subjects for each treatment group will be calculated.
15.8
Planned safety analyses
All safety variables will be analyzed for all subjects in the SS. 
Adverse events will be coded according to the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA®). The incidence of treatment-emergent adverse 
events (TEAEs) will be summarized descriptively by MedDRA system organ class, preferred 
term, and treatment group. Additional tables will summarize TEAEs by intensity and relationship 
to IMP, TEAEs leading to withdrawal from the study, serious TEAEs, and deaths. All AE 
information will be listed.
Laboratory values, ECGs, vital signs, physical examination, and extent of exposure will be 
presented descriptively by treatment group. The C-SSRS data will be listed only.
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15.9
Handling of protocol deviations
After all data have been verified/coded/entered into a database, a data review will be performed. 
The purpose of this review will be to check all protocol deviations, define the PPS, and check the 
quality of the data. The review will also help decide how to manage problems in the subjects’ 
data (eg, missing values, withdrawals, dropouts, and protocol deviations). 
Accepted deviations from theoretical time points will be described in the appropriate documents 
and included in the Trial Master File. After the pre-analysis review, resolution of all issues, and 
documentation of all decisions, the database will be locked.
15.10
Handling of dropouts or missing data
For the analysis of the primary efficacy variable, non-responder imputation will be used to 
impute missing data for subjects who have missing data at a specific visit and for subjects who 
discontinue early from the study during the Treatment Period for any reason. These subjects will 
be defined as non-responders at all subsequent visits after the time of study discontinuation. In 
additional sensitivity analyses, subjects who receive specific rescue therapy may also be 
considered a non-responder from the time that the rescue therapy was taken to the end of the 
Treatment Period.
Further details on all methods to be used for missing data imputation in the analysis of the 
efficacy variables will be included in the SAP.
15.11
Planned interim analysis and data monitoring
This study will include two unblinded interim analyses, the first after approximately 45 subjects 
have completed 4 weeks of the study and the second when the last randomized subject for this 
study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely.  The purpose of these interim analyses is for sponsor key 
personnel to review results from the primary efficacy analysis and a subset of the analyses of 
exploratory efficacy and safety outcomes to facilitate additional Clinical Planning or Portfolio 
Management decisions; consequently, neither analysis and will lead to any formal decision to 
alter or terminate the trial.  Interim analyses will be conducted by an unblinded study team and 
will follow internal SOPs for the formal process to control the unblinding of the study for interim 
analysis purposes. This process will ensure that no unnecessary or unintentional unblinding 
occurs. The unblinded team will not disclose any unblinded information to the blinded study 
team and the storage of all unblinded documentation will be held securely and separately from 
the rest of the study documentation and outputs up until the end of the study. All analyses and 
unblinding instructions will be prespecified in the interim SAP and SAP.
The conduct of the study and monitoring of the safety data will be supervised by an independent 
DMC to optimize subjects’ safety and to identify any safety signals. Full details of the DMC 
composition and roles will be described in a separate DMC Charter.
15.12
Determination of sample size
The predefined success criterion for declaring a positive study requires a posterior probability of 
at least 97.5% that the HiSCR rate at Week 12 for bimekizumab will be higher than that for 
placebo.  
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Additionally, the study has an exploratory objective to informally compare bimekizumab against 
the current standard of care for HS (adalimumab) using the 60% credible interval for the 
treatment difference.
Sample size calculations are based on the number of subjects required to meet the above success 
criterion assuming a true underlying HiSCR rate at Week 12 of 70% for bimekizumab. Published 
data from the PIONEER I and II studies (Kimball et al, 2016a) indicate that, when antibiotic 
therapy is allowed, the response rates for placebo and adalimumab at Week 12 are 27.6% and 
58.9% respectively. 
Using simulation, it was estimated that with data from 40 subjects on bimekizumab, 20 subjects 
on placebo and 20 subjects on adalimumab (80 subjects total), the study will provide at least an 
85% probability of meeting the success criterion and an 80% probability of meeting the 
exploratory criterion under the assumptions described below.
These simulations were based upon Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the placebo and adalimumab 
treatment arms in the current study. Based on historic data, the Bayesian model assumes an 
informative prior distribution for the placebo group HiSCR rate to be β (5.52,14.48). This prior 
distribution contributes an approximate effective sample size of 20 subjects for the placebo 
treatment group. Similarly, the Bayesian model assumes an informative prior distribution for the 
adalimumab group HiSCR rate to be β (11.78,8.22), which, with the parameterization in the 
model, is equivalent to an adalimumab response rate of 58.9%. This prior distribution contributes 
an approximate effective sample size of 20 subjects for the adalimumab group. For the 
bimekizumab HiSCR rate, a vague prior probability distribution N (0,1E4) was assumed.
16
ETHICS AND REGULATORY REQUIREMENTS
16.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
A separate ICF will be required for subjects participating in the pharmacogenetic substudy.
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 ICF should be signed and personally dated by the subject, 
or his/her legal representative, and by the person who conducted the informed consent discussion 
(Investigator or designee). The subject or his/her legal representative must receive a copy of the 
signed and dated ICF. 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 ICF 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 ICF by 
the IRB/IEC and use of the amended form.
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All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the ICF. An eCRF must not be 
started, nor may any study specific procedure be performed for a given subject, without having 
obtained his/her written consent to participate in the study.
16.2
Subject identification cards
Upon signing the ICF, the subject or legal representative will be provided with a subject 
identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times.
16.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, 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, 
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Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification.
16.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
16.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
17
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
18
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patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, 
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19
APPENDICES
19.1
Protocol Amendment 1
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.
The statistical analysis section of the protocol was also updated to include text describing the 
planned analysis of the primary efficacy variable, and text describing the planned interim 
analyses and sample size re-estimation was revised.  The rationale for this is that the observed 
pattern of subject recruitment is not as expected at the time of study planning. Consequently, an 
insufficient number of subjects will have completed the Week 12 visit and be evaluable for 
response at the time of the first interim analysis.  The risk of performing an analysis with a very 
small amount of data is that the estimates obtained from the analysis will be unstable and the risk 
of committing a Type II error will be inflated.  To mitigate these risks it was decided to remove 
the formal futility and sample size re-estimation aspects from the first interim analysis.
Minor formatting corrections were also made.
Modifications and changes
Specific changes
Change #1
Sponsor Study Physician
Name:
 MD
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Was changed to:
Name:
 MD
Address:
UCB Celltech, 208 Bath Rd, Slough, Berkshire, SL1 3WE, UK
Phone:
Change #2
List of Abbreviations
Inflammatory Bowel Disease (IBD) was added to the list  
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Change #3
Section 5.1.1 Study periods
The following paragraph was deleted:
A formal, unblinded interim analysis will be conducted when approximately 45 subjects have 
completed 4 weeks of the study. During this interim analysis, the sample size assumptions will 
be checked and the final sample size may be modified or the study may be stopped for futility. 
An informal, unblinded interim analysis will be performed when the last randomized subject for 
this study has completed the Week 12 Visit or the subject’s participation has ended prematurely
Change #4
Section 6.3 Withdrawal criteria
The following was added to the withdrawal criteria:
11. Subjects with newly diagnosed Inflammatory Bowel Disease (IBD) or with IBD flares 
during the study must:

Be referred, as appropriate, to a 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. 
Change #5
Section 6.4 Study stopping rules
Reasons for suspension or discontinuation of the study can fall into 1 of the following 3 principal 
categories: safety, futility, and other reasons.
Was changed to:
Reasons for suspension or discontinuation of the study can fall into 1 of the following 2 principal 
categories: safety and other reasons.
Change #6
Section 6.4.2 Futility
The following section was deleted:
6.4.2 Futility
A formal, unblinded interim analysis will be conducted when approximately 45 subjects have 
completed 4 weeks of the study, and the study may be stopped for futility (see Section 15.11).
Change #7
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Section 15.5.1 Analysis of the primary efficacy variable
The primary efficacy analysis will be the comparison between bimekizumab and placebo in the 
proportion of subjects achieving HiSCR at Week 12.
The number and percentage of subjects who achieved HiSCR at Week 12 will be presented by 
treatment group and the statistical analysis of this variable will be conducted following a 
Bayesian paradigm utilizing an informative prior on the placebo group response rate where the 
informative prior was derived from published summary data (Clinical Study Protocol M11 810   
PIONEER II). A vague prior is assumed for the bimekizumab treatment arm.
The Bayesian analysis of HiSCR at Week 12 will employ a logistic regression model including 
treatment group and adjusting for Baseline Hurley Stage.
The posterior distributions of the placebo and bimekizumab group response rates, and of the 
difference in response rates between the treatment groups will be summarized including 95% 
credible intervals. The posterior probability that the difference in response rates between the 
placebo and bimekizumab groups is greater than zero (ie, bimekizumab demonstrates a greater 
response compared with placebo) will also be presented. 
The study will be considered a success if this posterior probability is at least 97.5% (ie, the lower 
bound of the 95% credible interval of the difference between treatment groups (bimekizumab 
placebo) in HiSCR rates is greater than zero). 
If further information (independent to this study) regarding the placebo group response comes to 
light subsequent to writing this protocol then this study may be updated prior to study 
unblinding, and details of this will be supplied in the SAP and the CSR. Note that the prior for 
the placebo response rate may be updated based upon any observed differences in the response 
rate between Hurley Stages. If updated, priors will be fitted by Hurley Stage taking into account 
the relative proportions of Hurley Stage II and III subjects within the current study. In this case 
the priors will still be based upon the historic data.
Was changed to:
The primary efficacy analysis will be the comparison between bimekizumab and placebo in the 
proportion of subjects achieving HiSCR at Week 12, although the model used will analyze 
data from all three treatment groups. The number and percentage of subjects who achieved 
HiSCR at Week 12 will be presented by treatment group and the statistical analysis of this 
variable will be conducted following a Bayesian paradigm utilizing an informative prior on both
the placebo and adalimumab group response rates where these informative priors were derived 
from published summary data (Clinical Study Protocol M11 810   PIONEER II). A vague prior 
will be assumed for the bimekizumab treatment group.
The Bayesian analysis of HiSCR at Week 12 will employ a logistic regression model including 
treatment group (placebo, adalimumab, and bimekizumab) and adjusting for Baseline Hurley 
Stage.
The posterior distributions of the treatment group response rates together with 95% 
credible intervals for all three treatment group response rates, and of the difference in 
response rates between the treatment groups will be summarized. A 95% credible interval 
will be presented for the bimekizumab versus placebo comparison and a 60% credible 
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interval will be presented for the bimekizumab versus adalimumab comparison. This latter 
comparison of bimekizumab with adalimumab is an informal one to assess whether any 
improvements in response rate observed with bimekizumab (over placebo) are comparable 
to the current standard of care and will be used for internal decision making on the future 
development of the compound. This comparison will not be part of the evaluation of Proof 
of Concept for this study. The posterior probability that the difference in response rates 
between the placebo and bimekizumab treatment groups is greater than zero will also be 
presented.
The study will be considered a success if the posterior probability that the difference in 
response rates between the placebo and bimekizumab groups being greater than zero is at 
least 97.5% (ie, the lower bound of the 95% credible interval of the difference between 
bimekizumab and placebo in HiSCR rates is greater than or equal to zero).
If further information (independent to this study) regarding the placebo and/or 
adalimumab treatment group response rates comes to light subsequent to writing this 
protocol then this study may be updated prior to study unblinding, and details of this will 
be supplied in the SAP and the CSR. Note that the informative priors for the placebo and 
adalimumab treatment group response rates may be updated based upon any observed 
differences in the proportions of Baseline Hurley Stage II and III subjects as long as no 
response rate data from the current study, blinded or un-blinded, have been taken into 
consideration. For example, if updated, these priors may be fitted by Baseline Hurley Stage 
if the relative proportions of Baseline Hurley Stage II and III subjects within the current 
study differ substantially from those reported in the historical data. In this case the priors 
will still be based only on historic response data, but using the Hurley-stage specific 
information rather than the average information.
Change #8
Section 15.5.2 Supportive analysis of the primary efficacy variable
The following paragraph was deleted:
In addition to the primary comparison of the bimekizumab and placebo treatment groups, an 
additional comparison between bimekizumab and adalimumab in HiSCR at Week 12 will be 
performed using the methods as described above in Section 15.5.1 for the primary efficacy 
analysis. This will be an informal comparison to assess whether any improvements in response 
rate observed with bimekizumab (over placebo) are comparable to the current standard of care 
(adalimumab) and will be used for internal decision making on the future development of the 
compound.
Change #9
Section 15.11 Planned interim analysis and data monitoring
A formal unblinded non-binding interim analysis will be conducted when approximately 45 
subjects have completed 4 weeks of the study. During this interim analysis, the sample size 
assumptions will be checked and the final sample size may be modified if the sample size 
assumptions at study planning are no longer accurate. Also, at this interim analysis, the study 
may be stopped for futility. Sample size re-estimation criteria and methods along with futility 
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rules and operating characteristics will be detailed in the interim SAP. The futility rule will be 
chosen such that the overall power of the study remains high.
An informal, unblinded interim analysis will be performed when the last randomized subject for 
this study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely. The purpose of this informal interim analysis is for the 
Sponsor key personnel to review the results of the primary efficacy analysis and safety outcomes 
to facilitate additional Clinical Planning or Portfolio Management decisions.
All analyses and unblinding instructions will be prespecified in the interim SAP and SAP.
Was changed to:
This study will include two unblinded interim analyses, the first after approximately 45 
subjects have completed 4 weeks of the study and the second when the last randomized 
subject for this study has completed the Week 12 Visit at the end of the Treatment Period 
or this subject’s participation has ended prematurely.  The purpose of these interim 
analyses is for sponsor key personnel to review results from the primary efficacy analysis 
and a subset of the analyses of exploratory efficacy and safety outcomes to facilitate 
additional Clinical Planning or Portfolio Management decisions; consequently, neither 
analysis and will lead to any formal decision to alter or terminate the trial.  Interim 
analyses will be conducted by an unblinded study team and will follow internal SOPs for 
the formal process to control the unblinding of the study for interim analysis purposes. 
This process will ensure that no unnecessary or unintentional unblinding occurs. The 
unblinded team will not disclose any unblinded information to the blinded study team and 
the storage of all unblinded documentation will be held securely and separately from the 
rest of the study documentation and outputs up until the end of the study. All analyses and 
unblinding instructions will be prespecified in the interim SAP and SAP.
Change #10
Section 15.12 Determination of sample size
The predefined success criterion for declaring a positive study requires a posterior probability of 
at least 97.5% that the HiSCR rate at Week 12 for bimekizumab will be higher than that for 
placebo.  
Additionally, the study has an exploratory objective to informally compare bimekizumab against 
the current standard of care for HS (adalimumab) using the 60% posterior distribution of the 
treatment difference.
Sample size calculations are based on the number of subjects required to meet the above success 
criterion assuming a true underlying HiSCR rate at Week 12 of 64% for bimekizumab. Published 
data from the PIONEER I and II studies (Kimball et al, 2016a) indicate that, when antibiotic 
therapy is allowed, the response rates for placebo and adalimumab at Week 12 are 27.6% and 
58.9% respectively. 
Using simulation, it was estimated that with data from 40 subjects on bimekizumab, 20 subjects 
on placebo and 20 subjects on adalimumab (80 subjects total), the study will provide at least an 
85% probability of meeting the success criterion and an 80% probability of meeting the 
exploratory criterion under the assumptions described below.
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These simulations were based upon Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the placebo and adalimumab 
treatment arms in the current study. Based on historic data, the Bayesian model assumes an 
informative prior distribution for the placebo group HiSCR rate to be β (5.52,14.48). This prior 
distribution contributes an approximate effective sample size of 20 subjects for the placebo 
treatment group. Similarly, the Bayesian model assumes an informative prior distribution for the 
adalimumab group HiSCR rate to be β (15.83,4.17), which, with the parameterization in the 
model, is equivalent to an adalimumab response rate of 58.9%. This prior distribution contributes 
an approximate effective sample size of 20 subjects for the adalimumab group. For the 
bimekizumab HiSCR rate, a vague prior probability distribution N (0,1E4) was assumed.
Was changed to:
The predefined success criterion for declaring a positive study requires a posterior probability of 
at least 97.5% that the HiSCR rate at Week 12 for bimekizumab will be higher than that for 
placebo.  
Additionally, the study has an exploratory objective to informally compare bimekizumab against 
the current standard of care for HS (adalimumab) using the 60% credible interval for the 
treatment difference.
Sample size calculations are based on the number of subjects required to meet the above success 
criterion assuming a true underlying HiSCR rate at Week 12 of 70% for bimekizumab. Published 
data from the PIONEER I and II studies (Kimball et al, 2016a) indicate that, when antibiotic 
therapy is allowed, the response rates for placebo and adalimumab at Week 12 are 27.6% and 
58.9% respectively. 
Using simulation, it was estimated that with data from 40 subjects on bimekizumab, 20 subjects 
on placebo and 20 subjects on adalimumab (80 subjects total), the study will provide at least an 
85% probability of meeting the success criterion and an 80% probability of meeting the 
exploratory criterion under the assumptions described below.
These simulations were based upon Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the placebo and adalimumab 
treatment arms in the current study. Based on historic data, the Bayesian model assumes an 
informative prior distribution for the placebo group HiSCR rate to be β (5.52,14.48). This prior 
distribution contributes an approximate effective sample size of 20 subjects for the placebo 
treatment group. Similarly, the Bayesian model assumes an informative prior distribution for the 
adalimumab group HiSCR rate to be β (11.78,8.22), which, with the parameterization in the 
model, is equivalent to an adalimumab response rate of 58.9%. This prior distribution contributes 
an approximate effective sample size of 20 subjects for the adalimumab group. For the 
bimekizumab HiSCR rate, a vague prior probability distribution N (0,1E4) was assumed.
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20
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
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21
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
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SAP_001.pdf: 
UCB 
 
19Feb2019 
Statistical Analysis Plan Amendment 1 
Bimekizumab 
HS0001 
 
 
 
Confidential 
Page 1 of 91 
  
STATISTICAL ANALYSIS PLAN  
Study: HS0001 
Product: Bimekizumab 
A PHASE 2 MULTICENTER, INVESTIGATOR-BLIND, SUBJECT-BLIND, 
PLACEBO-CONTROLLED STUDY OF THE EFFICACY, SAFETY, AND 
PHARMACOKINETICS OF BIMEKIZUMAB IN SUBJECTS WITH MODERATE TO 
SEVERE HIDRADENITIS SUPPURATIVA 
 
SAP/Amendment Number Date 
Final  
28 November 2017 
Amendment 1 
19 February 2019 
  
 
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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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 7 
1 
INTRODUCTION ........................................................................................................... 11 
2 
PROTOCOL SUMMARY ............................................................................................... 11 
2.1 Study objectives ............................................................................................................... 11 
2.1.1 
Primary objective ................................................................................................. 11 
2.1.2 
Secondary objective ......................................................................................... ..  11 
2.1.3 
Exploratory objective ................................................................................. . ..... 11 
2.2 Study variables ..................................................................................................... ..........  11 
2.2.1 
Efficacy variables .......................................................................... . ........ ... ... 11 
2.2.1.1 
Primary efficacy variable ................................................. ........... ........... 11 
2.2.1.2 
Exploratory efficacy variables .................................. . .............. .............. 12 
2.2.2 
Pharmacokinetic, pharmacodynamic, pharmacogenomic, and pharmacogenetic 
variables ....................................................................... ......... . .. ........................ 12 
2.2.2.1 
Secondary pharmacokinetic variable .......... ............. . .............................. 12 
2.2.2.2 
Exploratory pharmacodynamic variables ........ . . .................................... 12 
2.2.2.3 
Exploratory nonhereditary pharmacogenomic variables ........................... 13 
2.2.2.4 
Exploratory pharmacogenetic variables ... ............................................... 13 
2.2.3 
Safety variables ............... ... ........ .. . ........ ... ..................................................... 13 
2.2.4 
Immunological variables .......... .......... .. ............................................................ 13 
2.2.5 
Exploratory Imaging variables......... ... ............................................................... 13 
2.3 Study design and conduct ......... .. ......... .. ..................................................................... 14 
2.4 Determination of sample size . .......... . ........................................................................... 14 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 15 
3.1 General presentation of summaries and analyses ............................................................ 15 
3.2 General study level definitions ........................................................................................ 17 
3.2.1 
Analysis time points ............................................................................................ 17 
3.2.1.1 
Relative day ............................................................................................... 17 
3.2.1 2 
Study periods ............................................................................................. 17 
3.3 Definition of Baseline values ........................................................................................... 17 
3.4 Protocol deviations ........................................................................................................... 18 
3.5 Analysis sets ..................................................................................................................... 19 
3.5.1 
Enrolled Set ......................................................................................................... 19 
3.5.2 
Randomized Set ................................................................................................... 19 
3.5.3 
Safety Set ............................................................................................................. 19 
3.5.4 
Full Analysis Set .................................................................................................. 20 
3.5.5 
Per-Protocol Set ................................................................................................... 20 
3.5.6 
Pharmacokinetics Per-Protocol Set ...................................................................... 20 
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3.5.7 
Pharmacodynamics Per-Protocol Set ................................................................... 20 
3.6 Treatment assignment and treatment groups ................................................................... 20 
3.7 Center pooling strategy .................................................................................................... 22 
3.8 Coding dictionaries .......................................................................................................... 22 
3.9 Changes to protocol-defined analyses.............................................................................. 22 
4 
STATISTICAL/ANALYTICAL ISSUES ......................................................................  23 
4.1 Adjustments for covariates........................................................................................... . . 23 
4.2 Handling of dropouts or missing data .................................................................... .. ..... 23 
4.2.1 
Efficacy data ......................................................................................... . .. ...... .. 23 
4.2.2 
Pharmacodynamic and pharmacokinetic data ................................. .. .........
. 24 
4.2.3 
Safety laboratory data ............................................................... ... . ....... .. . ....... 24 
4.2.4 
Dates ................................................................................... . .. ........ .. .............. 24 
4.3 Handling of repeated and unscheduled measurements ............... .. ......... ... .................. 25 
4.4 Handling of measurements obtained at the early withdrawal visit ... ..... ........................ 26 
4.5 Interim analyses and data monitoring ................. .......... ... ..... ... . .............................. 26 
4.5.1 
Data monitoring committee ........... .. . ....................... .. ..................................... 26 
4.5.2 
Interim analysis ......................... .... ......... . ......... ............................................. 27 
4.6 Multicenter studies .......................... .... ............ . ........... . .............................................. 27 
4.7 Multiple comparisons/multiplicity .... ........ .. . ........ . .................................................... 27 
4.8 Use of an efficacy subset of subjects .. ............. . ......................................................... 27 
4.9 Active-control studies intended to show equivalence ...................................................... 27 
4.10 Examination of subgroups ........ ........... . ....................................................................... 27 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 27 
5.1 Subject disposition ......... .. ........ ... ............................................................................... 27 
5.2 Protocol deviations .. ................. ..................................................................................... 28 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 28 
6.1 Derivation of variables ..................................................................................................... 28 
6.1.1 
Calculation of body mass index ........................................................................... 28 
6.1.2 
Classification of age categories ........................................................................... 29 
6.1.3 
Duration of disease .............................................................................................. 29 
6.2 Demographics and Baseline characteristics ..................................................................... 29 
6.3 Other Baseline characteristics .......................................................................................... 29 
6.4 Medical history and concomitant diseases ....................................................................... 30 
6.5 Hidradenitis suppurativa history ...................................................................................... 31 
6.6 Prior and concomitant medications .................................................................................. 31 
6.6.1 
Prior medication definition .................................................................................. 31 
6.6.2 
Concomitant medication definition ..................................................................... 31 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 32 
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8 
EFFICACY ANALYSES ................................................................................................ 32 
8.1 Lesion count assessment .................................................................................................. 32 
8.2 Primary efficacy variable ................................................................................................. 33 
8.2.1 
Derivation of the primary efficacy variable ......................................................... 34 
8.2.2 
Primary analysis of the primary efficacy variable ............................................... 34 
8.2.2.1 
Bayesian modeling ...................................................................................  34 
8.2.2.2 
Building the prior .................................................................................. . . 37 
8.2.2.3 
Prior data conflict ............................................................................ .. ..... 37 
8.2.2.4 
Presentation of results from the primary analysis of the primary efficacy 
variable .................................................................................. . ............ ...  37 
8.2.3 
Supportive and sensitivity analyses of the primary efficacy variable ........ ........ 38 
8.2.3.1 
Choice of analysis set ................................................. . .. ...... .. ... ........... 38 
8.2.3.2 
Comparison of bimekizumab and adalimumab .... . .. ......... . .................. 38 
8.2.3.3 
Observed case Bayesian analysis ....................... ............. . ...................... 38 
8.2.3.4 
Vague prior distribution ............ ................. ......... . .. ............................ 38 
8.2.3.5 
Concomitant antibiotic use – Bayesian analysis .. ................................... 38 
8.2.3.6 
Rescue therapy – Bayesian analysis . .............. ........................................ 39 
8.2.3.7 
Frequentist analysis – NRI ........ ... ......... ................................................. 39 
8.2.3.8 
Observed case frequentist analysis .... .... .................................................. 39 
8.2.3.9 
Concomitant antibiotic use – Frequentist analysis .................................... 39 
8.2.3.10 
Rescue therapy – Frequentist analysis ....................................................... 39 
8.2.4 
HiSCR depth ................. . ........... .. ................................................................... 39 
8.2.5 
Presentation of HiSCR . ....... . ............................................................................ 40 
8.3 Exploratory efficacy variables ...... ................................................................................. 41 
8.3.1 
Lesion count data ......... . ..................................................................................... 41 
8.3.1.1 
AN count ..... .. .......................................................................................... 42 
8.3.1.2 
Disease flare .............................................................................................. 42 
8.3.2 
International Hidradenitis Suppurativa Severity Scoring System ....................... 42 
8.3.3 
Patient's Global Assessment of Skin Pain ........................................................... 43 
8.3.4 
Modified Sartorius Score ..................................................................................... 43 
8.3 5 
Hidradenitis Suppurativa Physician’s Global Assessment – Derived ................. 45 
8.3.6 
Dermatology Life Quality Index ......................................................................... 47 
8.3.7 
European Quality of Life - 5 Dimensions-3 Level Questionnaire ....................... 48 
8.3.8 
Hurley Stage ........................................................................................................ 48 
8.3.9 
Erythema assessment ........................................................................................... 49 
8.3.10 
Hospital Anxiety and Depression Scale .............................................................. 49 
8.4 High Sensitivity C-Reactive Protein ................................................................................ 50 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 50 
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9.1 Pharmacokinetics ............................................................................................................. 50 
9.2 Pharmacodynamics .......................................................................................................... 51 
10 IMMUNOLOGICAL ANALYSES ................................................................................. 51 
11 SAFETY ANALYSES ..................................................................................................... 53 
11.1 Extent of exposure ........................................................................................................... 53 
11.2 Adverse events ................................................................................................................  53 
11.3 Clinical laboratory evaluations .................................................................................... . . 55 
11.4 Vital signs, physical findings, and other observations related to safety ................ .. ..... 58 
11.4.1 
Vital signs ............................................................................................. . .. ...... .. 58 
11.4.2 
Electrocardiograms .......................................................................... .. .........
. 58 
11.4.3 
Other safety variables ............................................................... ... . ....... .. . ....... 59 
11.4.3.1 
Physical examination ................................................ . .. ........ .. .............. 59 
11.4.3.2 
Columbia-Suicide Severity Rating Scale ............. .. ......... ... .................. 59 
11.4.3.3 
Chest X-ray and tuberculosis questionnaire ..... .. ...... ..... ........................ 59 
12 OTHER ANALYSES ......................................... .......... ... ..... ... . .............................. 60 
13 REFERENCES .......................................... .. . ....................... .. ..................................... 61 
14 APPENDICES ...................................... .... ......... . ......... ............................................. 63 
14.1 HS-Physician’s Global Assessment 6-point scale .......... . .............................................. 63 
14.2 Modified Sartorius Score ........... ...... ........ .. . ........ . .................................................... 63 
14.3 Dermatology Life Quality Index . ....... ............. . ......................................................... 64 
14.4 European Quality of Life 5 Dimensions-3 Level Questionnaire ..................................... 67 
14.5 Hospital Anxiety and Depression Scale . . ....................................................................... 68 
14.6 Treatment-emergent markedly abnormal laboratory values ............................................ 69 
14.7 Treatment-emergent abnormal liver values ..................................................................... 70 
14.8 Treatment-emergent markedly abnormal vital signs values ............................................ 71 
14.9 Adverse events for special monitoring ............................................................................ 71 
14.9.1 
Major cardiovascular events ................................................................................ 72 
14.9.2 
Serious infections, including opportunistic infections and tuberculosis ............. 72 
14.9.2.1 
Serious infections ...................................................................................... 72 
14 9 2.2 
Fungal infections ....................................................................................... 72 
14.9.2.3 
Opportunistic infections ............................................................................ 72 
14.9.3 
Malignancies including lymphoma ...................................................................... 73 
14.9.4 
Cytopenias ........................................................................................................... 73 
14.9.5 
Neuropsychiatric events ....................................................................................... 74 
14.9.6 
Inflammatory bowel disease ................................................................................ 74 
14.9.7 
Anaphylactic reaction .......................................................................................... 74 
14.9.7.1 
Anaphylactic reaction algorithm ............................................................... 74 
14.9.8 
Hepatic events and drug induced liver injury ...................................................... 78 
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14.10 
Treatment group assignment for the TFLs............................................................. 78 
15 AMENDMENTS TO THE SAP ...................................................................................... 79 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 91 
 
LIST OF TABLES 
Table 3‒1: 
Definition of Baseline .....................................................................................  17 
Table 3‒2: 
Administration of investigational medicinal product ............................ . ...... 21 
Table 11‒1: 
Laboratory measurements .................................................................... ......... . 56 
Table 14‒1: 
HS-Physician’s Global Assessment 6-point scale ..................... . ........ ... ... 63 
Table 14‒2: 
Modified Sartorius Score .................................................... .. . ..... .. . ......... 63 
Table 14‒3: 
Dermatology Life Quality Index .................................. .. .......... ..................... 64 
Table 14‒4: 
European Quality of Life-5 Dimensions-3 Level Questionnaire ..................... 67 
Table 14‒5: 
UK TTO Value Set .............................. .......... . ... ..... ... . ............................. 67 
Table 14‒6: 
Hospital Anxiety and Depression Scale .. ............. ... .................................... 68 
Table 14‒7: 
Definition of TEMA values for hematology ...... ............................................. 69 
Table 14‒8: 
Definition of TEMA values for chemistry . . .................................................. 69 
Table 14‒9: 
Definition of treatment-emergent liver function values................................... 70 
Table 14‒10: TEMA/PCS criteria for vital signs .. ................................................................ 71 
Table 14‒11: Treatment group assignment for the TFLs....................................................... 78 
 
 
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LIST OF ABBREVIATIONS 
%ΔAN 
percentage change from Baseline in abscess and inflammatory 
nodule count 
ACP 
above the cut point 
ADA 
adalimumab 
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 
AN 
abscess and inflammatory nodule 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
BCP 
below the cut point 
BKZ 
bimekizumab 
BLQ 
below the limit of quantification 
BMI 
body mass index 
bpm 
beats per minute 
BUN 
blood urea nitrogen 
CD 
cluster of differentiation 
CI 
confidence interval 
CP 
confirmed positive 
CSR 
clinical study report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CT 
controlled terminology 
CTCAE 
Common Terminology Criteria for Adverse Events 
DEM 
data evaluation meeting 
DLQI 
Dermatology Life Quality Index 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EQ-5D-3L 
European Quality of Life-5 Dimensions-3 Level questionnaire 
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ES 
Enrolled Set 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
EW 
early withdrawal  
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone 
geoCV 
geometric coefficient of variation 
GEE 
generalized estimating equation 
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  
HiSCR 
Hidradenitis Suppurativa Clinical Response 
HIV 
human immunodeficiency virus  
HLA 
human leukocyte antigen 
HLGT 
high level group term 
HLT 
high level term 
HS 
hidradenitis suppurativa 
hsCRP 
high sensitivity C-reactive 
ICH 
International Council for Harmonization 
IHS4 
International Hidradenitis Suppurativa Severity Scoring System 
IL 
interleukin 
IMP 
investigational medicinal product 
IPD 
important protocol deviation 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
LLOQ 
lower limit of quantification 
mHiSCR25 
modified Hidradenitis Suppurativa Clinical Response – 25% 
mHiSCR75 
modified Hidradenitis Suppurativa Clinical Response – 75% 
mHiSCR90 
modified Hidradenitis Suppurativa Clinical Response – 90% 
MCH 
mean corpuscular hemoglobin 
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MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
n 
number of subjects 
NA 
not applicable 
NCP 
not confirmed positive 
NRI 
non-responder imputation 
NRS 
numeric rating scale  
PBO 
placebo 
PCS 
potentially clinically significant 
PD 
pharmacodynamic(s) 
PDILI 
potential drug-induced liver injury 
PD-PPS 
Pharmacodynamic Per-Protocol Set 
PGA 
patient's global assessment 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
PoC 
proof of concept 
PPS 
Per-Protocol Set 
PT 
preferred term 
Q1 
first quartile 
Q3 
third quartile 
QoL 
quality of life 
QTcF 
QT corrected for heart rate using Fridericia’s formula 
RBC 
red blood cell 
RCTC 
Rheumatology Common Toxicity Criteria 
RS 
Randomized Set 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SD 
standard deviation 
SDTM 
Study Data Tabulation Model 
SFU 
Safety Follow-up 
SMQ 
standardized MedDRA query 
SOC 
system organ class 
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SS 
Safety Set 
TB 
Tuberculosis 
TEAE 
treatment-emergent adverse event 
TEMA 
treatment-emergent markedly abnormal 
TFLs 
tables, figures and listings 
ULN 
upper limit of normal 
VAS 
visual analogue scale  
WBC 
white blood cell 
WHODD 
World Health Organization Drug Dictionary 
 
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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 HS0001. 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 amendment 1, dated 08 March 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 must be modified or updated prior to database lock, a further SAP 
amendment will be required. If, after database lock, additional analyses are required to 
supplement the planned analyses described in this SAP, these changes will be described in the 
CSR together with the associated rationale. 
The content of this SAP is compatible with the International Council for Harmonization 
(ICH)/Food and Drug Administration (FDA) E9 Guidance documents (ICH, 1998). 
UCB is the Sponsor and PAREXEL is the Contract Research Organization for this study. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective of this study is to evaluate the efficacy of bimekizumab in subjects with 
moderate to severe hidradenitis suppurativa (HS). 
2.1.2 
Secondary objective 
The secondary objective of this study is to assess the safety, tolerability, immunogenicity, and 
pharmacokinetics (PK) of bimekizumab in subjects with moderate to severe HS. 
2.1.3 
Exploratory objective 
The exploratory objective of the study is to further assess the efficacy of bimekizumab and to 
explore the effect of bimekizumab on gene and protein expression, and to explore the 
relationship between pharmacodynamic (PD), nonhereditary pharmacogenomics, 
pharmacogenetic, and imaging biomarkers and HS disease biology, drug treatment, and 
inflammatory and immune responses. 
2.2 
Study variables 
2.2.1 
Efficacy variables 
2.2.1.1 
Primary efficacy variable 
The primary efficacy variable is the clinical response as measured by Hidradenitis Suppurativa 
Clinical Response (HiSCR) (defined as at least a 50% reduction from Baseline in the total AN 
(abscess and inflammatory nodule) count with no increase from Baseline in abscess or draining 
fistula count) at Week 12. 
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2.2.1.2 
Exploratory efficacy variables 
The exploratory efficacy variables are listed below and will be evaluated at scheduled visits in 
accordance with the schedule of assessments. 
 Proportion of subjects with a total abscess and inflammatory nodule count of 0, 1, or 2 at 
Week 12 
 Proportion of subjects with at least a 30% reduction and at least 1-unit reduction from 
Baseline in the Patient's Global Assessment (PGA) of Skin Pain (based on the subject’s worst 
pain over the previous 24 hours) at Week 12 
 Change from Baseline in Modified Sartorius Score at Week 12 
 Change and percentage change from Baseline in lesion count (abscess count, inflammatory 
nodule count, abscess and inflammatory nodule count, and draining fistula count) over time 
 Change from Baseline in International Hidradenitis Suppurativa Severity Scoring System 
(IHS4) score over time 
 Change from Baseline in erythema assessment over time 
 Change from Baseline in Hurley Stage over time 
 Change and percentage change from Baseline in PGA of Skin Pain (pain at its worst and pain 
on average over the last 24 hours) over time 
 Change from Baseline in the HS-Physician’s Global Assessment 6-point scale over time 
 Change from Baseline in the Dermatology Life Quality Index (DLQI) score over time 
 Change from Baseline in European Quality of Life-5 Dimensions-3 Level questionnaire 
(EQ-5D-3L) (index and visual analogue scale [VAS] scores) over time 
 Change from Baseline in Hospital Anxiety and Depression Scale (HADS), HADS-Anxiety 
(HADS-A) and HADS-Depression (HADS-D) scores over time 
2.2.2 
Pharmacokinetic, pharmacodynamic, pharmacogenomic, and 
pharmacogenetic variables 
2.2.2.1 
Secondary pharmacokinetic variable 
Blood samples will be collected for the measurement of plasma bimekizumab concentrations at 
scheduled visits in accordance with the schedule of assessments. 
2.2.2 2 
Exploratory pharmacodynamic variables 
The PD variables assessed are the blood or blood derivative (eg, plasma) concentrations of 
cytokines and chemokines of relevance to interleukin (IL) 17A/F signaling pathway and HS 
biology. 
Additional variables may include, but will not be limited to, serum complement concentrations 
and mononuclear cell subtypes. 
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2.2.2.3 
Exploratory nonhereditary pharmacogenomic variables  
Where local regulations permit, blood, urine and skin tissue biopsy samples will be collected and 
stored for up to 20 years to allow for potential exploratory analyses of ribonucleic acid, proteins, 
and metabolites biomarkers relevant to HS and the inflammatory and immune response 
processes. The nature and format of these tentative analyses will be determined at a later stage. 
The results of any pharmacogenomics analyses will be reported outside the CSR and are not 
further described in this SAP. 
2.2.2.4 
Exploratory pharmacogenetic variables  
Additional blood samples will be collected from subjects who consent to participate in the 
pharmacogenetic substudy and stored at -80°C for up to 20 years. Pharmacogenetic biomarkers 
may be measured to evaluate the relationship with response to treatment with bimekizumab or 
adalimumab, HS disease biology, and inflammatory and immune response processes. The nature 
and format of these tentative substudy analyses will be determined when the results of the main 
study are made available. The results of any pharmacogenetic analyses will be reported outside 
the CSR and are not further described in this SAP. 
2.2.3 
Safety variables 
As part of the secondary objective, the following secondary safety variables will be assessed: 
 Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) 
 Withdrawal due to AEs 
 Change from Baseline in vital signs (blood pressure, pulse rate and body temperature) and 
body weight 
 Change from Baseline in electrocardiogram (ECG) parameters 
 Change from Baseline in clinical laboratory parameters (hematology, biochemistry, and 
urinalysis) 
 Change from Baseline in physical examination 
2.2.4 
Immunological variables 
Blood samples will be collected for the measurement of anti-drug (bimekizumab) antibody 
(anti-bimekizumab antibody). 
2.2.5 
Exploratory Imaging variables 
Imaging biomarkers will be assessed by means of medical infrared imaging (thermography) and 
photography in specific centers with technological capabilities for subjects who consent to 
participate in the imaging substudy. Imaging biomarkers may be measured to evaluate the 
relationship with response to treatment with bimekizumab or adalimumab, HS disease biology, 
and inflammatory and immune response processes.  The thermography and photography results 
will not be a part of the CSR and are not further described in this SAP. 
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2.3 
Study design and conduct 
HS0001 is a Phase 2 multicenter, randomized, Investigator-blind, subject-blind, 
placebo-controlled, active-reference arm study to assess the efficacy, safety, and PK of 
bimekizumab in eligible adult subjects with moderate to severe HS.  
This study will include 3 periods: a Screening Period (≥2 weeks up to a maximum of 4 weeks 
prior to randomization), a Treatment Period (12 weeks), and a Safety Follow up (SFU) Period 
(20 weeks after the last dose of investigational medicinal product [IMP]).  
A sufficient number of subjects will be screened in order to have 80 subjects randomized 2:1:1 
(bimekizumab to placebo to adalimumab, stratified by Baseline Hurley Stage) to receive blinded 
IMP (all administered by subcutaneous injection by unblinded study personnel)  There will be 
approximately 40 subjects in the bimekizumab treatment group, 20 subjects in the placebo group, 
and 20 subjects in the adalimumab group. 
A data monitoring committee (DMC) will review the data on an ongoing basis. The composition 
and roles of the DMC are described in a separate DMC Charter. The analyses required and data 
to be presented are described in a separate DMC SAP. 
2.4 
Determination of sample size 
The predefined success criterion for declaring a positive study requires a posterior probability of 
at least 97.5% that the HiSCR rate at Week 12 for bimekizumab will be higher than that for 
placebo. 
Additionally, the study has an exploratory objective to informally compare bimekizumab against 
the current standard of care for HS (adalimumab) using the 60% credible interval for the 
treatment difference. 
Sample size calculations are based on the number of subjects required to meet the above success 
criterion (comparing against placebo) assuming a true underlying HiSCR rate at Week 12 of 70% 
for bimekizumab. Published data from the PIONEER I and II studies (Kimball et al, 2016a) 
indicate that, when antibiotic therapy at entry is allowed, the response rates for placebo and 
adalimumab at Week 12 are 27.6% and 58.9% respectively.  
Using simulation, it is estimated that with data from 40 subjects on bimekizumab, 20 subjects on 
placebo and 20 subjects on adalimumab (80 subjects total), the study will provide at least a 99% 
probability of meeting the success criterion and an 80% probability of meeting the exploratory 
criterion under the assumptions described below.  
These simulations were based on Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the placebo and adalimumab 
treatment arms in the current study. Based on historic data, the Bayesian model assumes an 
informative prior distribution for the placebo group HiSCR rate to be β (5.52,14.48). This prior 
distribution contributes an approximate effective sample size of 20 subjects for the placebo 
treatment group. Similarly, the Bayesian model assumes an informative prior distribution for the 
adalimumab group HiSCR rate to be β (11.78, 8.22) which, with the parametrization in the 
model, is equivalent to an adalimumab response rate of 58.9%.  This prior distribution 
contributes an approximate effective sample size of 20 subjects for the adalimumab group. For 
the bimekizumab HiSCR rate, a vague prior probability distribution N (0,1E4) was assumed. 
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3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical evaluation will be performed by PAREXEL with oversight and supervision by UCB. 
The datasets will follow the UCB analysis data model data specifications.  
All statistical analyses will be performed using SAS® version 9.4 or later (SAS Institute, Cary  
NC, USA) or R version 2.10.1 (R Development Core Team) or later, or WinBUGS 1.4.  
Descriptive statistics will be used to provide an overview of the Baseline, efficacy, PD, PK and 
safety results.  In this study, formal statistical testing will be conducted for this study for the 
primary efficacy variable only.  Exploratory efficacy variables will be summarized descriptively 
by treatment group.   
The primary treatment comparison for all analyses of efficacy will be between bimekizumab and 
placebo. 
Continuous variables will be summarized by treatment, visit (where applicable) including 
number of subjects (n), mean, standard deviation (SD), median, minimum and maximum. First 
and third quartiles (Q1 and Q3 respectively) and 95% confidence intervals (CI) for the mean will 
also be included where indicated.  
Categorical variables will be summarized by treatment, visit (where applicable) with frequency 
counts and percentages. Geometric coefficient of variation (geoCV), geometric mean and 95% 
CI for the geometric mean will also be presented in the descriptive statistics for the PK 
concentration 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 
 For the purpose of the tabulations the lower and upper 95% confidence limits for the 
percentages will be truncated at 0 and 100% respectively 
 Unless otherwise stated, the denominator for the percentages will be based on the number of 
subjects in the respective analysis set, treatment group, visit and any subgroup defined for the 
tabulations (eg, Baseline Hurley Stage) with non-missing data for the relevant classification 
Percentages displayed based on continuous data (eg, percentage changes from Baseline) will be 
displayed to 1 decimal place.  
When reporting descriptive statistics, the following rules will apply in general (with the 
exception of PK data, for which additional rules are stated below): 
 n will be an integer 
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 Mean (arithmetic and geometric), SD, median and CIs will use 1 decimal place more (or 1 
more significant figure, depending on the original data reporting format) than the original 
data 
 Coefficient of variation will be reported as a percentage to 1 decimal place 
 Minimum and maximum will be reported using the same number of decimal places as the 
original data 
 If no subjects have data at a given time point, then only n=0 will be presented. If n<3, then 
only n, minimum and maximum will be presented. If n=3, then only n, median, minimum 
and maximum will be presented. The other descriptive statistics will be left blank 
When reporting individual values and descriptive statistics for PK concentration data, the 
following rules will apply with regard to rounding and precision: 
 Individual values will be reported to the same level of precision as received from the 
bioanalytical laboratory 
 Descriptive statistics will be reported to the same level of precision as the individual data for 
the minimum and maximum, and to 1 additional significant figure for the mean (arithmetic 
and geometric), median, SD and 95% CI for the geometric mean  
 The geoCV will be reported as a percentage to 1 decimal place 
All statistical tests will be carried out 2 tailed at the 5% level of significance unless otherwise 
stated. The following rules will apply for the presentation of any results relating to inferential 
statistical analysis: 
 Posterior probabilities associated with the Bayesian analyses of the primary efficacy variable 
will be presented as percentages to 1 decimal place 
 Means, SDs, medians, 95% credible intervals and highest posterior density intervals obtained 
from the Bayesian analysis of the primary efficacy variable will be presented to 1 decimal 
place 
All statistical output will be presented in statistical appendices where appropriate. 
All tabulations will be performed by treatment group and visit (where applicable). In the TFLs 
the treatment groups will be displayed as follows, where BKZ refers to bimekizumab, ADA 
refers to adalimumab and PBO refers to placebo: 
 PBO 
 ADA 
 BKZ 
Subject data listings containing all documented data and all derived data will be generated and 
these will be presented by treatment group and subject. 
If Study Data Tabulation Model (SDTM) controlled terminology (CT) is defined for selected 
variables, it will be displayed similarly in the TFLs. Yes/No responses will be presented as Y/N 
consistent with the YN CT and Male and Female will be replaced with M/F respectively in the 
TFLs. 
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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 dose of IMP as reference. 
Relative days for an event or measurement occurring before the date of first dose will be 
calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦 =  𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒  
The relative day for an event or measurement occurring on or after the reference date to the date 
of the last dose will be calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦 = (𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒) +  1  
For events or measurements occurring after the date of the last dose, relative day will be prefixed 
with ‘+’ in the data listings and will be calculated as follows: 
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐷𝑎𝑦 =  𝐸𝑣𝑒𝑛𝑡 𝐷𝑎𝑡𝑒 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐷𝑜𝑠𝑒 
There is no relative Day 0. Relative day will not be calculated for partial dates in cases where 
relative day is shown in a subject data listing. In such cases, relative day will be presented as ‘-‘ 
in the subject data listings. 
3.2.1.2 
Study periods 
For each subject completing the study, their maximum study duration will be up to 34 weeks and 
will comprise the following: 
 Screening Period: ≥2 weeks with a maximum of 4 weeks prior to randomization 
 Treatment Period: 12 weeks 
 Safety Follow-Up Period: 20 weeks after the last dose of IMP (scheduled at Week 10, 2 
weeks prior to the end of the Treatment Period) 
The end of the study is defined as the date of the last visit of the last subject in the study. 
3.3 
Definition of Baseline values 
Baseline will be the last available value prior to the first dose of IMP. Scheduled or unscheduled 
measurements can be used as the Baseline value. If a measurement is repeated at Baseline and is 
obtained prior to receiving the first dose of IMP, then the last available measurement will be 
used as the Baseline value. 
Measurement-specific Baseline visits (based on the planned visits in the protocol) are presented 
in Table 3‒1.  
Table 3‒1: 
Definition of Baseline 
Category 
Measurement/Derivation 
Definition of Baseline 
Efficacy 
Lesion count (including Hurley 
Stage) 
Visit 2 (Day 1, predose) or if 
missing, the Screening value 
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Table 3‒1: 
Definition of Baseline 
Category 
Measurement/Derivation 
Definition of Baseline 
Erythema assessment 
HADS-A and HADS-D 
Modified Sartorius Score 
PGA of skin pain 
HS-Physician’s global 
assessment 
DLQI 
EQ-5D-3L 
 
Safety 
Vital signs 
12-lead ECG 
Safety laboratory tests 
C-SSRS 
Visit 2 (Day 1, predose) or if 
missing, the Screening value 
Pharmacodynamic 
Cytokines, candidate biomarkers 
and flow cytometry 
Visit 2 (Day 1, predose) 
Immunological 
Anti-bimekizumab antibody 
Visit 2 (Day 1) 
C-SSRS=Columbia-Suicide Severity Rating Scale; DLQI=Dermatology Life Quality Index; 
ECG=electrocardiogram; EQ-5D-3L=European Quality of Life 5 Dimensions-3 Level questionnaire; HADS= 
Hospital Anxiety and Depression Scale; HADS-A= Hospital Anxiety and Depression Scale-Anxiety; HADS-D= 
Hospital Anxiety and Depression Scale-Depression; PGA=Patient’s Global Assessment. 
 
The change from Baseline to any subsequent post-Baseline visit will be calculated as the simple 
difference between that post-Baseline visit’s value and the Baseline value, as below: 
Post-Baseline Visit Value – Baseline Visit Value 
The percentage change from Baseline to any subsequent post-Baseline visit will be calculated as 
follows: 
100 × (Post-Baseline Visit Value – Baseline Visit Value) / (Baseline Visit Value) 
3.4 
Protocol deviations 
Important protocol deviations (IPDs) are deviations from the protocol which potentially could 
have a meaningful impact on the primary objective of the study. The criteria for identifying such 
protocol deviations will be defined within the IPD document which is part of the data cleaning 
plan. Important protocol deviations will be classified as follows:  
 Inclusion/exclusion criteria deviations 
 Administration of prohibited concomitant medications 
 Deviations relating to withdrawal criteria 
 Visit schedule deviations 
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 Study drug administration deviations (including incorrect treatment received, handling and 
storage deviations and incorrect dosage received) 
 Treatment non-compliance 
 Procedural non-compliance 
 Missing data  
 Other 
Important protocol deviations will be reviewed as part of the ongoing data cleaning process and 
data evaluation.  
At least 3 data evaluation meetings (DEMs) will be performed for this study at the following 
time points: 
 Prior to the informal unblinded interim analysis planned after approximately 45 subjects have 
completed 4 weeks of the study.  
 Prior to the informal unblinded interim analysis planned after the last subject (excluding 2 
subjects from site 101 in Australia who entered the study outside of the original planned 
recruitment period) has completed 12 weeks of the study or has discontinued early. 
 Prior to the final analysis after all subjects have completed the SFU period and data have 
been verified/coded/entered into the database 
Additional DEMs may be conducted as deemed necessary. 
The purpose of these DEM reviews will be to review all protocol deviations, define the analysis 
sets, and check the quality of the data. The reviews will also help decide how to manage 
problems in the subjects’ data (eg, missing values and withdrawals).  
Accepted deviations from theoretical time points will be described in the appropriate documents 
and included in the Study Master File. After the pre-analysis review, resolution of all issues, and 
documentation of all decisions (including inclusion into each of the analysis sets) at the final 
DEM, the database will be locked. 
3.5 
Analysis sets 
3.5.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all subjects who have given informed consent (ie, all 
subjects screened). The ES will therefore include Screening failures. 
3.5.2 
Randomized Set 
The Randomized Set (RS) will consist of all subjects randomized into the study. 
3.5.3 
Safety Set 
The Safety Set (SS) will consist of all subjects who received at least 1 dose (full or partial) of 
IMP. The safety analysis will be conducted on the SS.  
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3.5.4 
Full Analysis Set 
The Full Analysis Set (FAS) is a subset of the RS and will consist of all subjects who received at 
least 1 dose (full or partial) of IMP and had a valid Baseline measurement and a post-Baseline 
measurement for at least 1 efficacy variable (as defined in Section 2.2.1).  The FAS will be used 
for the supportive and sensitivity analyses of the primary efficacy variable and for all exploratory 
efficacy analyses. 
3.5.5 
Per-Protocol Set 
The Per-Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had no IPDs 
affecting the primary efficacy variable, as confirmed during a pre-analysis review prior to 
unblinding of the data (at each of the interim and final analyses). All primary efficacy analyses 
will be performed for the PPS.  The PPS will also be used for the supportive and sensitivity 
analyses of the primary efficacy variable. 
Protocol deviations will be reviewed at the DEMs and any exclusions from analysis sets will be 
documented as described in Section 3.4.  It is anticipated that the PPS for the final analysis will 
differ from the PPS defined at the formal interim analysis as the primary efficacy variable is 
assessed at Week 12, whereas the formal interim analysis will be based on only 45 of the 80 
randomized subjects completing Week 4 of the study.  Therefore, all relevant data will not be 
available at the time of the interim analysis DEM.   
The PPS as agreed for the informal interim analysis may similarly be different from the PPS as 
agreed for the final analysis due to additional information obtained on subjects during the SFU 
Period.   
Following the final DEM, the inclusion into each of the analysis sets for all subjects will be 
confirmed. The DEM minutes will document the final agreed PPS to be applied to the final 
analysis, as well as document any changes to the PPS relative to the previously agreed PPS at the 
interim(s), if applicable.  
3.5.6 
Pharmacokinetics Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) will consist of all randomized subjects who 
received at least 1 dose of IMP and had at least 1 quantifiable post-dose plasma concentration. 
3.5.7 
Pharmacodynamics Per-Protocol Set 
The Pharmacodynamic Per-Protocol Set (PD-PPS) will be a subset of the FAS, consisting of 
those subjects who had no IPDs potentially affecting the PD data, as confirmed during 
pre-analysis review of the data prior to database lock. 
3.6 
Treatment assignment and treatment groups 
Listings and summaries will be presented by treatment group and for all subjects in the relevant 
analysis sets, where applicable. Treatment assignment is given in Table 14‒11.  
The following order will be used in the TFLs (with the treatments displayed accordingly): 
 Not randomized (if applicable) 
 PBO 
 ADA 
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 BKZ 
 All subjects 
The dosing schedules and number of injections given at each visit are described in Table 3‒2. 
Due to the differences in the dosing schedule between bimekizumab and adalimumab, placebo 
injections will be administered along with active drug such that all subjects will receive the same 
number of injections at each corresponding visit.   
Table 3‒2: 
Administration of investigational medicinal product 
Visit 
Treatment group 
Adalimumaba 
(Total # injections, # of 
placebo injections) 
Bimekizumabb 
(Total # injections, # of 
placebo injections) 
Placebo 
Baseline 
160mg (4 active 
injections, no placebo 
injections) 
640mg (4 active 
injections, no placebo 
injections) 
4 placebo injections 
Week 2 
80mg (2 active 
injections, no placebo 
injections) 
320mg (2 active 
injections, no placebo 
injections) 
2 placebo injections 
Weeks 4, 6, 8, and 10 
40mg (1 active injection, 
1 placebo injection) 
320mg (2 active 
injections, no placebo 
injections) 
2 placebo injections 
Weeks 5, 7, and 9 
40mg (1 active injection, 
no placebo injection) 
NA (no active injection, 
1 placebo injection) 
1 placebo injection 
NA=not applicable 
a Each individual adalimumab injection will be 40mg. 
b Each individual bimekizumab injection will be 160mg. 
 
In the case of dosing administration errors during the Treatment Period, all statistical analyses of 
safety data will be conducted according to the actual treatment received, ie, treatment assignment 
for the SS will be based on actual treatment with the following rules: 
 Subjects randomized to placebo who received at least 1 dose of bimekizumab will be 
summarized in the ‘BKZ’ treatment group 
 Subjects randomized to bimekizumab who received placebo throughout the Treatment Period 
will be summarized in the ‘PBO’ treatment group 
 Subjects randomized to bimekizumab who received any doses of placebo during the 
Treatment Period, but at least 1 dose of bimekizumab, will be summarized in the ‘BKZ’ 
treatment group 
 Subjects randomized to bimekizumab who received any doses of adalimumab during the 
Treatment Period, but at least 1 dose of bimekizumab, will be assessed at the DEM for the 
treatment group assignment, as it will depend on how many doses of each of the treatments 
were taken and at what time point during the study 
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 Subjects randomized to placebo who received at least 1 dose of adalimumab will be 
summarized in the ‘ADA’ treatment group 
 Subjects randomized to adalimumab who received placebo throughout the Treatment Period 
will be summarized in the ‘PBO’ treatment group 
 Subjects randomized to adalimumab who received any doses of placebo during the Treatment 
Period, but at least 1 dose of adalimumab, will be summarized in the ‘ADA’ treatment group 
 Subjects randomized to adalimumab who received any doses of bimekizumab during the 
Treatment Period, but at least 1 dose of adalimumab, will be assessed at the DEM for the 
treatment group assignment, as it will depend on how many doses of each of the treatments 
were taken and at what time point during the study 
 Subjects randomized to placebo who received at least 1 dose of adalimumab and at least 1 
dose bimekizumab will be assessed at the DEM for the treatment group assignment, as it will 
depend on how many doses of each of the active treatments were taken and at what time 
point during the study 
Subjects receiving the incorrect treatment at a particular visit will be excluded from the PPS, 
PD-PPS and the PK-PPS as this would be considered as an IPD. Subjects may be excluded from 
the analysis at a particular visit (or visits) only or overall, following discussion at the DEMs, and 
will be included in the analyses according to their randomized treatment (which would be 
equivalent to an analysis according to their actual treatment)  
All statistical analyses of the PK and immunological data will be conducted according to the 
actual treatment received, ie, treatment assignment for the PK-PPS will be based on actual 
treatment. 
Similarly, all statistical analyses of the PD data will be conducted according to the actual 
treatment received, ie, treatment assignment for the PD-PPS will be based on actual treatment. 
3.7 
Center pooling strategy 
The data from different sites will be pooled for all analyses. No stratification by site or country 
will be performed. 
3.8 
Coding dictionaries 
Adverse events and medical history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA®) version 19.0. 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD) version SEP2015. Medical procedures will not be coded. 
3.9 
Changes to protocol-defined analyses 
The following changes relative to the protocol-defined analyses have been included in the SAP: 
 The protocol defines the HiSCR as “at least a 50% reduction from Baseline in the total 
abscess and inflammatory nodule count, with no increase from Baseline in abscess or 
draining fistula count”.  The SAP defines this as “at least a 50% reduction from Baseline in 
the total abscess and inflammatory nodule count, with no increase from Baseline in abscess 
or draining tunnels (fistulas/sinus tracts) count” 
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 The section on the determination of the sample size in the protocol states that, with the 
planned sample size of 80 subjects, the probability of study success is 85%.  Subsequent 
simulations have been performed and the probability found to be 99%.  The SAP thus states 
this 99% probability in Section 2.4 instead. 
 The PD-PPS was included as an additional analysis set in the SAP and was not part of the 
clinical study protocol. This was added as it was deemed appropriate to review protocol 
deviations separately in relation to these data and to define a separate analysis set 
accordingly. 
 The definition of the FAS was updated to include all subjects with a valid Baseline 
measurement and a post-Baseline measurement for at least 1 efficacy variable. In the 
protocol, the definition included only subjects with a valid Baseline measurement and a 
post-Baseline measurement for the primary efficacy variable.  Since the primary efficacy 
variable is a composite endpoint based on abscess count, inflammatory nodule count and 
draining tunnel (fistula/sinus tract) count, using this definition, any subjects with at least 1 
missing component of the composite endpoint would not be included in any of the efficacy 
analyses. 
 Based on the second interim analysis for this study, additional exploratory efficacy variables 
based on the lesion count assessment data, HiSCR depth and disease flare status, have been 
defined in this SAP amendment.  Section 8.2.4 includes details on the derivation of different 
HiSCR depths and Section 8.2.5 describes the planned summaries of this additional variable.  
Section 8.3.1.2 defines disease flare and includes details on planned summaries of disease 
flare status and the number of visits at which a subject experienced a disease flare during the 
Treatment Period. 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
Randomization will be stratified by Baseline Hurley Stage in this study.  Accordingly, all 
statistical models fitted in the analyses of the primary efficacy variable will include the 
stratification factor for Baseline Hurley Stage as a covariate. 
In cases of classification errors at the time of randomization, subjects may be assigned to an 
incorrect stratum  In these cases, subjects will be included in the statistical modelling according 
to the observed values of Baseline Hurley Stage regardless of the value used by the site to 
stratify the subject at randomization. 
Concomitant antibiotic use at entry into the study will be included as an additional covariate in 
the supportive and sensitivity analyses of the primary efficacy variable. 
4.2 
Handling of dropouts or missing data 
4.2.1 
Efficacy data 
There will be no imputation of missing data for the individual components of the HiSCR 
(abscess count, inflammatory nodule count and draining tunnel (fistula/sinus tract) count).   
For subjects with a missing HiSCR due to missing component data at a specific visit, or due to 
early discontinuation from the study during the Treatment Period, non-responder imputation 
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(NRI) will be used for the primary analysis of the primary efficacy variable. These subjects will 
be defined as non-responders at a specific visit or at all subsequent visits after the time of study 
discontinuation. In additional sensitivity analyses, an ‘observed cases’ analysis will also be 
performed (no imputation of missing HiSCR) and subjects who receive specific rescue therapy 
will also be considered a non-responder from the time that the rescue therapy was taken to the 
end of the Treatment Period (Section 8.2.3). 
For the hsCRP data, measurements that are below the limit of quantification (BLQ) will be 
imputed with half of the lower limit of quantification (LLOQ) for the purpose of calculating 
summary statistics, changes from Baseline and ratio to Baseline. 
The handling of any missing data for the other exploratory efficacy data is described or 
referenced in the respective sections where the analysis of this data is described. 
4.2.2 
Pharmacodynamic and pharmacokinetic data 
For the PD data (cytokines, chemokines, flow cytometry and additional variables as measured), 
measurements that are BLQ will be imputed with half of the LLOQ for the purpose of 
calculating summary statistics and changes from Baseline. Measurements that are ALQ, if 
applicable, will be imputed to the upper quantification limit. 
Measurements of PK concentration that are BLQ will be imputed with half of the LLOQ for the 
purpose of calculating the geometric mean and its 95% CI, the geoCV, the arithmetic mean and 
SD for the summaries and figures. 
For the individual figures, any concentrations that are BLQ will be regarded as missing, with the 
exception of predose BLQ measurements on Day 1, which will be imputed with zero for linear 
scale plots. 
4.2.3 
Safety laboratory data 
The rules for handling values that are BLQ or ALQ in the safety laboratory data will be the same 
as those described for PK data in Section 4.2.2. 
4.2.4 
Dates 
Partial dates may be imputed for the following reasons: 
 Classification of AEs as treatment-emergent 
 Classification of medications as prior or concomitant 
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the 
database. 
The following rules will be applied for partial start dates: 
 If only the month and year are specified and the month and year of the first dose of IMP is 
not the same as the month and year of the start date then the 1st of the month will be used, or 
the date of Screening if this is later (if the latter imputation results in an end date that is 
earlier than the start date, then the 1st of the month will be used). If time is missing this will 
be imputed as 00:00 h 
 If only the month and year are specified and the month and year of the first dose of IMP is 
the same as the month and year of the start date, then the date of the first dose of IMP will be 
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used. If this results in an imputed start date that is after the specified end date, then the 1st of 
the month will be used, or the date of Screening if this is later (if the latter imputation results 
in an end date that is earlier than the start date, then the 1st of the month will be used). If the 
imputed date is the same as the date of the first dose of IMP then time will be imputed as the 
start time of the first injection (ie, an AE will be regarded as treatment-emergent and a 
medication will be classified as concomitant) 
 If only the year is specified, and the year of the first dose of IMP is not the same as the year 
of the start date then January 01 of the year of the start date will be used. If time is missing 
this will be imputed as 00:00 h 
 If only the year is specified, and the year of the first dose of IMP is the same as the year of 
the start date, then the date of the first dose of IMP will be used. If this results in an imputed 
start date that is after the specified end date, then January 01 of the year of the start date will 
be used, or the date of Screening if this is later (if the latter imputation results in an end date 
that is earlier than the start date, then January 01 will be used). If the imputed date is the 
same as the date of the first dose of IMP then time will be imputed as the start time of the 
injection (ie, an AE will be regarded as treatment-emergent and a medication will be 
classified as concomitant) 
The following rules will be applied to partial stop dates: 
 If only the month and year are specified, then the last day of the month will be used 
 If only the year is specified, then December 31 of the known year will be used 
 If the stop date is completely unknown, the stop date will not be imputed 
Partially missing dates will be imputed as described above and the duration of each AE will be 
calculated in days as follows: 
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝐴𝐸 = (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑂𝑢𝑡𝑐𝑜𝑚𝑒 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑂𝑛𝑠𝑒𝑡 ) +  1 
4.3 
Handling of repeated and unscheduled measurements 
All repeated and unscheduled measurements will be presented in the data listings, where 
applicable. The following general rules will apply to all repeated and unscheduled 
measurements: 
 For repeated measurements obtained prior to the first dose of IMP the latest value (which 
may be scheduled or unscheduled) will be used in the calculation of the descriptive statistics 
 For repeated measurements obtained at the designated Baseline visit, the latest value (which 
may be scheduled or unscheduled) will be defined as the Baseline provided that this occurred 
prior to the first dose of IMP 
 For repeated measurements obtained at any time point after the first dose of IMP, the values 
will not be included in the calculation of descriptive statistics or changes from Baseline. 
 Unscheduled measurements performed for the Early Withdrawal (EW) visit will be assigned 
to the appropriate visit (Section 4.4) and analyzed accordingly 
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4.4 
Handling of measurements obtained at the early withdrawal 
visit 
Subjects who withdraw early from the study for any reason, including those withdrawn from 
IMP, will be asked to return for the study assessments 12 weeks after the first dose of IMP (ie, 
the Week 12 Visit) and will then enter the SFU Period and will undergo the same assessments 
performed at the SFU Visit (20 weeks after the last dose of IMP). 
For subjects who return for the EW visit at any time other than the Week 12 visit, the following 
rules will apply with regard to the inclusion of the results obtained at the EW visit in the 
descriptive summaries and in the data listings: 
 Any measurements conducted at the EW visit should be included in the summaries for the 
respective scheduled visit, if the EW visit occurs at the time of the next scheduled visit. For 
example, if the EW visit occurs on Day 42, the results would be summarized together with 
the Visit 6 (Week 6, Day 42) results. 
 If the EW visit does not correspond to the day of a scheduled visit, the assessments of the 
EW visit should be mapped to the nearest scheduled visit, relative to the Baseline visit date, 
following the last scheduled visit where assessments are available  
 If the date of the EW visit is equidistant between 2 scheduled visits at which no scheduled 
assessments were performed, the assessments from the EW visit will be mapped to the 
earliest of these visits. 
 If an EW visit mapping results in data being mapped to a visit where the specific assessment 
is not actually collected per the protocol schedule of assessments, these data will not be 
included in the summary statistics and will be listed only 
 The only exception to the above rule is for anti-BKZ antibody assessments, in which all early 
withdrawal visit assessments will be assigned to the next scheduled visit at which anti-BKZ 
antibodies are assessed. The rationale for this is that anti-BKZ antibody positivity is 
summarized over a given study period. As part of that summary, a table indicating the first 
visit at which anti-BKZ antibody positivity is observed will be presented. In order to match 
the number of subjects who were anti-BKZ antibody positive at specific visits with the 
overall positivity for the period, it is necessary to ensure that anti-BKZ antibody positivity is 
attributed to a visit where anti-BKZ antibody assessments were performed. 
Assessments from the EW visit will be displayed as the mapped visit and will be flagged in the 
by-visit data listings  
4.5 
Interim analyses and data monitoring 
4.5.1 
Data monitoring committee 
The conduct of the study and monitoring of the safety data will be supervised by an independent 
DMC to optimize subjects’ safety and to identify any safety signals. Full details of the 
composition and roles of the DMC will be provided in a separate DMC Charter.  
The data to be reviewed by the DMC will be as detailed in the DMC Charter and will include 
unblinded safety data. The details regarding the outputs to be produced and the analyses to be 
performed will be provided in a separate DMC SAP. 
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4.5.2 
Interim analysis 
This study will include two informal unblinded interim analyses, the first after approximately 45 
subjects have completed 4 weeks of the study and the second when the last randomized subject 
for this study has completed the Week 12 Visit at the end of the Treatment Period or this 
subject’s participation has ended prematurely. This second planned interim analysis excludes the 
2 subjects from site 101 who entered the study outside of the recruitment period. The purpose of 
these interim analyses is for sponsor key personnel to review results from the primary efficacy 
analysis and a subset of the analyses of exploratory efficacy and safety outcomes to facilitate 
additional Clinical Planning or Portfolio Management decisions.  Neither interim analysis will 
lead to any formal decision to alter or terminate the trial.  
Details on the summaries and analyses to be presented at these informal interim analyses are 
included in the Interim Analysis SAP. 
All analyses and unblinding instructions will be pre-specified in the Interim Analysis SAP. 
4.6 
Multicenter studies 
The data summaries and statistical analyses will not be performed by center. 
4.7 
Multiple comparisons/multiplicity 
Not applicable. 
4.8 
Use of an efficacy subset of subjects 
In order to investigate the impact on the efficacy analyses, the PPS will be used to evaluate the 
subset of subjects in the FAS with no IPDs. 
4.9 
Active-control studies intended to show equivalence 
Not applicable. 
4.10 
Examination of subgroups 
Not applicable. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The number and percentage of subjects who were randomized into the study, subjects who 
completed or prematurely discontinued the study, as well as the primary reason for 
discontinuation will be presented by treatment group and for all subjects, based on the RS. A 
subject who completed the study is defined as a subject who completed all visits up to the last 
scheduled study visit, ie, Visit 12 (Week 30).  
In addition, the number and percentage of subjects completing Week 4 and Week 12 of the 
Treatment Period will be presented. A subject is defined as completing Week 4 and Week 12, 
respectively, if adequate efficacy data are available in the database to calculate the primary 
efficacy variable at the respective visit. 
The number and percentage of subjects who discontinued due to AEs will be summarized 
separately by treatment group and for all subjects, based on the RS. This will be used for 
European Union Drug Regulating Authorities Clinical Trials (EudraCT) reporting. 
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The number and percentage of subjects included in each of the analysis sets will be summarized 
by treatment group and for all subjects based on the ES. Percentages will be calculated based on 
the RS for the purpose of this summary. 
Screen failure reasons will be summarized for the ES. A listing of subjects who did not meet 
study eligibility criteria (including a glossary) will also be presented for the ES. 
In addition, the following listings will be presented by treatment group: 
 Subject disposition (ES) 
 Study discontinuation (RS) 
 Visit dates (SS) 
 Subject analysis sets (ES) 
The listing of subject disposition will include the date of informed consent, date of 
pharmacogenetic informed consent (for subjects participating in the pharmacogenetic substudy), 
date of randomization, date and time of first and last dose of IMP, date of premature study 
termination and primary reason (if applicable), and date of final contact. If applicable, the date 
and reason for premature unblinding will also be included. 
The listing of study discontinuation will include the primary reason for discontinuation and the 
number of days on IMP. 
The number of days on IMP will be calculated as follows: 
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑜𝑛 𝐼𝑀𝑃 = (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐷𝑜𝑠𝑒 𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒 𝑅𝑒𝑐𝑒𝑖𝑣𝑒𝑑) +  1 
5.2 
Protocol deviations 
Important protocol deviations will be identified and classified by the deviation types listed in the 
IPD document. A listing of all IPDs will be presented for all subjects in the RS and will include 
the deviation type and description. The number and percentage of subjects with IPDs will be 
summarized by treatment group and for all subjects for each deviation type (Section 5.2), based 
on the RS. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Derivation of variables 
6.1.1 
Calculation of body mass index 
The body mass index (BMI) in kg/m2 is calculated based on the height (in m) and the weight (in 
kg) using the following formula: 
𝐵𝑀𝐼 = 𝑊𝑒𝑖𝑔ℎ𝑡
𝐻𝑒𝑖𝑔ℎ𝑡2   
The BMI will be automatically derived by and recorded on the electronic case report form 
(eCRF). 
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6.1.2 
Classification of age categories 
Age will be classified into categories based on requirements for EudraCT and clinicaltrials.gov 
reporting. 
For the EudraCT reporting, the categories will include: 
 18 to <65 years 
 65 to <85 years 
 ≥85 years 
For the clinicaltrials.gov reporting, the categories will include: 
 ≤18 years 
 19 to <65 years 
 ≥65 years 
6.1.3 
Duration of disease 
The duration of disease will be calculated as follows and will be presented in years to 1 decimal 
place: 
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 =  𝐷𝑎𝑡𝑒 𝑜𝑓 𝑆𝑐𝑟𝑒𝑒𝑛𝑖𝑛𝑔 
 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐻𝑆 𝐷𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠 
In the event that the date of diagnosis is incomplete, it will be imputed to the most recent feasible 
date: 
 If only the day is missing, it will be imputed to the last day of the known month 
 If the day and month are missing, it will be imputed to December 31 in the known year 
 If the date of diagnosis is completely missing, the duration of disease will not be calculated 
6.2 
Demographics and Baseline characteristics 
A by-subject listing of Baseline demographic characteristics will be presented by treatment 
group. This will include the year of birth (if available), age (in years), sex, race, ethnicity, height 
(in cm), weight at Screening (in kg) and BMI for the ES. The age will be entered directly 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 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. Childbearing potential (as applicable) and lifestyle 
(alcohol, tobacco and caffeinated beverage use) will be listed for the SS. 
6.3 
Other Baseline characteristics 
The following Baseline disease characteristics will be listed for the SS, based on the Baseline 
definitions in Table 3‒1 unless otherwise specified: 
 Lesion counts by anatomical region and lesion type, total lesion counts across anatomical 
regions by lesion type, Hurley Stage by anatomical region and worst overall Hurley Stage 
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across anatomical regions; degree of erythema by anatomical region and worst overall 
erythema across all anatomical regions (Section 8.1) 
 IHS4 score, total HADS-A and HADS-D scores, Modified Sartorius Score, PGA of skin pain 
(average and worst pain over the last 24 hours), HS-Physician’s Global Assessment, total 
DLQI score and EQ-5D-3L (domain scores, index score and VAS score) (Section 8.3) 
 Duration of disease at Screening, based on date of diagnosis as captured in the eCRF 
 High sensitivity C-reactive protein (hsCRP) 
The above Baseline disease characteristics will be summarized by treatment group and for all 
subjects in the FAS.  
Baseline lesion counts will be summarized by lesion type and anatomical region, and total lesion 
counts across all anatomical regions will be summarized by lesion type.  
Baseline Hurley stage and degree of erythema will be summarized by treatment group and for all 
subjects by anatomical region.  The worst overall Hurley stage and erythema calculated across 
all anatomical regions will be summarized by treatment group and for all subjects. 
In addition, the following Baseline disease characteristics will be summarized by Baseline 
Hurley Stage and overall, and treatment group, for the FAS  
 IHS4 score 
 Total HADS-A and HADS-D scores 
 Modified Sartorius Score 
 PGA of skin pain (average and worst pain over the last 24 hours) 
 HS-Physician’s Global Assessment 
 Total DLQI score 
 EQ-5D-3L (domain scores, index score and VAS score) 
 Duration of disease 
 hsCRP 
 Total lesion counts 
 Worst overall erythema 
6.4 
Medical history and concomitant diseases 
Medical history will be listed for the RS and summarized for the SS by treatment group and for 
all subjects, and by MedDRA system organ class (SOC) and preferred term (PT). The reported 
term will be included in the listing. The summary will include the number and percentage of 
subjects, and will be sorted alphabetically by SOC and by descending incidence of PT within 
each SOC, based on the ‘All Subjects’ column. A glossary of all medical history conditions will 
be presented for the RS including the SOC, PT and reported term. 
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Procedure history will be listed separately by treatment group for the procedure reported term 
based on the RS. Concomitant medical procedures performed during the study will be listed for 
the RS. 
6.5 
Hidradenitis suppurativa history 
Date of initial diagnosis of HS and the date that HS symptoms first started will be listed. 
6.6 
Prior and concomitant medications 
Prior and concomitant medications (as defined below) will be listed for the RS by treatment 
group and subject, and summarized for the SS by WHODD Anatomical Main Group (Level 1), 
Pharmacological Subgroup (Level 3) and PT.  The reported term will be included in the listing, 
together with flags to identify antibiotic and rescue medications, respectively. Separate 
summaries will be presented for prior medications and concomitant medications and these will 
be presented by treatment group and for all subjects. Prior medications which continued into the 
study period are also classified as concomitant and are included in both summaries. 
Separate summaries will be presented for the following, identified using WHODD Anatomical 
Main Group codes, the indication recorded on the eCRF and medical review of the recorded 
data:   
 Prior and concomitant HS medications 
 Concomitant antibiotic medications at study entry 
 Rescue medication during study 
All HS medications, antibiotics and rescue medication given during the study will be identified 
via medical review of the concomitant medications and confirmed at the DEMs prior to 
unblinding. 
Concomitant antibiotic medication at study entry is defined as any antibiotic with start date on or 
prior to first dosing, and end date on or after screening. 
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. 
The listing will include a flag for prohibited prior and concomitant medications. These will be 
confirmed and documented at the final DEM. 
A glossary of all prior and concomitant medications will be presented for the RS including the 
Anatomical Main Group (Level 1), Pharmacological Subgroup (Level 3), PT and reported term.  
Any medications with partially missing dates will be handled as described in Section 4.2.4 in 
order to classify them as prior or concomitant. 
6.6.1 
Prior medication definition 
A medication with a start date that is prior to the date of first dose of IMP will be classified as a 
‘prior medication’. 
6.6.2 
Concomitant medication definition 
A medication with a start date that is on or after the date of first dose of IMP will be classified as 
a ‘concomitant medication’.  
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Any medication that started prior to the first dose of IMP and continued after will be classified as 
both prior and concomitant. Such medications will therefore be counted in the tabulations for 
both prior and concomitant medication. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
During the Treatment Period of this study, IMP will be administered in the clinic and compliance 
will be determined at the visit by study personnel. 
The number of injections and volume administered for each injection at each visit will be 
included in the listing of study drug administration as specified in Section 11.1. 
Any deviations from the planned dosing schedule will be addressed at the DEMs (including 
evaluation of any impact on the statistical analysis) and described in the CSR. No formal 
calculations of compliance will be presented as all IMP is administered on site. 
8 
EFFICACY ANALYSES 
8.1 
Lesion count assessment 
The primary efficacy variable and some of the exploratory efficacy variables discussed in 
Section 8.3 (IHS4, Modified Sartorius Score, HS-Physician’s Global Assessment, Hurley Stage 
and Erythema assessment) are based on the assessment and/or counts of different types of lesions 
in the following main anatomical regions at each visit.  
 Inguinal (groin)  
 Axillary (armpit) 
 Submammary and/or intermammary in women 
 Gluteal 
 Other 
These anatomical regions are further classified into the following locations, for the left and right 
sides of the body, as applicable: 
 Inguinal (groin) excluding genital and pubic area – Left, Right 
 Inguinal (groin) including genital and pubic area – Left, Right 
 Axillary (armpit) – Left, Right 
 Submammary – Left, Right 
 Intermammary 
 Gluteal – Buttocks – Left, Right 
 Gluteal – Perianal/Perineal  
All “Other” anatomical regions with lesions present will be specified in free text on the eCRF. 
Note that investigators will be asked to only select ‘Other’ regions with more severe lesions 
present. 
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The number of each of the following types of lesions (classified as relevant or non-relevant) will 
be recorded in each anatomical region, and then summed across all anatomical regions: 
Relevant Lesions: 
 Abscesses 
 Draining tunnels (fistulas/sinus tracts) 
 Inflammatory nodules  
Non-relevant Lesions: 
 Non-draining tunnels (fistulas/sinus tracts)  
 Non-inflammatory nodules  
 Hypertrophic scars  
If there are 2 or more relevant lesions present in an anatomical region  the longest distance 
between 2 relevant lesions will be recorded and an assessment of whether these 2 relevant 
lesions are clearly separated by normal skin will be made. 
If only 1 lesion is present in an anatomical region, then the diameter of the single lesion will be 
recorded. 
In addition to the lesion count data, the degree of erythema will be assessed for each anatomical 
region and scored as follows: 
 0 = No redness 
 1 = Faint but discernible pink coloration 
 2 = Moderate red coloration 
 3 = Very red or bright red coloration  
The worst overall erythema score across all anatomical regions will then be derived 
automatically in the database and used in the analyses. 
Hurley Stage (I, II and III) will also be recorded for each anatomical area and the worst overall 
Hurley Stage across all anatomical regions will then be derived automatically in the database and 
used in the analyses. 
8.2 
Primary efficacy variable 
The primary efficacy variable is the clinical response as measured by HiSCR (defined as at least 
a 50% reduction from Baseline in the total abscess and inflammatory nodule count [AN count], 
with no increase from Baseline in abscess or draining tunnel [fistula/sinus tract] count) at Week 
12.  
The HiSCR was developed to address issues with available HS scoring systems and is a 
validated variable that is responsive to improvement in disease activity, simplifies the scoring 
process, and increases the sensitivity to detect HS specific lesions (Kimball et al, 2014; Kimball 
et al, 2016b). 
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8.2.1 
Derivation of the primary efficacy variable 
The following algorithm will be applied to derive the HiSCR at each visit, based on total lesion 
counts across anatomical regions for the 3 relevant lesion types recorded as specified above in 
Section 8.1: 
1. Calculate the AN count at each visit as the total number of abscesses plus the total number of 
inflammatory nodules, across all anatomical regions 
2. Calculate the percentage change from Baseline in AN count (%ΔAN) at each visit as  
 
100 × (𝐴𝑁 𝑐𝑜𝑢𝑛𝑡 𝑎𝑡 𝑝𝑜𝑠𝑡-𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑖𝑠𝑖𝑡 𝑚𝑖𝑛𝑢𝑠 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝐴𝑁 𝑐𝑜𝑢𝑛𝑡) 
/ (𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝐴𝑁 𝑐𝑜𝑢𝑛𝑡) 
3. Calculate the change from Baseline in the abscess count by subtracting the Baseline abscess 
count from the abscess count at each post-Baseline visit  
4. Calculate the change from Baseline in the draining tunnel (fistula/sinus tract) count by 
subtracting the Baseline draining tunnel (fistula/sinus tract) count from the draining tunnel 
(fistula/sinus tract) count at each post-Baseline visit 
5. If the %ΔAN is less than or equal to -50%, and the change from Baseline in the abscess count 
is zero or negative (ie, non-positive) together with a non-positive change from Baseline in the 
draining tunnel (fistula/sinus tract) count, then the HiSCR will be assigned a value of 1 (ie, 
HiSCR is achieved); otherwise, the HiSCR will be assigned a value of 0 (ie, HiSCR is not 
achieved). 
There will not be any imputation of missing lesion count data in the derivation of the HiSCR at 
any visit.  In such cases the HiSCR will be missing and rules for handling missing HiSCR values 
in the analysis will be applied (Section 4.2.1 and Section 8.2.3). 
The primary efficacy variable is attained if the subject has a HiSCR of 1 at Week 12.   
8.2.2 
Primary analysis of the primary efficacy variable 
The primary efficacy analysis of the primary efficacy variable will be based on the PPS. 
8.2.2.1 
Bayesian modeling 
The primary Bayesian model (a logistic regression model for the mean binary response 𝐸[𝑦]) 
will be: 
ln (
𝐸(𝑦)
1−𝐸(𝑦)) = 𝛽𝑃𝐵𝑂 𝑋𝑃𝐵𝑂+ 𝛽𝐵𝐾𝑍 𝑋𝐵𝐾𝑍+ 𝛽𝐴𝐷𝐴 𝑋𝐴𝐷𝐴+ 𝛽ℎ𝐼𝐼 𝑋ℎ𝐼𝐼+ 𝛽ℎ𝐼𝐼𝐼 𝑋ℎ𝐼𝐼𝐼      (1) 
where 𝑋𝑃𝐵𝑂, 𝑋𝐵𝐾𝑍  and 𝑋𝐴𝐷𝐴 are dummy variables taking the value 1 or 0 according to whether 
or not each subject is in the PBO, BKZ or ADA treatment groups respectively, 𝑋ℎ𝐼𝐼 and 𝑋ℎ𝐼𝐼𝐼 are 
dummy variables taking the value 1 or 0 according to whether or not each subject is in the 
Baseline Hurley Stage II or III groups respectively. Proof-of-concept (PoC) will be declared in 
this study if the estimated posterior probability, using the above model, of the difference in 
response rates between the BKZ and PBO treatment groups is 0.975 or greater. 
For parameter estimation, the following constraint will be used: 
𝛽ℎ𝐼𝐼= −𝛽ℎ𝐼𝐼𝐼 
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giving the model: 
                    ln (
𝐸(𝑦)
1−𝐸(𝑦))  = 𝛽𝑃𝐵𝑂 𝑋𝑃𝐵𝑂+ 𝛽𝐵𝐾𝑍 𝑋𝐵𝐾𝑍+ 𝛽𝐴𝐷𝐴 𝑋𝐴𝐷𝐴+ 𝛽ℎ𝐼𝐼 (𝑋ℎ𝐼𝐼−𝑋ℎ𝐼𝐼𝐼)      (2) 
so that the influence of Baseline Hurley Stage on the model estimated treatment group mean 
responses are more evident. To see this, note that if 𝜂̅𝑃𝐵𝑂 represents the mean of the logit 
responses from model (2) for the PBO subjects (the simple “arithmetic” mean) then 
𝑙𝑜𝑔𝑖𝑡−1(𝜂̅𝑃𝐵𝑂) is the response probability associated with that mean logit response and is 1 type 
of estimate of the PBO group response rate. Accordingly: 
 𝑝𝑃𝐵𝑂 | 𝑝ℎ𝐼𝐼
𝑃𝐵𝑂, 𝑝ℎ𝐼𝐼𝐼
𝑃𝐵𝑂= 𝑙𝑜𝑔𝑖𝑡−1(𝜂̅𝑃𝐵𝑂) = 𝑙𝑜𝑔𝑖𝑡−1 (𝛽𝑃𝐵𝑂 + 𝛽ℎ𝐼𝐼 (𝑝ℎ𝐼𝐼
𝑃𝐵𝑂−𝑝ℎ𝐼𝐼𝐼
𝑃𝐵𝑂)) represents 
the probability of response in the PBO group conditional on 𝑝ℎ𝐼𝐼
𝑃𝐵𝑂 and 𝑝ℎ𝐼𝐼𝐼
𝑃𝐵𝑂, which are the 
Baseline Hurley Stage subject proportions chosen to evaluate the estimated PBO group mean 
at (here the observed proportions are chosen) 
 𝑝𝐵𝐾𝑍 | 𝑝ℎ𝐼𝐼
𝐵𝐾𝑍, 𝑝ℎ𝐼𝐼𝐼
𝐵𝐾𝑍= 𝑙𝑜𝑔𝑖𝑡−1(𝜂̅𝐵𝐾𝑍) = 𝑙𝑜𝑔𝑖𝑡−1(𝛽𝐵𝐾𝑍+ 𝛽ℎ𝐼𝐼 (𝑝ℎ𝐼𝐼
𝐵𝐾𝑍−𝑝ℎ𝐼𝐼𝐼
𝐵𝐾𝑍)) represents the 
probability of response in the BKZ group conditional on 𝑝ℎ𝐼𝐼
𝐵𝐾𝑍 and 𝑝ℎ𝐼𝐼𝐼
𝐵𝐾𝑍 which are the 
Baseline Hurley Stage subject proportions chosen to evaluate the estimated BKZ group mean 
at (here again the observed proportions are chosen) 
 𝑝𝐴𝐷𝐴 | 𝑝ℎ𝐼𝐼
𝐴𝐷𝐴, 𝑝ℎ𝐼𝐼𝐼
𝐴𝐷𝐴= 𝑙𝑜𝑔𝑖𝑡−1 (𝜂̅𝐴𝐷𝐴) = 𝑙𝑜𝑔𝑖𝑡−1 (𝛽𝐴𝐷𝐴+ 𝛽ℎ𝐼𝐼(𝑝ℎ𝐼𝐼
𝐴𝐷𝐴−𝑝ℎ𝐼𝐼𝐼
𝐴𝐷𝐴)) represents the 
probability of response in the ADA group conditional on 𝑝ℎ𝐼𝐼
𝐴𝐷𝐴 and 𝑝ℎ𝐼𝐼𝐼
𝐴𝐷𝐴 which are the 
Baseline Hurley stage subject proportions chosen to evaluate the estimated ADA group mean 
at (once more here the observed proportions are chosen) 
For brevity, and unless otherwise stated  the dependence of the above treatment group response 
rates on the chosen Baseline Hurley Stage subject proportions will be suppressed by denoting 
them as 𝑝𝑃𝐵𝑂, 𝑝𝐵𝐾𝑍 and 𝑝𝐴𝐷𝐴.  
For pragmatic reasons we will ignore the Hurley stage proportions and effects in the equations 
for the estimated group response rates and use the following relations to map between the 
probability scale priors for the group response rates and the logit scale treatment group 
parameters 
𝑝𝑃𝐵𝑂= 𝑙𝑜𝑔𝑖𝑡−1(𝛽𝑃𝐵𝑂)      
 
 
(3) 
𝑝𝐴𝐷𝐴= 𝑙𝑜𝑔𝑖𝑡−1(𝛽𝐴𝐷𝐴)   
 
      (4) 
The expectations of the prior distributions for the PBO and ADA group response rates will be set 
to match the observed treatment group response rates in the PII study.  
Accordingly, the priors to be used are 
                                   𝑝𝑃𝐵𝑂 ~ 𝛽(5.52,14.48)      
 
            (5) 
𝛽𝐵𝐾𝑍 ~ 𝑁(0,10000) 
𝑝𝐴𝐷𝐴 ~ 𝛽(11.78,8.22) 
𝛽ℎ𝐼𝐼 ~ 𝑁(0,10000) 
 
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which have expectations equal to 28% and 59% for the PBO and ADA groups respectively to 
match the observed treatment group response rates of the PIONEER II study. The implicit 
assumption using this simple approach is that 𝐸𝛽ℎ𝐼𝐼[𝛽ℎ𝐼𝐼(𝑝ℎ𝐼𝐼
𝐵𝐾𝑍−𝑝ℎ𝐼𝐼𝐼
𝐵𝐾𝑍)] ≈0. It is important to 
recognize that even if the proposed study also observes a similar Baseline Hurley Stage effect 
size and subject proportions as the PIONEER II study the priors (5) and equations (3) and (4), 
whilst yielding estimated treatment group response rates that should be consistent with those 
observed in the data, may cause the estimated logit coefficients 𝛽𝑃𝐵𝑂 and 𝛽𝐴𝐷𝐴 to be inaccurate.  
If the observed Baseline Hurley Stage effects and/or subject proportions in the proposed study 
are very different from those in the PIONEER II study then, and in addition to the possible 
invalid estimates of 𝛽𝑃𝐵𝑂 and 𝛽𝐴𝐷𝐴, the estimated treatment group response rates may no longer 
reflect those in the data since the means of the probability scale priors will no longer match the 
treatment group response rate means in the observed data.  
Both informative priors in (5) have been heavily discounted to account for study to study 
variation in both the ADA and PBO response rates, and also uncertainty in the agreement 
between the subject proportions and effect sizes observed in the Baseline Hurley Sage groups in 
the PIONEER II study and this proposed study.  
To protect against severe forms of study to study variation and/or mismatches between Baseline 
Hurley Stage subject proportions and effect sizes, prior data conflict will be investigated for all 
informative priors through use of graphical displays.  If there is evidence of prior data conflict 
for a given parameter, then a vague prior will be used for that parameter. Investigating any prior 
data conflict also provides some protection against model misspecification – for example if there 
turns out to be a Baseline Hurley Stage by treatment group interaction as the PIONEER II data 
suggest. 
To be consistent with models used in previous UCB studies which parameterize PBO as the 
model intercept with the active treatment being additive effects (on the logit scale) we note that 
model (2) can be re-parameterized as follows: 
                                       𝛽𝑃𝐵𝑂= 𝛾𝑃𝐵𝑂                                        (6) 
             𝛽𝐴𝐷𝐴= 𝛾𝑃𝐵𝑂+ 𝛾𝐴𝐷𝐴     
               𝛽𝐵𝐾𝑍= 𝛾𝑃𝐵𝑂+ 𝛾𝐵𝐾𝑍 
 𝛽ℎ𝐼𝐼= 𝛾ℎ𝐼𝐼 
giving the model 
                  ln (
𝐸(𝑦)
1−𝐸(𝑦)) = 𝛾𝑃𝐵𝑂+ 𝛾𝐵𝐾𝑍 𝑋𝐵𝐾𝑍+ 𝛾𝐴𝐷𝐴 𝑋𝐴𝐷𝐴+ 𝛾ℎ𝐼𝐼(𝑋ℎ𝐼𝐼−𝑋ℎ𝐼𝐼𝐼)   (7) 
Using this model, the process of mapping the informative priors in (5) to the logit coefficients is: 
                                        𝛽𝑃𝐿𝐵= 𝑙𝑜𝑔𝑖𝑡(𝑝𝑃𝐵𝑂)                             (8) 
   𝛽𝐴𝐷𝐴= 𝑙𝑜𝑔𝑖𝑡(𝑝𝐴𝐷𝐴) 
     𝛾𝐴𝐷𝐴= 𝛽𝐴𝐷𝐴−𝛽𝑃𝐵𝑂 
      𝛾𝐵𝐾𝑍= 𝛽𝐵𝐾𝑍−𝛽𝑃𝐵0 
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8.2.2.2 
Building the prior 
From the PIONEER II data, despite the strength of any interaction within treatment groups 
between antibiotic use and Baseline Hurley Stage being unknown, it is valid to pool the data 
across Baseline Hurley Stages within these groups to obtain estimates of the overall group 
response rates and their variability, and to use this information as the basis for building 
informative priors for the PBO and ADA treatment groups. In this respect, and from the reported 
event counts and subject numbers within each Baseline Hurley Stage group, we obtained the 
following Beta distributions that could be used to describe the observed group response rates in 
that study: 
𝑝𝑃𝐵𝑂 ~ 𝛽(45,118) 
𝑝𝐴𝐷𝐴 ~ 𝛽(48,67) 
After heavily discounting the above priors we obtain the priors given in Section 8.2.2.1. 
If further information (independent to this study) regarding the PBO and/or ADA treatment 
group response rates comes to light then the priors for this analysis may be updated prior to study 
unblinding, and details of this will be supplied in an amendment to this SAP or the CSR. In this 
case the priors will still be based upon historic data only. 
Note that the informative priors for the PBO and ADA treatment group response rates may be 
updated based upon any observed differences in the proportions of Baseline Hurley Stage II and 
III subjects as long as no response rate data from the current study, blinded or unblinded, are 
taken into consideration. For example, if updated, these priors may be fitted by Baseline Hurley 
Stage if the relative proportions of Baseline Hurley Stage II and III subjects within the current 
study differ substantially from those reported in the historical data. In this case the priors will 
still be based only on historic response data, but using the Hurley-stage specific information 
rather than the average information  
8.2.2.3 
Prior data conflict 
Prior data conflict will be investigated for all informative priors through use of graphical 
displays.  If there is evidence of prior data conflict for a given parameter, then a vague prior will 
be used for that parameter. 
8.2.2.4 
Presentation of results from the primary analysis of the primary 
efficacy variable 
The Bayesian analysis will be implemented using multiple chains each utilizing different starting 
values for the model specified parameters. The posterior samples from each chain will be 
combined into 1 dataset from which the posterior summaries will be estimated. Missing data will 
be handled as described in Section 4.2.1. 
The posterior distributions of the PBO and BKZ group response rates, and of the difference in 
response rates between the treatment groups, will be summarized using means, medians, SDs, 
95% credible intervals, and 95% highest posterior density intervals. The posterior probability 
that the difference in response rates between the PBO and BKZ groups is greater than zero (ie, 
BKZ demonstrates a greater response compared with PBO) will also be presented.  
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8.2.3 
Supportive and sensitivity analyses of the primary efficacy variable  
The primary efficacy analysis set is the PPS, however the primary analysis and all supportive and 
sensitivity analyses of the primary efficacy variable will be repeated using the FAS.   
The comparison of the BKZ treatment group to the ADA treatment group is described 
specifically in this section as a sensitivity analysis, however, it must be noted that the results 
from the BKZ versus ADA comparison will be presented for completeness in each of the 
sensitivity analyses described in Section 8.2.3.1 to 8.2.3.10 below. 
Further analyses of the primary efficacy variable may be performed adjusting for other Baseline 
covariates. Results from any additional analyses will not be used as a substitute for the planned 
analyses, but may be used as supplemental information for the CSR.  Should such analysis 
become necessary they will be defined in a further amendment to this SAP. 
All sensitivity analyses of the primary efficacy variable are specified in the sections below. 
8.2.3.1 
Choice of analysis set 
The primary analysis of the primary efficacy variable will be repeated for the FAS in order to 
evaluate the effect that any IPDs may have on the results of the analysis. The analysis and results 
presentation as specified in Section 8.2.2.4 will be applied  
8.2.3.2 
Comparison of bimekizumab and adalimumab 
In addition to the primary comparison of the BKZ and PBO treatment groups, the comparison 
between BKZ and ADA in HiSCR at Week 12 will be performed using the methods as described 
above in Section 8.2.2.4 for the primary efficacy analysis.  A 60% credible interval will be 
presented for the BKZ versus ADA comparison.  This will be an informal comparison to assess 
whether any improvements in response rate observed with BKZ (over PBO) are comparable to 
the current standard of care (ADA); it will not be part of the evaluation of PoC for this study. 
8.2.3.3 
Observed case Bayesian analysis 
The primary Bayesian analysis of HiSCR at Week 12 will be performed and reported as 
specified in Section 8.2.2 4 without applying NRI for missing response data, ie, observed case 
analysis. 
8.2.3.4 
Vague prior distribution 
A sensitivity analysis will be performed to investigate the influence of the choice of prior 
distribution on the results of the primary analysis. This will be performed and results reported 
using the same methodology as described in Section 8.2.2.4 but assuming vague priors for all 
Beta distributed parameters of the model (ie, Beta [0.5, 0.5]). 
8.2.3.5 
Concomitant antibiotic use – Bayesian analysis 
The primary Bayesian analysis of HiSCR at Week 12 will be repeated including treatment group, 
Baseline Hurley Stage, concomitant antibiotic use at study entry (coded as a binary [yes/no] 
variable) as an additional covariate, and a concomitant antibiotic use × Baseline Hurley Stage 
interaction term.  
The results of this analysis will be presented as specified in Section 8.2.2.4. 
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8.2.3.6 
Rescue therapy – Bayesian analysis 
The primary Bayesian analysis of HiSCR at Week 12 will be performed and reported as 
specified in Section 8.2.2.4 and will treat subjects who receive specific rescue medication prior 
to the Week 12 visit as non-responders, from the point of receiving the rescue medication. 
8.2.3.7 
Frequentist analysis – NRI 
An estimate of the treatment differences (BKZ versus PBO and BKZ versus ADA) at Week 12 
will be obtained from a longitudinal generalized estimating equation (GEE) model for a binary 
outcome, controlling for Baseline Hurley Stage and including treatment, visit and a treatment by 
visit (week) interaction term. An unstructured covariance matrix will be used for this analysis. In 
the event that the model does not converge, alternate covariance structures will be considered. 
For subjects who withdraw from the study, any missing responses from visits after the 
withdrawal will be imputed as non-response.  For any missing response data at any visit that is 
not due to a withdrawal, the response will not be imputed and the GEE model will analyze these 
as “missing at random”. 
At each visit, the number and percentage of responders in each treatment group, together with 
the estimated treatment differences (odds ratios [BKZ versus PBO and BKZ versus ADA]), will 
be reported, including 95% CI for the odds ratios. 
8.2.3.8 
Observed case frequentist analysis 
The same model as in Section 8.2.3.7 will be applied to analyze the data.  Missing data will not 
be handled using NRI (ie, observed cases analysis). 
The results of the analysis will be presented as described for the analysis in Section 8.2.3.7. 
8.2.3.9 
Concomitant antibiotic use – Frequentist analysis 
An estimate of the treatment differences (BKZ versus PBO and BKZ versus ADA) at Week 12 
will be obtained from a longitudinal GEE model for a binary outcome, controlling for Baseline 
Hurley Stage and including concomitant antibiotic use at study entry (coded as a binary [yes/no] 
variable), treatment, visit, treatment by visit (week) interaction term and antibiotic use by 
Baseline Hurley Stage interaction terms. Missing response data will not be handled using NRI 
(ie, observed cases analysis).  
An unstructured covariance matrix will be used for this analysis. In the event that the model does 
not converge, alternate covariance structures will be considered. 
The results of the analysis will be presented as for the analysis in Section 8.2.3.7. 
8.2.3.10 
Rescue therapy – Frequentist analysis 
Subjects who receive specific rescue medication will be considered as non-responders from the 
point of receiving the rescue medication and the model and presentation of data as specified in 
Section 8.2.3.7 will be applied. Missing response data will not be handled using NRI (ie, 
observed cases analysis). 
8.2.4 
HiSCR depth 
As an additional exploratory analysis of HiSCR, the algorithm applied to derive response at each 
visit (as described in Section 8.2.1) will be adapted to evaluate varying depths of HiSCR during 
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the Treatment Period.  A modified HiSCR will be calculated using different criteria for %ΔAN, 
namely 25%, 75% and 90%, in order to derive a response at each visit.  In the summaries of 
HiSCR depth, the primary efficacy variable will be referred to as HiSCR and the other depth 
variables referred to as modified (m) mHiSCR25, mHiSCR75 and mHiSCR90. 
8.2.5 
Presentation of HiSCR 
HiSCR will be listed together with the component efficacy data as specified in Section 8.3.1. 
This listing will include the different HiSCR depth variables (i.e. mHiSCR25, HiSCR, 
mHiSCR75 and mHiSCR90). 
The number and percentage of subjects who achieved HiSCR will be tabulated overall by 
treatment group and visit, and also by Baseline Hurley Stage and by concomitant antibiotic use at 
study entry; and also by Baseline Hurley Stage and rescue medication use at any time during the 
study. This summary will be presented for the PPS and will include the 95% CI for the 
percentage of subjects with an HiSCR, calculated using a Wilson approximation  The summary 
will be presented based on NRI and repeated for observed cases. For the observed cases analysis, 
the denominator for the percentage calculations will be the number of subjects with non-missing 
HiSCR data in the PPS for each treatment group, visit and Baseline Hurley Stage or concomitant 
antibiotic use at study entry (as applicable).  
The number and percentage of subjects who achieved mHiSCR25, mHiSCR75 and mHiSCR90, 
together with 95% confidence intervals, will be presented overall and by Baseline Hurley Stage, 
and by treatment group and visit based on observed cases for the PPS. 
All tabulations described in this section will be repeated for the FAS. For the observed cases 
analysis, the denominator for the percentage calculations will be the number of subjects in the 
FAS for each treatment group, visit and Baseline Hurley Stage or concomitant antibiotic use at 
study entry (as applicable) with non-missing HiSCR data.  Listings will be presented for the SS. 
A figure will be presented showing the percentage of subjects who achieved HiSCR, together 
with 95% CIs (calculated using a Wilson approximation), over time. All treatment groups will be 
overlaid on the same plot  The plot will be generated based on NRI and observed cases for the 
PPS and the FAS.  These plots will be repeated for the percentage of subjects who achieved the 
different HiSCR depths; mHiSCR25, mHiSCR75 and mHiSCR90. 
Additionally, for the PPS and FAS, based on NRI and observed cases,  the following bar charts 
will be presented showing the percentage of subjects who achieved HiSCR during the Treatment 
Period:  
 by treatment group and visit 
 by treatment group, visit and Baseline Hurley Stage 
 by treatment group and Baseline Hurley Stage at Week 12 
 by treatment group, Baseline Hurley Stage and concomitant antibiotic use at study entry, at 
Week 12 
 by treatment group, Baseline Hurley Stage and rescue medication use at any time during the 
study, at Week 12 
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In addition to the above bar charts, a stacked bar chart displaying whether the criteria are met 
(yes/no) for each of the component data used in the calculation of HiSCR (%ΔAN, abscess count 
and draining tunnel [fistula/sinus tract] count) will be generated by treatment group and visit for 
the PPS and FAS.  This graph will summarize the proportion of subjects in each of the 8 
different yes/no binary responses at each visit (2 x 2 x 2 response combination) at each visit. 
The following bar charts will be presented for the different HiSCR depths based on observed 
cases for the PPS and FAS: 
 by treatment group and visit 
 by treatment group, visit and Baseline Hurley Stage 
8.3 
Exploratory efficacy variables 
Observed values and changes (including percentage changes, where applicable) from Baseline in 
the continuous exploratory efficacy variables will be listed and summary statistics will be 
presented by treatment group and visit for the FAS. Changes from Baseline in the categorical 
exploratory efficacy variables will be summarized in shift tables presented by treatment group 
and each post-Baseline visit.  
The exploratory efficacy variables are listed in Section 2.2.1.2 and defined in more detail in each 
section below. 
8.3.1 
Lesion count data 
Lesion count data will be listed by treatment group and anatomical region and will show 
region-specific Hurley Stage and worst overall Hurley Stage for each subject and visit. The total 
count for each type of lesion, across all anatomical regions at each visit will be listed separately. 
For the total abscess count and total draining tunnel (fistula/sinus tract) count, the change from 
Baseline will be listed; for the AN count, the percentage change from Baseline will be listed. 
For each anatomical region, the longest distance between 2 relevant lesions (or the diameter of 
the single lesion if applicable) will be presented, and whether the specified regions were 
separated by normal skin. 
At each visit, lesion counts will be summarized by anatomical region and lesion type.  The 
following lesion types will be summarized: 
 Abscesses 
 Inflammatory nodules 
 Abscesses + inflammatory nodules (AN) 
 Draining tunnels (fistulas/sinus tracts)  
 Non-draining tunnels (fistulas/sinus tracts)  
 Non-inflammatory nodules  
 Hypertrophic scars  
Total lesion counts (ie, the total across all anatomical regions) will be summarized by visit and 
lesion type, treatment group, overall and by Baseline Hurley Stage. Summaries will also be 
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presented for the change and percentage change from Baseline in lesion counts by anatomical 
region and total lesion counts by lesion type.  
8.3.1.1 
AN count 
The number and percentage of subjects with an AN count of 0, 1, or 2 at Week 12 will be 
presented by treatment group, overall and by Baseline Hurley Stage. The denominator for the 
percentage calculations will be the number of subjects in each treatment group in the FAS with 
non-missing data and, in the summary by Baseline Hurley Stage, percentages will be calculated 
based on the number of subjects in each treatment group and each level of Baseline Hurley 
Stage.   
In addition, the following plots of AN count and %ΔAN over time will be generated for the PPS 
and FAS: 
 A violin plot of AN count (with box plot inlay) by treatment group and visit 
 Box plot of %ΔAN by treatment group and visit 
 Jitter plot of Baseline AN count by treatment group and country 
 Jitter plot of Baseline AN count by treatment group and site 
8.3.1.2 
Disease flare 
Disease flare is defined when at least a 25% increase in AN count with a minimum increase of 2 
AN relative to Baseline is observed.  A subject’s disease flare status (yes/no) will be determined 
at each visit using these criteria and will listed with the other lesion count assessment data in the 
data listings. 
Disease flare status will be summarized by treatment group and visit using frequencies and 
percentages.  The denominator for the percentage calculations will be the number of subjects 
with non-missing data in each treatment group.  The number and percentage of subjects who 
experienced a disease flare at any time during the Treatment Period will also be presented. 
A bar chart showing the percentage of subjects with disease flare will be presented by treatment 
group and visit.  A bar chart summarizing the percentage of subjects who experienced a disease 
flare at any time during the Treatment Period will also be presented by treatment group. 
In addition, for each subject, the number of visits at which a disease flare was observed during 
the Treatment Period will be calculated and summarized by treatment group.  Summary statistics 
will be presented together with a box plot showing the distribution of these data and a histogram 
summarizing the number of subjects who experienced 0, 1, 2, 3, 4, 5 and 6 visits during the 
Treatment Period with a disease flare status of ‘yes’. 
All summaries of disease flare status will be presented for the FAS. 
8.3.2 
International Hidradenitis Suppurativa Severity Scoring System 
The IHS4 is a validated scoring tool to dynamically assess HS severity to be used both in 
real-life and clinical trials settings (Zouboulis et al, 2017). The determination of the IHS4 score 
requires counting the inflammatory nodules, abscesses and draining tunnels (fistulas/sinus 
tracts), making it straightforward to apply in both research and clinical practice and easy to use 
in conjunction with the HiSCR. 
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𝐼𝐻𝑆4 = (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑖𝑛𝑓𝑙𝑎𝑚𝑚𝑎𝑡𝑜𝑟𝑦 𝑛𝑜𝑑𝑢𝑙𝑒𝑠× 1) + (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑎𝑏𝑠𝑐𝑒𝑠𝑠𝑒𝑠× 2) 
+ (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑟𝑎𝑖𝑛𝑖𝑛𝑔 𝑡𝑢𝑛𝑛𝑒𝑙𝑠 (𝑓𝑖𝑠𝑡𝑢𝑙𝑎𝑠/𝑠𝑖𝑛𝑢𝑠 𝑡𝑟𝑎𝑐𝑡𝑠 ) × 4) 
The IHS4 score will be derived based on observed component total lesion count data; in the case 
of missing component data, the IHS4 score will be missing. 
The observed IHS4 score, together with the change from Baseline and percentage change from 
Baseline will be listed with the component total lesion count data, by subject and visit, and 
summarized by treatment group, Baseline Hurley Stage and visit.   
Mean observed IHS4 score and percentage changes from Baseline (including 95% CIs) over time 
will be presented graphically by treatment group.  
8.3.3 
Patient's Global Assessment of Skin Pain 
The PGA of Skin Pain is a unidimensional numeric rating scale (NRS) that allows for rapid 
(often 1 item) measures of pain that can be administered multiple times with minimal 
administrative burden. The NRS consists of scores from 0 to 10 with 0 indicating “no skin pain” 
and 10 indicating “worst skin pain imaginable”. 
The PGA of Skin Pain NRS will be administered verbally. The pain will be described as “pain at 
its worst during the last 24 hours” and “pain on average in the last 24 hours”. 
Both parameters (pain at its worst and pain on average over the last 24 hours) will be listed by 
treatment group and subject at each visit, including observed values, changes from Baseline and 
percentage changes from Baseline. For pain at its worst during the last 24 hours, subjects with a 
30% reduction and at least 1-unit reduction from Baseline at Week 12 (for example a change 
from 7 at Baseline to 3 at Week 12) will be flagged   
Summary statistics will be presented for observed values, changes and percentage changes from 
Baseline in PGA of Skin Pain (pain at its worst and pain on average over the last 24 hours) by 
treatment group at each visit, overall and by Baseline Hurley Stage. 
In addition, the number and percentage of subjects with at least a 30% reduction and at least 1-
unit reduction from Baseline in the PGA of Skin Pain (based on the subject’s worst pain over the 
previous 24 hours) at Week 12, will be presented by treatment group. The denominator for the 
percentage calculations will be the number of subjects in the FAS for each treatment group. This 
summary will also be presented by Baseline Hurley Stage and percentages will be calculated 
based on the number of subjects in the FAS for each treatment group and each level of Baseline 
Hurley Stage. 
8.3.4 
Modified Sartorius Score  
The Sartorius scale was created as a more detailed and dynamic HS severity scale and was 
modified in order to further develop and simplify this assessment for the clinical setting 
(Sartorius et al, 2003; Sartorius et al, 2009; Sartorius et al, 2010). The Modified Sartorius Score 
was the first disease specific instrument for dynamically measuring clinical severity. 
The Modified Sartorius Score includes an assessment of the anatomical regions involved, the 
numbers and types of lesions in each anatomical region, the longest distance between 2 relevant 
lesions within an anatomical region (or size of a single lesion), and whether all relevant lesions 
are separated by normal skin (yes or no). Table 14‒2 shows the scoring for each criterion.   
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A Regional Modified Sartorius Score will be derived for each reported anatomical region as: 
𝑅𝑒𝑔𝑖𝑜𝑛𝑎𝑙 𝑀𝑜𝑑𝑖𝑓𝑖𝑒𝑑 𝑆𝑎𝑟𝑡𝑜𝑟𝑖𝑢𝑠 𝑆𝑐𝑜𝑟𝑒  =  
𝑅𝑒𝑔𝑖𝑜𝑛 + 4 ×  𝐷𝑇 +  2 × 𝐼𝑁 + 1 ×  𝐴𝐵 +  1 × 𝐻𝑌𝑆 + 1 ×  𝑁𝐼𝑁 + 1 ×  𝑁𝐷𝑇 
+  𝐷𝑖𝑠𝑡𝑎𝑛𝑐𝑒 +  𝑆𝑒𝑝𝑎𝑟𝑎𝑡𝑒 
where  
 Region = 3 if any lesion is present in the anatomical region, 0 otherwise 
 DT = number of draining tunnels (fistulas/sinus tracts) in the region 
 IN = number of inflammatory nodules in the region 
 AB = number of abscesses in the region 
 HYS = number of hypertrophic scars in the region 
 NIN = number of non-inflammatory nodules in the region 
 NDT = number of non-draining tunnels (fistulas/sinus tracts) in the region 
 Distance =  
 0 if no lesions are present in the anatomical region 
 2 if longest distance between 2 relevant lesions or diameter of a single lesion is < 50 mm 
 4 if longest distance between 2 relevant lesions or diameter of a single lesion is ≥ 50 mm 
and ≤ 100 mm 
 8 if longest distance between 2 relevant lesions or diameter of a single lesion is > 100 
mm 
 Separate = 0 if all relevant lesions are clearly separated by normal skin in the region, 6 
otherwise 
For the purpose of the Regional Modified Sartorius Score derivation, the left and right sides of 
the body (if applicable) will be treated as 1 anatomical region (ie, the lesion assessment data 
from both sides will be pooled).  For the Region, Distance and Separate variables defined above, 
the following will apply: 
 Region: a value of 3 will be applied if at least 1 lesion is present in either the left or right 
sides of an anatomical region; if 1 or more lesions are present in both left and right sides of 
the body, this will still be scored as 3 for the region overall 
 Distance: a score will be determined for each side of the body according to the scoring 
system above and the maximum of these scores will be used 
 Separate: 
 if both left and right sides have relevant lesions separated by normal skin then this will be 
scored as 0; 
 if only one of the left and right sides have relevant lesions separated by normal skin, then 
this will be scored as 6 
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 if both left and right sides have no relevant lesions separated by normal skin then this will 
be scored as 6 
The overall Modified Sartorius Score for a subject will then be calculated by summing the 
Regional Modified Sartorius Scores across all anatomical regions. 
The Regional Modified Sartorius Score together with the overall Modified Sartorius Score will 
be listed by treatment group, subject and visit, including the change from Baseline for the overall 
Modified Sartorius Score.  The observed overall Modified Sartorius Score and the changes from 
Baseline in the overall Modified Sartorius Score will be summarized by treatment group and 
visit. This summary will also be produced by Baseline Hurley Stage.   
8.3.5 
Hidradenitis Suppurativa Physician’s Global Assessment – Derived  
The HS-Physician’s Global Assessment is a validated 6-point scale that is used to measure 
improvement in inflammatory nodules, abscesses, and draining fistulas (Kimball et al, 2012; 
Zouboulis et al, 2015). The HS-Physician’s Global Assessment scale is defined in Section 14.1.  
The scale ranges from “Clear” (no inflammatory or non-inflammatory nodules) to “Very severe” 
(more than 5 abscesses or draining fistulas). The gradings will be derived on a subject-level basis 
(ie, across all anatomical regions) based on the following rules: 
 Clear:  
 number of abscesses = 0; 
 number of draining tunnels (fistulas/sinus tracts) = 0; 
 number of inflammatory nodules = 0; 
 number of non-inflammatory nodules = 0; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
 Minimal:  
 number of abscesses = 0; 
 number of draining tunnels (fistulas/sinus tracts) = 0; 
 number of inflammatory nodules = 0; 
 number of non-inflammatory nodules ≥ 1; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
 Mild:  
 number of abscesses = 0; 
 number of draining tunnels (fistulas/sinus tracts) = 0; 
 number of inflammatory nodules ≥ 1 and ≤ 4; 
 number of non-inflammatory nodules – no limit; 
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 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
OR 
 sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) = 1; 
 number of inflammatory nodules = 0; 
 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
 Moderate:  
 number of abscesses = 0; 
 number of draining tunnels (fistulas/sinus tracts) = 0; 
 number of inflammatory nodules ≥ 5; 
 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
OR 
 sum number of abscesses and number of draining tunnels (fistulas/sinus tracts) = 1; 
 number of inflammatory nodules ≥1; 
 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
OR 
 sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) ≥ 2 and 
≤ 5; 
 number of inflammatory nodules ≤ 10; 
 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
 Severe:  
 sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) ≥ 2 and 
≤ 5; 
 number of inflammatory nodules > 10; 
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 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit; 
 Very Severe:  
 sum of number of and number of draining tunnels (fistulas/sinus tracts) > 5; 
 number of inflammatory nodule – no limit; 
 number of non-inflammatory nodules – no limit; 
 number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
 number of hypertrophic scars – no limit 
The HS-Physician’s Global Assessment will be listed by treatment group and subject at each 
visit. The number and percentage of subjects at each level of the assessment scale (Clear, 
Minimal, Mild, Moderate, Severe and Very severe) will be presented by treatment group, visit, 
overall and by Baseline Hurley Stage.  The denominator for the percentages will be based on the 
number of subjects in the given treatment group, Baseline Hurley Stage and visit for which there 
are no missing data for the HS-Physician’s Global Assessment.  
Shift tables for the changes from Baseline in this scale will be presented for each post-Baseline 
visit by treatment group, overall and by Baseline Hurley Stage. The denominator for the 
percentages will be based on the number of subjects in the given treatment group, Baseline 
Hurley Stage and visit for which there is no missing data for the change from Baseline in 
HS-Physician’s Global Assessment  
8.3.6 
Dermatology Life Quality Index 
The DLQI is a questionnaire designed for use in adult subjects with inflammatory skin diseases 
and has been used in patients with HS (Finlay, 1998; Esmann et al, 2010; Basra et al, 2012). The 
DLQI is a skin disease specific questionnaire aimed at the evaluation of how symptoms and 
treatment affect subjects’ health related quality of life (QoL).  
This instrument asks subjects about symptoms and feelings, daily activities, leisure, work and 
school, personal relationships and treatment. The total DLQI score ranges from 0 to 30 with 
higher scores indicating lower health related QoL. The complete questionnaire is shown in 
Section 14 3 together with the scoring and derivation of the total DLQI. 
Each question on the DLQI will be listed by treatment group and subject for each visit.  The 
listing will also include the total DLQI score at each visit together with the changes from 
Baseline in the total DLQI score.  Summary statistics will be presented for the observed total 
DLQI score at each visit together with the changes from Baseline in the total DLQI score by 
treatment group, overall and by Baseline Hurley Stage. 
The number and percentage of subjects with a total DLQI score in each of the following 
categories will be summarized at each visit, by treatment group, overall and by Baseline Hurley 
Stage: 
 Total DLQI score of 0 or 1 
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 Change from Baseline in the total DLQI score of -4 or below 
For the summary of the change from Baseline in the total DLQI score of -4 or below, the 
denominator for the percentages will be the number of subjects with non-missing data and who 
had a total DLQI score of 4 or higher at Baseline. 
8.3.7 
European Quality of Life - 5 Dimensions-3 Level Questionnaire 
The EQ-5D-3L questionnaire is a standardized instrument developed as a measure of health-
related QoL that can be used in a wide range of health conditions and treatments.  The EQ 5D-
3L consists of a descriptive system and the EQ-5D-3L VAS. 
The descriptive system comprises 5 questions on the following dimensions: mobility, self care, 
usual activities, pain/discomfort and psychological status (anxiety/depression) with 3 possible 
answers for each item (1=no problem, 2=moderate problem, 3=severe problem).  The scores on 
these 5 dimensions (domain scores) represent a health profile for the subject and can be 
converted to a single summary index with a maximum score of 1 using a pre-defined algorithm 
and table of scores. The maximum index score of 1 indicates the best health state, by contrast 
with the scores of individual questions from the descriptive system, where higher scores indicate 
more severe or frequent problems. 
The EQ-5D-3L VAS records the subject’s self-rated health on a vertical 0 to 100 scale, with 100 
indicating the best health status. 
Section 14.4 shows the full questionnaire together with the derivation of the EQ-5D-3L index 
score (Dolan 1997). 
The 5 domain scores, derived EQ-5D-3L index score and VAS scores will be listed by treatment 
group for each subject at each visit, including changes from Baseline for the EQ-5D-3L index 
score and VAS score.   
The number and percentage of subjects giving each categorical response (1, 2 or 3) to the 
questions on the EQ-5D-3L domains will be summarized by visit and treatment group, overall 
and by Baseline Hurley Stage  Shifts from Baseline in the domain scores at each post-Baseline 
visit will also be presented by treatment group, overall and by Baseline Hurley Stage. Any 
questions with a missing or ambiguous response (eg, 2 boxes ticked for a single dimension) will 
be counted in the category “Missing” in the categorical summaries of the EQ-5D-3L domain 
scores. 
The numeric domain scores and changes from Baseline will also be summarized by treatment 
group, overall and by Baseline Hurley Stage as continuous variables using summary statistics at 
each visit.  Any questions with an ambiguous response (eg, 2 boxes ticked for a single 
dimension) will be regarded as missing for the tabulations. 
The derived EQ-5D-3L index score and VAS scores will be summarized using descriptive 
statistics together with changes from Baseline, by visit, treatment group, overall and by Baseline 
Hurley Stage. 
8.3.8 
Hurley Stage 
The Hurley Stage is a severity classification for HS that was developed in 1989 and is widely 
used for the determination of the severity of HS (Hurley, 1989). Stage I HS is the most common 
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(68% of patients), while Stage II occurs in about 28% of patients and Stage III only occurs in 
about 4% of patients. 
The Hurley Stage is defined by the following criteria and will be assessed for each anatomical 
region as part of the lesion count assessment (Section 8.1): 
 Stage I: Abscess formation, single or multiple, without sinus tracts and cicatrization 
(scarring) 
 Stage II: Recurrent abscesses with tract formation and cicatrization, single or multiple, 
widely separated lesions 
 Stage III: Diffuse or near diffuse involvement, or multiple interconnected tracts and 
abscesses across the entire area 
The Hurley Stage for each anatomical region will be recorded directly on the eCRF and the 
overall worst Hurley Stage (ie, the highest Hurley Stage) will be derived automatically in the 
database across all reported anatomical regions. Hurley Stage will be listed by treatment group, 
anatomical region and subject at each visit.  
A categorical summary of the overall worst Hurley Stage at each visit will be presented by 
treatment group. The changes from Baseline in the overall worst Hurley Stage will be 
summarized in shift tables by treatment group and post-Baseline visit. The denominator for the 
percentages will be the number of subjects in the FAS with non-missing overall worst Hurley 
Stage in the respective treatment group and visit. 
8.3.9 
Erythema assessment  
The erythema assessment will be recorded as specified in Section 8.1. 
Erythema assessment results will be listed by treatment group, subject, visit and anatomical 
region.  In addition, the overall worst erythema (highest score) will be derived automatically in 
the database across all reported anatomical regions and will be listed by treatment group, subject 
and visit.  
A categorical summary of the overall worst erythema scores, showing the number and 
percentage of subjects within each category at each visit, will be presented by treatment group, 
overall and by Baseline Hurley Stage.  The denominator for the percentages will be based on the 
number of subjects in the FAS in the given treatment group, Baseline Hurley Stage and visit with 
non-missing data for worst erythema. 
The changes from Baseline in the degree of erythema will be summarized in shift tables by 
treatment group, post-Baseline visit, overall and by Baseline Hurley Stage. The denominator for 
the percentages will be based on the number of subjects in the FAS in the given treatment group, 
Baseline Hurley Stage and visit with non-missing data for the Baseline worst erythema score at 
Baseline and at the respective visits. 
8.3.10 
Hospital Anxiety and Depression Scale 
The HADS was chosen for its well established psychometric properties and its use in clinical 
research on biological therapy in subjects with other inflammatory skin diseases (Dauden et al, 
2009; Langley et al, 2010).  
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The HADS is a commonly used instrument to determine the levels of anxiety and depression that 
a subject is experiencing.  The HADS is a 14-item scale that generates ordinal data.  Seven items 
relate to anxiety (assessed in the HADS-A) and seven relate to depression (assessed in the 
HADS-D).  Individual item scores range from 0 to 3 and are summed to give a total score on 
each of the individual HADS-A and HADS-D scales.  These total scores range from 0 to 21 with 
higher scores indicating a worse state.  
The full HADS questionnaire is shown in Section 14.5 together with the derivation of the total 
HADS-A and HADS-D scores. 
Scores for each item on the HADS-A and HADS-D will be listed at each visit by treatment group 
and subject.  This listing will also include the total HADS-A and HADS-D scores together with 
the changes from Baseline in the total HADS-A and total HADS-D scores at each visit  
Summary statistics will be presented by treatment group and Baseline Hurley Stage for the 
observed total HADS-A and HADS-D scores together with changes from Baseline at each visit. 
8.4 
High Sensitivity C-Reactive Protein 
Concentrations of hsCRP will be listed by treatment group, subject and visit for each subject 
including changes from Baseline and ratio to Baseline. The latter will be calculated as follows:  
Ratio to Baseline = hsCRP at post-Baseline / hsCRP at Baseline visit 
Observed values, changes from Baseline and ratio to Baseline will be summarized by treatment 
group, Baseline Hurley Stage and visit. For the observed values and changes from Baseline, 
summary statistics will include n, arithmetic mean, SD, median, Q1, Q3, minimum and 
maximum. For the ratio to Baseline, summary statistics will include n, geometric mean, geoCV, 
median, Q1, Q3, minimum and maximum   
The rules for handling any values that are BLQ are described in Section 4.2.1. 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
There will be no calculation of PK parameters for this study. The analysis of PK data for this 
study will focus on the trough plasma concentrations of BKZ only. Any additional PK analyses 
will be performed only if required. 
The actual blood sampling times for BKZ concentrations will be obtained in days relative to the 
start time of the first dose of IMP for all sampling time points.  
Individual blood sampling times and concentrations of BKZ will be listed for the SS and will 
include the actual sampling time in days relative to the first dose of IMP. Individual 
concentrations will be summarized at each scheduled time point based on the PK-PPS, using n, 
mean, median, SD, minimum, maximum, geometric mean and 95% CI, and geoCV (assuming 
log normally distributed data). 
Individual concentration versus time (day) profiles will be presented graphically on linear and 
semi-logarithmic scales with all subjects overlaid on the same plot (spaghetti plots). Geometric 
mean profiles of BKZ 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. All 
semi-logarithmic plots will include the LLOQ marked on the y axis. 
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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 (<LLOQ). Values that are BLQ will be replaced by 
the numerical values of the LLOQ/2 in this instance. However, if n≤3, then only n, minimum 
and maximum will be presented (where ‘n’ refers to the number of quantifiable values). The 
other descriptive statistics will be left blank. 
 The 95% CI for the geometric mean 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 
9.2 
Pharmacodynamics 
Blood sampling for exploratory PD analyses will be taken for the evaluation of the following: 
 Flow cytometry by fluorescence activated cell sorting analysis which might include, but will 
not be limited to: cluster of differentiation (CD) CD3, CD19, CD4, CD8, and CD69.  
 Candidate biomarkers might include, but will not be limited to: IL-17A/IL-17F pathway 
signaling and HS (eg, IL-17A, IL-17F, IL-23, IL-6, TNF, DC-STAMP, and circulating 
osteoclast precursors). 
The results for all exploratory PD variables will be listed by treatment group, subject and visit, 
together with the changes from Baseline, based on the SS. Observed values and changes from 
Baseline will be summarized by treatment group based on the PD-PPS.  
Figures of mean and mean changes from Baseline (including 95% CIs for the mean and mean 
change from Baseline) will be presented with separate plots for each variable and all 3 treatment 
groups overlaid on the same plot. 
The rules for handling any values that are BLQ or ALQ are described in Section 4.2.3. 
10 
IMMUNOLOGICAL ANALYSES 
All immunological analyses will be performed for the PK-PPS.  In this study, this will comprise 
an analysis of anti-BKZ antibody data only which will be listed and summarized at each 
scheduled visit, and the rate of anti-BKZ antibody positive subjects will be calculated. 
The results of the anti-BKZ antibody analysis will be listed by treatment group and visit based on 
the SS. This will include the screening assay, confirmatory assay, titre (if applicable) and 
confirmation of whether or not the sample contains BKZ concentration levels above the drug 
tolerance.  
A cut point will be determined by the bioanalytical laboratory that will be used to determine the 
status of anti-BKZ antibody as above the cut point (ACP) or below the cut point (BCP). For any 
anti-BKZ antibody 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 
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positive’ (NCP). For samples that are CP, a further titre assay will be performed and the 
anti-BKZ antibody titre will be reported.  
The following definitions will be applied: 
 An anti-BKZ antibody status of positive will be concluded for any subject with an anti-BKZ 
antibody level that is ACP and CP at any time point  
 An anti-BKZ antibody status of negative will be concluded for any subject with an anti-BKZ 
antibody level that is either BCP or ACP and NCP at any time point 
 A subject will be classified as having anti-BKZ antibody positivity at Baseline if the Day 1, 
predose result is ACP and CP 
 A subject will be classified as having treatment-induced anti-BKZ antibody positivity when 
meeting 1 of the following criteria: 
 The Baseline result is either BCP or ACP and NCP, and at least 1 post-Baseline time 
point is ACP and CP 
 The Baseline result is positive (ACP and CP) and at least 1 post-Baseline measurement 
shows a pre-defined fold increase in titre from the Baseline value (the fold increase from 
Baseline required to meet these 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 1 post-Baseline measurement is ACP 
and CP (this includes subject who have negative results at Baseline) 
 A subject will be classified as overall negative if at all post-Baseline visits the anti-BKZ 
antibody status is negative (this includes subjects who have positive [ACP and CP] results at 
Baseline) 
The number and percentage of subjects with a positive and negative anti-BKZ antibody status 
will be summarized at each visit and overall. This summary will exclude any samples with BKZ 
concentrations confirmed to be above the drug tolerance. 
In addition, the first occurrence of treatment-induced anti-BKZ antibody positivity (based on the 
definitions above) will be summarized at each post-Baseline visit. This tabulation will present 
the number and percentage of subjects at each post-Baseline visit who fulfill at least 1 of the 
above defined criteria for treatment-induced positivity; subjects will be counted in the numerator 
based on the earliest visit at which 1 of these criteria is fulfilled. At other visits, subjects will be 
counted in the denominator (assuming a measurement is available). This summary will exclude 
any samples with BKZ concentrations confirmed to be above the drug tolerance.  
For all tabulations, percentages will be calculated based on the number of subjects with 
non-missing data and anti-BKZ antibody levels that are not flagged as containing BKZ 
concentration levels above the drug tolerance at each respective visit.  
A separate listing will be presented showing the BKZ concentrations and anti-BKZ antibody 
measurements in the same output in adjacent columns, based on the PK-PPS. The listing will 
include the BKZ concentration, anti-BKZ antibody status (ACP or BCP) and confirmatory assay 
results if applicable (NCP or CP), together with the titre for results that are CP. In addition, the 
time since the previous administration of IMP will be reported (in days). 
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Finally, individual subject plots will be presented displaying the anti-BKZ antibody titre and 
BKZ concentrations overlaid on the same figure. The figure will also show the timing and dose 
of each administration of BKZ received during the study. The anti-BKZ antibody data will be 
plotted using a semi-logarithmic scale. This figure will exclude any samples with BKZ 
concentrations confirmed to be above the drug tolerance. 
The rules for handling values that are BLQ in the BKZ concentration data are described in 
Section 4.2.2. For the anti-BKZ antibody data, any negative results for which there are no titres 
available at a specific visit will be substituted with 0.001 for the purpose of the figure. 
11 
SAFETY ANALYSES 
All analysis of safety variables will be performed using the SS. 
11.1 
Extent of exposure 
All IMP administration details (including date, time and location of injection) will be listed.  
The percentage of injections administered will be included in the listing based on the number of 
planned injections. For subjects completing the study this will be 17 injections. The number of 
planned injections for subjects who withdraw early from the study will be reduced according to 
the number of injections planned up to EW visit  
All IMP administration details (including date, time and location of injection) will be listed. The 
percentage of injections administered will be included in the listing based on the number of 
planned injections. For subjects completing the study this will be 17 injections. The number of 
planned injections for subjects who withdraw early from the study will be reduced according to 
the number of injections planned up to EW visit. 
The duration of exposure to BKZ and PBO (days) will be calculated as follows: 
𝐸𝑥𝑝𝑜𝑠𝑢𝑟𝑒= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐷𝑜𝑠𝑒−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒) + 140 𝑑𝑎𝑦𝑠 
The duration of exposure to ADA (days) will be calculated as follows: 
𝐸𝑥𝑝𝑜𝑠𝑢𝑟𝑒= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝐿𝑎𝑠𝑡 𝐷𝑜𝑠𝑒−𝐷𝑎𝑡𝑒 𝑜𝑓 𝐹𝑖𝑟𝑠𝑡 𝐷𝑜𝑠𝑒) + 100 𝑑𝑎𝑦𝑠 
The number of days added to the BKZ and ADA exposure calculations are 5 times the half-life 
of each drug, respectively: 5 x 28 days for BKZ and 5 x 20 days for ADA. The number of days 
added to PBO is set to 140 days in order for PBO exposure to be comparable to that of BKZ. 
Missed doses will not be accounted for in the calculation above. 
Duration of exposure will be listed for each subject and summarized using descriptive statistics. 
11.2 
Adverse events 
Adverse events with a start date prior to the first dose of IMP will be defined as pre-treatment 
AEs. A treatment-emergent AE (TEAE) is defined as any AE with a start date/time at the time of 
or after the first dose of IMP up until 140 days after the last dose of IMP. Any AE with onset 
later than 140 days after the last dose of IMP will not be considered as treatment-emergent and 
therefore will not be included in the tabulations of TEAEs. 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 the first dose of IMP or later than the defined cutoff for TEAEs.  
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Handling of missing dates/times for classification of AEs as TEAEs is described in Section 4.2.4. 
All AEs will be recorded in the eCRF from informed consent until study completion or 
termination. All AEs will be coded and categorized by intensity (mild/moderate/severe) and 
relationship to IMP (related/not related). 
An overview of the number and percentage of subjects who experience TEAEs will be presented 
by treatment group, based on the SS. 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. 
In addition, the following summaries will be presented by treatment group, SOC, high level term 
(HLT) and PT, based on the SS: 
 Incidence of TEAEs 
 Incidence of TEAEs, stratified by overall anti-BKZ antibody status (positive/negative) as 
defined in Section 10  
 Incidence of serious TEAEs 
 Incidence of non-serious TEAEs 
 Incidence of TEAEs by relationship 
 Incidence of TEAEs by maximum relationship 
 Incidence of TEAEs by maximum intensity 
 Incidence of fatal TEAEs by relationship 
 Incidence of non-serious TEAEs by relationship 
 Incidence of serious TEAEs by relationship 
 Incidence of non-serious TEAEs above threshold of 5% of subjects 
 Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship 
 Incidence of TEAEs by SOC and PT (including the number and percentage of subjects and 
individual subject numbers for each PT stratified by intensity, relationship and seriousness) 
In addition, separate summaries by treatment group, SOC, HLT and PT will be included for the 
following AEs for special monitoring (AESM): 
 Major cardiovascular events  
 Serious infections, opportunistic infections, fungal infections and tuberculosis (TB) 
 Malignancies including lymphoma 
 Cytopenias 
 Neuropsychiatric events 
 Inflammatory bowel disease 
 Anaphylactic reaction (hypersensitivity and anaphylactic reactions) 
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 Hepatic events and drug induced liver injury 
The criteria for identifying and additional criteria for reporting AESM are provided in 
Section 14.9. 
All summary tables (including those for AESM) will contain the number and percentage of 
subjects and the number of events where applicable. A subject who has multiple events in the 
same SOC, HLT and PT will be counted only once in the subjects counts but all events will be 
included. 
In summaries including relationship to IMP, the following relationship categories will be 
included: 
 Related 
 Not related 
Subjects who experience the same event multiple times will be included in the most related 
category for tabulations by maximum relationship. Events with missing relationship will be 
considered as ‘Related’ for summary purposes but shown as missing in the data listings. 
In summaries including intensity, the following categories will be summarized: 
 Mild 
 Moderate 
 Severe 
Subjects who experience the same event multiple times will be included in the most severe 
category for tabulations by maximum intensity. Events with missing intensity will be considered 
as severe for summary purposes. All data will be presented as recorded in the database for the 
listings. 
Adverse event summaries will be ordered by alphabetical SOC, alphabetical HLT within SOC 
and decreasing frequency of PT in the ‘BKZ’ column for tables including event counts. For 
tables including only number and percentage of subjects, summaries will be ordered by 
alphabetical SOC, alphabetical HLT within SOC and decreasing incidence of PT within HLT 
and SOC in the ‘BKZ’ column. 
Listings will be presented by treatment group and subject for all AEs, SAEs, AEs leading to 
death and AEs leading to withdrawal. Listings will include the onset date/time and outcome 
date/time of the event (including relative days), the AE duration (derived), days since first dose 
of IMP, days since most recent dose of IMP, pattern of event, intensity, relationship, action taken 
and outcome. In addition, the listing will flag AEs that led to discontinuation, TEAEs, AESM 
and SAEs. All AE listings will be based on the ES, except where otherwise noted. 
A glossary of all TEAE terms will be provided including the SOC, HLT, PT and reported term, 
based on the SS. 
11.3 
Clinical laboratory evaluations 
Laboratory data (chemistry, hematology and urinalysis) and changes from Baseline (if 
applicable) for numeric variables will be listed by treatment group and visit. Any laboratory 
variables that are BLQ or ALQ will be handled as described in Section 4.2.3. Values outside the 
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reference range for the numeric variables will be flagged in the listings and in addition, will be 
listed separately. The reference ranges will also be reported in the listings. 
Chemistry and hematology variables presented in Table 11‒1 will be summarized by treatment 
group at each visit, for both observed values and changes from Baseline. Figures of mean and 
mean change from Baseline will be presented by treatment for the absolute neutrophil count 
(ANC). All treatment groups will be overlaid on the same plot and the plot will include the error 
bars based on the SD (ie, mean +/-SD). 
Laboratory variables will be grouped according to the laboratory function panel and categorized 
as normal, high or low, if applicable, based on the reference range supplied by the analytical 
laboratory. For selected variables that are identified in Table 11‒1, the change in category from 
Baseline will be presented in shift tables for all post-Baseline visits. 
The number and percentage of subjects with treatment-emergent markedly abnormal (TEMA) 
values will be tabulated by treatment group and visit. Markedly abnormal laboratory values will 
generally be defined as those categorized as Grade 3 or Grade 4 as per the Rheumatology 
Common Toxicity Criteria (RCTC) Version 2.0 (Woodworth et al, 2007). Communication with 
the lead author of the RCTC publication has revealed that the reference ranges for absolute 
lymphocyte counts (ALC) are in error, therefore ALC criteria will follow the ranges defined as 
per the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (United 
States Department of Health and Human Services, 2010)  Additional laboratory variables (not 
present in the RCTC publication) will also be categorized as per the CTCAE Version 4.03. The 
criteria for identifying TEMA values are presented in Table 14‒7 and Table 14‒8 for hematology 
and chemistry values respectively.  
Laboratory measurements meeting the criteria for TEMA will be listed separately for 
hematology and chemistry. The listings will include all measurements for any variable with at 
least 1 TEMA result for each subject  
Table 11‒1: Laboratory measurements 
Hematology 
Chemistry 
Urinalysis 
Serology 
Basophils 
Bicarbonate 
Albumin 
HIV 
Eosinophils 
Calcium 
Bacteria 
HLA-B27 
Lymphocytes 
Chloride 
Crystals 
Hepatitis B 
Atypical lymphocytes 
Creatinine 
Glucose 
Hepatitis C 
Monocytes 
hsCRPa 
pH 
 
Neutrophilsb 
Magnesium 
RBC 
 
Hematocrit 
Potassium 
WBC 
 
Hemoglobinb 
Sodium 
Urine dipstick for 
pregnancy testingc 
 
MCH 
Glucose 
Urine drug screen 
 
MCHC 
BUN 
 
 
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Table 11‒1: Laboratory measurements 
Hematology 
Chemistry 
Urinalysis 
Serology 
MCV 
ALPb 
 
 
Platelet count 
ASTb 
 
 
RBC count b 
ALTb 
 
 
WBC countb  
GGTb 
 
 
 
Total bilirubind 
 
 
 
Uric acid 
 
 
 
LDH 
 
 
 
Total cholesterolb 
 
 
 
Serum pregnancy 
testing 
 
 
 
Serum FSHe 
 
 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; FSH=follicle-stimulating hormone; GGT=gamma glutamyltransferase; hsCRP= high sensitivity C-reactive 
protein; HLA=human leukocyte antigen; HIV=human immunodeficiency virus; 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 To avoid duplication, hsCRP will be included in the listings and tabulations for the efficacy data and will not be 
included in the safety laboratory outputs  
b Shift tables of the change from Baseline in these variables will be presented. 
c Pregnancy testing will be done in all women of childbearing potential and will consist of serum testing at 
Screening and at the Safety Follow Up Visit and urine testing at all other visits. 
d If total bilirubin is >ULN (upper limit of normal), a direct bilirubin estimation (%) will be performed. 
e The serum FSH test (at Screening only) should only be performed on postmenopausal females who have been 
postmenopausal for ≥1 year and last menstrual cycle occurred <2 years ago. 
Any additional laboratory variables not included in the outputs described previously will be 
listed separately. These will include the following: 
 Serology  
 Urine drug screen 
 Pregnancy tests (serum and urine) 
 Follicle stimulating hormone (FSH) (only for postmenopausal women) 
The results of the TB questionnaire will be listed separately. 
Subjects with treatment-emergent liver function test abnormalities at any post-Baseline visit will 
be summarized (number and percentage of subjects) by treatment group. The criteria for this 
tabulation are presented in Table 14‒9. 
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11.4 
Vital signs, physical findings, and other observations related to 
safety 
11.4.1 
Vital signs 
The following vital signs measurements will be obtained: 
 Systolic and diastolic blood pressure 
 Pulse rate 
 Temperature (oral, axillary, or otic) 
A by-subject listing of all vital sign measurements and changes from Baseline will be presented 
by treatment group and visit. The listing will include a flag for measurements identified as 
TEMA/potentially clinically significant (PCS) as calculated by the criteria outlined in Table 14‒
10. Body weight will also be included in the listing. 
Descriptive statistics will be reported for all vital sign measurements (with the exception of body 
weight). Observed values and changes from Baseline will be summarized by treatment group for 
each vital signs variable and visit.  
Figures of mean change from Baseline over time will be presented for each variable by treatment 
group. 
The number and percentage of subjects with TEMA/PCS vital sign values will be summarized by 
treatment group at each visit. The denominator for the percentage calculations will be the 
number of subjects with a non-missing measurement for the variable at the specific visit. 
11.4.2 
Electrocardiograms 
Standard 12-lead ECG recordings will be obtained after 10 minutes of rest in the supine position. 
The following ECG variables will be reported together with the Investigator’s interpretation of 
the ECG profile: 
 PR interval 
 QRS interval 
 QT interval 
 Heart rate 
 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 changes from Baseline and percentage changes from Baseline and will be presented 
by treatment group and visit. 
Observed values, changes and percentage changes from Baseline will be summarized for each 
variable by treatment group and visit.  
The following cut points in QTcF (raw data and change from Baseline) will be summarized 
categorically by treatment group (number and percentage of subjects) and visit. The denominator 
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for the percentage calculations will be the number of subjects with a non-missing measurement 
for the variable at the specific visit. 
Observed QTcF data: 
 <450msec 
 ≥450msec to <480msec 
 ≥480msec to <500msec 
 ≥500msec 
Change from Baseline QTcF: 
 <30msec 
 ≥30ms to <60msec 
 ≥60msec 
Electrocardiogram findings including the Investigator’s interpretation of the ECG profile will be 
listed separately. 
11.4.3 
Other safety variables 
11.4.3.1 
Physical examination 
Subjects with abnormalities in the physical examination will be listed including details of the 
abnormality. 
11.4.3.2 
Columbia-Suicide Severity Rating Scale 
The C-SSRS is divided into 2 time intervals and further sub-divided as shown: 
 C-SSRS at Baseline – assessed at the Screening visit  
 Suicidal Ideation – over Lifetime and over Past 6 Months 
 Intensity of Ideation – over Lifetime and over Past 6 Months 
 Suicidal Behavior – over Lifetime and over Past 2 Years 
 C-SSRS Since Last Visit – assessed at all visits after Screening  
 Suicidal Ideation – Since Last Visit 
 Intensity of Ideation – Since Last Visit 
 Suicidal Behavior – Since Last Visit 
For Suicidal Ideation questions, only those questions where “Yes” has been answered will be 
listed. For Intensity of Ideation questions and Suicidal Behavior questions, any question for 
which an answer has been recorded will be listed.  
Results, as specified above, will be listed for each subject and visit. 
11.4.3.3 
Chest X-ray and tuberculosis questionnaire 
The results of the chest X-ray (or computed axial tomography scan if applicable), TB 
questionnaire and TB test will be listed for each subject. 
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12 
OTHER ANALYSES  
A listing of comments will be provided, if applicable. This will be based on the RS. 
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13 
REFERENCES 
Common Terminology Criteria for Adverse Events (CTCAE); Version 4.03 June 2010.U.S. 
Department of Health and Human Services 
Basra MK, Chowdhury MM, Smith EV, Freemantle N, Piquet V. A review of the use of the 
dermatology life quality index as a criterion in clinical guidelines and health technology 
assessments in psoriasis and chronic hand eczema. Dermatol Clin. 2012;30(2):237 44. 
Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the Minimal Clinically 
Important Difference and Responsiveness of the Dermatology Life Quality Index (DLQI): 
Further Data. Dermatology. 2015;230(1):27 33. 
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. 
Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35(11):1095-108. 
Esmann S, Dufour DN, Jemec GB. Questionnaire based diagnosis of hidradenitis suppurativa: 
specificity, sensitivity and positive predictive value of specific diagnostic questions. Br J 
Dermatol. 2010;163(1):102 6. 
Finlay AY. Quality of life assessments in dermatology. Semin Cutan Med Surg. 1998; 17(4):291 
6. 
Guidance for Industry: E9 Statistical Principles for Clinical Trials. US Department of Health and 
Human Services, Food and Drug Administration. ICH 1998. 
Hurley H. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial 
benign pemphigus: surgical approach  In: Dermatologic surgery. Roenigh R, Roenigh H, editors. 
Marcel Dekker. 1989:729 39. 
Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, Gniadecki R. Adalimumab for the 
treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern 
Med. 2012;157(12):846 55. 
Kimball AB, Jemec GB, Yang M, Kageliery A, Signorovitch JE, Okun MM, et al. Assessing the 
validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response 
(HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 
2014;171(6):1434 42. 
Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, et al. Two Phase 
3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016a;375(5):422 34. 
Kimball AB, Sobell JM, Zouboulis CC, Gu Y, Williams DA, Sundaram M, et al. HiSCR 
(Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic 
outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 
2 adalimumab study. J Eur Acad Dermatol Venereol. 2016b;30(6):989 94. 
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 
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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. 
Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG. Feasibility and 
Validation of a Computer Automated Columbia Suicide severity Rating Scale Using Interactive 
Voice Response Technology. J Psychiatr Res. 2010;44(16):1224 8. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia 
Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three 
Multisite Studies With Adolescents and Adults. Am J Psychiatry. 2011;168(12):1266 77. 
Sartorius K, Lapins J, Emtestam L, Jemec GB. Suggestions for uniform outcome variables when 
reporting treatment effects in hidradenitis suppurativa. Br J Dermatol. 2003;149(1):211 3. 
Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring of hidradenitis suppurativa 
reflecting the role of tobacco smoking and obesity. Br J Dermatol. 2009;161(4):831 9. 
Sartorius K, Killasli H, Heilborn J, Jemec GB, Lapins J, Emtestam L  Interobserver variability of 
clinical scores in hidradenitis suppurativa is low. Br J Dermatol. 2010;162(6):1261 8. 
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the irritability 
depression anxiety scale and the Leeds situational anxiety scale manual. 1994. 
UpToDate. 2011. Modified Hidradenitis Suppurativa Score (HSS). [ONLINE] Available at: 
http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?36/33/37400. [Accessed 27 
November 2017]. 
Zouboulis CC, Desai N, Emtestam L, Hunger RE, Loannides D, Juhász I, et al. European S1 
guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol 
Venereol. 2015; 29(4):619 44. 
Zouboulis CC, Kyrgidis A, Jemec GBE, Bechara FG, Giamarellos Bourboulis EJ, Ingram JR, et 
al. Development and validation of IHS4, a novel dynamic scoring system to assess hidradenitis 
suppurativa/acne inversa severity. British Journal of Dermatology. 2017 June 21.  
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14 
APPENDICES 
14.1 
HS-Physician’s Global Assessment 6-point scale 
The HS-Physician’s Global Assessment 6-point scale is scored according to the specifics in 
Table 14‒1. 
Table 14‒1: HS-Physician’s Global Assessment 6-point scale 
Score 
Rating 
Description 
0 
Clear 
No abscesses, no draining tunnels (fistulas/sinus tracts), no nodules 
1 
Minimal 
No abscesses, no draining tunnels (fistulas/sinus tracts)  no inflammatory 
nodules, presence of non-inflammatory nodules 
2 
Mild 
No abscesses or draining tunnels (fistulas/sinus tracts), and less than 5 
inflammatory nodules, or 
Single abscess or draining tunnel (fistula/sinus tract), and no 
inflammatory nodules 
3 
Moderate 
No abscesses or draining tunnels (fistulas/sinus tracts), and at least 5 
inflammatory nodules, or 
Single abscess or draining tunnel (fistula/sinus tract) in the presence of 
inflammatory nodules, or 
Between 2 and 5 abscesses or draining tunnels (fistulas/sinus tracts) with 
or without inflammatory nodules, up to 10 
4 
Severe 
Between 2 and 5 abscesses and draining tunnels (fistulas/sinus tracts), 
with inflammatory nodules that are greater than 10 
5 
Very severe 
More than 5 abscesses or draining tunnels (fistulas/sinus tracts) 
14.2 
Modified Sartorius Score   
The scoring system for the presence, counts and measurements of relevant lesions by type are 
given in Table 14‒2. 
Table 14‒2: Modified Sartorius Score 
Characteristics of HS lesions  
Points  
Anatomical region 
Any 
3 
None 
0 
Types of lesions 
Fistulaa 
4 
Noduleb 
2 
Abscess 
1 
Scarc 
1 
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Table 14‒2: Modified Sartorius Score 
Characteristics of HS lesions  
Points  
Other d 
1 
Total area involvede 
< 5 cm 
2 
5 to 10 cm 
4 
> 10 cm 
8 
Are all lesions clearly separated by normal skin?f 
Yes 
0 
No 
6 
HS=hidradenitis suppurativa 
Taken from http://cursoenarm net/UPTODATE/contents/mobipreview htm?36/33/37400 and adapted from: 
1. Sartorius, K, Lapins, J, Emtestam, L, Jemec, GB. Suggestions for uniform outcome variables when 
reporting treatment effects in hidradenitis suppurativa  Br J Dermatol 2003; 149:211.  
2. Mahmoud, BH, Tierney, E, Hexsel, CL, Pui, J, Ozog, DM, Hamzavi, IH  Prospective controlled clinical 
and histopathologic study of hidradenitis suppurativa treated with the long-pulsed neodymium:yttrium-
aluminium-garnet laser. J Am Acad Dermatol. 2010; 62:637-45. 
a Fistula includes draining tunnels (fistulas/sinus tracts) 
b Nodule refers to inflammatory nodules 
c Scar refers to hypertrophic scars 
d Other includes non-inflammatory nodules and non-draining tunnels (fistulas/sinus tracts). 
e Area is defined as the longest distance between 2 relevant lesions (ie, abscess, draining tunnel (fistula/sinus tract) 
or inflammatory nodule). If there is only 1 lesion it is the measurement of the single lesion diameter. 
f This refers to all relevant lesions. 
 
14.3 
Dermatology Life Quality Index 
The 10 questions and scoring of the DLQI are presented in Table 14‒3. 
Table 14‒3: Dermatology Life Quality Index 
Item 
Nr. 
Question 
Answers 
1 
Over the last week, how itchy, sore painful or stinging has 
your skin been? 
Very much 
A lot 
A little 
Not at all 
2 
Over the last week, how embarrassed or self-conscious have 
you been because of your skin? 
Very much 
A lot 
A little 
Not at all 
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Table 14‒3: Dermatology Life Quality Index 
Item 
Nr. 
Question 
Answers 
3 
Over the last week, how much has your skin interfered with 
you going shopping or looking after your home or garden? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
4 
Over the last week, how much has your skin influenced the 
clothes you wear? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
5 
Over the last week, how much has your skin affected any 
social or leisure activities? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
6 
Over the last week, how much has your skin made it difficult 
for you to do any sport? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
7 
Over the last week, has your skin prevented you from 
working or studying? 
 
If "No", over the last week how much has your skin been a 
problem at work or studying? 
Yes 
No 
   Not relevant 
A lot 
A little 
Not at all 
8 
Over the last week, how much has your skin created 
problems with your partner or any of your close friends or 
relatives? 
Very much 
A lot 
A little 
Not at all 
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Table 14‒3: Dermatology Life Quality Index 
Item 
Nr. 
Question 
Answers 
   Not relevant 
9 
Over the last week, how much has your skin caused any 
sexual difficulties? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
10 
Over the last week, how much of a problem has the 
treatment for your skin been, for example by making your 
home messy, or by taking up time? 
Very much 
A lot 
A little 
Not at all 
   Not relevant 
The following rules apply to the scores for the individual questions and the calculation of the 
total DLQI score: 
 Individual responses will be scored as follows, with separate rules for Question 7 below: 
 Very much = 3 
 A lot = 2 
 A little = 1 
 Not at all = 0 
 If 1 question is left unanswered this question will be scored as 3 and the scores for each 
question will be summed to give the total DLQI score. 
 If two or more questions are left unanswered a total DLQI will not be calculated. 
 If Question 7 is answered “Yes” this will be scored as 3. If question 7 is answered “No” the 
scoring will be as follows: 
 If “A lot”, “A little” or “Not at all” is ticked this will be scored as 2, 1 or 0 respectively.  
 If the second half of the questions is left incomplete, the score will be set to 3. 
 If a question is answered as “Not relevant” then this will be scored as 0. 
 If two or more response options are ticked, the response option with the highest score will be 
recorded. 
 If there is a response between two tick boxes, the lower of the two score options will be 
recorded. 
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 The total DLQI score will be calculated by summing the scores over all the questions. 
14.4 
European Quality of Life-5 Dimensions-3 Level Questionnaire 
The EQ-5D-3L comprises a descriptive aspect and the EQ-5D-3L VAS. Table 14‒4 presents the 
descriptive aspect of the EQ-5D-3L, with the 5 domains (1 question each) of the EQ-5D-3L 
questionnaire. There are 3 levels of response (a score of 1, 2 or 3) to each question. 
Table 14‒4: European Quality of Life-5 Dimensions-3 Level Questionnaire 
The EQ-5D-3L index score (the EuroQoL Group, 2015) will be derived using the UK time trade 
off  (TTO) value set as shown in Table 14‒5.  
The EQ-5D-3L index score will be derived as: 
EQ-5D-3L Index Score = 1 −(0.081 + 𝑀02 + 𝑀𝑂3 + 𝑆𝐶2 + 𝑆𝐶3 + 𝑈𝐴2 + 𝑈𝐴3 + 𝑃𝐷2 +
𝑃𝐷3 + 𝐴𝐷2 + 𝐴𝐷3 + 𝑁3) 
where the scores associated with each abbreviation above are explained in Table 14‒5 below. 
Table 14‒5: UK TTO Value Set 
Condition 
Score if condition is true; else zero 
Full Health (all questions have score 1) 
1 
At least one 2 or 3 
0.081 
At least one 3 (N3) 
0.269 
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Table 14‒5: UK TTO Value Set 
Condition 
Score if condition is true; else zero 
Mobility = 2 (MO2) 
0.069 
Mobility = 3 (MO3) 
0.314 
Self-care = 2 (SC2) 
0.104 
Self-care = 3 (SC3) 
0.214 
Usual activities = 2 (UA2) 
0.036 
Usual activities = 3 (UA3) 
0.094 
Pain/discomfort = 2 (PD2) 
0.123 
Pain/discomfort = 3 (PD3) 
0.386 
Anxiety/depression = 2 (AD2) 
0.071 
Anxiety/depression = 3 (AD3) 
0.236 
14.5 
Hospital Anxiety and Depression Scale 
The individual items on the HADS-A and HADS D scales are listed in Table 14‒6. 
 
Table 14‒6: Hospital Anxiety and Depression Scale 
Each item is scored from 0 to 3, with higher scores indicating more severe anxiety or depression. 
The total score for HADS-A and HADS-D will be derived by summing the scores over the 7 
items and will range from 0 to 21.  
In case of missing data, the following rules will be applied: 
 If a maximum of 1 item is missing in HADS-A or HADS-D, the missing item will be 
imputed with the mean score from the remaining completed items within the HADS-A or 
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 If more than 1 item is missing in HADS-A or HADS-D, the total HADS-A or HADS-D score 
will not be calculated. 
14.6 
Treatment-emergent markedly abnormal laboratory values 
The criteria for identifying TEMA laboratory values are provided for hematology in Table 14‒7 
and for chemistry in Table 14‒8. 
Table 14‒7: Definition of TEMA values for hematology 
Variable (SI units) 
Source 
Markedly abnormal definition 
Low Grade 4 
Low Grade 3 
High Grade 
3 
High Grade 4 
Hemoglobin (g/L) 
RCTC 
<70 OR 
decrease from 
Baseline of 
≥30 
70 to <80 OR 
value <LLN 
and decrease 
from Baseline 
of 21 to 29  
NA 
NA 
ALC (10^9/L) 
CTCAE 
<0.2 
0.2 to <0.5 
NA 
NA 
ANC (10^9/L) 
RCTC 
<0.5 
0.5 to <1.0 
NA 
NA 
WBC (10^9/L) 
RCTC 
<1.0 
1 0 to <2 0 
NA 
NA 
Platelets (10^9/L) 
RCTC 
<20 
20 to <50 
NA 
NA 
ALC=absolute lymphocyte count; ANC=absolute neutrophil count; CTCAE=Common Terminology Criteria for 
Adverse Events (CTCAE 2010); LLN=lower limit of normal; NA=not applicable; RCTC=Rheumatology Common 
Toxicity Criteria; WBC=white blood cell. 
 
Table 14‒8: Definition of TEMA values for chemistry 
Variable (SI units) 
 
Source 
Markedly abnormal definition 
Low Grade 4 
Low Grade 3 
High Grade 
3 
High Grade 
4 
ALP (U/L) 
RCTC 
NA 
NA 
>3.0 to 5.0 x 
ULN 
>5.0 x ULN 
ALT (U/L) 
RCTC 
NA 
NA 
>3.0 to 8.0 x 
ULN 
>8.0 x ULN 
AST (U/L) 
RCTC 
NA 
NA 
>3.0 to 8.0 x 
ULN 
>8.0 x ULN 
Creatinine (μmol/L) 
RCTC 
NA 
NA 
>1.8 to 3.0 x 
ULN 
>3.0 x ULN 
GGT (U/L) 
CTCAE 
NA 
NA 
>5.0 to 20.0 x 
ULN 
>20.0 x ULN 
Glucose (mmol/L) 
RCTC 
<1.67 
1.67 to <2.22 
>13.89 to 
27.78 
>27.78 
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Table 14‒8: Definition of TEMA values for chemistry 
Variable (SI units) 
 
Source 
Markedly abnormal definition 
Low Grade 4 
Low Grade 3 
High Grade 
3 
High Grade 
4 
Potassium (mmol/L) 
RCTC 
<2.5 
2.5 to <3.0 
>6.4 to 7.0 
>7.0 
Sodium (mmol/L)a 
RCTC 
<120 
120 to <125 
>155 to 160 
>160 
Total bilirubin 
(μmol/L) 
RCTC 
NA 
NA 
≥2.0 to 3.0 x 
ULN 
>3 0 x ULN 
Calcium (mmol/L) 
RCTC 
<1.63 
1.63 to <1.75 
>3.125 to 
3.375 
>3.375 
Cholesterol (total) 
(mmol/L) 
CTCAE 
NA 
NA 
>10.34 to 
12.92 
>12.92 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common 
Terminology Criteria for Adverse Events (CTCAE 2010); GGT=gamma glutamyltransferase; NA=not applicable; 
RCTC=Rheumatology Common Toxicity Criteria; ULN=upper imit of normal. 
a For sodium High Grade 3 and 4 are taken from CTCAE. 
14.7 
Treatment-emergent abnormal liver values 
The criteria for identifying treatment-emergent liver function abnormalities are presented in 
Table 14‒9. Subjects will be counted in all applicable categories for the tabulations ie, a subject 
with ≥5 x ULN in AST will also be counted in the ≥3 x ULN in AST category, the ≥3 x ULN in 
AST or ALT category and the ≥5x ULN in AST or ALT category. 
Table 14‒9: 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 
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Table 14‒9: Definition of treatment-emergent liver function values 
Criterion 
≥1.5 x ULN increase for bilirubin 
≥1.5 x ULN increase for ALP 
≥1 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit) 
≥2 x ULN increase for bilirubin and 3 x ULN increase of either AST or ALT (at the same visit) 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of 
normal. 
14.8 
Treatment-emergent markedly abnormal vital signs values 
The criteria for identifying TEMA/PCS vital signs values are provided in Table 14‒10. 
Table 14‒10: 
TEMA/PCS criteria for vital signs 
Variable 
Unit 
Lowa 
Higha 
Systolic blood pressure 
mmHg 
Value ≤90 and ≥30 
decrease from Baseline 
Value ≥180 and ≥40 
increase from Baseline 
Diastolic blood pressure 
mmHg 
Value ≤50 and ≥20 
decrease from Baseline 
Value ≥105 and ≥30 
increase from Baseline 
Pulse rate 
bpm 
Value ≤50 and ≥30 
decrease from Baseline 
Value ≥120 and ≥30 
increase from Baseline 
bpm=beats per minute. 
Note: the change in measurement (increase or decrease) will be calculated relative to the value obtained at Baseline. 
a Both conditions must be satisfied for a measurement to be considered PCS. 
14.9 
Adverse events for special monitoring 
The following AESM are defined for BKZ and will be summarized separately as described in 
Section 11.2: 
 Major cardiovascular events  
 Serious infections, including opportunistic infections and TB 
 Malignancies including lymphoma 
 Cytopenias 
 Neuropsychiatric events  
 Inflammatory bowel disease 
 Anaphylactic reaction (hypersensitivity and anaphylactic reactions) 
 Hepatic events and drug induced liver injury 
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14.9.1 
Major cardiovascular events 
Major adverse cardiovascular events will be tabulated separately and will be identified using the 
following UCB defined search criteria: 
 All serious TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow 
groups of the following standardized MedDRA queries (SMQ):  
 Haemorrhagic central nervous system vascular disorders  
 Ischaemic central nervous system vascular disorders 
 All serious TEAEs which code to a PT included in the HLT = ‘Ischaemic coronary artery 
disorders’ except events coding to PT = ‘Chest pain’ or PT = ‘Chest discomfort’ 
 All serious TEAEs which code to a PT = ‘Cardiac failure congestive’ 
14.9.2 
Serious infections, including opportunistic infections and 
tuberculosis 
14.9.2.1 
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. 
14.9.2.2 
Fungal infections 
Fungal infections will be summarized separately based on all TEAEs coding to the high level 
group term (HLGT) = ‘Fungal infectious disorders’. 
14.9.2.3 
Opportunistic infections 
Opportunistic infections (including TB) will be summarized in a separate table including all 
TEAEs identified using search criteria defined by UCB. 
Opportunistic infections are identified in 2 steps: 
 Step 1: Refer to column B of the spreadsheet which identifies the PTs to be classified as 
opportunistic infections using either a single ‘x’ or a double ‘xx’ 
 All TEAEs which code to a PT flagged with a single ‘x’ need to also be serious in order 
to be considered an opportunistic infection 
 All TEAEs which code to a PT flagged with a double ‘xx’ are considered to be an 
opportunistic infection, regardless of seriousness. 
All serious TEAEs in the study database which code to a PT flagged with a single ‘x’ and all 
TEAEs in the study database which code to a PT flagged with a double ‘xx’ will be summarized 
as an opportunistic infection in the stand alone table. 
 Step 2: Refer to column C of the spreadsheet which identifies the PTs that need to be 
evaluated on a case by case basis by the study physician in order to determine whether it is a 
true opportunistic infection or not. The process for physician review is as follows: 
 Study programming team creates a spreadsheet which lists all of the subjects with a 
TEAE present in the database which codes to a PT identified as needing case by case 
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review. Information from the AE dataset to be included in the spreadsheet: Subject ID, 
AE verbatim term, SOC, HLT, Lower Level Term, PT, AE start date, AE end date, 
seriousness, severity, relationship to study medication, action taken. Additionally, a 
column will be included where the study physician can document their decision on the 
case 
 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’ 
 Study programming team incorporates these decisions into the ADAE dataset by merging 
the study physician decisions for individual subjects / PTs and flagging the confirmed 
opportunistic infections as such in the dataset 
All subjects with an AE reported that has been confirmed by the study physician to be an 
opportunistic infection (based on case by case review) will be summarized as such in the stand 
alone table, together with all of the events identified in Step 1 of this process. 
The timing and frequency of Step 2 should be outlined and agreed to by the study team at the 
beginning of the study.  
Following the initial physician review of case by case events, subsequent reviews will be based 
on the cumulative set of case by case events present in the database at each time point of 
spreadsheet creation. Physician decisions from previous runs should be retained in each 
subsequent run. The final run of the spreadsheet, with all study physician decisions on the full set 
of case by case events, will be archived at the conclusion of the study. 
14.9.3 
Malignancies including lymphoma 
Malignancies will be presented in 2 separate tables based on the following SMQs: 
 Malignant or unspecified tumors 
 Malignant tumors 
Events included in the ‘Malignant tumors’ tabulation will be a subset of the events in the 
‘Malignant or unspecified tumors’ tabulation. The SMQ search should include all TEAEs which 
code to a PT included in the Scope=Narrow group within each SMQ. 
The output tables will include 2 different overall incidence rows: 
 The first overall incidence row will summarize ‘Any malignancies (including unspecified)’ 
or ‘Any malignancies’ (depending on the table) and this row will summarize the incidence of 
all AEs flagged for inclusion in the table, regardless of the HLT it codes to 
 The second overall incidence row will summarize ‘Any malignancy (including unspecified, 
excluding non-melanomic skin cancers)’ or ‘Any malignancy (excluding non-melanomic 
skin cancers)’ (depending on the table) and this row will summarize the incidence of AEs 
flagged for inclusion in the table, excluding those which code to an HLT of ‘skin neoplasms 
malignant and unspecified (excl melanoma)’ 
14.9.4 
Cytopenias 
Cytopenias will be tabulated separately based on the SMQ = ‘Haematopoietic cytopenias’. Only 
serious TEAEs will be included in the tabulation. The SMQ search should include all serious 
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TEAEs which code to a PT included in the Scope=Broad and/or Scope=Narrow groups within 
the SMQ. 
14.9.5 
Neuropsychiatric events 
Neuropsychiatric events (in particular depression, anxiety and suicide ideation or behavior) will 
be tabulated separately based on the SMQ = ‘Depression and suicide/self-injury’. The SMQ 
search should include all TEAEs which code to a PT included in the Scope=Broad and/or 
Scope=Narrow groups within the SMQ. 
14.9.6 
Inflammatory bowel disease 
Inflammatory bowel disease events will be tabulated separately, based on the HLGT = ‘Colitis 
excl infective’. 
14.9.7 
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 1 
hypersensitivity reaction or at least 1 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 1 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 1 anaphylactic reaction 
Following these three overall incidence rows, all TEAEs that have been identified as either a 
hypersensitivity reaction or an anaphylactic reaction will be summarized by SOC, HLT and PT 
(these will not be presented by subcategory). 
Hypersensitivity reactions and anaphylactic reactions will be identified as follows: 
 Hypersensitivity reactions: all TEAEs with onset (start date/time) within 24 hours after any 
administration of IMP, which code to a PT which contains the term ‘hypersensitivity’ will be 
considered 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 IMP, and 
which fulfill any of the 3 criteria described in Section 14.9.7.1 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. 
14.9.7.1 
Anaphylactic reaction algorithm 
The SMQ = ‘anaphylactic reaction’ consists of 3 parts: 
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 A narrow search containing PTs that represent core anaphylactic reaction terms. If a subject 
reports any TEAE which codes to a PT included in Category A, then the event will be 
flagged as an anaphylactic reaction and summarized as such in the table 
 Category A 
1. Anaphylactic reaction 
2. Anaphylactic shock 
3. Anaphylactic transfusion reaction 
4. Anaphylactoid reaction 
5. Anaphylactoid shock 
6. Circulatory collapse 
7. Dialysis membrane reaction 
8. Kounis syndrome 
9. Shock 
10. Shock symptom 
11. Type I hypersensitivity 
A broad search: If a subject reports any TEAE which codes to a PT included in Category B 
AND reports any TEAE which codes to a PT included in Category C, and both TEAEs have 
the same start date, then both events will be flagged as anaphylactic reactions and summarized 
as such in the table 
 Category B 
1. Acute respiratory failure 
2. Asthma 
3. Bronchial oedema 
4. Bronchospasm 
5. Cardio respiratory distress 
6. Chest discomfort 
7. Choking 
8. Choking sensation 
9. Circumoral oedema 
10. Cough 
11. Cyanosis 
12. Dyspnoea 
13. Hyperventilation 
14. Irregular breathing 
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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 
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 
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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 
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 
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 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 
14.9.8 
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 11.3 (with adjudication for PDILI cases) 
14.10 
Treatment group assignment for the TFLs 
The treatment group labels and tabulation requirements for each data type are displayed in 
Table 14‒11. 
Table 14‒11: 
Treatment group assignment for the TFLs 
TFL group 
Placebo 
Adalimumab 
Bimekizumab 
All Subjects 
Subject disposition 
X 
X 
X 
X 
Protocol deviations 
X 
X 
X 
X 
Demographics 
X 
X 
X 
X 
HS history and Baseline 
characteristics 
X 
X 
X 
X 
Medical history 
X 
X 
X 
X 
Prior/concomitant 
medications 
X 
X 
X 
X 
AEs 
X 
X 
X 
 
Safety data (including vital 
signs, ECG and laboratory 
tests) 
X 
X 
X 
 
Pharmacodynamic data 
X 
X 
X 
 
Efficacy data 
X 
X 
X 
 
Pharmacokinetic data 
 
 
X 
 
Anti-BKZ antibody 
 
 
X 
 
AEs=adverse events; ECG=electrocardiogram. 
 
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15 
AMENDMENTS TO THE SAP 
15.1.1 
Rationale for the amendment 
Various updates were suggested prior to and during the interim analysis in late 2018. 
15.1.2 
List of changes 
Change #1 
List of Abbreviations 
The following abbreviations have been added: 
mHiSCR25 
modified Hidradenitis Suppurativa Clinical Response – 25% 
mHiSCR75 
modified Hidradenitis Suppurativa Clinical Response – 75% 
mHiSCR90 
modified Hidradenitis Suppurativa Clinical Response – 90% 
PDILI 
potential drug-induced liver injury 
PoC 
proof of concept 
Change #2 
Introduction (Section 1), 2nd and 3rd paragraphs 
This SAP is based on, and assumes familiarity, with the following documents: 
 Protocol Amendment 1, dated 08 March 2018 
 Primary Analysis Document, dated 19 September 2017 
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 IA SAP will be amended accordingly. In addition, if 
analysis definitions have to be modified or updated prior to the cut-off for IA, an IA SAP 
amendment will be required. However, if any additional analyses are required to supplement the 
planned analyses after the cut-off, these analyses will be described in a separate analysis plan. 
Has been changed to: 
This SAP is based on, and assumes familiarity, with the following documents: 
 Final protocol amendment 1, dated 08 March 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 must be modified or updated prior to database lock, a further 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. 
Change #3 
Determination of sample size (Section 2.4), 2nd paragraph 
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Additionally, the study has an exploratory objective to informally compare BKZ against the 
current standard of care for HS (ADA) using the 60% credible interval for the treatment 
difference. 
Has been changed to: 
Additionally, the study has an exploratory objective to informally compare bimekizumab against 
the current standard of care for HS (adalimumab) using the 60% credible interval for the 
treatment difference. 
Change #4 
Determination of sample size (Section 2.4), 5th paragraph 
These simulations were based on Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the PBO and ADA treatment arms in 
the current study. Based on historic data, the Bayesian model assumes an informative prior 
distribution for the PBO group HiSCR rate to be β (5.52,14.48). This prior distribution 
contributes an approximate effective sample size of 20 subjects for the PBO treatment group. 
Similarly, the Bayesian model assumes an informative prior distribution for the ADA group 
HiSCR rate to be β (11.78, 8.22), which, with the parametrization in the model, is equivalent to 
an ADA response rate of 58.9%.  This prior distribution contributes an approximate effective 
sample size of 20 subjects for the ADA group. For the BKZ HiSCR rate, a vague prior 
probability distribution N (0,1E4) was assumed. 
Has been changed to: 
These simulations were based on Bayesian augmented control models in which the published 
summary data were used to construct informative priors for the placebo and adalimumab 
treatment arms in the current study. Based on historic data, the Bayesian model assumes an 
informative prior distribution for the placebo group HiSCR rate to be β (5.52,14.48). This prior 
distribution contributes an approximate effective sample size of 20 subjects for the placebo 
treatment group. Similarly, the Bayesian model assumes an informative prior distribution for the 
adalimumab group HiSCR rate to be β (11.78, 8.22) which, with the parametrization in the 
model, is equivalent to an adalimumab response rate of 58.9%.  This prior distribution 
contributes an approximate effective sample size of 20 subjects for the adalimumab group. For 
the bimekizumab HiSCR rate, a vague prior probability distribution N (0,1E4) was assumed. 
Change #5 
Protocol Deviations (Section 3.4), 3rd paragraph 
At least 3 data evaluation meetings (DEMs) will be performed for this study at the following 
time points: 
 Prior to the formal unblinded interim analysis planned after approximately 45 subjects have 
completed 4 weeks of the study.  
 Prior to the informal unblinded interim analysis planned after the last subject has completed 
12 weeks of the study or has discontinued early. 
 Prior to the final analysis after all subjects have completed the SFU period and data have 
been verified/coded/entered into the database 
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Has been changed to: 
At least 3 data evaluation meetings (DEMs) will be performed for this study at the following 
time points: 
 Prior to the informal unblinded interim analysis planned after approximately 45 subjects have 
completed 4 weeks of the study.  
 Prior to the informal unblinded interim analysis planned after the last subject (excluding 2 
subjects from site 101 in Australia who entered the study outside of the original planned 
recruitment period) has completed 12 weeks of the study or has discontinued early. 
 Prior to the final analysis after all subjects have completed the SFU period and data have 
been verified/coded/entered into the database 
Change #6 
Changes to protocol-defined analyses (Section 3.9) 
This final bullet has been added:- 
 Based on the second interim analysis for this study, additional exploratory efficacy variables 
based on the lesion count assessment data, HiSCR depth and disease flare status, have been 
defined in this SAP amendment.  Section 8 2.4 includes details on the derivation of different 
HiSCR depths and Section 8.2.5 describes the planned summaries of this additional variable.  
Section 8.3.1.2 defines disease flare and includes details on planned summaries of disease 
flare status and the number of visits at which a subject experienced a disease flare during the 
Treatment Period. 
Change #7 
Dates (Section 4.2.4) 
This final paragraph has been added:- 
Partially missing dates will be imputed as described above and the duration of each AE will be 
calculated in days as follows: 
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝐴𝐸 = (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑂𝑢𝑡𝑐𝑜𝑚𝑒 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑂𝑛𝑠𝑒𝑡 ) +  1 
Change #8 
Calculation rules for duration of adverse events (Table 4-1) 
This table has been removed. 
Change #9 
Interim analysis (Section 4.5.2) 
A formal unblinded non-binding interim analysis will be conducted when approximately 45 
subjects have completed 4 weeks of the study. During this interim analysis, the sample size 
assumptions will be checked and the final sample size may be modified if the sample size 
assumptions at study planning are no longer accurate. Also, at this interim analysis, the study 
may be stopped for futility. Sample size re-estimation criteria and methods along with futility 
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rules and operating characteristics will be detailed in the Interim Analysis SAP. The futility rule 
will be chosen such that the overall power of the study remains high. 
An informal, unblinded interim analysis will be performed when the last randomized subject for 
this study has completed the Week 12 Visit at the end of the Treatment Period or this subject’s 
participation has ended prematurely. The purpose of this informal interim analysis is for the 
Sponsor key personnel to review the results of the primary efficacy analysis and safety outcomes 
to facilitate additional Clinical Planning or Portfolio Management decisions. Details on the 
summaries and analyses to be presented at this informal interim analysis will be included in the 
Interim Analysis SAP. 
All analyses and unblinding instructions will be pre-specified in the Interim Analysis SAP  
Has been changed to: 
This study will include two informal unblinded interim analyses, the first after approximately 45 
subjects have completed 4 weeks of the study and the second when the last randomized subject 
for this study has completed the Week 12 Visit at the end of the Treatment Period or this 
subject’s participation has ended prematurely. This second planned interim analysis excludes the 
2 subjects from site 101 who entered the study outside of the recruitment period. The purpose of 
these interim analyses is for sponsor key personnel to review results from the primary efficacy 
analysis and a subset of the analyses of exploratory efficacy and safety outcomes to facilitate 
additional Clinical Planning or Portfolio Management decisions.  Neither interim analysis will 
lead to any formal decision to alter or terminate the trial.  
Details on the summaries and analyses to be presented at these informal interim analyses are 
included in the Interim Analysis SAP. 
All analyses and unblinding instructions will be pre-specified in the Interim Analysis SAP. 
Change #10 
Hidradenitis suppurativa history (Section 6.5) 
Detailed information of each subject’s HS history will be collected at Screening and will include, 
but will not be limited to, the following: 
 Date of Initial Diagnosis of HS 
 Date HS Symptoms First Started 
 The date, onset, and duration of past treatments for HS 
 The date of any prior surgeries for HS 
The HS history will be listed based on the RS. 
Has been changed to: 
Date of initial diagnosis of HS and the date that HS symptoms first started will be listed. 
Change #11 
Prior and concomitant medications (Section 6.6), 3rd and 4th paragraphs 
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Separate summaries will be presented for the following, identified using WHODD Anatomical 
Main Group codes, the indication recorded on the eCRF and medical review of the recorded 
data:   
 Prior and concomitant HS medications 
 Concomitant antibiotic medications at study entry 
 Rescue therapy medication during study 
All HS medications will be confirmed at the DEMs prior to unblinding. 
Has been changed to: 
Separate summaries will be presented for the following, identified using WHODD Anatomical 
Main Group codes, the indication recorded on the eCRF and medical review of the recorded 
data:   
 Prior and concomitant HS medications 
 Concomitant antibiotic medications at study entry 
 Rescue medication during study 
All HS medications, antibiotics and rescue medication given during the study will be identified 
via medical review of the concomitant medications and confirmed at the DEMs prior to 
unblinding. 
Concomitant antibiotic medication at study entry is defined as any antibiotic that was ongoing or 
started on the Screening visit. 
Change #12 
Bayesian Modelling (Section 8.2.2.1), 9th paragraph 
To protect against severe forms of study to study variation and/or miss-matches between 
Baseline Hurley Stage subject proportions and effect sizes, a prior data conflict test will be 
conducted using the above priors as detailed in Section 8.2.2.3 and vague priors for the PBO and 
ADA treatment groups will be used if either of the two null hypotheses of no prior data conflict 
are rejected at the 95% confidence level. The prior data conflict test also provides some 
protection against model miss-specification – for example if there turns out to be a Baseline 
Hurley Stage by treatment group interaction as the PIONEER II data suggest. 
Has been changed to: 
To protect against severe forms of study to study variation and/or mismatches between Baseline 
Hurley Stage subject proportions and effect sizes, prior data conflict will be investigated for all 
informative priors through use of graphical displays.  If there is evidence of prior data conflict 
for a given parameter, then a vague prior will be used for that parameter. Investigating any prior 
data conflict also provides some protection against model misspecification – for example if there 
turns out to be a Baseline Hurley Stage by treatment group interaction as the PIONEER II data 
suggest. 
Change #13 
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Building the Prior (S8.2.2.2), final paragraph 
If further information (independent to this study) regarding the PBO group response comes to 
light then the priors for this analysis may be updated prior to study unblinding, and details of this 
will be supplied in an amendment to this SAP or the CSR. In this case the priors will still be 
based upon historic data only. 
Has been changed to: 
If further information (independent to this study) regarding the PBO and/or ADA treatment 
group response rates comes to light then the priors for this analysis may be updated prior to study 
unblinding, and details of this will be supplied in an amendment to this SAP or the CSR. In this 
case the priors will still be based upon historic data only. 
Note that the informative priors for the PBO and ADA treatment group response rates may be 
updated based upon any observed differences in the proportions of Baseline Hurley Stage II and 
III subjects as long as no response rate data from the current study, blinded or unblinded, are 
taken into consideration. For example, if updated, these priors may be fitted by Baseline Hurley 
Stage if the relative proportions of Baseline Hurley Stage II and III subjects within the current 
study differ substantially from those reported in the h storical data. In this case the priors will 
still be based only on historic response data, but using the Hurley-stage specific information 
rather than the average information. 
Change #14 
Prior data conflict (Section 8.2.2.3) 
For each of the PBO and ADA groups separately, the prior data conflict test will consist of 
comparing the observed minimal sufficient statistic for the Binomial distribution (the number of 
HS events) to the prior predictive distribution of this minimal sufficient statistic. 
Has been changed to: 
Prior data conflict will be investigated for all informative priors through use of graphical 
displays.  If there is evidence of prior data conflict for a given parameter, then a vague prior will 
be used for that parameter. 
Change #15 
Supportive and sensitivity analyses of the primary efficacy variable (Section 8.2.3), 1st 
paragraph 
The primary efficacy analysis set is the PPS, however the primary analysis and all supportive and 
sensitivity analyses of the primary efficacy variable will be repeated using the FAS.  
Additionally, the comparison of the BKZ treatment group to the ADA treatment group is 
reported under the following sections. 
Has been changed to: 
The primary efficacy analysis set is the PPS, however the primary analysis and all supportive and 
sensitivity analyses of the primary efficacy variable will be repeated using the FAS.   
The comparison of the BKZ treatment group to the ADA treatment group is described 
specifically in this section as a sensitivity analysis, however, it must be noted that the results 
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from the BKZ versus ADA comparison will be presented for completeness in each of the 
sensitivity analyses described in Section 8.2.3.1 to 8.2.3.10 below. 
Change #16 
Comparison of bimekizumab and adalimumab (Section 8.2.3.2) 
In addition to the primary comparison of the BKZ and PBO treatment groups, the comparison 
between BKZ and ADA in HiSCR at Week 12 will be performed using the methods as described 
above in Section 8.2.2.4 for the primary efficacy analysis. This will be an informal comparison to 
assess whether any improvements in response rate observed with BKZ (over PBO) are 
comparable to the current standard of care (ADA). 
Has been changed to: 
In addition to the primary comparison of the BKZ and PBO treatment groups, the comparison 
between BKZ and ADA in HiSCR at Week 12 will be performed using the methods as described 
above in Section 8.2.2.4 for the primary efficacy analysis.  A 60% credible interval will be 
presented for the BKZ versus ADA comparison.  This will be an informal comparison to assess 
whether any improvements in response rate observed with BKZ (over PBO) are comparable to 
the current standard of care (ADA); it will not be part of the evaluation of PoC for this study. 
Change #17 
Frequentist analysis – NRI (Section 8.2.3.7), 1st paragraph 
An estimate of the treatment difference (BKZ versus PBO) at Week 12 will be obtained from a 
longitudinal generalized estimating equation (GEE) model for a binary outcome, controlling for 
Baseline Hurley Stage and including treatment, visit and a treatment by visit (week) interaction 
term. An unstructured covariance matrix will be used for this analysis. In the event that the 
model does not converge, alternate covariance structures will be considered. 
Has been changed to: 
An estimate of the treatment differences (BKZ versus PBO and BKZ versus ADA) at Week 12 
will be obtained from a longitudinal generalized estimating equation (GEE) model for a binary 
outcome, controlling for Baseline Hurley Stage and including treatment, visit and a treatment by 
visit (week) interaction term. An unstructured covariance matrix will be used for this analysis. In 
the event that the model does not converge, alternate covariance structures will be considered. 
Change #18 
Concomitant antibiotic use – Frequentist analysis (Section 8.2.3.9), 1st paragraph 
An estimate of the treatment difference (BKZ versus PBO) at Week 12 will be obtained from a 
longitudinal GEE model for a binary outcome, controlling for Baseline Hurley Stage and 
including concomitant antibiotic use at study entry (coded as a binary [yes/no] variable), 
treatment, visit, treatment by visit (week) interaction term and antibiotic use by Baseline Hurley 
Stage interaction terms. Missing response data will not be handled using NRI (ie, observed cases 
analysis).  
Has been changed to: 
An estimate of the treatment differences (BKZ versus PBO and BKZ versus ADA) at Week 12 
will be obtained from a longitudinal GEE model for a binary outcome, controlling for Baseline 
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Hurley Stage and including concomitant antibiotic use at study entry (coded as a binary [yes/no] 
variable), treatment, visit, treatment by visit (week) interaction term and antibiotic use by 
Baseline Hurley Stage interaction terms. Missing response data will not be handled using NRI 
(ie, observed cases analysis).  
Change #19 
HiSCR depth (Section 8.2.4) 
This section has been added: 
As an additional exploratory analysis of HiSCR, the algorithm applied to derive response at each 
visit (as described in Section 8.2.1) will be adapted to evaluate varying depths of HiSCR during 
the Treatment Period.  A modified HiSCR will be calculated using different criteria for %ΔAN, 
namely 25%, 75% and 90%, in order to derive a response at each visit.  In the summaries of 
HiSCR depth, the primary efficacy variable will be referred to as HiSCR and the other depth 
variables referred to as modified (m)HiSCR25, mHiSCR75 and mHiSCR90. 
Change #20 
Presentation of HiSCR (Section 8.2.5) 
The HiSCR will be listed together with the component efficacy data as specified in Section 8.3.1. 
The number and percentage of subjects who achieved HiSCR will be tabulated by treatment 
group and visit, based on the PPS. A summary will also be presented by Baseline Hurley Stage. 
All summaries will include the 95% CI for the percentage of subjects with an HiSCR, calculated 
using a Wilson approximation. The summary will be presented based on NRI and repeated for 
observed cases. For the observed cases analysis, the denominator for the percentage calculations 
will be the number of subjects with non-missing HiSCR data in the PPS for each treatment 
group, visit and Baseline Hurley Stage (as applicable).  
All tabulations described in this section will be repeated for the FAS. For the observed cases 
analysis, the denominator for the percentage calculations will be the number of subjects in the 
FAS for each treatment group, visit and Baseline Hurley Stage (as applicable) with non-missing 
HiSCR data.  Listings will be presented for the SS. 
A figure will be presented showing the percentage of subjects who achieved HiSCR, together 
with 95% CIs, over time  All treatment groups will be overlaid on the same plot. The plot will be 
generated based on the PPS and the FAS. 
Additionally, the following bar charts will be presented showing the percentage of subjects who 
achieved HiSCR at Week 12: 
 by treatment group and Baseline Hurley Stage 
 by treatment group, Baseline Hurley Stage and antibiotic use at study entry 
 by treatment group, Baseline Hurley Stage and rescue therapy use at any time during the 
study 
Has been changed to: 
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HiSCR will be listed together with the component efficacy data as specified in Section 8.3.1.  
This listing will include the different HiSCR depth variables (i.e. mHiSCR25, HiSCR, 
mHiSCR75 and mHiSCR90). 
The number and percentage of subjects who achieved HiSCR will be tabulated overall by 
treatment group and visit, and also by Baseline Hurley Stage and by concomitant antibiotic use at 
study entry; and also by Baseline Hurley Stage and rescue medication use at any time during the 
study. This summary will be presented for the PPS and will include the 95% CI for the 
percentage of subjects with an HiSCR, calculated using a Wilson approximation. The summary 
will be presented based on NRI and repeated for observed cases. For the observed cases analysis, 
the denominator for the percentage calculations will be the number of subjects with non-missing 
HiSCR data in the PPS for each treatment group, visit and Baseline Hurley Stage or concomitant 
antibiotic use at study entry (as applicable).  
The number and percentage of subjects who achieved mHiSCR25, mHiSCR75 and mHiSCR90, 
together with 95% confidence intervals, will be presented overall and by Baseline Hurley Stage, 
and by treatment group and visit based on observed cases for the PPS  
All tabulations described in this section will be repeated for the FAS. For the observed cases 
analysis, the denominator for the percentage calculations will be the number of subjects in the 
FAS for each treatment group, visit and Baseline Hurley Stage or concomitant antibiotic use at 
study entry (as applicable) with non-missing HiSCR data.  Listings will be presented for the SS. 
A figure will be presented showing the percentage of subjects who achieved HiSCR, together 
with 95% CIs (calculated using a Wilson approximation), over time. All treatment groups will be 
overlaid on the same plot. The plot will be generated based on NRI and observed cases for the 
PPS and the FAS.  These plots will be repeated for the percentage of subjects who achieved the 
different HiSCR depths; mHiSCR25, mHiSCR75 and mHiSCR90. 
Additionally, for the PPS and FAS, based on NRI and observed cases,  the following bar charts 
will be presented showing the percentage of subjects who achieved HiSCR during the Treatment 
Period:  
 by treatment group and visit 
 by treatment group, visit and Baseline Hurley Stage 
 by treatment group and Baseline Hurley Stage at Week 12 
 by treatment group, Baseline Hurley Stage and concomitant antibiotic use at study entry, at 
Week 12 
 by treatment group, Baseline Hurley Stage and rescue medication use at any time during the 
study, at Week 12 
In addition to the above bar charts, a stacked bar chart displaying whether the criteria are met 
(yes/no) for each of the component data used in the calculation of HiSCR (%ΔAN, abscess count 
and draining tunnel [fistula/sinus tract] count) will be generated by treatment group and visit for 
the PPS and FAS.  This graph will summarize the proportion of subjects in each of the 8 
different yes/no binary responses at each visit (2 x 2 x 2 response combination) at each visit. 
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The following bar charts will be presented for the different HiSCR depths based on observed 
cases for the PPS and FAS: 
 by treatment group and visit 
 by treatment group, visit and Baseline Hurley Stage 
Change #21 
Lesion Count Data (Section 8.3.1) 
Lesion count data will be listed by treatment group and anatomical region and will show 
region-specific Hurley Stage and worst overall Hurley Stage for each subject and visit  The total 
count for each type of lesion, across all anatomical regions at each visit will be listed separately. 
For the total abscess count and total draining tunnel (fistula/sinus tract) count, the change from 
Baseline will be listed; for the AN count, the percentage change from Baseline will be listed. 
For each anatomical region, the longest distance between 2 relevant lesions (or the diameter of 
the single lesion if applicable) will be presented, and whether the specified regions were 
separated by normal skin. 
Total lesion counts (ie, the total across all anatomical regions) will be summarized by lesion 
type, treatment group, overall and by Baseline Hurley Stage  The following lesion types will be 
summarized: 
 Abscesses 
 Inflammatory nodules 
 Abscesses + inflammatory nodules (AN) 
 Draining tunnels (fistulas/sinus tracts)  
 Non-draining tunnels (fistulas/sinus tracts)  
 Non-inflammatory nodules  
 Hypertrophic scars  
Summaries will also be presented for the change from Baseline in the total abscess count and 
total draining tunnel (fistula/sinus tract) count, and for the percentage change from Baseline in 
the AN count.  
The number and percentage of subjects with an AN count of 0, 1, or 2 at Week 12 will be 
presented by treatment group, overall and by Baseline Hurley Stage. The denominator for the 
percentage calculations will be the number of subjects in each treatment group in the FAS with 
non-missing data and, in the summary by Baseline Hurley Stage, percentages will be calculated 
based on the number of subjects in each treatment group and each level of Baseline Hurley 
Stage.   
Has been changed to: 
Lesion count data will be listed by treatment group and anatomical region and will show 
region-specific Hurley Stage and worst overall Hurley Stage for each subject and visit. The total 
count for each type of lesion, across all anatomical regions at each visit will be listed separately. 
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For the total abscess count and total draining tunnel (fistula/sinus tract) count, the change from 
Baseline will be listed; for the AN count, the percentage change from Baseline will be listed. 
For each anatomical region, the longest distance between 2 relevant lesions (or the diameter of 
the single lesion if applicable) will be presented, and whether the specified regions were 
separated by normal skin. 
At each visit, lesion counts will be summarized by anatomical region and lesion type.  The 
following lesion types will be summarized: 
 Abscesses 
 Inflammatory nodules 
 Abscesses + inflammatory nodules (AN) 
 Draining tunnels (fistulas/sinus tracts)  
 Non-draining tunnels (fistulas/sinus tracts)  
 Non-inflammatory nodules  
 Hypertrophic scars  
Total lesion counts (ie, the total across all anatomical regions) will be summarized by visit and 
lesion type, treatment group, overall and by Baseline Hurley Stage. Summaries will also be 
presented for the change and percentage change from Baseline in lesion counts by anatomical 
region and total lesion counts by lesion type.  
Change #22 
AN count (Section 8.3.1.1) 
This section has been added: 
The number and percentage of subjects with an AN count of 0, 1, or 2 at Week 12 will be 
presented by treatment group, overall and by Baseline Hurley Stage. The denominator for the 
percentage calculations will be the number of subjects in each treatment group in the FAS with 
non-missing data and, in the summary by Baseline Hurley Stage, percentages will be calculated 
based on the number of subjects in each treatment group and each level of Baseline Hurley 
Stage.   
In addition, the following plots of AN count and %ΔAN over time will be generated for the PPS 
and FAS: 
 A violin plot of AN count (with box plot inlay) by treatment group and visit 
 Box plot of %ΔAN by treatment group and visit 
 Jitter plot of Baseline AN count by treatment group and country 
 Jitter plot of Baseline AN count by treatment group and site 
Change #23 
Disease flare (Section 8.3.1.2) 
This section has been added: 
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Disease flare is defined when at least a 25% increase in AN count with a minimum increase of 2 
AN relative to Baseline is observed.  A subject’s disease flare status (yes/no) will be determined 
at each visit using these criteria and will listed with the other lesion count assessment data in the 
data listings. 
Disease flare status will be summarized by treatment group and visit using frequencies and 
percentages.  The denominator for the percentage calculations will be the number of subjects 
with non-missing data in each treatment group.  The number and percentage of subjects who 
experienced a disease flare at any time during the Treatment Period will also be presented. 
A bar chart showing the percentage of subjects with disease flare will be presented by treatment 
group and visit.  A bar chart summarizing the percentage of subjects who experienced a disease 
flare at any time during the Treatment Period will also be presented by treatment group. 
In addition, for each subject, the number of visits at which a disease flare was observed during 
the Treatment Period will be calculated and summarized by treatment group.  Summary statistics 
will be presented together with a box plot showing the distribution of these data and a histogram 
summarizing the number of subjects who experienced 0, 1, 2, 3, 4, 5 and 6 visits during the 
Treatment Period with a disease flare status of ‘yes’. 
All summaries of disease flare status will be presented for the FAS  
Change #24 
Definition of TEMA values for chemistry (Table 14‒8) 
This row has been added:- 
Variable (SI units) 
 
Source 
Markedly abnormal definition 
Low Grade 4 
Low Grade 3 
High Grade 
3 
High Grade 
4 
Glucose (mmol/L) 
RCTC 
<1 67 
1.67 to <2.22 
>13.89 to 
27.78 
>27.78 
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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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