Conditions: Psoriatic Arthritis
Keywords: Psoriatic Arthritis PsA Auto-Injector Bimekizumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 214
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate for each self-injecting device presentation the ability of subjects with psoriatic arthritis (PsA) to safely and effectively self-inject bimekizumab at study start and 4 weeks after training in self-injection technique using the bimekizumab safety syringe (SS) or the bimekizumab auto-injector (AI).

Detailed description:

Arms:
arm 1: Study participants randomized to this arm will receive assigned bimekizumab dose regimen using the prefilled safety syringe (SS). arm 2: Study participants randomized to this arm will receive assigned bimekizumab dose regimen using the auto-injector (AI).

Interventions: intervention 1: Bimekizumab
Intervention descriptions: intervention 1: Study participants will receive bimekizumab at pre-specified time points.

Protocol document:
Prot_000.pdf: 
UCB 
14 May 2020 
Clinical Study Protocol 
Bimekizumab 
DV0004 
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Page 1 of 49 
PROTOCOL DV0004 AMENDMENT 1 
(NORTH AMERICA AND EU SUBSTUDY TO PA0012) 
A MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO 
EVALUATE THE SAFE AND EFFECTIVE USE OF THE 
PREFILLED SAFETY SYRINGE OR AUTO-INJECTOR FOR 
THE SUBCUTANEOUS SELF-INJECTION OF BIMEKIZUMAB 
SOLUTION BY SUBJECTS WITH ACTIVE PSORIATIC 
ARTHRITIS 
PHASE 3 
IND Number: 128708 
EudraCT number: 2018-004725-86 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Protocol/Amendment number 
Date 
Type of amendment 
Final protocol 
05 Feb 2019 
Not applicable 
Protocol Amendment 1 
14 May 2020 
Nonsubstantial 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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Bimekizumab 
DV0004 
 
 
 
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STUDY CONTACT INFORMATION 
Sponsor 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Sponsor Study Physician 
Name: 
 
Address: 
UCB Celltech. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
Clinical Project Manager 
Name: 
 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
 
Address: 
UCB  
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
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Clinical Monitoring Contract Research Organization 
Name: 
PAREXEL International (IRL) Limited-Ireland 
Address: 
Ireland Limited at 70 Sir John Rogerson’s Quay, Dublin 2, 
Ireland 
Phone: 
+353 (1) 477 3171 
Fax: 
+353 (1) 477 3308 
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SERIOUS ADVERSE EVENT AND PRODUCT QUALITY COMPLAINTS 
REPORTING 
Serious adverse event reporting (24h) 
Email: 
DS_ICT@ucb.com 
Fax: 
+1 800 880 6949 or +1 866 890 3175 
Product Quality Complaints Reporting (24h) 
Email: 
qactscomplaints@ucb.com 
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Bimekizumab 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................... 5 
LIST OF ABBREVIATIONS .................................................................................................... 9 
1 
SUMMARY ..................................................................................................................... 11 
2 
INTRODUCTION ........................................................................................................... 13 
3 
STUDY OBJECTIVES .................................................................................................... 13 
3.1 
Primary objective ......................................................................................................... 13 
3.2 
Secondary objective ..................................................................................................... 14 
3.3 
Other objectives ........................................................................................................... 14 
4 
STUDY VARIABLES ..................................................................................................... 14 
4.1 
Outcome variables ....................................................................................................... 14 
4.1.1 
Primary outcome variable .................................................................................... 14 
4.1.2 
Secondary outcome variable ................................................................................ 14 
4.1.3 
Other variables ..................................................................................................... 15 
4.1.3.1 
Outcome variables ..................................................................................... 15 
4.1.3.2 
Pharmacokinetic variable .......................................................................... 15 
4.1.3.3 
Immunological variable ............................................................................. 15 
4.1.3.4 
Safety variable ........................................................................................... 15 
5 
STUDY DESIGN ............................................................................................................. 15 
5.1 
Study description ......................................................................................................... 15 
5.1.1 
Study duration per subject ................................................................................... 16 
5.1.2 
Planned number of subjects and sites .................................................................. 17 
5.1.3 
Anticipated regions and countries ....................................................................... 17 
5.2 
Schedule of study assessments..................................................................................... 17 
5.3 
Schematic diagram ....................................................................................................... 23 
5.4 
Rationale for study design and selection of dose ......................................................... 23 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................................... 23 
6.1 
Inclusion criteria .......................................................................................................... 23 
6.2 
Exclusion criteria ......................................................................................................... 24 
6.3 
Withdrawal criteria ...................................................................................................... 24 
7 
INVESTIGATIONAL MEDICINAL PRODUCT AND INVESTIGATIONAL DEVICE24 
7.1 
Description of device presentations ............................................................................. 24 
7.1.1 
Bimekizumab-SS-1mL ........................................................................................ 24 
7.1.1.1 
Instruction for use of bimekizumab-SS-1mL ............................................ 25 
7.1.2 
Bimekizumab-AI-1mL ........................................................................................ 25 
7.1.2.1 
Instruction for use of bimekizumab-AI-1mL ............................................ 26 
7.2 
Treatment to be administered....................................................................................... 26 
7.3 
Packaging ..................................................................................................................... 27 
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7.4 
Labeling ....................................................................................................................... 27 
7.5 
Handling and storage requirements ............................................................................. 27 
7.6 
Drug and device presentation accountability ............................................................... 27 
7.7 
Procedures for monitoring subject compliance ............................................................ 28 
7.8 
Concomitant medications/treatments ........................................................................... 28 
7.8.1 
Permitted concomitant treatments (medications and therapies) .......................... 28 
7.8.2 
Prohibited concomitant treatments (medications and therapies) ......................... 28 
7.9 
Blinding........................................................................................................................ 28 
7.10 
Randomization and numbering of subjects .................................................................. 28 
8 
STUDY PROCEDURES BY VISIT ............................................................................... 28 
8.1 
Treatment Period .......................................................................................................... 29 
8.1.1 
Unscheduled Visit ................................................................................................ 29 
9 
ASSESSMENT OF SELF-INJECTION .......................................................................... 29 
9.1 
Assessment of injection site pain ................................................................................. 29 
9.2 
Assessment of self-injection experience by SIAQ ....................................................... 29 
9.3 
Evaluation of post-use structural, mechanical, and functional integrity of 
self-injecting device presentations ............................................................................... 30 
10 ASSESSMENT OF PHARMACOKINETIC AND IMMUNOLOGICAL VARIABLES30 
11 ASSESSMENT OF SAFETY .......................................................................................... 31 
11.1 
Adverse events (device presentations) ......................................................................... 31 
11.1.1 
Definitions (device presentations) ....................................................................... 31 
11.1.1.1 
Adverse device effect (device presentations) ............................................ 31 
11.1.1.2 
Serious adverse device effects ................................................................... 31 
11.1.1.3 
Device deficiency (device presentations) .................................................. 32 
11.1.2 
Procedures for reporting and recording adverse device effects and device 
deficiencies .......................................................................................................... 32 
11.1.2.1 
Reporting of adverse device effects .......................................................... 33 
11.1.2.2 
Reporting of device deficiencies ............................................................... 33 
11.1.2.3 
Reporting of serious adverse device effects including device deficiencies 
with risk of serious adverse event ............................................................. 33 
11.1.2.4 
Rule for repetition of an adverse device effect, serious adverse device 
effect, and/or device deficiency ................................................................. 34 
11.1.3 
Follow up of adverse device effects and serious adverse device effects ............. 34 
11.2 
Pregnancy ..................................................................................................................... 35 
11.3 
Suspected transmission of an infectious agent............................................................. 35 
11.4 
Overdose of investigational medicinal product ........................................................... 35 
11.5 
Safety signal detection ................................................................................................. 35 
11.6 
Other safety measurements .......................................................................................... 35 
11.6.1 
Vital signs measurement ...................................................................................... 35 
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12 EFFICACY ASSESSMENTS FOR PA0012 ................................................................... 36 
13 STUDY MANAGEMENT AND ADMINISTRATION ................................................. 36 
13.1 
Adherence to protocol .................................................................................................. 36 
13.2 
Monitoring ................................................................................................................... 36 
13.2.1 
Definition of source data ..................................................................................... 36 
13.2.2 
Source data verification ....................................................................................... 37 
13.3 
Data handling ............................................................................................................... 37 
13.3.1 
Case Report form completion .............................................................................. 37 
13.3.2 
Database entry and reconciliation ........................................................................ 37 
13.3.3 
Subject Screening and Enrollment log/Subject Identification Code list.............. 38 
13.4 
Termination of the study .............................................................................................. 38 
13.5 
Archiving and data retention ........................................................................................ 38 
13.6 
Audit and inspection .................................................................................................... 39 
13.7 
Good Clinical Practice ................................................................................................. 39 
14 STATISTICS ................................................................................................................... 39 
14.1 
Definition of analysis sets ............................................................................................ 39 
14.2 
General statistical considerations ................................................................................. 40 
14.3 
Planned analyses of outcome variables ........................................................................ 40 
14.3.1 
Analysis of the primary outcome variable ........................................................... 40 
14.3.2 
Analysis of the secondary outcome variable ....................................................... 40 
14.3.3 
Analysis of other outcome variables .................................................................... 40 
14.4 
Planned pharmacokinetic analyses .............................................................................. 40 
14.5 
Planned safety analyses................................................................................................ 41 
14.6 
Planned efficacy analyses ............................................................................................ 41 
14.7 
Handling of protocol deviations................................................................................... 41 
14.8 
Handling of dropouts or missing data .......................................................................... 41 
14.9 
Planned interim analysis and data monitoring ............................................................. 42 
14.10 Determination of sample size ....................................................................................... 42 
15 ETHICS AND REGULATORY REQUIREMENTS ...................................................... 42 
15.1 
Informed consent ......................................................................................................... 42 
15.2 
Subject identification cards .......................................................................................... 43 
15.3 
Institutional Review Boards and Independent Ethics Committees .............................. 43 
15.4 
Subject privacy............................................................................................................. 44 
15.5 
Protocol amendments ................................................................................................... 44 
16 FINANCE, INSURANCE, AND PUBLICATION ......................................................... 44 
17 REFERENCES ................................................................................................................ 44 
18 APPENDICES ................................................................................................................. 45 
18.1 
Protocol Amendment 1 ................................................................................................ 45 
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19 DECLARATION AND SIGNATURE OF INVESTIGATOR ....................................... 48 
20 SPONSOR DECLARATION .......................................................................................... 49 
 
LIST OF TABLES 
Table 5‒1: 
Schedule of study assessments for DV0004 .................................................... 18 
Table 5‒2: 
Schedule of study assessments for corresponding visits in PA0012 ............... 20 
 
LIST OF FIGURES 
Figure 5‒1: 
Schematic diagram ........................................................................................... 23 
Figure 7-1: 
Bimekizumab-SS-1mL .................................................................................... 25 
Figure 7-2: 
Bimekizumab-AI-1mL ..................................................................................... 26 
 
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LIST OF ABBREVIATIONS 
ADE 
adverse device effect 
AE 
adverse event 
bimekizumab-AI-1mL 
1mL bimekizumab auto-injector  
bimekizumab-SS-1mL 
1mL bimekizumab safety syringe 
BMI 
body mass index 
CDMS 
clinical data management system 
CI 
confidence interval 
CRO 
contract research organization 
ECG 
electrocardiogram 
eCRF 
electronic Case Report form 
FAS 
Full Analysis Set(s) 
FAS-a 
Full Analysis Set for the bimekizumab-AI-1mL 
FAS-s 
Full Analysis Set for the bimekizumab-SS-1mL 
GCP 
Good Clinical Practice 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee  
IFU 
instructions for use 
IL 
interleukin 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
PFS 
prefilled syringe 
PK 
pharmacokinetic(s) 
PKS 
Pharmacokinetic Set 
PKS-a 
Pharmacokinetic Set for the bimekizumab-AI-1mL 
PKS-s 
Pharmacokinetic Set for the bimekizumab-SS-1mL 
PS 
Patient Safety 
PsA 
psoriatic arthritis 
Q4W 
every 4 weeks 
SADE 
serious adverse device effect 
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SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous 
SFU 
safety follow-up 
SIAQ 
Self-injection Assessment Questionnaire 
SOP 
Standard Operating Procedure 
SS 
Safety Set(s) 
SS-a 
Safety Set for the bimekizumab-AI-1mL  
SS-s 
Safety Set for the bimekizumab-SS-1mL 
USADE 
unanticipated serious adverse device effect 
VAS 
visual analog scale 
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1 
SUMMARY 
DV0004 is a Phase 3, multicenter, open-label, randomized, noncomparator, North America and 
Europe substudy to PA0012 in adult subjects with active psoriatic arthritis (PsA) to evaluate the 
safe and effective use of 2 single-use disposable self-injecting device presentations for the 
subcutaneous (sc) administration of bimekizumab solution (the investigational medicinal product 
[IMP]). To provide patients with PsA with options for the self-administration of bimekizumab, 
DV0004 will evaluate 2 investigational self-injecting device presentations, which are drug 
product (IMP) associated with a functional secondary packaging: the 1mL bimekizumab safety 
syringe (bimekizumab-SS-1mL) and the 1mL bimekizumab auto-injector 
(bimekizumab-AI-1mL). 
DV0004 is a substudy of PA0012, which is a multicenter, open-label, long-term safety study for 
subjects with PsA who complete 1 of the Phase 3 feeder studies (PA0010 or PA0011). The 
PA0012 study will evaluate the long-term safety, tolerability, and efficacy of bimekizumab in 
subjects with PsA, and study personnel qualified in sc injection technique will administer 
bimekizumab to subjects (except for specified study visits at which subjects may self-administer) 
in a 1mL True North prefilled syringe (referred to throughout this protocol as the 1mL PFS). 
Subjects will begin the DV0004 substudy and the PA0012 study at the same time. The DV0004 
substudy will include all PA0012 study assessments from Baseline to Week 4 (inclusive). 
However, subjects in the DV0004 substudy will self-administer bimekizumab at Baseline and at 
Week 4. 
During the 4-week Treatment Period of DV0004, subjects will receive bimekizumab 160mg 
every 4 weeks (Q4W). This dose regimen will remain stable for the entire 4-week Treatment 
Period of DV0004 (consistent with PA0012). In the DV0004 substudy, subjects will be randomly 
assigned to 1 of the 2 self-injecting device presentations and will self-administer bimekizumab at 
Baseline and at Week 4. A safety follow-up (SFU) telephone call will occur 1 week after the last 
self-administration in DV0004 (Week 5). After Week 5 in the DV0004 substudy, subjects will 
continue in PA0012 (the next visit after DV0004 completion will be the Week 8 Visit in 
PA0012). At Week 8 in PA0012, study personnel qualified in sc injection technique will 
administer bimekizumab to subjects in a 1mL PFS, or the subject/caregiver/appropriate designee 
will perform administration under the supervision of the site staff after training. 
To compensate for subjects who have different study treatments between the feeder studies and 
DV0004, DV0004 is planned to enroll approximately 200 subjects (100 subjects per device 
presentation arm) to ensure that approximately 50 subjects per device presentation arm are 
evaluable for steady state trough pharmacokinetic (PK) level analyses. Within each device 
presentation arm, subjects will be divided into tertiles by body mass index (BMI); there will be 
approximately 33 subjects per tertile, which is expected to yield approximately 16 to 17 subjects 
per tertile who are evaluable for steady state trough PK level analyses. 
The primary objective of the DV0004 substudy is to evaluate for each self-injecting device 
presentation the ability of subjects with PsA to safely and effectively self-inject bimekizumab 
4 weeks after training in self-injection technique using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL. The primary outcome variable is the percentage of subjects able to 
self-administer safe and effective injections using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL at Week 4. 
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Safe and effective self-injection will be evaluated by the study personnel and is defined as: 
• Complete dose delivery: Subject self-injects the complete dose of bimekizumab as confirmed 
by a visual inspection of the bimekizumab-SS-1mL or the bimekizumab-AI-1mL, which 
shows that the IMP is delivered completely (ie, container is empty), and 
• No adverse device effects (ADEs) that would preclude continued use of the device 
presentation for self-injection (ie, no serious adverse device effects [SADEs] and/or ADEs 
leading to withdrawal from the DV0004 substudy) 
The secondary study objectives and other study objectives are provided in Section 3.2 and 
Section 3.3, respectively. Of note, one of the other study objectives is to assess trough PK levels 
associated with self-injection using the test device presentation, injection by study personnel 
using the 1mL PFS, injection site (abdomen or thigh), and BMI category (by tertile). The 
secondary outcome variable, other outcome variables, and the other safety variable are listed in 
Section 4.1.2, Section 4.1.3, and Section 4.1.3.4, respectively. 
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2 
INTRODUCTION 
Psoriatic arthritis is a common, chronic inflammatory disease characterized by a series of linked 
cellular changes in the skin. Bimekizumab (UCB4940; the IMP) is an engineered, humanized 
full length monoclonal antibody of immunoglobulin G1 subclass that selectively and potently 
inhibits the activity of interleukin (IL)-17A and IL-17F in vitro. Interleukin-17A and IL-17F are 
key proinflammatory cytokines believed to play important roles in autoimmune and 
inflammatory diseases. Bimekizumab is being developed for the treatment of patients with 
inflammatory diseases such as PsA, psoriasis, and axial spondyloarthritis. 
It is important for patients who may use bimekizumab for the treatment of active PsA to have 
options for the self-injection of bimekizumab that fit their needs and preferences. Whilst some 
patients may prefer to manually regulate various tasks comprising the self-injection process (eg, 
needle visibility of skin penetration by needle, control speed of self-injection), others may prefer 
a more automated process (eg, do not wish to see the needle, desire an automatic injection). UCB 
therefore intends to provide patients with two different options to self-inject bimekizumab. 
The DV0004 study is a substudy of the PA0012 study. PA0012 will evaluate the long-term 
safety, tolerability, and efficacy of bimekizumab in subjects with PsA; study personnel will 
administer bimekizumab in a 1mL PFS (except at specified study visits at which subjects may 
self-administer). The DV0004 substudy will evaluate 2 self-injecting device presentations: the 
1mL bimekizumab-SS-1mL and the 1mL bimekizumab-AI-1mL. Subjects will begin the 
DV0004 substudy and the PA0012 study at the same time. The DV0004 substudy will include all 
PA0012 study assessments from Baseline to Week 4 (inclusive). However, subjects in the 
DV0004 substudy will self-administer bimekizumab at Baseline and at Week 4. 
In the DV0004 substudy, the self-injecting device presentations are drug product (IMP) 
associated with a functional secondary packaging (either the bimekizumab-SS-1mL or 
bimekizumab-AI-1mL). The bimekizumab-SS-1mL and the bimekizumab-AI-1mL are each 
single integral units which are intended exclusively for use in the given combination and are not 
reusable. Therefore, compliance to the EU Medical Device Regulation (except for Annex 1) and 
European Conformity marking (CE marking) is not foreseen. Full descriptions of the 2 devices 
are provided in Section 7.1.1 and Section 7.1.2, respectively. 
The proposed study is planned to demonstrate that adult subjects with PsA can safely and 
effectively self-inject bimekizumab using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL. 
3 
STUDY OBJECTIVES 
3.1 
Primary objective 
The primary objective of the study is to evaluate for each self-injecting device presentation the 
ability of subjects with PsA to safely and effectively self-inject bimekizumab 4 weeks after 
training in self-injection technique using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL. 
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3.2 
Secondary objective 
The secondary objective of the study is to evaluate the ability of subjects with PsA to safely and 
effectively self-inject bimekizumab immediately after training in self-injection technique using 
the bimekizumab-SS-1mL or the bimekizumab-AI-1mL. 
3.3 
Other objectives 
Other objectives of the study are to evaluate the following: 
• Subject experience of self-injection as assessed by the pain visual analog scale (VAS) for 
injection site pain and the Self-injection Assessment Questionnaire (SIAQ) 
• Trough PK (trough bimekizumab) levels associated with self-injection using the test 
self-injecting device presentations, injection by study personnel using the 1mL PFS, injection 
site (abdomen or thigh), and BMI category (by tertile) 
• Immunogenicity of bimekizumab associated with self-injection using the self-injecting 
device presentations and injection by study personnel using the 1mL PFS 
• The structural and mechanical integrity of the bimekizumab-SS-1mL and the 
bimekizumab-AI-1mL after completion of self-injection 
• The functional integrity of the bimekizumab-SS-1mL and the bimekizumab-AI-1mL after 
completion of self-injection 
• The overall safety and tolerability of self-injections using the self-injecting device 
presentations 
4 
STUDY VARIABLES 
4.1 
Outcome variables 
4.1.1 
Primary outcome variable 
The primary outcome variable is the ability to self-administer safe and effective injections using 
the bimekizumab-SS-1mL or the bimekizumab-AI-1mL at Week 4. Safe and effective 
self-injection will be evaluated by the study personnel and is defined as: 
• Complete dose delivery: Subject self-injects the complete dose of bimekizumab as confirmed 
by a visual inspection of the bimekizumab-SS-1mL or the bimekizumab-AI-1mL which 
shows that the IMP is delivered completely (ie, container is empty), and 
• No ADEs that would preclude continued use of the device presentations for self-injection 
(ie, no SADEs and/or ADEs leading to withdrawal from the DV0004 substudy). 
4.1.2 
Secondary outcome variable 
The secondary outcome variable is the ability to self-administer safe and effective injections 
using the bimekizumab-SS-1mL or the bimekizumab-AI-1mL at Baseline (the first self-injection 
visit, immediately after training in self-injection technique). Safe and effective self-injection will 
be evaluated by study personnel and is defined using the same criteria as the primary outcome 
variable (see Section 4.1.1). 
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4.1.3 
Other variables 
4.1.3.1 
Outcome variables 
The other outcome variables are: 
• Responses to pre-injection SIAQ (versions 2.0 and 2.1) at Baseline 
Whenever SIAQ is assessed, version 2.0 of the SIAQ will be used to assess 
bimekizumab-SS-1mL and version 2.1 of the SIAQ will be used to assess 
bimekizumab-AI-1mL (see Section 9.1). 
• Injection site pain (using a VAS; 100mm) by visit after self-injection using the assigned 
self-injecting device presentations at Baseline and Week 4 
• Responses to post-injection SIAQ (versions 2.0 and 2.1) by visit following self-injection 
using the assigned self-injecting device presentations at Baseline and Week 4 
• The structural and mechanical integrity of the bimekizumab-SS-1mL and the 
bimekizumab-AI-1mL after completion of self-injection using the assigned self-injecting 
device presentations 
• The functional integrity of the bimekizumab-SS-1mL and the bimekizumab-AI-1mL after 
completion of self-injection using the assigned self-injecting device presentations 
4.1.3.2 
Pharmacokinetic variable 
The PK variable is trough PK (bimekizumab) levels associated with self-injection using the test 
self-injecting device presentations, injection by study personnel using the 1mL PFS, injection 
site (abdomen or thigh), and BMI category (by tertile). Trough levels will be assessed at 
Baseline, Week 4, and Week 8 (in PA0012). 
4.1.3.3 
Immunological variable 
The immunological variable is the anti-bimekizumab antibody, which will be collected as 
described in the PA0012 protocol. 
4.1.3.4 
Safety variable 
The other safety variable is the occurrence of ADEs. Additional safety and tolerability variables 
will be collected as described in the PA0012 protocol. 
5 
STUDY DESIGN 
5.1 
Study description 
DV0004 is a Phase 3, multicenter, open-label, randomized, noncomparator, North America and 
Europe substudy to PA0012. PA0012 will evaluate the long-term safety, tolerability, and 
efficacy of bimekizumab in adult subjects with PsA. In the DV0004 substudy, the safe and 
effective use of the bimekizumab-SS-1mL or the bimekizumab-AI-1mL for the sc self-injection 
of bimekizumab solution by adult subjects with PsA will be evaluated. 
Subjects from sites in the PA0012 feeder studies, PA0010 and PA0011, will be eligible for the 
DV0004 substudy. The DV0004 substudy will maintain all study assessments of the main 
PA0012 study from Baseline to Week 4 (inclusive). However, only subjects in the DV0004 
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substudy will self-administer bimekizumab using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL at Baseline and Week 4. At DV0004 Baseline, each subject will be 
provided with training in self-injection and will receive the instructions for use (IFU) and any 
other applicable training materials. Subjects in the DV0004 substudy will perform self-injections 
at the DV0004 Baseline (corresponding to the Entry Visit of PA0012) with a subsequent 
self-injection at the DV0004 Week 4 Visit (corresponding to Week 4 of PA0012). 
During the 4-week Treatment Period of DV0004, subjects will receive bimekizumab 160mg 
Q4W. This dose regimen will remain stable for the entire 4-week Treatment Period of DV0004 
(consistent with PA0012). The DV0004 substudy will evaluate 2 self-injecting device 
presentations: the bimekizumab-SS-1mL and the bimekizumab-AI-1mL. Baseline for DV0004 
and the Entry Visit for PA0012 will occur at the same time, and the same interactive response 
technology (IRT) will be used for both studies. 
Eligible subjects will be randomly assigned in a 1:1 ratio to perform self-injection using either 
the bimekizumab-SS-1mL or the bimekizumab-AI-1mL (see Section 7.10). Subjects will 
perform self-injection with the assigned device presentation at Baseline (corresponding to the 
Entry Visit of PA0012) and at Week 4 (corresponding to Week 4 of PA0012). 
At Baseline, Week 4, and Week 8 (of PA0012), pre-injection blood samples for PK trough 
analysis will be collected. At Baseline and Week 4, subjects will self-inject 160mg bimekizumab 
using the assigned device presentation. Bimekizumab PK trough levels associated with injection 
by study personnel using the 1mL PFS (in PA0010 or PA0011) will be analyzed from the 
pre-injection PK sample collected at Baseline. Bimekizumab PK trough levels associated with 
subject self-injection using the assigned self-injecting device presentation will be analyzed from 
the pre-injection PK samples collected at Week 4 and Week 8 (of PA0012). 
In addition to self-injections, DV0004 substudy-specific assessments (eg, study personnel 
evaluation of safe and effective self-injection, VAS for injection site pain, SIAQ responses, and 
PK analyses; see Section 5.2) will be performed from Baseline through Week 4 (inclusive). An 
SFU telephone call will occur 1 week after the last self-administration in DV0004. 
After Week 5 of the DV0004 substudy, subjects will continue in PA0012 (the next visit after 
DV0004 completion will be the Week 8 Visit in PA0012). At Week 8 in PA0012, study 
personnel qualified in sc injection technique will administer bimekizumab to subjects in a 1mL 
PFS, or the subject/caregiver/appropriate designee will perform administration under the 
supervision of the site staff after training. Studies DV0004 and PA0012 will share a common 
database/electronic Case Report form (eCRF) system (including common adverse event [AE] 
reporting) and a common IRT. 
Subjects who are withdrawn from DV0004 but continue their PA0012 study participation will be 
required to perform an SFU telephone call 1 week after their final DV0004 dosing visit (see 
Section 6.3). Subjects who are withdrawn from bimekizumab treatment (PA0012 study) during 
the course of DV0004 will also be required to follow the PA0012 withdrawal procedures. 
5.1.1 
Study duration per subject 
The maximum DV0004 substudy duration will be 5 weeks for each subject. Subjects will then 
continue to receive treatment in PA0012 for the duration of the PA0012 study. 
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The end of the DV0004 substudy is defined as the date on which the last subject completes 
his/her Week 5 Visit or withdraws from the study. 
5.1.2 
Planned number of subjects and sites 
It is planned to enroll approximately 200 subjects; each device presentation arm will consist of 
approximately 100 subjects. It is anticipated that this study will involve up to 150 sites in North 
America and Europe. 
5.1.3 
Anticipated regions and countries 
This substudy will be conducted in North America and Europe. 
5.2 
Schedule of study assessments 
The schedule of assessments for DV0004 is presented in Table 5‒1 and includes assessments 
performed specifically in the DV0004 substudy. The schedule of assessment for PA0012 Entry 
Visit through Week 8 is presented in Table 5‒2 and includes assessments performed as part of 
the PA0012 study. 
 
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Table 5‒1: 
Schedule of study assessments for DV0004 
Visit a 
Week 
 
 
Procedures 
Visit 1 
Visit 2 
Visit 2a 
Telephone Call 
(Device SFU) 
Baseline/ Feeder Study 
Final Visit 
Week 4 
Week 5 
Informed consent for DV0004 assessments 
X 
 
 
Inclusion/exclusion 
X 
 
 
Concomitant medication 
X 
X 
X 
Adverse events b 
X 
X 
X 
Random assignment to device presentation 
X 
 
 
IRT contact 
X 
X 
X 
Subject training for VAS and SIAQ Questionnaire 
X 
 
 
Pre-injection SIAQ Questionnaire c 
X 
 
 
Subject training for self-injection 
X 
 
 
Subject self-injection of bimekizumab using the 
assigned device presentation 
X 
X 
 
Study personnel evaluation of self-injection 
X 
X 
 
Study personnel evaluation of post-use device 
presentation for visual signs of structural or mechanical 
integrity (such as cracks or loose parts) d 
X 
X 
 
VAS for injection site pain 
X 
X 
 
Post-injection SIAQ Questionnaire c 
X 
X 
 
Drug and device presentation accountability 
X 
X 
 
IRT=interactive response technology; SFU=safety follow-up; SIAQ=Self-injection Assessment Questionnaire; VAS=visual analog scale 
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) at all visits except Visit 2a (SFU telephone call). The SFU telephone call 
window is 7 days from the last dose in the DV0004 substudy, ±3 days. 
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Table 5‒1: 
Schedule of study assessments for DV0004 
Visit a 
Week 
 
 
Procedures 
Visit 1 
Visit 2 
Visit 2a 
Telephone Call 
(Device SFU) 
Baseline/ Feeder Study 
Final Visit 
Week 4 
Week 5 
b Adverse events not related to the device presentations will be reported in PA0012 and adverse device effects and device deficiencies will be reported in 
DV0004. A single safety database will be used for both studies. 
c Version 2.0 of the SIAQ will be used to assess bimekizumab-SS-1mL, while version 2.1 will be used to assess bimekizumab-AI-1mL (see Section 9.1). 
d Device presentations with visual signs of compromised structural or mechanical integrity should be returned to UCB after use. Used device presentations 
that functioned as intended (ie, complete dose delivered, no visual signs of compromised structural or mechanical integrity) should be stored at room 
temperature in a secured area and may only be destroyed following UCB’s instruction. 
 
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Table 5‒2: 
Schedule of study assessments for corresponding visits in PA0012 
Visit a 
Week 
 
Procedures 
Visit 1 
Visit 2 
Visit 3 
Entry Visit/ Feeder Study 
Final Visit 
Week 4 
Week 8 
Informed consent PA0012 assessments 
X 
 
 
Inclusion/exclusion 
X 
 
 
Concomitant medication 
X 
X 
X 
PHQ-9 
X 
 
 
eC-SSRS 
X 
X 
X 
Body weight 
X 
 
 
Vital signs (pulse, temperature, BP) b 
X 
X 
X 
ECG by central reader 
X 
 
 
Hematology/biochemistry/urine pregnancy c, d 
X 
X 
X 
Blood Sample for hs-CRP d 
X 
X 
X 
Blood sample for bimekizumab plasma concentrations c, d 
X 
X 
X 
Blood sample for anti-bimekizumab antibodies d 
X 
X 
X 
IGRA TB test 
X e 
 
 
TB questionnaire 
X 
 
 
Physical examination f 
X 
 
 
BSA affected by PSO (BSA palm method) 
X 
 
 
PASI g 
X 
 
 
IGA g 
X 
 
 
TJC (68) and SJC (66) 
X 
 
 
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Table 5‒2: 
Schedule of study assessments for corresponding visits in PA0012 
Visit a 
Week 
 
Procedures 
Visit 1 
Visit 2 
Visit 3 
Entry Visit/ Feeder Study 
Final Visit 
Week 4 
Week 8 
HAQ-DI 
X 
 
 
PtAAP 
X 
 
 
PhGA-PsA 
X 
 
 
PhGA-Arthritis 
X 
 
 
PGA-PsA 
X 
 
 
PGA-Arthritis 
X 
 
 
BASDAI 
X 
 
 
mNAPSI 
X 
 
 
LEI/SPARCC  
X 
 
 
LDI  
X 
 
 
PSAID-12 
X 
 
 
FACIT-F 
X 
 
 
SF-36 
X 
 
 
EQ-5D-3L 
X 
 
 
WPAI-SHP 
X 
 
 
Adverse events h 
X 
X 
X 
IRT contact 
X 
X 
X 
Bimekizumab administration by study personnel using 
the PFS 
 
 
X 
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Table 5‒2: 
Schedule of study assessments for corresponding visits in PA0012 
Visit a 
Week 
 
Procedures 
Visit 1 
Visit 2 
Visit 3 
Entry Visit/ Feeder Study 
Final Visit 
Week 4 
Week 8 
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BP=blood pressure; BSA=body surface area; ECG=electrocardiogram; eC-SSRS=electronic 
Columbia Suicide Severity Rating Scale; EQ-5D-3L=Euro-Quality of Life 5-Dimensions 3-level; FACIT-F=Functional Assessment of Chronic Illness 
Therapy—Fatigue; HAQ-DI=Health Assessment Questionnaire-Disability Index; hs-CRP=high sensitivity C-reactive protein; IGA=Investigator’s Global 
Assessment; IGRA=interferon-gamma release assay; IRT=interactive response technology; LDI=Leeds Dactylitis Index; LEI=Leeds Enthesitis Index; 
mNAPSI=modified Nail Psoriasis Severity Index; PASI=Psoriasis Area Severity Index; PGA-Arthritis=Patient’s Global Assessment of Arthritis; 
PGA-PsA=Patient’s Global Assessment of Psoriatic Arthritis; PhGA-Arthritis=Physician’s Global Assessment of Arthritis; PhGA-PsA=Physician’s Global 
Assessment of Psoriatic Arthritis; PHQ-9=Patient Health Questionnaire 9; PsAID=Psoriatic Arthritis Impact of Disease; PSO=psoriasis; PtAAP=Patient’s 
Assessment of Arthritis Pain; Q4W=every 4 weeks; SF-36=Short Form 36-item Health Survey; SFU=safety follow-up; SIAQ=Self-injection Assessment 
Questionnaire; SJC=swollen joint count; SPARCC=Spondyloarthritis Research Consortium of Canada; TB=tuberculosis; TJC=tender joint count; 
VAS=visual analog scale; WPAI-SHP=Work Productivity and Activity Impairment Questionnaire-specific health problem 
a Visit windows are ±7 days from the scheduled visit day (relative to the first dose) at all visits with a minimum of 21 days and a maximum of 35 days in 
between bimekizumab doses. 
b Adverse events not related to the device presentations will be reported in PA0012 and adverse device effects and device deficiencies will be reported in 
DV0004. A single safety database will be used for both studies. 
c If there has been a delay in menses, perform a urine pregnancy test. 
dAll blood samples are to be taken prior to bimekizumab dosing. 
e This assessment only needs to be performed at study entry if an IGRA negative result is not available from less than 6 weeks prior to the first dose of open 
label bimekizumab. 
f Includes evaluation of signs and symptoms of active TB and risk for exposure to TB. 
g If the BSA affected by PSO was ≥3% at Baseline from PA0010 or PA0011, determine the PASI and IGA. 
h Adverse events not related to the device presentations will be reported in PA0012 and adverse device effects and device deficiencies will be reported in 
DV0004. A single safety database will be used for both studies. 
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5.3 
Schematic diagram 
The study schematic diagram for DV0004 is presented in Figure 5‒1. 
Figure 5‒1: Schematic diagram 
 
OLE=open-label extension; Ph3=Phase 3; PK=pharmacokinetic; W=Week 
Note: The DV0004 substudy ends after the Week 5 SFU phone call. The Week 8 pre-injection PK sample is 
collected in PA0012. 
5.4 
Rationale for study design and selection of dose 
DV0004 is a Phase 3, multicenter, open-label, randomized, noncomparator, North America and 
Europe substudy to PA0012 for subjects with PsA who will self-inject bimekizumab. PA0012 is 
a multicenter, open-label, long-term study to evaluate the safety, tolerability, and efficacy of 
bimekizumab in subjects with PsA who complete 1 of the Phase 3 feeder studies (PA0010, 
PA0011). 
It is expected that most individuals who will use commercial bimekizumab for the treatment of 
PsA will self-inject bimekizumab and also that these individuals will prefer to have options for 
the self-administration of their medication. DV0004 will therefore evaluate the safe and effective 
use of 2 different self-injecting device presentations: bimekizumab-SS-1mL and 
bimekizumab-AI-1mL. In addition, DV0004 will assess trough PK levels associated with 
self-injection using the test self-injecting device presentation, injection by study personnel using 
the 1mL PFS, injection site (abdomen or thigh), by anti-bimekizumab antibody status, and BMI 
category (by tertile). 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1 
Inclusion criteria 
To be eligible for DV0004, subjects must meet all of the following criteria: 
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form (ICF) for DV0004 is signed and dated by the subject. 
2. Subject fulfills all inclusion criteria for the PA0012 study. 
3. Subject is considered reliable and capable of adhering to the DV0004 protocol (eg, able to 
understand and complete questionnaires, able to use investigational self-injecting device 
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presentation according to the IFU, and able to adhere to the visit schedule) according to the 
judgment of the Investigator. 
4. Subject is willing to self-inject. 
6.2 
Exclusion criteria 
Subjects are not permitted to enroll in DV0004 if any of the PA0012 study exclusion criteria are 
met. 
6.3 
Withdrawal criteria 
Since DV0004 is a substudy of PA0012, all DV0004 withdrawal criteria are captured in the 
PA0012 protocol. There are no additional DV0004-specific withdrawal criteria beyond those that 
are described in PA0012. Subjects are free to withdraw from DV0004 at any time, without 
prejudice to their continued care. Subjects who withdraw from DV0004 but remain eligible for 
PA0012 (ie, subjects who have a medical condition or personal preference that precludes further 
self-injection) may continue in PA0012. These subjects must perform an SFU telephone call 
1 week after their last self-injection in DV0004. 
Subjects who are withdrawn from bimekizumab treatment during DV0004 will also be required 
to follow the PA0012 withdrawal procedures. 
7 
INVESTIGATIONAL MEDICINAL PRODUCT AND 
INVESTIGATIONAL DEVICE 
In the DV0004 substudy, the term IMP refers to the bimekizumab drug product. The term 
investigational self-injecting device presentation refers to 2 different investigational 
self-injecting device presentations (bimekizumab-SS-1mL and bimekizumab-AI-1mL) that are 
comprised of drug product (IMP) associated with a functional secondary packaging. 
7.1 
Description of device presentations 
At DV0004 Baseline, each subject will be provided with self-injection training and the IFU for 
the appropriate device presentation. 
7.1.1 
Bimekizumab-SS-1mL 
The bimekizumab-SS-1mL, shown in Figure 7-1, consists of the naked PFS (primary packaging 
containing bimekizumab drug product for all Phase 3 studies) and a customized
 
safety syringe for sc bimekizumab administration. 
The naked PFS is a glass, 1mL long, primary container with small round flange and a 27G 
half-inch staked needle containing 1mL of bimekizumab. The 
 safety syringe is a 
single-use platform device with a passive needle stick safety mechanism. To enhance the device 
usability, UCB has customized the external 
components including adding an 
over-cap and modifying the extended finger flange and plunger rod. 
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7.3 
Packaging 
The site will receive uniquely-numbered device presentations (bimekizumab-SS-1mL and 
bimekizumab-AI-1mL) for use in the DV0004 substudy. 
7.4 
Labeling 
Clinical drug and device presentation supplies will be labeled in accordance with the current 
International Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and 
Good Manufacturing Practice and will include any locally required statements. If necessary, 
labels will be translated into the local language. 
7.5 
Handling and storage requirements 
The device presentation that houses the naked PFS including IMP must be securely stored at 
2ºC to 8ºC (ie, in a refrigerator), that is either in a locked room or in the pharmacy. Appropriate 
storage conditions must be ensured by controlling refrigerator temperature by using either an 
automated temperature monitoring and recording system or a minimum/maximum thermometer 
and completing a daily temperature log in accordance with local requirements. If an out-of-range 
temperature is noted, the Sponsor or designee must be notified so that a determination can be 
made whether the product should be used or not. 
The Investigator or hospital pharmacist is responsible for the appropriate storage and 
accountability of the device presentation at the site, as well as, for the documentation of 
appropriate storage and accountability. Refer to the IMP Handling Manual for additional 
information on handling and storage requirements. 
7.6 
Drug and device presentation accountability 
The Investigator will receive numbered treatments that will be assigned to eligible subjects by an 
IRT at Baseline. All IMP administrations will be observed by the Investigator or his/her 
appropriately trained designee. 
Appropriate accountability forms that reflect the receipt and use of the IMP and the device 
presentations will be supplied to the investigational site. Details of any loss of the self-injection 
device presentations due to breakage or wastage, non-use, destruction at the study site, or return 
to the Sponsor or designee must also be recorded on these 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 
IMP and device presentations until returned to UCB. Used or partially used devices are to be 
stored at room temperature in a secured area and may only be destroyed following UCB’s 
instruction. Devices with noted deficiencies (see Section 11.1.1.3) are to be returned to UCB 
immediately. The Investigator may assign some of the Investigator’s duties for drug 
accountability at the study site to an appropriate pharmacist/designee. 
The IMP and device presentations intended for the study cannot be used for any other purpose 
than that described in this protocol. 
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7.7 
Procedures for monitoring subject compliance 
During the Treatment Period of this study, IMP administration (self-administration) will be 
performed in the clinic and observed by the Investigator or his/her designee; monitoring subject 
compliance is therefore not applicable. 
7.8 
Concomitant medications/treatments 
Any specifications given in PA0012 regarding permitted and prohibited concomitant medications 
must be followed. 
7.8.1 
Permitted concomitant treatments (medications and therapies) 
Unless otherwise specified in PA0012, subjects are permitted to continue their prescribed 
medical therapy for the disease in accordance with the instructions of their treating physician. 
Concomitant medications and therapies, including over-the-counter products and supplements, 
must be recorded in the subject’s notes (source documentation) and provided 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. 
7.8.2 
Prohibited concomitant treatments (medications and therapies) 
In addition to the prohibited treatments described in PA0012, subjects are not permitted to use 
topical analgesics at the injection site at Baseline or Week 4 in the DV0004 substudy. 
7.9 
Blinding 
This is an open-label substudy. 
7.10 
Randomization and numbering of subjects 
The same unique 5-digit identification number used in the feeder study will be used in PA0012 
and in substudy DV0004. This subject number will be used to identify the subject throughout 
PA0012 and DV0004 and to maintain subject confidentiality. At study visits, an IRT will assign 
the applicable subject kits of IMP. Further instructions will be provided in the IRT manual. 
The IRT will generate individual assignments for the self-injection device presentations. Eligible 
subjects will be assigned to the device presentations based on a predetermined production 
randomization and/or packaging schedule provided by UCB (or designee). All eligible subjects 
will be randomly assigned to perform self-injection using either the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL at a 1:1 ratio. The IRT will allocate kit numbers to the subject based on 
the subject number during the study. 
Subject numbers and kit numbers will be tracked via the IRT. 
8 
STUDY PROCEDURES BY VISIT 
A general overview of the study assessments is provided in Table 5‒1 and Table 5‒2. Of note, 
DV0004 and PA0012 will share a common database/eCRF system (including common AE 
reporting) and a common IRT. 
The following visit windows are permitted: 
• As in PA0012, a 7-day visit window on either side of the scheduled dosing is permitted; 
however, the Investigator should try to keep the subjects on the original dosing schedule. 
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Changes to the dosing schedule outside of the 7-day window must be discussed with the 
Medical Monitor. 
• The SFU telephone call should occur within 7 days after the last dose in the DV0004 
substudy, ±3 days. 
8.1 
Treatment Period 
The DV0004 substudy will include all PA0012 study assessments from Baseline to Week 4 
(inclusive). All study procedures and assessments will be performed in accordance with 
Table 5‒1 and Table 5‒2. 
8.1.1 
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. 
At this visit, any of the following assessments may be performed, depending on the reason for 
the visit: 
• Record concomitant medication 
• Record AEs 
• If medically indicated, other assessments that are performed in PA0012 may be performed 
9 
ASSESSMENT OF SELF-INJECTION 
Evaluation of dose delivery and safe self-injection will be performed as described for the primary 
outcome variable (Section 4.1.1). 
9.1 
Assessment of injection site pain 
A VAS will be used to assess overall injection pain due to self-injection at Baseline and at 
Week 4. Subjects will be required to indicate their injection pain by placing a mark on a 100mm 
line from 0 (no pain) to 100 (worst possible pain). The subject will complete the VAS prior to 
completion of the post-injection SIAQ (refer to Section 9.1 for details). 
9.2 
Assessment of self-injection experience by SIAQ 
The SIAQ will be used to assess the subject’s self-injection experience. 
The SIAQ was developed by UCB to assess the perceived advantages and the potential 
limitations of self-injection of an sc medication (Keininger and Coteur, 2011). The pre-injection 
SIAQ is composed of 7 items grouped into 3 domains (feelings about injection, self-confidence, 
and satisfaction with the current mode of administration). The post-injection SIAQ is composed 
of 21 items grouped into 6 domains (feelings about injection, self-image, self-confidence, 
injection site reactions, ease of use, and satisfaction with self-injection). The pre-injection SIAQ 
will be completed at Baseline and the post-injection SIAQ will be completed within 30 minutes 
after each self-injection (ie, at Baseline and Week 4). 
Version 2.0 and version 2.1 of the SIAQ are identical, except for Question 11. In version 2.0 of 
the SIAQ, Question 11 discusses the use of a plunger, while in version 2.1 of the SIAQ, 
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Question11 discusses depression of the device. Version 2.0 will therefore be used to assess 
bimekizumab-SS-1mL, while version 2.1 will be used to assess bimekizumab-AI-1mL. 
9.3 
Evaluation of post-use structural, mechanical, and functional 
integrity of self-injecting device presentations 
Visual inspection of the used bimekizumab-SS-1mL and bimekizumab-AI-1mL devices will be 
performed by appropriately trained site staff to check for any signs of compromised structural or 
mechanical integrity (ie, clear evidence of damage, such as cracks or loose parts, and not any 
superficial, cosmetic imperfections, such as scratches or smudges, which have no impact on 
structural or mechanical integrity). Any device with compromised structural or mechanical 
integrity will be returned to UCB for further evaluation. The bimekizumab-SS-1mL and 
bimekizumab-AI-1mL have a lockout feature, which is activated upon completion of the 
injection and which ensures the needle guard is in position permanently to prevent post-use 
needle stick injuries. Devices determined to not have the lockout feature in place, as detailed in 
the IMP Handling Manual, will be packaged and returned to UCB for further evaluation. 
10 
ASSESSMENT OF PHARMACOKINETIC AND 
IMMUNOLOGICAL VARIABLES 
Blood samples for measurement of trough bimekizumab PK and anti-bimekizumab antibodies 
(Section 4.1.3) will be collected at the time points specified in the schedule of study assessments 
(Table 5‒1 and Table 5‒2). 
At dosing visits, blood samples will be drawn prior to dosing (at the same time of the sampling 
for clinical laboratory tests in PA0012). 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 PA0012). Detailed information on sample analysis will be 
provided in a bioanalytical report. 
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11 
ASSESSMENT OF SAFETY 
11.1 
Adverse events (device presentations) 
All AEs (including serious adverse events [SAEs]) will be reported in a common database for 
PA0012 and DV0004, but only ADEs, SADEs, and device deficiencies will be summarized in 
the DV0004 substudy. Specifically, only those AEs related to the use of the device presentations 
bimekizumab-SS-1mL or bimekizumab-AI-1mL (based on the Investigator’s judgement) will be 
assessed. All AEs (including SAEs) which are not assessed to be related to the device 
presentations will be summarized separately in the report for the main study, PA0012; please 
refer to the PA0012 protocol for information on reporting and recording AEs (including SAEs). 
11.1.1 
Definitions (device presentations) 
11.1.1.1 
Adverse device effect (device presentations) 
An ADE is an AE related to the use of a device presentation. An ADE must meet 1 or more of 
the following criteria: 
• Adverse event resulting from insufficiencies or inadequacies in the IFU, the deployment, the 
implantation, the installation, the operation, or any malfunction of the investigational medical 
device. 
• Adverse event that is a result of a use error or intentional misuse of the device presentation. 
11.1.1.1.1 
Unanticipated adverse device effect 
An unanticipated ADE is an ADE which by its nature, incidence, severity, or outcome has not 
been previously identified. 
11.1.1.2 
Serious adverse device effects 
A SADE is an ADE that has resulted in any of the consequences characteristic of an SAE. 
An SAE (and therefore a SADE) 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, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.) 
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• Initial inpatient hospitalization or prolongation of hospitalization 
(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.) 
11.1.1.2.1 
Anticipated and unanticipated serious adverse device effects 
An anticipated SADE is a SADE which by its nature, incidence, severity, or outcome has been 
identified in the risk analysis report (ISO 14155). 
An unanticipated serious adverse device effect (USADE) is a SADE which by its nature, 
incidence, severity, or outcome has not been identified in the current version of the risk analysis 
report. 
The Sponsor will determine if a SADE qualifies as an USADE. The Sponsor will also evaluate 
all SADEs to ensure that expedited reporting requirements are met according to UCB Standard 
Operating Procedures (SOPs) and applicable country-specific regulatory requirements for the 
device presentation. 
11.1.1.3 
Device deficiency (device presentations) 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. Device deficiencies include malfunctions, use 
errors, and inadequate labeling. 
11.1.2 
Procedures for reporting and recording adverse device effects and 
device deficiencies 
The subject will be given the opportunity to report ADEs, SADEs, and device deficiencies 
spontaneously. A general prompt will also be given at each study visit to detect AEs that qualify 
as ADEs, SADEs, and device deficiencies. Below is an example prompt: 
“Did you notice anything unusual about the injection?” 
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11.1.2.1 
Reporting of adverse device effects 
All ADEs and SADEs will be captured on the eCRF. The eCRF will allow Investigators to 
specify whether an AE or SAE is device-related and will clarify which device presentation is 
associated with the ADE or SADE. 
An Investigator Adverse Device Effect and Device Deficiency form will be provided to the 
Investigator. The Investigator Adverse Device Effect and Device Deficiency form must be 
completed in English. 
The Investigator (or designee) shall report all SADEs and device deficiencies that might have led 
to an SAE (if suitable action had not been taken, if intervention had not been made, or if 
circumstances had been less fortunate) to UCB within 24 hours after knowledge of the event 
using the appropriate forms in the electronic data capture system. When required by national or 
local regulations, the Investigator shall also notify the IRB/IEC and regulatory agencies of all 
reportable events according to national regulations in acceptable timely conditions, and may also 
be requested by the IRBs to provide annual reports. 
11.1.2.2 
Reporting of device deficiencies 
If a device deficiency related to the identity, quality, durability, reliability, safety, or performance 
of the device presentation is reported (even if the device presentation was not used), UCB must 
be informed within 1 business day (within 24 hours, as a rule) of receipt of this information by 
the site. The Investigator must forward to UCB (or designee) a duly completed Investigator 
Adverse Device Effect and Device Deficiency form provided by UCB, even if the data are 
incomplete or if it is obvious that more data will be needed to draw any conclusions. 
An Investigator Adverse Device Effect and Device Deficiency form will be provided to the 
Investigator. The Investigator Adverse Device Effect and Device Deficiency form must be 
completed in English. 
It is important for the Investigator, when completing the Investigator Adverse Device Effect and 
Device Deficiency form, to include an assessment and documentation of whether the device 
deficiency could have led to an SAE if any of the following occurred: 
• Suitable action had not been taken, or 
• Intervention had not been made, or 
• Circumstances had been less fortunate. 
All defective devices must be returned to UCB according to standard procedures (see 
Section 7.6). 
11.1.2.3 
Reporting of serious adverse device effects including device 
deficiencies with risk of serious adverse event 
If a device deficiency that could have led to an SAE (if suitable action had not been taken, or 
intervention had not been made, or circumstances had been less fortunate) is reported, UCB must 
be informed within 24 hours of receipt of this information by the site (see contact information for 
SAE reporting listed in the Serious Adverse Event Reporting section at the front of the protocol). 
The Investigator must forward to UCB (or designee) a duly completed “Investigator SAE Report 
Form for Investigational Medical Devices” provided by UCB, even if the data are incomplete, or 
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if it is obvious that more data will be needed to draw any conclusions. Information recorded on 
this form will be entered into the global safety database. 
An Investigator SAE Report Form for Investigational Medical Devices will be provided to the 
Investigator. The Investigator SAE Report Form for Investigational Medical Devices must be 
completed in English. 
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 for Investigational Medical Devices. 
The Investigator is specifically requested to collect and report to UCB (or designee) any ADEs 
or SADEs up to completion of the follow-up visit/telephone call for each subject, and to also 
inform participating subjects of the need to inform the Investigator of any ADEs or SADEs 
within this period. Serious AEs that the Investigator thinks may be associated with the device 
presentation must be reported to UCB regardless of the time between the event and the end of the 
study. 
Upon receipt of the Investigator SAE Report Form for Investigational Medical Devices, UCB 
will perform an assessment of whether the SADE is anticipated based on the current version of 
the risk analysis report. 
11.1.2.4 
Rule for repetition of an adverse device effect, serious adverse 
device effect, and/or device deficiency 
An increase in the intensity of an ADE or SADE should lead to the repetition of the ADE or 
SADE being reported with: 
• The outcome date of the first ADE or SADE that is not related to the natural course of the 
disease being the same as the start date of the repeated ADE or SADE, and the outcome of 
“worsening.” 
• The ADE or SADE verbatim term being the same for the first and repeated ADE or SADE, 
so that the repeated ADE or SADE can be easily identified as the worsening of the first one. 
11.1.3 
Follow up of adverse device effects and serious adverse device 
effects 
All ADEs and SADEs should be followed until they have resolved, have stable sequelae, the 
Investigator determines that they are no longer clinically significant, or the subject is lost to 
follow up. 
If an ADE or SADE 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. 
Information on SADEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time. 
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11.2 
Pregnancy 
All events of pregnancy or partner pregnancy will be followed and documented as described in 
the PA0012 protocol. 
11.3 
Suspected transmission of an infectious agent 
For the purposes of reporting, any suspected transmission of an infectious agent via medicinal 
products (device presentations or IMP) should be considered as an SAE or SADE; such cases 
must be reported immediately, recorded in the Adverse Event module of the eCRF, and followed 
as any other SAE or SADE. Any organism, virus, or infectious particle (eg, prion protein 
transmitting transmissible spongiform encephalopathy), pathogenic or nonpathogenic, is 
considered an infectious agent. 
There is no evidence that there is a risk of transmission of an infectious agent with the device 
presentations. 
11.4 
Overdose of investigational medicinal product 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SADE or nonserious ADE associated with excessive dosing must be 
followed as any other SADE or nonserious ADE. These events are only considered ADEs or 
SADEs if there are associated clinical signs and symptoms or if the act of taking the excess 
medicine itself is an ADE or SADE (eg, suicide attempt). 
There is no evidence that there is a risk of overdose with the IMP when used with the device 
presentations. 
11.5 
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 or the device presentation so that Investigators, clinical 
study subjects, regulatory authorities, and IRBs will be informed appropriately and as early as 
possible. 
The Study Physician (or medically qualified designee/equivalent) will conduct an ongoing 
review of SADEs and will perform ongoing SADE reconciliations in collaboration with the PS 
representative. Serious AEs not related to a device will be reported in PA0012. 
As appropriate for the stage of development and accumulated experience with the IMP and the 
device presentation, medically qualified personnel at UCB may identify additional safety 
measures (ie, vital signs) for which data will be periodically reviewed during the study. 
11.6 
Other safety measurements 
11.6.1 
Vital signs measurement 
No vital sign assessments will be performed for the DV0004 substudy. The vital sign 
assessments presented in Table 5‒2 will be captured as part of the PA0012 study and are 
described in the PA0012 protocol. 
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12 
EFFICACY ASSESSMENTS FOR PA0012 
No efficacy assessments will be performed for the DV0004 substudy. The efficacy assessments 
presented in Table 5‒2 will be captured as part of the PA0012 study and are described in the 
PA0012 protocol. 
13 
STUDY MANAGEMENT AND ADMINISTRATION 
13.1 
Adherence to protocol 
The Investigator should not deviate from the DV0004 protocol or the PA0012 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, or Sponsor. 
After implementation of such measure, the Investigator must notify the Clinical Project Manager 
of the Sponsor within 24 hours and follow any local regulatory requirements. 
13.2 
Monitoring 
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring SOPs, ICH-GCP 
guidelines, 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 contract 
research organization (CRO) or a contract monitor. 
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s). 
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities’ regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records. 
13.2.1 
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). 
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, electrocardiogram (ECG) or other printouts, completed scales, 
or quality of life questionnaires, for example. Source documents should be kept in a secure, 
limited access area. 
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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, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee). 
13.2.2 
Source data verification 
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 13.2.1. 
13.3 
Data handling 
13.3.1 
Case Report form completion 
This study is performed using remote data capture. The Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRFs and in all required reports. 
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Detailed instructions will be provided in the eCRF Completion Guidelines. 
13.3.2 
Database entry and reconciliation 
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used, in addition to manual review, to check for discrepancies and to ensure consistency 
of the data. The data are entered into the eCRFs 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. 
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13.3.3 
Subject Screening and Enrollment log/Subject Identification Code list 
The subject’s screening and enrollment will be recorded in the Subject Screening and 
Enrollment log. 
The Investigator will keep a Subject Identification Code list. This list will remain with the 
Investigator and be used for unambiguous identification of each subject. 
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation. 
13.4 
Termination of the study 
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity. 
The study may also be temporarily suspended or prematurely terminated in either of the 
following situations: 
• Severe or serious injection site reaction (eg, bleeding, bruising, pain) that, in the opinion of 
the Investigator, the overseeing IRB, or the Sponsor, is likely to be seen in other enrolled 
subjects who have not yet been injected with bimekizumab. 
• Unexpected device presentation malfunction leading to a failed or incomplete injection, or 
resulting in an SAE that, in the opinion of the Investigator, the overseeing IRB, or the 
Sponsor, is likely to be seen in other enrolled subjects who have not yet been injected with 
bimekizumab. 
If the study is prematurely terminated or suspended, UCB (or designee) 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 
used or unused IMP and other material in accordance with UCB procedures for the study. 
13.5 
Archiving and data retention 
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, informed consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data. 
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP or device presentations. 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 
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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. 
13.6 
Audit and inspection 
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities. 
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP and the device presentations have been processed and reported in compliance with the 
planned arrangements, the protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and 
applicable regulatory requirements. 
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee). 
13.7 
Good Clinical Practice 
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study. 
14 
STATISTICS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP). 
14.1 
Definition of analysis sets 
Two different Safety Sets (SS) will be generated (1 for each device presentation): the 
bimekizumab-SS-1mL Safety Set (SS-s) and the bimekizumab-AI-1mL Safety Set (SS-a). Each 
SS will consist of all subjects in the study who receive at least 1 dose of bimekizumab by the 
indicated self-injecting device presentations. Safety variables will be analyzed using the SS-s and 
SS-a. 
Two different Full Analysis Sets (FASs) will be generated (1 for each device presentation): the 
bimekizumab-SS-1mL Full Analysis Set (FAS-s) and the bimekizumab-AI-1mL Full Analysis 
Set (FAS-a). Each FAS will consist of all subjects in the SS-s or SS-a who self-inject at least 
1 dose of bimekizumab using the given device and who have an assessment of self-injection. All 
self-injection related endpoints will be analyzed using the FAS-s and FAS-a. 
Two different Pharmacokinetic Sets (PKS) will be generated (1 for each device presentation): the 
bimekizumab-SS-1mL PKS (PKS-s) and the bimekizumab-AI-1mL PKS (PKS-a). Each PKS 
will consist of all subjects who receive the same bimekizumab administration (frequency and 
dose) in the PA0012 feeder studies as in the DV0004 substudy and who have at least 1 evaluable 
PK assessment in the DV0004 substudy. Pharmacokinetic variables will be analyzed using the 
PKS-s and PKS-a. 
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14.2 
General statistical considerations 
This is an estimation study design with no formal statistical hypothesis testing. The study will 
estimate the true population proportion and/or mean of self-injection related endpoints for each 
device presentation separately. Summary statistics for continuous variables will include: number 
of available observations, mean, standard deviation, minimum, median, and maximum. For 
categorical variables, the number and proportion of subjects, along with the 90% confidence 
interval (CI) based on the Exact Binomial method, will be presented. 
The Baseline value is defined as the last nonmissing measurement prior to the first self-injection 
at Visit 1 (Baseline). No imputation of missing data will be performed. All data recorded in the 
eCRF and questionnaires will be listed. 
14.3 
Planned analyses of outcome variables 
All statistical analyses will be descriptive in nature. No inferential statistical analyses are 
planned. 
14.3.1 
Analysis of the primary outcome variable 
The primary outcome variable is the percentage of all subjects able to self-administer safe and 
effective injections using the given device presentation at Week 4. Safe and effective 
self-injection will be evaluated by the study personnel as defined in in Section 4.1.1. 
The number and percentage of subjects with safe and effective self-injections will be tabulated 
separately for each device presentation overall using the relevant FAS population (FAS-s or 
FAS-a). The 90% CIs based on the Exact Binomial method will be reported as well. 
14.3.2 
Analysis of the secondary outcome variable 
The secondary outcome variable is the percentage of subjects able to self-administer safe and 
effective injections using the given device presentation at Baseline (the first self-injection visit, 
immediately after training in self-injection technique). Safe and effective self-injection will be 
evaluated by the study personnel as defined in Section 4.1.1. 
The secondary outcome variables will be analyzed in the same manner as the primary outcome 
variable (see Section 14.3.1). 
14.3.3 
Analysis of other outcome variables 
The other outcome variables are defined in Section 4.1.3. These variables will be summarized 
using descriptive statistics and they will be tabulated separately for each device overall using the 
relevant FAS population (FAS-s or FAS-a). 
14.4 
Planned pharmacokinetic analyses 
The statistical analyses of the PK data will be descriptive in nature and will be summarized using 
the relevant device presentation-specific population (PKS-s or PKS-a). Data will be analyzed 
overall for each device presentation by injection type (self-administered or study 
personnel-administered), by injection site (abdomen or thigh), by anti-bimekizumab antibody 
status, and by BMI category. Three BMI categories will be defined based on tertiles derived 
from subjects’ Baseline BMI values. 
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To allow for an analysis of bimekizumab PK trough levels and anti-bimekizumab antibodies, 
blood samples will be taken before self-injection at the Baseline Visit (PK trough and 
anti-bimekizumab antibody analysis), Visit 2 Week 4 (PK trough analysis only), and Week 8 of 
PA0012 (PK trough and anti-bimekizumab antibody analysis). Anti-bimekizumab antibody 
status at or prior to the PK sampling (at Baseline, Week 4, and Week 8) will be used. The 
number and percentage of anti-bimekizumab antibody-positive and -negative subjects before 
self-injection (Baseline) and after self-injection (Week 8 of PA0012) will be summarized. 
Bimekizumab PK trough levels associated with injection by study personnel using the 1mL PFS 
(in PA0010 or PA0011) will be analyzed from the pre-injection PK sample collected at Baseline. 
Bimekizumab PK trough levels associated with subject self-injection using the assigned self-
injecting device presentation will be analyzed from the pre-injection PK samples collected at 
Week 4 and Week 8 (of PA0012). 
For the analysis of PK trough levels by injection site (abdomen or thigh) and by BMI category 
(by tertile), only self-administration PK trough levels will be used. 
14.5 
Planned safety analyses 
The safety variable is the occurrence of ADEs; additional safety and tolerability variables will be 
collected in PA0012 (see Section 4.1.3.4). Analyses of safety data will be done separately for 
each device presentation overall and within each device presentation using the relevant SS 
population (SS-s or SS-a). 
All ADE data will be listed and no statistical testing will be performed. Only treatment-emergent 
ADEs will be included in the summary tables. All ADEs will be coded and classified by system 
organ class, high level term, and preferred term according to the Medical Dictionary for 
Regulatory Activities v19.0. Adverse device effects will be summarized by the frequency and 
percentage of subjects having 1 or more of the events in question. Additional planned summaries 
include overall ADEs and SADEs. 
14.6 
Planned efficacy analyses 
No efficacy analyses are planned for the DV0004 substudy. 
14.7 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on the primary objective of the study. The criteria for identifying important 
protocol deviations and the classification of important protocol deviations will be defined within 
the project Data Cleaning Plan. To the extent feasible, the rules for identifying protocol 
deviations will be defined without review of the data and without consideration of the frequency 
of occurrence of such deviations. Whenever possible, criteria for identifying important protocol 
deviations will be implemented algorithmically to ensure consistency in the classification of 
important protocol deviations across all subjects. 
14.8 
Handling of dropouts or missing data 
There will be no special procedures for handling missing data. All imputation of missing or 
partial dates for safety assessments will be detailed in the SAP. 
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14.9 
Planned interim analysis and data monitoring 
No interim analysis is planned for the DV0004 substudy. 
14.10 
Determination of sample size 
This study will not be powered with respect to any endpoint, and sample size is based on 
practical considerations. In order to maintain blinding in the PA0012 feeder studies (PA0010 and 
PA0011), DV0004 will recruit all subjects who complete the PA0010 and PA0011 feeder studies 
(including those treated with a comparator or placebo in the feeder study) up to a total of about 
200 subjects. A total of 100 subjects (50 subjects per device presentation arm) are planned for 
PK trough level analyses, but these analyses will only be performed on subjects who were treated 
with bimekizumab 160mg Q4W (ie, not with placebo or comparator) in the feeder studies prior 
to rolling over into the DV0004 substudy. The DV0004 substudy will enroll approximately 
200 subjects (to compensate for subjects treated with placebo or comparator) to ensure that 
100 subjects with stable (160mg Q4W bimekizumab) PK trough levels are available for PK 
trough analysis. 
Subjects who enroll in the DV0004 substudy will be randomly assigned to the 
bimekizumab-SS-1mL or the bimekizumab-AI-1mL device presentation arms (each device 
presentation arm will consist of approximately 100 subjects). Within each device presentation 
arm, subjects will be divided into tertiles by BMI; there will be approximately 33 subjects per 
tertile, which is expected to yield approximately 16 to 17 subjects per tertile who are evaluable 
for steady state trough PK level analyses. 
15 
ETHICS AND REGULATORY REQUIREMENTS 
15.1 
Informed consent 
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator. 
Prior to participation in the study, the 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 US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form. 
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The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the 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. 
15.2 
Subject identification cards 
Upon signing the ICF, the subject will be provided with a subject identification card in the 
language of the subject. The Investigator will fill in the subject identifying information and 
medical emergency contact information. The Investigator will instruct the subject to keep the 
card with him/her at all times. 
15.3 
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, 
Investigator’s Brochure, 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 designee) 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 designee) with evidence of such IRB/IEC notification. 
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15.4 
Subject privacy 
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Visit 1. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study). 
15.5 
Protocol amendments 
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective. 
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB, and the regulatory authorities (if required), prior to being 
implemented. 
16 
FINANCE, INSURANCE, AND PUBLICATION 
Insurance coverage will be handled according to local requirements. 
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable. 
17 
REFERENCES 
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002. 
Keininger D, Coteur G. Assessment of self-injection experience in patients with rheumatoid 
arthritis: psychometric validation of the Self-Injection Assessment Questionnaire (SIAQ). 
Health and Quality of Life Outcomes. 2011;9:2. 
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18 
APPENDICES 
18.1 
Protocol Amendment 1 
The main purpose of this protocol amendment was to clarify study procedures and update the 
description of the IMP. 
Modifications and changes 
Global changes: 
The following changes were made throughout the protocol and are not included in specific 
changes section:  
• The company name was changed from UCB Biopharma SPRL to UCB Biopharma SRL 
• The term “legal representative” was deleted from protocol, as it is not applicable to DV0004 
or PA00012 
• Minor spelling, editorial, and formatting changes were made throughout the document  
 
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Specific changes: 
Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Change 1: Administrative section 
Study contact details 
  
UCB Celltech Ltd. 
208 Bath Road 
Slough SL1 3WE, UK 
 
  
UCB Celltech Ltd. 
208 Bath Road 
Slough SL1 3WE, UK 
UNITED KINGDOM 
The country name was added. 
 
... 
 
 
... 
 
The Clinical Project Manager has 
changed.  
 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
 
 
UCB BIOSCIENCES Inc. 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
 
The Clinical Trial Biostatistician 
has changed. 
Change 2: Minor updates to Schedule of study assessments for corresponding visits in PA0012 
Table 5-2 
h Only subjects affected by enthesitis 
or dactylitis at Baseline from 
PA0010 or PA0011. 
i 
Adverse events not related to the 
device presentations will be 
reported in PA0012 and adverse 
device effects and device 
deficiencies will be reported in 
DV0004. A single safety database 
will be used for both studies. 
h Only subjects affected by enthesitis 
or dactylitis at Baseline from 
PA0010 or PA0011. 
i 
Adverse events not related to the 
device presentations will be 
reported in PA0012 and adverse 
device effects and device 
deficiencies will be reported in 
DV0004. A single safety database 
will be used for both studies. 
Deleted original h footnote since 
there is no longer a restriction in 
PA0012 for LDI or LEI assessment 
to avoid potentially missing data. 
Analysis for LDI and LEI will still 
be performed on subjects having 
dactylitis or enthesitis at Baseline 
of PA0010 or PA0011. 
Footnote for adverse events moves 
from i to h. 
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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Change 3: Update schematic diagram 
Section 5.3,  
Figure 5-1 
Visit 3, Week 8 (in PA0012): 
• 
Pre-injection PK sample 
• 
Injection by study personnel  
OR self-injection after training 
Visit 3, Week 8 (in PA0012): 
• 
Pre-injection PK sample 
• 
Injection by study personnel  
OR self injection after training 
IMP administration at Week 8 
should be performed by study site 
staff only.  
Change 4: Update description of IMP  
Section 7.2 
Bimekizumab will be supplied at a 
concentration of 160mg/mL (55mM 
sodium acetate, 220mM glycine, 
0.04% polysorbate 80 at pH 5.0) for sc 
injection in the bimekizumab-SS-1mL 
or the bimekizumab AI 1mL device 
presentations. 
Bimekizumab will be supplied at a 
concentrationnominal formulation of 
160mg/mL (in 55mM sodium acetate, 
220mM glycine, and 0.04% 
polysorbate 80 at pH 5.0) for sc 
injection in the bimekizumab-SS-1mL 
or the bimekizumab AI 1mL device 
presentations. 
Updated to be consistent with other 
studies in bimekizumab clinical 
development program. 
 
 
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19 
DECLARATION AND SIGNATURE OF INVESTIGATOR 
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements. 
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol. 
I have received and read all study-related information provided to me. 
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially and will not be made available to third parties without prior authorization by UCB. 
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract. 
Investigator: 
 
 
  
Printed name 
 Date/Signature 
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20 
SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice. 
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SAP_001.pdf: 
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STATISTICAL ANALYSIS PLAN  
Study: DV0004 
Product: Bimekizumab 
NORTH AMERICA AND EU SUBSTUDY TO PA0012 
A MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO EVALUATE THE SAFE 
AND EFFECTIVE USE OF THE PREFILLED SAFETY SYRINGE OR AUTO-INJECTOR 
FOR THE SUBCUTANEOUS SELF-INJECTION OF BIMEKIZUMAB SOLUTION BY 
SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS 
 
SAP 
Date 
Final SAP  
16 Oct 2019 
SAP Amendment 
10 Jul 2020 
SAP Amendment 2 
12 Oct 2020 
SAP Amendment 3 
03 NOV 2021 
SAP Amendment 4 
16 DEC 2021 
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 .................................................................................................... 5 
1 
INTRODUCTION ............................................................................................................. 7 
2 
PROTOCOL SUMMARY ................................................................................................. 7 
2.1 
Study objectives ....................................................................................................... 7 
2.1.1 
Primary objective ........................................................................................... 7 
2.1.2 
Secondary objective ....................................................................................... 7 
2.1.3 
Other objectives ............................................................................................. 7 
2.2 
Study variables ......................................................................................................... 8 
2.2.1 
Outcome variables ......................................................................................... 8 
2.2.1.1 
Primary outcome variable .................................................................... 8 
2.2.1.2 
Secondary outcome variable ................................................................ 8 
2.2.1.3 
Other variables ..................................................................................... 8 
2.3 
Study design and conduct ........................................................................................ 9 
2.3.1 
Study description ........................................................................................... 9 
2.3.2 
Treatment Period .......................................................................................... 10 
2.3.3 
Safety Follow-Up ......................................................................................... 10 
2.3.4 
Withdrawal ................................................................................................... 10 
2.3.5 
Study duration per subject ........................................................................... 10 
2.3.6 
Planned number of subjects ......................................................................... 10 
2.4 
Determination of Sample Size ............................................................................... 10 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 11 
3.1 
General presentation of summaries and analyses .................................................. 11 
3.2 
General study level definitions .............................................................................. 12 
3.2.1 
Baseline values ............................................................................................ 12 
3.2.2 
Relative Day ................................................................................................ 12 
3.3 
Protocol deviations................................................................................................. 12 
3.4 
Analysis sets........................................................................................................... 13 
3.4.1 
Enrolled Set .................................................................................................. 13 
3.4.2 
Safety Set ..................................................................................................... 13 
3.4.3 
Full Analysis Set .......................................................................................... 13 
3.4.4 
Pharmacokinetic Per Protocol Set ................................................................ 13 
3.5 
Treatment assignment, treatment and device groups ............................................. 13 
3.6 
Center pooling strategy .......................................................................................... 14 
3.7 
Coding dictionaries ................................................................................................ 14 
3.8 
Changes to protocol-defined analyses ................................................................... 14 
3.8.1 
Changes related to COVID-19 ..................................................................... 15 
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4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 15 
4.1 
Adjustments for covariates .................................................................................... 15 
4.2 
Handling of dropouts or missing data .................................................................... 15 
4.3 
Interim analyses and data monitoring .................................................................... 16 
4.4 
Multicenter studies ................................................................................................. 16 
4.5 
Multiple comparisons/multiplicity ......................................................................... 17 
4.6 
Use of an efficacy subset of subjects ..................................................................... 17 
4.7 
Active-control studies intended to show equivalence ............................................ 17 
4.8 
Examination of subgroups ..................................................................................... 17 
4.9 
Additional study-specific information ................................................................... 17 
4.9.1 
COVID-19 category definition .................................................................... 17 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 17 
5.1 
Subject disposition ................................................................................................. 17 
5.1.1 
Impact of COVID-19 on subject disposition ............................................... 18 
5.2 
Protocol deviations................................................................................................. 18 
5.3 
Impact of COVID-19 ............................................................................................. 18 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 18 
6.1 
Demographics ........................................................................................................ 19 
6.2 
Other Baseline characteristics ................................................................................ 19 
6.3 
Medical history and concomitant diseases ............................................................. 20 
6.4 
Prior and concomitant medications ........................................................................ 20 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 20 
8 
EFFICACY ANALYSES ................................................................................................ 20 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 20 
9.1 
Pharmacokinetics ................................................................................................... 20 
9.2 
Immunogenicity ..................................................................................................... 21 
10 SAFETY ANALYSES ..................................................................................................... 23 
10.1 
Extent of exposure ................................................................................................. 23 
10.2 
Adverse events ....................................................................................................... 23 
10.2.1 
Adverse device effects ................................................................................. 23 
10.2.2 
Impact of COVID-19 on adverse events ...................................................... 24 
10.2.3 
Injection site reaction ................................................................................... 24 
10.3 
Clinical laboratory evaluations .............................................................................. 25 
10.4 
Vital signs, physical findings, and other observations related to safety ................ 25 
11 OTHER ANALYSES ...................................................................................................... 25 
11.1 
Primary outcome variable ...................................................................................... 25 
11.2 
Secondary outcome variable .................................................................................. 25 
11.3 
Other outcome variables ........................................................................................ 26 
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11.3.1 
Pre-injection SIAQ (versions 2.0 and 2.1) ................................................... 26 
11.3.1.1 
Additional Analyses for Pre-injection SIAQ summaries ................... 26 
11.3.2 
Post-injection SIAQ (versions 2.0 and 2.1) ................................................. 27 
11.3.2.1 
Additional Analysis for Post-injection SIAQ summaries .................. 27 
11.3.3 
Injection site pain ......................................................................................... 28 
11.3.3.1 
Additional Analysis for Injection site pain ........................................ 28 
11.3.4 
Structural and mechanical integrity of the devices ...................................... 28 
11.3.5 
Functional integrity of the devices ............................................................... 28 
12 REFERENCES ................................................................................................................ 29 
13 APPENDICES ................................................................................................................. 30 
13.1 
SAP Amendment 1 ................................................................................................ 30 
13.2 
SAP Amendment 2 ................................................................................................ 38 
13.3 
SAP Amendment 3 ................................................................................................ 43 
13.4 
SAP Amendment 4 ................................................................................................ 46 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 51 
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LIST OF ABBREVIATIONS 
ADAb 
anti-bimekizumab antibody 
ADE 
adverse device effect 
AE 
adverse event 
ATC 
anatomical therapeutic chemical 
bimekizumab-AI-1mL 
1mL bimekizumab auto-injector 
bimekizumab-SS-1mL 
1mL bimekizumab safety syringe 
BMI 
body mass index 
CI 
confidence interval 
CRF 
case report form 
CV 
coefficient of variation 
eCRF 
electronic case report form 
ES 
Enrolled Set 
ET 
early termination 
FAS 
Full Analysis Set(s) 
FAS-a 
Full Analysis Set for the bimekizumab-AI-1mL 
FAS-s 
Full Analysis Set for the bimekizumab-SS-1mL 
HLT 
high level term 
IFU 
instructions for use 
IMP 
investigational medicinal product 
LLOQ 
lower level of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
PFS 
prefilled syringe 
PK 
pharmacokinetic(s) 
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PK-PPS 
Pharmacokinetic Per Protocol Set 
PK-PPS-a 
Pharmacokinetic Per Protocol Set for the bimekizumab-AI-1mL 
PK-PPS-s 
Pharmacokinetic Per Protocol Set for the bimekizumab-SS-1mL 
PsA 
psoriatic arthritis 
PT 
preferred term 
Q4W 
every 4 weeks 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sc 
subcutaneous 
SD 
standard deviation 
SFU 
safety follow-up 
SIAQ 
Self-injection Assessment Questionnaire 
SOC 
system organ class 
SOP 
standard operating procedure 
SS 
Safety Set(s) 
SS-a 
Safety Set for the bimekizumab-AI-1mL 
SS-s 
Safety Set for the bimekizumab-SS-1mL 
TEADE 
treatment-emergent adverse device effect 
TEAE 
treatment-emergent adverse event 
USADE 
unanticipated serious adverse device effect 
VAS 
visual analog scale 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 
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1 
INTRODUCTION 
This statistical analysis plan (SAP) defines the scope of the statistical analyses and provides a 
detailed description of the statistical methodology for subject data obtained in this substudy of 
PA0012. The SAP is based on the following study documents:  
• Protocol amendment DV0004, 14 May 2020, 
• Electronic Case Report Form PA0012_DV0004 (v6.0), 03 June 2020.  
All references to the study protocol hereafter refer to this version of the protocol. 
To avoid premature unblinding of the PA0010 and PA0011 Feeder Study treatment allocation, a 
Blinding Maintenance Plan has been created for the PA0012/DV0004 studies. Please refer to this 
document for specifics regarding the handling of pharmacokinetic and pharmacodynamic data. 
The blinding plan is only applicable until both feeder studies have unblinded. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective of the study is to evaluate for each self-injecting device the ability of 
subjects with psoriatic arthritis (PsA) to safely and effectively self-inject bimekizumab 4 weeks 
after training in the self-injection technique using the 1mL bimekizumab safety syringe 
(bimekizumab-SS-1mL) or the 1mL bimekizumab auto-injector (bimekizumab-AI-1mL). 
2.1.2 
Secondary objective 
The secondary objective of the study is to evaluate the ability of subjects with PsA to safely and 
effectively self-inject bimekizumab immediately after training in the self-injection technique 
using the bimekizumab-SS-1mL or the bimekizumab-AI-1mL. 
2.1.3 
Other objectives 
Other objectives of the study are to evaluate the following: 
• Subject experience of self-injection as assessed by the pain visual analogue scale (VAS) for 
injection site pain and the Self-injection Assessment Questionnaire (SIAQ) 
• Trough pharmacokinetic (PK) (trough bimekizumab) levels associated with self-injection 
using the test self-injecting device, injection by study personnel using the 1mL prefilled 
syringe (PFS), injection site (abdomen or thigh), and body mass index (BMI) category (by 
tertile) 
• Immunogenicity of bimekizumab associated with self-injection using the self-injecting 
device presentations and injection by study personnel using the 1mL PFS 
• The structural and mechanical integrity of the bimekizumab-SS-1mL and the 
bimekizumab-AI-1mL after completion of self-injection 
• The functional integrity of the bimekizumab-SS-1mL and the bimekizumab-AI-1mL after 
completion of self-injection 
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• The overall safety and tolerability of self-injections using the self-injecting device 
presentations. 
2.2 
Study variables 
2.2.1 
Outcome variables 
2.2.1.1 
Primary outcome variable 
The primary outcome variable is the ability to self-administer safe and effective injections using 
the bimekizumab-SS-1mL or the bimekizumab-AI-1mL at Week 4.  
Safe and effective self-injection will be evaluated by the study personnel and is defined as: 
• Complete dose delivery: Subject self-injects the complete dose of bimekizumab as confirmed 
by a visual inspection of the bimekizumab-SS-1mL or the bimekizumab-AI-1mL, which 
shows that the investigational medicinal product (IMP) is delivered completely (i.e., 
container is empty), and 
• No adverse device events (ADEs) that would preclude continued use of the device for 
self-injection (i.e., no serious adverse device events [SADEs] and/or ADEs leading to 
withdrawal from the DV0004 substudy). 
2.2.1.2 
Secondary outcome variable 
The secondary outcome variable is the ability to self-administer safe and effective injections 
using the bimekizumab-SS-1mL or the bimekizumab-AI-1mL at DV0004 Baseline (for first self-
injection visit, immediately after training in the self-injection technique).  
Safe and effective self-injection will be evaluated by study personnel and is defined using the 
same criteria as the primary outcome variable (see Section 2.2.1.1).  
2.2.1.3 
Other variables 
2.2.1.3.1 
Outcome variables 
The other outcome variables are: 
• Responses to pre-injection SIAQ (versions 2.0 and 2.1) at DV0004 Baseline 
Whenever SIAQ is assessed, version 2.0 of the SIAQ will be used to assess 
bimekizumab-SS-1mL and version 2.1 of the SIAQ will be used to assess 
bimekizumab-AI-1mL. 
• Injection site pain (using a VAS; 100mm) by visit after self-injection using the assigned 
self-injecting device presentations at DV0004 Baseline and Week 4. 
• Responses to post-injection SIAQ (versions 2.0 and 2.1) by visit following self-injection 
using the assigned self-injecting device presentations at DV0004 Baseline and Week 4. 
• The structural and mechanical integrity of the bimekizumab-SS-1mL and the 
bimekizumab-AI-1mL after completion of the self-injection using the assigned self-injecting 
device presentations. This is based on a visual examination of the device that shows clear 
evidence of damage and/or compromised structural or mechanical integrity. 
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• The functional integrity of the bimekizumab-SS-1mL and the bimekizumab-AI-1mL after 
completion of self-injection using the assigned self-injecting device presentations. This is 
based on a visual examination of the device that shows clear evidence of damage and/or 
compromised functional integrity. 
2.2.1.3.2 
Pharmacokinetic variable 
The PK variable is trough PK (bimekizumab) levels associated with self-injection using the test 
self-injecting device presentations, injection by study personnel using the 1mL PFS, injection 
site (abdomen or thigh), and BMI category (by tertile). Trough levels will be assessed at DV0004 
Baseline, DV0004 Week 4, and PA0012 Week 8. 
2.2.1.3.3 
Immunological variable 
The immunological variable is the anti-bimekizumab antibody, which will be collected as 
described in the PA0012 study protocol. 
2.2.1.3.4 
Safety variable 
The other safety variable is the occurrence of ADEs. An ADE is an adverse event (AE) related to 
the use of an investigational device. An ADE must meet 1 or more of the following criteria: 
• Adverse event resulting from insufficiencies or inadequacies in the instructions for use (IFU), 
the deployment, the implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
• Adverse event that is a result of a use error or intentional misuse of the investigational 
device. 
Additional safety and tolerability variables will be collected as described in the PA0012 study 
protocol. 
2.3 
Study design and conduct 
2.3.1 
Study description 
DV0004 is a Phase 3, multicenter, open-label, randomized, noncomparator, North America and 
Europe substudy to PA0012. PA0012 will evaluate the long-term safety, tolerability, and 
efficacy of 160mg bimekizumab every 4 weeks (Q4W) in adult subjects with PsA; study 
personnel will administer bimekizumab to subjects in a 1mL PFS. The DV0004 substudy will 
evaluate 2 self-injection investigational devices: the 1mL bimekizumab-SS-1mL and the 1mL 
bimekizumab-AI-1mL.  
In the DV0004 substudy, the safe and effective use of the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL for the sc self-injection of bimekizumab solution by adult subjects with 
PsA will be evaluated. 
Subjects from selected sites in the PA0012 feeder studies, PA0010 and PA0011, will be eligible 
for the DV0004 substudy. The DV0004 substudy will maintain all study assessments of the main 
PA0012 study from DV0004 Baseline to Week 4 (inclusive). However, only subjects in the 
DV0004 substudy will self-administer bimekizumab using the bimekizumab-SS-1mL or the 
bimekizumab-AI-1mL at DV0004 Baseline and Week 4. At DV0004 Baseline, each subject will 
be provided with training in self-injection and will receive the IFU and any other applicable 
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training materials. Subjects in the DV0004 substudy will perform self-injections at the DV0004 
Baseline (corresponding to the Entry Visit of PA0012) with a subsequent self-injection at the 
DV0004 Week 4 Visit (corresponding to Week 4 of PA0012). 
2.3.2 
Treatment Period 
During the 4-week Treatment Period of DV0004, subjects will receive bimekizumab 160mg 
Q4W. This dose regimen will remain stable for the entire 4-week Treatment Period of DV0004 
(consistent with PA0012).  
Eligible subjects will be randomly assigned in a 1:1 ratio to perform self-injection using either 
the bimekizumab-SS-1mL or the bimekizumab-AI-1mL. Subjects will perform self-injection 
with the assigned device presentation at DV0004 Baseline (corresponding to the Entry Visit of 
PA0012) and at Week 4 (corresponding to Week 4 of PA0012). After Week 5 of the DV0004 
substudy, subjects will continue in PA0012 (the next visit after DV0004 completion will be the 
Week 8 Visit in PA0012).  
2.3.3 
Safety Follow-Up 
A device Safety Follow-up (SFU) telephone call will occur 1 week after the last 
self-administration (at Week 5). Subjects who are withdrawn from DV0004 but continue their 
PA0012 study participation will be required to perform an SFU telephone call 1 week after their 
final DV0004 dosing visit. 
2.3.4 
Withdrawal 
Subjects who are withdrawn from bimekizumab treatment (PA0012 study) during the course of 
DV0004 will also be required to follow the PA0012 withdrawal procedures that means subjects 
will undergo the Early Termination (ET) Visit assessments and will enter the SFU Period. 
2.3.5 
Study duration per subject 
The maximum DV0004 substudy duration will be 4 weeks for each subject. Subjects will then 
continue to receive treatment in PA0012 for the duration of the PA0012 study. The end of the 
DV0004 substudy is defined as the date on which the last subject completes his/her DV0004 
Week 4 Visit or withdraws from the study. 
2.3.6 
Planned number of subjects 
It is planned to enroll approximately 200 subjects; each device presentation arm will consist of 
approximately 100 subjects. It is anticipated that this study will involve up to 150 sites in North 
America and Europe. 
2.4 
Determination of Sample Size 
This study will not be powered with respect to any endpoint, and sample size is based on 
practical considerations. In order to maintain blinding in the PA0012 feeder studies (PA0010 and 
PA0011), DV0004 will recruit all subjects who complete the PA0010 and PA0011 studies 
(including those treated with a comparator or placebo in the feeder study) up to a total of about 
200 subjects. A total of 100 subjects (50 subjects per device presentation arm) are planned for 
PK trough level analyses, but these analyses will only be performed on subjects who were treated 
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with bimekizumab 160mg Q4W (i.e., not with placebo or comparator) to ensure that 100 subjects 
with stable (160mg Q4W bimekizumab) PK trough levels are available for PK trough analysis. 
Subjects who enroll in the DV0004 substudy will be randomly assigned to the 
bimekizumab-SS-1mL or the bimekizumab-AI-1mL device presentation arms (each device 
presentation arm will consist of approximately 100 subjects). Within each device presentation 
arm, subjects will be divided into tertiles by BMI; there will be approximately 33 subjects per 
tertile, which is expected to yield approximately 16 to 17 subjects per tertile who are evaluable 
for steady state trough PK level analyses (approximately 100 subjects in total). 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be performed using SAS Version 9.3 or higher. All tables and listings will use Courier New 
font size 9.  
Descriptive statistics will be displayed to provide an overview of the study results. For 
continuous variables, descriptive statistics will include number of subjects with available 
measurements (n), mean, standard deviation (SD), median, minimum, and maximum. 
For categorical variables, the number and proportion of subjects, will be presented. In addition, 
for the primary, secondary and other variables the 90% confidence interval (CI) based on the 
Exact Binomial, will also be presented. Unless otherwise noted, the denominator for percentages 
should be based on the number of subjects included in the respective analysis set. Subjects with 
missing data can generally be accounted for using either of the following approaches: 
• For summaries of demographics and Baseline characteristics: summarize percentages based 
on all subjects in the analysis set and include 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. 
• For summaries of outcome and safety variables, unless otherwise specified: percentages will 
be summarized based only on those subjects with observed data for the variable being 
summarized. As the denominator may be different from the number of subjects in the 
analysis set being considered, the denominator should be displayed in the table. The general 
format for displaying this will be “n/NSub (%)”, unless otherwise specified. 
Percentages will be presented to 1 decimal place. If the percentage is 100 or 0, no decimal will 
be presented. Typically, the % sign should be presented in the column header, but not with each 
individual value. 
For bimekizumab PK concentrations, summary statistics will include geometric mean, geometric 
coefficient of variation (CV), 95% confidence intervals for geometric mean, arithmetic mean, 
SD, median, minimum, and maximum. All summaries of PK variables will be based on the 
observed values. No imputation will be used. 
Decimal places for descriptive statistics will always apply the following rules: 
• “n” will be an integer 
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• Mean, SD, and median will use one additional decimal place compared to the original data 
• CV [%] will be presented with one decimal place 
• Minimum and maximum will have the same number of decimal places as the original value. 
Derived variables in general will display the mean, SD, and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied, then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics. 
A complete set of data listings containing all documented data as well as calculated data will be 
generated. 
3.2 
General study level definitions 
3.2.1 
Baseline values 
The DV0004 Baseline value is defined as the last non-missing measurement prior to the first 
self-injection at Visit 1 (Baseline). If a scheduled Baseline assessment is taken on the same day 
as the first administration of study medication, then the assessment will be assumed to have been 
performed prior to study medication. 
3.2.2 
Relative Day 
The relative day will be included in different listings and will be calculated as follows: 
• If the start (stop) date occurred on or after the first dose in DV0004, but prior to the drug 
stop date, relative day is calculated as start (stop) date minus first dose date + 1 
• If the start (stop) date occurred after the last dose of bimekizumab, the relative day to 
the most recent dose is calculated as start (stop) date minus most recent dose date. The 
relative day in this situation should be preceded by a ‘+’ 
• If the start (stop) date occurred before the first dose in DV0004, the relative day is calculated 
as start (stop) date minus first dose date. The relative day in this situation should be preceded 
by a ‘-’. 
Relative day will only be computed for fully completed dates and will be missing for partial 
dates. 
3.3 
Protocol deviations 
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on the primary objective of the study. The criteria for identifying important 
protocol deviations and the classification of important protocol deviations will be defined within 
the project Data Cleaning Plan. To the extent feasible, the rules for identifying protocol 
deviations will be defined without review of the data and without consideration of the frequency 
of occurrence of such deviations. Whenever possible, criteria for identifying important protocol 
deviations will be implemented algorithmically to ensure consistency in the classification of 
important protocol deviations across all subjects.  
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Following the declaration of the global COVID-19 pandemic by the World Health Organization 
in March 2020, protocol deviations will be identified as “related to COVID-19” where 
applicable.   
3.4 
Analysis sets 
3.4.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all subjects who have given informed consent for DV0004. 
3.4.2 
Safety Set 
Two different Safety Sets (SS) will be generated (1 for each device presentation): the 
bimekizumab-SS-1mL Safety Set (SS-s) and the bimekizumab-AI-1mL Safety Set (SS-a). Each 
SS will consist of all subjects in the study who receive at least 1 dose of bimekizumab by the 
indicated self-injecting device presentations. Safety variables will be analyzed using the SS-s and 
SS-a. 
3.4.3 
Full Analysis Set 
Two different Full Analysis Sets (FAS) will be generated (1 for each device presentation): the 
bimekizumab-SS-1mL Full Analysis Set (FAS-s) and the bimekizumab-AI-1mL Full Analysis 
Set (FAS-a). Each FAS will consist of all subjects in the SS-s or SS-a who self-inject at least 1 
dose of bimekizumab using the given device and who have an assessment of self-injection. All 
self-injection related endpoints will be analyzed using the FAS-s and FAS-a. 
3.4.4 
Pharmacokinetic Per Protocol Set 
Two different Pharmacokinetic Per Protocol Sets (PK-PPS) will be generated (1 for each device 
presentation): the bimekizumab-SS-1mL PK-PPS (PK-PPS-s) and the bimekizumab-AI-1mL 
PK-PPS (PK-PPS-a). Each PK-PPS will consist of all subjects who receive the same 
bimekizumab administration (frequency and dose) in the PA0012 feeder studies as in the 
DV0004 substudy and who have at least 1 evaluable PK assessment in the DV0004 substudy 
without important protocol deviations that would affect the concentration. Pharmacokinetic 
variables will be analyzed using the PK-PPS-s and PK-PPS-a. 
All PK assessments after baseline assessments from the feeder study will be considered for the 
one evaluable PK assessment. 
3.5 
Treatment assignment, treatment and device groups 
This is an open-label study and as such all subjects will be summarized according to the 
treatment that was assigned. The treatment group will be allocated in PA0012 and the device 
group will be allocated in DV0004. 
PA0012 treatment groups 
This refers to the study treatment assigned to the subject at the beginning of PA0012 and does 
not account for the treatment received in the relevant Feeder Study.  
All subjects will receive bimekizumab 160mg Q4W sc. 
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DV0004 device groups 
This refers to the study device assigned to the subject at the beginning of DV0004. The DV0004 
device groups are as follows: 
− Bimekizumab-SS-1mL 
− Bimekizumab-AI-1mL. 
The outcome variables will be summarized by assigned DV0004 device group. The different 
DV0004 device groups are reflected in the use of the corresponding analysis set SS-s, SS-a, 
FAS-s, FAS-a, PK-PPS-s and PK-PPS-a.  
3.6 
Center pooling strategy 
No pooling of centers is planned for this study. 
3.7 
Coding dictionaries 
All ADEs will be coded and classified by system organ class (SOC), high level term (HLT), and 
preferred term (PT) according version 19.0 of the Medical Dictionary for Regulatory Activities 
(MedDRA®). 
All medications other than the study drug will be classified by World Health Organization 
(WHO) Anatomical Therapeutic Chemical (ATC) classification, presenting Anatomical Main 
Group (ATC Level 1), Pharmacological Subgroup (ATC Level 3), and preferred term (PT), using 
version SEP/2015 of the World Health Organization Drug Dictionary (WHO-DD), according to 
UCB standard operating procedures (SOP). 
Previous and ongoing medical history will be classified by version 19.0 of MedDRA® SOC and 
PT. 
3.8 
Changes to protocol-defined analyses 
1. Study duration per subject in the protocol is specified as 5 weeks. In this document it is 
defined as 4 weeks. This accounts for 4 weeks of treatment. The additional week of Safety 
Follow-Up is still included in the allocation of adverse device events, which includes events 
occurring up to last dose + 7 days.  
2. The analysis sets to be used for the PK data have been amended from the PK Analysis set to 
the PK Per Protocol Analysis set (PK-PPS) throughout which will allow the exclusion of 
subjects with important protocol deviations related to PK from the primary analysis. 
3. Subjects who had important protocol deviations affecting the primary outcome variable, as 
confirmed during ongoing data cleaning meetings prior to database lock, will not be excluded 
from the FAS-s or FAS-a. 
4. The pharmacokinetic assessment of anti-bimekizumab antibody status will be measured 
before self-injection at DV0004 Baseline, and after self-injection at DV0004 Baseline and 
DV0004 Week 4 (the assessment is taken at Week 4 and Week 8 visits). This is different 
from the protocol, which incorrectly stated the following: 
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• Blood samples will be taken before self-injection at the Baseline Visit (PK trough and anti-
bimekizumab antibody analysis), Visit 2 Week 4 (PK trough analysis only) and Week 8 of 
PA0012 (PK trough and anti-bimekizumab antibody analysis). 
This text has been updated to the following as presented in Section 9.1: 
• […] blood samples will be taken before self-injection using the assigned self-injecting device 
presentation at the DV0004 Baseline Visit and DV0004 Week 4 (Visit 2), and before 
injection by site personnel at PA0012 Week 8 (Visit 3 of PA0012).  
3.8.1 
Changes related to COVID-19 
The impact of the COVID-19 pandemic on study procedures and/or conduct and on the primary 
safety endpoints (TEADEs, serious TEADEs, and study withdrawal due to TEADEs) will be 
investigated and additional outputs provided as appropriate. These analyses were not planned as 
part of the protocol as the pandemic scale was unprecedented. 
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) 
• Protocol deviations potentially related to COVID-19 (Section 5.2)  
• Impact of COVID-19 on study (Section 5.3 ) 
• Demographics, baseline characteristics (Sections 6.1 and 6.2 ) 
• Adverse events (Section 10.2.2) 
• Primary outcome variable (Section 11.1 ) 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
Not applicable. 
4.2 
Handling of dropouts or missing data 
For analyses of ADEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the ADE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for ADEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of ADEs or 
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed 
values will be displayed in data listings). 
Partial ADE and concomitant medication start dates will be imputed as follows:  
Imputation of Partial Start Dates 
• If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month 
• If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start date, then use the date of first dose 
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• If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use the 1st of January of the year of the start date 
• If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose 
• If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose. 
Imputation of Partial Stop Dates 
• If only the month and year are specified, then use the last day of the month 
• If only the year is specified, then use December 31st of that year 
• If the stop date is completely unknown, do not impute the stop date. 
If the imputed stop date is prior to the imputed start date:  
• For missing start day and start month:  
− If the year of start date is the same as the year of first dose and the imputed stop date is 
on or after the date of first dose, then set the start date to the date of first dose 
− Otherwise set to the 1st January of the year of the start date 
• For missing start day only 
− If the month and year of the start date is the same as the month and year of first dose and 
the imputed stop date is on or after the date of first dose, then set the start date to the date 
of first dose 
− If the month and year of the start date is the same as the month and year of first dose and 
the imputed stop date is before the date of first dose, then set the start date to the 1st of 
that month 
In the event of ambiguity or incomplete data which makes it impossible to determine whether a 
medication was concomitant, or an adverse event was treatment emergent, the medication will be 
considered as concomitant or the adverse event will be considered treatment emergent. 
If the intensity of an ADE is unknown, it will be considered as severe. If the relationship to study 
drug is missing, it is considered as related. 
There will be no special procedures for handling missing data for any other data points. 
4.3 
Interim analyses and data monitoring 
No interim analysis is planned for this study. No Data Monitoring Committee will be established 
for this study. 
4.4 
Multicenter studies 
Individual center results will not be directly presented. Centers are only located in North 
America and Europe. 
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4.5 
Multiple comparisons/multiplicity 
Not applicable. 
4.6 
Use of an efficacy subset of subjects 
Not applicable. 
4.7 
Active-control studies intended to show equivalence 
Not applicable. 
4.8 
Examination of subgroups 
Not applicable. 
4.9 
Additional study-specific information 
The subjects of DV0004 are ongoing subjects of PA0012. Data cut off for the final analysis in 
DV0004 will be after the follow-up of the last subject. Data cut off rules will be applied for 
ongoing ADEs and ongoing concomitant medication, such that any ADE or concomitant 
medication which has no stop date, or a stop date after the data cut off for DV0004 will be 
assigned as “Ongoing”. 
A number of parameters in the PA0012 and DV0004 studies have the potential to break the 
blinding of the feeder study treatment allocations. In order to safeguard against unscheduled 
unblinding of the PA0010 and PA0011 studies before their respective database locks, a blinding 
maintenance plan will be developed and implemented for DV0004 and PA0012. This will ensure 
both PA00012 & DV0004 remain blinded to feeder study treatment allocation, until after both 
feeder studies have been unblinded. This plan will document in detail how the DV0004 Data 
Evaluation Meetings and final delivery will be handled prior to Feeder Study unblinding.  
4.9.1 
COVID-19 category definition 
The coronavirus disease of 2019 (COVID-19) pandemic was declared by the WHO on 11 March 
2020. The worldwide pandemic restricted travel and had potential impact on ongoing clinical 
trials. The following definitions will be used to present pre-specified summaries: 
• Pre-pandemic: Events or assessments occurring before 11-Mar-2020 
• During pandemic: Events or assessments occurring on or after 11-Mar-2020 
A post-pandemic definition is not applicable to this short study. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The disposition of subjects including the number of subjects in ES and all device-specific 
analysis sets (SS-s, FAS-s, PK-PPS-s or SS-a, FAS-a, PK-PPS-a) will be summarized. This 
summary will be based on ES and will present subjects overall and by site and country/region 
(North America/Europe). 
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The number and percentage of subjects who entered the substudy, completed, discontinued with 
the reasons for discontinuation of the substudy will be presented. This summary will be based on 
the ES and will present all bimekizumab treated subjects broken out by DV0004 device group. 
The following listings for subject disposition will be produced based on the ES and presented by 
DV0004 device group: 
• A listing of subjects who did not meet the eligibility criteria 
• A listing of subject disposition 
• A listing of discontinuation 
• A listing of visit dates 
• A listing of subjects excluded from analysis sets 
• A listing of subject analysis sets 
5.1.1 
Impact of COVID-19 on subject disposition 
Subject disposition will also be summarized by COVID-19 enrollment period (pre- and during-
pandemic), as defined in Section 4.9.1.  The number of completed, missed and partial visits will 
be presented by COVID-19 enrollment period.  
5.2 
Protocol deviations 
A summary of number and percentage of subjects with an important protocol deviation 
(including a summary of subjects excluded from any analysis set due to important protocol 
deviations) by DV0004 device group will be provided for the SS-s and SS-a. A summary of 
COVID-19 related important device protocol deviations will be presented by visit for the SS-s 
and SS-a. COVID-19 related important protocol deviations will be identified by the prefix of 
“COVID” in the deviation verbatim text. 
By-subject listings of important protocol deviations and COVID-related important device 
protocol deviations will be provided separately. 
5.3 
Impact of COVID-19 
The impact of the COVID-19 pandemic on study procedures and conduct, such as missed/remote 
visits, interruption of study treatment, will be documented using the information collected on a 
dedicated eCRF page. The number and percentage of subjects impacted by COVID-19 will be 
presented overall and by country.  
A by-subject listing of the impact of COVID-19 on study visits will be provided. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
All summaries detailed in this section will be performed on the SS-a and SS-s. Demographics 
and other baseline characteristics will be extracted from the Feeder Study Baseline data. 
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6.1 
Demographics 
The following continuous variables will be summarized using descriptive statistics (number of 
subjects, mean, standard deviation (SD), minimum, median and maximum). 
• Age at the time of Feeder Study entry (years) 
• Height at Feeder Study Baseline (cm) 
• Weight (kg) at DV0004 Baseline: This will be derived from the weight from the last visit of 
the feeder study or DV0004 Entry Visit, since these visits will occur on the same day and 
weight is only collected once 
• DV0004 Baseline BMI (kg/m2) 
BMI (kg/m2) will be calculated as: 
𝐵𝑀𝐼=
𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔) 𝑎𝑡 𝐷𝑉0004 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒
[𝐻𝑒𝑖𝑔ℎ𝑡 (𝑚) 𝑎𝑡 𝐹𝑒𝑒𝑑𝑒𝑟 𝑆𝑡𝑢𝑑𝑦 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒]2 
The following categorical variables will be summarized using frequency counts and percentages: 
• Age group (≤18, 19-<65, ≥65 years) 
• Body Weight at DV0004 Baseline (≤100kg, >100kg) 
• BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2) 
• BMI tertiles (≤t1 kg/m2, >t1 kg/m2 to ≤t2 kg/m2,>t2 kg/m2) based on the respective PK 
populations (PK-PPS-s, PK-PPS-a) 
• Gender 
• Race 
• Ethnicity 
• Country 
By-subject listings of demographics will be provided. 
Demographics will also be summarized by COVID-19 enrollment period (pre- and during-
pandemic), as defined in Section 4.9.1.  
6.2 
Other Baseline characteristics 
Generally, the following continuous variables will be summarized using descriptive statistics 
(number of subjects, mean, SD, minimum, median and maximum): 
• Duration of disease (years) 
Duration of disease (years) will be calculated as: 
𝐷𝑖𝑠𝑒𝑎𝑠𝑒 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑟𝑎𝑛𝑑𝑜𝑚𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝐷𝑉0004 −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑜𝑛𝑠𝑒𝑡 𝑜𝑓 𝑃𝑠𝐴1)
365.25
 
1 If the date of onset of PsA is partial, it should be imputed to the most recent feasible date (i.e., 
last day of the month if only day is missing, or last day of the year if day and month are missing).  
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Baseline characteristics will also be summarized by COVID-19 enrollment period (pre- and 
during-pandemic), as defined in Section 4.9.1.  
6.3 
Medical history and concomitant diseases 
Previous and ongoing medical history from the feeder study will be based on SS-s and SS-a and 
summarized by system organ class (SOC) and preferred term (PT) using MedDRA®. Medical 
procedures are not coded.  
Previous and ongoing medical history will be presented in a by-subject listing for SS-s and SS-a, 
respectively. 
All medical conditions not yet occurred and reported in the feeder studies will be presented in a 
table and a by-subject listing for SS-s and SS-a, respectively. 
6.4 
Prior and concomitant medications 
Concomitant medication details are collected at each visit of DV0004. Concomitant medications 
are medications taken with at least one day in common with the DV0004 study medication 
dosing period (DV0004 Baseline to DV0004 Week 4). 
Imputation of missing start and stop dates are described in Section 4.2.  
All concomitant medication will be listed for SS-s and SS-a, respectively. 
Concomitant medication which started before DV0004 Week 4 and were ongoing at the data cut 
off will be included with the status remaining as ongoing. Concomitant medication which were 
ongoing at DV0004 Week 4 but with an end date before the data cut off will be included with 
their end date as recorded. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
During the Treatment Period of this study, IMP administration (either self-administration or 
study personnel-administration) will be performed in the clinic and observed by the Investigator 
or his/her designee; monitoring subject compliance is therefore not applicable. 
8 
EFFICACY ANALYSES 
No efficacy summaries are planned for the DV0004 substudy. 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
The statistical analyses of the PK data will be descriptive in nature and will be summarized using 
the relevant device presentation-specific population (PK-PPS-s or PK-PPS-a). Data will be 
analyzed overall for each device presentation by injection type (self-administered or study 
personnel-administered), by injection site (abdomen or thigh), by anti-bimekizumab antibody 
visit status, and by BMI category. Three BMI categories will be defined based on tertiles derived 
from subjects' DV0004 Baseline BMI values. See Section 9.2 for details on classification of anti-
bimekizumab antibody status.  
To allow for an analysis of bimekizumab PK trough levels, blood samples will be taken before 
self-injection using the assigned self-injecting device presentation at the DV0004 Baseline Visit 
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and DV0004 Week 4 (Visit 2), and before injection by site personnel at PA0012 Week 8 (Visit 3 
of PA0012).  
PK samples at DV0004 baseline will be summarized under administration by site personnel 
(since the previous dose was given by site personnel). PK samples associated with self-
administration (at Week 4 and Week 8), but where the previous injection was done by site 
personnel or care-giver, will be listed but not be used for summary statistics.   
Only pre-dose (trough) concentrations will be included while summarizing tables and figures. If 
the dosing for a visit is +/- 7 days out of window, then the plasma concentration from that visit 
will be excluded from the PK summary. PK samples are expected to be collected prior to dosing. 
PK samples collected >14 days after the preceding dose and no later than 1 hour after the current 
dose will be included in the summary. PK samples collected later than 1 hour after dosing will be 
excluded from summary statistics. PK results at visits following a previous non-dosing visit will 
be excluded from summary statistics. 
PK summaries will be based on observed values. No imputation will be used. However, if 
plasma concentration measurements are below the level of quantification, then for calculation of 
the derived statistics the result will be set to ½ of the lower level of quantification (LLOQ). 
Descriptive statistics including the geometric mean, geometric coefficient of variation, and 
geometric mean 95% confidence interval (CI) if applicable will be calculated if at least ⅔ of the 
values of interest are above the LLOQ. If this is not the case, only median, minimum, and 
maximum will be presented. Time from previous bimekizumab dose to DV0004 visit will be 
summarized by device presentation. 
A minimum of 3 values are required to calculate summary statistics. If only 2 values are 
available, then these should be presented as the minimum and maximum with other descriptive 
statistics reported as missing. 
Boxplots and summaries of plasma concentration will be presented by visit, by device 
presentation, and by cumulative ADAb status considering DV0004 alone and considering 
DV0004 and the feeder studies (see Section 9.2). Cumulative ADAb status is defined in Section 
9.2. Boxplots and summaries of plasma concentration will be presented by visit, by device 
presentation and by injection site, and by BMI tertile. 
All PK results will be listed. Baseline PK samples are the PK samples prior to first dose of 
Bimekizumab at DV0004 entry visit.  
In addition, the PK results from all subjects not in PK-PPS-s or PK-PPS-a will be listed based on 
the SS-a and SS-s. All concentrations will be listed as received, prior to any substitution of BLQ 
and LLOQ values. The listing will include flags for concentration that were excluded from the 
summary statistics, with the reason for exclusion. 
9.2 
Immunogenicity 
The immunological variable is anti-bimekizumab antibodies (ADAb) evaluated at DV0004 
Baseline and Week 4, and PA0012 Week 8 visits. To allow for an analysis of ADAb, blood 
samples will be taken before self-injection at the DV0004 Baseline Visit and DV0004 Week 4 
(Visit 2), and before injection by site personnel at PA0012 Week 8 (Visit 3 of PA0012). ADAb 
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status at or prior to the PK sampling (at DV0004 Baseline, DV0004 Week 4, and PA0012 Week 
8) will be used in the summaries. 
The ADAb will be assessed using a 3-tiered assay approach: Screening, confirmatory, and 
titration assays. Screening, confirmatory and titer cut points of the respective assays will be 
determined by the bioanalytical laboratory. The relevant statistical reports will be provided as 
part of the bioanalytical reports. 
The Screening cut point will be used to determine the ADAb status in the test sample as 
“Positive Screen” (PS) or “Negative Screen” (NS). For samples presenting anti-BKZ antibody 
levels that are PS, further confirmatory assay will be performed, and the result of which will be 
reported as either “Positive Immunodepletion” (PI) or “Negative Immunodepletion” (NI). 
Positive immunodepletion samples will be titrated, and the ADAb titer (reciprocal dilution factor 
including minimum required dilution [MRD]) reported. 
ADAb status for each visit will be derived as follows:  
− Sample values that are either NS or PS and NI, and where the BKZ concentration is less 
than the validated ADAb assay drug tolerance limit (200 μg/mL), will be defined as 
ADAb negative. 
− Sample values that are either NS or PS and NI and where the BKZ concentration exceeds 
the validated ADAb assay drug tolerance limit (200 μg/mL) will be defined as 
inconclusive. 
− Sample values that are PS and PI will be defined as ADAb positive (regardless whether a 
titer is available or not) 
− Missing if it does not go into one of the above categories. 
If a sample is collected within 21 days (inclusive) before or after the visit date at which the drug 
was administered, the ADAb results for that sample will be associated with the scheduled visit 
and summarized accordingly. Samples collected outside this window will be excluded from the 
by-visit ADAb summaries and figures and will be listed only. This window will not apply to the 
summary of cumulative ADAb status, all available data will be used to derive the cumulative 
ADAb status. 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-injection 
(DV0004 Baseline) and after self-injection (at DV0004 Week 4 and PA0012 Week 8) will be 
summarized by visit. The ADAb visit status will be based on the confirmatory assay at the 
respective visit. This visit status and the overall status (considering data in DV0004 only and 
data in DV0004 and the feeder studies) will be used for the summary tables and will be based on 
the Safety Set. 
Cumulative ADAb status is used for the box plots and summaries described in Section 9.1. 
Cumulative and overall ADAb status is derived as follows: 
a. Considering data in DV0004 only: 
• If a subject is ADAb positive at any time during DV0004 up to and including the respective 
DV0004 visit, they are assigned ADAb cumulative positive status for that and all subsequent 
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visits. This will be based on the confirmatory assay at each visit in DV0004 (Baseline, Week 
4, Week 8). 
• If a subject has only negative ADAb samples or only one missing/inconclusive sample with 
all negative ADAb samples up to that timepoint, the subject will be classified as negative. 
• Otherwise, the study participant will be classified in the missing ADAb category. 
b. Considering data in the feeder studies (PA0010, PA00011) and DV0004: 
• If a subject is ADAb positive at any time in PA0010/PA0011 and DV0004 up to and 
including the respective DV0004 visit, they are assigned ADAb cumulative positive status 
for that and all subsequent visits. This will be based on the cumulative status at DV0004 
Entry Visit (last visit in Feeder Study) and the confirmatory assay results in DV0004 (Week 
4 and Week 8). 
• If a subject has only negative ADAb samples or only one missing/inconclusive sample with 
all negative ADAb samples up to that timepoint, the subject will be classified as negative. 
• Otherwise, the study participant will be classified in the missing ADAb category. 
10 
SAFETY ANALYSES 
All safety analysis will be performed for SS-s and SS-a. 
10.1 
Extent of exposure 
Extent of exposure is not relevant for the DV0004 substudy. Occurrence of adverse device 
effects in this substudy will not be affected by the duration of medication exposure. 
10.2 
Adverse events 
All AEs (including serious adverse events [SAEs]) will be reported in a common database for 
PA0012 and DV0004, but only adverse device effects (ADEs), serious adverse device effects 
(SADEs), and device deficiencies will be summarized in the DV0004 substudy. Specifically, 
only those AEs related to the use of the investigational medical devices bimekizumab-SS-1mL or 
bimekizumab-AI-1mL (based on the Investigator’s judgement) will be assessed. All AEs 
(including SAEs) which are not assessed to be related to the investigational devices will be 
summarized separately in the report for the main PA0012 study. An exception are AEs that are 
indicated as injection site reactions during self-injection. These will be listed in DV0004 as well 
as in PA0012. 
10.2.1 
Adverse device effects 
Adverse events are recorded at the AE CRF page at the time when they occur. If an AE is related 
to the device by assessment of the investigator it is counted as an ADE. 
All ADE data will be listed, and no statistical testing will be performed. Only 
treatment-emergent ADEs will be included in the summary tables. Treatment-emergent ADEs 
(TEADEs) will be defined as events related to the study device that have a start date on or 
following the first self. administration of study treatment in DV0004 through the final self-
administration of study treatment + 7 days. The device SFU will occur 1 week after the last self-
administration. 
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All ADEs will be coded and classified by system organ class, high level term, and preferred 
term. Adverse device effects will be summarized by the frequency and percentage of subjects 
having 1 or more of the events in question. Additional planned summaries include overall ADEs 
and SADEs. Summaries to be presented include: 
• Incidence of TEADEs – Overview 
• Incidence of TEADEs by SOC, HLT, and PT 
• Incidence of serious TEADEs by SOC, HLT, and PT 
• Incidence of TEADEs leading to death 
• Incidence of TEADEs leading to discontinuation 
• Incidence of non-TEADEs (only listed and not summarized in a table) 
For definition of serious, unanticipated and unanticipated serious ADEs (USADEs) see protocol 
of DV0004. 
Adverse device effects which started before DV0004 Week 4 and were ongoing at the data cut 
off will be included with the status remaining as ongoing. Adverse device effects which were 
ongoing at DV0004 Week 4 but with an end date before the data cut off will be included with 
their end date as recorded. 
10.2.2 
Impact of COVID-19 on adverse events 
In order to assess the impact of the COVID-19 global pandemic on the primary safety endpoint 
of incidence of TEADEs and serious TEADEs, additional summaries will be presented. 
Summaries of TEADEs and Serious TEADEs will be presented by COVID-19 enrollment period 
and timing of the ADE relative to the WHO declared COVID-19 pandemic (enrolled prior to 
pandemic – ADE prior to pandemic, enrolled prior to pandemic – ADE during pandemic, 
enrolled during pandemic– ADE during pandemic), as defined in Section 4.9.1. ADEs leading to 
discontinuation will be presented by COVID-19 enrollment period and timing of ADE relative to 
the pandemic period as well.   
For reporting purposes, AEs will be assigned to ‘Prior to COVID-19 pandemic’ or ‘During the 
COVID-19 pandemic’ based on the following: 
• If the date of AE or ADE onset (based on imputed start date) is prior to 11 March 2020 the 
AE/ADE will be assigned as ‘Prior to COVID-19 pandemic’ 
• If the date of AE or ADE onset (based on imputed start date) is on or after 11 March 2020 the 
AE/ADE will be assigned as ‘During the COVID-19 pandemic’ 
A ‘Post the COVID-19 pandemic’ phase will not be assigned for AE reporting as the pandemic is 
expected to be ongoing at the time of last subject last visit. 
10.2.3 
Injection site reaction 
Injection site reactions are recorded on the AE CRF page at the time when they occur. All AEs 
will be coded and classified by system organ class, high level term, and preferred term. An AE 
with High Level Terms of “Administration site reactions NEC” and “Injection site reactions” 
will be evaluated as injection site reaction. 
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All injection site reactions for self-injection with a start date on or following the first self-
administration of study treatment through the final self-administration of study treatment + 7 
days will be listed. 
10.3 
Clinical laboratory evaluations 
All clinical laboratory evaluations including hematology, chemistry and urinalysis will be 
collected in PA0012. 
10.4 
Vital signs, physical findings, and other observations related to 
safety 
Electronic case report form (eCRF) data of vital signs, electrocardiograms, physical examination 
and pregnancy test results will be collected in PA0012. 
11 
OTHER ANALYSES  
This section contains a detailed description of the analysis of the primary, secondary and other 
outcome variables. All statistical analyses will be descriptive in nature. No inferential statistical 
analyses are planned. The analysis is done on FAS-s and FAS-a, respectively. 
11.1 
Primary outcome variable 
The primary outcome variable is the percentage of all subjects able to self-administer safe and 
effective injections using the given device at DV0004 Week 4. Safe and effective self-injection 
will be evaluated by the study personnel as defined below: 
• Complete dose delivery: Subject self-injects the complete dose of bimekizumab as confirmed 
by a visual inspection of the bimekizumab-SS-1mL or the bimekizumab-AI-1mL which 
shows that the IMP is delivered completely (i.e., the container is empty), and 
• No ADEs that would preclude continued use of the device presentations for self-injection 
(i.e., no SADEs and/or ADEs leading to withdrawal from the DV0004 substudy). 
All data to assess the primary outcome is collected on the subject self-injection of bimekizumab 
CRF page for DV0004 Week 4. For the number of subjects with safe and effective self-injections 
simply the cases which indicated “yes” for the question “Did the subject self-inject the complete 
dose of Bimekizumab” and “no” for the question “Were there any AEs related to use of the 
investigational device for self-injection” at DV0004 Week 4 are counted. 
The number and percentage of subjects with safe and effective self-injections will be tabulated 
separately for each device presentation using the relevant FAS population (FAS-s or FAS-a). The 
90% CIs based on the Exact Binomial method will be reported as well. The number and 
percentage of subjects with safe and effective self-injections is tabulated for each device 
presentation by COVID-19 enrollment period, as described in Section 4.9.1. 
Assessments where the self-injection was not performed by the subject will not be included in 
any summary statistics.  
11.2 
Secondary outcome variable 
The secondary outcome variable is the percentage of subjects able to self-administer safe and 
effective injections using the given device at DV0004 Baseline (the first self-injection visit, 
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immediately after training in the self-injection technique). Safe and effective self-injection will 
be evaluated by the study personnel. 
The secondary outcome variable will be analyzed in the same manner as the primary outcome 
variable. All data to assess the secondary outcome is collected on “Subject self-injection of 
Bimekizumab” CRF page for DV0004 Baseline. 
Assessments where the self-injection was not performed by the subject will not be included in 
any summary statistics. 
11.3 
Other outcome variables 
The other outcome variables will be summarized using descriptive statistics and they will be 
tabulated separately for each device using the relevant FAS population.  
Assessments where the self-injection was not performed by the subject will not be included in 
any summary statistics. 
11.3.1 
Pre-injection SIAQ (versions 2.0 and 2.1) 
The pre-injection SIAQ (versions 2.0 and 2.1) will be performed at DV0004 Baseline prior to 
subject self-administration of treatment. Version 2.0 of the SIAQ will be used to assess 
bimekizumab-SS-1mL and version 2.1 of the SIAQ will be used to assess bimekizumab-AI-1mL. 
There are no differences in Version 2.0 to Version 2.1 in pre-injection SIAQ. 
The pre-injection SIAQ consists of 7 items each with a scale of 1 to 5. There are three individual 
subscales (feelings about injections [FL, 3 items], self-confidence [CO, 3 items] and satisfaction 
with current mode of administration [SA, 1 item]). Each subscale score will be calculated using 
the average of the individual transformed item scores. The item score will be transformed using 
the following rule: 
𝑇𝑟𝑎𝑛𝑠𝑓𝑜𝑟𝑚𝑒𝑑 𝐼𝑡𝑒𝑚 𝑆𝑐𝑜𝑟𝑒= ((𝑟𝑎𝑤 𝑖𝑡𝑒𝑚 𝑠𝑐𝑜𝑟𝑒) −1) × 2.5 
In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing. The subscale scores will be calculated out of the non-missing 
individual transformed item scores. 
Higher individual scores of the pre-injection indicate more confidence, higher satisfaction and 
less concerns with self-injections. 
Summary statistics for all individual items and each subscale score will be produced for DV0004 
Baseline. 
11.3.1.1 
Additional Analyses for Pre-injection SIAQ summaries 
There will be an additional analysis to present the summary described in Section 11.3.1 for the 
subgroup of subjects who completed both the pre-injection SIAQ and the post-injection SIAQ  
correctly. This is defined as the pre-injection SIAQ being administered before injection, and the 
post-injection SIAQ being administered after injection. The subgroup will include subjects who 
completed both the pre-injection SIAQ and post-injection SIAQ correctly in relation to injection 
administration, and also completed the correct version of the questionnaire assigned based on the 
device group. A pre-injection SIAQ is considered to be impacted if it is administered after self-
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injection. Summary statistics for all individual items and each subscale score will be produced 
for DV0004 Baseline. 
11.3.2 
Post-injection SIAQ (versions 2.0 and 2.1) 
The post-injection SIAQ (versions 2.0 and 2.1) will be performed after subject self-
administration of treatment. This will be performed at DV0004 Baseline and Week 4. Version 
2.0 of the SIAQ will be used to assess bimekizumab-SS-1mL and version 2.1 of the SIAQ will 
be used to assess bimekizumab-AI-1mL. Version 2.0 and 2.1 of the SIAQ are identical, except 
for Question 11 due to different handling of the devices. 
The post-injection SIAQ consists of 21 items on 6 individual subscales (FL [3 items], self-image 
[IM, 1 item], CO [3 items], injection-site reactions [RE, 2 items], ease of use [EU, 5 items] and 
satisfaction with self-injection [SA, 7 items]). The items of the individual subscale EU have a 
score range of 1 to 6, the other individual subscales have a score range of 1 to 5. Each subscale 
score will be calculated using the average of the individual transformed item scores. The item 
scores for the EU subscale will be transformed using the following rule: 
𝑇𝑟𝑎𝑛𝑠𝑓𝑜𝑟𝑚𝑒𝑑 𝐼𝑡𝑒𝑚 𝑆𝑐𝑜𝑟𝑒= ((𝑟𝑎𝑤 𝑖𝑡𝑒𝑚 𝑠𝑐𝑜𝑟𝑒) −1) × 2 
The item scores for the other remaining subscales will be transformed using the following rule: 
𝑇𝑟𝑎𝑛𝑠𝑓𝑜𝑟𝑚𝑒𝑑 𝐼𝑡𝑒𝑚 𝑆𝑐𝑜𝑟𝑒= ((𝑟𝑎𝑤 𝑖𝑡𝑒𝑚 𝑠𝑐𝑜𝑟𝑒) −1) × 2.5 
In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing. The subscale scores will be calculated out of the non-missing 
individual transformed item scores. If a subject completed the incorrect version of the 
questionnaire (for example, a subject randomized to bimekizumab-SS-1mL and completed 
version 2.1 of the post-injection SIAQ), then Q11 will be excluded from the derivation of Ease of 
Use subscale. 
Higher individual subscale scores of the post-injection indicate more confidence, higher 
satisfaction and less concerns with self-injections. 
Summary statistics for all individual items and each subscale score will be produced for DV0004 
Baseline and Week 4. 
11.3.2.1 
Additional Analysis for Post-injection SIAQ summaries 
There will be an additional analysis performed for post-injection SIAQ. It will repeat the analysis 
described in Section 11.3.2 only including the subgroup of subjects who completed both the pre-
injection SIAQ and the post-injection SIAQ correctly. A post-injection questionnaire is 
considered to be impacted if it is administered before self-injection, or if the incorrect post-
injection SIAQ version has been administered for the randomized device group. Version 2.0 of 
the SIAQ will be used to assess bimekizumab-SS-1mL and version 2.1 of the SIAQ will be used 
to assess bimekizumab-AI-1mL. Subjects who either have an impacted pre- or post-injection 
SIAQ at any visit will be excluded from the summary. Note that subjects complete both pre- and 
post-injection questionnaires at Baseline, and only post-injection SIAQ at Week 4. Summary 
statistics for all individual items and each subscale score will be produced for DV0004 Baseline 
and Week 4. 
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11.3.3 
Injection site pain 
The visual analog scale (VAS) of injection site pain indicates the level of pain during the 
injection. It reaches from 0-100 mm with higher values for more severe pain and 0 for no pain. 
Summary statistics of actual values at DV0004 Baseline and Week 4 and change from DV0004 
Baseline values will be used to summarize injection site pain by visit after self-injection. 
11.3.3.1 
Additional Analysis for Injection site pain 
There will be an additional analysis of the summary described in Section 11.3.3 limited to 
subjects who correctly completed the visual analog scale of injection site pain after the injection 
at both visits. Summary statistics of actual values at DV0004 Baseline and Week 4 and change 
from DV0004 Baseline values will be used to summarize injection site pain by visit after self-
injection.  
11.3.4 
Structural and mechanical integrity of the devices 
The structural and mechanical integrity of the device after completion of self-injection will be 
assessed by the investigator after each injection in the “Subject self-injection of bimekizumab” 
CRF page. The assessment will be done using the questions for structural integrity.  The 
structural integrity is based on a visual examination of the device that shows clear evidence of 
damage, compromised structural or mechanical integrity not superficial and/or cosmetic 
imperfections. 
Frequency tables will be produced to show the number and percentage of devices with used 
bimekizumab-SS-1mL and bimekizumab-AI-1mL syringes identified as having structural 
integrity issues after completion of self-injection. 
The 90% CIs based on the Exact Binomial method will be reported as well. 
11.3.5 
Functional integrity of the devices 
The functional integrity of the device after completion of self-injection will be assessed by the 
investigator after each injection in the “Subject self-injection of bimekizumab” CRF page. The 
assessment will be done using the questions for function compromise. The functional integrity 
will be based on a visual examination of the device that shows clear evidence of damage and/or 
device does not function normally.  
Frequency tables will be produced to show the number and percentage of devices with used 
bimekizumab-SS-1mL and bimekizumab-AI-1mL syringes identified as functionally 
compromised. 
The 90% CIs based on the Exact Binomial method will be reported as well. 
 
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12 
REFERENCES 
 
 
 
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13 
APPENDICES 
13.1 
SAP Amendment 1 
Rational for the amendment 
Details regarding the handling of the early termination visit mapping, and the handling of 
missing dates have been updated following developments on other BKZ studies. 
Modifications and changes 
Global changes 
The following changes were made throughout the SAP: 
• The DV0004 study number was added before the study visit where it was necessary to 
distinguish it from the PA0012 study visits. 
• The list of abbreviations was updated accordingly. 
• Minor spelling, editorial, and formatting changes were made throughout the document. 
• “Study participant” has been updated to “subject” throughout the document. 
• Note that large sections of unchanged text have been substituted in this section with “[…]”. 
Specific changes 
In addition to the global changes, the following specific changes have been made: 
Change #1 
Section 2.3.5 Study duration per subject 
The maximum DV0004 substudy duration will be 5 weeks for each study subject. Study subjects 
will then continue to receive treatment in PA0012 for the duration of the PA0012 study. The end 
of the DV0004 substudy is defined as the date on which the last study subject completes his/her 
Week 5 Visit or withdraws from the study. 
Has been changed to: 
The maximum DV0004 substudy duration will be 4 weeks for each subject. Subjects will then 
continue to receive treatment in PA0012 for the duration of the PA0012 study. The end of the 
DV0004 substudy is defined as the date on which the last subject completes his/her DV0004 
Week 4 Visit or withdraws from the study. 
Change #2 
Section 4.2 Handling of dropouts or missing data 
Partial ADE and concomitant medication start dates will be imputed as follows:  
Imputation of Partial Start Dates 
• If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month 
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• If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start date, then use the date of first dose 
• If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use the 1st of January of the year of the start date 
• If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose 
• If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose. 
Imputation of Partial Stop Dates 
• If only the month and year are specified, then use the last day of the month 
• If only the year is specified, then use December 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 a 
medication was concomitant, or an adverse event was treatment emergent, the medication will be 
considered as concomitant or the adverse event will be considered treatment emergent. 
Has been changed to: 
Partial ADE and concomitant medication start dates will be imputed as follows:  
Imputation of Partial Start Dates 
• If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month 
• If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start date, then use the date of first dose 
• If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use the 1st of January of the year of the start date 
• If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose 
• If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose. 
Imputation of Partial Stop Dates 
• If only the month and year are specified, then use the last day of the month 
• If only the year is specified, then use December 31st of that year 
• If the stop date is completely unknown, do not impute the stop date. 
If the imputed stop date is prior to the imputed start date 
• If the year of start date is the same as the year of first dose and the stop date is after the 
date of first dose then set the start date to the date of first dose 
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• Otherwise set to the 1st January of the year of the start date 
In the event of ambiguity or incomplete data which makes it impossible to determine whether a 
medication was concomitant, or an adverse event was treatment emergent, the medication will be 
considered as concomitant or the adverse event will be considered treatment emergent. 
Change #3 
Section 6.1 Demographics 
[…] 
• DV0004 Baseline Weight (kg): will be derived from the weight from the last visit of the 
feeder study 
• DV0004 Baseline BMI (kg/m2) 
BMI (kg/m2) will be calculated as: 
𝐵𝑀𝐼= 𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
[𝐻𝑒𝑖𝑔ℎ𝑡 (𝑚)]2 
The following categorical variables will be summarized using frequency counts and percentages: 
• Age group (≤18, 19-<65, ≥65 years) 
• DV0004 Body Weight (≤100kg, >100kg) 
Has been changed to: 
[…] 
• Weight (kg) at DV0004 Baseline: This will be derived from the weight from the last visit 
of the feeder study or DV0004 Entry Visit, since these visits will occur on the same day 
and weight is only collected once 
• DV0004 Baseline BMI (kg/m2) 
BMI (kg/m2) will be calculated as: 
𝐵𝑀𝐼=
𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔) 𝒂𝒕 𝑫𝑽𝟎𝟎𝟎𝟒 𝑩𝒂𝒔𝒆𝒍𝒊𝒏𝒆
[𝐻𝑒𝑖𝑔ℎ𝑡 (𝑚) 𝒂𝒕 𝑭𝒆𝒆𝒅𝒆𝒓 𝑺𝒕𝒖𝒅𝒚 𝑩𝒂𝒔𝒆𝒍𝒊𝒏𝒆]2 
The following categorical variables will be summarized using frequency counts and percentages: 
• Age group (≤18, 19-<65, ≥65 years) 
• Body Weight at DV0004 Baseline (≤100kg, >100kg) 
 
Change #4 
Section 6.2 Other Baseline characteristics 
Generally, the following continuous variables will be summarized using descriptive statistics 
(number of participants, mean, SD, minimum, median and maximum): 
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• Duration of disease (years) 
Duration of disease (years) will be calculated as: 
𝐷𝑖𝑠𝑒𝑎𝑠𝑒 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑟𝑎𝑛𝑑𝑜𝑚𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝐹𝑆−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑜𝑛𝑠𝑒𝑡 𝑜𝑓 𝑃𝑠𝐴1)
365.25
 
1 If the date of onset of PsA is partial, it should be imputed to the most recent feasible date (i.e., 
last day of the month if only day is missing, or last day of the year if day and month are missing).  
The following categorical variables will be summarized using frequency counts and percentages: 
• Duration of disease (<median, ≥median) based on the respective SS populations (SS-s and 
SS-a). 
Has been changed to: 
Generally, the following continuous variables will be summarized using descriptive statistics 
(number of subjects, mean, SD, minimum, median and maximum): 
• Duration of disease (years) 
Duration of disease (years) will be calculated as: 
𝐷𝑖𝑠𝑒𝑎𝑠𝑒 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛= (𝐷𝑎𝑡𝑒 𝑜𝑓 𝑟𝑎𝑛𝑑𝑜𝑚𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝒊𝒏 𝑫𝑽𝟎𝟎𝟎𝟒 −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑜𝑛𝑠𝑒𝑡 𝑜𝑓 𝑃𝑠𝐴1)
365.25
 
1 If the date of onset of PsA is partial, it should be imputed to the most recent feasible date (i.e., 
last day of the month if only day is missing, or last day of the year if day and month are missing).  
The following categorical variables will be summarized using frequency counts and percentages: 
• Duration of disease (<median, ≥median) based on the respective SS populations (SS-s and 
SS-a). 
Change #5 
Section 9.1 Pharmacokinetics 
The statistical analyses of the PK data will be descriptive in nature and will be summarized using 
the relevant device presentation-specific population (PK-PPS-s or PK-PPS-a). Data will be 
analyzed overall for each device presentation by injection type (self-administered or study 
personnel-administered), by injection site (abdomen or thigh), by anti-bimekizumab antibody 
status, and by BMI category. Three BMI categories will be defined based on tertiles derived 
from participants’ Baseline BMI values. […] 
Bimekizumab PK trough levels associated with injection by study personnel using the 1mL PFS 
(in PA0010 or PA0011) will be analyzed from the pre-injection PK sample collected at Baseline. 
Bimekizumab PK trough levels associated with participant self-injection using the assigned self-
injecting device presentation will be analyzed from the pre-injection PK samples collected at 
Week 4 and Week 8 (of PA0012). 
[…]  
PK samples for self-administration where the injection was done by site personnel will be listed 
but not be used for summary statistics.  PK samples for personnel administration where the 
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injection was done by the participant or caregiver, if applicable, will be listed but not be used for 
summary statistics. 
[…] 
Boxplots of plasma concentration will be presented by visit and by device presentation. 
All PK results will be listed.  
In addition, the PK results from all participants not in PK-PPS-s or PK-PPS-a will be listed based 
on the SS-a and SS-s.  
Has been changed to: 
The statistical analyses of the PK data will be descriptive in nature and will be summarized using 
the relevant device presentation-specific population (PK-PPS-s or PK-PPS-a). Data will be 
analyzed overall for each device presentation by injection type (self-administered or study 
personnel-administered), by injection site (abdomen or thigh), by anti-bimekizumab antibody 
visit status, and by BMI category. Three BMI categories will be defined based on tertiles derived 
from subjects' DV0004 Baseline BMI values. See Section 9.2 for details on classification of 
anti-bimekizumab antibody status.  […] 
Bimekizumab PK trough levels associated with injection by study personnel using the 1mL PFS 
(in PA0010 or PA0011) will be analyzed from the pre-injection PK sample collected at Baseline. 
Bimekizumab PK trough levels associated with subject self-injection using the assigned self-
injecting device presentation will be analyzed from the pre-injection PK samples collected at 
DV0004 Week 4 and PA0012 Week 8 (of PA0012). 
[…] 
PK samples for self-administration where the injection was done by site personnel or care-giver 
will be listed but not be used for summary statistics.  PK samples for personnel administration 
where the injection was done by the subject or caregiver, if applicable, will be listed but not be 
used for summary statistics. 
Only pre-dose (trough) concentrations will be included while summarizing tables and 
figures. If the dosing for a visit is +/- 7 days out of window, then the plasma concentration 
from that visit and all subsequent visits will be excluded from the PK summary. PK 
samples collected after dosing will be excluded from summary statistics. 
[…] Time from previous bimekizumab dose to DV0004 visit will be summarized by device 
presentation. 
Boxplots of plasma concentration will be presented by visit and by device presentation, overall 
and by cumulative ADAb status. Cumulative ADAb status is defined in Section 9.2.  
All PK results will be listed. Baseline PK samples are the PK samples prior to first dose of 
Bimekizumab at DV0004 entry visit. 
In addition, the PK results from all subjects not in PK-PPS-s or PK-PPS-a will be listed based on 
the SS-a and SS-s.  
 
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Change #6 
Section 9.2 Pharmacodynamics 
Not applicable. 
Has been changed to 
Section 9.2 Pharmacodynamics and Immunogenicity 
The immunological variable is ADAb evaluated at DV0004 Baseline and DV0004 Week 4 visits.  
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. 
If a sample is collected within 7 days (inclusive) before or after the visit date at which the 
drug was administered, the ADAb results for that sample will be associated with the 
scheduled visit and summarized accordingly. Samples collected outside this window and all 
subsequent samples for that subject will be excluded from the ADAb summaries and 
figures and will be listed only. 
ADAb status will be derived as follows:  
• Samples 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) 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-
injection (DV0004 Baseline) and after self-injection (at DV0004 Baseline and DV0004 Week 
4) will be summarized by visit. The ADAb visit status will be based on the confirmatory 
assay at the respective visit. This visit status will be used for the summary tables. 
Cumulative ADAb status is used for the box plots described in Section 9.1. Cumulative 
ADAb status is derived as follows: 
• If a subject is ADAb positive at any time up to and including the respective visit, they 
are assigned ADAb cumulative positive status for that and all subsequent visits.  
• Otherwise, the subject remains negative at that respective visit and assigned ADAb 
cumulative negative. 
 
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Change #7 
Section 10.2 Adverse events 
All AEs (including serious adverse events [SAEs]) will be reported in a common database for 
PA0012 and DV0004, but only adverse device effects (ADEs), serious adverse device effects 
(SADEs), and device deficiencies will be summarized in the DV0004 substudy. Specifically, 
only those AEs related to the use of the investigational medical devices bimekizumab-SS-1mL or 
bimekizumab-AI-1mL (based on the Investigator’s judgement) will be assessed. All AEs 
(including SAEs) which are not assessed to be related to the investigational devices will be 
summarized separately in the report for the main PA0012 study. 
[…] 
Additional planned summaries include overall ADEs and SADEs. Summaries to be presented 
include: 
• Incidence of TEADEs – Overview 
• Incidence of TEADEs by SOC, HLT, and PT 
• Incidence of serious TEADEs by SOC, HLT, and PT 
• Incidence of TEADEs leading to death 
• Incidence of TEADEs leading to discontinuation 
• Incidence of non-TEADEs  
For definition of serious, unanticipated and unanticipated serious ADEs (USADEs) see protocol 
of DV0004. 
Adverse device effects which started before Week 4 and were ongoing at the data cut off will be 
included with the status remaining as ongoing. Adverse device effects which were ongoing at 
Week 4 but with an end date before the data cut off will be included with their end date as 
recorded. 
Has been changed to: 
10.2 Adverse events 
All AEs (including serious adverse events [SAEs]) will be reported in a common database for 
PA0012 and DV0004, but only adverse device effects (ADEs), serious adverse device effects 
(SADEs), and device deficiencies will be summarized in the DV0004 substudy. Specifically, 
only those AEs related to the use of the investigational medical devices bimekizumab-SS-1mL or 
bimekizumab-AI-1mL (based on the Investigator’s judgement) will be assessed. All AEs 
(including SAEs) which are not assessed to be related to the investigational devices will be 
summarized separately in the report for the main PA0012 study. An exception are AEs that are 
indicated as injection site reactions during self-injection. These will be listed in DV0004 as 
well as in PA0012. 
10.2.1 Adverse device effects 
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Adverse events are recorded at the AE CRF page at the time when they occur. If an adverse 
event is related to the device by assessment of the investigator it is counted as an adverse device 
event. 
[…] 
Additional planned summaries include overall ADEs and SADEs. Summaries to be presented 
include: 
• Incidence of TEADEs – Overview 
• Incidence of TEADEs by SOC, HLT, and PT 
• Incidence of serious TEADEs by SOC, HLT, and PT 
• Incidence of TEADEs leading to death 
• Incidence of TEADEs leading to discontinuation 
• Incidence of non-TEADEs (only listed and not summarized in a table) 
For definition of serious, unanticipated and unanticipated serious ADEs (USADEs) see protocol 
of DV0004. 
Adverse device effects which started before Week 4 and were ongoing at the data cut off will be 
included with the status remaining as ongoing. Adverse device effects which were ongoing at 
Week 4 but with an end date before the data cut off will be included with their end date as 
recorded. 
10.2.2 Injection site reaction 
Injection site reactions are recorded at the AE CRF page at the time when they occur. All 
AEs will be coded and classified by system organ class, high level term, and preferred term. 
An AE with High Level Terms of “Administration site reactions NEC” and “Injection site 
reactions” will be evaluated as injection site reaction. 
All injection site reactions for self-injection with a start date on or following the first self-
administration of study treatment through the final self-administration of study treatment 
+ 7 days will be listed. 
 
 
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13.2 
SAP Amendment 2 
Rational for the amendment 
Details regarding the handling of COVID-19 pandemic data have been added to the SAP. The 
summaries for the PK data have been updated following discussions in the Data Evaluation 
Meeting (#2). A sensitivity analysis for the SIAQ data has been added following DEM2. 
Modifications and changes 
Global changes 
The following changes were made throughout the SAP: 
• The addition of clarification of which outputs are to be presented to assess the impact of 
COVID-19 pandemic.  
• Sections have been renumbered to account for new COVID-related sections. These will not 
be individually noted. 
Specific changes 
Change #1 
Text added at the end of Section. 
Section 3.3 Protocol deviations 
[..] Following the declaration of the global COVID-19 pandemic by the World Health 
Organization in March 2020, protocol deviations will be identified as “related to COVID-
19” where applicable.   
Change #2 
Subsection added for Section 3.8 Changes to protocol-defined analyses. 
Section 3.8.1 Changes related to COVID-19 
The impact of the COVID-19 pandemic on study procedures and/or conduct and on the primary 
safety endpoints (TEADEs, serious TEADEs, and study withdrawal due to TEADEs) will be 
investigated and additional outputs provided as appropriate. These analyses were not planned as 
part of the protocol as the pandemic scale was unprecedented. 
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) 
• Protocol deviations potentially related to COVID-19 (Section 5.2)  
• Impact of COVID-19 on study (Section 5.3 ) 
• Demographics, baseline characteristics (Sections 6.1 and 6.2 ) 
• Adverse events (Section 10.2.2) 
• Primary outcome variable (Section 11.1 ) 
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Change #3 
Subsection added to Section 4.9 Additional study-specific information.  
Section 4.9.1 COVID-19 category definition 
The coronavirus disease of 2019 (COVID-19) pandemic was declared by the WHO on 11 March 
2020. The worldwide pandemic restricted travel and had potential impact on ongoing clinical 
trials. The following definitions will be used to present pre-specified summaries: 
• Pre-pandemic: Events or assessments occurring before 11-Mar-2020 
• During pandemic: Events or assessments occurring on or after 11-Mar-2020 
A post-pandemic definition is not applicable to this short study. 
Change #4 
Subsection added to Section 5.1 Subject disposition. 
Section 5.1.1 Impact of COVID-19 on subject disposition 
Subject disposition will also be summarized by COVID-19 enrollment period (pre- and during-
pandemic), as defined in Section 4.9.1.  The number of completed, missed and partial visits will 
be presented by COVID-19 enrollment period.  
Change #5 
Section 5.2 Protocol deviations 
A summary of number and percentage of subjects with an important protocol deviation 
(including a summary of subjects excluded from any analysis set due to important protocol 
deviations) by DV0004 device group will be provided for the SS-s and SS-a. 
A by-subject listing of important protocol deviations will be provided. 
Has been changed to 
A summary of number and percentage of subjects with an important protocol deviation 
(including a summary of subjects excluded from any analysis set due to important protocol 
deviations) by DV0004 device group will be provided for the SS-s and SS-a. A summary of 
COVID-19 related important device protocol deviations will be presented by visit for the 
SS-s and SS-a. COVID-19 related important protocol deviations will be identified by the 
prefix of “COVID” in the deviation verbatim text. 
By-subject listings of important protocol deviations and COVID-related important device 
protocol deviations will be provided separately. 
Change #6 
Section added: 
Section 5.3 Impact of COVID-19 
The impact of the COVID-19 pandemic on study procedures and conduct, such as missed/remote 
visits, interruption of study treatment, will be documented using the information collected on a 
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dedicated eCRF page. The number and percentage of subjects impacted by COVID-19 will be 
presented overall and by country.  
A by-subject listing of the impact of COVID-19 on study visits will be provided. 
Change #7 
Text added to section. 
9.1 Pharmacokinetics 
PK samples at DV0004 baseline will be summarized under administration by site personnel 
(since the previous dose was given by site personnel). PK samples associated with self-
administration (at Week 4 and Week 8), but where the previous injection was done by site 
personnel or care-giver, will be listed but not be used for summary statistics.   
Only pre-dose (trough) concentrations will be included while summarizing tables and figures. If 
the dosing for a visit is +/- 7 days out of window, then the plasma concentration from that visit 
will be excluded from the PK summary. PK samples are expected to be collected prior to 
dosing. PK samples collected >14 days after the preceding dose and no later than 1 hour 
after the current dose will be included in the summary. PK samples collected later than 1 
hour after dosing will be excluded from summary statistics. PK results at visits following a 
previous non-dosing visit will be excluded from summary statistics. 
[…] 
Boxplots of plasma concentration will be presented by visit, by device presentation, and by 
cumulative ADAb status. Cumulative ADAb status is defined in Section 9.2. Boxplots of 
plasma concentration will be presented by visit, by device presentation and by injection 
site, and by BMI tertile. 
All PK results will be listed. Baseline PK samples are the PK samples prior to first dose of 
Bimekizumab at DV0004 entry visit.  
In addition, the PK results from all subjects not in PK-PPS-s or PK-PPS-a will be listed based on 
the SS-a and SS-s. All concentrations will be listed as received, prior to any substitution of 
BLQ and LLOQ values. The listing will include flags for concentration that were excluded 
from the summary statistics, with the reason for exclusion. 
Change #8 
Section 9.2 “Pharmacodynamics and Immunogenicity” renamed to “Immunogenicity”. 
[..] 
If a sample is collected within 7 days (inclusive) before or after the visit date at which the drug 
was administered, the ADAb results for that sample will be associated with the scheduled visit 
and summarized accordingly. Samples collected outside this window and all subsequent samples 
for that subject will be excluded from the ADAb summaries and figures and will be listed only. 
[..] 
Cumulative ADAb status is used for the box plots described in Section 9.1. Cumulative ADAb 
status is derived as follows: 
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• If a subject is ADAb positive at any time up to and including the respective visit, they are 
assigned ADAb cumulative positive status for that and all subsequent visits.  
• Otherwise, the subject remains negative at that respective visit and assigned ADAb 
cumulative negative. 
Has changed to 
[..] 
If a sample is collected within 21 days (inclusive) before or after the visit date at which the drug 
was administered, the ADAb results for that sample will be associated with the scheduled visit 
and summarized accordingly. Samples collected outside this window and all subsequent samples 
for that subject will be excluded from the by-visit ADAb summaries and figures and will be 
listed only. This window will not apply to the summary of cumulative ADAb status, all 
available data will be used to derive the cumulative ADAb status. 
[..] 
Cumulative ADAb status is used for the box plots described in Section 9.1. Cumulative ADAb 
status is derived as follows: 
a. Considering data in DV0004 only: 
• If a subject is ADAb positive at any time during DV0004 up to and including the respective 
DV0004 visit, they are assigned ADAb cumulative positive status for that and all subsequent 
visits. This will be based on the confirmatory assay at each visit in DV0004 (Baseline, 
Week 4, Week 8). 
• Otherwise, the subject remains negative at that respective DV0004 visit and assigned ADAb 
cumulative negative. 
b. Considering data in the feeder studies (PA0010, PA00011) and DV0004: 
• If a subject is ADAb positive at any time in PA0010/PA0011 and DV0004 up to and 
including the respective DV0004 visit, they are assigned ADAb cumulative positive 
status for that and all subsequent visits. This will be based on the cumulative status at 
DV0004 Entry Visit (last visit in Feeder Study) and the confirmatory assay results in 
DV0004 (Week 4 and Week 8). 
• Otherwise, the subject remains negative at that respective DV0004 visit and assigned 
ADAb cumulative negative. 
 
Change #9 
Subsection 10.2.2 Impact of COVID-19 on adverse events added. 
Section 10.2.2 Impact of COVID-19 on adverse events 
In order to assess the impact of the COVID-19 global pandemic on the primary safety endpoint 
of incidence of TEADEs and serious TEADEs, additional summaries will be presented. 
Summaries of TEADEs and Serious TEADEs will be presented by COVID-19 enrollment period 
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and timing of the ADE relative to the WHO declared COVID-19 pandemic (enrolled prior to 
pandemic – ADE prior to pandemic, enrolled prior to pandemic – ADE during pandemic, 
enrolled during pandemic– ADE during pandemic), as defined in Section 4.9.1. ADEs leading to 
discontinuation will be presented by COVID-19 enrollment period and timing of ADE relative to 
the pandemic period as well.   
For reporting purposes, AEs will be assigned to ‘Prior to COVID-19 pandemic’ or ‘During the 
COVID-19 pandemic’ based on the following: 
• If the date of AE or ADE onset (based on imputed start date) is prior to 11 March 2020 the 
AE/ADE will be assigned as ‘Prior to COVID-19 pandemic’ 
• If the date of AE or ADE onset (based on imputed start date) is on or after 11 March 2020 the 
AE/ADE will be assigned as ‘During the COVID-19 pandemic’ 
A ‘Post the COVID-19 pandemic’ phase will not be assigned for AE reporting as the pandemic is 
expected to be ongoing at the time of last subject last visit. 
[..] 
 
 
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13.3 
SAP Amendment 3 
Rational for the amendment 
An additional set of analyses for the SIAQ and VAS data has been added following data 
cleaning. The details for this analysis have been added to the SAP text in Section 11.3.1, Section 
11.3.2 and Section 11.3.3. 
Modifications and changes 
Specific changes 
Change #1 
Clarification added to the derivation of the subscale scores when missing data occurs. 
Section 9.1 Pharmacokinetics 
[…] 
PK summaries will be based on observed values. No imputation will be used. However, if 
plasma concentration measurements are below the level of quantification, then for calculation of 
the derived statistics the result will be set to ½ of the lower level of quantification (LLOQ). 
Descriptive statistics including the geometric mean, geometric coefficient of variation, and 
geometric mean 95% confidence interval (CI) if applicable will be calculated if at least ⅔ of the 
values of interest are above the LLOQ. If this is not the case, only median, minimum, and 
maximum will be presented. Time from previous bimekizumab dose to DV0004 visit will be 
summarized by device presentation. 
Has changed to 
[…] 
PK summaries will be based on observed values. No imputation will be used. However, if 
plasma concentration measurements are below the level of quantification, then for calculation of 
the derived statistics the result will be set to ½ of the lower level of quantification (LLOQ). 
Descriptive statistics including the geometric mean, geometric coefficient of variation, and 
geometric mean 95% confidence interval (CI) if applicable will be calculated if at least ⅔ of the 
values of interest are above the LLOQ. If this is not the case, only median, minimum, and 
maximum will be presented. Time from previous bimekizumab dose to DV0004 visit will be 
summarized by device presentation. 
A minimum of 3 values are required to calculate summary statistics. If only 2 values are 
available, then these should be presented as the minimum and maximum with other 
descriptive statistics reported as missing 
 
Change #2 
Clarification added to the derivation of the subscale scores when missing data occurs. 
Section 11.3.1 Pre-injection SIAQ (versions 2.0 and 2.1) 
[…] 
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In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing.  
Has changed to 
[…] 
In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing. The subscale scores will be calculated out of the non-missing 
individual transformed item scores. 
 
Change #3 
Subsection 11.3.1.1 has been added. 
Section 11.3.1.1 Additional Analysis for Pre-injection SIAQ 
There will be an additional analysis to present the summary described in Section 11.3.1 for the 
subgroup of subjects who completed both the pre-injection SIAQ and the post-injection SIAQ 
per protocol. The subgroup will include subjects who completed the pre-injection SIAQ and 
post-injection SIAQ correctly in relation to injection administration, and also completed the 
correct version of the questionnaire assigned based on the device group. A pre-injection SIAQ is 
considered to be impacted if it is administered after self-injection. Summary statistics for all 
individual items and each subscale score will be produced for DV0004 Baseline. 
 
Change #4 
Clarification added to the derivation of Ease of Use subscale and the derivation of the subscale 
scores when missing data occurs. 
Section 11.3.2 Post-injection SIAQ (versions 2.0 and 2.1) 
[…] 
In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing.  
[…] 
Has changed to 
[…] 
In the case of missing values, no subscale score will be calculated if more than 50% of the items 
within the subscale are missing. The subscale scores will be calculated out of the non-missing 
individual transformed item scores. If a subject completed the incorrect version of the 
questionnaire (for example, a subject randomized to bimekizumab-SS-1mL and completed 
version 2.1 of the post-injection SIAQ), then Q11 will be excluded from the derivation of 
Ease of Use subscale. 
[…] 
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Change #5 
Subsection 11.3.2.1 has been added. 
Section 11.3.2.1 Additional Analysis for Post-injection SIAQ 
There will be an additional analysis performed for post-injection SIAQ. It will repeat the analysis 
described in Section 11.3.2 only including the subgroup of subjects who completed both the pre-
injection SIAQ and the post-injection SIAQ correctly as described in the protocol. A post-
injection questionnaire is considered to be impacted if it is administered before self-injection, or 
longer than 30 minutes after self-injection, or if the incorrect post-injection SIAQ version has 
been administered for the randomized device group. Version 2.0 of the SIAQ will be used to 
assess bimekizumab-SS-1mL and version 2.1 of the SIAQ will be used to assess bimekizumab-
AI-1mL. Subjects who have an impacted pre- or post-injection SIAQ at any visit will be 
excluded from the summary. Note that subjects complete both pre- and post-injection 
questionnaires at Baseline, and only post-injection SIAQ at Week 4. Summary statistics for all 
individual items and each subscale score will be produced for DV0004 Baseline and Week 4. 
 
Change #6 
Subsection 11.3.3.1 has been added. 
Section 11.3.3.1 Additional Analysis for Injection site pain 
There will be an additional analysis of the summary described in Section 11.3.3 limited to 
subjects who correctly completed the visual analog scale of injection site pain after the injection 
at both visits. Summary statistics of actual values at DV0004 Baseline and Week 4 and change 
from DV0004 Baseline values will be used to summarize injection site pain by visit after self-
injection.  
 
 
 
 
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13.4 
SAP Amendment 4 
Rational for the amendment 
Aligning the immunogenicity text to use the terminology for ADAb samples consistent with the 
BKZ program. No change to analyses, administrative change. 
Specific Changes 
Change #1 
Section 9.1 Pharmacokinetics 
[…] 
Boxplots of plasma concentration will be presented by visit, by device presentation, and by 
cumulative ADAb status. Cumulative ADAb status is defined in Section 9.2. Boxplots of plasma 
concentration will be presented by visit, by device presentation and by injection site, and by BMI 
tertile. 
[…] 
Has been updated to 
[…] 
Boxplots and summaries of plasma concentration will be presented by visit, by device 
presentation, and by cumulative ADAb status considering DV0004 alone and considering 
DV0004 and the feeder studies (see Section 9.2). Cumulative ADAb status is defined in 
Section 9.2. Boxplots and summaries of plasma concentration will be presented by visit, by 
device presentation and by injection site, and by BMI tertile. 
[…] 
Change #2 
Section 9.2 Immunogenicity 
The immunological variable is anti-bimekizumab antibodies (ADAb) evaluated at DV0004 
Baseline and Week 4, and PA0012 Week 8 visits. To allow for an analysis of ADAb, blood 
samples will be taken before self-injection at the DV0004 Baseline Visit and DV0004 Week 4 
(Visit 2), and before injection by site personnel at PA0012 Week 8 (Visit 3 of PA0012). ADAb 
status at or prior to the PK sampling (at DV0004 Baseline, DV0004 Week 4, and PA0012 Week 
8) will be used in the summaries. 
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 ADAb 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 
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will be determined by the bioanalytical laboratory which will report the bioanalytical result from 
the respective assays. 
If a sample is collected within 21 days (inclusive) before or after the visit date at which the drug 
was administered, the ADAb results for that sample will be associated with the scheduled visit 
and summarized accordingly. Samples collected outside this window will be excluded from the 
by-visit ADAb summaries and figures and will be listed only. This window will not apply to the 
summary of cumulative ADAb status, all available data will be used to derive the cumulative 
ADAb status. 
ADAb status will be derived as follows:  
• Samples 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) 
[…] 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-injection 
(DV0004 Baseline) and after self-injection (at DV0004 Week 4 and PA0012 Week 8) will be 
summarized by visit. The ADAb visit status will be based on the confirmatory assay at the 
respective visit. This visit status will be used for the summary tables. 
[…] 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-injection 
(DV0004 Baseline) and after self-injection (at DV0004 Week 4 and PA0012 Week 8) will be 
summarized by visit. The ADAb visit status will be based on the confirmatory assay at the 
respective visit. This visit status and the overall status (considering data in DV0004 only and 
data in DV0004 and the feeder studies) will be used for the summary tables and will be based on 
the Safety Set. 
Cumulative ADAb status is used for the box plots and summaries described in Section 9.1. 
Cumulative ADAb status is derived as follows: 
a. Considering data in DV0004 only: 
• If a subject is ADAb positive at any time during DV0004 up to and including the respective 
DV0004 visit, they are assigned ADAb cumulative positive status for that and all subsequent 
visits. This will be based on the confirmatory assay at each visit in DV0004 (Baseline, Week 
4, Week 8). 
• Otherwise, the subject remains negative at that respective DV0004 visit and assigned ADAb 
cumulative negative. 
b. Considering data in the feeder studies (PA0010, PA00011) and 
DV0004: 
• If a subject is ADAb positive at any time in PA0010/PA0011 and DV0004 up to and 
including the respective DV0004 visit, they are assigned ADAb cumulative positive status 
for that and all subsequent visits. This will be based on the cumulative status at DV0004 
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Entry Visit (last visit in Feeder Study) and the confirmatory assay results in DV0004 (Week 
4 and Week 8). 
• Otherwise, the subject remains negative at that respective DV0004 visit and assigned ADAb 
cumulative negative. 
 
Has been updated to 
The immunological variable is anti-bimekizumab antibodies (ADAb) evaluated at DV0004 
Baseline and Week 4, and PA0012 Week 8 visits. To allow for an analysis of ADAb, blood 
samples will be taken before self-injection at the DV0004 Baseline Visit and DV0004 Week 4 
(Visit 2), and before injection by site personnel at PA0012 Week 8 (Visit 3 of PA0012). ADAb 
status at or prior to the PK sampling (at DV0004 Baseline, DV0004 Week 4, and PA0012 Week 
8) will be used in the summaries. 
ADAb will be assessed using a tiered approach: screening, confirmatory, and titer assays will be 
used. The ADAb will be assessed using a 3-tiered assay approach: Screening, confirmatory, 
and titration assays. 
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 ADAb 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 Screening cut point will be used to determine the ADAb status in the test sample as 
“Positive Screen” (PS) or “Negative Screen” (NS). For samples presenting anti-BKZ 
antibody levels that are PS, further confirmatory assay will be performed, and the result of 
which will be reported as either “Positive Immunodepletion” (PI) or “Negative 
Immunodepletion” (NI). 
ADAb status for each visit will be derived as follows:  
− Samples that are either NS or PS and NI will be defined as ADAb negative. 
− Sample values that are either NS or PS and NI and where the BKZ concentration 
exceeds the validated ADAb assay drug tolerance limit (200 μg/mL) will be defined 
as inconclusive. 
− Sample values that are PS and PI will be defined as ADAb positive (regardless 
whether a titer is available or not) 
− Missing if it does not go into one of the above categories. 
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If a sample is collected within 21 days (inclusive) before or after the visit date at which the drug 
was administered, the ADAb results for that sample will be associated with the scheduled visit 
and summarized accordingly. Samples collected outside this window will be excluded from the 
by-visit ADAb summaries and figures and will be listed only. This window will not apply to the 
summary of cumulative ADAb status, all available data will be used to derive the cumulative 
ADAb status. 
ADAb status will be derived as follows:  
• Samples 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) 
[…] 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-injection 
(DV0004 Baseline) and after self-injection (at DV0004 Week 4 and PA0012 Week 8) will be 
summarized by visit. The ADAb visit status will be based on the confirmatory assay at the 
respective visit. This visit status and the overall status (considering data in DV0004 only and 
data in DV0004 and the feeder studies) will be used for the summary tables and will be based 
on the Safety Set. 
[…] 
The number and percentage of ADAb-positive and ADAb-negative subjects before self-injection 
(DV0004 Baseline) and after self-injection (at DV0004 Week 4 and PA0012 Week 8) will be 
summarized by visit. The ADAb visit status will be based on the confirmatory assay at the 
respective visit. This visit status and the overall status (considering data in DV0004 only and 
data in DV0004 and the feeder studies) will be used for the summary tables and will be based on 
the Safety Set. 
Cumulative ADAb status is used for the box plots and summaries described in Section 9.1. 
Cumulative and overall ADAb status is derived as follows: 
a. Considering data in DV0004 only: 
• If a subject is ADAb positive at any time during DV0004 up to and including the respective 
DV0004 visit, they are assigned ADAb cumulative positive status for that and all subsequent 
visits. This will be based on the confirmatory assay at each visit in DV0004 (Baseline, Week 
4, Week 8). 
• Otherwise, the subject remains If a subject has only negative at that respective DV0004 visit 
and assigned ADAb cumulative samples or only one missing/inconclusive sample with all 
negative ADAb samples up to that timepoint, the subject will be classified as negative. 
• Otherwise, the study participant will be classified in the missing ADAb category. 
b. Considering data in the feeder studies (PA0010, PA00011) and 
DV0004: 
• If a subject is ADAb positive at any time in PA0010/PA0011 and DV0004 up to and 
including the respective DV0004 visit, they are assigned ADAb cumulative positive status 
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for that and all subsequent visits. This will be based on the cumulative status at DV0004 
Entry Visit (last visit in Feeder Study) and the confirmatory assay results in DV0004 (Week 
4 and Week 8). 
• Otherwise, the subject remains If a subject has only negative at that respective DV0004 visit 
and assigned ADAb cumulative samples or only one missing/inconclusive sample with all 
negative ADAb samples up to that timepoint, the subject will be classified as negative. 
• Otherwise, the study participant will be classified in the missing ADAb category. 
 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
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Approval Signatures
Name:
dv0004-sap-amend-4
Version:
1. 0
Document Number:
CLIN-000182610
Title:
dv0004-sap-amend-4
Approved Date:
16 Dec 2021
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 16-Dec-2021 12:04:58 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 16-Dec-2021 13:56:03 GMT+0000
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