Clinical trial NCT03355573
Conditions: Ankylosing Spondylitis
Keywords: Bimekizumab Ankylosing Spondylitis AS
Sponsor: UCB Biopharma SRL
Start date: 2017-11-28; Completion date: 2022-10-19
Enrollment: 255 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a study to assess the long term safety and tolerability of bimekizumab in subjects with ankylosing spondylitis

Detailed description:

Arms: arm 1: Subjects will receive bimekizumab up to 4 years.
Interventions: intervention 1: Bimekizumab
Intervention descriptions: intervention 1: Bimekizumab at a prespecified dose.

Protocol documents:
Prot_000.pdf: 
UCB 
 
06 Feb 2020 
Clinical Study Protocol 
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AS0009 
 
 
 
Confidential 
Page 1 of 119 
PROTOCOL AS0009 AMENDMENT 3 
A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO 
EVALUATE THE LONG TERM SAFETY AND EFFICACY OF 
BIMEKIZUMAB IN SUBJECTS WITH ANKYLOSING 
SPONDYLITIS 
PHASE 2B 
EudraCT Number: 2017-001002-15 
IND Number: 128708 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
 
 
Protocol/Amendment number 
Date 
Type of amendment 
Final protocol 
15 May 2017 
Not applicable 
Protocol amendment 1 
17 July 2017 
Not applicable 
Protocol amendment 2 
21 March 2018 
Substantial 
Protocol amendment 2.1 Czech Republic 
08 Jun 2018 
Substantial 
Protocol amendment 3 
06 Feb 2020 
Non-substantial  
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
 
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STUDY CONTACT INFORMATION 
Sponsor 
UCB BIOPHARMA SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Sponsor Study Physician 
Name: 
 MD, FNWC 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Straße 10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
Clinical Project Manager 
Name: 
 
Address: 
UCB Pharma Ltd. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM  
Phone: 
 
Clinical Trial Biostatistician 
Name: 
, MSc 
Address: 
UCB Pharma Ltd. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
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Clinical Monitoring Contract Research Organization (CRO) 
Name: 
PRA Health Sciences 
Address: 
4130 Park Lake Avenue, Suite 400 
Raleigh, NC 27612 
UNITED STATES 
Phone: 
+1 919 786 8200 
Fax: 
+1 919 786 8201 
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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06 Feb 2020 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 9 
1 
SUMMARY ..................................................................................................................... 13 
2 
INTRODUCTION ........................................................................................................... 13 
2.1 
Axial spondyloarthritis................................................................................................. 13 
2.1.1 
Clinical studies ..................................................................................................... 15 
2.1.1.1 
Completed studies ..................................................................................... 15 
2.1.1.2 
Ongoing studies ......................................................................................... 15 
2.1.2 
Nonclinical studies ............................................................................................... 15 
3 
STUDY OBJECTIVES .................................................................................................... 16 
3.1 
Primary objective ......................................................................................................... 16 
3.2 
Secondary objectives ................................................................................................... 16 
3.3 
Other objectives ........................................................................................................... 16 
4 
STUDY VARIABLES ..................................................................................................... 16 
4.1 
Primary variables ......................................................................................................... 16 
4.1.1 
Primary safety variables ...................................................................................... 16 
4.2 
Secondary variables ..................................................................................................... 16 
4.2.1 
Secondary safety variable .................................................................................... 16 
4.2.2 
Secondary efficacy variables ............................................................................... 17 
4.3 
Other variables ............................................................................................................. 17 
4.3.1 
Safety variables .................................................................................................... 17 
4.3.2 
Efficacy variables ................................................................................................ 17 
4.3.3 
PK variable .......................................................................................................... 18 
4.3.4 
Immunological variable ....................................................................................... 18 
5 
STUDY DESIGN ............................................................................................................. 18 
5.1 
Study description ......................................................................................................... 18 
5.1.1 
Rescue therapy ..................................................................................................... 18 
5.1.2 
Study duration per subject ................................................................................... 19 
5.1.3 
Planned number of subjects and sites .................................................................. 19 
5.1.4 
Anticipated regions and countries ....................................................................... 19 
5.2 
Schedule of study assessments..................................................................................... 19 
5.3 
Schematic diagram ....................................................................................................... 26 
5.4 
Rationale for study design and selection of dose ......................................................... 26 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................................... 27 
6.1 
Inclusion criteria .......................................................................................................... 27 
6.2 
Exclusion criteria ......................................................................................................... 28 
6.3 
Withdrawal criteria ...................................................................................................... 28 
6.3.1 
Potential drug-induced liver injury IMP discontinuation criteria ........................ 30 
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7 
STUDY TREATMENT(S) .............................................................................................. 30 
7.1 
Description of investigational medicinal product ........................................................ 30 
7.2 
Treatment(s) to be administered .................................................................................. 31 
7.3 
Packaging ..................................................................................................................... 31 
7.4 
Labeling ....................................................................................................................... 32 
7.5 
Handling and storage requirements ............................................................................. 32 
7.6 
Drug accountability ...................................................................................................... 32 
7.7 
Procedures for monitoring subject compliance ............................................................ 33 
7.8 
Concomitant medications/treatments ........................................................................... 33 
7.8.1 
Permitted concomitant treatments (medications and therapies) .......................... 34 
7.8.2 
Prohibited concomitant treatments (medications and therapies) ......................... 35 
7.9 
Blinding........................................................................................................................ 35 
7.10 
Randomization and numbering of subjects .................................................................. 36 
8 
STUDY PROCEDURES BY VISIT ............................................................................... 36 
8.1 
AS0009 study entry (Visit 1) ....................................................................................... 36 
8.2 
Week 4 (Visit 2) and Week 8 (Visit 3) ........................................................................ 37 
8.3 
Week 12 (Visit 4), Week 24 (Visit 5), Week 36 (Visit 6), Week 72 (Visit 9) ............ 38 
8.4 
Week 16, Week 20, Week 28, Week 32, Week 40, Week 44, Week 52, Week 56, 
Week 64, Week 68, Week 76, Week 80, Week 88, Week 92, Week 100, and Week 
104................................................................................................................................ 38 
8.5 
Week 48 (Visit 7) and Week 96 (Visit 11) .................................................................. 39 
8.6 
Week 60 (Visit 8) and Week 84 (Visit 10) .................................................................. 40 
8.7 
Week 108 (Visit 12), Week 132 (Visit 14), and Week 180 (Visit 18) ........................ 40 
8.8 
Week 112, Week 116, Week 124, Week 128, Week 136, Week 140, Week 148, Week 
152, Week 160, Week 164, Week 172, Week 176, Week 184, Week 188, Week 196, 
and Week 200 .............................................................................................................. 41 
8.9 
Week 120 (Visit 13) and Week 168 (Visit 17) ............................................................ 41 
8.10 
Week 144 (Visit 15) and Week 192 (Visit 19) ............................................................ 42 
8.11 
Week 156 (Visit 16) ..................................................................................................... 43 
8.12 
Week 204 (Visit 20) ..................................................................................................... 43 
8.13 
Week 208 (Visit 21)/Early Termination Visit ............................................................. 44 
8.14 
SFU Visit ..................................................................................................................... 45 
8.15 
Unscheduled Visit ........................................................................................................ 45 
9 
ASSESSMENT OF SAFETY .......................................................................................... 46 
9.1 
Adverse events ............................................................................................................. 46 
9.1.1 
Definition of AE .................................................................................................. 46 
9.1.2 
AEs of special interest ......................................................................................... 47 
9.1.3 
Other safety topics of interest .............................................................................. 47 
9.1.4 
Procedures for reporting and recording AEs ....................................................... 47 
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9.1.5 
Description of AEs .............................................................................................. 47 
9.1.6 
Follow-up of AEs ................................................................................................ 48 
9.1.7 
Rule for repetition of an AE ................................................................................ 48 
9.1.8 
Pregnancy ............................................................................................................ 48 
9.1.9 
Suspected transmission of an infectious agent via a medicinal product .............. 49 
9.1.10 
Overdose of investigational medicinal product ................................................... 49 
9.1.11 
Safety signal detection ......................................................................................... 49 
9.1.12 
Definition of SAEs .............................................................................................. 50 
9.1.13 
Procedures for reporting serious adverse events ................................................. 51 
9.1.14 
Follow-up of SAEs .............................................................................................. 51 
9.2 
Immediate reporting of AEs......................................................................................... 51 
9.3 
Anticipated SAEs ......................................................................................................... 52 
9.4 
Laboratory measurements ............................................................................................ 53 
9.4.1 
Evaluation of PDILI ............................................................................................ 54 
9.4.1.1 
Consultation with Medical Monitor and local hepatologist ...................... 57 
9.4.1.2 
Immediate action: determination of IMP discontinuation ......................... 57 
9.4.1.3 
IMP restart/rechallenge ............................................................................. 57 
9.4.1.4 
Testing: identification/exclusion of alternative etiology ........................... 57 
9.4.1.5 
Follow-up evaluation ................................................................................. 59 
9.5 
Other safety measurements .......................................................................................... 59 
9.5.1 
Vital signs ............................................................................................................ 59 
9.5.2 
Body weight ......................................................................................................... 60 
9.5.3 
Physical examination ........................................................................................... 60 
9.5.4 
12-lead ECG ........................................................................................................ 60 
9.5.5 
Tuberculosis and TB risk factor assessment and management ........................... 60 
9.5.5.1 
Tuberculosis assessment by IGRA ............................................................ 61 
9.5.5.2 
Tuberculosis questionnaire ........................................................................ 61 
9.5.5.3 
Tuberculosis management ......................................................................... 61 
9.5.6 
Pregnancy testing ................................................................................................. 62 
9.5.7 
Assessment of suicidal ideation and behavior ..................................................... 62 
10 ASSESSMENT OF EFFICACY ...................................................................................... 63 
10.1 
ASAS20, ASAS40, ASAS 5/6 response and ASAS partial remission ........................ 63 
10.2 
ASDAS-CRP................................................................................................................ 63 
10.3 
BASDAI ....................................................................................................................... 64 
10.3.1 
 item of the BASDAI ............................................................................... 64 
10.4 
Function – BASFI ........................................................................................................ 64 
10.5 
BASMI ......................................................................................................................... 65 
10.6 
MASES ........................................................................................................................ 65 
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10.7 
PGADA ........................................................................................................................ 65 
10.8 
Total and nocturnal spinal pain .................................................................................... 65 
10.9 
Short-Form 36-item Health Survey ............................................................................. 65 
10.10 ASQoL ......................................................................................................................... 66 
10.11 HADS ........................................................................................................................... 66 
11 ASSESSMENT OF IMMUNOGENICITY ..................................................................... 66 
12 STUDY MANAGEMENT AND ADMINISTRATION ................................................. 66 
12.1 
Adherence to protocol .................................................................................................. 66 
12.2 
Monitoring ................................................................................................................... 66 
12.2.1 
Definition of source data ..................................................................................... 67 
12.2.2 
Source data verification ....................................................................................... 67 
12.3 
Data handling ............................................................................................................... 67 
12.3.1 
Case Report form completion .............................................................................. 67 
12.3.2 
Database entry and reconciliation ........................................................................ 68 
12.3.3 
Subject Screening and Enrollment log/Subject Identification Code list.............. 68 
12.4 
Termination of the study .............................................................................................. 68 
12.5 
Archiving and data retention ........................................................................................ 69 
12.6 
Audit and inspection .................................................................................................... 69 
12.7 
Good Clinical Practice ................................................................................................. 69 
13 STATISTICS ................................................................................................................... 69 
13.1 
Definition of analysis sets ............................................................................................ 69 
13.2 
General statistical considerations ................................................................................. 70 
13.3 
Planned safety analyses................................................................................................ 70 
13.3.1 
Safety analyses ..................................................................................................... 70 
13.4 
Planned efficacy analyses ............................................................................................ 70 
13.4.1 
Subgroup analysis ................................................................................................ 71 
13.5 
Planned immunogenicity analyses ............................................................................... 71 
13.6 
Other analyses .............................................................................................................. 71 
13.7 
Handling of protocol deviations................................................................................... 71 
13.8 
Handling of dropouts or missing data .......................................................................... 71 
13.9 
Planned interim analysis and data monitoring ............................................................. 72 
13.10 Determination of sample size ....................................................................................... 72 
14 ETHICS AND REGULATORY REQUIREMENTS ...................................................... 72 
14.1 
Informed consent ......................................................................................................... 72 
14.2 
Subject identification cards .......................................................................................... 73 
14.3 
Institutional Review Boards and Independent Ethics Committees .............................. 73 
14.4 
Subject privacy............................................................................................................. 73 
14.5 
Protocol amendments ................................................................................................... 74 
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15 FINANCE, INSURANCE, AND PUBLICATION ......................................................... 74 
16 REFERENCES ................................................................................................................ 74 
17 APPENDICES ................................................................................................................. 78 
17.1 
Markedly abnormal laboratory values ......................................................................... 78 
17.2 
Protocol Amendment 1 ................................................................................................ 79 
17.3 
Protocol Amendment 2 ................................................................................................ 83 
17.4 
Protocol Amendment 3 ................................................................................................ 99 
18 SPONSOR DECLARATION ........................................................................................ 119 
 
LIST OF TABLES 
Table 5‒1: 
Schedule of study assessments (Week 1 through Week 104) .......................... 20 
Table 5‒2: 
Schedule of study assessments (Week 108 through Week 208) ...................... 23 
Table 7‒1: 
Prohibited or restricted medications ................................................................ 35 
Table 9‒1: 
Anticipated SAEs for the population of subjects with AS ............................... 52 
Table 9-2: 
Laboratory measurements ................................................................................ 53 
Table 9-3: 
Required investigations and follow-up for PDILI ........................................... 55 
Table 9‒4: 
PDILI laboratory measurements ...................................................................... 58 
Table 9‒5: 
PDILI information to be collected ................................................................... 59 
Table 17-1 
Definitions of markedly abnormal hematology values .................................... 78 
Table 17‒2: 
Definitions of markedly abnormal biochemistry values .................................. 78 
 
LIST OF FIGURES 
Figure 5‒1: 
Schematic diagram ........................................................................................... 26 
 
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AS0009 
 
 
 
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LIST OF ABBREVIATIONS 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AS 
ankylosing spondylitis 
ASAS 
Assessment of SpondyloArthritis International Society 
ASAS20, 40, 5/6 
Assessment in Axial SpondyloArthritis International Society 20%, 
40%, 5 out of 6 response criteria 
ASDAS-CRP 
Ankylosing Spondylitis Disease Activity Score-C-reactive protein 
ASDAS-ID 
Ankylosing Spondylitis Disease Activity Score Inactive Disease 
ASQoL 
Ankylosing Spondylitis Quality of Life 
AST 
aspartate aminotransferase 
axSpA 
axial spondyloarthritis 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
BASMI 
Bath Ankylosing Spondylitis Metrology Index 
BP 
blood pressure 
CDMS 
clinical data management system 
CI 
confidence interval 
COX-2 
cyclooxygenase 2 
CPM 
Clinical Project Manager 
CPMP 
Committee for Proprietary Medicinal Products 
CRF 
Case Report form 
CRO 
contract research organization 
CRP 
C-reactive protein 
CZP 
certolizumab pegol 
DMARD 
disease-modifying antirheumatic drug 
DVU 
disco-vertebral units 
EAER 
exposure adjusted event rate 
EAIR 
exposure adjusted incidence rate 
ECG 
electrocardiogram 
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eCRF 
electronic Case Report form 
eC-SSRS 
electronic Columbia-Suicide Severity Rating Scale 
EDC 
electronic data capture 
ES 
Enrolled Set 
ET 
Early Termination 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HADS 
Hospital Anxiety and Depression Scale 
HADS-A 
Hospital Anxiety and Depression Scale-Anxiety 
HADS-D 
Hospital Anxiety and Depression Scale-Depression 
HCQ 
hydroxychloroquine 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
HS 
hidradenitis suppurativa 
IB 
Investigator’s Brochure 
IBD 
inflammatory bowel disease 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
IGRA 
Interferon-Gamma Release Assay 
IL17 
Interleukin-17 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
iv 
intravenous (ly) 
IXRS 
interactive voice or web response system  
LEF 
leflunomide 
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LTB 
latent tuberculosis 
MASES 
Maastricht Ankylosing Spondylitis Enthesitis Score 
MCID 
minimal clinically important difference 
MCMC 
Markov Chain Monte Carlo 
MedDRA® 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
MTX 
methotrexate 
nr-axSpA 
nonradiographic-axial spondyloarthritis 
NRI 
nonresponder imputation 
NRS 
Numeric Rating Scale 
NSAID 
nonsteroidal anti-inflammatory drug 
NTMB 
nontuberculous mycobacteria 
OLE 
open-label extension 
OMERACT 
Outcome Measures in Rheumatology Clinical Trials 
PD 
pharmacodynamics 
PDILI 
potential drug-induced liver injury 
PFS 
prefilled syringe 
PGADA 
Patient’s Global Assessment of Disease Activity 
PK 
pharmacokinetics 
PS 
Patient Safety 
PsA 
psoriatic arthritis 
PSO 
psoriasis 
Q4W 
every 4 weeks (monthly) 
RA 
rheumatoid arthritis 
RCTC 
Rheumatology Common Toxicity Criteria 
SAE 
serious adverse event 
sc 
subcutaneous(ly) 
SD 
standard deviation 
SF-36 
Short-Form 36-item Health Survey 
SFU 
Safety Follow-up 
SI 
sacroiliac 
SOP 
standard operating procedure 
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SpA 
spondyloarthritis 
SPARCC 
Spondyloarthritis Research Consortium of Canada 
SS 
Safety Set 
SSZ 
sulfasalazine 
STIR 
short-tau-inversion recovery 
TEAE 
treatment-emergent adverse event 
TB 
tuberculosis 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
VAS 
visual analog scale 
 
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1 
SUMMARY 
AS0009 is a multicenter, 208-week, open-label extension (OLE) study to evaluate the long-term 
safety, tolerability, and efficacy of bimekizumab for eligible subjects with ankylosing 
spondylitis (AS) who complete AS0008 (Phase 2b). 
AS0008 is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, 
parallel-group, dose-ranging study to evaluate the efficacy and safety of bimekizumab in subjects 
with active AS. At Week 48 of AS0008, all subjects continuing into AS0009 will undergo the 
final lead-in study assessments and any nonoverlapping AS0009 study entry assessments, and 
will then receive their first open-label dose of bimekizumab. 
In the AS0009 OLE study, bimekizumab will be administered at a dose of 160mg every 4 weeks 
(Q4W) subcutaneously (sc) for all subjects regardless of treatment received in AS0008. 
Up to 285 subjects from the ongoing AS0008 Phase 2b study could be enrolled into this study.  
The primary objective is to assess the long-term safety and tolerability of bimekizumab 
administered over a period of up to 204 weeks (~4 years). The primary safety variables are the 
incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). 
The secondary objective is to assess the long-term efficacy. The secondary efficacy variables 
include the Assessment of SpondyloArthritis International Society 40% response criteria 
(ASAS40) at Week 48, ASAS20 response at Week 48, and the change from Baseline of AS0008 
in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 48. The 
secondary safety variable is the withdrawal due to TEAEs. 
Other objectives are to assess impact on enthesitis and on patient-reported quality of life and to 
assess the plasma concentrations and immunogenicity of bimekizumab. 
The study duration for each subject is estimated to be up to a maximum of 224 weeks: an 
Open-Label Treatment Period of up to 204 weeks (~4 years), followed by a Safety Follow-up 
(SFU) Visit 20 weeks after the last dose of bimekizumab. 
2 
INTRODUCTION 
2.1 
Axial spondyloarthritis 
Spondyloarthritis (SpA) is an umbrella term applied to a family of rheumatic diseases (including 
axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], reactive arthritis, arthritis of 
inflammatory bowel disease [IBD], and undifferentiated spondyloarthritis) that have features in 
common with each other and distinct from other inflammatory arthritides, particularly 
rheumatoid arthritis (RA). 
Axial SpA is a chronic inflammatory disease that impacts a substantial proportion of the 
population. Limited evidence exists regarding the exact prevalence of axSpA; however, recent 
data suggest that the prevalence is similar to that of RA in the US (axSpA: 0.7% to 1.4%; 
RA: 0.5% to 1.0%) (Reveille et al, 2012; Myasoedova et al, 2010; Helmick et al, 2008).  
The Assessment of SpondyloArthritis International Society (ASAS) working group established 
classification criteria to distinguish 2 broad categories of SpA: peripheral SpA and axSpA 
(Rudwaleit et al, 2011; Rudwaleit, 2010; Rudwaleit et al, 2009b). This division is based on the 
body part predominantly involved in the inflammatory process. Therefore, peripheral SpA 
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includes diseases affecting mainly peripheral joints, such as reactive arthritis and PsA, whereas 
axSpA comprises those diseases with mainly axial involvement (SI joints and spine), including 
AS diagnosed with radiographic involvement and nonradiographic axial spondyloarthritis 
(nr-axSpA).  
Patients with axSpA have inflammatory back pain. The disease typically originates in the 
sacroiliac joints, then progresses to the spine. In the sacroiliac joints and the spine, active 
inflammation results in erosions, sclerosis, and fatty lesions seen on magnetic resonance 
imaging. However, the most characteristic feature is new bone formation leading to ankylosis of 
the sacroiliac joints and syndesmophytes attached to the vertebral bodies. As a result of extended 
syndesmophyte formation, the spine may become fused over time. Objective signs of 
inflammation (such as enthesitis, dactylitis, peripheral arthritis, or uveitis), genetic features (such 
as the presence of human leukocyte antigen B27), and laboratory parameters (such as elevated 
C-reactive protein [CRP]) may also be present (Braun, 2012; Rudwaleit et al, 2009a; 
Braun and Sieper, 2007). Disability in axSpA is related to both the degree of inflammatory 
activity, causing pain, stiffness, fatigue, and poor quality of sleep, and to the degree of bony 
ankylosis, causing loss of spinal mobility. Patients with AS show radiographic progression of 
disease with x-ray identified sacroiliitis, while "Bamboo spine" may develop when the outer 
fibers of the fibrous ring of the intervertebral discs ossify, which results in the formation of 
marginal syndesmophytes between adjoining vertebrae. 
Nonsteroidal anti-inflammatory drugs (NSAIDs) are often rapidly effective for the symptoms 
(pain and stiffness) of axSpA (Poddubnyy, 2013; Poddubnyy et al, 2012), but many patients lose 
or never have symptomatic response and structural damage often progresses despite their use. 
Conventional disease-modifying antirheumatic drugs (DMARDs; eg, methotrexate [MTX] and 
sulfasalazine [SSZ]) have unproven efficacy in axial disease, but may benefit patients with 
peripheral joint disease (Haibel et al, 2007; Braun et al, 2006; Haibel et al, 2005). Therefore, 
DMARDs are recommended only in patients with predominantly peripheral manifestations 
(Braun et al, 2011). Patients who are intolerant of or have inadequately responded to NSAIDs, or 
those in whom NSAIDs are contraindicated, have effective and approved treatment options such 
as tumor necrosis factor (TNF)-alpha inhibitors. 
Recently, the interleukin-17 (IL-17) cytokine family has been identified as a therapeutic target in 
axSpA and secukinumab, an IL-17A monoclonal antibody, has recently been approved as a 
treatment option in active AS. 
Bimekizumab (UCB4940) is an engineered, humanized full-length monoclonal antibody of 
immunoglobulin (Ig) G1 subclass of approximately 150,000 Dalton, which is expressed in a 
genetically engineered Chinese Hamster Ovarian cell line. Bimekizumab has a high affinity for 
human IL-17A and 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. Therefore, bimekizumab permits an evaluation of the 
potential for additional efficacy, which may be conferred by dual inhibition of both cytokines, in 
patients suffering from diseases in which both cytokines are active. Bimekizumab is being 
developed for the treatment of patients with inflammatory diseases such as PsA, PSO, and 
axSpA. 
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2.1.1 
Clinical studies 
2.1.1.1 
Completed studies 
Seventeen clinical studies of bimekizumab have been completed: RA0124 in 30 healthy 
volunteers, UP0031 in 12 healthy volunteers, UP0033 in 189 healthy volunteers, UP0034 in 
56 healthy volunteers, UP0042 in 48 healthy Japanese or Caucasian volunteers, UP0074 in 
37 healthy volunteers, RA0123 in 159 subjects with moderate to severe RA, UP0008 in 
39 subjects with mild-to-moderate plaque PSO, PS0010 in 250 subjects with moderate to severe 
chronic plaque PSO and the corresponding extension study (PS0011), PS0016 in 49 subjects 
with moderate to severe chronic plaque PSO and the corresponding extension study (PS0018), 
PA0007 in 53 subjects with PsA, PA0008 in 206 subjects with PsA, UC0011 in 23 subjects with 
moderate to severe active ulcerative colitis, HS0001 in 90 subjects with moderate to severe 
hidradenitis suppurativa (HS), and AS0008 in 303 subjects with AS. 
Information on the clinical data for bimekizumab from completed studies is available in the 
current version of the Investigator’s Brochure (IB). 
2.1.1.2 
Ongoing studies 
Several additional studies of bimekizumab in subjects with AS are ongoing: 
 Feeder studies AS0010 and AS0011: 
 AS0010 is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the 
efficacy and safety of bimekizumab in subjects with active nr-axSpA. 
 AS0011 is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the 
efficacy and safety of bimekizumab in subjects with active AS. 
 AS0013 is a Phase 2a Investigator- and subject-blind parallel-group study to evaluate the 
efficacy and safety of bimekizumab and certolizumab pegol (CZP) in subjects with active 
AS. 
Bimekizumab is also being evaluated in the treatment of other indications (eg, PsA, PSO, and 
HS). 
Additional information on the ongoing studies for bimekizumab is available in the current 
version of the IB. 
2.1.2 
Nonclinical studies 
Parallel inhibition of IL-17A and IL-17F has shown potent effects in a variety of animal models 
of inflammatory disease. Intravenously administered bimekizumab was well tolerated in 
repeat-dose toxicology studies in Cynomolgus monkeys with a no adverse effect level of 
200mg/kg/week. The findings of note in toxicity studies were diarrhea related to infectious 
enteritis (observed in the single dose study) and asymptomatic mild colonic ulceration in a 
proportion of animals (in the repeat-dose study); this latter finding was not associated with 
hematology abnormalities. Data suggest that bimekizumab induced primary lesions to the 
mucosa-associated lymphoid tissue via a pharmacologically-related mechanism. In a second 
repeat-dose study, none of the minor apoptosis/necrosis findings observed in gut-associated 
lymph nodes were seen. In animals given the highest dose of bimekizumab in the study 
(20mg/kg/week), a slightly higher number of protozoa (Balantidium coli) was observed in the 
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cecum and colon as compared to the control animals and low dose animals. Therefore, the 
gut-associated lymph node lesions observed in the first study are considered to be accidental 
and/or linked to exaggerated pharmacology and proliferation of Balantidium coli and are 
considered to be the result of a change in local mucosal immunity.  
Additional information on the nonclinical data for bimekizumab is available in the current 
version of the IB. 
3 
STUDY OBJECTIVES 
3.1 
Primary objective 
The primary objective of this open-label study is to assess the long-term safety and tolerability of 
bimekizumab administered over a period of up to 204 weeks (~4 years). 
3.2 
Secondary objectives 
The secondary objectives are:  
 To assess the long-term efficacy of bimekizumab 
3.3 
Other objectives 
The other objectives are: 
 To assess the impact on patient-reported quality of life 
 To assess the impact on enthesitis  
 To assess the plasma concentrations of bimekizumab 
 To assess the immunogenicity of bimekizumab 
4 
STUDY VARIABLES 
Changes from Baseline will be calculated relative to the Baseline of AS0008. Variables 
measured at the start of AS0009 will be referred to as AS0009 entry values. 
4.1 
Primary variables 
4.1.1 
Primary safety variables 
The primary safety variables are the incidences of TEAEs and SAEs. 
4.2 
Secondary variables 
4.2.1 
Secondary safety variable 
The secondary safety variable is the withdrawal due to TEAEs. 
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4.2.2 
Secondary efficacy variables 
The secondary efficacy variables are: 
 ASAS40 response at Week 48 
 ASAS20 response at Week 48 
 Change from Baseline of AS0008 in BASDAI at Week 48 
4.3 
Other variables 
4.3.1 
Safety variables 
Other safety variables are listed below. 
 Change from Baseline and AS0009 entry value in clinical laboratory variables (hematology 
and biochemistry) 
 Change from Baseline and AS0009 entry value in vital signs (pulse, temperature, and blood 
pressure) and body weight  
4.3.2 
Efficacy variables 
Other efficacy variables are listed below and will be evaluated at scheduled visits in accordance 
with the schedules of assessments in Table 5‒1 and Table 5‒2. 
 ASAS40 response 
 ASAS20 response 
 ASAS5/6 response 
 ASAS partial remission 
 Change from Baseline of AS0008 in Ankylosing Spondylitis Disease Activity Score-
C-reactive protein (ASDAS-CRP) 
 Ankylosing Spondylitis Disease Activity Score Inactive Disease (ASDAS-ID) 
 Change from Baseline of AS0008 in Bath Ankylosing Spondylitis Disease Activity Index 
(BASDAI) 
 Change from Baseline of AS0008 in Bath Ankylosing Spondylitis Functional Index (BASFI) 
 Change from Baseline of AS0008 in Bath Ankylosing Spondylitis Metrology Index 
(BASMI) 
 Change from Baseline of AS0008 in the MASES Index 
 Change from Baseline of AS0008 in Patient's Global Assessment of Disease Activity 
(PGADA) 
 Change from Baseline of AS0008 in total and nocturnal spinal pain 
 Change from Baseline of AS0008 in Short Form 36-item Health Survey (SF-36) 
 Change from Baseline of AS0008 in Ankylosing Spondylitis Quality of Life (ASQoL) 
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 Change from Baseline of AS0008 in the Hospital Anxiety and Depression Scale-Anxiety 
(HADS-A) and Hospital Anxiety and Depression Scale-Depression (HADS-D) scores 
 Depression and anxiety status “normal” as defined by HADS-D and HADS-A <8 
4.3.3 
PK variable 
The PK variable is the plasma concentration of bimekizumab evaluated at scheduled visits in 
accordance with the schedule of assessments in Table 5‒1 and Table 5‒2. 
4.3.4 
Immunological variable 
The immunological variable is the anti-bimekizumab antibody detection evaluated at scheduled 
visits in accordance with the schedule of assessments in Table 5‒1 and Table 5‒2. 
5 
STUDY DESIGN 
5.1 
Study description 
AS0009 is a multicenter OLE study to assess the long-term safety, tolerability, and efficacy of 
bimekizumab in eligible adult subjects with AS who completed the Phase 2b study AS0008. At 
Week 48 of AS0008, all subjects continuing into AS0009 will undergo the final AS0008 study 
assessments and any nonoverlapping AS0009 entry assessments, and will then receive their first 
open-label dose of bimekizumab. 
The OLE study will assess the safety, tolerability, and efficacy of bimekizumab for a period of 
up to 204 weeks (~4 years). Bimekizumab will be administered at a dose of 160mg Q4W upon 
entry into AS0009, regardless of the dose received in AS0008.  
Additionally, as described in (Section 5.1.1), other treatments may be used in addition to 
bimekizumab per Investigator discretion. Subjects not responding to treatment may be 
withdrawn from the treatment and study at the discretion of the Investigator.  
Following study completion or early termination, subjects will return for a SFU Visit 20 weeks 
after their last dose of bimekizumab. 
Schedules of study assessments are presented in Table 5‒1 and Table 5‒2. 
A study schematic diagram of AS0009 is presented in Figure 5‒1. 
5.1.1 
Rescue therapy 
In this OLE study, some subjects may require additional treatment in addition to medications 
received during AS0008 to control their AS symptoms. The decision to implement such therapy 
will be at the discretion of the Investigator. Therapies that are permitted for their disease within 
the context of the study are provided in Section 7.8.1 (Permitted concomitant treatments). 
Concomitant medication that is currently not considered safe or best medical practice should be 
avoided. See Section 7.8.2 for medications that are specifically prohibited. 
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5.1.2 
Study duration per subject 
The study duration for each subject is estimated to be up to a maximum of 224 weeks: 
 Open-Label Treatment Period: up to 204 weeks (~4 years)  
 SFU Visit: 20 weeks after the final dose of bimekizumab 
The subject may remain in the study until the study ends after 224 weeks, until the Sponsor 
decides to close the study, or until bimekizumab development is stopped by the Sponsor, 
whichever comes first. The Sponsor may consider transitioning the subject into another 
bimekizumab study or program. 
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 
Up to 285 subjects (from the ongoing AS0008 Phase 2b study) could be enrolled into this study 
at sites specified in AS0008. 
5.1.4 
Anticipated regions and countries 
The regions planned for study conduct are the same as in AS0008 (Europe and North America).  
5.2 
Schedule of study assessments 
Schedules of study assessments for Week 1 to Week 104 and for Week 108 to Week 208 are 
provided in Table 5‒1 and Table 5‒2. 
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Table 5‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
Informed consent 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
Xf 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Adverse events 
Xf 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
eC-SSRS 
Xe,f 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HADS 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
ASQoL 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BASDAI 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BASFI 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
SF-36 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
PGADA 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Total and nocturnal spinal pain 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
TB questionnaire 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Vital signs (pulse, temperature, 
BP)g 
Xe,f 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Body weight 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Physical examinationh 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
MASES 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
BASMI 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
ECG 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
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Table 5‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
Hematology/biochemistry/urine 
pregnancyi, j 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Blood Sample for CRPj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Blood sample for bimekizumab 
plasma concentrationsj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
Blood sample for anti-
bimekizumab antibodiesj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
IGRA TB testk 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
IXRS  
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Bimekizumab administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ASQoL=Ankylosing Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis 
Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; BASFI=Bath Ankylosing Spondylitis Metrology Index; BP=blood pressure; 
CRP=C-reactive protein; ECG=electrocardiogram; eC SSRS=electronic Columbia-Suicide Severity Rating Scale; EV=Entry Visit; H=home; 
HADS=Hospital Anxiety and Depression Scale; IGRA=interferon gamma release assay; IMP: investigational medicinal product; IXRS=interactive 
voice or web response system; MASES= Maastricht Ankylosing Spondylitis Enthesitis Index; PGADA=Patient's Global Assessment of Disease 
Activity; SF 36=36 item short form health survey; SFU=Safety Follow Up; TB=tuberculosis;  
Note: The SFU Visit will occur 20 weeks after the last dose of IMP. 
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a minimum of 21 days and a maximum of 35 days in between 
doses at all visits except the SFU Visit which 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).  
b AS0009 entry will occur at the end of the lead-studies. At Week 48 of AS0008, all subjects continuing into AS0009 will undergo the final 
AS0008 study assessments and any nonoverlapping AS0009 entry assessments, and will then receive their first open label dose of 
bimekizumab. 
c From the Entry Visit onwards, self-administration training will be provided to the subject/caregivers/appropriate designee by the study nurse. At 
Week 8 and Week 12, the subject/caregiver/appropriate designee will perform administrations under the supervision of the site staff to ensure that study 
medication is being properly and safely injected. 
d Ensure that a separate Informed Consent form was completed by the subject for AS0009 prior to study entry. 
e To be performed prior to the first dose of open-label bimekizumab. 
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Table 5‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
f Assessment will be performed at Week 48 of the lead-in study AS0008 and will be used as the AS0009 entry value. 
g At AS0009 study entry, collect pulse and BP prior to drug administration and then at 30 minutes and 1 hour after dosing. At all other visits collect 
pulse and BP prior to drug administration and once after dosing (any time). All other procedures will only be done prior to dosing.  
h Includes evaluation of signs and symptoms of active TB and risk for exposure to TB. 
i If there has been a delay in menses, perform a urine pregnancy test. 
j All blood samples are to be taken prior to dosing. 
k It is recommended that the QuantiFERON TB Test be performed. This assessment will be performed at study entry, unless an IGRA negative result is 
available less than 6 weeks prior to the first dose of open-label bimekizumab. 
 
 
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Table 5‒2: 
Schedule of study assessments (Week 108 through Week 208) 
Protocol activity 
Treatment Period 
 
Weeksa 
10
8 
112 
120 
124 
132 
136 
144 
148 
156 
160 
168 
172 
180 
184 
192 
196 
204 
208/ET 
SFU 
 
 
116 
 
128 
 
140 
 
152 
 
164 
 
176 
 
188 
 
200 
 
 
Visita 
12 
Hb 
13 
Hb 
14 
Hb 
15 
Hb 
16 
Hb 
17 
Hb 
18 
Hb 
19 
Hb 
20 
21 
 
Concomitant medications 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Adverse events 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
eC-SSRS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
HADS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
ASQoL 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
BASDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
BASFI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
SF-36 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
PGADA 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Total and nocturnal spinal 
pain 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
TB questionnaire 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Vital signs (pulse, 
temperature, BP)c 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Body weight 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Physical examinationd 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
MASES 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
BASMI 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
ECG 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
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Table 5‒2: 
Schedule of study assessments (Week 108 through Week 208) 
Protocol activity 
Treatment Period 
 
Weeksa 
10
8 
112 
120 
124 
132 
136 
144 
148 
156 
160 
168 
172 
180 
184 
192 
196 
204 
208/ET 
SFU 
 
 
116 
 
128 
 
140 
 
152 
 
164 
 
176 
 
188 
 
200 
 
 
Visita 
12 
Hb 
13 
Hb 
14 
Hb 
15 
Hb 
16 
Hb 
17 
Hb 
18 
Hb 
19 
Hb 
20 
21 
 
Hematology/biochemistry
/urine pregnancye,f 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Blood Sample for CRPf 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Blood sample for 
bimekizumab plasma 
concentrationsf 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
Blood sample for anti-
bimekizumab antibodiesf 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
IGRA TB testg 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
IXRS  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Bimekizumab 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ASQoL=Ankylosing Spondylitis Quality of Life; BASMI=Bath Ankylosing Spondylitis Metrology Index; BASDAI=Bath Ankylosing Spondylitis 
Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BP=blood pressure; CRP=C-reactive protein; ECG=electrocardiogram; 
eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; H=home; HADS=Hospital Anxiety and Depression Scale; IGRA=interferon gamma 
release assay; IMP: investigational medicinal product; IXRS=interactive voice or web response system; MASES=Maastricht Ankylosing Spondylitis 
Enthesitis Index; PGADA=Patient's Global Assessment of Disease Activity; SF-36=36-item short form health survey; SFU=Safety Follow-Up; 
TB=tuberculosis;  
Note: The SFU Visit will occur 20 weeks after the last dose of IMP.  
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a minimum of 21 days and a maximum of 35 days in between 
doses at all visits except the SFU Visit which 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). 
b Self-administration by the subject/caregivers/appropriate designee will be possible. 
c At all visits except AS0009 study entry, collect pulse and BP prior to drug administration and once after dosing (any time). All other procedures will only 
be done prior to dosing.  
d Includes evaluation of signs and symptoms of active TB and risk for exposure to TB. 
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Table 5‒2: 
Schedule of study assessments (Week 108 through Week 208) 
Protocol activity 
Treatment Period 
 
Weeksa 
10
8 
112 
120 
124 
132 
136 
144 
148 
156 
160 
168 
172 
180 
184 
192 
196 
204 
208/ET 
SFU 
 
 
116 
 
128 
 
140 
 
152 
 
164 
 
176 
 
188 
 
200 
 
 
Visita 
12 
Hb 
13 
Hb 
14 
Hb 
15 
Hb 
16 
Hb 
17 
Hb 
18 
Hb 
19 
Hb 
20 
21 
 
e If there has been a delay in menses, perform a urine pregnancy test. 
f All blood samples are to be taken prior to dosing. 
g It is recommended that the QuantiFERON TB Test be performed. This assessment will be performed at study entry, unless an IGRA negative result is 
available less than 6 weeks prior to the first dose of open-label bimekizumab. 
 
 
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5.3 
Schematic diagram 
A study schematic diagram of AS0009 is provided in Figure 5‒1. 
Figure 5‒1: Schematic diagram 
 
 
IMP=investigational medicinal product; Q4W=every 4 weeks; sc=subcutaneous; SFU=Safety Follow-up 
Note: Self-administration will be allowed after 3 months of treatment (from Week 16 onwards) as described in 
Table 5‒1. 
Note: Additionally, as described in Section 5.1.1 and Section 7.8.1; other treatments may be used in addition to 
bimekizumab per Investigator discretion. Subjects not responding to treatment may be withdrawn from the study at 
the discretion of the Investigator. 
a Subjects will receive their final dose of IMP on Week 204 and the SFU Visit will be conducted 20 weeks after the 
last dose of IMP.  
 
5.4 
Rationale for study design and selection of dose 
A dose of 160 mg Q4W was selected based on the current understanding of PK/PD of 
bimekizumab in PsA (data from PA0007) and a literature meta-analysis of biologics in AS. 
Based on this analysis, a dose of 160mg Q4W is expected to provide maximum response in most 
of the subjects. Based on the modeling outcome, UCB expects that the ASAS40 response would 
maximize at a dose of 160mg Q4W, and hence, this dose was selected for AS0009 (Diderichsen, 
2016).  
A bimekizumab dose of 160mg Q4W is currently being used in ongoing Phase 2b clinical 
studies. 
Doses greater than 160mg have been previously studied in the development of bimekizumab. In 
the single ascending dose study UP0008, a single dose of bimekizumab 640mg was tested. In the 
multiple dose study PA0007, a bimekizumab 560mg loading dose followed by 2 subsequent 
320mg doses every 3 weeks was tested. At exposure levels achieved at these doses, the 
compound had no significant safety concerns. In the previous clinical studies, bimekizumab was 
administered iv and in the current study bimekizumab will be administered sc (bioavailability of 
bimekizumab is 64%). Due to lower bioavailability, bimekizumab exposure is expected to be 
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lower with sc administration compared with after iv administration, therefore, the dose regimens 
are expected to be 
 
As more data for bimekizumab become available in this indication, doses and dosing regimen 
may be modified accordingly. 
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: 
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent Form (ICF) is signed and dated by the subject. 
2a. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand 
and complete questionnaires), visit schedule, or medication intake according to the judgment 
of the Investigator. 
3. In the opinion of the Investigator, the subject is expected to benefit from participation in an 
OLE study. 
4. Subject completed AS0008 without meeting any withdrawal criteria. 
5. Female subjects must be postmenopausal, permanently sterilized (eg, tubal occlusion, 
hysterectomy, bilateral salpingectomy) or, if of childbearing potential (and engaged in sexual 
activity that could result in procreation), must be willing to use a highly effective method of 
contraception until 20 weeks after last administration of IMP, and have a negative pregnancy 
test at the last visit of AS0008. The following methods are considered highly effective when 
used consistently and correctly: 
 combined (estrogen and progestogen) hormonal contraception associated with inhibition 
of ovulation (oral, intravaginal or transdermal)  
 progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable) 
 intrauterine device (IUD) 
 intrauterine hormone-releasing system (IUS) 
 bilateral tubal occlusion 
 vasectomized partner  
 sexual abstinence if it is in accordance with a subject’s preferred and common lifestyle. 
Subjects who use abstinence as a form of birth control must agree to abstain from 
heterosexual intercourse until 20 weeks after the last dose of IMP. Study personnel must 
confirm the continued use of abstinence is still in accordance with the subject’s lifestyle 
at regular intervals during the study. 
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up until 20 weeks after the last administration of IMP (anticipated 
5 half-lives). 
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6.2 
Exclusion criteria 
Subjects are not permitted to enroll in the study if any of the following criteria are met: 
1. Female subjects who plan to become pregnant during the study or within 20 weeks following 
the last dose of IMP. Male subjects who are planning a partner pregnancy during the study or 
within 20 weeks following the last dose. 
2. Subjects with any current sign or symptom that may indicate a medically significant active 
infection (except for the common cold) or has had an infection requiring systemic antibiotics 
within 2 weeks of study entry. The medical monitor must be consulted prior to subject’s 
entry into AS0009 in such cases. 
3. Subjects who meet any withdrawal criteria in AS0008. For any subject with an ongoing SAE, 
or a history of serious infections (including hospitalizations) in the lead-in study, the Medical 
Monitor must be consulted prior to the subject’s entry into AS0009. 
6.3 
Withdrawal criteria 
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care. 
Subjects should be withdrawn from the study and will be asked to complete the Early 
Termination Visit and SFU Visit (20 weeks after the last received dose) if any of the following 
events occur: 
1. Subject withdraws his/her consent. 
2. There is confirmation of a pregnancy in a female subject during the study, as evidenced by a 
positive pregnancy test. 
3. The Sponsor or a regulatory agency requests withdrawal of the subject. 
4. Subject develops an illness that in the opinion of the Investigator would interfere with his/her 
continued participation, if the risk of continuing participation outweighs the potential benefit.  
5. Subject develops erythrodermic, guttate, or generalized pustular form of PSO. 
6. Subject considered to have either a suspected new latent tuberculosis (LTB) infection or who 
develops active tuberculosis (TB) or nontuberculosis mycobacteria (NTMB) infection during 
the study (including but not limited to, conversion demonstrated by Interferon Gamma 
Release Assay (IGRA) or other diagnostic means) must be immediately discontinued from 
IMP and an unscheduled visit must be conducted as soon as possible, but not later than the 
next regular visit. 
The subject must be permanently withdrawn if further examinations result in a diagnosis of 
active TB, or if the subject is diagnosed with LTB infection with no initiation of prophylactic 
treatment, prematurely discontinues prophylactic treatment, or, in the opinion of the 
Investigator or Sponsor, is noncompliant with prophylactic TB therapy. 
Confirmed active TB is 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.  
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7. Subject is noncompliant with the study procedures or medications which may present a risk 
to the safety of the subject in the opinion of the Investigator. 
8. Subject uses prohibited concomitant medications as defined in Section 7.8 that may present a 
risk to the safety of the subject in the opinion of the Investigator and/or the Medical Monitor. 
9. Subject develops laboratory abnormalities (with or without clinical symptoms) of alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST) as defined in Section 6.3.1; 
neutrophils <0.5x109/L (neutropenia); lymphocytes <0.5x109/L (lymphopenia). Any 
laboratory value or change judged to be clinically significant by the Investigator should 
prompt consideration of whether the subject should continue on IMP. For clarification, 
laboratory values that are markedly abnormal as per Table 17-1 and Table 17‒2 will be 
flagged to the Investigator and to the medical monitor but do not trigger mandatory 
withdrawal unless listed above. (Refer to Section 6.3.1 for withdrawal criteria in relation to 
potential drug-induced liver injury [PDILI].) 
10. Subject has active suicidal ideation as indicated by a positive response (“Yes”) to questions 4 
or 5 or to the suicidal behavior questions of the “Since Last Visit” version of the self-rated 
electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). The subject should be 
referred immediately to a Mental Healthcare Professional and must be withdrawn from the 
study. 
11. 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. 
12. Subjects with newly diagnosed IBD or with IBD flares during the study must: 
 Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist 
 Discontinue IMP and be followed-up until resolution of active IBD symptoms 
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact the 
Medical Monitor and UCB study physician to confirm the subject's suitability for continued 
participation in the study. 
All subjects who withdraw from the study due to an AE must be followed until resolution of the 
event or until the event is considered stable. All subjects who withdraw from the study due to 
development of a laboratory abnormality must be closely monitored. 
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The electronic Case Report form (eCRF) must document the primary reason for 
withdrawal or discontinuation. 
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Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance. 
6.3.1 
Potential drug-induced liver injury IMP discontinuation criteria 
Subjects with 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 discontinuation of IMP:  
Subjects with either of the following:  
 ALT or AST ≥5x upper limit of normal (ULN) 
 ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN  
 Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).  
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator.  
 Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness).  
Evaluation of PDILI must be initiated as described in Section 9.4.1.  
If subjects are unable to comply with the applicable monitoring schedule, IMP must be 
discontinued immediately. 
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The CRF must document the primary 
reason for IMP discontinuation. 
7 
STUDY TREATMENT(S) 
7.1 
Description of investigational medicinal product 
Bimekizumab will be supplied by UCB Clinical Trial Supply Operations or designee. 
The IMP will consist of the following: 
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative-free solution in a 1mL prefilled syringe (PFS). 
 
 
 
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Further details of the IMP and specifications are provided in the Investigational Medicinal 
Product Handling Manual. 
7.2 
Treatment(s) to be administered 
All subjects will receive bimekizumab 160mg Q4W sc (Section 5.1). 
The IMP is to be administered in the clinic by study site staff as 1 sc injection for the 160mg 
dose. Suitable areas for sc injections are the lateral abdominal wall and upper outer thigh and 
upper arm if the IMP is injected by a healthcare provider or a caregiver. Injection sites should be 
rotated and injections should not be given into areas where the skin is tender, bruised, red, or 
hard. 
The IMP (bimekizumab) will be administered at the visits indicated in the schedules of 
assessments in Table 5‒1 and Table 5‒2. The minimum time between doses should be no less 
than 21 days and no more than 35 days for Q4W dosing. 
Administration will occur at the study site for the first 3 months of AS0009.  
Thereafter and in between the quarterly study visits at the site, the subjects will have the option 
to perform self-administration at home. From the Entry Visit onwards, self-administration 
training will be provided to the subject/and or caregivers/appropriate designee by the study 
nurse. At Week 8 and Week 12, the subject/caregiver/appropriate designee will perform 
administration under the supervision of the site staff to ensure that study medication is being 
properly and safely injected.  
Once subjects/caregivers/appropriate designees as determined by the Investigator (or designee) 
have been trained, the study medication may be administered at home. The subject will receive 
the required number of injections at each visit needed to perform the monthly administrations at 
home. Subjects who are unable to or decide not to self‑administer or those without a family 
member/friend/caregiver (or appropriate designee) who can help will not be discontinued, but 
may continue to visit the site for study treatment administration only. If administered at home, 
the subject/caregiver (or appropriate designee) will document the date, body location, and time 
point of administration of study medication.  
All used PFS will be disposed of by subjects/caregivers/appropriate designee as determined by 
the Investigator in an acceptable disposal (sharps) container directly after the administration. The 
subjects/caregivers return the documentation together with any used/unused containers at the 
next scheduled clinic visit. 
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing. 
7.3 
Packaging 
Bimekizumab will be packaged and labeled according to Good Manufacturing Practice (GMP) 
guidelines and applicable laws or regulations. It will be suitably packaged in such a way as to 
protect the product from deterioration during transport and storage. Further information 
regarding storage and transport conditions are provided in the IMP Handling Manual. 
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7.4 
Labeling 
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and GMP and will include any 
locally required statements. If necessary, labels will be translated into the local language. 
7.5 
Handling and storage requirements 
Investigational Medicinal Product must be stored under refrigerated conditions (2ºC to 8ºC) 
protected from light. The IMP must not be frozen.  
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access. 
Appropriate storage conditions must be ensured either by controlled room temperature or by 
completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a week), showing minimum and maximum temperatures reached over the time interval. 
In case an out-of-range temperature is noted, it must be immediately communicated to the 
Clinical Project Manager (CPM) (or designee) before further use of the IMP. 
Investigational Medicinal Product will be shipped to the study sites in temperature controlled 
containers. Out-of-range shipping or storage conditions must be brought to the attention of the 
Sponsor or designee, immediately. Authorization to use any out-of-range IMP must be 
documented and received prior to dispensing or administering the IMP at the study site. 
In addition, the Investigator (or designee) will instruct the subject how to handle the IMP during 
the transport and how to store the IMP following the instruction guide. Cooler bags with freezer 
packs will be provided to the subjects. Specific attention will be put on the transport from site to 
home using cold bags, the subject will be instructed to put the IMP as quickly as possible into 
his/her refrigerator. In case of broken refrigerator, broken or lost syringes, the subject will inform 
the site immediately and new IMP will be prepared. All efforts should be made to follow the 
treatment scheme as per protocol. 
7.6 
Drug accountability 
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the 
study site, or returned to the sponsor or designee must also be recorded on the appropriate forms. 
All supplies and pharmacy documentation must be made available throughout the study for UCB 
(or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the IMP is used only in accordance with the protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers), partially used, unused, damaged, and/or expired IMP must be reconciled and either 
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destroyed at the site according to local laws, regulations, and UCB Standard Operating 
Procedures (SOPs) or returned to UCB (or designee). Onsite destruction of used kits only may be 
allowed with prior approval from the Sponsor or designee after reconciliation. The 
subjects/caregivers (or appropriate designee) return the documentation together with any 
used/unused containers at the next scheduled clinic visit. Investigational medicinal product 
intended for the study cannot be used for any other purpose than that described in this protocol. 
7.7 
Procedures for monitoring subject compliance 
During the Treatment Period of this study, IMP will be administered in the clinic during the first 
3 months of treatment (Visit 1 [Entry Visit] through Visit 4 [W12]) and compliance will be 
determined at the visit by study personnel. Thereafter, self-administration at home will be 
possible at the following weeks: Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 100, 
104, 112, 116, 124, 128, 136, 140, 148, 152, 160, 164, 172, 176, 184, 188, 196, and 200. Dates 
and time of self-administration will be captured using a subject diary. All used PFS will be 
disposed of by subjects/caregivers/appropriate designee as determined by the Investigator in an 
acceptable disposal (sharps) container directly after the administration.  
Drug accountability must be recorded on the Drug Accountability Form. If a subject is 
noncompliant with the study procedures or medications that may present a risk to the safety of 
the subject in the opinion of the Investigator, then the subject should be withdrawn as described 
in Section 6.3. 
7.8 
Concomitant medications/treatments 
All concomitant medications, including over the counter products, herbal, traditional remedies, 
vitamin/mineral supplements, other dietary supplements, “nutraceuticals,” and hormones must be 
recorded in the subject’s source documentation (eg, clinical chart) and on the eCRF. This record 
should include the name of the drug, the dose, the route and date(s) of administration, and the 
indication for use. 
The Investigator should examine the acceptability of all concomitant procedures, medications, 
topical preparations, and dietary supplements not explicitly prohibited in this study, and if 
necessary, discuss with the Medical Monitor. 
In order to ensure that appropriate concomitant therapy is administered, subjects will be 
instructed to consult with the Investigator prior to taking any medication (either 
self-administered nonprescription drugs or prescription therapy prescribed by another physician). 
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7.8.1 
Permitted concomitant treatments (medications and therapies) 
Medication changes are permitted at any time after enrollment into this OLE study. Medication 
changes and additions are permitted with the following guidelines: 
 Nonsteroidal anti-inflammatory drugs (NSAIDs), DMARDs (MTX, SSZ, leflunomide [LEF], 
and/or joint injections may be given if deemed appropriate by the Investigator as outlined 
below. Subjects may receive these add-on therapies while continuing to receive 
bimekizumab. Under no circumstances should subjects have a concomitant biologic agent 
while receiving bimekizumab. 
 For subjects taking NSAIDs/cyclooxygenase 2 (COX-2) inhibitors, a change can be made 
to a different NSAID/COX-2. Changes from an NSAID to a COX-2 inhibitor or from a 
COX-2 inhibitor to an NSAID are permitted up to the maximum approved or tolerated 
dose, whichever is less. Only 1 NSAID/COX-2 inhibitor may be taken at a given time. 
 For subjects not taking NSAID/COX-2 inhibitors, either can be initiated, up to the 
maximum approved or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 
inhibitor may be taken at a given time. 
 Methotrexate in oral or sc administration may be added or increased to a maximum dose 
of 25mg/week, or to the maximum tolerated dose, whichever is lower, for peripheral 
arthritis symptoms. The route of administration may be changed from oral to sc or from 
sc to oral. It is strongly recommended that subjects taking MTX should also take folic 
acid supplementation. 
 Sulfasalazine may be added or increased up to a maximum dose of 3g/day, or the 
maximum tolerated dose, whichever is lower, for peripheral arthritis symptoms.  
 Leflunomide may be started or increased to a maximum dose of 20mg/day (or an average 
of 20mg/day if not dosed daily), or the maximum tolerated dose, whichever is lower, for 
peripheral arthritis symptoms. Leflunomide (LEF) should not be used concomitantly with 
MTX. 
 Hydroxychloroquine may be started or increased to a maximum of 400mg/day. 
 Combination DMARDs (optimally 2) are allowed except that LEF and MTX may not be 
given together. 
 No other oral DMARDs are permitted during this OLE study. 
 Steroid tapers for disease activity or disease-related reasons are allowed with an average 
daily dose of 20mg prednisone or prednisone equivalent per day for a maximum of 14 days.  
 Up to 1 injection per joint for up to 3 discrete joints is permitted per 12-month period with 
the exception of the sacroiliac joints, which may each be injected up to twice per year. 
Injected joints are censored for the joint examination.  
 Intra-articular hyaluronic acid injections are permitted into joints for which they are approved 
as per local labels.  
 Intra-bursal corticosteroid injections are also permitted at the discretion of the Investigator. 
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 A decrease in dose or dosing frequency of any agent (except bimekizumab) is permitted at 
any time. 
 Subjects with persistent active disease in spite of added concomitant therapy/therapies 
mentioned above may be withdrawn from the study at the discretion of the Investigator. 
7.8.2 
Prohibited concomitant treatments (medications and therapies) 
Medications listed in Table 7‒1 are prohibited or restricted as follows: 
Table 7‒1: 
Prohibited or restricted medications 
Drug class 
Dose 
Comments 
Analgesics, including opioid 
analgesics 
(acetaminophen/paracetamol, 
etc) 
Any dose  
Any ad hoc use in the 24 hours 
prior to any study visit is 
prohibited.  
 
Stable doses of analgesics 
(including opioids) permitted. 
TNF inhibitors 
-infliximab 
-adalimumab 
-etanercept  
-golimumab  
-certolizumab pegol  
Any dose 
This applies to biosimilar 
versions of any TNF inhibitor. 
Any non-TNF biologic 
medications 
Any dose 
Any exposure history is 
prohibited. 
All other DMARDs 
Any dose 
Only permitted medications as 
per Section 7.8.1. 
DMARD=disease-modifying antirheumatic drug; TNF=tumor necrosis factor 
Subjects who take prohibited medications may be withdrawn from study treatment but followed 
until the SFU Visit. The decision to withdraw a subject for taking prohibited medications should 
be made in consultation with the Medical Monitor.  
Vaccines 
Administration of live, attenuated vaccines is not allowed during the conduct of the study or for 
20 weeks after the last dose of IMP. Administration of non-live, inactivated vaccines is allowed 
during the study at the discretion of the Investigator. 
Live vaccinations include, but are not limited to, the following: anthrax vaccine, intranasal 
influenza vaccine, measles-mumps-rubella vaccine, polio live oral vaccine, smallpox vaccine, 
TB Bacillus Calmette-Guérin vaccine, typhoid live oral vaccine, varicella vaccine, and yellow 
fever vaccine. 
7.9 
Blinding 
This is an open-label study. All subjects’ treatment assignments during the lead-in study AS0008 
will remain blinded until final database lock of AS0008. 
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7.10 
Randomization and numbering of subjects 
This is an OLE study and no randomization will be performed. All subjects will receive 
bimekizumab 160mg Q4W sc (see Section 5.1 for further details). 
Subjects will continue with the 5-digit subject numbers assigned by the interactive web or voice 
response system (IXRS) in the preceding study.  
8 
STUDY PROCEDURES BY VISIT  
The schedules of study assessments (Table 5‒1 and Table 5‒2) provide a general overview of 
study assessments. A list of procedures to be completed at each visit is provided in the sections 
that follow.  
 Visit windows of ±7 days on either side of the scheduled dosing are permitted for all visits 
other than the SFU Visit (see below); however, the Investigator should try to keep the 
subjects on the original dosing schedule. The window of ±7 days is relative to the first dose 
(AS0009 entry) and applicable for all subsequent visits. Changes to the dosing schedule 
outside of the 14-day window must be discussed with the Medical Monitor. 
 The minimum time between doses should be no less than 21 days and no more than 35 days 
for Q4W dosing. 
 For the SFU Visit (20 weeks after the last dose), the visit should occur no more than 3 days 
prior to the scheduled visit date and within 7 days after the scheduled visit date 
(-3 days/+7 days). 
The Investigator should make efforts to maintain the original visit schedule. Changes to the 
dosing schedule outside of the allowed windows must be discussed with the Medical Monitor 
and may result in subject withdrawal. 
8.1 
AS0009 study entry (Visit 1) 
The AS0009 entry assessments noted with an asterisk “*” will be obtained at the Week 48 Visit 
of AS0008 and do not need to be recorded on the eCRF for this study.  
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Ensure that a separate ICF was completed by the subject for AS0009 (must be done prior to 
any AS0009 study procedures) 
 Assessment of inclusion/exclusion criteria 
 Concomitant medications* 
 Record AEs* 
 eC-SSRS* 
 HADS* 
 ASQoL* 
 BASDAI* 
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 BASFI* 
 SF-36* 
 PGADA* 
 Total and nocturnal spinal pain* 
 TB questionnaire* 
 Measure vital signs (temperature and blood pressure [BP])* 
 Body weight* 
 Physical examination (includes evaluation of signs and symptoms of active TB and risk for 
exposure to TB).* 
 MASES* 
 Bath Ankylosing Spondylitis Metrology Index (BASMI)* 
 Electrocardiogram (ECG)* 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry)* 
 CRP* 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations* 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test (unless an IGRA negative result is available less than 6 weeks prior to the first 
dose of open-label bimekizumab) 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.2 
Week 4 (Visit 2) and Week 8 (Visit 3) 
All procedures or assessments will be performed prior to administration of IMP. 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 Measure vital signs (temperature, pulse, and BP) Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
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8.3 
Week 12 (Visit 4), Week 24 (Visit 5), Week 36 (Visit 6), Week 72 
(Visit 9) 
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 MASES 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.4 
Week 16, Week 20, Week 28, Week 32, Week 40, Week 44, 
Week 52, Week 56, Week 64, Week 68, Week 76, Week 80, 
Week 88, Week 92, Week 100, and Week 104 
 Subjects will be given the opportunity for self-administration of bimekizumab. Adverse 
events will be captured spontaneously if the subject decides to visit the site to receive the 
bimekizumab administration.  
 
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8.5 
Week 48 (Visit 7) and Week 96 (Visit 11) 
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP)  
 Body weight 
 Physical examination (includes evaluation of signs and symptoms of active TB and risk for 
exposure to TB) 
 MASES 
 BASMI 
 ECG 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
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8.6 
Week 60 (Visit 8) and Week 84 (Visit 10) 
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.7 
Week 108 (Visit 12), Week 132 (Visit 14), and Week 180 (Visit 18) 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 BASDAI 
 BASFI 
 PGADA 
 Total and nocturnal spinal pain 
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 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.8 
Week 112, Week 116, Week 124, Week 128, Week 136, Week 140, 
Week 148, Week 152, Week 160, Week 164, Week 172, Week 176, 
Week 184, Week 188, Week 196, and Week 200 
 Subjects will be given the opportunity for self-administration of bimekizumab. Adverse 
events will be captured spontaneously if the subject decides to visit the site to receive the 
bimekizumab administration.  
 
8.9 
Week 120 (Visit 13) and Week 168 (Visit 17)  
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 MASES 
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 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.10 
Week 144 (Visit 15) and Week 192 (Visit 19) 
 Concomitant medications 
 Record AEs 
 eC SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 MASES 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test 
 Contact the IXRS  
 Administer bimekizumab (after all other visit assessments are completed) 
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8.11 
Week 156 (Visit 16) 
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 BASDAI 
 BASFI 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Physical examination (includes evaluation of signs and symptoms of active TB and risk for 
exposure to TB) 
 BASMI 
 ECG 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.12 
Week 204 (Visit 20) 
The following procedures or assessments will be performed prior to administration of IMP, 
unless otherwise noted: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
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 HADS 
 BASDAI 
 BASFI 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Perform a urine pregnancy test if there has been a delay in menses 
 BASMIContact the IXRS 
 Administer bimekizumab (after all other visit assessments are completed) 
 
8.13 
Week 208 (Visit 21)/Early Termination Visit 
The following procedures or assessments will be performed: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Physical examination (includes evaluation of signs and symptoms of active TB and risk for 
exposure to TB) 
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 MASES 
 ECG 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 Contact the IXRS 
 
8.14 
SFU Visit  
The following procedures or assessments will be performed: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 ASQoL 
 BASDAI 
 BASFI 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Physical examination 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test 
 Contact the IXRS 
8.15 
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. 
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If an Unscheduled Visit is conducted due to safety or efficacy reasons, an eC-SSRS assessment 
will be performed with the subject during the visit. If an Unscheduled Visit is conducted for 
reasons other than safety or efficacy concerns (eg, replacement of lost medication, repeated 
collection of a laboratory specimen due to collection or analysis issues) an eC-SSRS will not be 
required at these visits. 
At this visit, any of the following assessments may be performed, depending on the reason for 
the visit: 
 Record concomitant medication 
 Record AEs 
 eC-SSRS 
 Measure vital signs (temperature, pulse, and BP) 
 Physical examination 
 Record 12-lead ECG  
 If medically indicated, obtain blood sample(s) for standard safety laboratory tests 
(hematology, serum chemistry)  
 Obtain urine sample for standard safety laboratory tests (including urine pregnancy test in 
women of childbearing potential).  
9 
ASSESSMENT OF SAFETY 
9.1 
Adverse events 
9.1.1 
Definition of AE 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the Case Report form (CRF) even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit. 
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
investigator from the subject’s history or study entry. 
Adverse events that occurred during the AS0008 lead-in study and are still deemed ongoing at 
the time of enrolment (signed ICF) will be captured in the database and followed up, as 
described in Section 9.1.6. 
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9.1.2 
AEs of special interest 
An AE of special interest (AESI) is any AE that a regulatory authority has mandated be reported 
on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. 
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN alkaline phosphatase (ALP), with no alternative explanation for the 
biochemical abnormality, must ALWAYS be reported to UCB as an AESI (ie, without waiting 
for any additional etiologic investigations to have been concluded). Follow-up information 
should then be reported if an alternative etiology is identified during investigation and 
monitoring of the subject. 
9.1.3 
Other safety topics of interest 
Pre-specified safety topics of interest for the study are: infections (serious, opportunistic, fungal, 
and TB), neutropenia, hypersensitivity, suicidal ideation and behavior, depression, major 
cardiovascular events, liver function test changes/enzyme elevations, malignancies, and 
inflammatory bowel diseases (with gastroenterology referral, as appropriate). This is based on 
findings from the IMP clinical program to date, potential risks generally associated with biologic 
immunomodulators, or findings from other medicines with a related mechanism of action. There 
are no specific AE reporting requirements for these topics, however special monitoring, 
additional data collection activities, and/or enhanced signal detection activities (within UCB) are 
in place. 
9.1.4 
Procedures for reporting and recording AEs 
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example: 
“Did you notice anything unusual about your health (since your last visit)?” 
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study. 
9.1.5 
Description of AEs 
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation. 
When recording the intensity of an AE in the CRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria: 
 Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere with 
his/her usual activities and/or is of no clinical consequence 
 Moderate: the AE interferes with the usual activities of the subject or it is of some clinical 
consequence 
 Severe: the subject is unable to work normally or to carry out his/her usual activities, or the 
AE is of definite clinical consequence 
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Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines. 
9.1.6 
Follow-up of AEs 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and other safety topics of interest; further 
details regarding follow-up of PDILI events are provided in Section 9.4.1.5. Information on 
SAEs obtained after clinical database lock will be captured through the Patient Safety (PS) 
database without limitation of time. 
If an AE is ongoing at the end of the study for a subject, follow-up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow-up. If no follow-up is provided, the 
Investigator must provide a justification. The follow-up will usually be continued for 20 weeks 
after the subject has discontinued his/her IMP. 
9.1.7 
Rule for repetition of an AE 
An increase in the intensity of an AE should lead to the repetition of the AE being reported with: 
 The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening” 
 The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one 
9.1.8 
Pregnancy 
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by providing the completed 
Pregnancy Report and Outcome Form (for contact details see SAE reporting information at the 
beginning of this protocol). The subject should be withdrawn from the study as soon as 
pregnancy is known (by positive pregnancy test), and the following should be completed: 
 The subject should return for the Early Termination (ET) Visit. 
 The subject should immediately stop the intake of the IMP. 
 An SFU Visit should be scheduled 20 weeks after the subject has discontinued her IMP. 
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives. 
The pregnancy will be documented on the Pregnancy Report and Outcome Form provided to the 
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome Form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow-up is continued for a period longer than 30 days. If 
the subject is lost to follow-up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
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UCB’s Drug Safety department is the primary contact for any questions related to the data 
collection for the pregnancy, eventual birth, and follow-up. 
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent Form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/Contract Research Organization (CRO) contract monitor for 
the study. The Investigator will complete the Pregnancy Report and Outcome Form and send it to 
UCB’s PS department (for contact details see SAE reporting information at the beginning of this 
protocol) only after the partner has agreed that additional information can be captured and has 
provided the signed Partner Pregnancy Consent Form. UCB’s PS department is also the primary 
contact for any questions related to the data collection for the partner pregnancy, eventual birth, 
and follow-up. 
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective abortion 
when medically indicated (e.g. when pregnancy is endangering life or health of woman or when 
fetus will be born with severe abnormalities), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally 
reported using the Investigator SAE Report form. 
9.1.9 
Suspected transmission of an infectious agent via a medicinal 
product 
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent. 
9.1.10 
Overdose of investigational medicinal product 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if 
there are associated clinical signs and symptoms or if the act of taking the excess medicine itself 
is an AE or SAE (eg, suicide attempt). 
9.1.11 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative. 
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
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signs, laboratory or ECG results) for which data will be periodically reviewed during the course 
of the study. 
In addition, Cardiovascular and Neuropsychiatric Adjudication Committees will also periodically 
review and monitor the safety data from this study and advise UCB. Details are provided in the 
Adjudication Committee Charters. Serious AEs 
9.1.12 
Definition of SAEs 
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria: 
 Death 
 Life-threatening 
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.) 
 Significant or persistent disability/incapacity 
 Congenital anomaly/birth defect (including that occurring in a fetus) 
 Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious. 
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 9.1.2], allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, blood dyscrasias that do not result in inpatient hospitalization, or the development 
of drug dependency or drug abuse.) 
 Initial inpatient hospitalization or prolongation of hospitalization 
A patient admitted to a hospital, even if he/she is released on the same day, meets the criteria 
for the initial inpatient hospitalization. An emergency room visit that results in admission to 
the hospital would also qualify for the initial inpatient hospitalization criteria. However, 
emergency room visits that do not result in admission to the hospital would not qualify for 
this criteria and, instead, should be evaluated for 1 of the other criteria in the definition of 
serious (eg, life-threatening adverse experience, important medical event). 
Hospitalizations for reasons not associated with the occurrence of an AE (eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner) do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined. 
Note: Confirmed active TB is always to be considered as an SAE and must be captured on an 
SAE Report Form and provided to the Sponsor in accordance with SAE reporting requirements. 
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9.1.13 
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. 
9.1.14 
Follow-up of SAEs 
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and other safety topics of interest; further 
details regarding follow-up of PDILI events are provided in Section 9.4.1.5. Information on 
SAEs obtained after clinical database lock will be captured through the PS database without 
limitation of time. 
9.2 
Immediate reporting of AEs 
The following AEs must be reported immediately: 
 SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality 
 Suspected transmission of an infectious agent via a medicinal product 
 AEs of special interest as defined in Section 9.1.2  
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9.3 
Anticipated SAEs 
The following list of Anticipated SAEs (Table 9‒1) 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 9.1.13. 
Table 9‒1: 
Anticipated SAEs for the population of subjects with AS 
MedDRA system organ class 
MedDRA preferred term 
Skin and subcutaneous tissue disorders 
Psoriasis 
Eye disorders 
Uveitis 
Musculoskeletal and connective tissue disorders 
Dactylitis 
Tendonitis 
Atlantoaxial instability 
Gastrointestinal disorders 
Colitis ulcerative 
Crohn's disease 
Cardiac disorders 
Aortic valve incompetence 
Atrial tachycardia 
Atrioventricular block 
Bundle branch block 
Cardiomyopathy 
Vascular disorders 
Aortitis 
Respiratory, thoracic, and mediastinal disorders 
Pulmonary fibrosis 
Nervous system disorders 
Cauda equina syndrome 
Injury, poisoning, and procedural complications 
Spinal cord injury 
Spinal fracture 
Cervical Vertebral fracture 
Lumbar Vertebral fracture  
Thoracic Vertebral fracture 
Immune system disorders 
Amyloidosis 
Psychiatric disorders 
Depression 
AS=ankylosing spondylitis; 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. 
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9.4 
Laboratory measurements 
Clinical laboratory assessments consist of serum chemistry, and hematology (Table 9-2). A 
centralized laboratory will be used to supply all laboratory test supplies and analyze all blood 
samples for hematology, and biochemistry measurements. Any unscheduled laboratory testing 
should also be collected using the central laboratory.  
Specific details regarding the handling and processing of serum chemistry, hematology, and 
urinalysis samples are provided in the study laboratory manuals. 
Table 9-2: 
Laboratory measurements 
Hematology 
Chemistry 
Urinalysis 
Basophils 
Calcium 
Urine dipstick for pregnancy testing a 
Eosinophils 
Chloride 
Urinalysisb 
Lymphocytes 
Magnesium 
 
Atypical lymphocytes 
Potassium 
 
Monocytes 
Sodium 
 
Neutrophils 
Glucose (random) 
 
Hematocrit 
BUN 
 
Hemoglobin 
Creatinine 
 
MCH 
AST 
 
MCHC 
ALT 
 
MCV 
ALP 
 
Platelet count 
GGT 
 
RBC count  
Total bilirubin 
 
WBC count  
LDH 
 
 
Total cholesterol 
 
 
Uric acid 
 
 
CRP  
 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=C-reactive protein; GGT=gamma glutamyltransferase; LDH=lactate dehydrogenase; MCH=mean 
corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; 
RBC=red blood cell; WBC=white blood cell  
 a A urine pregnancy test will be performed for women of childbearing potential if there is a suspicion of 
pregnancy. A positive urine pregnancy test should always be confirmed with a serum pregnancy test. 
b These measurements will be performed only if a urinalysis is required for safety reasons. 
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9.4.1 
Evaluation of PDILI 
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1 , with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AE of special interest (see Section 9.1.2), and, if applicable, also reported as an 
SAE (see Section 9.1.12).  
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 9-3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 9.4.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 9.4.1.5).  
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 9-3 summarizes the approach to investigate PDILI. 
 
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Table 9-3: 
Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 IMP 
discontinuationd. 
 
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 9.4.1.4); 
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.e 
 
 
 
 
 
 
 
 
 
≥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 24hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP. 
Immediate IMP 
discontinuationd. 
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Table 9-3: 
Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 9.4.1.2). 
IMP discontinuation 
required if any of the 
following occur: 
 Subject cannot comply 
with monitoring 
schedule.  
 
Liver chemistry 
values continue to 
increase  
 
Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 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 48hours at the 
site with HCP (see 
Section 9.4.1.4). 
Monitoring of liver chemistry values at 
least twice per week for 2 weeks.e 
 
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 resolutione  
Continue to monitor until values 
normalize, stabilize, or return to within 
baseline valuese. 
 
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 9.4.1.1. 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 Details are provided in Section 9.4.1.2. 
e Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
 
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9.4.1.1 
Consultation with Medical Monitor and local hepatologist 
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 9.4.1.4) and SAE report (if applicable). 
9.4.1.2 
Immediate action: determination of IMP discontinuation 
All PDILI events require immediate action, testing, and monitoring.  
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate discontinuation (see Section 6.3.1 and Table 9-3 for details). 
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative. 
9.4.1.3 
IMP restart/rechallenge 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, maybe 
fatal, and must not occur. 
9.4.1.4 
Testing: identification/exclusion of alternative etiology 
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are included, but not 
limited to those listed in Table 9‒4 (laboratory measurements) and Table 9‒5 (additional 
information). Results of the laboratory measurements and information collected are to be 
submitted to the sponsor on the corresponding eCRF. If the medical history of the subject 
indicates a requirement for other assessments not included below, these additional assessments 
should be completed and submitted, as applicable. 
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory. 
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The following measurements are to be assessed (Table 9‒4): 
Table 9‒4: 
PDILI laboratory measurements 
Virology-
related 
Hepatitis A IgM antibody 
HBsAg 
Hepatitis E IgM antibody 
HBcAb-IgM 
Hepatitis C RNA 
Cytomegalovirus IgM antibody 
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophil 
antibody or monospot testing) 
Immunology 
Anti-nuclear antibody (qualitative and quantitative) 
Anti-smooth muscle antibody (qualitative and quantitative) 
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative) 
Hematology 
Eosinophil count 
Urinalysis 
Toxicology screen a 
Chemistry 
Amylase 
ALT, AST 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin 
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation 
Additional 
Prothrombin time/INR b 
Serum pregnancy test 
PK sample 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetics; RNA=ribonucleic acid; ULN=upper limit of normal 
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history. 
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause). 
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The following additional PDILI information is to be collected (Table 9‒5): 
Table 9‒5: 
PDILI information to be collected 
New or updated information 
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included. 
Pertinent medical history, including the following: 
 
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty liver 
disease”) 
 
Adverse reactions to drugs 
 
Allergies 
 
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency) 
 
Recent travel  
 
Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, should 
not be used as an explanation for significant AST and/or ALT elevations.) 
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash) 
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function 
Alcohol and illicit drug use 
Results of liver imaging or liver biopsy, if done 
Results of any specialist or hepatology consult, if done 
Any postmortem/pathology reports 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury 
9.4.1.5 
Follow-up evaluation 
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 9-3. Monitoring should continue until liver chemistry values normalize, stabilize, or return 
to baseline. Determination of stabilization is at the discretion of the Investigator in consultation 
with the hepatologist (as applicable) and UCB responsible physician, as needed. 
9.5 
Other safety measurements 
9.5.1 
Vital signs 
The Investigator or designee should measure all vital signs (systolic and diastolic blood pressure 
[BP], temperature [oral, axillary, or otic], pulse rate) after the subject has been sitting for at least 
5 minutes, and the subject should remain seated during the measurements. Body temperature 
should be obtained prior to dosing with IMP at study visits when IMP is administered. At 
AS0009 study entry, collect pulse and BP prior to drug administration and then at 30 minutes 
and 1 hour after dosing. At all other visits collect pulse and BP prior to drug administration and 
once after dosing (any time). 
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9.5.2 
Body weight  
The Investigator or designee will measure the weight of the subject in kilograms at the time 
points listed in Table 5‒1 and Table 5‒2. The same scale should be utilized throughout the study 
where possible. 
9.5.3 
Physical examination 
The physical examination should be conducted by the Investigator or designee at the time points 
listed in Table 5‒1 and Table 5‒2 and will include general appearance; ear, nose, and throat; 
eyes, hair, and skin; respiratory; cardiovascular; gastrointestinal; musculoskeletal; hepatic; 
neurological (including limb reflexes); and mental status. Findings considered clinically 
significant changes since the physical examination at the Baseline of the lead-in study will be 
recorded as AEs. 
9.5.4 
12-lead ECG 
The Investigator or designee will perform the ECG at the time points listed in Table 5‒1 and 
Table 5‒2. The ECGs will be read locally.  
9.5.5 
Tuberculosis and TB risk factor assessment and management 
All subjects will be assessed for TB at prior to administration of IMP in AS0009 and at the time 
points specified in the Schedules of Assessments (Table 5‒1 and Table 5‒2) through physical 
examination for signs and symptoms of TB, laboratory testing (Section 9.5.5.1), and subject 
questionnaire (Section 9.5.5.2).  
Prior to administration of IMP, subjects will have an IGRA test (QuantiFERON TB Test is 
recommended) and examination for signs and symptoms of TB unless an IGRA negative result is 
available less than 6 weeks prior to the first dose of open-label bimekizumab. 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 were negative. All subjects with TB test conversion must immediately 
stop IMP administration. In case of a TB test conversion, the subject must be considered as 
having either a suspected new latent or an active TB infection and be promptly referred to an 
appropriate specialist (eg, pulmonologist, infectious disease specialist) for further evaluation. If 
test conversion indicates LTB infection, active TB, or NTMB then, per UCB TB working 
instructions, TB test conversion (confirmed) should be classified adequately, either as due to 
LTB infection, active TB infection, or NTMB, respectively. Additional assessments (eg, blood 
tests or IGRA, chest x-rays, or other imaging) should be performed where medically relevant and 
documented. Such conversions should be reported to the UCB PS function. 
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. 
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If prophylaxis is not initiated, the subject must be withdrawn. 
Every related action should be discussed in advance with the Medical Monitor.  
Once withdrawn from study treatment, subjects should return for the ET Visit, complete all 
ET Visit assessments, and complete a SFU Visit (20 weeks after the last dose of IMP). 
Active TB or NTMB infection  
Subjects who develop active TB or NTMB infection during the study must be withdrawn from 
the study. The subject must be immediately discontinued from IMP and an ET Visit must be 
scheduled as soon as possible, but no later than the next scheduled visit. The subject should be 
encouraged to keep the SFU Visit as specified by the protocol. Treatment should be started 
immediately. 
Note that subjects with history of NTMB or active NTMB infection are excluded from the study 
regardless of prior or current therapy for this condition.  
9.5.5.1 
Tuberculosis assessment by IGRA 
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB Test is 
recommended) will be performed at study entry (unless an IGRA negative result is available less 
than 6 weeks prior to the first dose of open-label bimekizumab) and should be repeated at 
Week 48, Week 96, Week 144, Week 192, and the SFU Visit for all subjects. The test results 
will be reported as positive, negative, or indeterminate. UCB also recommends that a TB 
specialist be consulted where TB (latent or active) is suspected or if there are doubts regarding 
test results. If latent or active TB is identified, subject must undergo appropriate study-specified 
withdrawal procedures.  
9.5.5.2 
Tuberculosis questionnaire  
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will be completed at AS0009 entry, every 12 weeks 
throughout the study, at Week 208, and at the SFU Visit . The questionnaire will assist with the 
identification of subjects who may require therapy for TB. A “Yes” response to any of the 
questions during the study should trigger further assessments to determine if the subject has 
either LTB or active TB infection. 
Subjects with a confirmed latent TB (where no prophylactic treatment is initiated) or active TB 
infection must be withdrawn from the study (as further detailed in Section 9.5.5). 
9.5.5.3 
Tuberculosis management 
LTB infection and active TB identified during study 
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of IMP and will be referred to an appropriate TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Evidence of 
LTB infection is defined as subject’s IGRA test converts to positive or indeterminate (and 
confirmed indeterminate on repeat), or the subject’s questionnaire or history and physical 
indicates that TB infection or exposure may have occurred. Evidence of active TB includes, in 
addition to the aforementioned tests, signs, and symptoms of organ involvement. In either 
situation, the subject should be carefully assessed by a TB specialist for active TB. Subjects 
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diagnosed with active TB or LTB infection should be withdrawn from the study and receive 
appropriate TB or prophylaxis therapy.  
If a TB specialist excludes an active TB infection the subject can proceed with the IMP no earlier 
than 4 weeks after the start of an appropriate prophylactic therapy. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Confirmed active 
TB must be reported as an SAE. The Investigator is to complete and submit the TB follow-up 
form provided. 
The subject should be transferred to the care of his/her physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the ET Visit as soon as possible, but no 
later than the next scheduled study visit and complete all ET Visit assessments.  
The subject should be encouraged to complete a SFU Visit (20 weeks after the last dose of IMP). 
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed. 
9.5.6 
Pregnancy testing 
A urine pregnancy test will be performed at any scheduled or unscheduled visit if there is 
suspicion of pregnancy and will be confirmed with a serum pregnancy test if the urine test is 
positive. 
Pregnancy test results must be negative prior to administering IMP. 
9.5.7 
Assessment of suicidal ideation and behavior 
Suicidal ideation and behavior will be assessed by trained study personnel using the eC-SSRS. 
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the eC-SSRS assessments will be performed are specified in the schedule of 
study assessments (Section 5.2). 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Posner et al, 2011; Mundt et al, 2010). 
Subjects respond to standardized clinical questions that are presented in a uniform fashion. The 
eC-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The eC-SSRS takes approximately 3 to 10 minutes to complete. 
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10 
ASSESSMENT OF EFFICACY 
The timing for all assessments described below is specified in Table 5‒1 and Table 5‒2.  
10.1 
ASAS20, ASAS40, ASAS 5/6 response and ASAS partial 
remission 
The ASAS20 is defined as an improvement of at least 20% and absolute improvement of at least 
1 unit on a 0 to 10 numeric rating scale (NRS) in at least 3 of the 4 following domains: 
 PGADA (see Section 10.7) 
 Pain assessment (the total spinal pain NRS score; Section 10.8) 
 Function (represented by BASFI, Section 10.4) 
 Inflammation (the mean of the BASDAI Questions 5 and 6, concerning 
 
)  
 and absence of deterioration in the potential remaining domain (deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit). 
The ASAS criteria for 40% improvement are defined as relative improvements of at least 40%, 
and absolute improvement of at least 2 units on a 0 to 10 NRS in at least 3 of the 4 domains and 
no worsening at all in the remaining domain. 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and CRP as more objective measures (Brandt et al, 2004). 
The ASAS partial remission response is defined as a score of ≤2 units on a 0 to 10 unit scale in 
all 4 domains listed above for ASAS20. 
10.2 
ASDAS-CRP 
The ASDAS is comprised of a number of assessments which are scored by the subject and 
Investigator and multiplied by a validated formula (van der Heijde et al, 2009) as listed: 
 0.121 x 
 (BASDAI Question 2 result, Section 10.3) 
 0.058 x 
 (BASDAI Question 6 result, Section 10.3) 
 0.110 x PGADA (Section 10.7) 
 0.073 x 
 (BASDAI Question 3 result, Section 10.3) 
 0.579 x (natural logarithm of the CRP [mg/L] + 1)  
, PGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009). The results of these calculations 
are summed to calculate the ASDAS.  
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The following definition applies for ASDAS Disease Activity categories: 
 ASDAS-ID: ASDAS <1.3 
 ASDAS-Moderate Disease: ASDAS ≥1.3, <2.1 
 ASDAS-High Disease activity: ASDAS ≥2.1, ≤3.5 
 ASDAS-very High Disease activity: ASDAS >3.5 
10.3 
BASDAI 
The most common instrument used to measure the disease activity of AS from the subject’s 
perspective is the BASDAI (Garrett et al, 1994). The BASDAI is a validated self-reported 
instrument which consists of six 10-unit horizontal NRSs to measure severity of 
 
(both severity and 
duration, respectively) over the last week (van Tubergen et al, 2015). The final BASDAI score 
ranges from 0 to 10, with lower scores indicating lower disease activity. Question 2 of the 
BASDAI asks the subject 
 
 factor in the calculation of ASDAS-CRP. 
Question 3 of the BASDI asks the subject to 
 
 
 factor in the calculation of ASDAS-CRP. Question 6 of the BASDAI asks the 
, and the 
score is used as the 
 factor in the calculation of ASDAS-CRP. 
The BASDAI is calculated as follows:  
𝐵𝐴𝑆𝐷𝐴𝐼=
Q1 + Q2 + Q3 + Q4 + (𝑄5 + 𝑄6
2
)
5
 
10.3.1 
 item of the BASDAI 
 as a major symptom of AS can effectively be measured with single-item questions such 
as the BASDAI item (van Tubergen et al, 2002b). This item has shown moderate to good 
reliability and responsiveness (van Tubergen et al, 2002b). The same minimal clinically 
important difference (MCID) will be used for the 
 item of the BASDAI as for the total 
BASDAI score, ie, a change of 1 unit on the NRS. 
10.4 
Function – BASFI 
The BASFI is a validated disease-specific instrument for assessing physical function (van der 
Heijde et al, 2005; Calin et al, 1994). The BASFI comprises 10 items relating to the past week. 
The NRS version will be used for the answering options of each item on a scale of 0 (“Easy”) to 
10 (“Impossible”) (van Tubergen et al, 2015 and van Tubergen et al, 2002a). The BASFI is the 
mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating 
better physical function. The MCID used to interpret scores is 7mm on a 0 to 100mm VAS or 
17.5% of the Baseline score (Pavy et al, 2005); an MCID of 1 unit will be used for the NRS 
version.  
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10.5 
BASMI 
The BASMI characterizes the spinal mobility of subjects with AS. The BASMI is a disease-
specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; 
tragus to wall distance; lateral spinal flexion; modified Schober test; intermalleolar distance. 
Each of the 5 movements is scored according to the linear BASMI definition. The mean of the 5 
scores provides the BASMI score. The higher the BASMI score the more severe the subject’s 
limitation of movement due to their AS. 
10.6 
MASES 
Enthesitis is assessed via MASES. The MASES is an index that measures the severity 
(ie, intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003) each scored as 0 or 1 and then summed for a possible 
score of 0 to 13. 
10.7 
PGADA 
Subjects will score their global assessment of their disease activity in response to the question 
“How active was your spondylitis on average during the last week?” using a NRS where 0 is 
“not active” and 10 is “very active” (van Tubergen et al, 2015). 
10.8 
Total and nocturnal spinal pain 
The pain experienced by AS subjects is adequately measured by 2 separate questions: (1) total 
pain in the spine due to AS (ie, “How much pain of your spine due to spondylitis do you have?”); 
and (2) pain in the spine at night due to AS (ie, “How much pain of your spine due to spondylitis 
do you have at night?”) (Sieper et al, 2009; van der Heijde et al, 2005; Committee for Proprietary 
Medicinal Product [CPMP]/EWP/556/95). When responding to each question, the subject is to 
consider the average amount of pain in the preceding week.  
10.9 
Short-Form 36-item Health Survey 
The SF-36 (Version 2, standard recall) is a 36-item generic health-related quality of life 
(HRQoL) instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as 
follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General 
Health (5 items),Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), 
Mental Health (5 items), and 1 item for perceived stability or change in health (Health 
Transition) during the last year. The concepts represented by these domains contribute to 
physical, mental, and social aspects of HRQoL. 
In addition to domain scores, the Physical Component Summary and Mental Component 
Summary scores are calculated from the 8 domains (excluding the Health Transition item). 
Component scores appreciate the impact of each domain on physical and mental health status 
(Maruish, 2011). Each of the 8 domain scores and the component summary scores range from 
0 to 100, with a higher score indicating a better health status. The 2 component summary scores 
are standardized with a mean of 50 and a standard deviation (SD) of 10 in the general US 
population.  
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10.10 
ASQoL 
The ASQoL, a validated disease-specific 18-item questionnaire, has been developed specifically 
for measuring HRQoL in subjects with AS (Doward et al, 2003). The ASQoL has been used and 
has shown to be responsive in axSpA (Barkham et al, 2009; Haibel et al, 2008). The ASQoL 
score ranges from 0 to 18 with higher score indicating worse HRQoL.  
10.11 
HADS 
The HADS was chosen for its well-established psychometric properties and its use in clinical 
research on biological therapy in subjects with chronic plaque PSO (Langley et al, 2010; 
Dauden et al, 2009). The HADS scores for anxiety and for depression range from 0 to 21 with 
higher scores indicating worse state. A score below 8 is considered to be normal whereas a score 
of 15 and above is considered severe (Snaith and Zigmond, 1994). 
11 
ASSESSMENT OF IMMUNOGENICITY 
The Investigator or designee will obtain blood samples for measurement of bimekizumab plasma 
concentrations and antibodies to bimekizumab at the time points specified in Table 5‒1 and 
Table 5‒2. When these samples are required at a visit during which the subject is dosed with 
IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at the same time 
of the sampling for clinical laboratory tests. The time and date of collection will be recorded in 
the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, and 
shipping are provided in the laboratory manual for this study. The presence of antibodies to 
bimekizumab will be determined using a validated bioanalytical method. Detailed information on 
sample analysis will be provided in a bioanalytical report. 
12 
STUDY MANAGEMENT AND ADMINISTRATION  
12.1 
Adherence to protocol 
The investigator should not deviate from the protocol. However, the investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
sponsor. 
After implementation of such measure, the investigator must notify the CPM of the sponsor 
within 24 hours and follow any local regulatory requirements. 
12.2 
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 CRFs, ensure that all protocol 
requirements, applicable authorities’ regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records. 
12.2.1 
Definition of source data  
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of CRFs are not considered acceptable source 
documents.  
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, or quality of life 
questionnaires, for example. Source documents should be kept in a secure, limited access area. 
Sponsor or designee will review to ensure that computerized source documents produced by the 
site are compliant with Food and Drug Administration (FDA) Part 11 requirements and 
document appropriately. Source documents that are computer generated and stored electronically 
must be printed for review by the monitor (eg, ECG reports). Once printed, these copies should 
be signed and dated by the Investigator and become a permanent part of the subject’s source 
documents. The Investigator will facilitate the process for enabling the monitor to compare the 
content of the printout and the data stored in the computer to ensure all data are consistent. 
Electronic data records must be saved and stored as instructed by UCB (or designee). 
12.2.2 
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 CRF should be supported by source 
documents, unless otherwise specified in Section 12.2.1. 
12.3 
Data handling 
12.3.1 
Case Report form completion 
This study will use electronic data capture (EDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRF and in all required reports. 
This study will also use an electronic device (Site Tablet) to capture patient reported outcomes. 
Serious AE reporting will be done using the SAE Report Form (see Section 9.1.13) 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. 
12.3.2 
Database entry and reconciliation 
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. This study is performed using EDC: the data are entered into the electronic CRFs once 
and are 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. 
12.3.3 
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. 
12.4 
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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12.5 
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. 
12.6 
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). 
12.7 
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. 
13 
STATISTICS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan. 
13.1 
Definition of analysis sets 
The Enrolled Set (ES) will consist of all subjects who have given informed consent for AS0009. 
The Safety Set (SS) will consist of all subjects who receive at least 1 dose of the IMP in AS0009. 
The Full Analysis Set (FAS) will consist of all enrolled subjects who receive at least 1 dose of 
the IMP and have a valid measurement for at least 1 efficacy variable at AS0009 study entry.  
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13.2 
General statistical considerations 
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, summary statistics will consist of number of available observations, arithmetic mean, 
standard deviation (SD), median, minimum, and maximum unless stated otherwise. 
Two subpopulations will be defined for this study. Subpopulation 1 will consist of all subjects 
who do not receive rescue therapy according to the criteria outlined in Section 5.1.1. 
Subpopulation 2 will consist of all subjects who receive rescue therapy according to the criteria 
outlined in Section 5.1.1. Analyses of the primary and secondary variables will also be done on 
both subpopulations. 
Changes from Baseline will be calculated relative to the Baseline of studies AS0008. Variables 
measured at the start of AS0009 will be referred to as AS0009 entry values. 
13.3 
Planned safety analyses 
13.3.1 
Safety analyses 
Safety variables will be analyzed for all subjects in the SS. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities.  
Adverse events will be summarized descriptively by treatment group at completion of the lead-in 
study, primary system organ class, high level term, and preferred term. This summary will 
include raw incidence rates, exposure adjusted incidence rate (EAIR) with associated 95% 
confidence interval, and the exposure adjusted event rate (EAER), where the EAIR and EAER 
are expressed per 100 patient-years of exposure.  
Patient exposure at risk in days will be defined as date of last administration of 
bimekizumab - date of first administration of bimekizumab +20 weeks. If a subject has an 
adverse event with fatal outcome, patient exposure at risk is censored at the date of death.  
The extent of exposure to IMP in AS0009 will be summarized using descriptive statistics by 
treatment group at AS0009 entry. 
Change from AS0009 entry values in laboratory and vital signs variables will be summarized 
descriptively by visit and by treatment group at completion of the lead-in study. 
The results of the eC-SSRS will be summarized by visit and by treatment group at completion of 
the lead-in study using number of subjects and percentages with events in: each of the eC-SSRS 
questions, suicidal behavior, suicidal ideation, suicidal behavior and ideation, and self-injurious 
behavior without suicidal intent. 
All safety analyses will be conducted for both subpopulations. 
13.4 
Planned efficacy analyses 
Secondary and other efficacy variables will be summarized for all subjects in the FAS; efficacy 
analyses will be performed over the 208 weeks (4 years).  
Responder variables (eg, ASAS20 response) will be derived relative to Baseline of AS0008, and 
summarized descriptively. Percentages will be summarized descriptively by visit, by randomized 
treatment group, and by treatment group at completion of the lead-in study.  
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Change from Baseline of AS0008 of all continuous variables will be summarized descriptively 
by visit, by randomized treatment group, and by treatment group at completion of the lead-in 
study. 
13.4.1 
Subgroup analysis 
Subgroup analyses will be performed on the efficacy variables. The following variables for 
subgroup analyses will be defined: 
 Region 
 Previous TNF inhibitor exposure 
 Concomitant NSAID status at AS0009 entry  
13.5 
Planned immunogenicity analyses 
Immunogenicity variables will be analyzed for all subjects in the SS.  
Bimekizumab plasma concentration and anti-bimekizumab antibody appearance will be 
summarized by visit, by randomized treatment group, and by treatment group at completion of 
the lead-in study. The first occurrence of anti-bimekizumab antibody positivity as well as 
persistent and transient anti-bimekizumab antibody positivity will be summarized by visit, by 
randomized treatment group, and by treatment group at completion of the lead-in study. Figures 
on persistent and transient anti-bimekizumab antibody positivity over time and on the 
relationship between ASAS40 response and anti-bimekizumab antibody positivity over time will 
be produced. 
13.6 
Other analyses 
Other variables will be summarized using descriptive statistics using the treatment group at 
completion of lead-in study. 
13.7 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the safety or efficacy outcomes for an individual 
subject. The criteria for identifying important protocol deviations will be defined within the 
appropriate protocol-specific document. Important protocol deviations will be reviewed as part 
of the ongoing data cleaning process and all important deviations will be identified and 
documented prior to unblinding to confirm exclusion from analysis sets 
13.8 
Handling of dropouts or missing data 
Missing binary efficacy variables will be imputed using nonresponder imputation (NRI). In NRI, 
each subject with missing data or who has prematurely finished the study will be counted as a 
nonresponder. 
For missing continuous efficacy variables, a multiple imputation (MI) approach will be used. In 
MI, the missing value is replaced by a set of plausible values, where each value is a Bayesian 
draw from the conditional distribution of the missing data given the observed data. 
Non-monotone missing data (ie, intermittent missing data) will be imputed several times with the 
Markov Chain Monte Carlo (MCMC) method and monotone missing data will be imputed using 
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a monotone regression model. Each set of imputed data will then be summarized and the 
summaries will be combined into a single inference (Carpenter and Kenward, 2013). 
Safety data will not be imputed. 
As a sensitivity analysis, all efficacy variables will be analyzed based on observed data. Subjects 
with missing data or who have prematurely finished the study will be treated as missing. 
13.9 
Planned interim analysis and data monitoring 
An interim analysis and data cuts may be performed for regulatory and publication purposes. 
13.10 
Determination of sample size 
There is no formal sample size for this study. The sample size is determined by the number of 
subjects in AS0008 who are eligible for AS0009. Up to 285 subjects from AS0008 could be 
enrolled into this study.  
14 
ETHICS AND REGULATORY REQUIREMENTS 
14.1 
Informed consent 
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator. 
Prior to participation in the study, the written ICF should be signed and personally dated by the 
subject and by the person who conducted the informed consent discussion (Investigator or 
designee). The subject must receive a copy of the signed and dated 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. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the 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. 
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14.2 
Subject identification cards 
Upon signing the Informed Consent, the subject will be provided with a subject identification 
card in the language of the subject. The Investigator will fill in the subject identifying 
information and medical emergency contact information. The Investigator will instruct the 
subject to keep the card with him/her at all times. 
14.3 
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, 
investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
14.4 
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. 
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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). 
14.5 
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. 
15 
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. 
16 
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spondylitis: a multireader experiment. J of Rheum. 2007;34(4):862-70. 
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an 
ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. 
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QualityMetric Incorporated; 2011. 
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Validation of a Computer-Automated Columbia-Suicide severity Rating Scale Using Interactive 
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rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007. Arthritis 
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bath ankylosing spondylitis indices: a prospective study. J Rheumatol. 2005;32:80-5. 
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Study of Adalimumab in Spondyloarthritis, as Assessed by the Berlin and Spondyloarthritis 
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Dis. 2013(1);5:45-54. 
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estimates from a cross-sectional survey. Arthritis Care Res (Hoboken). 2012;64:905-10. 
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Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, et al. The 
Assessment of SpondyloArthritis International Society classification criteria for peripheral 
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disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception 
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van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. 
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2002b;47:8-16. 
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17 
APPENDICES 
17.1 
Markedly abnormal laboratory values 
Table 17-1 
Definitions of markedly abnormal hematology values 
Parameter (SI units) 
Markedly Abnormal Definition 
Low 
High 
Hemoglobin (g/dL) 
<LLN 
AND 
>2.0 decrease from baseline 
N/A 
Hemoglobin (g/dL) 
<8.0 
N/A 
Leukocytes (total x 1000) 
<2.0 
N/A 
Lymphocytes (x 1000) 
<0.5 
N/A 
Neutrophils (x 1000) 
<1.0 
N/A 
Platelets (x 1000) 
<50 
N/A 
LLN=lower limit of normal; N/A = Not Applicable: SI=standard international 
a Withdrawal criteria for neutrophils is <0.5 (Section 6.3). 
Data source: modified from Appendix Rheumatology Common Toxicity Criteria v.2.0 presented in 
Woodworth et al, 2007 
 
Table 17‒2: Definitions of markedly abnormal biochemistry values 
Parameter (SI units) 
Markedly Abnormal Definition 
Low 
High 
Alkaline Phosphatase 
N/A 
>3 x ULN 
ALT 
N/A 
>3 x ULN 
AST 
N/A 
>3 x ULN 
Calcium (mg/dL) 
<7.0 
>12.5 
Creatinine (mg/dL) 
N/A 
>1.8 x ULN 
Glucose (mg/dL) 
<40 
>250 
Potassium (mmol/L) 
<3.0 
>6.4 
Sodium (mmol/L) 
<125 
N/A 
Total bilirubin 
N/A 
≥2 x ULN 
Uric acid 
N/A 
≥3 x ULN 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; SI=standard international; 
ULN=upper limit of normal 
 
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17.2 
Protocol Amendment 1 
Rationale for the amendment 
The purpose of this protocol amendment is the following: 
• 
Clarify procedures and assessments during visits 
• 
Revise language around self-administration of bimekizumab 
• 
Revise language around description of vital signs 
• 
Remove MRI substudy 
• 
Remove serology tests 
• 
Remove inclusion of Data Monitoring Committee 
• 
Clarified language around vaccinations 
 
Modifications and changes 
Global Changes 
Change #1 
Removal of the MRI substudy from the protocol. As a result, all mention of MRIs in the entire 
document was removed to include the list of abbreviations. The following sections had MRI 
information deleted: 
• 
Summary, 2nd to last paragraph, last sentence 
• 
Section 3.3 Other objectives, bullet 5 
• 
Section 4.3.2 Efficacy variables, bullet 14 
• 
Section 5.1.2 Imaging evaluation 
• 
Table 5-1 Schedule of study assessments (Week 1 through Week 104): MRI for subjects in 
the MRI substudy in AS0008 protocol activity row and footnote l 
• 
Table 5-2 Schedule of study assessments (Week 108 through Week 208): MRI for subjects in 
the MRI substudy in AS0008 protocol activity row and footnote h 
• 
Sections 8.1, 8.5, 8.11, 8.12: Obtain MRI of spine and the SI joint if the subject is 
participating in the MRI substudy 
• 
Section 10.12 MRI Assessment (SPARCC and ASspiMRI) 
 
 
 
 
 
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The following global change was made for all visits in Section 8 that included a vital signs 
measurement: 
Change #2 
Vital signs (prior to drug administration, and 30 minutes and 1 hour after dosing)* 
Has been changed to: 
Measure vital signs (temperature, dose, and blood pressure [BP])* 
 
Change #3 
Vital signs (prior to drug administration and once after dosing) 
Has been changed to: 
Measure vital signs (temperature, dose, and BP) 
 
Specific changes 
Change #1 
List of Abbreviations 
The following abbreviations have been deleted: 
• 
ASspiMRI-a Ankylosing Spondylitis spine Magnetic Resonance Imagine-activity• DMC
 
Data Monitoring Committee 
• 
MRI 
Magnetic Resonance Imaging 
 
Change #2 
Table 5-1: Schedule of study assessments 
eC-SSRS was added to Weeks 4 and 8 schedule of assessments table.  
Change #3 
Table 5-1: Schedule of study assessments 
Vital signs was added to Weeks 4 and 8 schedule of assessments table.  
 
Change #4 
Table 5-2: Schedule of study assessments 
Removal of the IXRS from the schedule of assessments table for Week 196. 
 
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Change #5 
Section 7.8.2: Prohibited concomitant treatments (medications and 
therapies); Vaccines 
Administration of live, attenuated vaccines is not allowed during the conduct of the study or for 
20 weeks after the last dose of IMP. Administration of non-live, attenuated vaccines is allowed 
during the study at the discretion of the Investigator. 
Has been changed to: 
Administration of live, attenuated vaccines is not allowed during the conduct of the study or for 
20 weeks after the last dose of IMP. Administration of non-live, inactivated vaccines is allowed 
during the study at the discretion of the Investigator. 
 
Change #6 
Section 8.2: Week 4 (Visit 2) and Week 8 (Visit 3) 
eC-SSRS was added to Weeks 4 and 8 procedures or assessments bulleted list. 
 
Change #7 
Section 8.2: Week 4 (Visit 2) and Week (Visit 3) 
“Measure vital signs (temperature, pulse, and BP)” was added to Weeks 4 and 8 procedures or 
assessments bulleted list. 
 
Change #8 
Section 8.4: Week 16, Week 20, Week 28, Week 32, Week 40, Week 44,  
Week 52, Week 56, Week 64, Week 68, Week 76, Week 80, Week 88,        
Week 92, Week 100, and Week 104 
Administer bimekizumab (after all other visit assessments are completed) 
 Has been changed to: 
Subjects will be given the opportunity for self-administration of bimekizumab. Adverse 
events will be captured spontaneously if the subject decides to visit the site to receive the 
bimekizumab administration.  
 
Change #9 
Section 8.8: Week 112, Week 116, Week 124, Week 128, Week 136,        
Week 140, Week 148, Week 152, Week 160, Week 164, Week 172, Week 176, 
Week 184, Week 188, Week 196, and Week 200 
Administer bimekizumab (after all other visit assessments are completed) 
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 Has been changed to: 
Subjects will be given the opportunity for self-administration of bimekizumab. Adverse 
events will be captured spontaneously if the subject decides to visit the site to receive the 
bimekizumab administration.  
 
Change #10 
Section 9.1.11: Safety signal detection, 4th paragraph 
In addition, an independent Data Monitoring Committee (DMC) will periodically review and 
monitor the safety data from this study and advise UCB. Details are provided in the DMC 
Charter. Cardiovascular and Neuropsychiatric Adjudication Committees will also periodically 
review and monitor the safety data from this study. Details are provided in the Adjudication 
Committee Charters.  
Has been changed to: 
In addition, Cardiovascular and Neuropsychiatric Adjudication Committees will also 
periodically review and monitor the safety data from this study and advise UCB. Details are 
provided in the Adjudication Committee Charters. 
 
Change #11 
Section 9.5: Laboratory measurement, 1st paragraph, last sentence 
The following sentence has been deleted: 
 Testing to rule out hepatitis B, hepatitis C, and HIV will be performed at AS0009 entry in 
addition to those measurements listed in Table 9 2.  
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17.3 
Protocol Amendment 2 
Rationale for the amendment 
The purpose of this amendment is as follows:  
 To update the study contact details for the sponsor study physician, clinical project manager 
and clinical trial biostatistician. 
 Amend the open-label treatment period for clarification, as per request from the regulatory 
agency. 
 Amend the study procedures and assessments to be performed at the Safety Follow-up visit. 
Efficacy assessments were removed since they are not required at the SFU visit. 
 Amend the time frame for the availability of negative results from the QuantiFERON TB 
Test, to be aligned with the TB Standard Operating Procedure. 
 Include additional wording to the inclusion criteria (criterion #5) listing acceptable methods 
of contraception for female subjects. 
 Amend the exclusion criteria (criterion #2) to include further clarification on when to consult 
the medical monitor.  
 To revise the withdrawal criteria section to provide instructions for the management of 
subjects with newly diagnosed IBD or with IBD flares during the study. 
 To revise and clarify the SAE criteria for pregnancy for consistency. 
 Amend the table for identification/exclusion of alternative etiology to include ALT and AST. 
 Amend and remove wording from the criteria determined for handling of dropouts or missing 
data. 
Modifications and changes 
Global change 
The following global change was made for the duration of the open-label treatment period and 
period for administration of bimekizumab:  
208 weeks (4 years)  
Has been changed to: 
204208 weeks (~4 years) 
 
Specific changes 
Change #1 
List of Abbreviations 
The following abbreviations have been added:  
IUD 
intrauterine device 
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IUS 
intrauterine hormone-releasing system 
MCMC 
Markov Chain Monte Carlo 
RCTC 
Rheumatology Common Toxicity Criteria 
 
Change #2 
Sponsor Study Physician 
Name: 
, MD 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
Phone: 
 (office) 
 (mobile) 
Clinical Project Manager 
Name: 
, PhD 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Str.10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
, Senior Biostatistician 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
 
UNITED STATES 
Phone: 
  
Has been changed to:  
Sponsor Study Physician 
Name: 
, MD, MSc, PhD 
, MD 
Address: 
UCB Pharma Ltd. UCB BIOSCIENCES Inc. 
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208 Bath Road 8010 Arco Corporate Drive 
Slough, SL1 3WE Raleigh, NC 27617 
UNITED KINGDOM UNITED STATES 
Phone: 
 
 
Clinical Project Manager 
Name: 
, PhD 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Str.10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
, MSSenior Biostatistician 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
 
UNITED STATES 
Phone: 
  
 
Change #3 
Section 5.1 Study design, 3rd paragraph  
Additionally, as described in (Section 5.1.1), other treatments may be used in addition to 
bimekizumab per Investigator discretion. Subjects not responding to treatment may be 
withdrawn from the study at the discretion of the Investigator. 
Has been changed to:  
Additionally, as described in (Section 5.1.1), other treatments may be used in addition to 
bimekizumab per Investigator discretion. Subjects not responding to treatment may be 
withdrawn from the treatment and study at the discretion of the Investigator. 
 
Change #4 
Section 5.1.2 Study duration per subject  
The study duration for each subject is estimated to be up to a maximum of 224 weeks: 
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 Open Label Treatment Period: up to 208 weeks (4 years) 
 SFU Visit: 20 weeks after the final dose of bimekizumab 
The subject may remain in the study until the study ends after 4 years (224 weeks of treatment), 
until the Sponsor decides to close the study, or until bimekizumab development is stopped by the 
Sponsor, whichever comes first. The Sponsor may consider transitioning the subject into another 
bimekizumab study or program. 
The end of the study is defined as the date of the last visit of the last subject in the study.  
Has been changed to:  
The study duration for each subject is estimated to be up to a maximum of 224 weeks: 
 Open-Label Treatment Period: up to 2048 weeks (~4 years)  
 SFU Visit: 20 weeks after the final dose of bimekizumab 
The subject may remain in the study until the study ends after 224 weeks4 years (208 weeks of 
treatment), until the Sponsor decides to close the study, or until bimekizumab development is 
stopped by the Sponsor, whichever comes first. The Sponsor may consider transitioning the 
subject into another bimekizumab study or program. 
The end of the study is defined as the date of the last visit of the last subject in the study. 
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Change #5 
Section 5.2 Schedule of study assessments, Table 5-1 
 
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Has been changed to:  
 
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Change #6 
Section 5.2 Schedule of study assessments (Week 1 through Week 104), Table 5-1 (Schedule of 
study assessments [Week 1 through Week 104]), Footnote ‘k’ 
k It is recommended that the QuantiFERON TB GOLD test be performed. This assessment will 
be performed at study entry, unless an IGRA negative result is available less than 4 weeks prior 
to the first dose of open-label bimekizumab. 
Has been changed to:  
k It is recommended that the QuantiFERON TB GOLD test Test be performed. This 
assessment will be performed at study entry, unless an IGRA negative result is available less 
than 64 weeks prior to the first dose of open-label bimekizumab. 
 
Change #7 
Section 5.2 Schedule of study assessments (Week 1 through Week 104), Table 5-2 (Schedule of 
study assessments [Week 108 through Week 208]), Footnote ‘g’ 
g It is recommended that the QuantiFERON TB GOLD test be performed. This assessment will 
be performed at study entry, unless an IGRA negative result is available less than 64 weeks prior 
to the first dose of open-label bimekizumab. 
Has been changed to:  
g It is recommended that the QuantiFERON TB GOLD test Test be performed. This 
assessment will be performed at study entry, unless an IGRA negative result is available less 
than 64 weeks prior to the first dose of open-label bimekizumab. 
 
Change #8 
Section 6.1 Inclusion criteria (criterion #5) 
5. Female subjects must be postmenopausal (at least 1 year), permanently sterilized (eg, tubal 
occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing potential (and 
engaged in sexual activity that could result in procreation), must be willing to use a highly 
effective method of contraception until 20 weeks after last administration of study 
medication, and have a negative pregnancy test at the last visit of AS0008. 
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up until 20 weeks after the last administration of study medication 
(anticipated 5 half-lives). 
Has been changed to:  
5. Female subjects must be postmenopausal (at least 1 year), permanently sterilized (eg, tubal 
occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing potential (and 
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engaged in sexual activity that could result in procreation), must be willing to use a highly 
effective method of contraception until 20 weeks after last administration of study 
medication, and have a negative pregnancy test at the last visit of AS0008. The following 
methods are considered highly effective when used consistently and correctly: 
 combined (estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation (oral, intravaginal or transdermal)  
 progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable) 
 intrauterine device (IUD) 
 intrauterine hormone-releasing system (IUS) 
 bilateral tubal occlusion 
 vasectomized partner  
 sexual abstinence if it is in accordance with a subject’s preferred and common 
lifestyle. Subjects who use abstinence as a form of birth control must agree to 
abstain from heterosexual intercourse until 20 weeks after the last dose of IMP. 
Study personnel must confirm the continued use of abstinence is still in accordance 
with the subject’s lifestyle at regular intervals during the study. 
Male subjects with a partner of childbearing potential must be willing to use a condom when 
sexually active, up until 20 weeks after the last administration of study medication (anticipated 
5 half-lives). 
 
Change #9 
Section 6.2 Exclusion criteria (criterion #2) 
2. Subjects with any current sign or symptom that may indicate a medically significant active 
infection (except for the common cold) or has had an infection requiring systemic antibiotics 
within 2 weeks of study entry. 
Has been changed to:  
2. Subjects with any current sign or symptom that may indicate a medically significant active 
infection (except for the common cold) or has had an infection requiring systemic antibiotics 
within 2 weeks of study entry. The medical monitor must be consulted prior to subject’s 
entry into AS0009 in such cases. 
 
Change #10 
Section 6.3 Withdrawal criteria 
The following was added to the withdrawal criteria: 
12. Subjects with newly diagnosed IBD or with IBD flares during the study must: 
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 Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist 
 Discontinue IMP and be followed-up until resolution of active IBD symptoms 
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue in the study and contact 
the Medical Monitor and UCB study physician to confirm the subject's suitability for 
continued participation in the study. 
 
Change #11 
Section 8.1 AS0009 study entry (Visit 1), bullet #22 
 IGRA TB test (unless an IGRA negative result is available less than 4 weeks prior to the first 
dose of open-label bimekizumab) 
Has been changed to:  
 IGRA TB test (unless an IGRA negative result is available less than 64 weeks prior to the 
first dose of open-label bimekizumab) 
 
Change #12 
Section 8.14 SFU Visit (Visit 23) 
The following procedures or assessments will be performed: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Physical examination 
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 MASES 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test 
 Contact the IXRS 
Has been changed to:  
The following procedures or assessments will be performed: 
 Concomitant medications 
 Record AEs 
 eC-SSRS 
 HADS 
 ASQoL 
 BASDAI 
 BASFI 
 SF-36 
 PGADA 
 Total and nocturnal spinal pain 
 TB questionnaire 
 Measure vital signs (temperature, pulse, and BP) 
 Body weight 
 Physical examination 
 MASES 
 Obtain blood samples for: 
 Standard safety laboratory tests (hematology and biochemistry) 
 CRP 
 Anti-bimekizumab antibodies and bimekizumab plasma concentrations 
 Perform a urine pregnancy test if there has been a delay in menses 
 IGRA TB test 
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 Contact the IXRS 
 
Change #13 
Section 9.1 Definition of AE 
The following was added to the definition of AEs: 
Adverse events that occurred during the AS0009 lead-in study and are still deemed ongoing 
at the time of enrolment (signed ICF) will be captured in the database and followed up, as 
described in Section 9.16 . 
 
Change #14 
Section 9.1.8 Pregnancy, 5th paragraph 
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective for 
a medical condition or spontaneous), unintended pregnancy after hormonal contraceptive failure 
(if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal demise, or any 
congenital anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report Form. 
Has been changed to:  
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective 
abortion when medically indicated (e.g. when pregnancy is endangering life or health of 
woman or when fetus will be born with severe abnormalities), unintended pregnancy after 
hormonal contraceptive failure (if the hormonal contraceptive was correctly used), ectopic 
pregnancy, fetal demise, or any congenital anomaly/birth defect of the baby. Those SAEs 
must be additionally reported using the Investigator SAE Report form. 
 
Change #15 
Section 9.4.1.4 
 Testing: identification/exclusion of alternative etiology, Table 9-4 (PDILI 
laboratory measurements)   
Virology-
related 
Hepatitis A IgM antibody 
HBsAg 
Hepatitis E IgM antibody 
HBcAb-IgM 
Hepatitis C RNA 
Cytomegalovirus IgM antibody 
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing) 
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Immunology Anti-nuclear antibody (qualitative and quantitative) 
Anti-smooth muscle antibody (qualitative and quantitative) 
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative) 
Hematology 
Eosinophil count 
Urinalysis 
Toxicology screena 
Chemistry 
Amylase 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin 
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation 
Additional 
Prothrombin time/INRb 
Serum pregnancy test 
PK sample 
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal 
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history. 
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause). 
Has been changed to:  
Virology-
related 
Hepatitis A IgM antibody 
HBsAg 
Hepatitis E IgM antibody 
HBcAb-IgM 
Hepatitis C RNA 
Cytomegalovirus IgM antibody 
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophile antibody or monospot testing) 
Immunology Anti-nuclear antibody (qualitative and quantitative) 
Anti-smooth muscle antibody (qualitative and quantitative) 
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Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative) 
Hematology 
Eosinophil count 
Urinalysis 
Toxicology screena 
Chemistry 
Amylase 
ALT, AST 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin 
Serum CPK and LDH to evaluate possible muscle injury causing transaminase 
elevation 
Additional 
Prothrombin time/INRb 
Serum pregnancy test 
PK sample 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal 
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history. 
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause). 
 
 
Change #16 
Section 9.5.5  Tuberculosis and TB risk factor assessment and management, 2nd paragraph 
Prior to administration of IMP, subjects will have an IGRA test (QuantiFERON TB GOLD is 
recommended) and examination for signs and symptoms of TB unless an IGRA negative result is 
available less than 4 weeks prior to the first dose of open label bimekizumab. In addition, each 
subject will complete a TB questionnaire with questions directed at symptoms of TB and 
potential exposure to TB. 
Has been changed to: 
Prior to administration of IMP, subjects will have an IGRA test (QuantiFERON TB TestGOLD 
is recommended) and examination for signs and symptoms of TB unless an IGRA negative result 
is available less than 64 weeks prior to the first dose of open label bimekizumab. In addition, 
each subject will complete a TB questionnaire with questions directed at symptoms of TB and 
potential exposure to TB. 
 
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Change #17 
Section 9.5.5.1 
 Tuberculosis assessment by IGRA 
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD is 
recommended) will be performed at study entry (unless an IGRA negative result is available less 
than 4 weeks prior to the first dose of open-label bimekizumab) and should be repeated at 
Week 48, Week 96, Week 144, Week 192, and the SFU Visit for all subjects. The test results 
will be reported as positive, negative, or indeterminate. UCB also recommends that a TB 
specialist be consulted where TB (latent or active) is suspected or if there are doubts regarding 
test results. If latent or active TB is identified, subject must undergo appropriate study-specified 
withdrawal procedures.  
Has been changed to: 
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB TestGOLD is 
recommended) will be performed at study entry (unless an IGRA negative result is available less 
than 64 weeks prior to the first dose of open-label bimekizumab) and should be repeated at 
Week 48, Week 96, Week 144, Week 192, and the SFU Visit for all subjects. The test results 
will be reported as positive, negative, or indeterminate. UCB also recommends that a TB 
specialist be consulted where TB (latent or active) is suspected or if there are doubts regarding 
test results. If latent or active TB is identified, subject must undergo appropriate study-specified 
withdrawal procedures.  
 
Change #18 
Section 13.8  Handling of dropouts or missing data  
Missing binary efficacy variables will be imputed using nonresponder imputation (NRI). In NRI, 
each subject with missing data or who has prematurely finished the study will be counted as a 
nonresponder. 
For missing continuous efficacy variables, a multiple imputation (MI) approach will be used. In 
MI, the missing value is replaced by a set of plausible values, where each value is a Bayesian 
draw from the conditional distribution of the missing data given the observed data. 
Non-monotone missing data (ie, intermittent missing data) will be imputed several times with the 
Markov Chain Monte Carlo (MCMC) method and monotone missing data will be imputed using 
a monotone regression model. Each set of imputed data will then be summarized and the 
summaries will be combined into a single inference (Carpenter and Kenward, 2013). 
Imputation of efficacy data will be performed for only those assessments that the patient had in 
PA0008. Safety data will not be imputed. 
As a sensitivity analysis, all efficacy variables will be analyzed based on observed data. Subjects 
with missing data or who have prematurely finished the study will be treated as missing. 
Has been changed to: 
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Missing binary efficacy variables will be imputed using nonresponder imputation (NRI). In NRI, 
each subject with missing data or who has prematurely finished the study will be counted as a 
nonresponder. 
For missing continuous efficacy variables, a multiple imputation (MI) approach will be used. In 
MI, the missing value is replaced by a set of plausible values, where each value is a Bayesian 
draw from the conditional distribution of the missing data given the observed data. Non 
monotone missing data (ie, intermittent missing data) will be imputed several times with the 
Markov Chain Monte Carlo (MCMC) method and monotone missing data will be imputed using 
a monotone regression model. Each set of imputed data will then be summarized and the 
summaries will be combined into a single inference (Carpenter and Kenward, 2013). 
Imputation of efficacy data will be performed for only those assessments that the patient had in 
PA0008. Safety data will not be imputed. 
As a sensitivity analysis, all efficacy variables will be analyzed based on observed data. Subjects 
with missing data or who have prematurely finished the study will be treated as missing. 
 
Change #19 
Section 17.1  Markedly abnormal laboratory values, Tables 17-1 (Definitions of markedly 
abnormal hematology values) and 17-2 (Definitions of markedly abnormal biochemistry values) 
Amended units in both table headers:  
Parameter (SI units) 
Markedly Abnormal Definition 
Low 
High 
  Has been changed to: 
Parameter (SIRCTC units) 
Markedly Abnormal Definition 
Low 
High 
 
Change #20 
Section 17.1  Markedly abnormal laboratory values, Table 17-1 (Definitions of markedly 
abnormal hematology values), abbreviations in table footer: 
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international 
Has been changed to: 
LLN=lower limit of normal; N/A = Not Applicable; SI = standard international RCTC= 
Rheumatology Common Toxicity Criteria 
 
Change #21 
Section 17.1  Markedly abnormal laboratory values, Table 17-2 (Definitions of markedly 
abnormal biochemistry values), abbreviations in table footer: 
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ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/A=Not applicable; 
SI=standard international; ULN=upper limit of normal 
Has been changed to: 
LLN=lower limit of normal; N/A = Not Applicable; SI=standard international RCTC= 
Rheumatology Common Toxicity Criteria 
 
 
 
 
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17.4 
Protocol Amendment 3 
Rationale for the amendment 
Key changes are summarized below. The purposes of the amendment are: 
 To change the sponsor company name from “UCB Biopharma SPRL” to 
“UCB Biopharma SRL” since the name of the legal form of the entity UCB Biopharma has 
changed into “société à responsabilité limitée” abbreviated “SRL”. 
 To clarify that changes from Baseline will be calculated only in relation to the Baseline of 
AS0008 for efficacy variables. 
 To add ASAS partial remission as an “other efficacy variable”. 
 To clarify that interim analyses may be performed as needed. 
 To clarify that protected adults will not be enrolled in the study. 
 To update the Sponsor contact information. 
 To confirm that treatment-emergent adverse events only are to be considered in primary and 
secondary safety variables. 
 To harmonize language related to other safety topics of interest with other studies. 
 To harmonize the description of bimekizumab with other studies. 
 To update the clinical part of the introduction. 
In addition, a few minor updates including consistency changes for PDILI-related text, the list of 
abbreviations, and minor editorial changes for the purpose of clarity have been made. 
Modifications and changes 
Global changes 
No global changes have been made. 
Specific changes 
Change #1 
Sponsor name on the title page and in study contact information 
Sponsor name: 
UCB Biopharma SPRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
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Has been changed to:  
Sponsor name: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Change #2 
Study contact information 
Sponsor Study Physician 
Name: 
, MD, MSc, PhD  
Address: 
UCB Pharma Ltd. 
208 Bath Road  
Slough, SL1 3WE 
UNITED KINGDOM  
Phone: 
 
Clinical Project Manager 
Name: 
 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Str.10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
, MS 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
Phone: 
  
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Has been changed to:  
Sponsor Study Physician 
Name: 
 MD, FNWC 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Straße 10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
Clinical Project Manager 
Name: 
 
Address: 
UCB Pharma Ltd. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM  
Phone: 
 
Clinical Trial Biostatistician 
Name: 
 MSc 
Address: 
UCB Pharma Ltd. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
 
Change #3 
Section 1 Summary, paragraphs 5 and 6  
The primary objective is to assess the long-term safety and tolerability of bimekizumab 
administered over a period of up to 204 weeks (~4 years). The primary safety variables are the 
incidences of adverse events (AEs) and serious adverse events (SAEs). 
The secondary objective is to assess the long-term efficacy. The secondary efficacy variables 
include the Assessment of SpondyloArthritis International Society 40% response criteria 
(ASAS40) at Week 48, ASAS20 response at Week 48, and the change from Baseline and 
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AS0009 entry value in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 
Week 48. The secondary safety variable is the withdrawal due to AEs. 
Has been changed to:  
The primary objective is to assess the long-term safety and tolerability of bimekizumab 
administered over a period of up to 204 weeks (~4 years). The primary safety variables are the 
incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). 
The secondary objective is to assess the long-term efficacy. The secondary efficacy variables 
include the Assessment of SpondyloArthritis International Society 40% response criteria 
(ASAS40) at Week 48, ASAS20 response at Week 48, and the change from Baseline of AS0008 
and AS0009 entry value in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
at Week 48. The secondary safety variable is the withdrawal due to TEAEs. 
Change #4 
Section 2.1.1 Clinical studies  
Four clinical studies of bimekizumab have been completed: UP0008 in 39 subjects with mild to 
moderate plaque PSO, RA0124 in 30 healthy volunteers, UP0031 in 12 healthy volunteers, and 
PA0007 in 53 subjects with PsA.  
UP0008 was a Phase 1, single ascending dose study in adults with mild to moderate PSO 
affecting ≤5% body surface area. In this blinded study, single doses of bimekizumab up to 
640mg (approximately 8mg/kg in an 80kg adult) were evaluated. A total of 26 subjects with PSO 
with <5% of body surface involvement were treated with a range of single intravenous (iv) doses 
from 8 to 640mg. The pharmacokinetics (PK) of bimekizumab was linear in the tested dose 
range. There were no clinically relevant safety findings identified at any dose and all doses were 
well tolerated. The prespecified exploratory assessment of disease activity showed clinically 
relevant and statistically significant improvements at the higher doses studied. 
RA0124 was a Phase 1, open-label, parallel-group, single-dose study in healthy subjects. The 
primary objective of this study was to determine the absolute bioavailability of single sc doses of 
bimekizumab (80mg and 160mg). The secondary objectives were to evaluate the dose 
proportionality of bimekizumab 80mg and 160mg sc, and to evaluate the safety and tolerability 
of these sc doses and 160mg given by intravenous (iv) infusion. In RA0124, the absolute 
bioavailability was similar for the 2 doses tested (0.656 and 0.631 for the bimekizumab 80mg 
and 160mg sc doses, respectively). The median half-life following sc administration was similar 
to that following iv administration (27.81 days and 28.25 days for bimekizumab 160mg sc and 
bimekizumab 160mg iv, respectively). 
An additional Phase 1 study, UP0031, evaluated the relative bioavailability and safety and 
tolerability of 2 bimekizumab formulations (a 
-based formulation 2x80mg and an 
-based formulation 1x160mg) administered by sc injection to healthy volunteers. Results 
show similar geometric means for AUC between the 2 bimekizumab formulations 
(2 x 80mg=653.8day*μg/mL; 1x160mg=628.3day*μg/mL) and the relative bioavailability for the 
bimekizumab 1x160mg versus 2x80mg formulations was calculated as 96.1% with a 95% 
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confidence interval (CI): 72.7,127.0. The wide 95% CI was expected due to the small sample 
size in UP0031. 
Bimekizumab has also been investigated in a Phase 1b, proof of concept, randomized, 
placebo-controlled, multiple-dose study (PA0007). A total of 53 subjects have been randomized. 
The primary objective of PA0007 was to assess the safety and PK of multiple dose 
administration of iv bimekizumab in subjects with PsA. Four active doses and a placebo were 
tested. Drug was administered as a loading dose of bimekizumab 80mg, 160mg, 240mg, or 
560mg at Week 1, and 2 additional doses of bimekizumab 40mg, 80mg, 160mg, or 320mg at 
Week 4 and Week 7. In each treatment group, subjects received a total of 3 doses of 
bimekizumab, administered every 3 weeks. There were no unexpected clinically relevant safety 
findings and all doses were well tolerated. The PK was linear across the tested dose range and no 
change in PK was observed following multiple doses. Observed changes in inflammatory 
biomarkers were consistent with expectations based on the IL-17A and IL-17F mechanism of 
action. The exploratory analysis showed clinically relevant improvement in activity of PsA and 
in skin involvement in those subjects with concomitant active psoriatic lesions. Data from the top 
3 bimekizumab dose groups pooled showed that by Week 9, 80% [95% CI: 62.7, 90.5] of 
subjects achieved an American College of Rheumatology 20% response criteria response (vs 
16.7% [95% confidence interval (CI): 4.7, 44.8] in the placebo group) and 100% [95% CI: 79.6, 
100.0] of 26 subjects with active psoriatic lesions had achieved a Psoriasis Area and Severity 
Index 75% response (vs 0% [95% CI: 0.0, 43.4] in the placebo group). 
Infections (mostly nasopharyngitis) were the most commonly reported events in both the active 
(36.8% of subjects) treatment and the placebo group (35.7% of subjects). None of the infections 
were considered serious or required treatment with antibiotics. Two subjects in the active 
treatment group experienced 1 local candida infection each (oropharyngitis and vulvovaginitis, 
respectively) that were nonserious and resolved with topical therapy. There was a reduction in 
mean neutrophil count in the active treatment group, although this drop was not clinically 
relevant and a clear relationship with dose or time was not evident. Interleukin-17 plays a 
significant role in regulating neutrophil recruitment and granulopoiesis and thus, receipt of an 
anti-IL-17 antibody may be associated with effects on neutrophil count. Previous clinical 
experience with administration of anti-IL-17 antibodies in humans indicates that this potential 
risk is low and reversible. Some increases in liver function tests were reported, but none had a 
convincing relationship to exposure to investigational medicinal product (IMP). 
In the bimekizumab clinical studies to date, the most commonly reported gastrointestinal adverse 
events were abdominal distension, abdominal pain, diarrhea, flatulence, nausea, and vomiting. 
All of these events, except 1 event of vomiting, were mild or moderate in intensity. The 
T helper-17 and other IL-17-producing cell types are present in a high frequency in the 
physiologic, healthy state of the intestinal mucosa. Interleukin-17 is recognized as an important 
player in the pathophysiology of infectious and immune-mediated gastrointestinal diseases, and 
has been shown to contribute to the gut barrier function (Ivanov et al, 2008). Clinical data with 
secukinumab suggest that the drug may worsen symptoms of co-existing Crohn’s disease in 
patients with PSO and AS (Baeten et al, 2015).  
Several additional studies of bimekizumab are ongoing. RA0123 is a Phase 2a, double-blind, 
randomized, placebo-controlled, multiple dose study to evaluate the safety, PK, 
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pharmacodynamics (PD), and efficacy of multiple doses of bimekizumab administered as add-on 
therapy to stable certolizumab pegol (CZP; Cimzia®) therapy in subjects with moderate to severe 
RA. UC0011 is a Phase 2 study, which will evaluate the efficacy, safety, tolerability, and PK of 
an iv loading dose and 2 sc maintenance doses of bimekizumab in subjects with moderate to 
severe active ulcerative colitis. PS0016 will evaluate the pharmacodynamic response, safety and 
PK and PS0010 will evaluate the pharmacodynamics, PK, safety, and efficacy of bimekizumab 
administered sc to subjects with PSO. PA0008 is a Phase 2, double-blind, randomized, 
placebo-controlled, multiple dose study to evaluate the efficacy and safety of bimekizumab in 
subjects with active PsA 
AS0008 is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, 
parallel-group, dose-ranging study to evaluate the efficacy and safety of bimekizumab in subjects 
with active AS. The current Phase 2b OLE study (AS0009) will allow access to bimekizumab for 
subjects who completed the lead-in study AS0008, while allowing the collection of further data 
on the long-term safety and efficacy of bimekizumab in this subject population.  
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB). 
Has been changed to:  
Section 2.1.1 Clinical studies  
Section 2.1.1.1 Completed studies  
Seventeen clinical studies of bimekizumab have been completed: RA0124 in 30 healthy 
volunteers, UP0031 in 12 healthy volunteers, UP0033 in 189 healthy volunteers, UP0034 in 
56 healthy volunteers, UP0042 in 48 healthy Japanese or Caucasian volunteers, UP0074 in 
37 healthy volunteers, RA0123 in 159 subjects with moderate to severe RA, UP0008 in 
39 subjects with mild-to-moderate plaque PSO, PS0010 in 250 subjects with moderate to severe 
chronic plaque PSO and the corresponding extension study (PS0011), PS0016 in 49 subjects 
with moderate to severe chronic plaque PSO and the corresponding extension study (PS0018), 
PA0007 in 53 subjects with PsA, PA0008 in 206 subjects with PsA, UC0011 in 23 subjects with 
moderate to severe active ulcerative colitis, HS0001 in 90 subjects with moderate to severe 
hidradenitis suppurativa (HS), and AS0008 in 303 subjects with AS. 
Information on the clinical data for bimekizumab from completed studies is available in the 
current version of the Investigator’s Brochure (IB). 
Section 2.1.1.2 Ongoing studies  
Several additional studies of bimekizumab in subjects with AS are ongoing: 
 Feeder studies AS0010 and AS0011: 
 AS0010 is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the 
efficacy and safety of bimekizumab in subjects with active nr-axSpA. 
 AS0011 is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the 
efficacy and safety of bimekizumab in subjects with active AS. 
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 AS0013 is a Phase 2a Investigator- and subject-blind parallel-group study to evaluate the 
efficacy and safety of bimekizumab and certolizumab pegol (CZP) in subjects with active 
AS. 
Bimekizumab is also being evaluated in the treatment of other indications (eg, PsA, PSO, and 
HS). 
Additional information on the ongoing studies for bimekizumab is available in the current 
version of the IB. 
Change #5 
Section 4.1.1 Primary safety variables  
The primary safety variables are the incidences of AEs and SAEs. 
Has been changed to:  
The primary safety variables are the incidences of TEAEs and SAEs. 
Change #6 
Section 4.2.1 Secondary safety variables  
The secondary safety variable is the withdrawal due to AEs. 
Has been changed to:  
The secondary safety variable is the withdrawal due to TEAEs. 
Change #7 
Section 4.2.2 Secondary efficacy variables  
The secondary efficacy variables are: 
 ASAS40 response at Week 48 
 ASAS20 response at Week 48 
 Change from Baseline and AS0009 entry value in BASDAI at Week 48 
Have been changed to:  
The secondary efficacy variables are: 
 ASAS40 response at Week 48 
 ASAS20 response at Week 48 
 Change from Baseline of AS0008 and AS0009 entry value in BASDAI at Week 48 
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Change #8 
Section 4.3.2 Efficacy variables  
Other efficacy variables are listed below and will be evaluated at scheduled visits in accordance 
with the schedules of assessments in Table 5‒1 and Table 5‒2. 
 ASAS40 response 
 ASAS20 response 
 ASAS5/6 response 
 Change from Baseline and AS0009 entry value in Ankylosing Spondylitis Disease Activity 
Score-C-reactive protein (ASDAS-CRP) 
 Ankylosing Spondylitis Disease Activity Score Inactive Disease (ASDAS-ID) 
 Change from Baseline and AS0009 entry value in Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) 
 Change from Baseline and AS0009 entry value in Bath Ankylosing Spondylitis Functional 
Index (BASFI) 
 Change from Baseline and AS0009 entry value in Bath Ankylosing Spondylitis Metrology 
Index (BASMI) 
 Change from Baseline and AS0009 entry value in the MASES Index 
 Change from Baseline and AS0009 entry value in Patient's Global Assessment of Disease 
Activity (PGADA) 
 Change from Baseline and AS0009 entry value in total and nocturnal spinal pain 
 Change from Baseline and AS0009 entry value in Short Form 36-item Health Survey (SF-36) 
 Change from Baseline and AS0009 entry value in Ankylosing Spondylitis Quality of 
Life (ASQoL) 
 Change from Baseline and AS0009 entry value in the Hospital Anxiety and Depression 
Scale-Anxiety (HADS-A) and Hospital Anxiety and Depression Scale-Depression 
(HADS-D) scores 
 Depression and anxiety status “normal” as defined by HADS-D and HADS-A <8 
Have been changed to:  
Other efficacy variables are listed below and will be evaluated at scheduled visits in accordance 
with the schedules of assessments in Table 5‒1 and Table 5‒2. 
 ASAS40 response 
 ASAS20 response 
 ASAS5/6 response 
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 ASAS partial remission 
 Change from Baseline of AS0008 and AS0009 entry value in Ankylosing Spondylitis 
Disease Activity Score-C-reactive protein (ASDAS-CRP) 
 Ankylosing Spondylitis Disease Activity Score Inactive Disease (ASDAS-ID) 
 Change from Baseline of AS0008 and AS0009 entry value in Bath Ankylosing Spondylitis 
Disease Activity Index (BASDAI) 
 Change from Baseline of AS0008 and AS0009 entry value in Bath Ankylosing Spondylitis 
Functional Index (BASFI) 
 Change from Baseline of AS0008 and AS0009 entry value in Bath Ankylosing Spondylitis 
Metrology Index (BASMI) 
 Change from Baseline of AS0008 and AS0009 entry value in the MASES Index 
 Change from Baseline of AS0008 and AS0009 entry value in Patient's Global Assessment of 
Disease Activity (PGADA) 
 Change from Baseline of AS0008 and AS0009 entry value in total and nocturnal spinal pain 
 Change from Baseline of AS0008 and AS0009 entry value in Short Form 36-item Health 
Survey (SF-36) 
 Change from Baseline of AS0008 and AS0009 entry value in Ankylosing Spondylitis Quality 
of Life (ASQoL) 
 Change from Baseline of AS0008 and AS0009 entry value in the Hospital Anxiety and 
Depression Scale-Anxiety (HADS-A) and Hospital Anxiety and Depression Scale-
Depression (HADS-D) scores 
 Depression and anxiety status “normal” as defined by HADS-D and HADS-A <8 
Change #9 
Section 4.3.3 PK variable  
The PK variable is the plasma concentration of bimekizumab evaluated at scheduled visits up to 
208 weeks (4 years) in accordance with the schedule of assessments in Table 5‒1 and Table 5‒2. 
Has been changed to:  
The PK variable is the plasma concentration of bimekizumab evaluated at scheduled visits up to 
208 weeks (4 years) in accordance with the schedule of assessments in Table 5‒1 and Table 5‒2. 
Change #10 
Section 4.3.4 Immunological variable  
The immunological variable is the anti-bimekizumab antibody detection evaluated at scheduled 
visits up to 208 weeks (4 years) in accordance with the schedule of assessments in Table 5‒1 and 
Table 5‒2. 
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Has been changed to:  
The immunological variable is the anti-bimekizumab antibody detection evaluated at scheduled 
visits up to 208 weeks (4 years) in accordance with the schedule of assessments in Table 5‒1 and 
Table 5‒2. 
Change #11 
Table 5-1: Schedule of study assessments (Week 1 through Week 104) and Table 5-2: 
Schedule of study assessments (Week 108 through Week 208), footnote a  
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a 
minimum of 21 days and a maximum of 35 days in between doses at all visits except the SFU 
Visit.  
Has been changed to:  
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a 
minimum of 21 days and a maximum of 35 days in between doses at all visits except the SFU 
Visit which 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).  
Change #12 
Section 6.1 Inclusion criteria, Criteria #1 and #2  
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 legal representative. 
2. Subject or legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete questionnaires), visit schedule, or medication intake 
according to the judgment of the Investigator. 
Have been changed to:  
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent Form (ICF) is signed and dated by the subject or by legal representative. 
2a. Subject or legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete questionnaires), visit schedule, or medication intake 
according to the judgment of the Investigator. 
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Change #13 
Section 6.3.1, Potential drug-induced liver injury IMP discontinuation criteria, 
paragraph 2 
The PDILI criteria below require immediate and permanent discontinuation of IMP:   
Has been changed to:  
The PDILI criteria below require immediate and permanent discontinuation of IMP:   
Change #14 
Section 7.1, Description of investigational medicinal product, paragraph 3 
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative-free solution in a 
 
 for sc injection. 
Has been changed to:  
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly brown, sterile, 
preservative-free solution in a 1mL prefilled syringe (PFS). 
 
 
 for sc injection. 
Change #15 
Section 8.14, SFU Visit, section header 
SFU Visit (Visit 23) 
Has been changed to:  
SFU Visit (Visit 23) 
Change #16 
Section 9.1.3, Other safety topics of interest  
Section 9.1.3 AEs for special monitoring 
UCB has identified AEs for special monitoring (AESM). An AESM is an AE or safety topic for 
which special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB), are considered appropriate. Identified AESM can be of particular 
concern based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or comorbidities and risk factors prevalent in the 
study population. 
Adverse events for special monitoring for this study include: serious infections (including 
opportunistic infections and TB, see Section 9.5.5), cytopenias, hypersensitivities, suicide 
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ideation or behavior (assessed using the eC-SSRS), depression and anxiety (assessed using the 
HADS, see Section 10.11), major cardiovascular events and liver function test changes/enzyme 
elevations (ALT, AST, and bilirubin; see Section 9.4.1), malignancies, and inflammatory bowel 
diseases.  
Has been changed to:  
Section 9.1.3, AEs for special monitoring Other safety topics of interest 
Pre-specified safety topics of interest for the study are: infections (serious, opportunistic, 
fungal, and TB), neutropenia, hypersensitivity, suicidal ideation and behavior, depression, 
major cardiovascular events, liver function test changes/enzyme elevations, malignancies, 
and inflammatory bowel diseases (with gastroenterology referral, as appropriate). This is 
based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or findings from other medicines with a 
related mechanism of action. There are no specific AE reporting requirements for these 
topics, however special monitoring, additional data collection activities, and/or enhanced 
signal detection activities (within UCB) are in place. 
Change #17 
Section 9.1.6, Follow-up of AEs, paragraph 1 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 9.4.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the Patient Safety (PS) database without 
limitation of time. 
Has been changed to:  
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs other safety topics of 
interest; further details regarding follow-up of PDILI events are provided in Section 9.4.1.5. 
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time. 
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Change #18 
Section 9.1.14, Follow-up of SAEs 
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs; further details regarding 
follow-up of PDILI events are provided in Section 9.4.1.5. Information on SAEs obtained after 
clinical database lock will be captured through the PS database without limitation of time. 
Has been changed to:  
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, AESIs, and AESMs other safety topics of 
interest; further details regarding follow-up of PDILI events are provided in Section 9.4.1.5. 
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time. 
 
 
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Change #19 
Table 12-3, Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 9.4.1.4); 
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 24hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP. 
Immediate, permanent 
IMP discontinuation 
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Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 9.4.1.2). 
IMP discontinuation 
required if any of the 
following occur: 
 Subject cannot comply 
with monitoring 
schedule.  
 
Liver chemistry 
values continue to 
increase  
 
Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 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 48hours at the 
site with HCP (see 
Section 9.4.1.4). 
Monitoring of liver chemistry values at 
least twice per week for 2 weeks.d 
 
Immediate IMP discontinuation 
required if liver chemistry values 
continue to increase.  
After 2 weeks of monitoring liver 
chemistry values:  
 
Discontinue IMP if levels remain 
≥3xULN (and ≥2x baseline) 
without evidence of resolutiond  
Continue to monitor until values 
normalize, stabilize, or return to within 
baseline valuesd. 
 
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 9.4.1.1. 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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Has been changed to:  
Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 discontinuationd. 
 
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 9.4.1.4); 
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.e 
 
 
 
 
 
 
 
 
 
≥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 24hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP. 
Immediate permanent 
IMP discontinuationd. 
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Laboratory value 
 
Immediate 
Follow-up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
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 9.4.1.2). 
IMP discontinuation 
required if any of the 
following occur: 
 Subject cannot comply 
with monitoring 
schedule.  
 
Liver chemistry 
values continue to 
increase  
 
Liver chemistry 
values remain 
≥3xULN (and 
≥2xbaseline) 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 48hours at the 
site with HCP (see 
Section 9.4.1.4). 
Monitoring of liver chemistry values at 
least twice per week for 2 weeks.e 
 
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 resolutione  
Continue to monitor until values 
normalize, stabilize, or return to within 
baseline valuese. 
 
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 9.4.1.1. 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 Details are provided in Section 9.4.1.2. 
e 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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Change #20 
Section 9.4.1.2, Immediate action: determination of IMP discontinuation, paragraph 2  
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 9-3 for details). 
Has been changed to:  
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 9-3 for details). 
Change #21 
Section 13.4, Planned efficacy analyses  
Secondary and other efficacy variables will be summarized for all subjects in the FAS; efficacy 
analyses will be performed over the 208 weeks (4 years).  
Responder variables (eg, ASAS20 response) will be derived relative to Baseline and AS0009 
entry values, and summarized descriptively. Percentages will be summarized descriptively by 
visit, by randomized treatment group, and by treatment group at completion of the lead-in study.  
Change from Baseline or AS0009 entry values of all continuous variables will be summarized 
descriptively by visit, by randomized treatment group, and by treatment group at completion of 
the lead-in study. 
Has been changed to:  
Secondary and other efficacy variables will be summarized for all subjects in the FAS; efficacy 
analyses will be performed over the 208 weeks (4 years).  
Responder variables (eg, ASAS20 response) will be derived relative to Baseline of AS0008 and 
AS0009 entry values, and summarized descriptively. Percentages will be summarized 
descriptively by visit, by randomized treatment group, and by treatment group at completion of 
the lead-in study.  
Change from Baseline of AS0008 or AS0009 entry values of all continuous variables will be 
summarized descriptively by visit, by randomized treatment group, and by treatment group at 
completion of the lead-in study. 
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Change #22 
Section 13.9, Planned interim analysis and data monitoring 
No formal interim analysis is planned for this study. 
Has been changed to:  
An interim analysis and data cuts may be performed for regulatory and publication 
purposes. 
Change #23 
Section 14.1, Informed consent, paragraph 3 
Prior to participation in the study, the written 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. 
Has been changed to:  
Prior to participation in the study, the written 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. 
Change #24 
Section 14.2, Subject identification cards 
Upon signing the Informed Consent, the subject or legal representative will be provided with a 
subject identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times. 
Has been changed to:  
Upon signing the Informed Consent, the subject or legal representative will be provided with a 
subject identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times. 
 
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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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18 
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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Approval Signatures
Name:
as0009-protocol-amend-3
Version:
1. 0
Document Number:
CLIN-000146755
Title:
AS0009 Clinical Study Protocol Amendment 3
Approved Date:
07 Feb 2020
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 06-Feb-2020 10:05:45 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Qualified Person
Date of Signature: 06-Feb-2020 11:26:07 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 07-Feb-2020 08:22:56 GMT+0000
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SAP_001.pdf: 
UCB 
 
10Jan2023 
Statistical Analysis Plan 
Bimekizumab 
AS0009 
 
 
 
 
Confidential 
Page 1 of 115 
 
 
STATISTICAL ANALYSIS PLAN  
Study: AS0009 
Product: Bimekizumab 
A MULTICENTER, PHASE 2B, OPEN-LABEL EXTENSION 
STUDY TO EVALUATE THE LONG-TERM SAFETY AND 
EFFICACY OF BIMEKIZUMAB IN SUBJECTS WITH 
ANKYLOSING SPONDYLITIS 
 
SAP/Amendment Number Date 
Final SAP 1.0 
09 Feb 2018 
Final SAP 2.0  
26 Mar 2018 
SAP Amendment 1  
04 Aug 2020 
SAP Amendment 2  
13 Jun 2022 
SAP Amendment 3 
10 Jan 2023 
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 ........................................................................................................... 10 
2 
PROTOCOL SUMMARY ............................................................................................... 10 
2.1 
Study objectives ........................................................................................................... 10 
2.1.1 
Primary objective ................................................................................................. 10 
2.1.2 
Secondary objectives ........................................................................................... 10 
2.1.3 
Other objectives ................................................................................................... 10 
2.2 
Study variables ............................................................................................................. 11 
2.2.1 
Safety variables .................................................................................................... 11 
2.2.1.1 
Primary safety variables ............................................................................ 11 
2.2.1.2 
Secondary safety variables ........................................................................ 11 
2.2.1.3 
Other safety variables ................................................................................ 11 
2.2.2 
Efficacy variables ................................................................................................ 11 
2.2.2.1 
Primary efficacy variable .......................................................................... 11 
2.2.2.2 
Secondary efficacy variables ..................................................................... 11 
2.2.2.3 
Other efficacy variables ............................................................................. 11 
2.2.3 
Pharmacokinetic/pharmacodynamic variables .................................................... 13 
2.2.3.1 
Other pharmacokinetic variable ................................................................ 13 
2.2.4 
Other pharmacogenomic variables ...................................................................... 13 
2.2.5 
Other immunological variables ............................................................................ 13 
2.3 
Study design and conduct ............................................................................................ 13 
2.4 
Determination of sample size ....................................................................................... 20 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 20 
3.1 
General presentation of summaries and analyses ........................................................ 20 
3.2 
General study level definitions .................................................................................... 21 
3.2.1 
Relative day ......................................................................................................... 21 
3.2.2 
Study periods ....................................................................................................... 22 
3.3 
Definition of Baseline values ....................................................................................... 22 
3.4 
Protocol deviations....................................................................................................... 22 
3.5 
Mapping of assessments .............................................................................................. 23 
3.6 
Analysis sets................................................................................................................. 24 
3.6.1 
Enrolled Set ......................................................................................................... 24 
3.6.2 
Safety Set ............................................................................................................. 25 
3.6.3 
Full Analysis Set .................................................................................................. 25 
3.7 
Treatment assignment and treatment groups ............................................................... 25 
3.8 
Center pooling strategy ................................................................................................ 26 
3.9 
Coding dictionaries ...................................................................................................... 26 
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3.10 
Changes to protocol-defined analyses ......................................................................... 27 
3.10.1 
Changes related to COVID-19 ............................................................................. 27 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 28 
4.1 
Adjustments for covariates .......................................................................................... 28 
4.2 
Handling of dropouts or missing data .......................................................................... 28 
4.2.1 
Handling of missing data for efficacy analysis .................................................... 28 
4.2.2 
Handling of missing data for adverse events ....................................................... 35 
4.2.3 
Handling of missing data for prior and concomitant medication ........................ 37 
4.2.4 
Handling of partial treatment end dates ............................................................... 38 
4.3 
Interim analyses and data monitoring .......................................................................... 39 
4.4 
Multicenter studies ....................................................................................................... 39 
4.5 
Multiple comparisons/multiplicity ............................................................................... 39 
4.6 
Use of an efficacy subset of subjects ........................................................................... 39 
4.7 
Active-control studies intended to show equivalence .................................................. 40 
4.8 
Examination of subgroups ........................................................................................... 40 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 40 
5.1 
Subject disposition ....................................................................................................... 40 
5.1.1 
Impact of COVID-19 ........................................................................................... 41 
5.2 
Protocol deviations....................................................................................................... 42 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 43 
6.1 
Demographics .............................................................................................................. 43 
6.2 
Other baseline characteristics ...................................................................................... 43 
6.3 
Medical history and concomitant diseases ................................................................... 45 
6.4 
Past, prior and concomitant medications ..................................................................... 45 
6.5 
Prohibited medication and rescue therapy ................................................................... 46 
6.6 
Concomitant medical procedures and procedure history ............................................. 47 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 47 
8 
EFFICACY ANALYSES ................................................................................................ 48 
8.1 
Derivation of efficacy variables ................................................................................... 48 
8.1.1 
Assessment in Axial Spondyloarthritis International Society Response Criteria 49 
8.1.1.1 
Data Handling Rules for ASAS40 and ASAS20 ....................................... 49 
8.1.1.2 
Data Handling Rules for ASAS5/6............................................................ 51 
8.1.2 
Ankylosing Spondylitis Disease Activity Score – C-reactive Protein ................. 52 
8.1.3 
Bath Ankylosing Spondylitis Functional Index ................................................... 53 
8.1.4 
Bath Ankylosing Spondylitis Disease Activity Index ......................................... 53 
8.1.5 
Bath Ankylosing Spondylitis Metrology Index ................................................... 54 
8.1.6 
Maastricht Ankylosing Spondylitis Enthesitis Index .......................................... 55 
8.1.7 
Patient’s Global Assessment of Disease Activity ................................................ 56 
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8.1.8 
Total and Nocturnal Spinal Pain .......................................................................... 56 
8.1.9 
Short Form – 36 Items Health Survey ................................................................. 56 
8.1.10 
Ankylosing Spondylitis Quality of Life .............................................................. 57 
8.1.11 
Hospital Anxiety and Depression Scale .............................................................. 57 
8.1.12 
High-sensitivity C-reactive protein levels ........................................................... 57 
8.2 
Statistical analyses of secondary efficacy variables .................................................... 58 
8.3 
Statistical analyses of other efficacy variables ............................................................ 58 
8.3.1 
Maintenance of response ..................................................................................... 59 
8.4 
Subgroup analysis ........................................................................................................ 59 
8.5 
Impact of COVID-19 ................................................................................................... 60 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 60 
9.1 
Pharmacokinetics ......................................................................................................... 60 
9.2 
Pharmacodynamics and immunogenicity .................................................................... 62 
10 SAFETY ANALYSES ..................................................................................................... 68 
10.1 
Extent of exposure ....................................................................................................... 68 
10.2 
Adverse events ............................................................................................................. 71 
10.2.1 
Adverse event duration and time since first/last dose.......................................... 75 
10.2.2 
Exposure-adjusted incidence rate and exposure-adjusted event rate ................... 77 
10.2.3 
Adverse event of special interest and safety topics of interest ............................ 78 
10.2.4 
Impact of COVID-19 ........................................................................................... 83 
10.3 
Clinical laboratory evaluations .................................................................................... 89 
10.4 
Potential drug-induced liver Injury assessment ........................................................... 94 
10.5 
Vital Signs and Other Observations Related to Safety ................................................ 96 
10.5.1 
Vital signs ............................................................................................................ 96 
10.5.2 
Electrocardiograms .............................................................................................. 97 
10.5.3 
Other safety variables .......................................................................................... 98 
Assessment of Tuberculosis........................................................................................... 98 
Electronic Columbia Suicide Severity Rating Scale ...................................................... 98 
Health Care Provider Consultations .............................................................................. 99 
Extra-articular assessments ............................................................................................ 99 
10.5.4 
Comments ............................................................................................................ 99 
11 REFERENCES .............................................................................................................. 100 
12 APPENDICES ............................................................................................................... 102 
12.1 
Data Handling Rules for ASAS20, ASAS40 and ASAS5/6 Response ..................... 102 
12.2 
Classification of the SF-36 questionnaire .................................................................. 103 
12.3 
Identification of Opportunistic infections .................................................................. 105 
12.4 
MedDRA algorithmic approach to anaphylaxis ........................................................ 106 
12.5 
COVID-19 data collection ......................................................................................... 107 
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13 AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN .................................. 109 
13.1 
Amendment 1 ............................................................................................................. 109 
13.1.1 
Rationale for the amendment ............................................................................. 109 
13.1.2 
Modifications and changes ................................................................................ 109 
13.2 
Amendment 2 ............................................................................................................. 112 
13.2.1 
Rationale for the amendment ............................................................................. 112 
13.2.2 
Modifications and changes ................................................................................ 112 
13.3 
Amendment 3 ............................................................................................................. 114 
13.3.1 
Rationale for the amendment ............................................................................. 114 
13.3.2 
Modifications and changes ................................................................................ 114 
14 STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ........................................... 115 
 
 
 
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LIST OF TABLES 
Table 2‒1: 
Schedule of study assessments (Week 1 through Week 104) .......................... 15 
Table 2‒2: 
Schedule of study assessments (Week 108 through Week 208) ...................... 18 
Table 3‒1: 
Decimal places for derived efficacy variables ................................................. 21 
Table 4‒1: 
Allowable ranges for continuous efficacy variables ........................................ 31 
Table 4‒2: 
Missing data handling ...................................................................................... 34 
Table 8-1: 
BASMI linear definition .................................................................................. 54 
Table 8-2: 
BASMI linear definition permitted ranges ...................................................... 54 
Table 10‒1: 
Study medication duration ............................................................................... 69 
Table 10‒2: 
Exposure time at risk ....................................................................................... 69 
Table 10‒3: 
Extended MACE types .................................................................................... 79 
Table 10‒4: 
Inflammatory bowel disease types ................................................................... 81 
Table 10-5: 
Calculation of exposure time at risk in relation to COVID-19 ........................ 85 
Table 10‒6: 
Laboratory measurements ................................................................................ 89 
Table 10‒7: 
Definitions of markedly abnormal hematology values .................................... 90 
Table 10‒8: 
Definitions of markedly abnormal biochemistry values .................................. 90 
Table 10‒9: 
Definitions of CTCAE grade by hematology parameter ................................. 92 
Table 10‒10: Definitions of CTCAE grade by biochemistry parameter ............................... 92 
Table 10‒11: Additional potential drug-induced liver injury information ............................ 94 
Table 10‒12: Potential drug-induced liver injury laboratory measurements ......................... 95 
Table 10‒13: Definitions of markedly abnormal blood pressure values ............................... 97 
Table 12-1: 
Data Handling Rules for ASAS20 and ASAS40 ........................................... 102 
Table 12-2: 
Data Handling Rules for ASAS5/6 Response ................................................ 103 
Table 12‒3: 
Classification of the SF-36 questionnaire ...................................................... 104 
 
 LIST OF FIGURES 
Figure 2‒1: 
Schematic diagram ........................................................................................... 14 
 
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LIST OF ABBREVIATIONS 
 
ACP 
above the cut point 
ADAb 
anti-bimekizumab antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AS 
ankylosing spondylitis 
ASAS20,40,5/6 
Assessment in SpondyloArthritis International Society 20%, 40%, 5 
out of 6 response criteria 
ASAS-PR 
Assessment in SpondyloArthritis International Society Partial 
Remission response 
ASDAS-CRP 
Ankylosing Spondylitis Disease Activity Score-C-reactive protein 
ASQoL 
Ankylosing Spondylitis Quality of Life 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
BASMI 
Bath Ankylosing Spondylitis Metrology Index 
BCP 
below the cut point 
BKZ 
bimekizumab 
BLQ 
below the limit of quantification 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CP 
confirmed positive 
CRP 
high-sensitivity C-reactive protein 
Note: High-sensitivity CRP is referred to as CRP throughout the 
SAP and is therefore abbreviated as CRP. 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV (%) 
coefficient of variation  
DMARD 
disease-modifying antirheumatic drug 
EAER 
exposure adjusted event rate 
EAIR 
exposure adjusted incidence rate 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form  
eC-SSRS 
electronic Columbia-Suicide Severity Rating Scale 
ES 
Enrolled Set 
ET 
early termination 
EV 
entry visit 
FAS 
Full Analysis Set 
GGT 
gamma glutamyltransferase 
HADS 
Hospital Anxiety and Depression Scale 
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HADS-A 
Hospital Anxiety and Depression Scale - Anxiety 
HADS-D 
Hospital Anxiety and Depression Scale - Depression 
HLGT 
high level group term 
HLT 
high level term 
HRQoL 
health-related quality of life 
IBD 
inflammatory bowel disease 
IGRA 
interferon-gamma release assay 
IMP 
investigational medicinal product 
IXRS 
interactive voice or web response system 
LDH 
lactate dehydrogenase 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
MASES 
Maastricht Ankylosing Spondylitis Enthesitis Index 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCMC 
Markov-Chain Monte Carlo 
MCS 
Mental Component Summary 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
MRD 
minimum required dilution 
MTX 
methotrexate 
n 
number of observations 
NCP 
not confirmed positive 
NRI 
non-responder imputation 
NRS 
numeric rating scale 
NSAID 
nonsteroidal anti-inflammatory drug 
OC 
observed case 
OLE 
open-label extension 
PCS 
Physical Component Summary 
PDILI 
potential drug-induced liver injury 
PGADA 
Patient’s Global Assessment of Disease Activity 
PT 
preferred term 
Q4W 
every 4 weeks  
QTcB 
QT interval corrected for heart rate using Bazett’s formula 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sc 
subcutaneous(ly) 
SD 
standard deviation 
SF-36 
Short-Form 36-item Health Survey 
SFU 
Safety Follow-up 
SIB 
suicidal ideation and behavior 
SOC 
system organ class 
SMQ 
standardized MedDRA query 
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SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
TNF 
tumor necrosis factor 
TNSP 
Total Nocturnal and Spinal Pain 
ULN 
upper limit of normal 
WBC 
white blood cell 
WHO-DD 
World Health Organization Drug Dictionary 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all necessary information to 
perform the required statistical analysis for AS0009. It also defines the summary tables, figures, 
and listings to be generated in the clinical study report according to the protocol. 
The SAP is based on the following study documents:  
• Final protocol, 15 May 2017.  
• Protocol Amendment 1, 17 July 2017. 
• Protocol Amendment 2, 21 Mar 2018. 
• Protocol Amendment 3, 06 Feb 2020. 
The content of this SAP is compatible with the International Council for Harmonisation/ Food 
and Drug Administration E9 Guidance documents (1998). 
2 
PROTOCOL SUMMARY 
This is a Phase 2b, multicenter, 208-week, open-label extension (OLE) study to evaluate the 
long-term safety, tolerability, and efficacy of bimekizumab (also known as UCB4940), in up to 
285 subjects with ankylosing spondylitis (AS). Only subjects who complete AS0008, a Phase 2b 
study, are eligible for enrollment into AS0009. At Week 48 of AS0008, all subjects continuing 
into AS0009 will undergo the final AS0008 study assessments and any non-overlapping AS0009 
study entry assessments, and will then receive their first open-label dose (160mg every 4 weeks 
[Q4W] subcutaneously [sc]) of bimekizumab.  
The study duration for each subject is up to a maximum of 224 weeks: an Open-Label Treatment 
Period of up to 204 weeks, followed by a Safety Follow-up (SFU) Visit 20 weeks after the last 
dose of bimekizumab. 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective is to assess the long-term safety and tolerability of bimekizumab 
administered sc Q4W at a dose of 160mg over a period of up to 204 weeks. 
2.1.2 
Secondary objectives 
The secondary objective is to assess the long-term efficacy of bimekizumab. 
2.1.3 
Other objectives 
• To assess the impact on patient-reported quality of life 
• To assess the impact on enthesitis 
• To assess the plasma concentration of bimekizumab 
• To assess the immunogenicity of bimekizumab 
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2.2 
Study variables 
2.2.1 
Safety variables 
2.2.1.1 
Primary safety variables 
The primary safety variables are the incidences of treatment-emergent adverse events (TEAEs) 
and treatment-emergent serious adverse events (SAEs). The latter is measured by the incidence 
of serious TEAEs. 
2.2.1.2 
Secondary safety variables 
The secondary safety variable is the withdrawal from the study due to TEAEs. This is measured 
by the incidence of TEAEs leading to study discontinuation and/or permanent withdrawal of 
study medication. 
2.2.1.3 
Other safety variables 
Other safety variables are: 
• Change from AS0009 Laboratory Baseline (as defined in Section 3.3) in clinical laboratory 
variables (hematology and biochemistry, with the exception of high-sensitivity C-reactive 
protein [CRP]) at each visit (AS0009 Week 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 
156, 168, 180, 192, 204, 208, SFU). 
• Change from AS0008 Baseline in vital signs (pulse, temperature and blood pressure) 
(AS0009 Entry Visit [EV], Week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 
168, 180, 192, 204, 208, Completion/ET, SFU) and body weight (AS0009 EV, Week 12, 24, 
36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 208, SFU). 
Note that the change from AS0009 EV variables specified in the protocol will not be reported, 
since the EV assessment is made after 36 or 48 weeks of bimekizumab treatment and there is 
unlikely to be any further important change. 
2.2.2 
Efficacy variables 
2.2.2.1 
Primary efficacy variable 
There is no primary efficacy variable for this study because the primary objective of this study is 
to assess long-term safety and tolerability.  
2.2.2.2 
Secondary efficacy variables 
The secondary efficacy variables are: 
• Assessment in Spondyloarthritis International Society (ASAS) 40% response criterion 
(ASAS40) at AS0009 Week 48, relative to AS0008 Baseline. 
• ASAS 20% response criterion (ASAS20) at AS0009 Week 48, relative to AS0008 Baseline. 
• Change from AS0008 Baseline in the Bath Ankylosing Spondylitis Disease Activity Index 
(BASDAI) at AS0009 Week 48. 
2.2.2.3 
Other efficacy variables 
The other efficacy variables are: 
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• ASAS40 and ASAS20 response at each visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 
96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 208), relative to AS0008 Baseline.  
− ASAS40 and ASAS20 response will also be reported at each post-AS0008 Baseline visit 
in AS0008 through to AS0009 Week 208 (AS0008 Week 1, 2, 4, 8, 12, 16, 24 and 36 and 
AS0009 EV [AS0008 Week 48], Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 
156, 168, 180, 192, 204, 208), for subjects who were responders at AS0008 Week 12. 
These are additional variables to those specified in the protocol and will be used to assess 
maintenance of response. 
• ASAS 5/6 response criterion (ASAS5/6) response at each visit (AS0009 EV, Week 48, 96, 
156 and 204), relative to AS0008 Baseline. 
− ASAS5/6 response will also be reported at each post-AS0008 Baseline visit in AS0008 
through to AS0009 Week 204 (AS0008 Week 4, 8, 12, 16, 24 and 36 and AS0009 EV 
[AS0008 Week 48], Week 48, 96, 156 and 204), for subjects who were responders at 
AS0008 Week 12. These are additional variables to those specified in the protocol and 
will be used to assess maintenance of response. 
• ASAS partial remission (ASAS-PR) response at each visit (AS0009 EV, Week 12, 24, 36, 
48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 208), relative to AS0008 
Baseline.  
• Change from AS0008 Baseline in Ankylosing Spondylitis Disease Activity Score-C-reactive 
protein (ASDAS-CRP) at each visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 
120, 132, 144, 156, 168, 180, 192, 204, 208). 
• Ankylosing Spondylitis Disease Activity Score Inactive Disease (ASDAS-ID) at each visit 
(AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 
204, 208). 
• Change from AS0008 Baseline in BASDAI at each visit (AS0009 EV, Week 12, 24, 36, 48, 
60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 208). 
• Change from AS0008 Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at 
each visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 
180, 192, 204, 208). 
• Change from AS0008 Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at 
each visit (AS0009 EV, Week 48, 96, 156, 204). 
• Change from AS0008 Baseline in the Maastricht Ankylosing Spondylitis Enthesitis Score 
(MASES) Index at each visit (AS0009 EV, Week 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 
208). 
• Change from AS0008 Baseline in Patient’s Global Assessment of Disease Activity 
(PGADA) at each visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 
156, 168, 180, 192, 204, 208). 
• Change from AS0008 Baseline in total and nocturnal spinal pain (TNSP) at each visit 
(AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 
204, 208).  
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• Change from AS0008 Baseline in Short-Form 36-Item Health Survey (SF-36) at each visit 
(AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 208). 
• Change from AS0008 Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at each 
visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 208). 
• Change from AS0008 Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety 
(HADS-A) and HADS - Depression (HADS-D) scores at each visit (AS0009 EV, Week 12, 
24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 208). 
• Incidence of “normal” depression and anxiety status (HADS-D<8 and HADS-A<8) at each 
visit (AS0009 EV, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 
192, 204, 208). 
2.2.3 
Pharmacokinetic/pharmacodynamic variables 
2.2.3.1 
Other pharmacokinetic variable 
The pharmacokinetic variable is the plasma concentration of bimekizumab at each visit (AS0009 
EV, Week 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 208, SFU). 
No pharmacodynamic variables are defined. 
2.2.4 
Other pharmacogenomic variables 
No analyses of genomic, genetic, proteomic, or metabolomic biomarkers relevant to disease 
biology and progression, response to therapy, and the inflammatory and immune response 
processes are specified. 
2.2.5 
Other immunological variables 
The immunological variable is the anti-bimekizumab antibody (ADAb) level at each visit 
(AS0009 EV, Week 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 208, SFU). 
2.3 
Study design and conduct 
AS0009 is a multicenter OLE study to assess the long-term safety, tolerability, and efficacy of 
bimekizumab in eligible adult subjects with AS who completed the Phase 2b study AS0008. At 
Week 48 of AS0008, all eligible subjects continuing into AS0009 will undergo their final 
AS0008 study assessments and any non-overlapping AS0009 entry assessments, and will then 
receive their first open-label dose of bimekizumab.  
Up to 285 subjects could be enrolled into this OLE study. The study duration for each subject is 
up to a maximum of 224 weeks. No randomization will be performed and all subjects will 
receive open-label treatment with bimekizumab 160mg Q4W sc for a maximum of 204 weeks 
(~4 years) followed by a SFU visit 20 weeks after the last dose of bimekizumab. 
Subjects may require additional treatment in addition to medications received during AS0008 to 
control their AS symptoms. Such rescue therapies are defined in Section 6.5. The decision to 
implement such therapy will be at the discretion of the Investigator.  
Subjects withdrawing early from the study will undergo the ET Visit assessments and will enter 
the SFU Period. 
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A study schematic diagram of AS0009 is provided in Figure 2‒1. 
Figure 2‒1: Schematic diagram 
 
Q4W=every 4 weeks; sc=subcutaneous; SFU=Safety Follow-up 
Note: Self-administration will be allowed after 3 months of treatment (from Week 16 onwards) as described in Table 
2‒1. 
a Subjects will receive their final dose of study drug on Week 204 and the SFU Visit will be conducted 20 weeks 
after the last dose of investigational medicinal product (IMP). 
Schedules of study assessments for Week 1 to Week 104 and for Week 108 to Week 208 are 
provided in Table 2‒1 and Table 2‒2. 
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Table 2‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
Informed consent 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
Xf 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Adverse events 
Xf 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
eC-SSRS 
Xe,f 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HADS 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
ASQoL 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BASDAI 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BASFI 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
SF-36 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
PGADA 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Total and nocturnal spinal pain 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
TB questionnaire 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Vital signs (pulse, temperature, 
BP)g 
Xe,f 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Body weight 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Physical examinationh 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
MASES 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
BASMI 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
ECG 
Xf 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
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Table 2‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
Hematology/biochemistry/urine 
pregnancyi, j 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Blood Sample for CRPj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Blood sample for bimekizumab 
plasma concentrationsj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
Blood sample for anti-
bimekizumab antibodiesj 
Xf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
IGRA TB testk 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
IXRS  
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Bimekizumab administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ASQoL=Ankylosing Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis 
Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; BASFI=Bath Ankylosing Spondylitis Metrology Index; BP=blood pressure; 
CRP=C-reactive protein; ECG=electrocardiogram; eC SSRS=electronic Columbia-Suicide Severity Rating Scale; EV=Entry Visit; H=home; 
HADS=Hospital Anxiety and Depression Scale; IGRA=interferon gamma release assay; IMP: investigational medicinal product; IXRS=interactive 
voice or web response system; MASES= Maastricht Ankylosing Spondylitis Enthesitis Index; PGADA=Patient's Global Assessment of Disease 
Activity; SF 36=36 item short form health survey; SFU=Safety Follow Up; TB=tuberculosis;  
Note: The SFU Visit will occur 20 weeks after the last dose of IMP. 
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a minimum of 21 days and a maximum of 35 days in between 
doses at all visits except the SFU Visit which should occur no more than 3 days prior the scheduled visit date and within 7 days after the scheduled visit 
date (-3 days /+7 days).  
b AS0009 entry will occur at the end of the lead-studies. At Week 48 of AS0008, all subjects continuing into AS0009 will undergo the final AS0008 
study assessments and any nonoverlapping AS0009 entry assessments and will then receive their first open label dose of bimekizumab. 
c From the Entry Visit onwards, self-administration training will be provided to the subject/caregivers/appropriate designee by the study nurse. At 
Week 8 and Week 12, the subject/caregiver/appropriate designee will perform administrations under the supervision of the site staff to ensure that study 
medication is being properly and safely injected. 
d Ensure that a separate Informed Consent form was completed by the subject for AS0009 prior to study entry. 
e To be performed prior to the first dose of open-label bimekizumab. 
f Assessment will be performed at Week 48 of the lead-in study AS0008 and will be used as the AS0009 entry value. 
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Table 2‒1: 
Schedule of study assessments (Week 1 through Week 104) 
Protocol activity 
Treatment Period 
Weeksa 
EVb 
4 
12 
16 
24 
28 
36 
40 
48 
52 
60 
64 
72 
76 
84 
88 
96 
100 
 
 
8 
 
20 
 
32 
 
44 
 
56 
 
68 
 
80 
 
92 
 
104 
Visita 
1 
2/3 
4 
Hc 
5 
Hc 
6 
Hc 
7 
Hc 
8 
Hc 
9 
Hc 
10 
Hc 
11 
Hc 
g At AS0009 study entry, collect pulse and BP prior to drug administration and then at 30 minutes and 1 hour after dosing. At all other visits collect 
pulse and BP prior to drug administration and once after dosing (any time). All other procedures will only be done prior to dosing.  
h Includes evaluation of signs and symptoms of active TB and risk for exposure to TB. 
i If there has been a delay in menses, perform a urine pregnancy test. 
j All blood samples are to be taken prior to dosing. 
k It is recommended that the QuantiFERON TB Test be performed. This assessment will be performed at study entry, unless an IGRA negative result is 
available less than 6 weeks prior to the first dose of open-label bimekizumab. 
 
 
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Table 2‒2: 
Schedule of study assessments (Week 108 through Week 208) 
Protocol activity 
Treatment Period 
Weeksa 
108 
112 
120 
124 
132 
136 
144 
148 
156 
160 
168 
172 
180 
184 
192 
196 
204 
208/ET 
SFU 
 
 
116 
 
128 
 
140 
 
152 
 
164 
 
176 
 
188 
 
200 
 
 
Visita 
12 
Hb 
13 
Hb 
14 
Hb 
15 
Hb 
16 
Hb 
17 
Hb 
18 
Hb 
19 
Hb 
20 
21 
 
Concomitant medications 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Adverse events 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
eC-SSRS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
HADS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
ASQoL 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
BASDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
BASFI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
SF-36 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
PGADA 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Total and nocturnal spinal pain 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
TB questionnaire 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Vital signs (pulse, temperature, 
BP)c 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Body weight 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Physical examinationd 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
MASES 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
BASMI 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
ECG 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Hematology/biochemistry/urine 
pregnancye,f 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Blood Sample for CRPf 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
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Table 2‒2: 
Schedule of study assessments (Week 108 through Week 208) 
Protocol activity 
Treatment Period 
Weeksa 
108 
112 
120 
124 
132 
136 
144 
148 
156 
160 
168 
172 
180 
184 
192 
196 
204 
208/ET 
SFU 
 
 
116 
 
128 
 
140 
 
152 
 
164 
 
176 
 
188 
 
200 
 
 
Visita 
12 
Hb 
13 
Hb 
14 
Hb 
15 
Hb 
16 
Hb 
17 
Hb 
18 
Hb 
19 
Hb 
20 
21 
 
Blood sample for bimekizumab 
plasma concentrationsf 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
Blood sample for anti-
bimekizumab antibodiesf 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
IGRA TB testg 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
IXRS  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Bimekizumab administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ASQoL=Ankylosing Spondylitis Quality of Life; BASMI=Bath Ankylosing Spondylitis Metrology Index; BASDAI=Bath Ankylosing Spondylitis 
Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BP=blood pressure; CRP=C-reactive protein; 
ECG=electrocardiogram; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; H=home; HADS=Hospital Anxiety and Depression Scale; 
IGRA=interferon gamma release assay; IMP: investigational medicinal product; IXRS=interactive voice or web response system; MASES=Maastricht 
Ankylosing Spondylitis Enthesitis Index; PGADA=Patient's Global Assessment of Disease Activity; SF-36=36-item short form health survey; 
SFU=Safety Follow-Up; TB=tuberculosis;  
Note: The SFU Visit will occur 20 weeks after the last dose of IMP.  
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) with a minimum of 21 days and a maximum of 35 days in between 
doses at all visits except the SFU Visit which should occur no more than 3 days prior the scheduled visit date and within 7 days after the scheduled visit 
date (-3 days /+7 days). 
b Self-administration by the subject/caregivers/appropriate designee will be possible. 
c At all visits except AS0009 study entry, collect pulse and BP prior to drug administration and once after dosing (any time). All other procedures will 
only be done prior to dosing.  
d Includes evaluation of signs and symptoms of active TB and risk for exposure to TB. 
e If there has been a delay in menses, perform a urine pregnancy test. 
f All blood samples are to be taken prior to dosing. 
g It is recommended that the QuantiFERON TB Test be performed. This assessment will be performed at study entry, unless an IGRA negative result is 
available less than 6 weeks prior to the first dose of open-label bimekizumab. 
 
 
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2.4 
Determination of sample size 
There is no formal sample size for this study. The sample size is determined by the number of 
subjects in AS0008 who are eligible for AS0009. Up to 285 subjects from AS0008 could be 
enrolled into this study. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
All computations and generation of outputs will be performed using SAS® Version 9.3 or later. 
UCB uses SAS in a 64-bit Windows environment, and it is well-documented that in this 
environment the maximum accuracy of any numeric value is 15 significant digits. However, SAS 
by default does not limit the accuracy of numeric values to 15 significant digits which, in certain 
instances, may result in inaccurate representation of the data and cause errors when used in 
subsequent calculations, particularly when comparing a value to a chosen threshold. This, in 
turn, could potentially result in a change in classification of a subject from a responder to a non-
responder (and vice versa) if these values occur on a threshold used in the evaluation of response 
(or a critical laboratory value for example). 
Therefore, in order to avoid issues caused by inaccurate floating point representation of numeric 
values, temporary variables are created (ie, for absolute values, change and percentage change 
from Baseline) during programming which are rounded to 12 decimal places prior to comparison 
to a specific threshold in the derivation of a response parameter. This does not imply inherent 
rounding on the ADaM variables AVAL (absolute value), CHG (change) or PCHG (percentage 
change) which are retained unrounded in the final ADaM dataset. Thus, rounding is applied 
exclusively during the derivation of new response parameters or critical value variables, and the 
rounded values are created on a temporary basis only. 
All tables and listings will use Courier New font size 9. 
Descriptive statistics will be displayed to provide an overview of the study results. For 
categorical variables, the number and percentage of subjects in each category will be presented. 
The denominator for percentages will be based on the number of subjects included in the 
respective analysis set. For observed case (OC) summaries, or summaries of data where no 
imputation is made for missing data, subjects with missing data will be accounted for by 
including a “Missing” category (corresponding to subjects with missing data for the variable 
being summarized) as the last row in the list of categories being summarized. Percentages will be 
displayed to 1 decimal place. No percentage will be displayed for zero counts, and no decimal 
will be presented when the percentage is 100%. The % sign will be presented in the column 
header, but not with each individual value.  
For continuous variables, descriptive statistics will include number of subjects with available 
measurements (n), mean, standard deviation (SD), median, minimum, and maximum. Decimal 
places for descriptive statistics will always apply the following rules: 
• “n” will be an integer. 
• Arithmetic and geometric mean, SD, and median will use 1 additional decimal place 
compared to the original data. 
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• Coefficient of variation (CV [%]) will be presented with 1 decimal place. 
• Minimum and maximum will have the same number of decimal places as the original value. 
The number of decimal places used for derived efficacy variables is shown in Table 3‒1. 
Table 3‒1: 
Decimal places for derived efficacy variables 
Variable 
Decimal places used for minimum 
and maximum 
Decimal places used for mean, SD 
and median 
ASDAS-CRP 
1 
2 
BASDAI 
1 
2 
BASFI 
1 
2 
BASMI 
1 
2 
MASES 
1 
2 
TNSP 
1 
2 
SF-36 MCS 
2 
3 
SF-36 PCS 
2 
3 
ASQoL 
0 
1 
HADS-A 
0 
1 
HADS-D 
0 
1 
The abbreviation BKZ will be used in tables and listings headers.  
All data will be presented in by-subject data listings sorted by planned (randomized) treatment 
group at completion of AS0008 (for efficacy listings) or actual treatment group at completion of 
AS0008 (for all other listings), site, subject number, variables (where applicable) and visit 
(where applicable). All listings will include scheduled, repeated, and unscheduled measurements 
in chronological order. Dates will be presented in the format “YYYY-MM-DD” and times will 
be presented in 24h clock format as “hh:mm”. 
In all listings (where applicable) the subject level demographic information (i.e., gender, age, 
race, weight) will be based on the data reported at AS0008 Baseline. 
3.2 
General study level definitions 
3.2.1 
Relative day 
Two relative days will be calculated, these will be relative to the following reference dates; the 
first relative to the start date of study medication (placebo or bimekizumab) in AS0008 and the 
second relative to the start date of study medication in AS0009. Relative day will be calculated 
as: 
𝐶𝑢𝑟𝑟𝑒𝑛𝑡 𝑑𝑎𝑡𝑒−𝑟𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒+ 1 
(1) 
for dates on or after the reference date, and: 
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𝐶𝑢𝑟𝑟𝑒𝑛𝑡 𝑑𝑎𝑡𝑒−𝑟𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒 
(2) 
for dates before the reference date. 
Additional character relative day variables will be derived for inclusion in listings: 
𝐶𝑢𝑟𝑟𝑒𝑛𝑡 𝑑𝑎𝑡𝑒−𝑟𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒+ 1 
(3) 
for dates on or after the reference date and on or before the end date of study medication (no 
prefix), 
𝐶𝑢𝑟𝑟𝑒𝑛𝑡 𝑑𝑎𝑡𝑒−𝑟𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒 
(4) 
for dates before the reference date (‘-‘ prefix), and: 
𝐶𝑢𝑟𝑟𝑒𝑛𝑡 𝑑𝑎𝑡𝑒−𝑒𝑛𝑑 𝑑𝑎𝑡𝑒 𝑜𝑓 𝑠𝑡𝑢𝑑𝑦 𝑚𝑒𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝐴𝑆0009 
(5) 
for dates after the end date of study medication (with ‘+’ prefix). 
Relative day will not be calculated if dates are partial or missing.  
3.2.2 
Study periods 
The following study periods are defined: 
• Treatment Period: The Treatment Period (204 weeks), starts with the first dose of open-label 
bimekizumab in AS0009 and ends with the last dose of study medication. 
• Dosing period: The dosing period starts at the start date of study medication in AS0009 and 
ends at 1 dosing interval (28 days) after the end date of study medication. 
• Safety follow-up (SFU): The SFU is the period after the last dose of bimekizumab 
administration with the SFU visit scheduled for 20 weeks after the last dose of bimekizumab.  
3.3 
Definition of Baseline values 
The Baseline value defined in the AS0008 database will be used as a Baseline for AS0009, 
without additional derivation. The change from AS0008 Baseline will be calculated. 
Due to a change in laboratory vendor between AS0008 and AS0009, laboratory values (with the 
exception of CRP) will use the AS0009 Laboratory Baseline, defined as the earliest post-EV 
value recorded in AS0009 at or prior to AS0009 Week 12 (excluding any local laboratory 
measurements). Change from AS0009 Laboratory Baseline will be calculated for these 
parameters. Change from Baseline will not be calculated for local laboratory measurements as 
there is no Baseline defined for these values. 
The CRP values from the two laboratory vendors have been calibrated, so change from AS0008 
Baseline will be calculated for CRP. 
3.4 
Protocol deviations 
Important protocol deviations are defined as those deviations from the protocol likely to have a 
meaningful impact on study conduct, or on the safety or efficacy outcomes for an individual 
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subject. The criteria for identifying important protocol deviations will be defined within the 
appropriate protocol-specific document. All potential protocol deviations will be reviewed as 
part of the ongoing data cleaning process and documented prior to database lock. 
All deviations will be identified and classified as important or not important. Important protocol 
deviations will be identified and classified by the deviation types: 
• Inclusion criteria deviation 
• Exclusion criteria deviation 
• Withdrawal criteria deviation 
• Prohibited concomitant medication use 
• Incorrect treatment or dose 
• Treatment non-compliance 
• Procedural non-compliance 
The process for identifying and categorizing prohibited medications is described in Section 6.5. 
The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on study 
procedures/conduct (eg, missed visits, remote visits, interruption of study treatment) will be 
documented using the information collected on a dedicated eCRF page the details for which are 
included in Section 12.5. All data reported on this eCRF page will be reviewed during ongoing 
data cleaning meetings in order to determine if these should be considered as important protocol 
deviations. 
3.5 
Mapping of assessments 
Study assessments at an Early Termination (ET) visit where the visit date is within the 
protocol-defined visit window of a scheduled site visit will be mapped to that scheduled site visit 
(this does not include home visits). Visit windows will be calculated relative to the date of first 
dose in AS0009 (planned at the AS0009 EV), but if the dose was missed at that visit, the date of 
the AS0009 EV will be used instead. The following rules will also be applied: 
• If there is an existing scheduled site visit in the window, and the specific assessment was 
performed at that scheduled site visit, then the relevant assessments at the ET visit will be 
mapped to the next scheduled site visit (regardless of whether this is within the protocol-
defined visit window for that site visit).  
• Study assessments at an ET visit that does not fall into the protocol-defined visit window of a 
scheduled site visit will be assigned to the next scheduled site visit after the date of the ET 
visit (regardless of whether this is within the protocol-defined visit window for that site 
visit). 
• Mapping of an assessment to a scheduled visit will occur regardless of whether the 
assessment was planned to be conducted at that visit (with the exception of ADAb). For 
ADAb however, data will only be mapped to scheduled site visits where ADAb levels are 
planned to be measured. Any PK samples taken at the same ET visit will be mapped to the 
same scheduled visit as the ADAb. 
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• Additional rules regarding visit mapping are provided in Section 8.1.5 for BASMI and 
Section 9.1 and Section 9.2 for PK and ADAb summaries respectively. 
Unscheduled assessments where the visit date is within the protocol-defined visit window of a 
scheduled site visit will be mapped to that scheduled site visit (this does not include home visits). 
Visit windows will be calculated relative to the date of first dose in AS0009. But if the dose was 
missed at that visit, the date of the AS0009 EV will be used instead. The following rules will also 
be applied: 
• If there is an existing assessment with a non-missing response (from a scheduled site visit or 
ET visit) in the window, the assessment will be left as unscheduled. 
• Unscheduled assessments which do not fall within a protocol-defined visit window based on 
time since first dose (or date of AS0009 EV if the first dose was missed) will be left as 
unscheduled. 
• Unscheduled assessments obtained at specific time points (e.g., vital signs) will only be 
mapped to a scheduled site visit for the equivalent time point. Thus, if an assessment falls 
within the protocol-defined visit window of a scheduled site visit but the scheduled visit does 
not have a corresponding time point, the measurement will be left as unscheduled (e.g., if the 
unscheduled time point was ‘1 HOUR POST DOSE’ this will not be mapped to a visit at 
which only ‘PRE DOSE’ time points are scheduled). 
• Unscheduled PK and ADAb assessments may also be mapped to a scheduled site visit if the 
visit date is within the protocol-defined visit window of that visit. For ADAb this will only 
apply to scheduled site visits where ADAb levels are planned to be measured. For any PK 
samples obtained at the same unscheduled visit, these will be mapped to the same scheduled 
visit as the ADAb. 
If there are multiple unscheduled assessments in a specific visit window, the first non-missing 
assessment will be mapped to the scheduled visit and used for summary statistics or frequency 
counts. Similarly, if there are multiple scheduled assessments performed on the same visit date, 
the first non-missing assessment will be used for summary statistics or frequency counts. 
Assessments will be reported according to the planned Schedule of Assessments (Table 2‒1) and 
each scheduled visit summary will include actual data and any data mapped from an ET visit to 
that scheduled visit.  The final visit will be labeled “Week 208”. Data obtained at scheduled 
visits will be reported as per the database (i.e., these will not be remapped as described above). 
Assessments mapped to visits at which the assessment was not planned, unscheduled visits and 
unscheduled assessments which are not mapped to scheduled visit at which the assessment was 
planned will be listed only. 
3.6 
Analysis sets 
Three analysis sets will be defined for this study. 
3.6.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all subjects who have given informed consent for AS0009. 
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3.6.2 
Safety Set 
The Safety Set (SS) will consist of all subjects in the ES who received at least one dose of study 
medication in AS0009. 
All safety variables will be summarized for the SS. Pharmacokinetic and immunological 
variables will also be summarized on the SS. 
Two sub-populations of the SS will be defined for this study: Sub-population 1 will consist of all 
subjects in the SS who took no concomitant rescue medication in AS0009, and Sub-population 2 
will consist of all subjects in the SS who took concomitant rescue medication in AS0009, as 
outlined in Section 6.5. Rescue medications will be identified in the study database using the flag 
collected in the electronic case report form (eCRF). Concomitant medications are defined in 
Section 6.4. 
Selected summaries of the primary and secondary safety variables will be repeated for both SS 
Sub-populations only in the event that the number of subjects receiving rescue medication is 
>=10% of the total number of subjects in the SS. 
3.6.3 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all subjects in the ES who received at least one dose 
of study medication in AS0009 and have a valid measurement for at least one efficacy variable at 
any scheduled visit (excluding SFU visits) after AS0009 EV where efficacy is planned to be 
collected. This will include any data collected at an unscheduled or ET visit, and which has been 
remapped to a scheduled visit where efficacy data are planned. The protocol definition suggested 
that a valid measurement for at least one efficacy variable at AS0009 EV was required, but in 
order to identify subjects who have had assessments during AS0009, the requirement has been 
changed to ‘after’. This has been further clarified to include scheduled visits in AS0009 (where 
efficacy data is planned), excluding SFU visits, in order to ensure that all subjects in the FAS 
have data available to contribute to any of the efficacy analyses. 
Secondary and other efficacy variables will be summarized for the FAS. Immunological 
variables will also be summarized on the FAS where specified in Section 9.2. 
3.7 
Treatment assignment and treatment groups 
This is an open label, single arm study.  
Treatment group at the completion of AS0008 (presented as ‘BKZ 160mg’ or ‘BKZ 320mg’) and 
an overall ‘BKZ Total’ column will be used to summarize data in AS0009. 
The endpoints assessing maintenance of ASAS response over time will be summarized by 
treatment sequence across AS0008 and AS0009, and overall. Treatment sequences take the form 
‘A/ B/ C’, where A is the treatment in the first 12 weeks of AS0008, B is the treatment from 
Week 12 to Week 48 of AS0008, and C is the treatment in AS0009. The eight planned treatment 
sequences are as follows:  
• Placebo/BKZ 160mg/BKZ 160mg. 
• Placebo/BKZ 320mg/BKZ 160mg. 
• BKZ 16mg/BKZ 160mg/BKZ 160mg. 
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• BKZ 16mg/BKZ 320mg/BKZ 160mg. 
• BKZ 64mg/BKZ 160mg/BKZ 160mg. 
• BKZ 64mg/BKZ 320mg/BKZ 160mg. 
• BKZ 160mg/BKZ 160mg/BKZ 160mg. 
• BKZ 320mg/BKZ 320mg/BKZ 160mg. 
Safety summaries including AS0009 data only will be presented by treatment group at the 
completion of AS0008 and overall. Safety summaries including data from both AS0008 and 
AS0009 combined will be presented for ‘BKZ 160mg’, ‘BKZ 320mg’, and ‘BKZ Total’, based 
on the SS for AS0009. Subjects who took bimekizumab 320mg during AS0008 will contribute to 
all three columns. Subjects who did not take 320mg in AS0008 will contribute to the ‘BKZ 
160mg’ and ‘BKZ Total’ columns. The combined summaries will present data from AS0008 and 
AS0009 for the subjects who were enrolled in AS0009. The AS0009 only summaries will 
include only data collected in AS0009 (unless otherwise stated). 
Subjects will be summarized and listed based on the actual/received treatment or the planned 
treatment for different analysis sets as follows: 
• ES: planned treatment. 
• SS and Sub-populations: actual treatment. 
• FAS: planned treatment. 
For actual and planned treatments in AS0008, the data will be used directly from the AS0008 
analysis database without any rederivation of treatment assignments in each period. 
In AS0009 it will be assumed that all subjects received the correct treatment as the dose level of 
bimekizumab is the same for all subjects and throughout the study (160mg). If a subject missed a 
dose at AS0008 Week 48, they will also be considered to have received the planned treatment. 
Thus for all subjects in AS0009 the actual treatment will be the same as the planned treatment. 
3.8 
Center pooling strategy 
Centers will be grouped in the geographic regions North America (country codes USA, CAN), 
Western Europe (country codes DEU, ESP) and Eastern Europe (country codes BGR, CZE, 
HUN, POL, RUS and UKR) for use as a covariate in statistical analyses and for sub-group 
analyses (see Section 4.1 and Section 8.4). An additional region grouping of North America 
(country codes USA, CAN) and Europe (country codes BGR, CZE, DEU, ESP, HUN, POL, 
RUS and UKR) will be derived in the datasets for possible use in future integration. 
3.9 
Coding dictionaries 
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 19.0. Medical history conditions and AEs will be classified by primary 
system organ class (SOC) and preferred term (PT). AEs will be classified by primary system 
organ class (SOC), high level term (HLT) and preferred term (PT). 
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Prior and concomitant medications will be coded using version MAR2021 of the World Health 
Organization Drug Dictionary and will be classified by Anatomical Therapeutic Chemical (ATC) 
Main Group, Pharmacological Subgroup, and PT.  
Medical procedures will not be coded. 
3.10 
Changes to protocol-defined analyses 
The following changes have been made to the protocol-defined analyses: 
• Change from AS0009 EV for safety variables will no longer be presented, since the EV 
assessment is made after 36 or 48 weeks of bimekizumab treatment and there is unlikely to 
be any further important change.  
• Change from AS0008 Baseline and AS0009 EV for laboratory variables will not be 
presented, due to a change in laboratory vendor between AS0008 and AS0009. Laboratory 
Baseline has been defined as the earliest value in AS0009 at or prior to AS0009 Week 12. 
• Summaries of ASAS40, ASAS20 and ASAS5/6 response at each post-AS0008 Baseline visit 
have been added for subjects who were responders at AS0008 Week 12. These summaries 
include all post-AS0008 Baseline visits through to AS0009 Week 208, for subjects in the 
FAS for AS0009, and will be used to assess maintenance of response. 
• The protocol describes the FAS as consisting of all enrolled subjects who receive at least 1 
dose of IMP and have a valid measurement for at least 1 efficacy variable at AS0009 study 
entry. This has been updated to include all subjects in the ES who received at least one dose 
of study medication in AS0009 and have a valid measurement for at least one efficacy 
variable at a scheduled visit (excluding SFU visits) after AS0009 EV. This was updated in 
order to identify subjects who have had assessments during AS0009 and which contribute to 
any of the efficacy analyses. 
• Summaries by randomized treatment in AS0008 will not be produced, as subjects will have 
been on a constant dose of bimekizumab 160mg or 320mg for at least 36 weeks prior to 
AS0009 entry. Maintenance of response displays will be split by treatment sequence across 
AS0008 and AS0009. Safety displays using AS0008 information will incorporate exposure in 
AS0008. 
• The protocol defines subgroups based on ‘Concomitant non-steroidal anti-inflammatory drug 
(NSAID) status at AS0009 entry. This has been updated to ‘Concomitant NSAID status at 
start of AS0008’.  
• The protocol stated that all safety analysis would be performed for both Sub-populations; 
instead only key safety analyses will be repeated by Sub-population as identified in 
Section 10. These analyses will be performed only in the event that the number of subjects 
receiving rescue medication is >=10% of the total number of subjects in the SS. 
3.10.1 
Changes related to COVID-19 
The impact of the COVID-19 pandemic on study procedures/conduct and on the primary safety 
endpoints (TEAEs, serious TEAEs and study withdrawal due to TEAEs) will be investigated and 
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additional outputs provided as appropriate. These analyses were not planned as part of the 
protocol as the pandemic was not ongoing at the time of protocol finalization. 
The additional analyses are described in the following sections of the SAP: 
• Subject disposition, including details of impacted visits and effects on collection and 
reporting of efficacy data (Section 5.1.1) 
• Adverse events (Section 10.2.4) 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
All multiple imputation (MI) models (see Section 4.2.1) will include the following covariates: 
• Geographic region at AS0008 Baseline (North America, Western Europe, Eastern Europe), 
as defined in Section 3.8. 
• Previous (past) tumor necrosis factor (TNF) inhibitor agent exposure in AS0008. The value 
in the AS0008 database for past anti-TNF therapy (as collected on the eCRF) will be used for 
AS0009, without additional derivation. 
Missing efficacy data will be handled as described in Section 4.2.1. No imputation will be made 
for missing safety or background data, except as described in Section 4.2.2 and Section 4.2.3. 
4.2 
Handling of dropouts or missing data 
4.2.1 
Handling of missing data for efficacy analysis 
Calculation of derived efficacy variables in the presence of missing data is described in 
individual sub-sections of Section 8.1. All derived efficacy variables will be calculated using 
observed data, and any resulting missing data will be handled as described in this section. All 
non-responder imputation (NRI) and multiple imputation (MI) as described below will be 
performed only for subjects in the FAS for AS0009. 
For assessments missing during AS0008 which are used in AS0009 for reporting maintenance of 
response, the imputed value (based on NRI) from the AS0008 database will be used. 
For all visits in AS0009 (including AS0009 EV), missing values or values which cannot be 
constructed due to missing components for binary secondary/other efficacy variables (ASAS40, 
ASAS20, ASAS5/6) will be imputed using NRI. For each visit, subjects with missing data or 
who have dropped out of the study will be counted as non-responders. This includes any subjects 
with missing baseline values. 
For missing continuous secondary/other efficacy variables an MI approach will be used. This 
will be performed for the following variables/endpoints: 
• ASAS components: 
− Total Spinal Pain, Question 1 from TNSP 
− Inflammation, derived as the mean of Question 5 and 6 from the BASDAI 
• ASDAS-CRP components: 
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− Total Back Pain, Question 2 from the BASDAI 
− Duration of Morning Stiffness, Question 6 from the BASDAI 
− PGADA (this is already included below as this is required as a standalone endpoint) 
− Peripheral Pain/Swelling, Question 3 from the BASDAI 
− CRP 
ASDAS-CRP and ASDAS-ID will be determined after MI of the individual components 
of the ASDAS-CRP (ie, MI will not be applied to the overall ASDAS-CRP score). Note 
that for CRP the rules for handling measurements that are below the limit of 
quantification (BLQ) should be followed as per Section 8.1.2. Thus, if any imputed 
values are <2mg/L these will be replaced with a constant value of 2mg/L for subsequent 
derivation of ASDAS-CRP. For the ASDAS-ID, the number of subjects within each 
disease activity category will be derived for each imputation and the mean number of 
subjects within each category across imputations will be presented. 
• BASDAI 
• BASFI 
• BASMI 
• MASES 
− For MASES the MI model will be restricted to subjects with a MASES score > 0 at 
AS0008 Baseline. Subjects with a MASES score of zero at AS0008 Baseline will be 
excluded prior to performing the procedure outlined below. 
• PGADA 
• TNSP 
• SF-36 
− For SF-36 this will be performed for the Physical Component Summary score (PCS) and 
Mental Component Summary score (MCS) and for each of the 8 domain scores (Physical 
Functioning, Role Physical, General Health, Bodily Pain, Vitality, Social Functioning, 
Role Emotional and Mental Health). 
• ASQoL 
• HADS-A and HADS-D 
− Incidence of normal HADS-A and HADS-D scores (defined as having HADS-D<8 and 
HADS-A<8 at the same visit) will be derived at each visit using the values for HADS-A 
and HADS-D obtained after MI 
• CRP 
− Note that for CRP as a standalone endpoint the rules for handling measurements that are 
below the limit of quantification should be followed as per Section 8.1.12. Thus, if any 
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imputed values are <0.16mg/L these will be replaced with 0.08mg/L prior to any 
subsequent reporting. 
The missing absolute value (not the change from baseline) will be replaced by one of a set of 
plausible values, where each value is a Bayesian draw from the conditional distribution of the 
missing data given the observed data. The basic assumption in MI is that the underlying missing 
data mechanism is ignorable, e.g. the missing data are missing at random.  
All MI procedures will be performed using data from both AS0008 and AS0009 such that 
missing data across both studies will be imputed. Any previous MI or last observation carried 
forward (LOCF) (or other e.g., next observation carried backward) imputation performed in 
AS0008 will not be considered for AS0009 such that the procedure will use OC data only across 
both studies.  
As the AS0008 Week 48 time point is synonymous with the AS0009 EV time point, this will be 
incorporated once only into the model. 
The SAS® PROC MI procedure will be used for the imputation. 
The MI consists of 3 steps: 
• The missing data are imputed m times to create m complete datasets. 
• The m datasets are summarized. 
• The results of the m summaries are combined into a single result. 
The MI method will be applied as follows:  
Step 1 
• Create a data set, sorted by treatment group at completion of AS0008, of subjects with 
observed values and missing values needing imputation. Missing values will be separated 
into non-monotone (ie, intermittent missing values between completed assessments) and 
monotone (ie, missing values after the subject dropped out). The procedure will sequentially 
estimate an imputation model for the efficacy variable at each post-AS0008 Baseline visit 
where efficacy variables are collected, with AS0008 Baseline, geographic region, and past 
TNF inhibitor exposure (as collected on the eCRF in AS0008 for past anti-TNF exposure) as 
covariates, separately for each treatment group at the completion of AS0008. 
• Intermittent missing data will be imputed by draws from the imputation model using the 
Markov-Chain Monte Carlo (MCMC) method with multiple chains and monotone imputing. 
A total number of imputations will be 100. The seed used for these imputations will be 2017.  
Note: All MI procedures described in this SAP will use the same seed. 
• The post-AS0008 Baseline values will be specified in chronological order in the imputation 
model so that the SAS® PROC MI imputes variables from left to right. In case an AS0008 
Baseline raw value is missing, the study participant will be excluded. The imputation model 
based on the MCMC method will only allow multivariate normal continuous variables as 
predictors. Therefore, past TNF inhibitor exposure and geographic region will be re-coded as 
indicator variables. For past TNF inhibitor exposure, this will be 0 for no past exposure and 1 
for past TNF exposure. For region, there will be 2 indicator variables, the first of which will 
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be 1 for subjects from Western Europe and 0 for all other subjects and the second of which 
will be 1 for subjects from Eastern Europe and 0 for all other subjects. The order of the 
covariates in the model will be as follows: region indicator variables (Western Europe =1, 
Other =0; Eastern Europe=1, Other=0), past TNF inhibitor exposure (Yes=1, No=0), 
Baseline and then the visit variables. 
• Once the intermittent missing data are imputed, the monotone missing data will be imputed 
including covariates as defined above, based on the datasets created by the intermittent 
missing data MI. Since this dataset already has 100 imputed values at each visit, only 1 
imputation will be performed. 
Step 2 
The dataset with the imputed results for each treatment arm will be combined into one 
complete dataset including each of the 100 imputations. If any imputed value is less than the 
lower limit of the allowable range for that parameter (as shown in Table 4‒1), it will be 
changed to the lower limit of the range, and similarly for values higher than the allowable 
range. This dataset will be used to calculate the change from AS0008 Baseline variable when 
appropriate.  
Table 4‒1: 
Allowable ranges for continuous efficacy variables 
Variable 
Minimum 
Maximum 
BASDAI 
0 
10 
BASFI 
0 
10 
BASMI 
0 
10 
MASES 
0 
13 
PGADA 
0 
10 
TNSP 
0 
10 
SF-36 MCSa 
-3.33 
80.09 
SF-36 PCS 
5.02 
79.78 
SF-36 Bodily Pain 
21.68 
62 
SF-36 General Health 
18.95 
66.5 
SF-36 Mental Health 
11.63 
63.95 
SF-36 Physical Functioning 
19.26 
57.54 
SF-36 Role Emotional 
14.39 
56.17 
SF-36 Role Physical 
21.23 
57.16 
SF-36 Social Functioning 
17.23 
57.34 
SF-36 Vitality 
22.89 
70.42 
ASQoL 
0 
18 
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Table 4‒1: 
Allowable ranges for continuous efficacy variables 
HADS-A 
0 
21 
HADS-D 
0 
21 
ASAS component score (Total 
Spinal Pain [Question 1 from 
TNSP]) 
0 
10 
ASAS component score 
(Morning stiffness [the mean of 
BASDAI Questions 5 and 6]) 
0 
10 
ASDAS-CRP component score 
(Total Back Pain [Question 2 
from the BASDAI]) 
0 
10 
ASDAS-CRP component score 
(Duration of Morning Stiffness 
[Question 6 from the BASDAI]) 
0 
10 
ASDAS-CRP (Peripheral 
Pain/Swelling [Question 3 from 
the BASDAI]) 
0 
10 
ASDAS-CRP component score 
(CRPb) 
2 
NA 
CRPc 
0.08 
NA 
ASAS=Assessment in SpondyloArthritis International Society; ASDAS-CRP=Ankylosing Spondylitis Disease 
Activity Score-C-reactive protein; ASQoL=Ankylosing Spondylitis Quality of Life; BASDAI=Bath Ankylosing 
Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI= Bath 
Ankylosing Spondylitis Metrology Index; CRP=high sensitivity C-reactive protein; HADS-A=Hospital Anxiety and 
Depression Scale – Anxiety; HADS-D=Hospital Anxiety and Depression Scale – Depression; MASES=Maastricht 
Ankylosing Spondylitis Enthesitis Index; PGADA=Patient’s Global Assessment of Disease Activity; SF-36 
MCS=Short Form 36-Item – Mental Component Summary;  SF-36 PCS=Short Form 36-Item – Physical Component 
Summary; TNSP=Total Nocturnal and Spinal Pain. 
a SF-36 ranges are used for imputation purposes only. Any observed values outside the ranges based on norm-based 
scores will be reported as calculated in all tables and listings. 
b For the purposes of the MI any numerical CRP values obtained in AS0009 that were <0.16mg/L will be 
substituted with half the lower limit of quantification (LLOQ) from AS0008 (ie, 0.08mg/L) prior to performing the 
MI. Subsequently any observed or imputed values of <2mg/L will be replaced by the value of 2mg/L for the 
purposes of deriving the ASDAS-CRP. Any CRP values of >=500mg/L will be set to missing prior to performing 
the MI procedure. 
c For the purposes of the MI any numerical CRP values obtained in AS0009 that were <0.16mg/L will be 
substituted with half the LLOQ from AS0008 (ie, 0.08mg/L) prior to performing the MI. Subsequently any 
imputed values of <0.16mg/L will be replaced by the value of 0.08mg/L for the purpose of summaries based on 
imputed data. Listings will display the original result. CRP values of >=500mg/L will be set to missing prior to 
performing the MI procedure; the subsequently imputed CRP value will be included in the summary tables. 
Step 3 (Excluding CRP) 
The 100 imputed datasets will be combined, and simple means and standard errors will be 
calculated using Rubin’s rules (via SAS® PROC MIANALYZE). For calculation of other 
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descriptive statistics (median, Q1, Q3, minimum and maximum), Rubin’s rules do not apply. 
Multiple imputation estimates will be computed by calculating arithmetic means of the estimates 
from the multiple repetitions of the imputation algorithm. Thus, for median, Q1, Q3, minimum 
and maximum the following approach will apply: 
• The data will be summarized by treatment, visit and imputation and the summary statistics 
will be computed.  
• Results will be summarized by taking the mean value of each summary statistic at each visit 
across all imputations.  
The number of decimal places will remain the same as the original for display purposes (ie, if the 
mean was presented to 1 decimal place, the mean of the means will also be presented to 1 
decimal place). 
Step 3 (CRP only) 
The CRP data will be presented using the geometric mean, 95% confidence interval (CI) for the 
geometric mean, median, Q1, Q3, minimum and maximum. The change from Baseline will be 
expressed as the ratio to Baseline in the summaries. The following approach will be applied: 
• Following the MI procedure the ratio to Baseline will be calculated for any of the imputed 
values  
• The natural logarithm of the absolute values and of the ratios to Baseline will be calculated 
• The logged values will be summarized by treatment, visit and imputation  
• The datasets will be combined using PROC MIANALYZE in order to get the mean and 95% 
CI estimates from the absolute values and ratios to Baseline (based on logged data) across 
imputations 
• The estimates of the mean and 95% CI will be back-transformed to obtain the geometric 
mean and 95% CI on the original scale 
• For the median, Q1, Q3, minimum and maximum the procedure outlined above for the other 
endpoints will be followed 
As a sensitivity analysis, certain efficacy variables will be summarized based on observed data 
(see Section 8).  
As a further sensitivity analysis for ASAS40 and ASAS20 responses, the response variables will 
be derived following MI of the individual components. The ASAS responses will then be derived 
for each subject and each imputation (where each imputation is performed across all individual 
components) and the number and percentage of subjects with each ASAS response in each 
imputation will be calculated. The mean value (across imputations) for the percentage of subjects 
with each ASAS response will be reported. Further details regarding data handling for the 
derivation of the ASAS response are provided in Section 8.1.1.1 and will be implemented 
accordingly. 
A similar approach will be followed for the calculation and summary of the number and 
percentage of subjects with normal HADS scores (defined as having HADS-D<8 and 
HADS-A<8 at the same visit) based on the HADS-D and HADS-A values after MI. 
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Primary and sensitivity analyses are summarized in Table 4‒2. All summaries presenting data 
following MI will include only visits from AS0009 EV onwards (although the MI procedure will 
incorporate data from both AS0008 and AS0009). 
Table 4‒2: 
Missing data handling 
Variable 
Type 
Missing data handling approach 
NRI 
MI/MCMC 
(monotone 
regression) 
OC 
ASAS40, 20 
Responder 
P 
Sa 
S 
ASAS component score (Total Spinal 
Pain [Question 1 from TNSP]) 
Continuous 
 
P 
 
ASAS component score (Morning 
stiffness [the mean of BASDAI 
Questions 5 and 6]) 
Continuous 
 
P 
 
ASAS5/6 
Responder 
P 
 
S 
BASDAI 
Continuous 
 
P 
S 
ASAS-PR 
Responder 
P 
 
S 
ASDAS-CRP 
Continuous 
 
Pb 
 
ASDAS-CRP component score (Total 
Back Pain [Question 2 from the 
BASDAI]) 
Continuous 
 
P 
 
ASDAS-CRP component score 
(Duration of Morning Stiffness 
[Question 6 from the BASDAI]) 
Continuous 
 
P 
 
ASDAS-CRP (Peripheral 
Pain/Swelling [Question 3 from the 
BASDAI]) 
Continuous 
 
P 
 
ASDAS-CRP (CRPc) 
Continuous 
 
P 
 
ASDAS-ID (including Moderate, High 
and Very High Disease Activity 
Categories) 
Responder 
 
Pa 
 
BASFI 
Continuous 
 
P 
 
BASMI 
Continuous 
 
P 
 
MASES 
Continuous 
 
P 
 
PGADA 
Continuous 
 
P 
 
TNSP 
Continuous 
 
P 
 
SF-36 PCS, MCS and domain scores 
Continuous 
 
P 
 
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Table 4‒2: 
Missing data handling 
ASQoL 
Continuous 
 
P 
 
HADS-A, HADS-D 
Continuous 
 
P 
 
Incidence of normal depression/anxiety 
status (using HADS) 
Responder 
 
Pa 
 
CRPd 
Continuous 
 
P 
 
ASAS=Assessment in SpondyloArthritis International Society; ASAS-PR= Assessment in SpondyloArthritis 
International Society Partial Remission; ASDAS-CRP=Ankylosing Spondylitis Disease Activity Score-C-reactive 
protein; ASDAS-ID=Ankylosing Spondylitis Disease Activity Score-Inactive Disease; ASQoL=Ankylosing 
Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath 
Ankylosing Spondylitis Functional Index; BASMI= Bath Ankylosing Spondylitis Metrology Index; CRP=high 
sensitivity C-reactive protein; HADS-A=Hospital Anxiety and Depression Scale – Anxiety; HADS-D=Hospital 
Anxiety and Depression Scale – Depression; MASES=Maastricht Ankylosing Spondylitis Enthesitis Index; 
P=primary method;PGADA=Patient’s Global Assessment of Disease Activity; S=sensitivity method; SF-36 
MCS=Short Form 36-Item – Mental Component Summary;  SF-36 PCS=Short Form 36-Item – Physical 
Component Summary; TNSP=Total Nocturnal and Spinal Pain. 
a Imputation method is applied on continuous data, and responder variable is derived from the continuous data based 
on complete dataset. 
b Imputation for ASDAS-CRP overall score is based on the MI of the individual components of the ASDAS-CRP 
with subsequent recalculation of the overall ASDAS-CRP based on each imputation in turn; for each subject the 
mean of the ASDAS-CRP scores will be used in the summaries. Direct MI of the ASDAS-CRP overall score is not 
performed. 
c Refers to imputation of CRP for the purposes of calculating the ASDAS-CRP. 
d Refers to imputation of CRP for the summaries of CRP as a standalone endpoint. 
4.2.2 
Handling of missing data for adverse events 
A complete date must be established to correctly identify the AE as treatment-emergent. For 
purposes of imputing missing components of partially reported start and stop dates for AEs, the 
algorithms listed below will be followed. Start and stop dates of AEs will be displayed as 
reported in the subject data listings (ie, no imputed values will be displayed in data listings). 
Partial or missing start dates for events recorded during AS0008 (including those which were 
ongoing at the start of AS0009) will be imputed using the imputed start date from the AS0008 
database. 
Imputation of partial AE start dates for events reported in AS0009 only will follow the rules 
below (treatment switching rules refer to AS0008 only and data were used directly from the 
AS0008 database): 
• If only the month and year of the AE start date are specified, and the month and year of the 
start date of study medication in AS0009 are not the same as the month and year of the AE 
start date, and the subject did not switch treatment during that month and year, then use the 
1st of the month of the AE start date. 
• If only the month and year of the AE start date are specified, and the month and year of the 
start date of study medication in AS0009 are not the same as the month and year of the AE 
start date, and the subject switched treatment during the month and year of the AE start date, 
then use the date of treatment switch. 
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• If only the month and year of the AE start date are specified, and the month and year of the 
start date of study medication in AS0009 are the same as the month and year of the AE start 
date, then use the start date of study medication in AS0009 (regardless of treatment 
switching). If this results in a start date after a known end date use the 1st of the month of the 
AE start date. 
• If only the year of the AE start date is specified, and the year of the start date of study 
medication in AS0009 is not the same as the year of the AE start date, and the subject did not 
switch treatment during the year of the AE start date, then use the 1st of January of the year 
of the AE start date. 
• If only the year of the AE start date is specified, and the year of the start date of study 
medication in AS0009 is not the same as the year of the AE start date, and the subject 
switched treatment during the year of the AE start date, then use the date of treatment switch. 
• If only the year of the AE start date is specified, and the year of the start date of study 
medication in AS0009 is the same as the year of the AE start date, then use the start date of 
study medication in AS0009 (regardless of treatment switching). If this results in a start date 
after a known end date use the 1st of January of the year of the AE start date. 
• If only the year and day of the AE start date are specified, and the year of the start date of 
study medication in AS0009 is not the same as the year of the AE start date, then use January 
of the year of the AE start date together with the known day. 
• If only the year and day of the AE start date are specified, and the year of the start date of 
study medication in AS0009 is the same as the year of the AE start date, then use the start 
month of study medication in AS0009 together with the known day.  
− If this results in a start date after a known end date use January of the year of the AE start 
date together with the known day. 
− If this results in a start date prior to the start date of study medication in AS0009 (in the 
imputed month) the event will be considered to be treatment-emergent. 
• If the AE start date is completely unknown and the AE stop date is unknown or not prior to 
the start date of study medication in AS0009, then use the start date of study medication in 
AS0009. 
Imputation of partial AE stop date: 
• If only the month and year are specified, then use the last day of the month. 
• If only the day and year are specified, then use December of that year 
• If only the year is specified, then use December 31st of that year. 
• If the stop date is completely unknown, do not impute the stop date. 
In the event of ambiguity or incomplete data which makes it impossible to determine whether the 
AE was treatment-emergent, the AE will be considered treatment-emergent. For subjects who 
may have died during the study, imputed dates will be truncated at the date of death. 
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If the intensity of an AE is unknown, it is considered as severe. If the relationship to study drug 
is missing, it is considered as related. 
If the seriousness of an AE is unknown, no imputation will be performed. Such events will 
therefore be excluded from any listings or summaries of SAEs. If the seriousness of an AE is 
unknown, every attempt should be made to resolve this prior to database lock. 
4.2.3 
Handling of missing data for prior and concomitant medication 
A complete start and stop date must be established to correctly identify the medication as prior or 
concomitant. For purposes of imputing missing components of partially reported start and stop 
dates for medications, the algorithms listed below will be followed. Start and stop dates of 
medications will be displayed as reported in the subject data listings (i.e. no imputed values will 
be displayed in data listings). 
Partial start dates for medications which started during AS0008 and were ongoing at the start of 
AS0009 will be taken from the AS0008 database based on the dedicated eCRF page for imported 
medications in AS0009 
Imputation of all partial start dates for medications (including those reported on the ‘imported’ 
page) will follow the rules below (treatment switching rules refer to AS0008 only): 
• If only the month and year of the medication start date are specified, and the month and year 
of the start date of study medication in AS0009 are not the same as the month and year of the 
medication start date, and the subject did not switch treatment during that month and year, 
then use the 1st of the month of the medication start date. 
• If only the month and year of the medication start date are specified, and the month and year 
of the start date of study medication in AS0009 are not the same as the month and year of the 
medication start date, and the subject switched treatment during the month and year of the 
medication start date, then use the date of treatment switch. 
• If only the month and year of the medication start date are specified, and the month and year 
of the start date of study medication in AS0009 are the same as the month and year of the 
medication start date, then use the start date of study medication in AS0009 (regardless of 
treatment switching). If this results in a start date after a known end date use the 1st of the 
month of the medication start date. 
• If only the year of the medication start date is specified, and the year of start date of study 
medication in AS0009 is not the same as the year of the medication start date, and the subject 
did not switch treatment during the year of the medication start date, then use the 1st of 
January of the year of the medication start date. 
• If only the year of the medication start date is specified, and the year of the start date of study 
medication in AS0009 is not the same as the year of the medication start date, and the subject 
switched treatment during the year of the medication start date, then use the date of treatment 
switch. 
• If only the year of the medication start date is specified, and the year of the start date of study 
medication in AS0009 is the same as the year of the medication start date, then use the start 
date of study medication in AS0009 (regardless of treatment switching). If this results in a 
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start date after a known end date use the 1st of January of the year of the medication start 
date. 
• If only the year and day of the medication start date are specified, and the year of the start 
date of study medication in AS0009 is not the same as the year of the medication start date, 
then use January of the year of the medication start date together with the known day. 
• If only the year and day of the medication start date are specified, and the year of the start 
date of study medication in AS0009 is the same as the year of the medication start date, then 
use the start month of study medication in AS0009 together with the known day.  
− If this results in a start date after a known end date use January of the year of the 
medication start date together with the known day. 
− If this results in a start date prior to the start date of study medication in AS0009 (in the 
imputed month) the medication will be considered to be concomitant. 
• If the medication start date is completely unknown and the medication stop date is unknown 
or not prior to the start date of study medication in AS0009, then use the start date of study 
medication in AS0009. 
Imputation of partial medication stop dates: 
• If only the month and year of the medication stop date are specified, then use the last day of 
that month and that year. 
• If only the day and year are specified, then use December of that year 
• If only the year of the medication stop date is specified, then use December 31st of that year. 
• If the medication stop date is completely unknown, do not impute the stop date. 
In the event of ambiguity or incomplete data which makes it impossible to determine whether the 
medication was prior or concomitant, the medication will be considered concomitant. For 
subjects who may have died during the study, imputed dates will be truncated at the date of 
death. 
There will be no imputation of any other missing data for concomitant medications. 
4.2.4 
Handling of partial treatment end dates 
The date of last study drug administration in AS0009 may be completely unknown (e.g., if the 
subject is lost to follow-up) or partially known. In the latter case, it is possible to enter a known 
month and year into the database but to leave the day as missing (i.e., YYY-MMM-XX) on the 
study termination page of the CRF.  
Missing or partial treatment end dates will be handled according to the following rules: 
• For subjects for whom the treatment end date is completely missing on the study termination 
page, the date of last dose in AS0009 will be the date/time of the last known dose as reported 
on the study medication administration page of the CRF. 
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− For any subjects who terminated the study in AS0009 without receiving a dose of study 
medication, the treatment end date will be the last date of last study drug administration 
in AS0008. 
• For subjects for whom the treatment end date is partially missing (i.e., only the month and 
year are known) the following rules will be applied: 
− The treatment end date will be imputed as date of last known study medication 
administration + 28 days (i.e., equivalent to the dosing interval), assuming this gives an 
imputed date in the known month and year 
− If the above rule results in an imputed date that is not in the known month and year the 
following will apply: 
◦ 
If the date of last known study medication +28 days results in a month PRIOR to the 
month of the partial date, then the imputed date of last dose will be set to the 1st of the 
known month i.e., YYYY-MMM-01. 
◦ 
If the date of last known study medication +28 days results in a month AFTER the 
month of the partial date, then the imputed date of last dose will be set to the last day 
of the known month e.g., YYYY-MM-31 (modified according to the calendar 
month). 
In the listings the date of last study drug administration will be displayed as received in the data 
i.e., without imputation. 
4.3 
Interim analyses and data monitoring 
An interim analysis will be performed after the final subject has reached AS0009 Week 108, 
based on two years’ exposure in the study. All outputs described in this SAP will be presented 
with the exception of COVID-19 related tables and listings. The datasets for the interim analysis 
will include all data collected up to this point; the ‘by-visit’ summaries will present data only up 
to the Week 108 time point; summaries of AEs and exposure will present all data collected up to 
the time of the database cut-off date (ie, when the final subject has reached AS0009 Week 108). 
Additional data cuts may also be performed for regulatory and publication purposes. 
4.4 
Multicenter studies 
The data from all centers will be pooled for the purposes of the analysis. There will be no formal 
statistical evaluation of the effect of center on the results obtained. 
Centers will be grouped into the geographic regions of North America, Western Europe and 
Eastern Europe as described in Section 3.8 for use as a covariate in statistical analyses and for 
sub-group analyses. 
4.5 
Multiple comparisons/multiplicity 
Not applicable. 
4.6 
Use of an efficacy subset of subjects 
Not applicable. 
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4.7 
Active-control studies intended to show equivalence 
Not applicable. 
4.8 
Examination of subgroups 
Subgroup analyses will be performed for the following secondary efficacy variables: 
•  ASAS20, ASAS40 and ASAS5/6 response at AS0009 Week 48. 
• Change from Baseline in BASDAI at AS0009 Week 48.  
The following variables for subgroup analyses will be used: 
• Geographic region at AS0008 Baseline (North America, Western Europe and Eastern 
Europe) 
• Previous (past) TNF inhibitor exposure at AS0008 Baseline (yes, no).  The value in the 
AS0008 database for past anti-TNF therapy (as collected on the eCRF) will be used for 
AS0009, without additional derivation. 
• Concomitant NSAID status at start of AS0008 (yes, no). The value in the AS0008 database 
for past NSAID therapy (as collected on the eCRF) will be used for AS0009, without 
additional derivation.  
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
Subject disposition (date of first and last subject visit, number of subjects included in each 
analysis set [ES, SS, and FAS]) will be presented overall, by region and for each site by 
treatment group at completion of AS0008 and overall for the ES. 
The number and percentage of subjects in each analysis set (ES, SS and Sub-populations, and 
FAS) will be presented by treatment group at completion of AS0008 and overall.  
The number and percentage of subjects who started, completed and discontinued the study, along 
with the primary reason for discontinuation will be summarized by treatment group at 
completion of AS0008 and overall for the SS (a subject will be considered to have completed the 
study if they attended Visit 21 [Week 208]). For the purposes of the summaries the data will be 
taken directly from the eCRF page for study termination. 
The number and percentage of subjects who started, completed and discontinued study 
medication, along with the primary reason for medication discontinuation will be summarized by 
treatment group at completion of AS0008 and overall for the SS (a subject will be considered to 
have completed study treatment if they received a dose at Visit 20 [Week 204]). For the purposes 
of the summaries the data will be taken directly from the eCRF page for study medication 
discontinuation. 
For any subjects where the data on the study termination and study medication discontinuation 
eCRF pages are inconsistent, the data reported on the study termination page will be considered 
as primary i.e., if a subject is reported as discontinuing from the study, they will be regarded as 
discontinuing study medication as well (regardless of whether this is reported in the eCRF). 
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Discontinuations due to AEs will also be summarized by treatment group at completion of 
AS0008 and overall for the SS. 
Subjects who did not meet the eligibility criteria and the inclusion and/or exclusion criteria not 
met will be listed for the ES. 
Subject disposition (subject status, date of informed consent, date of enrollment into AS0009, 
treatment sequence across AS0008 and AS0009, treatment received at completion of AS0008, 
start and end date/time and relative days of study medication in AS0009, date of premature study 
discontinuation and date of final contact) will be listed for the ES. Days relative to the start date 
of study medication in AS0008 and to the start of study medication in AS0009 will be included 
for the end date of study medication.  
Subject inclusion in each analysis set will be listed for the ES. 
Subjects excluded from at least one analysis set, with reason for exclusion, will be listed for the 
ES. Subjects who were excluded from the SS will have a reason of ‘Subject did not receive at 
least one dose of study medication during AS0009’, and subjects who were excluded from the 
FAS will have a reason of ‘Subject did not have a valid measurement of at least one efficacy 
variable after AS0009 study entry’. 
Study and treatment discontinuation reasons and the name of any subsequent treatment will be 
listed for the ES. Total days on study medication from the start date in AS0008 and from the start 
date in AS0009 will be included. 
These will be calculated as described below: 
𝑇𝑜𝑡𝑎𝑙 𝑑𝑎𝑦𝑠 𝑜𝑛 𝑠𝑡𝑢𝑑𝑦 𝑚𝑒𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑓𝑟𝑜𝑚 𝑠𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒 𝑖𝑛 𝐴𝑆0009
= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 𝑖𝑛 𝐴𝑆0009 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 𝑖𝑛 𝐴𝑆0009)
+ 1 
(6) 
𝑇𝑜𝑡𝑎𝑙 𝑑𝑎𝑦𝑠 𝑜𝑛 𝑠𝑡𝑢𝑑𝑦 𝑚𝑒𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑓𝑟𝑜𝑚 𝑠𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒 𝑖𝑛 𝐴𝑆0008
= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 𝑖𝑛 𝐴𝑆0009 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 𝑖𝑛 𝐴𝑆0008)
+ 1 
(7) 
For the total days on study medication in AS0008 this will be calculated from the first dose of 
any medication received regardless of treatment assignment. 
Visit dates, including the day relative to the start of study medication in AS0008 and in AS0009, 
will be listed for the ES. 
5.1.1 
Impact of COVID-19 
A listing of all visits affected by COVID-19 will be presented based on the Enrolled Set 
including the impacted visit (if applicable), date of visit (if applicable), relationship to 
COVID-19, impact category and a narrative (short description) of the event. These data will also 
be summarized by treatment group at completion of AS0008, and overall for the ES for the 
following: 
• Impact of COVID-19 for any reason 
• Impact of COVID-19 for any reason by country 
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In addition, in order to assess the potential impact of COVID-19 on the collection and reporting 
of efficacy data a separate listing and summary table will be presented to display missing data 
and data collected via an alternative modality (eg, phone, video call). For the purpose of these 
displays, missing data will be presented only for visits affected by COVID-19 (as reported on the 
dedicated eCRF page) ie, missing data at other visits and for other reasons will not be included. 
The following efficacy assessments may be collected remotely: 
• HADS 
• ASQoL 
• BASDAI 
• BASFI 
• SF-36 
• PGADA 
• TNSP 
For visits conducted remotely (as reported on the dedicated eCRF page) it is not possible to 
assess MASES or BASMI and therefore these assessments will be missing at the specified visit. 
In addition, for any missed visit or a visit conducted remotely, the CRP assessment will also be 
missing. Such assessments will be considered as missing due to COVID-19. For these visits it 
will therefore not be possible to assess ASAS 5/6 response or ASDAS-CRP. 
A listing will be presented showing each impacted visit, based on the FAS. This will include the 
planned visit, the visit date and details of the assessments conducted remotely and/or those 
missing as a result of COVID-19. 
These data will be presented in a summary table by treatment group at completion of AS0008 
and overall, for the FAS. 
For both the listing and the summary table, only visits at which efficacy assessments are 
scheduled will be included. 
5.2 
Protocol deviations 
The number and percentage of subjects with an important protocol deviation and with each 
category of important protocol deviation (as described in Section 3.4) will be presented by 
treatment group at completion of AS0008 and overall for the ES. 
Important protocol deviations, including deviation type and description, will be listed for the ES. 
A separate listing of COVID-19 related important protocol deviations will be presented, based on 
the ES. COVID-19 related important deviations will be identified by the prefix of ‘COVID’ in 
the deviation verbatim text. 
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6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Demographics 
Demographic variables (age [at time of informed consent], gender, racial group, ethnicity, 
weight, height, body mass index [BMI], country, and geographic region) will be summarized by 
treatment group at completion of AS0008 and overall for the SS. 
One summary table will be produced for AS0008 Baseline values. Age, sex, weight and BMI 
collected at AS0009 EV will be listed only. 
Age and BMI will be summarized as continuous and as categorical variables: 
Age will be categorized as: 
• ≤18, 19-<65, ≥65 years (clinicaltrials.gov requirement). 
• 18-<65, 65-<85, ≥85 years (EudraCT requirement). 
• 18-<45, ≥45-<65, ≥65 years (bimekizumab program conventions). 
BMI (kg/m^2) is calculated based on the height (in m) and the weight (in kg) using the formula: 
𝐵𝑀𝐼= 𝑤𝑒𝑖𝑔ℎ𝑡
ℎ𝑒𝑖𝑔ℎ𝑡2
 
(8) 
Even if available in the database, BMI will be re-calculated. BMI is rounded to 1 decimal place. 
BMI will be categorized as follows: <25, 25-<30, ≥30 kg/m^2. 
Demographic data, including AS0008 Baseline and AS0009 EV values for the repeated 
variables, will be listed for the ES. 
6.2 
Other baseline characteristics 
AS history including the time since first diagnosis of AS (at time of enrolment in AS0008 and at 
time of enrolment in AS0009), time since first symptoms of AS (at time of enrolment in AS0008 
and at time of enrolment in AS0009), age at first diagnosis date, and AS subtype (clinical 
criterion a, b, c or radiologic criterion) will be summarized by treatment group at completion of 
AS0008 and overall for the SS.  
Time since first diagnosis will be summarized as a continuous variable and as categorical 
variable. Time since first diagnosis of AS at time of enrolment in AS0008 will be taken from the 
AS0008 database. Time since first diagnosis of AS at time of enrolment in AS0009 will be 
calculated as below, where date of diagnosis will be taken from the AS0008 database: 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑓𝑖𝑟𝑠𝑡 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠 
= 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑖𝑛𝑓𝑜𝑟𝑚𝑒𝑑 𝑐𝑜𝑛𝑠𝑒𝑛𝑡 𝑖𝑛 𝐴𝑆0009  
− 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠 𝑖𝑛 𝐴𝑆0008 
(9) 
Time since first diagnosis for each study will be categorized as: <5, ≥5 years. 
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Time since first symptoms of AS at time of enrolment in AS0008 will be taken from the AS0008 
database. Time since first symptoms at time of enrolment in AS0009 will be calculated as: 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑓𝑖𝑟𝑠𝑡 𝑠𝑦𝑚𝑝𝑡𝑜𝑚 
= 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑖𝑛𝑓𝑜𝑟𝑚𝑒𝑑 𝑐𝑜𝑛𝑠𝑒𝑛𝑡 𝑖𝑛 𝐴𝑆0009                                        (10) 
− 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑠𝑦𝑚𝑝𝑡𝑜𝑚 𝑖𝑛 𝐴𝑆0008 
Age at first diagnosis will be taken from the AS0008 database. AS history will be listed for the 
ES. 
The following baseline characteristics will be summarized by treatment group at the completion 
of AS0008 and overall for SS: 
• BASDAI total score. 
• BASDAI spinal pain (Question 2). 
• PGADA. 
• Total spinal pain (Question 1 of the TNSP questionnaire). 
• BASFI. 
• ASDAS-CRP. 
• CRP. 
• HLA-B27 (positive, negative). 
• Anti-TNF therapy prior to first dose in AS0008 (yes, no). The value in the AS0008 database 
for past anti-TNF therapy (as collected on the eCRF) will be used for AS0009, without 
additional derivation. 
• NSAID therapy prior to first dose to first dose in AS0008 (yes, no). The value in the AS0008 
database for past NSAID therapy (as collected on the eCRF) will be used for AS0009, 
without additional derivation. 
• Current number of NSAID therapies (0, 1, 2, ≥3).  
• Current synthetic disease modifying anti-rheumatic drugs (DMARDs) (methotrexate [MTX], 
sulfasalazine, hydroxychloroquine) (yes, no). 
• Current corticosteroid use (yes, no) 
One summary table will be produced for AS0008 Baseline values and another for AS0009 EV 
values. NSAID, HLA-B27 and anti-TNF therapy prior to first dose will be based on data 
collected in AS0008 and will be included in the AS0008 Baseline table only.  
BASDAI, BASDAI spinal pain (Q2), PGADA, total spinal pain (Q1 of the TNSP questionnaire), 
BASFI, ASDAS-CRP, CRP, current NSAID, current synthetic DMARDs and current 
corticosteroids will be included in both tables. CRP values at AS0009 EV will be taken from the 
Week 48 record in the AS0008 database. For the summary of AS0009 EV data, current NSAID, 
current synthetic DMARD and current corticosteroid therapy are defined as medications that are 
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ongoing at the AS0009 EV, or that started on the date of the AS0009 EV. This does not include 
medications that were stopped on the date of the AS0009 EV. In addition, for AS0009, current 
corticosteroid therapy will include oral medications only. 
Baseline characteristics, including AS0008 Baseline and AS0009 EV values for the repeated 
variables, will be listed for the ES. 
6.3 
Medical history and concomitant diseases 
Medical history and ongoing medical conditions collected prior to first study medication 
administration in AS0008 and any additional conditions collected prior to first dose of study 
medication in AS0009 will be summarized together. The number and percentage of subjects with 
any condition, and with each condition in each MedDRA SOC and PT, will be presented by 
treatment group at the completion of AS0008 and overall, for the SS.  
Medical history and ongoing medical conditions, including the start date and end date (or 
ongoing if applicable), will be listed for the SS. The listing will indicate whether the condition 
was reported in AS0009. 
A glossary of all medical history conditions including the reported term, PT and SOC will also 
be presented. 
The number and percentage of subjects with a history of each category of extra-articular 
manifestations (uveitis, inflammatory bowel disease [IBD], psoriasis, peripheral arthritis, 
enthesitis, dactylitis) will be summarized by treatment group at completion of AS0008 and 
overall, for the SS, based on data collected at the AS0009 EV. The number and percentage of 
subjects with an occurrence of extra-articular manifestations (uveitis, IBD, psoriasis) post-EV 
will be summarized by treatment group at completion of AS0008 and overall, for the SS. 
Extra-articular assessments will be listed for the SS. 
6.4 
Past, prior and concomitant medications 
Only medications that were ongoing at the end of AS0008 or were started during AS0009 will be 
reported. 
Concomitant medications are medications taken at least 1 day in common with the study 
medication dosing period in AS0009 (as defined in Section 3.2.2). A medication is classed as 
concomitant if the start date is no later than the end date of study medication in AS0009 + 28 
days, and the stop date is either missing or on or after the start date of study medication in 
AS0009. This includes medications that started prior to dosing in AS0009 and continued after. 
For the purposes of the analysis, past medications are medications that started and stopped prior 
to dosing in AS0008. These include past TNF therapy (for subgroup analyses, MI modelling and 
baseline characteristics) and past NSAID therapy (for Baseline characteristics). 
Missing or partial medication start and stop dates will be imputed as described in Section 4.2.3. 
Imputations of missing data will be performed before calculation of relative study days and 
classification as concomitant.  
The number and percentage of subjects taking concomitant medications will be summarized by 
ATC class, presenting Anatomical Main Group (ATC Level 1), Pharmacological Subgroup 
(ATC level 3), and PT, by treatment group at completion of AS0008 and overall for the SS.  
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All medications reported in AS0009, including flags to identify concomitant and rescue 
medications, and start and stop days relative to the start date of study medication in AS0008 and 
start and stop days relative to the start of study medication in AS0009, will be listed for the ES. 
A glossary of all medications including the Anatomical Main Group (ATC Level 1), 
Pharmacological Subgroup (ATC level 3) PT and reported term will also be presented, based on 
the ES. 
6.5 
Prohibited medication and rescue therapy 
The following medication categories will be identified: 
• Rescue medications as defined below. Subjects in the category ‘Any concomitant rescue 
therapy in AS0009’ will be considered SS Sub-population 2 and other subjects will be 
considered SS Sub-population 1. Rescue medications will be identified using the flag 
collected in the eCRF. 
• NSAIDs to identify subgroups/covariates. 
• Prohibited medications. 
Rescue medications and NSAIDs will be classified into subcategories for reporting purposes. 
The identification and classification of concomitant medications will be performed by merging 
an external physician-reviewed spreadsheet (which includes relevant flags for selecting 
medications in each category) with the data entered into the study database in order to categorize 
the medications correctly for the tables.  
The number and percentage of subjects who receive the following categories of rescue 
medication will be summarized by treatment group at completion of AS0008 and overall for the 
SS. 
• Any rescue medication in AS0009 that is classified as a concomitant medication as defined in 
Section 6.4. 
• NSAID at AS0009 EV 
• No NSAID at AS0009 EV 
− No NSAID at AS0009 EV and initiate NSAID [but not Cox-2 inhibitors] in AS0009 
(only the initiation of NSAIDs that are classified as concomitant medications as defined 
in Section 6.4 will be included). 
− No NSAID at AS0009 EV and initiate Cox-2 inhibitors in AS0009 (only the initiation of 
Cox-2 inhibitors that are classified as concomitant medications as defined in Section 6.4 
will be included). 
• Use of any DMARDs in AS0009 alone or in combination (includes MTX, sulfasalazine, 
leflunomide and hydroxychloroquine). Only concomitant medications will be included as 
defined in Section 6.4.  
• Intra-articular corticosteroid in AS0009 that is classified as concomitant as defined in 
Section 6.4. 
• Oral corticosteroid in AS0009 that is classified as concomitant as defined in Section 6.4. 
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• Analgesics in AS0009 that are classified as concomitant as defined in Section 6.4.  
Rescue therapy category and medication name, start date and day relative to start of study 
medication in AS0008 and AS0009 will be listed for the SS. 
PRN analgesic and PRN opioid analgesic use within 24 hours prior to study visits will be listed 
for the ES, based on the dedicated eCRF page for prohibited medications. 
6.6 
Concomitant medical procedures and procedure history 
A listing of concomitant medical procedures and a separate listing of procedure history will be 
presented for the ES. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Compliance will be summarized as the number of doses received relative to the number of doses 
expected: 
𝑃𝑒𝑟𝑐𝑒𝑛𝑡 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡 𝑐𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 100 ∗(Number of doses received)
Number of doses expected
 
(11) 
where the total number of expected doses is derived relative to when the subject finishes 
treatment. If a subject completes OLE treatment 52 doses are expected (EV and every 4th week 
afterwards until AS0009 Week 204). If a subject discontinues early, then the number of expected 
doses is based on the time of study discontinuation relative to the planned dosing visits (taking 
into account the permitted visit window). If the date of study discontinuation is missing the final 
contact date (as reported on the eCRF) will be used instead.   
A summary of percent treatment compliance, both continuous and categorized as ≤75% and 
>75%, will be provided by treatment group at completion of AS0008 (see Section 3.7) and 
overall for the SS. 
Treatment compliance will be listed for the SS.  
A summary of the injection setting (study site/home) and person performing the injection (site 
personnel/subject/caregiver) will be presented by dosing visit (excluding unscheduled dosing 
visits) and treatment at completion of AS0008 and overall for the SS. The summary will include 
the total number of subjects injected at each visit and the number and percentage of subjects in 
each category for injection setting and person performing the injection. Percentages will be based 
on the number of subjects injected at each visit. 
An additional summary, by treatment at completion of AS0008 and overall, will present the 
number and percentage of subjects in each of the following categories: 
• One or more self-administrations during the study 
• One or more home administrations during the study 
• One or more self-administrations also performed at home during the study 
Percentages will be based on the number of subjects in the SS for each treatment group or 
overall, as applicable. 
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A listing of study medication administration (including injection dates and times, kit numbers, 
who performed the injection, and the location of the injection) will be presented. 
8 
EFFICACY ANALYSES 
Missing efficacy data will be imputed as described in Section 4.2.1 prior to reporting. As a 
sensitivity analysis, summaries will be repeated based on non-imputed (OC) data for the 
following variables: 
• ASAS40 response relative to AS0008 Baseline at each visit in AS0009. 
• ASAS20 response relative to AS0008 Baseline at each visit in AS0009. 
• ASAS 5/6 response relative to AS0008 Baseline at each visit in AS0009. 
• Change from AS0008 Baseline in BASDAI at each visit in AS0009. 
A further sensitivity analysis will be performed for ASAS40 and ASAS20 response relative to 
AS0008 Baseline. The response endpoint will be re-derived and summarized based on the mean 
value (across multiple imputations) of the individual component scores after imputation for 
missing data. 
Efficacy variables will be summarized and listed for the FAS. Summaries of MASES will be 
restricted to subjects with a MASES >0 at AS0008 Baseline. Maintenance of response 
summaries will be restricted to subjects who achieved a response at AS0008 Week 12 for the 
specific endpoint (where the response at AS0008 Week 12 is taken directly from the AS0008 
datasets). 
Responder variables (e.g. ASAS40 response) will be derived relative to the AS0008 Baseline and 
summarized using n and percentage at each visit, by treatment group at completion of AS0008 
and overall. 
Maintenance of response will be assessed for ASAS40, ASAS20 and ASAS5/6. The responses 
will be derived relative to AS0008 Baseline and summarized using n and percentage at each 
post-AS0008 Baseline visit, by treatment sequence across AS0008 and AS0009. These 
summaries will therefore include AS0008 Week 1, 2, 4, 8 12, 16, 24, and 36 and AS0009 EV 
(AS0008 Week 48), Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 
204, and Week 208. AS0008 Week 1 and 2 are not applicable for ASAS5/6 response. 
Absolute and change from AS0008 Baseline for all continuous efficacy variables will be 
summarized descriptively by visit, by treatment group at completion of AS0008 and overall. 
Any data collected at the SFU visit will be excluded from all efficacy summaries; this data will 
be included in the listings only. 
8.1 
Derivation of efficacy variables 
Derived efficacy variables at AS0008 Baseline will be taken from the AS0008 database. 
Derivations described below will only be performed for data in the AS0009 database (which 
includes AS0008 Week 48 re-labelled as AS0009 EV). 
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For composite endpoints, component assessments will be combined based on the visit 
assignment following any mapping as described in Section 3.5. Assessments from the same 
assigned visit will be used, regardless of actual assessment date. 
8.1.1 
Assessment in Axial Spondyloarthritis International Society 
Response Criteria 
The ASAS20 response is defined as an improvement (decrease) of at least 20% and absolute 
improvement of at least 1 unit on a 0 to 10 numeric rating scale (NRS) in at least 3 of the 4 
following domains (Anderson, 2001): 
• PGADA 
• Pain assessment (total spinal pain, question 1 from total and nocturnal spinal pain 
questionnaire) 
• Function (represented by the BASFI) 
• Inflammation (the mean of the BASDAI questions 5 and 6, concerning morning stiffness, 
intensity and duration) 
This must be accompanied by the absence of deterioration in the potential remaining domain. 
Deterioration is defined as a relative worsening of at least 20% and an absolute worsening of at 
least 1 unit. 
The ASAS criteria for 40% improvement are defined as relative improvement of at least 40% 
and absolute improvement of at least 2 units on a 0 to 10 NRS in at least 3 of the 4 domains and 
no worsening at all in the remaining domain (where worsening is defined as any worsening at all 
relative to baseline). 
The comparison of changes to the specified cut-offs (i.e., >=1 or >=2 units) will be based on 
non-rounded data. 
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, which 
includes, in addition to the 4 domains above, spinal mobility (lateral spinal flexion as recorded 
for BASMI) and CRP as more objective measures (Brandt et al, 2004).  In the calculation of the 
ASAS 5/6 response the actual assessment value for the lateral spinal flexion will be used and not 
the transformed value used in the calculation of the BASMI score. 
If the CRP value is below the lower limit of quantification (LLOQ) defined in AS0008 then it 
will be set to half of the LLOQ (as described in Section 8.1.12). 
The ASAS partial remission (ASAS-PR) response is defined as a score of ≤2 units on a 0 to 10 
unit scale in all 4 domains listed above.  
8.1.1.1 
Data Handling Rules for ASAS40 and ASAS20 
The ASAS40 and ASAS20 will be derived based on the data handling rules below. These rules 
will be implemented prior to performing any NRI or MI procedures, and will therefore be 
integrated as part of any OC summaries i.e., they are considered as OC data.  
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The rules will apply for all visits in AS0009 where at least one component is present at the 
specific visit. For summaries of maintenance of response, the ASAS responses at visits in 
AS0008 will not be re-derived and will be taken directly from the AS0008 database. 
• If 3 components are present (and the other component is missing), and all 3 components meet 
the criteria for improvement, the remaining component will be assumed not to have 
deteriorated and the subject will be considered a responder for ASAS40 (or ASAS20). 
• If at least 1 component is present (and 1 or more other components are missing) and meets 
the criteria for a deterioration, the subject is a non-responder for ASAS40 (or ASAS20) 
• If a single component value is missing at Baseline (and the other 3 components are not 
missing), the percent and absolute improvement from Baseline for all visits for that 
component will be set to 0 for purposes of ASAS response calculations. Thus, the subject 
may still be considered a responder for ASAS40 (or ASAS20) if the other 3 components all 
meet the criteria for improvement. 
− Note that for MI any component with a missing Baseline will be excluded from the MI 
modelling as Baseline is included as a covariate in the model. 
− Thus, for the MI this will mean that a maximum of 3 components only will be available 
at each visit and all 3 components must therefore demonstrate an improvement based on 
the imputed values in order for the subject to be defined as a responder at that visit. In all 
other cases the subject will be regarded as a non-responder when the response is re-
derived based on the imputed components. 
• If more than 1 component value is missing at Baseline, the percent and absolute 
improvement from Baseline for all visits for those components will be set to 0 for purposes 
of ASAS response calculations. Thus, the subject would be considered a non-responder for 
ASAS40 (and ASAS20) at all visits. 
− Any subject with more than 1 component missing at Baseline will therefore be excluded 
from any summaries based on MI as there would be insufficient data available to derive a 
response. 
• If the Baseline value for a given component is 0 the percent improvement from Baseline is 
not calculable. In this case the following rules will apply: 
− If the post-Baseline value is also 0, the percent and absolute improvement at that visit 
will be treated as 0 for purposes of ASAS response calculations.  
− If the post-Baseline value is greater than 0 and the arithmetic change from Baseline is 
>=1.0, then that component will be treated as having a 20% worsening and a 1-unit 
absolute worsening from Baseline for purposes of ASAS response calculations (i.e., the 
component has deteriorated). 
− If the post-Baseline value is greater than 0 and the arithmetic change from Baseline is 
<1.0, then that component will be treated as having neither improved nor worsened for 
purposes of ASAS response calculations. 
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− If the post-Baseline value is missing, it will be regarded as 0 and the percent and absolute 
improvement at that visit will be treated as 0 for purposes of ASAS response calculations 
(NB: For the MI procedure the observed data will be included in the model as received 
without imputation with 0, and the percent and absolute improvement will be assumed to 
be 0 after performing the MI, regardless of the imputed absolute values) 
• For component scores with a Baseline value >0 and a post-Baseline value of 0, percentage 
improvement will be calculated as for any other non-missing data. 
With regards to the BASFI component see Section 8.1.3 for calculation in case of missing values 
of single questionnaire items. 
With regards to the BASDAI component see Section 8.1.4 for calculation in case of missing 
values of single questionnaire items. 
Further details regarding the assumptions and assignment of worst-case imputations for NRI are 
provided in Section 12.1. 
8.1.1.2 
Data Handling Rules for ASAS5/6 
The ASAS5/6 will be derived based on the data handling rules below. These rules will be 
implemented prior to performing any NRI procedures and will therefore be integrated as part of 
any OC summaries.  
The rules will apply for all visits in AS0009 where at least one component is present at the 
specific visit. For summaries of maintenance of response, the ASAS responses at visits in 
AS0008 will not be re-derived and will be taken directly from the AS0008 database. 
• If 5 components are present (and the other component is missing), and all 5 components meet 
the criteria for improvement, the subject will be considered a responder for ASAS5/6. 
• If all components are present and 5 components meet the criteria for improvement, the 
subject will be considered a responder for ASAS5/6 regardless of whether the remaining 
component has stayed the same or deteriorated. 
• If a single component value is missing at Baseline (and the other 5 components are not 
missing), the percent and absolute improvement from Baseline for all visits will be treated as 
0 for purposes of ASAS response calculations. Thus, the subject may still be considered a 
responder for ASAS5/6 if the other 5 components all meet the criteria for improvement. 
• If more than 1 component value is missing at Baseline, the percent and absolute 
improvement from Baseline for all visits for those components will be set to 0 for purposes 
of ASAS response calculations. Thus, the subject would be considered a non-responder for 
ASAS5/6 at all visits. 
• If the Baseline value for a given component is 0 the percent improvement from Baseline is 
not calculable. In this case the following rules will apply: 
− If the post-Baseline value is also 0, the percent and absolute improvement at that visit 
will be treated as 0 for purposes of ASAS response calculations.  
− If the post-Baseline value is greater than 0 and the arithmetic change from Baseline is 
>=1.0, then that component will be treated as having a 20% worsening and a 1-unit 
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absolute worsening from Baseline for purposes of ASAS response calculations (i.e., the 
component has deteriorated). This will not affect the ASAS5/6 response as this is based 
on improvement only. 
− If the post-Baseline value is greater than 0 and the arithmetic change from Baseline is 
<1.0, then that component will be treated as having neither improved nor worsened for 
purposes of ASAS response calculations. This will not affect the ASAS5/6 response as 
this is based on improvement only. 
− If the post-Baseline value is missing, it will be regarded as 0 and the percent and absolute 
improvement at that visit will be treated as 0 for purposes of ASAS response calculations  
• For component scores with a Baseline value >0 and a post-Baseline value of 0, percentage 
improvement will be calculated as for any other non-missing data 
With regards to the BASFI component see Section 8.1.3 for calculation in case of missing values 
of single questionnaire items. 
With regards to the BASDAI component see Section 8.1.4 for calculation in case of missing 
values of single questionnaire items. 
Further details regarding the assumptions and assignment of worst case for NRI are provided in 
Section 12.1. 
8.1.2 
Ankylosing Spondylitis Disease Activity Score – C-reactive Protein 
The ASDAS-CRP consists of a number of assessments which are scored by the subject and 
physician and multiplied by a proven formula (van der Heijde et al, 2009) as shown below: 
• 0.121 x Total Back pain (BASDAI Question 2 result) 
• 0.058 x Duration of morning stiffness (BASDAI Question 6 result) 
• 0.110 x PGADA 
• 0.073 x Peripheral pain/swelling (BASDAI Question 3 result) 
• 0.579 x (natural logarithm of the (CRP [mg/L] + 1)) 
Back pain, PGADA, duration of morning stiffness and peripheral pain/swelling are all assessed 
on a numerical scale (0 to 10 units) (Lukas et al, 2009). If the CRP value is <2mg/L, the constant 
value of 2mg/L should be used in the calculation. The sum of these weighted components gives 
the ASDAS-CRP. 
If any individual components of the ASDAS-CRP are missing then the ASDAS-CRP will be 
regarded as missing. The imputed value for ASDAS-CRP will then be based on the imputed 
values for the individual components.  
Disease activity categories based on ASDAS-CRP are as follows: 
• ASDAS-ID: ASDAS-CRP <1.3 
• ASDAS-Low Disease Activity: ASDAS-CRP >=1.3 to <2.1 
• ASDAS-High Disease Activity: ASDAS-CRP >=2.1 to <=3.5 
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• ASDAS-Very High Disease Activity: ASDAS-CRP >3.5 
For classification of the above, MI methods will be used to impute the individual components of 
the ASDAS-CRP, the ASDAS-CRP will be re-derived and this will subsequently be used to 
derive the appropriate disease activity category. 
8.1.3 
Bath Ankylosing Spondylitis Functional Index 
The BASFI contains 10 questions. The first 8 questions evaluate activities related to functional 
anatomical limitations due to the course of this inflammatory disease. The final 2 questions 
evaluate the subjects’ ability to cope with everyday life. An NRS ranging from 0 to 10 is used to 
answer the questions on the test. 
The arithmetic mean of the 10 scales gives the BASFI score, which is a value between 0 and 10.  
In case of missing answers to 1 or 2 of the single items within the BASFI questionnaire, the 
BASFI score will be calculated by imputing missing items with the mean of the completed items. 
Then, the BASFI score will be calculated as described above. If more than 2 of the items are 
missing, the BASFI score will be left missing. 
8.1.4 
Bath Ankylosing Spondylitis Disease Activity Index 
The BASDAI is the most commonly used instrument to measure the disease activity of AS. The 
BASDAI is a validated self-reported instrument which consists of 6 NRSs, each with 10 units to 
measure the severity of the 5 major symptoms: fatigue, spinal pain, peripheral joint pain and 
swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. To 
give each symptom equal weighting, the average of the 2 scores relating to morning stiffness is 
taken. The resulting 0 to 50 sum score is divided by 5 to give a final BASDAI score between 0 
and 10, with lower scores indicating lower disease activity. 
The BASDAI is calculated as follows: 
𝐵𝐴𝑆𝐷𝐴𝐼= (Q1 + Q2 + Q3 + Q4 + (Q5 + Q6
2
))
5
 
(12) 
where Q1 – Q6 are the six questions from the BASDAI questionnaire. 
If 1 of the 2 morning stiffness measurements (ie, questions: 
 
 
) is missing, the other one will be used for the 
morning stiffness calculation. The same imputation is also applied for the calculation of the 
ASAS inflammation component, which is calculated as the average of the 2 morning stiffness 
measurements. 
If 1 major symptom of the BASDAI is missing, the sum score of the remaining symptoms will be 
divided by the number of symptoms assessed. If more than 1 major symptom is missing, the sum 
score will be set to missing. 
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8.1.5 
Bath Ankylosing Spondylitis Metrology Index 
The BASMI characterizes the spinal mobility of a subject with AS and consists of 5 clinical 
measures to reflect axial status: cervical rotation; tragus-to-wall distance; lateral spinal flexion; 
lumbar flexion (modified Schober); intermalleolar distance. Each of the 5 movements is scored 
according the linear BASMI definition (van der Heijde et al, 2008) (Table 8-1). The mean of the 
5 scores provides the BASMI score. The BASMI score ranges from 0 to 10. The higher the 
BASMI score, the more severe the subject’s limitation of movement due to their AS. 
Table 8-1: 
BASMI linear definition 
Clinical Movement (Unit) 
S=0 If: 
S Between 0 and 10: 
S=10 If: 
Lateral spinal flexiona  (cm) 
A≥21.1 
S = (21.1cm – A) / 2.1cm 
A≤0.1 
Tragus-to-wall distancea (cm) A≤8 
S = (A – 8cm) / 3cm 
A≥38 
Lumbar flexiona (modified 
Schober) (cm) 
A≥7.4 
S = (7.4cm – A) / 0.7cm 
A≤0.4 
Intermalleolar distance (cm) 
A≥124.5 
S = (124.5cm – A) / 10cm 
A≤24.5 
Cervical rotation anglea (°) 
A≥89.3 
S = (89.3° – A) / 8.5° 
A≤4.3 
S=BASMI Score; A=assessment. 
a For cervical rotation and lateral spinal flexion, the mean of the left and right measurements will be calculated, if 
both are available. Otherwise, the available measurement will be used. If multiple attempted measurements are 
obtained, calculate the mean of the attempts. The mean of the attempts should be calculated after averaging the left 
and right measurements, where applicable. 
For all clinical measures, values outside the ranges presented in Table 8-2 (Maksymowych, 
2006) will be regarded as invalid and set to missing in the calculation of the component scores. 
For clinical movement parameters with repeated attempts at the same visit (ie, lateral spinal 
flexion, tragus-to-wall distance, cervical rotation and lumbar flexion), if only 1 attempt is 
considered valid per the ranges below, then this attempt will be used to calculate the BASMI 
score. If both attempts are considered invalid, the specific movement clinical movement 
parameter will be regarded as missing. 
Table 8-2: 
BASMI linear definition permitted ranges 
Clinical Movement 
Range 
Lateral spinal flexion (mean right/left) 
0.75 to 25.00cm 
Tragus-to-wall distance (mean right/left) 
9.00 to 37.50cm 
Lumbar flexion (modified Schober) 
0.00 to 9.00cm 
Intermalleolar distance 
13.00 to 160.00cm 
Cervical rotation (mean right/left) 
0.00 to 94.00 ° 
For calculation of the overall BASMI score the following imputation rules will be applied: 
• If 1 or 2 clinical measures for the BASMI are missing at one visit, the missing measure will 
be imputed by carrying the last observation forward, and the BASMI will be calculated 
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accordingly. This will include using AS0008 values as the last observation if applicable. In 
this case missing values will be carried forward from the relevant AS0008 visit until the next 
valid, non-missing value is present. 
• If more than 2 clinical measures are missing, the BASMI score will be regarded as missing. 
• Missing AS0008 Baseline values will not be imputed. 
The following sequential steps will be followed when calculating the BASMI score: 
• Individual assessment values (A) that are considered invalid (Table 8-2) will be discarded (ie, 
set to missing). 
• The mean of the (valid) left and right assessment (A) values will be calculated per subject, 
analysis visit, parameter, and attempt (for those parameters where more than 1 attempt has 
been performed and there is more than 1 valid value available). 
• The mean of the assessment (A) values will be calculated across attempts per subject, 
analysis visit and parameter (only for visits having more than 1 attempt with a valid value). 
• The BASMI component score (S) will be calculated from the averaged assessment (A) values 
per subject, analysis visit and parameter. 
• Values obtained at the ET visit and values obtained at unscheduled visits will be re-mapped 
as described in Section 3.5. Re-mapping will be performed on a per-parameter basis prior to 
the calculation of the BASMI score (this method is adopted in the event that not all 
parameters are assessed at each visit). 
• If 1 or 2 BASMI component scores (S) are missing for a given subject and analysis visit, the 
most recent non-missing value will be carried forward and used at the current analysis visit. 
• The final BASMI score will be calculated for a given subject and analysis visit if 1 value is 
available for each component score (including values that have been carried forward); in this 
case the BASMI score is the mean of the 5 component scores (S). If 1 value is not available 
for each component score the BASMI score will be set to missing for that subject and 
analysis visit. 
8.1.6 
Maastricht Ankylosing Spondylitis Enthesitis Index 
The MASES Index comprises 13 items (bilateral costochondral 1, costochondral 7, anterior 
superior iliac spine, posterior iliac spine, iliac crest and proximal insertion of the achilles tendon 
sites, and the fifth lumbar vertebral body spinous process) (Heuft-Dorenbosch et al, 2003) each 
scored as 0 = yes or 1 = no and then summed for a possible score of 0 to 13, with higher scores 
indicating worse enthesitis.  
If 7 or more items are available, MASES will be imputed by dividing the sum score with the 
number of assessments and multiplying the result with 13. If less than 7 items are available, 
MASES will be treated as missing. 
Presence of enthesitis at Baseline should be defined as a Baseline MASES score >0. 
Summaries of MASES will be restricted to subjects with a MASES >0 at AS0008 Baseline. 
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8.1.7 
Patient’s Global Assessment of Disease Activity 
Subjects will complete the PGADA using a NRS. The range covers 0 (not active) to 10 (very 
active). 
8.1.8 
Total and Nocturnal Spinal Pain 
The pain experienced by AS subjects is measured by 2 separate questions: 1) total pain in the 
spine due to AS (i.e. “How much pain of your spine due to spondylitis do you have?”); and 2) 
pain in the spine at night due to AS (i.e. “How much pain of your spine due to spondylitis do you 
have at night?”) (Sieper et al, 2009; van der Heijde et al, 2005; Committee for Proprietary 
Medicinal Product/EWP/556/95, 2002). 
The arithmetic mean of both questions describes the TNSP. If the response to one question is 
missing the TNSP will be taken as the response to the non-missing question. If both responses 
are missing, the TNSP will be regarded as missing. 
8.1.9 
Short Form – 36 Items Health Survey 
The SF-36 (Version 2, standard recall) is a 36-item generic health-related quality of life 
(HRQoL) instrument that uses a recall period of 4 weeks. Items are grouped into 8 health 
domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 
items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role 
Emotional (3 items), Mental Health (5 items). The concepts represented by these scales 
contribute to physical, mental, and social aspects of HRQoL One additional item (Question 2) 
asks respondents about perceived stability or change in health (Health Transition) over the past 
year. The classification of the questionnaire items to the health scales is shown in Section 12.2. 
In addition to the domain scores, the Physical Component Score (PCS) and Mental Component 
Score (MCS) are calculated from the 8 domains (excluding the Health Transition item). 
Component scores appreciate the impact of each domain on physical and mental health status. 
The 2 SF-36 component summaries (PCS and MCS) and the 8 domain scores are standardized 
with a mean of 50 and a SD of 10 in the general US population. An individual respondent’s score 
that falls outside the T-score range of 45 to 55 should be considered outside the average range 
for the general US population. When considering group-level data, a score below 47 should be 
considered indicative of impaired functioning within that health domain or dimension. Similar to 
individual respondent data, group mean scores 47 or greater should be considered average or 
above average as compared to the general US population. Higher scores indicate a better health 
status. 
For the calculation of the SF-36 domain scores and the component summaries PCS and MCS, the 
scoring software Quality Metric’s PRO CoRE will be used). The software uses updated 2009 US 
population norms and applies a Full Missing Score Estimation method as follows:  
• A health domain score (except the Physical Functioning domain) will be estimated provided 
that at least 1 non-missing response is available within that domain. 
• For the Physical Functioning domain item response theory will be used to develop a model 
for estimates of the missing score. 
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• Regression methods are then applied to estimate the PCS and the MCS on the basis of the 
scores for each domain. 
8.1.10 
Ankylosing Spondylitis Quality of Life 
The ASQoL consists of 18 items, each with a score of 0 = no or 1 = yes, so that the sum score 
ranges from 0 to 18, with higher scores indicating worse quality of life.  
If 3 or fewer items are missing, the missing responses will be imputed with the mean of the 
available responses from that visit to calculate a total score. If more than 3 items are missing, the 
total score will be left missing. 
Note that in the raw data the results are coded as 1 = yes and 2 = no; these will be re-coded as 
above prior to calculation of the ASQoL score. 
8.1.11 
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 chronic plaque psoriasis (Langley et al, 2010; 
Dauden et al, 2009). The HADS consists of 14 items, each scored from 0 to 3. 
HADS-A will be calculated as the sum of the scores for items 1, 3, 5, 7, 9, 11, 13, and HADS-D 
will be calculated as the sum of the scores for items 2, 4, 6, 8, 10, 12, 14. Each score ranges from 
0 to 21 with higher scores indicating a worse state. A score below 8 is considered normal and a 
score of 15 and above is considered severe (Snaith and Zigmond, 1994). If any of the 7 items 
required to calculate the HADS-A or HADS-D are missing then the HADS-A or HADS-D will 
be treated as missing. 
A flag to identify “normal” depression and anxiety status at each visit (defined as having 
HADS-D and HADS-A <8 at the same visit) will be derived. 
8.1.12 
High-sensitivity C-reactive protein levels 
Note that high sensitivity C-reactive protein will be referred to as CRP throughout this SAP. 
CRP levels will be analyzed by the central laboratory. Any CRP assessments performed at local 
laboratories will not be considered for efficacy analyses (including ASDAS-CRP). 
Due to a change in laboratory vendor between AS0008 and AS0009, CRP values from the 
AS0009 laboratory have been calibrated to match those from the AS0008 laboratory, and these 
values will be used for all CRP summaries and listings.  
In AS0008 the LLOQ was 0.16mg/L, however in AS0009 it was possible to measure 
concentrations below this value and report these as a numeric result. The LLOQ in AS0008 will 
therefore be applied to the AS0009 data in order to retain consistency in reporting across the 
studies. Thus, numeric values of less than 0.16mg/L (<0.16mg/L) in AS0009 will be imputed 
with half the LLOQ from AS0008 (ie, 0.08mg/L) prior to summary reporting or any derivation 
of composite parameters (NB different criteria apply for the derivation of ASDAS-CRP as 
described in Section 8.1.2). The original values will be included in the listing.  
CRP values at AS0008 Baseline and AS0009 EV will be taken from the AS0008 database 
(Baseline and Week 48 records respectively). 
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Any CRP values >=500mg/L will be set to missing prior to performing the MI procedure 
(Table 4‒1) as these are considered to be extreme outliers. 
8.2 
Statistical analyses of secondary efficacy variables 
The following secondary efficacy variables will be summarized for the FAS by treatment group 
at the completion of AS0008 and overall: 
• ASAS40 response relative to AS0008 Baseline at AS0009 Week 48  
• ASAS20 response relative to AS0008 Baseline at AS0009 Week 48  
• Change from AS0008 Baseline in BASDAI at AS0009 Week 48  
One set of summaries will be produced using data following NRI (ASAS responses) or MI 
(BASDAI) and another set using OC data. For ASAS responses, a further set of tables will be 
produced after the response variables have been derived following MI of the individual 
components. Summaries will not be presented for individual components of the ASAS (with the 
exception of PGADA which is a standalone endpoint). 
8.3 
Statistical analyses of other efficacy variables 
The following other efficacy variables will be summarized for the FAS at scheduled visits in 
accordance with the schedule of study assessments in Table 2‒1, by treatment group at 
completion of AS0008 and overall: 
• ASAS40, ASAS20 and ASAS5/6 response at each visit in AS0009, relative to AS0008 
Baseline. 
− Summaries will not be presented for individual components of the ASAS with the 
exception of PGADA which is a standalone endpoint. 
• ASAS-PR response at each visit in AS0009, relative to AS0008 Baseline. 
• Change from AS0008 Baseline in ASDAS-CRP at each visit in AS0009. 
− Summaries will not be presented for the individual components of the ASDAS-CRP with 
the exception of PGADA which is a standalone endpoint. 
• ASDAS-ID at each visit in AS0009 (including Low Disease Activity, High Disease Activity 
and Very High Disease Activity categories). 
• Change from AS0008 Baseline in BASDAI at each visit in AS0009. 
• Change from AS0008 Baseline in BASFI at each visit in AS0009. 
• Change from AS0008 Baseline in BASMI at each visit in AS0009. 
• Change from AS0008 Baseline in MASES at each visit in AS0009. 
− Only subjects with MASES >0 at AS0008 Baseline will be included. 
• Change from AS0008 Baseline in PGADA at each visit in AS0009. 
• Change from AS0008 Baseline in TNSP at each visit in AS0009. 
• Change from AS0008 Baseline in SF-36 PCS and MCS at each visit in AS0009. 
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• Change from AS0008 Baseline in SF-36 domain scores (Physical Functioning, Role 
Physical, General Health, Bodily Pain, Vitality, Social Functioning, Role Emotional and 
Mental Health) at each visit in AS0009. 
• Change from AS0008 Baseline in ASQoL at each visit in AS0009. 
• Change from AS0008 Baseline in HADS-A and HADS-D scores at each visit in AS0009. 
• Incidence of depression and anxiety status “normal” as defined by HADS-A and HADS-D 
scores below 8 at each visit in AS0009 
• Change from AS0008 Baseline (expressed as ratio to Baseline) in CRP at each visit in 
AS0009 
− For CRP the rules for handling values that are lower than the LLOQ identified in AS0008 
will be followed as per Section 8.1.12.  
One set of summaries will be produced for all the above parameters using data following NRI or 
MI as appropriate, as described in Section 4.2.1.  
For ASAS40, ASAS20, ASAS5/6 and BASDAI, an additional set of summaries will be produced 
using OC data.  
Finally, for ASAS40 and ASAS20 responses only, a further set of tables will be produced after 
the response variables have been derived following MI of components. 
The summary tables for CRP will display the absolute value and ratio to AS0008 Baseline and 
will contain n, geometric mean (and 95% CI), median, first and third quartile (Q1 and Q3), 
minimum. Any values for the ratio to AS0008 Baseline below 0.01 will be presented as <0.01 in 
the listing and summary table. 
8.3.1 
Maintenance of response 
ASAS20, ASAS40 and ASAS5/6 response relative to AS0008 Baseline will, in addition, be 
summarized at each post-Baseline visit in AS0008 through to AS0009 Week 208 (or to AS0009 
Week 204 for ASAS5/6 response), by treatment sequence as defined in Section 3.7. These 
summaries will be restricted to subjects with a response at AS0008 Week 12, and data will be 
reported following NRI. Summaries will be based on the FAS for AS0009. 
8.4 
Subgroup analysis 
Subgroup summaries will be performed on the following efficacy variables for the FAS: 
• ASAS20 response at AS0009 Week 48, relative to AS0008 Baseline. 
• ASAS40 response at AS0009 Week 48, relative to AS0008 Baseline.  
• ASAS5/6 response at AS0009 Week 48, relative to AS0008 Baseline.  
• BASDAI change from AS0008 Baseline at AS0009 Week 48.  
Subgroups are defined in Section 4.8. 
All subgroup analyses are based on imputed data using either NRI (ASAS endpoints) or MI 
(BASDAI). 
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8.5 
Impact of COVID-19 
Additional sensitivity analyses as a result of the global COVID-19 pandemic are not anticipated 
as the onset of the pandemic was subsequent to all subjects completing Week 48 and therefore 
there is no impact on the analysis of the secondary efficacy endpoint. 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
Bimekizumab plasma concentrations will be summarized at each scheduled visit in AS0009 by 
treatment at completion of AS0008 and overall, using the SS. 
If bimekizumab plasma concentration measurements are deemed to be BLQ, then for calculation 
of the derived statistics this sample result will be set to half the LLOQ. Descriptive statistics will 
be calculated only if at least 2/3 of the values are above the LLOQ at a given visit and n≥3. If 
this is not the case, only median, minimum, and maximum will be presented. 
In addition, geometric mean bimekizumab plasma concentration (with 95% CI) time curves will 
be plotted versus time on linear and semi-logarithmic scales by treatment group at completion of 
AS0008.  
The summary table for bimekizumab plasma concentrations will display n, geometric mean (and 
95% CI), geometric CV%, arithmetic mean, SD, median, minimum, and maximum, where the 
geometric CV% is calculated using the following formula: 
𝐶𝑉% = √𝑒𝑆𝐷𝑙𝑛
2 −1 × 100 
(13) 
here SDln represents the standard deviation of the ln-transformed plasma concentration values.  
Geometric mean plots will be repeated by cumulative ADAb positivity and treatment: 
• The ADAb positive status will be considered in a cumulative manner at each time point: 
− A subject will be counted positive from the first time point at which the subject had a 
positive ADAb sample resultregardless of any subsequent missing or negative ADAb 
sample results.  
− If a subject has only negative ADAb samples or only one missing sample with all 
negative ADAb samples up to a specific time point, the subject will be classified as 
negative at that time point. If the AS0008 Baseline sample is missing, then the sample 
will be classified as being negative for the cumulative ADAb status. 
− Thus, the number of subjects included in the geometric mean for positive and negative 
categories will vary by time point for each treatment. 
• Two plots will be presented each displaying bimekizumab plasma concentration data in 
AS0009 only: 
− Considering cumulative ADAb in status in AS0009 only at each time point in AS0009 
− Considering cumulative ADAb status in AS0008 and AS0009 at each time point in 
AS0009 
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• Each plot (linear and semi-logarithmic) will be presented by treatment group at completion 
of AS0008 and ADAb positive status (4 lines per plot) 
The following rules will be implemented for PK concentration summaries and corresponding 
figures: 
• If the dosing for a visit is performed more than 14 days prior to, or more than 14 days after 
the scheduled dosing interval (28 days), then the plasma concentration obtained at that dosing 
visit will be excluded from the PK summaries and figures. Thus, if the dosing interval is less 
than 14 days or greater than 42 days, this rule will apply. This will also apply to doses 
administered at an unscheduled visit. 
• If a PK sample is collected >14 days after the preceding dose and up to 1 hour after the dose 
at the current visit, the PK concentration for that sample will be associated with the 
scheduled visit and summarized accordingly. This will include unscheduled assessments as 
described in Section 3.5 (if a dose was administered at an unscheduled visit). Samples 
collected outside this window will be excluded from the PK summaries and figures and will 
be listed only.  
• Individual samples collected at a scheduled visit at which dosing was not performed (eg, due 
to AE) will be retained in the PK summaries and figures for the specific visit if these are 
collected >14 days and <42 days after the preceding dose, as these reflect the trough 
concentration from the preceding dose. The sample obtained at the subsequent scheduled 
visit will be excluded from the summaries (regardless of dosing) as this will not reflect a 
steady-state trough concentration (as the previous dose was not administered). Thereafter PK 
samples will be included in the summaries assuming dosing has resumed and the sample was 
obtained within the required window of >14 days after the preceding dose and up to 1 hour 
after the dose at the current visit. 
− Note samples collected at Week 208 or at the ET visit will be retained in the PK 
summaries and figures if they are collected >14 days and <42 days after the last dose 
received 
These rules will not apply for the SFU visit as no dosing is planned at this visit. All 
concentrations obtained at the SFU visit will be included in the summary tables (but will not be 
included in the figures). 
Bimekizumab plasma concentrations will be listed for the SS, separately for AS0009 and for data 
from AS0008 and AS0009 combined. All concentrations will be listed as received, prior to 
substitution of any BLQ values. The listing of the AS0009 data will include flags for 
concentrations that were excluded from the summary statistics where the reason for exclusion 
will be one of the following: 
• Dosing performed out of window 
• Sample collected out of window relative to current dose 
• Sample collected out of window relative to previous dose 
• Missed dose at preceding visit 
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• More than one sample obtained at the same visit 
All plasma concentration data will be reported in ug/mL in the tables, figures and listings. 
9.2 
Pharmacodynamics and immunogenicity 
The immunological variable is the ADAb evaluated at scheduled visits up to 208 weeks in 
accordance with the schedule of assessments in Table 2‒1 and Table 2‒2. 
ADAb will be assessed using a tiered approach: screening, confirmatory, and titer assays will be 
used.  
Samples will first be evaluated in the screening assay using a false positivity rate of 5% (reported 
as ‘above the cut-point’ [ACP] or ‘below the cut-point’ [BCP]), followed by analysis of screened 
positive samples (reported as ACP) in the confirmatory assay (which is a drug depletion assay) 
to confirm the true positivity of the samples (reported as either ‘confirmed positive’ [CP] or ‘not 
confirmed positive’ [(NCP]). Samples that are CP will be evaluated in a titration assay to 
quantify the ADA level and will be reported as titer (reciprocal dilution factor including 
minimum required dilution [MRD]). Screening, confirmatory and titer cut points of the 
respective assays will be determined by the bioanalytical laboratory which will report the 
bioanalytical result from the respective assays. 
The following rule will be implemented for by-visit ADAb summaries where applicable: 
• If the ADAb sample is collected within ±21 days relative to the visit date at which the drug 
was administered (or ±21 days from a scheduled visit at which dosing was not performed), 
the ADAb result for that sample will be associated with the scheduled visit and summarized 
accordingly. This will include unscheduled assessments as described in Section 3.5 (if a dose 
was administered at an unscheduled visit). Samples collected outside this window will be 
excluded from the ADAb summaries and will be listed only.  
The rule above will apply to by-visit summaries only; summaries of cumulative ADAb status and 
time to treatment-emergent positivity will use all available data. This rule will not apply for 
Visit 21 (Week 208), ET visit or the SFU visit as no dosing is planned at these time points. Thus, 
all ADAb data obtained at these visits will be included in the by-visit summaries. 
ADAb status will be derived as follows:  
• Sample that are either BCP or ACP and NCP will be defined as ADAb negative 
• Sample values that are ACP and CP will be defined as ADAb positive (regardless of whether 
or not a titer is available) 
In addition the ADAb status will be further classified on a subject level as outlined below: 
• Pre ADAb negative – treatment emergent ADAb negative (Category 1):  
− Considering AS0009 data only (Category 1a): includes subjects who are negative at 
AS0008 Baseline and ADAb negative at all sampling points in AS0009 (including SFU). 
− Considering AS0008 and AS0009 data (Category 1b): includes subjects who are negative 
at AS0008 Baseline and ADAb negative at all sampling points in AS0008 and AS0009 
(including AS0009 SFU). 
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• Pre ADAb negative – treatment emergent ADAb positive (Category 2):  
− Considering AS0009 data only (Category 2a): Includes subjects who are negative at 
AS0008 Baseline and ADAb positive at any sampling point in AS0009 (up to and 
including SFU and including the AS0009 EV). This group also includes subjects who 
have a missing pre-treatment sample (either missing or insufficient volume) at AS0008 
Baseline with one or more ADAb positive samples in AS0009. 
− Considering AS0008 and AS0009 data (Category 2b):  Includes subjects who are 
negative at AS0008 Baseline and ADAb positive at any sampling point post treatment in 
AS0008 and/or AS0009 (up to and including AS0009 SFU). This group also includes 
subjects who have a missing pre-treatment sample (either missing or insufficient volume) 
at AS0008 Baseline with one or more ADAb positive samples in AS0008 or AS0009. 
• Pre ADAb positive – treatment emergent reduced ADAb (Category 3):  
− Considering AS0009 data only (Category 3a): Includes subjects who are positive at 
AS0008 Baseline, and ADAb negative at all sampling points in AS0009 (including 
SFU).  
− Considering AS0008 and AS0009 data (Category 3b): Includes subjects who are positive 
at AS0008 Baseline, and ADAb negative at all sampling points in AS0008 and AS0009 
(including SFU).  
• Pre ADAb positive – treatment emergent unaffected ADAb positive (Category 4):  
− Considering AS0009 data only (Category 4a): Includes subjects who are positive at 
AS0008 Baseline and are positive at any sampling point in AS0009 (including SFU) with 
titer values of the same magnitude as AS0008 Baseline (i.e. less than a predefined fold 
increase from the AS0008 Baseline value defined within the validation of the assay). 
− Considering AS0008 and AS0009 data (Category 4b): Includes subjects who are positive 
at AS0008 Baseline and are positive at any sampling point in AS0008 or AS0009 
(including SFU) with titer values of the same magnitude as AS0008 Baseline (i.e. less 
than a predefined fold increase from the AS0008 Baseline value defined within the 
validation of the assay). 
For the purposes of this study, this is set at an increase of less than or equal to a 3-fold 
difference from AS0008 Baseline.  
• Pre ADAb positive – treatment emergent ADAb boosted positive (Category 5):  
− Considering AS0009 data only (Category 5a): Includes subjects who are positive at 
AS0008 Baseline and are positive at any sampling point in AS0009 (including AS0009 
EV and SFU) with increased titer values compared to AS0008 Baseline.  
− Considering AS0008 and AS0009 data (Category 5b): Includes subjects who are positive 
at AS0008 Baseline and are positive at any sampling point post treatment in AS0008 
and/or AS0009 (including SFU) with increased titer values compared to AS0008 
Baseline.  
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The increase in titer values is defined as an increase greater than a predefined fold increase 
from AS0008 Baseline value which is defined within the validation of the assay. For the 
purposes of this study, this is set at an increase greater than a 3-fold difference (ie, a 
minimum of a 4-fold increase). 
The fold increase in ADAb is calculated as follows: 
𝐹𝑜𝑙𝑑 𝑖𝑛𝑐𝑟𝑒𝑎𝑠𝑒= [𝐴𝐷𝐴𝑏 𝑡𝑖𝑡𝑒𝑟 𝑎𝑡 𝑡𝑖𝑚𝑒 𝑝𝑜𝑖𝑛𝑡−𝐴𝐷𝐴𝑏 𝑡𝑖𝑡𝑒𝑟 𝑎𝑡 𝐴𝑆0008 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒
𝐴𝐷𝐴𝑏 𝑡𝑖𝑡𝑒𝑟 𝑎𝑡 𝐴𝑆0008 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒
] 
(14) 
Note: For any subject who is positive at AS0008 Baseline and positive at a post-Baseline 
time point, but for whom titers are not available to determine treatment unaffected or 
treatment boosted status, the subject will be considered as treatment boosted (i.e., 
Category 5), assuming no other samples are available. 
• Inconclusive (Category 6):  
− Considering AS0009 data only (Category 6a): Includes subjects who have a positive pre-
treatment sample at AS0008 Baseline and some AS0009 samples are missing, while other 
AS0009 samples are ADAb negative. 
− Considering AS0008 and AS0009 data (Category 6b): Includes subjects who have a 
positive pre-treatment sample at AS0008 Baseline and some AS0008 or AS0009 samples 
are missing, while other AS0008 and AS0009 samples are all ADAb negative. 
• Total treatment-emergent (Category 7 [Categories 2 and 5 combined]):  
− Considering AS0009 data only (Category 8a): Includes subjects who are pre ADAb 
negative – treatment emergent ADAb positive (Category 2a) and pre ADAb positive – 
treatment boosted ADAb positive (Category 5a).  
− Considering AS0008 and AS0009 data (Category 8b): Includes subjects who are pre 
ADAb negative – treatment emergent ADAb positive (Category 2b) and pre ADAb 
positive – treatment boosted ADAb positive (Category 5b).  
• Total pre ADAb positive (Category 8 [Categories 3, 4, 5 and 6 combined]): Subjects that 
are tested ADAb positive at AS0008 Baseline. 
• Missing (Category 9):  
− Considering AS0009 data only (Category 9a): Includes subjects who have a missing or 
negative pre-treatment sample at AS0008 Baseline and all AS0009 samples are either 
missing or ADAb negative. 
− Considering AS0008 and AS0009 data (Category 9b): Includes subjects who have a 
missing or negative pre-treatment sample at AS0008 Baseline and all AS0008 or AS0009 
samples are either missing or ADAb negative. 
The following summaries, figures and listings will be produced: 
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• Summary tables displaying the number and percentage of subjects with a positive ADAb 
status at each AS0009 visit and at any visit by treatment group at completion of AS0008 and 
overall. Two tables will be presented: 
− Considering ADAb status in AS0009 only  
− Considering ADAb status in AS0008 and AS0009 (this table will include only the overall 
summary visits as detailed below). 
For the overall summary at any visit two summaries will be presented as follows (all 
summaries exclude data obtained at AS0008 Baseline): 
− AS0009 data only: Including any visit during the AS0009 treatment period (as defined in 
Section 3.2.2). Thus, this summary will exclude data obtained at the SFU visit and will 
include data obtained at the AS0009 EV. 
− AS0009 data only: Including any visit during AS0009. Thus, this summary will include 
both data obtained at the SFU visit and at the AS0009 EV. 
− AS0008 and AS0009 data: Including any visit during the AS0008 and AS0009 treatment 
period. Thus, this summary will exclude data obtained at the AS0009 SFU visit. 
− AS0008 and AS0009 data: Including any visit during AS0008 and AS0009. Thus, this 
summary will include data obtained at the AS0009 SFU visit. 
• Summary tables (by treatment at completion of AS0008 and overall) of the time point of the 
first occurrence of ADAb treatment-emergent positivity during AS0009, including the 
AS0009 EV and the SFU visit. This summary will include the following categories: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive 
The table will summarize the number and percentage of subjects who are either treatment-
emergent ADAb positive or treatment-boosted ADAb positive for the first time at the 
specified time point in AS0009 and will include the cumulative number and percentage of 
subjects with treatment-emergent ADAb positive results at each time point. 
The table will be repeated considering ADAb status at each visit in both AS0008 and 
AS0009 and will therefore display all visits in both AS0008 and AS0009.  
An additional table will be presented considering ADAb status at each visit in both AS0008 
and AS0009, and will be presented by actual treatment at randomization in AS0008 only. 
• Summary tables displaying the number and percentage of subjects in each of the ADAb 
categories as defined above by treatment at completion of AS0008. Two tables will be 
presented: 
− Considering data from AS0009 only 
− Considering data from AS0008 and AS0009 
• The time to achieving treatment-emergent ADAb positivity, by treatment group at 
completion of AS0008 and overall (3 lines per plot), will be graphically presented. Subjects 
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will be considered to have an event at the time point at which treatment-emergent ADAb 
positivity is first achieved. This plot will display the cumulative percentage of subjects with 
treatment-emergent positivity and will include the following categories: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive 
◦ 
Category 2 and Category 5 subjects will be combined in 1 group (3 lines per plot) if 
the percentage of subjects in each treatment group in Category 5 is <10%. 
The figure will be repeated considering data from both AS0008 and AS0009 and will 
therefore display all visits in both AS0008 and AS0009. 
In the event that >=10% of subjects in either treatment group are classified as Category 5 the 
figure will be repeated by treatment at completion of AS0008 and overall and by ADAb 
status (6 lines per plot). This will be implemented for both plots (considering only AS0009 
and considering data from both AS0008 and AS0009). 
An additional figure will be presented considering data from both AS0008 and AS0009, and 
will be presented by actual treatment at randomization in AS0008 only. This figure will be 
presented as follows: 
− If <10% of subjects in each treatment group (based on treatment at randomization) are 
classified as Category 5, the figure will be presented with 5 lines on 1 plot (1 for each 
treatment) and both categories combined 
− If ≥10% of subjects in any treatment group (based on treatment at randomization) are 
classified as Category 5, the figure will be presented by category and treatment at 
randomization with separate plots (each with 5 lines) for each category 
• A summary of efficacy response (ASAS40 responders [based on NRI]) as a function of 
ADAb titer will be presented graphically. The x-axis will display the ADAb titer at the 
AS0009 Week 48 time point (categorized as negative, Q1, Q2, Q3 and Q4 where the latter 
represents the quartiles for the ADAb titers at Week 48) and the y-axis will display 
percentage of ASAS40 responders at the Week 48 time point within each titer category.  
Subjects with negative ADAb results at the Week 48 time point will be included in the 
‘negative’ category on the x-axis; subjects with missing ADAb data at the Week 48 time 
point will be excluded from the plot. The figure will be based on the FAS. 
• A summary of efficacy response (ASAS40 responders) versus time will be presented 
graphically including the following ADAb groups (3 lines per plot): 
− ADAb positive 
◦ 
Defined as subjects having at least 2 ADAb positive samples during AS0009 
(including AS0009 EV and excluding SFU) regardless of other ADAb negative 
samples and/or missing or inconclusive samples 
− ADAb negative 
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◦ 
Defined as subjects for whom either (1) all samples in AS0009 (including AS0009 
EV and excluding SFU) are ADAb negative and there are no missing or inconclusive 
samples or (2) only 1 sample in AS0009 is ADAb positive and all other samples in 
AS0009 (including AS0009 EV and excluding SFU) are ADAb negative or 
missing/inconclusive or (3) only 1 sample is missing/inconclusive and the remaining 
samples are ADAb negative (excluding SFU). 
− Missing 
◦ 
Defined as subjects who do not fulfil the criteria for one of the 2 groups listed above. 
The figure will be repeated considering ADAb status based on AS0008 and AS0009 
combined, with the following definitions: 
− ADAb positive 
◦ 
Defined as subjects having at least 2 ADAb positive samples during AS0008 and 
AS0009 (excluding AS0008 Baseline and AS0009 SFU and including AS0009 EV) 
regardless of other ADAb negative samples and/or missing or inconclusive samples 
− ADAb negative 
◦ 
Defined as subjects for whom either (1) all samples in AS0008 and AS0009 are 
ADAb negative and there are no missing or inconclusive samples or (2) only 1 
sample in AS0008 or AS0009 is ADAb positive and all other samples in AS0008 and 
AS0009 are ADAb negative or missing/inconclusive or (3) only 1 sample is 
missing/inconclusive and the remaining samples in AS0008 and AS0009 are ADAb 
negative. All 3 definitions exclude AS0008 Baseline and AS0009 SFU and include 
AS0009 EV. 
− Missing 
◦ 
Defined as subjects who do not fulfil the criteria for one of the 2 groups listed above. 
Both figures described above will be based on the FAS and the data for ASAS responders 
will be based on NRI. If the percentage of subjects in the missing category is ≤5%, this 
category will be omitted from the plot. 
• Spaghetti plots of ADAb titer (y-axis) by visit (x-axis), separated by treatment group at 
completion of AS0008 for all ADAb positive subjects. This plot will include the following 
ADAb categories, based on data collected in AS0009: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive 
Separate plots will be presented for each treatment group with both categories on the same 
plot. Plots will be presented using a semi-logarithmic scale for the ADAb titers (ADAb 
negative samples will therefore be excluded from the plot). The x-axis will reflect time from 
the AS0009 EV. 
• Listings of individual subject-level ADAb results will be presented for the following: 
− Including only data from AS0009. 
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− Including data from both AS0008 and AS0009.  
The listing of AS0009 data will also include flags for ADAb measurements that were 
excluded from the by-visit summaries. The reason for exclusion will be one of the following: 
− Dosing performed out of window 
− Sample collected out of window relative to current or previous dose 
− Sample collected out of window relative to previous dose (missed or no dose at current 
visit) 
− More than one sample obtained at the same visit 
− Sample collected out of window relative to current dose or visit date (applicable to ADAb 
data only) 
Any ADAb measurements that were outside the tolerance limit of the assay will also be 
flagged in the listing. 
All outputs described in this section will be presented using the SS, unless otherwise stated. 
10 
SAFETY ANALYSES 
AEs will be coded according to MedDRA. 
AEs will be summarized by treatment group at completion of AS0008 and overall, by primary 
SOC, HLT, and PT in alphabetical order. This summary will include incidence, exposure-
adjusted incidence rates (EAIRs) with associated 95% CIs, and exposure-adjusted event rates 
(EAERs) where the EAIR and EAER are expressed per 100 subject-years of exposure. Subject 
exposure at risk is defined in Section 10.1. 
Change from AS0009 Laboratory Baseline in laboratory variables (except CRP) will be 
summarized descriptively by visit and by treatment group at completion of AS0008 and overall. 
Change from AS0008 Baseline in ECG and vital signs variables will be summarized 
descriptively by visit and by treatment group at completion of AS0008 and overall. 
Safety variables will be reported for the SS. Key safety analyses will be repeated for both SS 
Sub-populations (see Section 3.6.2) and/or will include data from AS0008 for subjects who 
continued in to AS0009, as described below. 
10.1 
Extent of exposure 
Study medication duration will be calculated for each of the following using the imputation rules 
in Section 4.2.4 for partial treatment end dates:  
• Total bimekizumab duration: Between the first dose of bimekizumab in AS0008 and last 
dose of bimekizumab in AS0009. 
• Total duration on bimekizumab 160mg: Between the first and last dose of bimekizumab 
160mg (in AS0008 or AS0009). 
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• Duration on bimekizumab 320mg: Between the first dose of bimekizumab 320mg in AS0008 
and first dose of bimekizumab 160mg in AS0009 (calculated only for subjects who took 
bimekizumab 320mg in AS0008). 
• Duration on bimekizumab 160mg in AS0009: Between the first and last dose of 
bimekizumab 160mg in AS0009. 
The duration of exposure will be calculated as outlined in Table 10‒1.  
Table 10‒1: Study medication duration 
Duration Category 
Start date 
End date 
Study medication duration 
Total BKZ duration 
First dose of BKZ in 
AS0008 
Last dose of BKZ in 
AS0009 
End date – start date + 28a 
Total duration on BKZ 
160mg 
First dose of BKZ 
160mg in AS0008 or 
AS0009 
Last dose of BKZ 
160mg in AS0009 
End date – start date + 28a 
Duration on BKZ 
320mg 
First dose of BKZ 
320mg in AS0008 
First dose of BKZ 
160mg in AS0009  
End date – start date + 1 
Duration on BKZ 
160mg in AS0009 
First dose of BKZ 
160mg in AS0009 
Last dose of BKZ 
160mg in AS0009 
End date – start date + 28a 
Subjects who diedb 
Start date for each 
option as above 
Date of death 
End date – start date + 1 
BKZ=bimekizumab. 
a 28 days refer to one half-life of BKZ. 
b For subjects who died, the date of death will be used to replace the end date in the calculation of study medication 
duration only if the subject died within the dosing interval (i.e., within 28 days following the last dose [not 
applicable for duration on BKZ 320mg]) or if the subject died before dosing in AS0009 (for duration on BKZ 
320mg). If the subject died more than 28 days after the last dose of BKZ in AS0009 the study medication duration 
will be calculated using the dosing interval of 28 days. 
The exposure time at risk will be calculated as outlined in Table 10‒2. 
Table 10‒2: Exposure time at risk 
Exposure Category 
Start date 
End date 
Duration of Exposure 
Total BKZ exposure 
First dose of 
BKZ in AS0008 
Last dose of BKZ in 
AS0009 
Minimum of [(End date – 
start date + 140a) +1] and 
(Date of last clinical 
contactb – start date + 1) 
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Table 10‒2: Exposure time at risk 
Exposure Category 
Start date 
End date 
Duration of Exposure 
Total exposure to 
BKZ 160mg 
First dose of 
BKZ 160mg in 
AS0008 or 
AS0009 
Last dose of BKZ 160mg in 
AS0009 
Minimum of [(End date – 
start date + 140a) +1] and 
(Date of last clinical 
contactb – start date + 1) 
Exposure to BKZ 
320mg 
First dose of 
BKZ 320mg in 
AS0008 
First dose of BKZ 160mg in 
AS0009 for subjects who 
were dosed in AS0009c. 
 
Last dose of BKZ 320mg in 
AS0008 for subjects who 
were not dosed in AS0009 
(End date – start date + 1) 
for subjects who were 
dosed in AS0009.  
 
Minimum of [(End date – 
start date + 140a) +1] and 
(Date of last clinical 
contactb – start date + 1) 
for subjects who were not 
dosed in AS0009 
Exposure to BKZ 
160mg in AS0009 
First dose of 
BKZ 160mg in 
AS0009 
Last dose of BKZ 160mg in 
AS0009 
Minimum of [(End date – 
start date + 140a)+1] and 
(Date of last clinical 
contactb – start date + 1) 
Subjects who diedd 
Start date for 
each option as 
above 
Date of death 
End date – start date + 1 
BKZ=bimekizumab. 
a 140 days refer to 5 half-lives of BKZ. 
b Date of last clinical contact for each subject is defined as the maximum of [last visit date including SFU visit 
(including unscheduled SFU visits), last AE start date (including imputed AE start dates), date of study 
termination or completion, last date of study drug administration following rules for partial treatment end dates as 
per Section 4.2.4]. 
c In the event that the first dose in AS0009 was more than 140 days after the last dose in AS0008, the exposure time 
at risk for 320mg will be calculated using AS0008 end date – AS0008 start date + 140 days. 
d For subjects who died, the date of death will be used to replace the end date in the calculation of exposure time at 
risk only if the subject died within the ‘at risk’ interval (i.e., within 140 days following the last dose [not 
applicable for duration on BKZ 320mg]) or if the subject died before dosing in AS0009 (for time at risk on BKZ 
320mg). If the subject died more than 140 days after the last dose of BKZ in AS0009 the exposure time at risk will 
be calculated using the ‘at risk’ interval of 140 days. Note that date of death should be equivalent to date of last 
clinical contact. 
In the event that a subject received an incorrect (unplanned) treatment sequence the calculations 
for study medication duration and exposure time at risk will be adjusted accordingly following 
the principles outlined above and this will be documented in the relevant dataset specifications. 
Three summaries of exposure will be provided: two for exposure in AS0009 and one for 
exposure in AS0008 and AS0009 combined.  
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• For the AS0009 summary, durations of exposure and times at risk will be summarized by 
treatment group at completion of AS0008 and overall. This summary will be repeated by SS 
Sub-population. 
• For the AS0008 and AS0009 combined table, the duration of exposure and time at risk for 
‘BKZ 160mg’, ‘BKZ 320mg’ and ‘BKZ Total’ will be summarized. Subjects who took 
bimekizumab 320mg during AS0008 will contribute to all three columns. Subjects who did 
not take bimekizumab 320mg in AS0008 will contribute to the ‘BKZ 160mg’ and ‘BKZ 
Total’ columns. 
The total study medication duration and total time at risk will be included in the exposure tables. 
These will be calculated by summing the study medication duration (or time at risk) across all 
subjects (per treatment group) and will be expressed in years and presented to 1 decimal place. 
Start date of study medication in AS0008, start and end dates of study medication in AS0009, the 
durations of exposure and the times at risk will be listed. 
10.2 
Adverse events 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
AEs that occurred during the AS0008 study and are ongoing at the time of enrolment (signed 
informed consent) in AS0009 will be captured in the AS0009 database and followed up until the 
AEs have resolved, have 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, AEs of special interest (AESIs), and AEs 
defined as Safety Topics of Interest; further details regarding follow-up of Potential Drug-
induced Liver Injury (PDILI) events are provided in Section 9.4.1 of the protocol. Information 
on SAEs obtained after clinical database lock will be captured through the Patient Safety 
database without limitation of time. 
If an AE is ongoing at the end of the AS0009 study, 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. 
All AEs occurring during the AS0009 study (i.e. after signature of the informed consent 
document) will be recorded in the eCRF. For each AE the following information will be recorded 
in the eCRF: AE term (verbatim term), date of onset, whether or not the AE was classified as a 
SAE, as an AESI, intensity, relationship to study medication, action taken with study medication, 
other action taken, outcome, date of outcome, and whether the AE led to study drug 
discontinuation or to study discontinuation. 
The following code lists will be used for AE recording: 
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• Pattern of event: intermittent or continuous 
• Intensity of event: mild, moderate or severe 
• Relationship: related or not related 
• Action taken with IMP: dose not changed, dose reduced, dose increased, drug temporarily, 
interrupted, drug permanently withdrawn or not applicable 
• Outcome: resolving, not resolved, resolved, resolved with sequelae, worsened, fatal or 
unknown 
AEs (including SAEs) are characterized as either non-treatment-emergent or treatment emergent 
according to the following criteria: 
• Non-treatment emergent AEs are those with onset date after a 140-day period after the end 
date of study medication. 
− Any AE occurring more than 140 days after the last administration of study medication in 
AS0008 and prior to the first administration of study medication in AS0009 will also be 
considered as non-treatment emergent, and will therefore be excluded from the summary 
tables. Such events will be included in the listings. 
• TEAEs are those with onset date on or after the start date of study medication in AS0009. 
• Events that were ongoing at the end of AS0008 will have their treatment-emergent status 
taken from the AS0008 database. 
For all AEs the following variables will be calculated (see Section 10.2.1): 
• Duration. 
• Time since first bimekizumab dose. 
• Time since last/latest bimekzumab dose. 
AE summaries will, in general, include only events with onset on or after the start date of study 
treatment in AS0009. Certain displays will be repeated including all AEs in AS0008 (with the 
exception of those with onset during placebo treatment) and AS0009 as outlined below. These 
displays will include only subjects from AS0008 who were enrolled in AS0009.  
In general, the attributes of these events (for AEs that started and were resolved in AS0008) will 
be taken from the AS0008 database. However, the identification of Safety Topics of Interest will 
be made across all events in AS0008 and AS0009 using the criteria defined in this SAP.  
For events which were ongoing at the end of AS0008, the following rules will be implemented: 
• Onset date (and derived variables) will be taken from the AS0008 database 
• End date, outcome, actions taken and seriousness will be taken from the AS0009 database. 
• In order to ensure that AEs are not duplicated in the outputs these will be merged across the 
studies by Subject ID, verbatim term (AETERM), dictionary-derived term (AEDECOD), 
start date (AESTDTC), relationship (AEREL) and severity (AESEV) to create one record for 
the specific event. 
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Summaries of AEs in AS0008 and AS0009 will include AEs with onset on the first dose of 
bimekizumab in AS0008 up to 140 days after the last dose of bimekizumab in AS0009. AEs 
which occur on the day of a treatment switch will be considered to have begun on the previous 
treatment, with the exception of the following AEs which will be considered to have begun on 
the new treatment: 
• Events that fulfill the anaphylaxis criteria for acute events (see Section 10.2.3). 
• Events that fulfill the hypersensitivity reaction criteria for (see Section 10.2.3). 
• Events with a HLT of “Administration site reactions NEC”. 
• Events with an HLT of “Injection site reactions”. 
AEs which occur on the first day of bimekizumab treatment in AS0008 following initial 
treatment with placebo will not be included in the summaries, unless they fulfill 1 of the 4 
exception criteria above. AEs which occur after the last dose of bimekizumab in AS0009 and up 
to 140 days after the last dose of bimekizumab in AS0009 will be assigned to bimekizumab 
160mg. 
AEs will be presented as “number of subjects (percentage of subjects) [number of events]”. 
“[number of events]” will include all cases of an AE including repeat occurrences in individual 
subjects, while “number of subjects” will count each subject only once.  
An overview of TEAE (number and percentage of subjects with any TEAE, serious TEAE, 
TEAE leading to study discontinuation, TEAE leading to permanent withdrawal of study 
medication, drug-related TEAE, severe TEAE, fatal AE [see note below], fatal TEAE and TEAE 
with missing seriousness) will be provided by treatment group at completion of AS0008 and 
overall. This summary will be repeated by SS Sub-population. It will also be repeated including 
all TEAEs in AS0008 and AS0009 reported for subjects in the AS0009 SS (with the exception of 
those with onset during placebo treatment) combined. 
The category for fatal AEs will be based on all subjects enrolled in AS0009 in all the above 
summaries. 
The following categories of TEAE will be summarized by MedDRA SOC, HLT and PT, 
including EAIR and EAER (calculated as described in Section 10.2.2), where all summaries refer 
to AEs reported in AS0009 only except where stated: 
• All TEAEs by treatment group at completion of AS0008 and overall.  
• All TEAEs by treatment group at completion of AS0008 and overall, by SS Sub-population. 
• Serious TEAEs by treatment group at completion of AS0008 and overall. 
• Serious TEAEs by treatment group at completion of AS0008 and overall, by SS Sub-
population. 
• All TEAEs in AS0008 and AS0009 by treatment at time of AE onset (BKZ 160mg, BKZ 
320mg and BKZ Total). 
• Serious TEAEs in AS0008 and AS0009 by treatment at time of AE onset (BKZ 160mg, BKZ 
320mg and BKZ Total). 
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• All TEAEs AS0008 and AS0009 by timing of onset relative to ADAb status in AS0008 and 
AS0009. This will include columns for the following: 
− TEAEs starting before the first ADAb positive result in AS0008 and AS0009 (includes 
ADAb Categories 2b only) 
− TEAEs starting on the same date or after the first ADAb positive result in AS0008 and 
AS0009 (includes ADAb Categories 2b, 3b, 4b, 5b and 6b) 
− TEAEs for subjects who are ADAb negative at all time points in AS0008 and AS0009 
(includes ADAb Categories 1b only) 
Note that any TEAEs occurring for a subject who was ADAb positive at AS0008 Baseline 
will therefore all occur after ADAb positivity; such subjects will be excluded from the first 
column in the above table. Subjects in Category 9b (missing) will not be included in the 
table. 
The following categories of TEAE will be summarized by MedDRA SOC, HLT and PT, by 
treatment group at completion of AS0008 and overall: 
• TEAEs leading to study discontinuation and/or permanent withdrawal of study medication. 
• TEAEs leading to permanent withdrawal of study medication. 
• TEAEs with a fatal outcome. 
• All TEAEs by maximum relationship.  
• Serious TEAEs by maximum relationship.  
• TEAEs with a fatal outcome by maximum relationship.  
• All TEAEs by maximum intensity. 
• Non-serious TEAEs reported by more than the reporting threshold of 5% of subjects. The 
cut-off will be applied before rounding on each treatment group and overall. 
A further summary will be presented by treatment group at completion of AS0008 and overall 
displaying the frequency of TEAEs by descending frequency of PT. 
An additional table will be presented by MedDRA SOC, HLT and PT, by treatment at time of 
AE onset (BKZ 160mg, BKZ 320mg and BKZ Total) for all TEAEs in AS0009 and all TEAEs 
that were ongoing from AS0008 at the time of the AS0009 EV. Ongoing TEAEs are defined as 
TEAEs that started prior to the AS0009 EV and continued after the first dose of study medication 
in AS0009. 
Summaries will be based on treatment at onset and include columns for BKZ 160mg, BKZ 
320mg and BKZ Total (where BKZ Total includes all other doses, if applicable, excluding 
placebo). Tables will include only n and %, the denominator (i.e. N) will be as for the current 
tables (total number of subjects receiving at least one dose for each column) 
TEAEs classified as Safety Topics of Interest and associated tables are defined in Section 10.2.3. 
The following AE listings will be provided based on the ES: 
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• Glossary table for all TEAEs (this listing will include all events in AS0008 and AS0009 for 
subjects that were enrolled in AS0009 [with the exception of AEs with onset during placebo 
treatment]). 
• All AEs (this listing will include all events in AS0008 and AS0009 for subjects that were 
enrolled in AS0009 [with the exception of AEs with onset during placebo treatment]). 
• All SAEs (this listing will include all events in AS0008 and AS0009 for subjects that were 
enrolled in AS0009 [with the exception of AEs with onset during placebo treatment]). 
• All AEs leading to study discontinuation.  
• All deaths. 
The following listings will be provided based on the SS: 
• Serious Infections TEAEs. 
• Fungal infectious disorder TEAEs. 
• Opportunistic infection (including tuberculosis [TB]) TEAEs. 
• Malignant or unspecified tumor TEAEs. 
• Malignant tumor TEAEs. 
• Adjudicated cardiovascular TEAEs by event type. 
• Adjudicated cardiovascular TEAEs by event type for major adverse cardiac events (MACE)  
• Adjudicated cardiovascular TEAEs by event type for extended MACE 
• TEAEs identified for potential review by the Cardiovascular Event Adjudication Committee. 
• Neutropenia TEAEs. 
• Suicidal ideation and behavior TEAEs 
• TEAEs identified for potential review by the Neuropsychiatric Adjudication Committee. 
• TEAEs adjudicated by the Neuropsychiatric Adjudication Committee. 
• Inflammatory bowel disease TEAEs. 
• Hypersensitivity reaction TEAEs. 
• Anaphylactic reaction TEAEs 
• Hepatic events TEAEs.  
• Hospitalization/Emergency Room Visits. 
10.2.1 
Adverse event duration and time since first/last dose 
Missing start or end dates will be imputed as described in Section 4.2.2 prior to any calculation 
described in this section. 
The duration of each AE will be calculated as follows: 
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𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 (𝑑𝑎𝑦𝑠) = 𝑑𝑎𝑡𝑒 𝑜𝑓 𝑜𝑢𝑡𝑐𝑜𝑚𝑒−𝑑𝑎𝑡𝑒 𝑜𝑓 𝑜𝑛𝑠𝑒𝑡+ 1 
(15) 
The time since first bimekizumab dose for each TEAE will be calculated three times for each of 
the reference dates below:  
• Relative to the date of first administration of bimekizumab in AS0008. 
• Relative to the date of the first dose of bimekizumab 160mg, only for AEs with onset during 
treatment with bimekizumab 160mg OR  
• Relative to the date of the first dose of bimekizumab 320mg, only for AEs with onset during 
treatment with bimekizumab 320mg.  
− For these criteria during treatment refers to TEAEs with onset up to 140 days after the 
last dose on that treatment. 
• Relative to the start date of study medication in AS0009.  
Time since first dose will be calculated as follows for AEs occurring on or after the reference 
date (as defined above): 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑓𝑖𝑟𝑠𝑡 𝐵𝐾𝑍 𝑑𝑜𝑠𝑒 (𝑑𝑎𝑦𝑠)
= 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸 𝑜𝑛𝑠𝑒𝑡−𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒+ 1 
(16) 
The time since most recent bimekizumab dose for each TEAE will be calculated as follows for 
AEs occurring on or after the reference date (as defined above): 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑚𝑜𝑠𝑡 𝑟𝑒𝑐𝑒𝑛𝑡 𝐵𝐾𝑍 𝑑𝑜𝑠𝑒 (𝑑𝑎𝑦𝑠)
= 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸 𝑜𝑛𝑠𝑒𝑡 
−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑚𝑜𝑠𝑡 𝑟𝑒𝑐𝑒𝑛𝑡 𝑑𝑜𝑠𝑒 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝐴𝐸+ 1  
(17) 
For any AE occurring on the same day as a given dosing occasion the most recent dose will be 
considered to be the dose given on the same day i.e., time since most recent dose would be equal 
to 1 for all such AEs. 
For AEs occurring prior to the reference date (as defined above) the time since dosing will be 
calculated as follows for first/most recent BKZ dose: 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝐵𝐾𝑍 𝑑𝑜𝑠𝑒 (𝑑𝑎𝑦𝑠) = 𝐷𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸 𝑜𝑛𝑠𝑒𝑡−𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒 
(18) 
Days on treatment at AE onset will be calculated three times using the same three reference dates 
as for time since first dose. Days on treatment at AE onset will be calculated as: 
𝐷𝑎𝑦𝑠 𝑜𝑛 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡 𝑎𝑡 𝐴𝐸 𝑜𝑛𝑠𝑒𝑡
= 𝐷𝑎𝑡𝑒 𝑜𝑓𝑙𝑎𝑠𝑡 𝑜𝑟 𝑙𝑎𝑡𝑒𝑠𝑡 𝑑𝑜𝑠𝑒 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝐴𝐸 𝑜𝑛𝑠𝑒𝑡
−𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑑𝑎𝑡𝑒+ 1 
(19) 
As above, for any AE occurring on the same day as a given dosing occasion the last or latest 
dose prior to AE onset will be considered to be the dose given on the same day as the event. 
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For AEs occurring prior to the reference date, the days on treatment will be 0. 
10.2.2 
Exposure-adjusted incidence rate and exposure-adjusted event rate 
The time at risk (in days) at AE onset is the same as the time since first bimekizumab dose as 
described in Section 10.2.1.  
Total time at risk (as defined in Section 10.1) and time at risk at AE onset will be divided by 
365.25 to give years at risk. 
EAIR and EAER will be calculated separately for tables including all events in AS0008 and 
AS0009 combined, and for tables including events with onset in AS0009 only. The former tables 
will use time at risk relative to the start date of bimekizumab 160mg or 320mg (for the ‘BKZ 
160mg’ and ‘BKZ 320mg’ columns) and time at risk relative to the date of the first dose of 
bimekizumab (for the ‘BKZ Total’ column). The latter table will use time at risk relative to the 
start date of study medication in AS0009. 
The EAIR is defined as the number of subjects with a specific AE adjusted for the exposure and 
will be scaled to 100 patient-years: 
𝐸𝐴𝐼𝑅= 100 ∗𝑛𝐴𝐸
∑
𝑇𝐸𝑥𝑝,𝑖
𝑛𝐴𝐸
𝑖=1
+ ∑
𝑇𝑅𝑖𝑠𝑘,𝑗
𝑛𝑛𝑜𝐴𝐸
𝑗=1
 
 
(20) 
Where 𝑛𝐴𝐸 is the number of subjects with the AE, 𝑇𝐸𝑥𝑝,𝑖 is a subject’s time at risk at AE onset in 
years (equation [15] in years) and 𝑇𝑅𝑖𝑠𝑘,𝑗 is the time at risk in years for subjects who did not 
experience the AE of interest. 
If a subject has multiple events at the level of coding evaluated, the time at risk at AE onset is 
calculated to the first occurrence of the AE.  
Exact Poisson 95% CIs for incidence rates are calculated using the relationship between the 
Poisson and the chi-square distribution (Ulm, 1990; Fay and Feuer, 1997): 
𝐿𝐶𝐿= (𝜒2𝑛,𝛼
2
2
)
2
 
(21) 
𝑈𝐶𝐿= 
𝜒2(𝑛+1),1−𝛼
2
2
2
 
(22) 
𝐶𝐼𝐿𝑜𝑤𝑒𝑟= 100 ∗ 
𝐿𝐶𝐿
∑
𝑇𝐸𝑥𝑝,𝑖
𝑛𝐴𝐸
𝑖=1
+ ∑
𝑇𝑅𝑖𝑠𝑘,𝑗
𝑛𝑛𝑜𝐴𝐸
𝑗=1
 
 
(23) 
𝐶𝐼𝑈𝑝𝑝𝑒𝑟=  100 ∗𝑈𝐶𝐿
∑
𝑇𝐸𝑥𝑝,𝑖
𝑛𝐴𝐸
𝑖=1
+ ∑
𝑇𝑅𝑖𝑠𝑘,𝑗
𝑛𝑛𝑜𝐴𝐸
𝑗=1
 
(24) 
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where nAE is the number of subjects with the AE  and is the basis for the number of the degrees 
of freedom for the chi-square quantile for the upper tail probability χ2, 𝑇𝐸𝑥𝑝,𝑖 is a subject’s time at 
risk at AE onset in years, nnoAE the number of subjects without the specific AE and 𝑇𝑅𝑖𝑠𝑘,𝑗 the 
total time at risk for subjects who did not experience the AE. 
The EAER is defined as the number of AEs reported up to 140 days after last dose, including 
repeat occurrences in individual subjects, and adjusted for exposure, and will be scaled to 100 
subject-years: 
𝐸𝐴𝐸𝑅=  100 ∗𝑁𝐴𝐸
∑
𝑇𝑅𝑖𝑠𝑘,𝑗
𝑛𝐴𝑙𝑙
𝑗=1
 
(25) 
where NAE is the total number of AEs, 𝑇𝑅𝑖𝑠𝑘,𝑗 is a subject’s total time at risk in years and nAll the 
number of subjects. 
No CI will be computed for EAER. 
10.2.3 
Adverse event of special interest and safety topics of interest 
AESI (in the opinion of the investigator) will be flagged in the study database. In addition, an 
AESI is considered to have occurred if any TEAE which meets the Hy’s Law criteria, defined as 
≥3x upper limit of normal (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) with coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase 
(ALP), with no alternative explanation for the biochemical abnormality. Hy’s law criteria will be 
summarized as described in Section 10.3. 
TEAEs are defined as Safety Topics of Interest and reported as follows: 
1. Infections (serious, opportunistic, fungal and TB) 
• Serious infections will be identified based on MedDRA classification (SOC “Infections and 
infestations”). (Although not required by the ‘Safety Topics of Interest for the Bimekizumab 
Program’ document, a separate table will be created for these events.) 
• Fungal infections will be summarized in a stand-alone table. The table will include all 
TEAEs (serious and non-serious) which code into the High Level Group Term “Fungal 
infectious disorders”.  
• Opportunistic infections (including TB) will be summarized in a stand-alone table. The table 
will include all opportunistic infection TEAEs identified using UCB-defined search criteria 
which were adjudicated as opportunistic infections. The process for identifying opportunistic 
infections is outlined in Section 12.3.  
 
2. Malignancies  
• One table will be based on the criteria standardized MedDRA query (SMQ)=“Malignant or 
unspecified tumours (SMQ)”.  
• One table will be based on the criteria SMQ=”Malignant tumours (SMQ)”.  
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SMQ search should include all TEAEs which code to a PT included in the Scope=Narrow group 
within each SMQ.  
Note that the events included in the “Malignancies” table will be a subset of the events included 
in the “Malignancies (including unspecified)” table. While the “Malignant tumours (SMQ)” is 
most relevant, “Malignant or unspecified tumours (SMQ)” must be reviewed for potential 
malignancies.  
The output tables will include 2 different overall incidence rows:  
• The first overall incidence row will summarize “Any Malignancy” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table (using the appropriate 
SMQ depending on the table), regardless of the HLT it codes to.  
• The second overall incidence row will summarize “Any Malignancy excluding non 
melanomic skin cancers HLT” and this row will summarize the incidence of AEs flagged for 
inclusion in the table (using the appropriate SMQ depending on the table), excluding those 
which code to an HLT of “skin neoplasms malignant and unspecified (excl melanoma)”.  
 
3. MACE  
Major adverse cardiac events will be presented in a table. The classification of an event as 
MACE is determined by an external cardiovascular event adjudication committee.  
A separate table and listing will present adjudicated cardiovascular events by type. For each 
cardiovascular event type (24 in total), the individual PTs which fall within each event type will 
be summarized.  
 
Extended MACE events will be presented in a separate table and listing. All events which are 
classified by the adjudication committee as any of the event types in Table 10‒3 will be 
considered an extended MACE event. 
 
Table 10‒3: Extended MACE types 
Event Type Code 
Event Type 
1 
Non-Fatal Myocardial Infarction (MI) 
2 
Non-Fatal Stroke: hemorrhagic 
3 
Non-Fatal Stroke: ischemic 
4 
Non-Fatal Stroke: embolic 
5 
Non-Fatal Stroke: undeterminable 
6 
Hospitalization or ER for Unstable Angina with urgent revascularization 
8 
Hospitalization for Heart Failure 
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Table 10‒3: Extended MACE types 
Event Type Code 
Event Type 
10 
Coronary Revascularization Procedures (e.g. percutaneous coronary 
intervention, coronary artery bypass grafting) 
11 
Urgent Revascularization Procedures (i.e. due to symptoms of brain ischemia or 
pending infarction) 
18 
Death due to Myocardial Infarction (MI) 
19 
Death due to Stroke 
20 
Sudden Cardiac Death 
21 
Other CV Death (e.g. heart failure, pulmonary embolism, cardiovascular 
procedure-related) 
22 
Cardiovascular Undetermined Cause of Death (ie, cause of death unknown) 
CV=cardiovascular; ER=emergency room; MI=myocardial infarction. 
Additionally, a listing of all events identified for potential review by the cardiovascular event 
adjudication committee will be produced. This listing will indicate whether each event was 
escalated to the committee for formal review/adjudication.  
4. Neutropenia  
A table will be created based on the following PTs (regardless of seriousness):  
• Autoimmune neutropenia  
• Band neutrophil count decreased  
• Cyclic neutropenia  
• Febrile neutropenia  
• Idiopathic neutropenia  
• Neutropenia  
• Neutropenic infection  
• Neutropenic sepsis  
• Neutrophil count decreased  
 
5. Suicidal Ideation and Behavior  
An external neuropsychiatric adjudication committee will evaluate potential neuropsychiatric 
events and determine whether any of those events were associated with suicidal ideation and 
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behavior (SIB). A table and listing for SIB events as determined by the adjudication committee 
will be produced.  
A separate table will present the adjudicated neuropsychiatric events by type. For each 
neuropsychiatric event type (6 in total), the individual PTs which fall within each event type will 
be summarized.  The table will include events adjudicated as SIB and events adjudicated as 
non-suicidal (note that the event type ‘Suicidal ideation’ may be classified as either SIB or 
non-suicidal). The neuropsychiatric event types/codes are as follows: 
• Event type code 1: Suicidal events/completed suicide 
• Event type code 2: Suicide attempt 
• Event type code 3: Preparatory acts toward imminent suicidal behavior 
• Event type code 4: Suicidal ideation 
• Event type code 7: Nonsuicidal Self-injurious behavior 
• Event type code 8: Nonsuicidal Other 
 
Additionally, a listing of all events identified for potential review by the neuropsychiatric 
adjudication committee will be produced. This listing will indicate whether each event was 
escalated to the committee for formal review/adjudication. A separate listing will also be 
produced to summarize the adjudicated results of all events escalated to the full committee. 
 
6. Inflammatory bowel disease  
An external IBD adjudication committee will evaluate potential IBD events and will classify 
these according to the event type in Table 10‒4. 
 
Table 10‒4: Inflammatory bowel disease types 
Event Type Code 
Event Type 
1 
Possible IBD – Crohn’s Disease 
2 
Probable IBD – Crohn’s Disease 
3 
Definite IBD – Crohn’s Disease 
4 
Possible IBD – Ulcerative Colitis 
5 
Probable IBD – Ulcerative Colitis 
6 
Definite IBD - Ulcerative Colitis 
7 
Possible IBD - Unclassified 
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Table 10‒4: Inflammatory bowel disease types 
Event Type Code 
Event Type 
8 
Probable IBD - Unclassified 
9 
Definite IBD - Unclassified 
10 
Symptoms not consistent with IBD 
11 
Possible IBD – Microscopic Colitis 
12 
Probable IBD – Microscopic Colitis 
13 
Definite IBD - Microscopic Colitis 
14 
Possible IBD – no further differentiation possible 
15 
Probable IBD – no further differentiation possible 
16 
Definite IBD - no further differentiation possible 
99 
Not enough information to adjudicate 
IBD=inflammatory bowel disease. 
A table for adjudicated IBD events (event type codes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15 
and 16) as determined by the adjudication committee will be produced. It will summarize events 
determined by the adjudication committee as definite IBD (event type codes 3, 6, 9, 13, and 16), 
probable IBD (event type codes 2, 5, 8, 12, and 15) and possible IBD (event type codes 1, 4, 7, 
11, and 14). Definite and probable IBD events will also be aggregated and summarized in the 
same table. This table will be stratified by subjects with or without a previous medical history of 
IBD. Previous medical history of IBD will be determined using the information recorded on the 
Extra-Articular Assessment form at Screening in AS0008 ("Does subject have a history of 
IBD?”). 
A separate table will present the adjudicated gastrointestinal events by type. For each 
gastrointestinal event type (event type codes 1 through 16 and 99; 17 in total), the individual PTs 
which fall within each event type will be summarized. This table will include events determined 
by the adjudication committee as definite IBD, probable IBD, and possible IBD. It will also 
include events determined as ‘Symptoms not consistent with IBD’ (event type code 10) and ‘Not 
enough information to adjudicate’ (event type code 99). A corresponding listing by event type 
will also be presented. 
A listing of all events identified for potential review by the IBD adjudication committee will be 
presented. This listing will indicate whether each event was escalated to the committee for 
formal review and adjudication. 
Finally, a separate listing will be presented showing individual diagnostic criteria met for each 
adjudicated IBD event. 
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7. Hypersensitivity (including Anaphylaxis)  
A separate table will be prepared based on the MedDRA anaphylaxis algorithm (Section 12.4) 
for acute anaphylactic events (reported on the same day as when an injection was administered 
or one day after). An AE glossary table will also be produced to summarize the MedDRA coding 
for these events. The glossary table will include the following fields: reported term, PT, LLT, 
HLT, and SOC. 
A separate table will be prepared to summarize hypersensitivity events, identified using the SMQ 
“Hypersensitivity (SMQ)”. All TEAEs which code to a PT included in the Scope=Narrow search 
will be included in this table. An AE glossary table will also be produced to summarize the 
MedDRA coding for these events. The glossary table will include the following fields: reported 
term, PT, LLT, HLT, and SOC. 
Injection site reactions will be evaluated based on the “any TEAE” table by looking under the 
following HLTs: “Administration site reactions NEC” and “Injection site reactions”.  
 
8. Hepatic events and DILI  
A table for hepatic events will be created based on the SMQ of “Drug related hepatic disorders - 
comprehensive search (SMQ)”. However, these 2 sub-SMQs are to be excluded: “Liver 
neoplasms, benign (incl cysts and polyps) (SMQ)” and “Liver neoplasms, malignant and 
unspecified (SMQ)”. For each of the above SMQs, all TEAEs will be included which code to a 
PT included in the Scope=Broad and/or Scope=Narrow.  
Note that all AEs meeting the above criteria will be included, and will not be limited to events 
that the investigator determined to be related to study drug.  
The incidence of AEs defined as Safety Topics of Interest will be summarized by MedDRA 
SOC, HLT, and PT (apart from the summary of each cardiovascular event type which will use 
PT only). The EAIR with associated 95% CI and the EAER will be included in the summary 
tables. 
10.2.4 
Impact of COVID-19 
In order to assess the impact of the COVID-19 global pandemic on the primary safety endpoint 
of incidence of TEAEs and serious TEAEs, additional listings and summaries will be presented.  
For reporting purposes AEs will be assigned to ‘Prior to COVID-19 pandemic’, ‘During the 
COVID-19 pandemic’ or ‘Post the COVID-19 pandemic’ based on the following: 
• If the date of AE onset (based on imputed start date) is prior to 11 March 2020 the AE will be 
assigned as ‘Prior to COVID-19 pandemic’ 
• If the date of AE onset (based on imputed start date) is on or after 11 March 2020 the AE will 
be assigned as ‘During the COVID-19 pandemic’ 
− The date of 11 March 2020 is chosen as the date the World Health Organization declared 
COVID-19 as a pandemic. 
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• If the date of AE onset (based on imputed start date) is after the date on which the World 
Health Organization declares the end of the COVID-19 pandemic the AE will be assigned as 
‘Post the COVID-19 pandemic’ 
− If the date of the end of the COVID-19 pandemic is on or after the date of last subject, 
last visit, the ‘Post the COVID-19 pandemic’ phase will not apply. 
The following categories of TEAE will be summarized by MedDRA SOC, HLT and PT, 
including EAIR and EAER: 
• All TEAEs by time of onset relative to COVID-19 pandemic (‘Prior to COVID-19 
pandemic’, ‘During the COVID-19 pandemic’ and ‘Post the COVID-19 pandemic’)  
• All serious TEAEs by time of onset relative to COVID-19 pandemic (‘Prior to COVID-19 
pandemic’, ‘During the COVID-19 pandemic’ and ‘Post the COVID-19 pandemic’)  
• All COVID-19 related TEAEs by treatment at completion of AS0008 and overall 
− COVID-19 related TEAEs will be identified based on the verbatim term including the 
text string ‘COVID’. These will include confirmed or suspected COVID-19 infections. 
TEAEs leading to study discontinuation and/or permanent withdrawal of study medication will 
be summarized by MedDRA SOC, HLT, and PT, and by time of onset relative to COVID-19 
pandemic (‘Prior to COVID-19 pandemic’, ‘During the COVID-19 pandemic’ and ‘Post the 
COVID-19 pandemic’). 
A separate listing of all COVID-19 related AEs will be presented, where COVID-related AEs are 
identified as described above. In addition, the time of onset of each AE relative to the COVID-19 
pandemic will be flagged in all AE listings. 
For all listings and summaries described above the ‘Post the COVID-19 pandemic’ phase will be 
omitted if the date of the end of the COVID-19 pandemic is on or after the date of last subject, 
last visit. 
For the purpose of calculating EAIR and EAER prior to, during, and post the COVID-19 
pandemic the rules in Table 10-5 will be applied in the calculation of exposure time at risk. An 
individual subject may therefore be counted in the denominator for all applicable periods (‘Prior 
to COVID-19 pandemic’, ‘During the COVID-19 pandemic’ and ‘Post the COVID-19 
pandemic’), dependent on whether the subject is still considered at risk at the time of the start 
date for each successive period. The time at risk will be calculated separately for each period in 
which the subject is counted. Subjects who are no longer in the exposure time at risk period 
(Table 10‒2) on the start date of a specific COVID-19 reporting period will not be counted in the 
denominator for that period ie, a subject who has withdrawn from the study prior to 11 March 
2020 and is no longer at risk will not be included in the denominator for the ‘During the 
COVID-19 pandemic’ or the ‘Post the COVID-19’ pandemic periods. 
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Table 10-5: Calculation of exposure time at risk in relation to COVID-19 
Study 
Period 
Start Date 
End Date 
Duration of Exposure 
Prior to 
COVID-19 
pandemic 
 
First dose of 
BKZ 160mg 
in AS0009 
10MAR2020 
This period is applicable for all subjects in the SS. The 
following rules will be applied: 
 
For subjects who did not discontinue medication in the 
‘Prior to COVID-19 pandemic’ phase (ie, where the last 
dose of BKZ 160mg is on or after 11MAR2020): 
(End date – start date + 1) 
 
For subjects who discontinued medication in the ‘Prior to 
COVID-19 pandemic’ phase (ie, where the last dose of 
BKZ 160mg is prior to 11MAR2020): 
If the following is true: 
Minimum of (Last dose date in AS0009 + 140a) and (Date 
of last clinical contactb) is ≥11MAR2020  
Then the duration of exposure will be calculated as 
follows: 
(End date – start date + 1) 
Else duration of exposure will be calculated as follows: 
Minimum of [(Last dose date in AS0009 – First dose date 
in AS0009 + 140a) +1] and (Date of last clinical contactb – 
First dose date in AS0009 + 1) 
For subjects that died on or before 10MAR2020: 
Date of death – Start date + 1 
Note: If the date of death is later than 140 days following 
the last dose of BKZ, this rule does not apply. 
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During the 
COVID-19 
pandemic 
11MAR2020 
Date of end 
of pandemic 
This period is applicable for all subjects in the SS who are 
still considered at risk on the 11MAR2020 (ie, those for 
whom either dosing is continuing or for whom the 140 day 
SFU period after last dose has not been completed [in the 
case of premature treatment discontinuation]). The 
following rules will be applied: 
 
For subjects who did not discontinue medication in the 
‘During the COVID-19 pandemic’ phase (ie, where the last 
dose of BKZ 160mg is on or after the date of the end of the 
pandemic +1): 
(End date – start date + 1) 
 
For subjects who discontinued medication  
in the ‘Prior to COVID-19 pandemic’ phase (ie, where the 
last dose of BKZ 160mg is prior to 11MAR2020): 
If the following is true: 
Minimum of (Last dose date in AS0009 + 140a) and (Date 
of last clinical contactb) is ≥11MAR2020  
Then the duration of exposure will be calculated as 
follows: 
Minimum of [(Last dose date in AS0009 – 11MAR2020 + 
140a) +1] and (Date of last clinical contactb – 11MAR2020 
+ 1) 
For subjects that died in the ‘During the COVID-19 
pandemic’ phase: 
Date of death – 11MAR2020 + 1 
Note: If the date of death is later than 140 days following 
the last dose of BKZ, this rule does not apply. 
 
For subjects who discontinued medication  
in the ‘During the COVID-19 pandemic’ phase (ie, where 
the last dose of BKZ 160mg is on or after 11MAR2020 and 
on or before the date of the end of the pandemic): 
If the following is true: 
Minimum of (Last dose date in AS0009 + 140a) and (Date 
of last clinical contactb) is > the date of the end of the 
pandemic  
Then the duration of exposure will be calculated as 
follows: 
(Date of end of pandemic – 11MAR2020 + 1) 
 
Else duration of exposure will be calculated as follows: 
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Table 10-5: Calculation of exposure time at risk in relation to COVID-19 
Study 
Period 
Start Date 
End Date 
Duration of Exposure 
Minimum of [(Last dose date in AS0009 – 11MAR2020 + 
140a) +1] and (Date of last clinical contactb – 11MAR2020 
+ 1) 
 
For subjects that died in the ‘During the COVID-19 
pandemic’ phase: 
Date of death – 11MAR2020 + 1 
Note: If the date of death is later than 140 days following 
the last dose of BKZ, this rule does not apply. 
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Table 10-5: Calculation of exposure time at risk in relation to COVID-19 
Study 
Period 
Start Date 
End Date 
Duration of Exposure 
Post the 
COVID-19 
pandemic 
Date of end 
of pandemic 
+ 1 
Last dose of 
BKZ 160mg 
in AS0009 
This period is applicable for all subjects in the SS who are 
still considered at risk on the day after the end date of the 
pandemic (ie, those for whom either dosing is continuing 
or for whom the 140 day SFU period after last dose has not 
been completed [in the case of premature treatment 
discontinuation]). The following rules will be applied: 
 
For subjects who did not discontinue medication in the 
‘During the COVID-19 pandemic’ phase (ie, where the last 
dose of BKZ 160mg is on or after the date of the end of 
pandemic +1): 
Minimum of [(Last dose date in AS0009 – (date of the end 
of pandemic +1) + 140a) + 1] and (Date of last clinical 
contactb – (date of the end of pandemic +1) + 1) 
For subjects that died: 
Date of death – (date of the end of pandemic +1) + 1. 
Note: If the date of death is later than 140 days following 
the last dose of BKZ, this rule does not apply. 
 
For subjects who discontinued medication in the ‘During 
the COVID-19 pandemic’ phase (ie, where the last dose of 
BKZ 160mg is on or before the date of the end of 
pandemic): 
If the following is true: 
Minimum of (Last dose date in AS0009 + 140a) and (Date 
of last clinical contactb) is ≥ the date of the end of 
pandemic +1 
  
Then the duration of exposure will be calculated as 
follows: 
[Minimum of [(Last dose date in AS0009 – (date of the end 
of pandemic +1) + 140a) +1] and (Date of last clinical 
contactb – (date of the end of pandemic +1) +1)] 
For subjects that died within 140 days following the last 
dose of BKZ this rule be adjusted to: 
Date of death – (date of the end of pandemic +1) + 1 
 
a 140 days refer to 5 half-lives of BKZ. 
b Date of last clinical contact for each subject is defined as the maximum of [last visit date including SFU visit, last 
AE start date (including imputed AE start dates), date of study termination or completion, last date of study drug 
administration following rules for partial treatment end dates as per Section 4.2.4]. 
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BKZ=bimekizumab. 
10.3 
Clinical laboratory evaluations 
The routine clinical laboratory evaluations specified in Table 10‒6 will be summarized. If any 
additional analytes are also recorded they will be listed only. 
Table 10‒6: Laboratory measurements 
Hematology 
Biochemistry 
Urinalysis 
Basophils  
Calcium 
Urine dipstick for pregnancy testinga 
Eosinophils 
Chloride 
Urinalysisb 
Lymphocytes 
Magnesium 
 
Atypical lymphocytes 
Potassium 
 
Monocytes 
Sodium 
 
Neutrophils 
Glucose (random) 
 
Hematocrit 
BUN 
 
Hemoglobin 
Creatinine 
 
MCH 
AST 
 
MCHC 
ALT 
 
MCV 
ALP 
 
Platelet count 
GGT 
 
RBC count 
Total bilirubin 
 
WBC count 
LDH 
 
 
Total cholesterol 
 
 
Uric acid 
 
 
CRP 
 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; CRP=high sensitivity C-reactive protein; GGT=gamma glutamyltransferase; LDH=lactate dehydrogenase; 
MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean 
corpuscular volume 
a A urine pregnancy test will be performed for women of childbearing potential if there is a suspicion of pregnancy. 
A positive urine pregnancy test should always be confirmed with a serum pregnancy test. 
b These measurements will be performed only if a urinalysis is required for safety reasons. 
Separate summary tables for hematology and biochemistry variables will be provided, based on 
central laboratory data only, from scheduled visits (including the SFU visit). Observed values 
and changes from AS0009 Laboratory Baseline will be summarized, by treatment group at 
completion of AS0008 and overall. CRP will be summarized separately as described in 
Section 8. 
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In the case where laboratory values (with the exception of CRP) are below the LLOQ, then these 
will be set to the midpoint between 0 and the LLOQ for the purpose of summarizing the data and 
calculating changes from Baseline. The original value will be reported in any listings. 
Summary tables of the number and percentage of subjects experiencing at least 1 on-treatment 
markedly abnormal value during the Treatment Period (including unscheduled and repeat 
assessments, but excluding any measurements that occurred prior to the first administration of 
study medication in AS0009 or more than 140 days after the last administration of study 
medication) for each hematology and biochemistry variable will be presented by treatment group 
at completion of AS0008 and overall. Markedly abnormal values for hematology and 
biochemistry are defined in Table 10‒7 and Table 10‒8. 
Tables of markedly abnormal laboratory data subject numbers will be provided including all 
values classified as markedly abnormal at scheduled and unscheduled visits. For all outputs 
presenting markedly abnormal laboratory values, only central laboratory data will be included. 
Table 10‒7: Definitions of markedly abnormal hematology values 
Variable (SI Units) 
Markedly Abnormal Definition 
Low 
High 
Hemoglobin (g/L) 
<80 
>40 above ULN 
Lymphocytes (109/L) 
<0.5 
>20.0 
Neutrophils (109/L) 
<1.0 a 
N/A 
Platelets (109/L) 
<50 
N/A 
Leukocytes (109/L) 
<2.0 
>100 
N/A=not applicable; ULN=upper limit of normal 
Data source: modified from Appendix Rheumatology Common Toxicity Criteria v.2.0 presented in 
Woodworth et al, 2007  
a Withdrawal criteria for neutrophils is <0.5 
 
Table 10‒8: Definitions of markedly abnormal biochemistry values 
Variable (SI Units) 
Markedly Abnormal Definition 
Low 
High 
ALP 
N/A 
>5.0 x ULN 
ALT 
N/A 
>5.0 x ULN 
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Table 10‒8: Definitions of markedly abnormal biochemistry values 
Variable (SI Units) 
Markedly Abnormal Definition 
Low 
High 
AST 
N/A 
>5.0 x ULN 
Total bilirubin 
N/A 
>3.0 x ULN 
GGT 
N/A 
>5.0 x ULN 
Creatinine (umol/L) 
N/A 
>3.0 x ULN or >3 x Baseline 
valuea 
Glucose (mmol/L) 
<2.2 
>13.9 
Calcium (mmol/L) 
<1.75 
>3.1 
Magnesium (mmol/L) 
<0.4 
>1.23 
Potassium (mmol/L) 
<3.0 
>6.0 
Sodium (mmol/L) 
<130 
>155 
Total cholesterol (mmol/L) 
N/A 
>10.34 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma 
glutamyl transferase; N/A=Not applicable; ULN=upper limit of normal. 
a The markedly abnormal definitions for creatinine are based on the logical OR; if either criterion is met the 
creatinine value will be designated as abnormal high. 
A summary of the number and percentage of subjects with a given Common Terminology 
Criteria for Adverse Events (CTCAE) grade (0, 1, 2, 3 or 4) based on minimum/maximum 
on-treatment value in AS0009 (including unscheduled and repeat assessments, but excluding any 
measurements that occurred prior to the first administration of study medication in AS0009 or 
more than 140 days after the last administration of study medication), will be presented by 
laboratory variable and treatment group at completion of AS0008. This summary will be 
provided only for selected laboratory variables and using central laboratory data only. 
Definitions of CTCAE grades are given in Table 10‒9 and Table 10‒10. 
A shift table of the number and percentage of subjects experiencing CTCAE grade 0, 1, 2, 3 or 4 
values (as applicable) at AS0009 Laboratory Baseline to minimum/maximum post-AS0009 
Laboratory Baseline CTCAE grade will be presented by laboratory variable and treatment group 
at completion of AS0008. The minimum/maximum post-AS0009 Laboratory Baseline CTCAE 
grade will include all scheduled and unscheduled on-treatment central laboratory assessments 
(excluding any measurements that occurred prior to the first administration of study medication 
in AS0009 or more than 140 days after the last administration of study medication). 
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Table 10‒9: Definitions of CTCAE grade by hematology parameter 
Parameter 
(unit) 
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Low 
g/L 
100-<LLN 
80-<100 
<80 
N/A 
Hemoglobina 
High 
g/L 
>0-20 above 
ULN, or >0-20 
above Baseline 
if Baseline is 
above ULN 
>20-40 
above ULN, 
or >20-40 
above 
Baseline if 
Baseline is 
above ULN 
>40 above 
ULN, or >40 
above 
Baseline if 
Baseline is 
above ULN 
N/A 
Platelets 
Low 
109/L 
75-<LLN 
50-<75 
25-<50 
<25 
WBC 
Low 
109/L 
3-<LLN 
2-<3 
1-<2 
<1 
WBC 
High 
109/L 
N/A 
N/A 
>100 
N/A 
Lymphocytes 
Low 
109/L 
0.8-<LLN 
0.5-<0.8 
0.2-<0.5 
<0.2 
Lymphocytes 
High 
109/L 
N/A 
>4-20 
>20 
N/A 
Neutrophils 
Low 
109/L 
1.5-<LLN 
1.0-<1.5 
0.5-<1.0 
<0.5 
LLN=lower limit of normal, ULN=upper limit of normal. 
a The CTCAE grade definitions to be applied are dependent on the Baseline hemoglobin value. If the Baseline value is 
>ULN then the criteria relative to Baseline are applicable; otherwise the criteria relative to ULN are applicable. 
Table 10‒10: 
Definitions of CTCAE grade by biochemistry parameter 
Parameter 
(unit) 
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Creatininea 
High 
umol/L 
>1-1.5 x 
Baseline or 
>ULN-1.5 
x ULN 
>1.5-3.0 x 
Baseline or 
>1.5 – 3.0 x 
ULN 
>3.0 x 
Baseline or 
>3.0 – 6.0 x 
ULN 
>6.0 x 
ULN 
Sodium 
Low 
mmol/L 
130-<LLN 
N/A 
120-<130 
<120 
Sodium 
High 
mmol/L 
>ULN-150 
>150-155 
>155-160 
>160 
Potassiumb 
Low 
mmol/L 
3.0-<LLN 
3.0-<LLN 
2.5-<3.0 
<2.5 
Potassium 
High 
mmol/L 
>ULN-5.5 
>5.5-6.0 
>6.0-7.0 
>7.0 
Calcium 
Low 
mmol/L 
2.0-<LLN 
1.75-<2.0 
1.5-<1.75 
<1.5 
Calcium 
High 
mmol/L 
>ULN-2.9 
>2.9-3.1 
>3.1-3.4 
>3.4 
Magnesium 
Low 
mmol/L 
0.5-<LLN 
0.4-<0.5 
0.3-<0.4 
<0.3 
Magnesium 
High 
mmol/L 
>ULN-1.23 
N/A 
>1.23-3.30 
>3.30 
Cholesterol 
High 
mmol/L 
>ULN-7.75 
>7.75-10.34 
>10.34-12.92 
>12.92 
LLN=lower limit of normal, ULN=upper limit of normal. 
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a The CTCAE grade definitions for creatinine are based on the logical OR; the highest applicable CTCAE grade 
should be assigned to a specific creatinine value. 
b Note that subjects who meet the decreased potassium criterion of 3.0-<LLN, which is specified as the decreased 
potassium lab criterion for both CTCAE Grade 1 and Grade 2, will be counted as Grade 2. 
The number and percentage of subjects with elevated liver function tests will be presented by 
treatment group at completion of AS0008 and overall, using on-treatment assessments 
(excluding any measurements that occurred prior to the first administration of study medication 
in AS0009 or more than 140 days after the last administration of study medication) from all 
visits in AS0009 including those at AS0009 Laboratory Baseline, unscheduled, ET and SFU 
visits. Assessments performed at both central and local laboratories will be included. Each 
subject will be counted once only. The number and percentage of subjects in the following 
categories at any time during the study will be presented:  
• AST: >3xULN, >5xULN, >8xULN, >10xULN, >20xULN. 
• ALT: >3xULN, >5xULN, >8xULN, >10xULN, >20xULN. 
• AST or ALT: >3xULN, >5xULN, >8xULN, >10xULN, >20xULN. 
• Total bilirubin: >1.5xULN, >2xULN. 
• ALP: >1.5xULN. 
The number and percentage of subjects who meet Hy’s Law criteria (Section 10.2.3) will be 
presented by treatment group at completion of AS0008 and overall, using on-treatment 
assessments (excluding any measurements that occurred prior to the first administration of study 
medication in AS0009 or more than 140 days after the last administration of study medication) 
from all visits including those at AS0009 Laboratory Baseline, unscheduled, ET and SFU visits. 
Hy’s Law criteria are displayed below: 
•  (AST ≥3xULN or ALT ≥3xULN) and Total Bilirubin ≥2xULN in the absence of ALP 
≥2xULN. 
To meet the above criteria, a subject must experience the elevation in total bilirubin and ALT or 
AST and the absence of ALP elevation at the same visit.    
All hematology and biochemistry laboratory data (except CRP) will be listed, including age, sex, 
race, weight, changes from AS0009 Laboratory Baseline for numeric variables, flags for 
measurements outside the normal ranges, flags for measurements meeting the criteria for each 
CTCAE grade (Table 10‒9 and Table 10‒10) the relative study day, a flag for whether the test 
was not done and a flag for whether the subject was fasting.  
CRP will be listed separately as described in Section 8. 
Values that are below the lower limit of the reference range will be flagged as ‘L’ (low) and 
values that are above the upper limit of the reference range will be flagged as ‘H’ (high) in 
listings. Values that meet the criteria for each CTCAE grade will be flagged as ‘LGrx’ or ‘HGrx’ 
accordingly. 
The markedly abnormal laboratory results will be listed separately. 
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Any additional laboratory assessments performed during the study will be listed separately. 
10.4 
Potential drug-induced liver Injury assessment 
All PDILI events require immediate action, testing, and monitoring. The measurements and 
additional information required for the assessment of PDILI events when there is a reasonable 
possibility that they may have been caused by the study medication are included but not limited 
to those listed in Table 10‒11 and Table 10‒12. 
PDILI laboratory results and additional PDILI information will be listed by treatment group at 
completion of AS0008 and subject. Where appropriate data will be included in the standard 
listings as indicated below:  
• Family medical history, including any DILI-relevant medical conditions or inheritable 
disorders, start year and end year (or ongoing if applicable) (presented in the demographics 
section only for subjects with PDILI events) 
• Study medication administration, including the date and time of most recent study 
medication administration, whether the subject discontinued study medication and the reason 
for discontinuation (presented in the compliance and drug concentration data section with a 
separate listing for PDILI events). 
• Blood sample collection for PK including the variable, unit, date and time the sample was 
taken, and the result (presented in the compliance and drug concentration data section as part 
of the standard listing). 
• Laboratory tests as detailed in Table 10‒6 (presented in the laboratory measurements section 
with a separate listing of PDILI events). 
• Vital signs (presented in the safety analysis section as part of the standard listing) 
• Lifestyle, including whether the subject has used alcohol in the past six months and whether 
the subject has used illicit drugs in the past six months (presented in the demographics 
section only for subjects with PDILI events). 
• Hepatic event medical history, including any medical conditions which could have 
contributed to the suspected hepatic event prior to study entry will be listed together with all 
medical history data (presented in the demographics section). 
• Symptoms of hepatitis and hypersensitivity, including whether the subject has taken any 
potentially hepatotoxic medications, whether the subject is experiencing symptoms of 
hepatitis, and whether the subject is experiencing symptoms of hypersensitivity (presented in 
the safety analysis section only for subjects with PDILI events). 
Table 10‒11: 
Additional potential drug-induced liver injury information 
New or updated information 
Concomitant prescription and over-the-counter medications (e.g. acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included. 
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Table 10‒12: 
Potential drug-induced liver injury laboratory measurements 
Virology-related 
Hepatitis A IgM antibody 
HBsAg 
Hepatitis E IgM antibody 
HBcAb-IgM 
Hepatitis C RNA 
Cytomegalovirus IgM antibody 
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain 
heterophil antibody or monospot testing) 
Immunology 
Anti-nuclear antibody (qualitative and quantitative) 
Anti-smooth muscle antibody (qualitative and quantitative) 
Pertinent medical history, including the following: 
• 
History of liver disease (e.g. autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”) 
• 
Adverse reactions to drugs 
• 
Allergies 
• 
Relevant family history or inheritable disorders (e.g. 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 (e.g. 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 
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Table 10‒12: 
Potential drug-induced liver injury laboratory measurements 
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative) 
Hematology 
Eosinophil count 
Urinalysis 
Toxicology screena 
Chemistry 
Amylase 
ALT, AST 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin 
Serum CPK and LDH to evaluate possible muscle injury causing 
transaminase elevation 
Additional 
Prothrombin time/INRb 
Serum pregnancy test 
PK sample 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; HBcAb-
IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; 
PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal 
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
patient’s history. 
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; 
hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative cause). 
10.5 
Vital Signs and Other Observations Related to Safety 
10.5.1 
Vital signs 
The following vital signs measurements will be assessed: 
• Systolic Blood Pressure (mmHg) 
• Diastolic Blood Pressure (mmHg)  
• Pulse Rate (bpm) 
• Temperature (C) 
• Body weight (kg) 
The following summaries will be provided:  
• A summary of the absolute and change from AS0008 Baseline for each vital sign variable at 
each visit, by treatment group at the completion of AS0008 and overall. 
− This summary will include the derived BMI at each time point. 
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• A summary of the number and percentage of subjects experiencing at least 1 on-treatment 
markedly abnormal value), as defined in Table 10‒13, for a vital sign variable during the 
treatment period (excluding any measurements that occurred prior to the first administration 
of study medication in AS0009 or more than 140 days after the last administration of study 
medication) by treatment group at the completion of AS0008 and overall (based on change 
from AS0008 Baseline). 
Table 10‒13: 
Definitions of markedly abnormal blood pressure values 
Variable (Unit) 
Markedly abnormal low 
Markedly abnormal high 
Systolic blood pressure (mmHg)  
<90 and a decrease from AS0008 
Baseline of ≥20 
>180 and an increase from 
AS0008 Baseline of ≥20 
Diastolic blood pressure (mmHg) 
<50 and a decrease from 
AS0008 Baseline of ≥15 
>105 and an increase from 
AS0008 Baseline of ≥15 
 
Vital signs measurements, including age, sex, race, weight and flags to identify markedly 
abnormal values, will be listed. The listing will include the derived BMI at each time point. 
10.5.2 
Electrocardiograms 
A summary of the number and percentage of subjects with normal, abnormal not clinically 
significant and abnormal clinically significant ECG results by visit will be presented by 
treatment group at completion of AS0008 and overall. 
The following ECG variables will be summarized by visit (absolute values and change from 
AS0008 Baseline), by treatment group at completion of AS0008 and overall: 
• PR interval (ms) 
• RR interval (ms) 
• QRS duration (ms) 
• QT interval (ms) 
• QTcF interval (ms) 
• QTcB interval (ms) 
Outliers in QTcF and QTcB are defined as values meeting the following criteria at any on-
treatment assessment in AS0009: 
• QTcF or QTcB >450 ms OR 
• QTcF or QTcB change from AS0008 Baseline >30 ms 
Outliers will be summarized using the following categories: 
• Values >450 ms, >480 ms and >500 ms 
• Increase from AS0008 Baseline of >30 ms, >60 ms and >90 ms 
• Value >450 ms AND increase from AS0008 Baseline of >30 ms 
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• Value >500 ms AND increase from AS0008 Baseline of >60 ms 
The summary will include the number and percentage of subjects who meet the criteria above at 
any on-treatment (scheduled or unscheduled) assessment (excluding any measurements that 
occurred prior to the first administration of study medication in AS0009 or more than 140 days 
after the last administration of study medication).  
All ECG variables will be listed, including unscheduled and repeat visits, if applicable. A 
separate listing of ECG findings will be presented together with the interpretation (normal, 
abnormal not clinically significant, or abnormal clinically significant). 
10.5.3 
Other safety variables 
Assessment of Tuberculosis 
Scheduled TB laboratory test results will be included in the laboratory data listings. Results of 
unscheduled TB testing at local laboratories will be listed separately. The response to the first 
question of the ‘Evaluation of signs and symptoms of tuberculosis’ questionnaire will be listed. 
Electronic Columbia Suicide Severity Rating Scale 
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a standardized and 
validated instrument developed for the assessment of the severity and frequency of suicidal 
ideation and behavior (Posner et al, 2011; Mundt et al, 2010). 
Suicidal ideation is defined as an event in any of the following 5 categories:  
  
Suicidal behavior is defined as an event in any of the following 4 categories:  
Suicidal ideation or behavior is defined as an event in any of the above 9 categories.  
Self-injurious behavior without suicidal intent will also be reported. 
The eC-SSRS can be administered to assess suicidal ideation and behavior over a lifetime, or 
since the last time it was assessed. The intent in this OLE study was to assess suicidal ideation 
and behavior since the last time it was assessed and refer back to the lifetime assessment 
conducted at the start of AS0008. However, some subjects completed the ‘lifetime’ assessment 
(in error) at one or more visits in AS0009 and recorded positive responses to some questions. 
Based on a review of their original lifetime assessment in AS0008, these positive responses are 
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not considered to represent a change in suicidal ideation and behavior during the study. The 
summary tables will include only the ‘since last assessment’ responses; all responses will be 
listed. 
The incidence of subjects with suicidal ideation, suicidal behavior, suicidal ideation or behavior 
and self-injurious behavior at least once for any on-treatment assessment (including unscheduled 
assessments, but excluding any measurements that occurred prior to the first administration of 
study medication in AS0009 or more than 140 days after the last administration of study 
medication) during AS0009, will be summarized by treatment group at completion of AS0008.  
eC-SSRS data will be listed. 
Health Care Provider Consultations 
Out-patient non-protocol health care provider consultations will be listed. 
Extra-articular assessments 
Extra-articular assessments performed after the AS0009 EV will be listed separately for the SS. 
10.5.4 
Comments 
A listing of comments will be presented, based on the ES. This listing will include comments 
received from the laboratory vendors (including safety laboratory data, PK and ADAb data). 
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11 
REFERENCES 
Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylsoing spondylitis 
assessment group preliminary definition of short-term improvement in ankylosing spondylitis. 
Arthritis Rheum. 2001 Aug;44(8):1876-86. 
Brandt J, Listing J, Sieper J, Rudwaleit M, van der Heijde D, Braun J. Development and 
preselection of criteria for short term improvement after anti-TNFa treatment in ankylosing 
spondylitis. Ann Rheum Dis. 2004;63(11):1438-44. 
Committee for Proprietary Medicinal Product/ICH/135/95. Note for guidance on good clinical 
practice. July 2002. 
Daudén E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or 
paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol 
Venereol. 2009;23(12), 1374-82. 
Fay MP, Feuer EJ. Confidence intervals for directly standardized rates: a method based on the 
Gamma distribution. Statistics in Medicine. 1997;16(7), 791-801. 
Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewé R, van der Tempel H, Mielants 
H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62(2):127-32. 
International Conference on Harmonization/ Food and Drug Administration E9 Guidance 
documents; 1998. 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E9/Step4/E9
_Guideline.pdf 
Langley RG, Feldman SR, Han C, Schenkel B, Szapary P, Hsu MC, et al. Ustekinumab 
significantly improves symptoms of anxiety, depression, and skin-related quality of life in 
patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo 
controlled phase III trial. J Am Acad Dermatol. 2010;63(3):457-65. 
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-
endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum 
Dis. 2009;68(1):18-24. 
Maksymowych WP, Mallon C, Richardson R, et al. Development and Validation of the 
Edmonton Ankylosing Spondylitis Metrology Index. Arthritis Rheum. 2006;55(4):575-82. 
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 Dec;44(16):1224-8. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin 
GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity 
and internal consistency findings from three multisite studies with adolescents and adults. Am J 
Psychiatry. 2011 Dec;168(12):1266-77. 
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Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment 
of SpondyloArthritis International Society (ASAS) handbook: a guide to assess 
spondyloarthritis. Ann Rheum Dis. 2009;68(Supple 2):ii1-44. 
Snaith RP, Zigmond AS. The hospital anxiety and depression scale, with the irritability-
depression-anxiety scale and the Leeds situational anxiety scale manual. 1994. 
Ulm K. A simple method to calculate the confidence interval of a standardized mortality ratio. 
American Journal of Epidemiology. 1990;131(2), 373-375. 
van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. 
Assessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of 
America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis 
Rheum. 2005;52(2):386-94. 
van der Heijde D, Landewé R, Feldtkeller, F. Proposal of a linear definition of the Bath 
Ankylosing Spondylitis Metrology Index (BASMI) and comparison with the 2-step and 10-step 
definitions. Ann Rheum Dis. 2008 Apr;67(4):489-93. 
van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, et al. Adalimumab 
effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-
term results from the ATLAS trial. Ann Rheum Dis. 2009;68(6):922-9. 
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12 
APPENDICES 
12.1 
Data Handling Rules for ASAS20, ASAS40 and ASAS5/6 
Response 
The rules for handling missing data in relation to defining the achievement of ASAS20 and 
ASAS40 responses are provided in Table 12-1. This table also indicates, where appropriate, the 
imputation as a non-responder (DTYPE = WC) in the analysis datasets for the NRI analyses. For 
tables presented on OC data, the data selected will include all instances where DTYPE is not 
populated in the analysis datasets. 
Table 12-1: Data Handling Rules for ASAS20 and ASAS40 
Components  
Component Status 
ASASa 
DTYPE 
4 components present 
3 or more components improved 
>=40% and >=2 units AND no 
deterioration in remaining 
component 
Y 
 
4 components present 
3 components improved >=40% and 
>=2 units AND remaining 
component deteriorated >=20% and 
>=1 unit 
N 
 
At least 1 component 
present 
1 or more component(s) has 
deteriorated >=20% and >=1 unit 
N 
 
3 components present 
3 or more components improved 
>=40% and >=2 units  
Y 
 
3 components present 
2 components improved >=40% and 
>=2 units AND no deterioration in 
remaining component(s) 
N 
WC 
3 components present 
1 or 0 components improved >=40% 
and >=2 units AND no deterioration 
in remaining component(s) 
N 
 
2 components present 
2 or 1 components improved AND 
no deterioration in remaining 
component(s) 
N 
WC 
2 components present 
0 components improved  
N 
 
1 or 0 components 
present 
1 or 0 components improved >=40% 
and >=2 units AND no deterioration 
in remaining component(s) 
N 
WC 
a Rules are based on ASAS40, similar rules will be implemented for ASAS20 response where improvement is 
defined as a change >=20% and >=1 units. 
WC = worst case. 
Similar rules for defining the achievement of ASAS5/6 response are presented in Table 12-2. 
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Table 12-2: Data Handling Rules for ASAS5/6 Response 
Components 
Component Status 
ASAS 
DTYPE 
6 components present  
5 or more components 
improved >=20% 
Y 
 
6 components present 
4 or fewer components 
improved >=20% 
N 
 
5 components present  
5 components 
improved >=20% 
Y 
 
5 components present 
4 components 
improved >=20% 
N 
WC 
5 components present 
3 or fewer components 
improved >=20% 
N 
 
4 components present 
4 or 3 components 
improved >=20% 
N 
WC 
4 components present 
2 or fewer components 
improved >=20% 
N 
 
3 components present 
3 or 2 components 
improved >=20% 
N 
WC 
3 components present 
1 or 0 component(s) 
improved >=20% 
N 
 
2 components present 
2 or 1 components 
improved >=20% 
N 
WC 
2 components present 
0 component(s) 
improved >=20% 
N 
 
1 or 0 components 
present 
1 or 0 components 
improved >=20% 
N 
WC 
WC = worst case. 
12.2 
Classification of the SF-36 questionnaire 
Table 12‒3 describes the 8 different scores calculated from the SF-36 questionnaire.  
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Table 12‒3: Classification of the SF-36 questionnaire 
Scales 
Physical Functioning 
Role-Physical 
Bodily Pain 
General Health 
Vitality 
Social Functioning 
Role-Emotional 
Mental Health 
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12.3 
Identification of Opportunistic infections 
Opportunistic infections are identified in two steps: 
Step 1: Refer to column B of the spreadsheet (Opportunistic infections MedDRA v 19.xlsx) 
which identifies the PTs to be classified as opportunistic infections using either a single “x” or a 
double “xx”. 
• 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 “x” will be summarized 
as an opportunistic infection in the stand-alone table. 
Step 2: Refer to column C of the spreadsheet which identifies the PTs that need to be evaluated 
on a case-by-case basis by the study physician in order to determine whether it is a true 
opportunistic infection or not. The process for physician review is as follows: 
1. Study programming team creates a spreadsheet which lists all of the subjects with a TEAE 
present in the database which codes to a PT identified as case-by-case. Information from the 
AE dataset to be included in the spreadsheet: Subject ID, AE verbatim term, SOC, High 
Level Term, Lower Level Term, PT, AE start date, AE end date, seriousness, severity, 
relationship to study medication, action taken. Additionally, a column will be included where 
the study physician can document their decision on the case. 
2. Study physician reviews the cases in the spreadsheet and indicates in the additional column 
which AEs are confirmed to be opportunistic infections via a single “x”. 
3. Study programming team incorporates these decisions into the AE dataset by merging the 
study physician decisions for individual subjects / PTs and flagging the confirmed 
opportunistic infections as such in the dataset. 
All subjects enrolled with a case-by-case PT reported that has been confirmed by the study 
physician to be an opportunistic infection will be summarized as such in the stand-alone table, 
along with all of the events identified in Step 1 of this process. 
The timing and frequency of Step 2 should be outlines and agreed to by the study team at the 
beginning of the study. It is suggested that this process be executed multiple times throughout the 
course of the study, more frequently in the weeks leading up to database lock, and one final time 
immediately prior to database lock. 
Following the initial physician review of case-by-case events, subsequent reviews will be based 
on the cumulative set of case-by-case events present in the database at each time point of 
spreadsheet creation. Physician decisions from previous runs should be retained in each 
subsequent run. The final run of the spreadsheet, with all study physician decisions on the full set 
of case-by-case events, will be archived at the conclusion of the study. 
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12.4 
MedDRA algorithmic approach to anaphylaxis 
The SMQ Anaphylactic reaction consists of three parts: 
• A narrow search containing PTs that represent core anaphylactic reaction terms  
 
• A broad search that contains additional terms that are added to those included in the narrow 
search. These additional terms are signs and symptoms possibly indicative of anaphylactic 
reaction and categorized in B, C or D 
− Cat B 
 
 
− Cat C 
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− Cat D 
 
• An algorithmic approach which combines a number of anaphylactic reaction symptoms in 
order to increase specificity. A case must include one of the following where both occur on 
either the same day as when an injection was administered or one day after, and for scenarios 
where two events must have been reported, both events must have occurred within one day of 
each other:  
− A narrow term or a term from Category A;  
− A term from Category B - (Upper Airway/Respiratory) AND a term from Category C - 
(Angioedema/Urticaria/Pruritus/Flush);  
− A term from Category D - (Cardiovascular/Hypotension) AND [a term from Category B - 
(Upper Airway/Respiratory) OR a term from Category C - (Angioedema/Urticaria/ 
Pruritus/Flush)]  
• Hypersensitivity events will be identified using the “Hypersensitivity (SMQ)”. All TEAEs 
which code to a PT included in the Scope=Narrow search will be included.   
12.5 
COVID-19 data collection 
For study visits impacted by COVID-19, additional data will be collected on a separate dedicated 
eCRF page.  
The following information will be reported: 
• Specification of the impacted visit (eg, Visit 5) 
• Date of the impacted visit 
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• Category of the impact (multiple categories may apply to the same visit) 
− Visit not done 
− Visit performed out of window 
− Home visit 
− Visit performed by video call 
− Visit performed by telephone 
− Investigational product shipped to study participant 
− Home administration of investigational product by participant or caregiver 
− Home administration of investigational product by a healthcare professional 
− Missed study drug administration/dispensation 
− Temporary discontinuation of study drug 
− Permanent discontinuation of study drug 
− Termination of study participation 
− Other 
• Relationship to COVID-19 
− Confirmed COVID-19 infection 
− Suspected COVID-19 infection 
− General circumstances around COVID-19 without infection 
− Other 
A narrative of the event will also be collected. 
 
 
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13 
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN 
13.1 
Amendment 1 
13.1.1 
Rationale for the amendment 
The main objective of this SAP amendment is to incorporate relevant updates based on Protocol 
Amendment 2, dated 09 Mar 2018 and Protocol Amendment 3, dated 06 Feb 2020. Additional 
details and modifications have been made throughout the document in order to align with the 
most recent bimekizumab program conventions. 
13.1.2 
Modifications and changes 
The following modifications and changes have been made: 
• Efficacy measurements at the SFU visit have been removed from the list of assessments for 
the other efficacy endpoints (Section 2.2.2.3). 
• Key inclusion criteria have been removed from the SAP as these are available in the final 
protocol and not relevant to the analyses described within the SAP 
• Change from AS0009 EV for safety variables will no longer be presented, since the EV 
assessment is made after 36 or 48 weeks of bimekizumab treatment and there is unlikely to 
be any further important change. 
• Change from AS0008 Baseline and from AS0009 EV for laboratory parameters (with the 
exception of CRP) will not be presented, due to a change in laboratory vendor between 
AS0008 and AS0009. Laboratory Baseline is defined as the earliest value in AS0009 at or 
prior to AS0009 Week 12. 
• Summaries of ASAS40, ASAS20 and ASAS5/6 response at each post-AS0008 Baseline visit 
in AS0008 through to AS0009 Week 208 have been added for subjects who were responders 
at AS0008 Week 12. These summaries will be used to assess maintenance of response. 
• The relative day will now be calculated twice, once relative to the start of study medication 
in AS0008 and once relative to the start of study medication in AS0009. 
• A definition of the dosing period has been added. 
• Baseline values (with the exception of AS0009-Laboratory Baseline values) will now be 
taken directly from the AS0008 database, and not re-derived. 
• The previous version of the SAP stated that ET visits would be mapped to a scheduled site 
visit if they fell on the scheduled date for that visit. This has been updated to say that they 
will be mapped to a scheduled visit if they fall within the protocol-defined visit window for 
that visit, unless there is an existing scheduled site visit in that window, in which case they 
will be mapped to the next scheduled site visit. Unscheduled visits will now also mapped to 
scheduled visits if they fall within the protocol-defined window for that visit, unless there is 
already a scheduled site visit or ET visit in that window. The wording has been clarified 
regarding unscheduled assessments performed at specific time points. 
• The definition of the sub-populations for the SS has been clarified to be based on 
concomitant rescue medications only. 
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• Sub-populations of the SS are used to report only TEAEs, serious TEAEs, AE Overview and 
Exposure rather than all primary and secondary safety variables. 
• Summaries based on sub-populations of the SS will only be reported in the event that the 
number of subjects receiving rescue medication is >=10% of the total number of subjects in 
the SS. 
• The protocol and previous version of the SAP describe the FAS as consisting of all enrolled 
subjects who receive at least 1 dose of IMP and have a valid measurement for at least 1 
efficacy variable at AS0009 study entry. This has been updated to include all subjects in the 
ES who received at least one dose of study medication in AS0009 and have a valid 
measurement for at least one efficacy variable after AS0009 EV in order to identify subjects 
who have had assessments during AS0009. 
• Summaries by randomized treatment in AS0008 will not be produced, as subjects will have 
been on a constant dose of bimekizumab 160mg or 320mg for at least 36 weeks prior to 
AS0009 entry. Maintenance of response displays will be split by treatment sequence across 
AS0008 and AS0009. Safety displays using AS0008 information will incorporate exposure in 
AS0008. 
• The protocol defines subgroups based on ‘Concomitant non-steroidal anti-inflammatory drug 
(NSAID) status at AS0009 entry. This has been updated to ‘Concomitant NSAID status at 
start of AS0008’. 
• The rules for NRI and MI for missing efficacy data have been clarified to state that 
imputations will only be performed for subjects in the FAS for AS0009. In addition the SAP 
has been updated to state that for NRI, the imputation will be re-derived at the AS0009 EV 
instead of using the AS0008 Week 48 imputed value; this is due to slight differences in the 
derivation rules for some endpoints between the AS0008 and AS0009 SAPs. 
• The MI procedures have been updated for all endpoints to use OC data from both AS0008 
and AS0009 studies such that missing data across both studies will be imputed. Thus, the 
procedure will estimate an imputation model at each post-AS0008 Baseline visit where 
efficacy variables are collected. The covariate for AS0009 EV has therefore been deleted 
from the model. 
• The endpoints/components for which MI will be performed have been clarified in the section 
on handling missing data for the efficacy analyses. 
• The presentation of CRP data following MI has been updated to use the geometric mean and 
95% CI for the geometric mean 
• The handling of missing data for AEs and concomitant medications has been updated to 
clarify the rules in the presence of a partial start date and a known end date. 
• For summaries based on MI of missing data, the covariates in the MI model will no longer 
include disease duration and concomitant NSAID status. 
• The seed used for all MI procedures has been updated to 2017. 
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• A summary of study medication discontinuation and a listing of subjects excluded from at 
least one analysis set have been added. 
• Methods for calculating total days on study medication have been added to the SAP 
• Tables and listings presenting the impact of COVID-19 on the study data collection have 
been added 
• The listing of lifestyle data has been removed, as this data is not generally collected in 
AS0009. Lifestyle data may be collected for PDILI cases, and this data will be listed. 
• The categories and rules for identifying rescue medications have been updated 
• Efficacy data collected after a subject has used a prohibited medication will no longer be 
treated as missing since the primary purpose of this study is to assess safety. 
• Compliance categories have been updated from <=80% and >80% to <=75% and > 75% to 
match the overall program conventions for bimekizumab. 
• Sensitivity analyses based on OC data were restricted to ASAS40, 20, ASAS5/6 and 
BASDAI. Additional sensitivity analyses based on MI of component scores were added for 
ASAS40 and ASAS20 response variables.  
• The data handling rules for ASAS response derivations have been updated and clarified to 
match the overall program conventions for bimekizumab 
• Summaries of MASES were restricted to subjects with enthesitis (MASES > 0) at AS0008 
Baseline 
• CRP values below the LLOQ will now be set to half LLOQ (0.08mg/L) prior to reporting 
(rules for calculation of ASDAS-CRP use different conventions for values that are below the 
LLOQ). 
• Plots of geometric mean bimekizumab plasma concentration versus time by treatment group 
and cumulative ADAb status have been added based on ADAb status in AS0008 and 
AS0009. 
• ADAb status categories have been redefined and appropriate plots and summaries have been 
added based on the most recent bimekizumab program conventions. 
• Summaries of all TEAEs and serious TEAEs in AS0008 and AS0009 combined, a 
corresponding AE overview table and a table of exposure across AS0008 and AS0009 have 
been added. 
• Summaries have been added for fatal TEAEs; TEAEs leading to permanent withdrawal of 
study medication; serious TEAEs by maximum relationship and fatal TEAEs by maximum 
relationship. The Adverse Drug Reaction summary has been removed. A listing of 
Hospital/ER visits has been added. 
• A summary of TEAEs by descending frequency of PT has been added 
• A summary of TEAEs in AS0009 and ongoing TEAEs from AS0008 has been added 
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• Tables and listings have been added to evaluate the effect of COVID-19 on reporting of 
TEAEs 
• The summaries and listings for AEs of special interest have been updated to match more 
recent guidelines. 
• Further clarification has been added to the definitions of EAIR and EAER. 
• Summaries and shift tables of subjects experiencing a given CTCAE grade for selected 
laboratory parameters have been added. 
• Summaries presenting outliers for QTcB and QTcB have been added 
• A listing of ECG findings has been added 
• Body weight and BMI have been added to the listing and summary table for vital signs 
variables 
• Physical examination data will no longer be listed as this data is not collected. 
• A listing of healthcare provider consultations listing has been added. 
• A listing of comments has been added. 
• A listing of procedure history has been added. 
• The appendices containing the copies of the individual questionnaires have been removed 
13.2 
Amendment 2 
13.2.1 
Rationale for the amendment 
The main objectives of this SAP amendment are to incorporate relevant updates in order to align 
with the most recent bimekizumab program conventions and make other modifications following 
the review of the results from the interim analysis. 
13.2.2 
Modifications and changes 
The following modifications and changes have been made: 
• Section 3.3 was updated to clarify that local laboratory measurements will not be considered 
in the definition of Baseline for laboratory data. 
• The endpoints/components for which MI will be performed have been updated in the section 
on handling missing data for the efficacy analyses; these now include each of the 8 individual 
domains of the SF-36, in addition to the PCS and MCS scores. The domain scores will also 
be summarized in a corresponding table. In addition, the minimum and maximum allowable 
ranges for PCS and MCS for imputation purposes have been updated using the most recently 
available norm-based scores. 
• In Table 4‒2, the OC analysis has been added as the secondary analysis for ASAS-PR; this 
was omitted in error in the previous version of the SAP. 
• The disease categories for ASDAS-CRP have been updated to reference ‘low’ disease 
activity instead of ‘moderate’ disease activity. 
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• Section 8.1.12 has been updated to clarify that CRP assessments performed at local 
laboratories will not be considered for efficacy analyses (including ASDAS-CRP). 
• The methodology for calculation of the BASMI scores has been updated in line with the most 
recent bimekizumab program conventions. The reference list has been updated accordingly. 
• The analysis set used to present the impact of the COVID-19 pandemic on the conduct of the 
efficacy assessments has been updated from the SS to the FAS. 
• Section 6.2 was updated to clarify that the summary of current corticosteroid therapy for 
AS0009 will include oral medications only. 
• Section 6.5 was updated to clarify how different medication types will be identified and 
classified for reporting purposes. 
• A summary of the injection setting and person performing the injection at each dosing visit 
has been added. An additional overall summary has been added showing the overall number 
of subjects having self- and home-administrations of study medication. 
• The calculation rules for exposure time at risk relative to the COVID-19 pandemic have been 
updated to take into account treatment discontinuation within each period.  
• The summaries of TEAEs by time of onset relative to the COVID-19 pandemic and by 
region have been removed due to the small number of events within each region. 
• The data handling rules for PK concentration data have been updated with respect to the 
exclusion rules used for the summary statistics. In addition, the rules for determining 
cumulative ADAb positivity have been clarified. 
• The method for calculating the fold change from Baseline for the ADAb titers has been 
added to the SAP. 
• The summary table of ADAb status by visit has been updated to include a summary for the 
BKZ Total group in addition to the summaries by treatment at completion of AS0008. 
• The reference to the use of Kaplan-Meier methods for the plot of time to treatment-emergent 
ADAb positivity has been removed as this is not applicable. 
• The summary tables and corresponding figures for time to treatment-emergent ADAb 
positivity have been updated to include a summary for the BKZ Total group in addition to the 
summaries by treatment at completion of AS0008. Further details regarding the presentation 
of the figures were also added to the text for clarity. 
• The categories for the figure of ASAS40 responders over time by ADAb status have been 
updated to exclude the AS0009 SFU visit in the derivations. 
• The description of the figure for ASAS40 responders over time by ADAb status has been 
updated to clarify that the missing category will be omitted from the plot if there are <=5% of 
subjects in this category. Additional modifications to the text describing the ADAb-related 
figures have been made to clarify the requirements where needed. 
• The summary table of TEAEs by timing of onset relative to ADAb status was clarified with 
respect to the ADAb categories to be included. 
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• An additional table was added to the SAP summarizing neuropsychiatric TEAEs by event 
type. 
• Additional categories for the adjudicated IBD AESI have been added to the SAP, per the 
latest IBD adjudication committee criteria. 
• The rules for handling safety laboratory data reported as below the LLOQ were updated in 
line with the most recent bimekizumab program conventions. Additional clarification was 
added regarding the presentation of markedly abnormal laboratory results and CTCAE 
grades to highlight that only central laboratory results will be included in these outputs. 
• The criteria for TEMA laboratory results have been updated for creatinine and total 
cholesterol. 
• The CTCAE grades for hemoglobin and creatinine have been updated. 
• ALP was added to the list of elevated liver function tests and the text has been updated to 
clarify that results from both central and local laboratories will be considered in this 
tabulation. 
13.3 
Amendment 3 
13.3.1 
Rationale for the amendment 
The purpose of this SAP amendment is to clarify the definition of the FAS in order to ensure that 
all subjects included in the FAS have data available to contribute to the efficacy analyses. 
13.3.2 
Modifications and changes 
The following modifications and changes have been made: 
• Section 2.2.2.3 was updated to remove the Week 132 visit for the ASQoL efficacy endpoint; 
this was an error in the previous versions of the SAP. 
• Section 3.6.3 was updated to the following: 
The Full Analysis Set (FAS) will consist of all subjects in the ES who received at least one 
dose of study medication in AS0009 and have a valid measurement for at least one efficacy 
variable at any scheduled visit (excluding SFU visits) after AS0009 EV where efficacy is 
planned to be collected. This will include any data collected at an unscheduled or ET visit, 
and which has been remapped to a scheduled visit where efficacy data are planned. The 
protocol definition suggested that a valid measurement for at least one efficacy variable at 
AS0009 EV was required, but in order to identify subjects who have had assessments during 
AS0009, the requirement has been changed to ‘after’. This has been further clarified to 
include scheduled visits in AS0009 (where efficacy data is planned), excluding SFU visits, in 
order to ensure that all subjects in the FAS have data available to contribute to any of the 
efficacy analyses. 
• Section 3.10 was updated to add additional detail to the change from the protocol-defined 
definition of the FAS. 
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14 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
 
 
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Approval Signatures
Name:
as0009-sap-amend-3
Version:
1. 0
Document Number:
CLIN-000209689
Title:
as0009-Statistical Analysis Plan Amendment 3
Approved Date:
11 Jan 2023
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 11-Jan-2023 08:59:19 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 11-Jan-2023 09:31:13 GMT+0000
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