Clinical trial NCT03895203
Conditions: Psoriatic Arthritis
Keywords: Psoriatic Arthritis PsA Bimekizumab
Sponsor: UCB Biopharma SRL
Start date: 2019-04-03; Completion date: 2022-07-11
Enrollment: 852 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study to demonstrate the clinical efficacy, safety and tolerability of bimekizumab administered subcutaneously (sc) compared with placebo in the treatment of subjects with active Psoriatic Arthritis (PsA).

Detailed description:

Arms: arm 1: Subjects randomized to this arm will receive assigned bimekizumab dosage regimen and placebo to maintain the blinding with adalimumab and placebo arms during the Treatment Period. arm 2: Subjects randomized to this arm will receive the assigned adalimumab dosage regimen during the Treatment Period. arm 3: Subjects randomized to this arm will receive placebo during the Double-Blind Treatment Period and will be reallocated to receive bimekizumab dosage regimen during the Maintenance Period.
Interventions: intervention 1: Bimekizumab intervention 2: Adalimumab intervention 3: Placebo
Intervention descriptions: intervention 1: Subjects will receive bimekizumab at pre-specified time-points. intervention 2: Adalimumab will be administered according to the labeling recommendations. intervention 3: Subjects will receive placebo at pre-specified time-points.

Protocol documents:
Prot_000.pdf: 
UCB 
 
22 Feb 2021 
Clinical Study Protocol 
Bimekizumab 
PA0010 
 
 
 
Confidential 
Page 1 of 189 
PROTOCOL PA0010 AMENDMENT 2 
 
A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, ACTIVE REFERENCE 
(ADALIMUMAB) STUDY EVALUATING THE EFFICACY AND 
SAFETY OF BIMEKIZUMAB IN THE TREATMENT OF 
SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS 
PHASE 3 
EudraCT Number: 2017-002322-20 
IND Number: 128708 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
 
Protocol/Amendment number 
Date 
Type of amendment 
 Final Protocol 
28 Nov 2018 
Not applicable 
Protocol Amendment 0.1 (Japan) 
05 Feb 2019 
Not applicable 
Protocol Amendment 1 
10 Jan 2020 
Substantial 
Protocol Amendment 1.1 (Japan) 
04 Feb 2020 
Substantial 
Protocol Amendment 2 
22 Feb 2021 
Substantial 
 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 


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STUDY CONTACT INFORMATION 
Sponsor 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Sponsor Study Physician 
Name: 
 
Address: 
UCB Celltech Ltd 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
Clinical Project Manager 
Name: 
 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Str. 10 
40789 Monheim 
GERMANY 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
 
Address: 
UCB 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 
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 REPORTING 
Serious adverse event reporting (24h) 
All serious adverse events will be reported and transmitted to Patient Safety through the 
eCRF system. The numbers below are to be used to send ancillary documentation only 
(discharge summaries, death certificates, etc) or in the event that the electronic reporting 
(eCRF) is not available. 
Fax 
Europe and Rest of the World: +32-2-386-24-21 
USA and Canada: +1-800-880-6949 or +1-866-890-3175 
Email 
Global: DS_ICT@ucb.com  
 


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TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................... 4 
LIST OF TABLES ................................................................................................................... 10 
LIST OF FIGURES ................................................................................................................. 10 
LIST OF ABBREVIATIONS .................................................................................................. 11 
1 
SUMMARY ..................................................................................................................... 16 
2 
INTRODUCTION ........................................................................................................... 17 
2.1 
Psoriatic arthritis .......................................................................................................... 17 
2.1.1 
Psoriatic arthritis epidemiology ........................................................................... 17 
2.1.2 
Current treatments for psoriatic arthritis .............................................................. 17 
2.2 
Bimekizumab ............................................................................................................... 18 
2.2.1 
Nonclinical ........................................................................................................... 18 
2.2.2 
Clinical ................................................................................................................. 19 
2.2.2.1 
Completed studies ..................................................................................... 19 
2.2.2.2 
Ongoing studies ......................................................................................... 22 
2.3 
Adalimumab ................................................................................................................. 23 
3 
STUDY OBJECTIVES .................................................................................................... 23 
3.1 
Primary objective ......................................................................................................... 23 
3.2 
Secondary objectives ................................................................................................... 23 
3.3 
Other objectives ........................................................................................................... 24 
4 
STUDY VARIABLES ..................................................................................................... 24 
4.1 
Efficacy variables......................................................................................................... 24 
4.1.1 
Primary efficacy variable ..................................................................................... 24 
4.2 
Secondary variables ..................................................................................................... 24 
4.2.1 
Secondary efficacy variables ............................................................................... 24 
4.2.2 
Secondary safety variables .................................................................................. 25 
4.3 
Other variables ............................................................................................................. 25 
4.3.1 
Other efficacy variables ....................................................................................... 25 
4.3.2 
Other safety variables .......................................................................................... 27 
4.3.3 
Pharmacokinetic variable ..................................................................................... 27 
4.3.4 
Pharmacogenomic variables ................................................................................ 28 
4.3.5 
Immunological variables ..................................................................................... 28 
5 
STUDY DESIGN ............................................................................................................. 28 
5.1 
Study description ......................................................................................................... 28 
5.2 
Screening Period/Baseline ........................................................................................... 29 
5.2.1 
Within-study rescreening/retesting requirements ................................................ 29 
5.3 
Treatment Period .......................................................................................................... 30 
5.3.1 
Double-Blind Treatment Period .......................................................................... 30 


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5.3.2 
Active Treatment-Blind Period ............................................................................ 30 
5.4 
Permitted rescue therapy after Week 16 ...................................................................... 31 
5.5 
Safety Follow-Up Visit ................................................................................................ 32 
5.6 
Study duration per subject ........................................................................................... 32 
5.7 
Planned number of subjects and sites .......................................................................... 32 
5.7.1 
Enrollment of hs-CRP/bone erosion positive subjects ........................................ 32 
5.8 
Anticipated regions and countries ................................................................................ 33 
5.9 
Schedule of study assessments..................................................................................... 33 
5.10 
Schematic diagram ....................................................................................................... 40 
5.11 
Rationale for study design and selection of dose ......................................................... 40 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................................... 41 
6.1 
Inclusion criteria .......................................................................................................... 41 
6.2 
Exclusion criteria ......................................................................................................... 42 
6.3 
Withdrawal criteria ...................................................................................................... 46 
6.3.1 
Potential drug-induced liver injury IMP discontinuation criteria ........................ 48 
7 
STUDY TREATMENTS ................................................................................................. 49 
7.1 
Description of investigational medicinal products ...................................................... 49 
7.2 
Treatments to be administered ..................................................................................... 49 
7.3 
Packaging ..................................................................................................................... 51 
7.4 
Labeling ....................................................................................................................... 51 
7.5 
Handling and storage requirements ............................................................................. 51 
7.6 
Drug accountability ...................................................................................................... 51 
7.7 
Procedures for monitoring subject compliance ............................................................ 52 
7.8 
Concomitant medications/treatments ........................................................................... 52 
7.8.1 
Permitted concomitant treatments (medications and therapies) .......................... 52 
7.8.1.1 
Psoriasis treatments ................................................................................... 52 
7.8.2 
Prohibited concomitant treatments (medications and therapies) ......................... 53 
7.8.3 
Vaccines ............................................................................................................... 54 
7.9 
Blinding........................................................................................................................ 54 
7.9.1 
Procedures for maintaining and breaking the treatment blind ............................. 55 
7.9.1.1 
Maintenance of study treatment blind ....................................................... 55 
7.9.1.2 
Breaking the treatment blind in an emergency situation ........................... 55 
7.10 
Randomization and numbering of subjects .................................................................. 55 
8 
STUDY PROCEDURES BY VISIT ............................................................................... 56 
8.1 
Screening Period/Baseline ........................................................................................... 56 
8.1.1 
Screening ............................................................................................................. 56 
8.1.2 
Baseline (Day 1) .................................................................................................. 57 
8.2 
Treatment Period .......................................................................................................... 59 


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8.2.1 
Double-Blind Treatment Period .......................................................................... 59 
8.2.1.1 
Week 2 ....................................................................................................... 59 
8.2.1.2 
Week 4 ....................................................................................................... 59 
8.2.1.3 
Weeks 6, 10, and 14 .................................................................................. 61 
8.2.1.4 
Week 8 ....................................................................................................... 61 
8.2.1.5 
Week 12 ..................................................................................................... 62 
8.2.1.6 
Week 16 ..................................................................................................... 63 
8.2.2 
Active Treatment-Blind Period ............................................................................ 64 
8.2.2.1 
Weeks 18 and 22 ....................................................................................... 64 
8.2.2.2 
Week 20 ..................................................................................................... 64 
8.2.2.3 
Week 24 ..................................................................................................... 65 
8.2.2.4 
Weeks 26, 30, 34, 38, 42, 46, and 50 ........................................................ 66 
8.2.2.5 
Week 28 ..................................................................................................... 67 
8.2.2.6 
Week 32 ..................................................................................................... 67 
8.2.2.7 
Week 36 ..................................................................................................... 68 
8.2.2.8 
Week 40 ..................................................................................................... 69 
8.2.2.9 
Week 44 ..................................................................................................... 69 
8.2.2.10 
Week 48 ..................................................................................................... 70 
8.2.2.11 
Week 52 ..................................................................................................... 70 
8.3 
Early Termination Visit ............................................................................................... 72 
8.4 
Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final dose) ................. 73 
8.5 
Unscheduled Visits ...................................................................................................... 74 
9 
ASSESSMENT OF EFFICACY ...................................................................................... 75 
9.1 
Joint assessments ......................................................................................................... 75 
9.1.1 
68/66 joint evaluation for ACR response and verification of Inclusion 
Criterion 5 ............................................................................................................ 75 
9.1.2 
28 joint evaluation for determination of DAS28(CRP) ....................................... 76 
9.2 
ACR20, ACR50, and ACR70 response ....................................................................... 76 
9.3 
Patient’s Global Assessments ...................................................................................... 76 
9.3.1 
Patient’s Global Assessment of Psoriatic Arthritis (PGA-PsA) .......................... 76 
9.3.2 
Patient’s Global Assessment of Arthritis (PGA-arthritis) ................................... 77 
9.4 
Physician’s Global Assessments .................................................................................. 77 
9.4.1 
Physician’s Global Assessment of Psoriatic Arthritis (PhGA-PsA) .................... 77 
9.4.2 
Physician’s Global Assessment of Arthritis (PhGA-Arthritis) ............................ 77 
9.5 
Patient’s Assessment of Arthritis Pain (PtAAP) .......................................................... 77 
9.6 
Health Assessment Questionnaire-Disability Index score (HAQ-DI) ......................... 78 
9.7 
High sensitivity C-reactive protein levels (hs-CRP) .................................................... 78 
9.8 
Evaluation of psoriasis ................................................................................................. 78 


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9.8.1 
Body surface area-psoriasis (BSA-PSO) ............................................................. 78 
9.8.2 
Psoriasis Area and Severity Index (PASI) ........................................................... 78 
9.8.3 
Investigator’s Global Assessment (IGA) ............................................................. 79 
9.8.4 
Modified Nail Psoriasis Severity Index (mNAPSI) ............................................. 80 
9.9 
Minimal Disease Activity (MDA) and Very Low Disease Activity (VLDA) ............. 80 
9.10 
Disease Activity Index for Psoriatic Arthritis (DAPSA) ............................................. 80 
9.11 
Van der Heijde modified Total Sharp Score (vdHmTSS) ........................................... 81 
9.12 
Disease Activity Score-28 based on C-reactive protein (DAS28[CRP]) ..................... 81 
9.13 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ............................... 81 
9.14 
Leeds Enthesitis Index (LEI) ....................................................................................... 81 
9.15 
Spondyloarthritis Research Consortium of Canada (SPARCC) .................................. 82 
9.16 
Leeds Dactylitis Index (LDI) ....................................................................................... 82 
9.17 
Psoriatic Arthritis Quality of Life (PsAQoL) .............................................................. 82 
9.18 
Psoriatic Arthritis Impact of Disease-12 (PsAID-12) .................................................. 82 
9.19 
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale ......... 82 
9.20 
Short-Form 36-item Health Survey (SF-36) ................................................................ 83 
9.21 
Euro Quality of life 5-Dimensions-3 Level (EQ-5D-3L) ............................................ 83 
9.22 
Work Productivity and Activity Impairment Questionnaire–Specific Health Problem 
(WPAI-SHP) ................................................................................................................ 83 
9.23 
Psoriatic Arthritis Response Criteria (PsARC) ............................................................ 83 
9.24 
Psoriatic Arthritis Disease Activity Score (PASDAS) ................................................ 84 
10 ASSESSMENT OF PHARMACOKINETIC AND PHARMACOGENOMIC 
VARIABLES ................................................................................................................... 84 
10.1 
Pharmacokinetic variable ............................................................................................. 84 
10.2 
Pharmacogenomic variables ........................................................................................ 84 
11 ASSESSMENT OF IMMUNOLOGICAL VARIABLES ............................................... 85 
12 ASSESSMENT OF SAFETY .......................................................................................... 86 
12.1 
Adverse events ............................................................................................................. 86 
12.1.1 
Definitions ........................................................................................................... 86 
12.1.1.1 
Adverse event ............................................................................................ 86 
12.1.1.2 
Serious adverse event ................................................................................ 86 
12.1.1.3 
Adverse events of special interest ............................................................. 88 
12.1.1.4 
Other safety topics of interest .................................................................... 88 
12.1.2 
Procedures for reporting and recording adverse events ....................................... 89 
12.1.2.1 
Description of adverse events .................................................................... 89 
12.1.2.2 
Rule for repetition of an adverse event...................................................... 89 
12.1.2.3 
Additional procedures for reporting serious adverse events ..................... 89 
12.1.3 
Follow-up of adverse events ................................................................................ 90 
12.1.4 
Pregnancy ............................................................................................................ 91 


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12.1.5 
Suspected transmission of an infectious agent via a medicinal product .............. 92 
12.1.6 
Overdose of investigational medicinal product ................................................... 92 
12.1.7 
Safety signal detection ......................................................................................... 92 
12.2 
Laboratory measurements ............................................................................................ 92 
12.2.1 
Evaluation of potential drug-induced liver injury................................................ 94 
12.2.1.1 
Consultation with Medical Monitor and local hepatologist ...................... 99 
12.2.1.2 
Immediate action: determination of IMP discontinuation ......................... 99 
12.2.1.3 
Testing: identification/exclusion of alternative etiology ......................... 100 
12.2.1.4 
Follow-up evaluation ............................................................................... 102 
12.3 
Other safety measurements ........................................................................................ 102 
12.3.1 
Vital signs .......................................................................................................... 102 
12.3.2 
Body weight and height ..................................................................................... 103 
12.3.3 
Physical examination ......................................................................................... 103 
12.3.4 
12-lead electrocardiogram ................................................................................. 103 
12.3.5 
Assessment and management of TB and TB risk factors .................................. 103 
12.3.5.1 
Tuberculosis assessment by IGRA .......................................................... 107 
12.3.5.2 
Chest x-ray for tuberculosis .................................................................... 107 
12.3.5.3 
Tuberculosis questionnaire ...................................................................... 107 
12.3.5.4 
Tuberculosis management ....................................................................... 107 
12.3.6 
Pregnancy testing ............................................................................................... 108 
12.3.7 
Assessment of suicidal ideation and behavior ................................................... 108 
12.3.8 
Patient Health Questionnaire-9 (PHQ-9) ........................................................... 108 
13 STUDY MANAGEMENT AND ADMINISTRATION ............................................... 109 
13.1 
Adherence to protocol ................................................................................................ 109 
13.2 
Monitoring ................................................................................................................. 109 
13.2.1 
Definition of source data ................................................................................... 109 
13.2.2 
Source data verification ..................................................................................... 110 
13.3 
Data handling ............................................................................................................. 110 
13.3.1 
Case Report form completion ............................................................................ 110 
13.3.2 
Database entry and reconciliation ...................................................................... 111 
13.3.3 
Subject Screening and Enrollment log/Subject Identification Code list............ 111 
13.4 
Termination of the study ............................................................................................ 111 
13.5 
Archiving and data retention ...................................................................................... 111 
13.6 
Audit and inspection .................................................................................................. 112 
13.7 
Good Clinical Practice ............................................................................................... 112 
14 STATISTICS ................................................................................................................. 112 
14.1 
Definition of analysis sets .......................................................................................... 112 
14.2 
General statistical considerations ............................................................................... 113 


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14.3 
Planned efficacy analyses .......................................................................................... 113 
14.3.1 
Analysis of the primary and secondary efficacy variables ................................ 113 
14.3.1.1 
Analysis of the primary efficacy variable ............................................... 114 
14.3.1.2 
Analysis of the secondary efficacy variables .......................................... 116 
14.3.2 
Analysis of the other efficacy variables ............................................................. 118 
14.3.3 
Subgroup analyses ............................................................................................. 119 
14.4 
Planned safety analyses.............................................................................................. 120 
14.4.1 
Safety analyses ................................................................................................... 120 
14.5 
Other planned analyses .............................................................................................. 120 
14.5.1 
Pharmacokinetics analyses ................................................................................ 120 
14.5.2 
Immunological analyses .................................................................................... 120 
14.6 
Handling of protocol deviations................................................................................. 120 
14.7 
Handling of dropouts or missing data ........................................................................ 121 
14.8 
Planned interim analyses and data monitoring .......................................................... 122 
14.8.1 
Interim analyses ................................................................................................. 122 
14.8.2 
Data monitoring ................................................................................................. 122 
14.9 
Determination of sample size ..................................................................................... 123 
14.9.1 
Power calculation for primary endpoint ............................................................ 123 
14.9.2 
Power calculations for secondary endpoints ...................................................... 123 
15 ETHICS AND REGULATORY REQUIREMENTS .................................................... 126 
15.1 
Informed consent ....................................................................................................... 126 
15.2 
Subject identification cards ........................................................................................ 126 
15.3 
Institutional Review Boards and Independent Ethics Committees ............................ 126 
15.4 
Subject privacy........................................................................................................... 127 
15.5 
Protocol amendments ................................................................................................. 127 
16 FINANCE, INSURANCE, AND PUBLICATION ....................................................... 128 
17 REFERENCES .............................................................................................................. 128 
18 APPENDICES ............................................................................................................... 133 
18.1 
Classification Criteria for Psoriatic Arthritis ............................................................. 133 
18.2 
Protocol Amendment 1 .............................................................................................. 134 
18.3 
Protocol Amendment 2 .............................................................................................. 171 
19 DECLARATION AND SIGNATURE OF INVESTIGATOR ..................................... 188 
20 SPONSOR DECLARATION ........................................................................................ 189 
 


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LIST OF TABLES 
Table 5-1: 
Schedule of study assessments......................................................................... 34 
Table 7-1: 
Dosing scheme ................................................................................................. 50 
Table 7-2: 
Prohibited or restricted medications and required wash-out periods ............... 53 
Table 7-3 
Additional prohibited psoriasis treatments ...................................................... 54 
Table 9-1: 
Swelling and tenderness grading ..................................................................... 76 
Table 9-2: 
Body areas for calculation of percent BSA for PASI ...................................... 79 
Table 9-3: 
Five-point IGA ................................................................................................. 79 
Table 12-1: 
Anticipated SAEs for the population of subjects with PsA ............................. 88 
Table 12-2: 
Laboratory measurements ................................................................................ 93 
Table 12‒3: 
Required investigations and follow-up for PDILI ........................................... 96 
Table 12-4: 
PDILI laboratory measurements .................................................................... 101 
Table 12-5: 
PDILI information to be collected ................................................................. 102 
Table 14‒1: 
Treatment effect by elevated hs-CRP and/or bone erosion at Baseline for 
secondary efficacy analyses ........................................................................... 125 
Table 18-1: 
CASPAR Criteria ........................................................................................... 133 
 
LIST OF FIGURES 
Figure 5-1: 
Study schematic diagram ................................................................................. 40 
Figure 12-1: 
Schematic diagram of TB test results and study eligibility ........................... 105 
Figure 12‒2: Schematic diagram of TB test results during the study ................................. 106 
Figure 14-1: 
Sequential testing procedure of primary/secondary efficacy endpoints 
(fixed sequence testing procedure) ................................................................ 114 
 


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LIST OF ABBREVIATIONS 
ACR 
American College of Rheumatology 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AMS 
Active Medication Set 
ANCOVA 
analysis of covariance 
AS 
ankylosing spondylitis 
AST 
aspartate aminotransferase 
ATS 
Active Treatment-Blind Set 
BA 
bioavailability 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
bDMARD 
biologic disease modifying antirheumatic drug  
BP 
blood pressure 
BSA 
body surface area 
CASPAR 
Classification Criteria for Psoriatic Arthritis 
CCP 
cyclic citrullinated peptide 
CD 
cluster of differentiation 
cDMARD 
conventional disease-modifying antirheumatic drug 
CDMS 
clinical data management system 
CI 
confidence interval 
COX-2 
cyclooxygenase-2 
CPM 
Clinical Project Manager 
CRO 
contract research organization 
CRP 
C-reactive protein 
CSR 
Clinical Study Report 
CZP 
certolizumab pegol 
DAPSA 
Disease Activity Index for Psoriatic Arthritis 
DAS28(CRP) 
Disease Activity Score-28 based on C-reactive protein 
DIP 
distal interphalangeal 
DMARD 
disease modifying antirheumatic drug 
DMC 
Data Monitoring Committee 


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ECG 
electrocardiogram 
eCRF 
electronic Case Report form 
eC-SSRS 
electronic Columbia-Suicide Severity Rating Scale 
EDC 
electronic data capture 
ePRO 
Electronic Patient-Reported Outcome 
EQ-5D-3L 
EuroQol-5 Dimensions-3 Level 
ES 
Enrolled Set 
ET 
Early Termination 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HAQ-DI 
Health Assessment Questionnaire – Disability Index 
HCQ 
hydroxychloroquine 
HCV 
hepatitis C virus 
HDL 
high density lipoprotein 
HIV 
human immunodeficiency virus 
HLA-B27 
human leukocyte antigen B27 
HRQoL 
Health-Related Quality of Life 
HS 
hidradenitis suppurativa 
hs-CRP 
high sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
IBD 
inflammatory bowel disease 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IGA 
Investigator’s Global Assessment 
IGRA 
interferon gamma release assay 
IL 
interleukin 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 


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iv 
intravenous 
IXRS 
interactive voice or web response system  
LDI 
Leeds Dactylitis Index 
LDL 
low density lipoprotein 
LEF 
leflunomide 
LEI 
Leeds Enthesitis Index 
LN 
natural logarithm 
LS 
least squares 
LTB 
latent tuberculosis 
MAR 
missing at random 
MCMC 
Markov-Chain Monte Carlo 
MCS 
Mental Component Summary 
MDA 
Minimal Disease Activity 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
mNAPSI 
modified Nail Psoriasis Severity Index 
MTX 
methotrexate 
NHP 
nonhuman primate 
NRI 
nonresponder imputation 
NSAID 
nonsteroidal anti-inflammatory drug 
NTMB 
nontuberculous mycobacteria 
OC 
observed case 
PASI 
Psoriasis Area and Severity Index 
PASDAS 
Psoriatic Arthritis Disease Activity Score 
PCS 
Physical Component Summary 
PD 
pharmacodynamic 
PDILI 
potential drug-induced liver injury 
PFS 
prefilled syringe 
PGADA 
Patient’s Global Assessment of Disease Activity 
PGA-Arthritis 
Patient’s Global Assessment of Arthritis 
PGA-PsA 
Patient’s Global Assessment of Psoriatic Arthritis 
PhGADA 
Physician’s Global Assessment of Disease Activity 


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PhGA-Arthritis 
Physician’s Global Assessment of Arthritis 
PhGA-PsA 
Physician’s Global Assessment of Psoriatic Arthritis 
PHQ-9 
Patient Health Questionnaire-9 
PK 
pharmacokinetic 
PK-PPS 
Pharmacokinetics Per-Protocol Set 
PPS 
Per-Protocol Set 
PS 
Patient Safety 
PsA 
psoriatic arthritis 
PsAID-12 
Psoriatic Arthritis Impact of Disease-12 
PsARC 
Psoriatic Arthritis Response Criteria  
PsAQoL 
Psoriatic Arthritis Quality of Life 
PSO 
psoriasis 
PtAAP 
Patient’s Assessment of Arthritis Pain 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
R/L 
right/left 
RA 
rheumatoid arthritis 
RNA 
ribonucleic acid 
RS 
Randomized Set 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous(ly) 
SD 
standard deviation 
SF-36 
Short-Form 36-item Health Survey 
SFU 
Safety Follow-up 
SJC 
swollen joint count 
SOP 
standard operating procedure 
SPARCC 
Spondyloarthritis Research Consortium of Canada 
SS 
Safety Set 
SSZ 
sulfasalazine 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 


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TNF 
tumor necrosis factor  
TNFα 
tumor necrosis factor alpha 
UC 
ulcerative colitis 
ULN 
upper normal limit 
VAS 
Visual Analog Scale 
vdHmTSS 
van der Heijde modified Total Sharp Score 
VLDA 
Very Low Disease Activity 
WPAI-SHP 
Work Productivity and Activity Impairment Questionnaire–Specific 
Health Problem 


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1 
SUMMARY 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, noninferential 
active reference study to evaluate the efficacy and safety of bimekizumab in subjects with active 
psoriatic arthritis (PsA) who are biologic disease-modifying antirheumatic drug (bDMARD) 
naïve. To be eligible to participate in this study, subjects must be adults with a diagnosis of 
active PsA based on the Classification Criteria for Psoriatic Arthritis (CASPAR) and have 
disease with tender joint count (TJC) ≥3 and swollen joint count (SJC) ≥3. In addition, subjects 
should not have been previously exposed to any bDMARD for PsA or psoriasis (PSO) to be 
eligible for the study.  
The primary objective is to demonstrate the efficacy of bimekizumab administered 
subcutaneously (sc) every 4 weeks (Q4W) for 16 weeks compared with placebo in the treatment 
of subjects with active PsA as assessed by the American College of Rheumatology (ACR) 
50% response. The secondary efficacy and safety objectives of the study are listed in Section 3.2, 
and other objectives are listed in Section 3.3. In this study, the efficacy of bimekizumab will be 
assessed with reference to the active-reference drug, adalimumab (HUMIRA®; AbbVie 
Pharmaceuticals, North Chicago, IL); however, no formal statistical comparisons of adalimumab 
to bimekizumab or placebo are planned. 
The primary efficacy variable for this study is the ACR50 at Week 16. The secondary and other 
efficacy variables are listed in Section 4.2.1 and Section 4.3.1, respectively. 
Safety variables are listed in Section 4.2.2 (secondary) and Section 4.3.2 (other). The 
pharmacokinetic (PK), and pharmacogenomic variables are listed in Section 4.3.3, and 
Section 4.3.4 , respectively. The immunological variable is listed in Section 4.3.5.  
PA0010 will evaluate the efficacy and safety of bimekizumab 160mg sc Q4W in adult subjects 
with active PsA. The dose regimens were selected based on currently available safety and 
efficacy data from a Phase 2b study, and PK/pharmacodynamics (PD) modeling.  
The overall study design consists of a Screening Period (≥14 days to ≤35 days), a 16-week 
placebo-controlled Double-Blind Treatment Period, a 36-week Active Treatment-Blind Period, 
and a Safety Follow-Up (SFU) Visit 20 weeks after the final dose of investigational medicinal 
product (IMP) (for subjects not entering the extension study or who discontinue early, including 
those withdrawn from IMP). The maximum study duration per subject will be up to 73 weeks.  
It is planned to enroll a minimum of 45% of subjects who are positive for elevated high 
sensitivity C-reactive protein (hs-CRP ≥6mg/L) and/or who have at least 1 bone erosion at 
Screening. 
During the Double-Blind Treatment and Active Treatment-Blind Periods, permitted rescue 
therapy after Week 16 is described in Section 5.4. Subjects’ permitted background medications 
may be changed if the subject is not responding as per Investigator assessment. 
Subjects completing Week 52 are eligible for enrollment in an extension study where all subjects 
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Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
bone erosion [0, ≥1]) to the following treatment groups: bimekizumab 160mg sc Q4W 
(420 subjects), placebo (280 subjects), and adalimumab sc 40mg every 2 weeks (Q2W) 
(140 subjects). The planned number of study sites is approximately 150. 
2 
INTRODUCTION 
2.1 
Psoriatic arthritis 
Psoriatic arthritis is a chronic inflammatory musculoskeletal disorder, which occurs in 
approximately 6% to 41% of people affected by PSO (Ogdie and Weiss, 2015). A substantial 
proportion of subjects have polyarthritis (McHugh et al, 2003). These disorders are distinct from 
rheumatoid arthritis (RA), the prototypical inflammatory arthritis, and generally have an earlier 
onset, distal interphalangeal (DIP) joint involvement, asymmetric distribution, dactylitis 
(inflammation of the whole digit), enthesitis (inflammation at the site of tendon insertion into 
bone), spinal involvement, and an association with the human leukocyte antigen (HLA)-B27 
allele.  
Previous work has implicated various isoforms of the interleukin (IL)-17 cytokine family in the 
pathophysiology of PSO and of PsA (Raychaudhuri et al, 2012; Fujishima et al, 2010; 
Watanabe et al, 2009; Harper et al, 2009; Johansen et al, 2009). Numbers of IL-17A-positive 
cells are increased and localized in psoriatic skin lesions (Fujishima et al, 2010; 
Watanabe et al, 2009; Harper et al, 2009; Johansen et al, 2009), and IL-17A and IL-17F are 
overexpressed in the serum and skin lesions of subjects with PSO (Johansen et al, 2009), while 
IL-17F in particular is a key inflammatory cytokine contributing to PSO pathology 
(Fujishima et al, 2010; Watanabe et al, 2009). Cluster of differentiation (CD) 4 + T helper 17 
(Th17) cells, IL-17A, and IL-17 receptor A (IL-17-RA) have recently been shown to play a role 
in PsA (Raychaudhuri et al, 2012). Anti-IL-17 antibodies have been shown to be effective 
treatments for PSO (Papp et al, 2012; Leonardi et al, 2012; Hueber et al, 2010) and have also 
shown activity in subjects with RA, PsA, and ankylosing spondylitis (AS) (McInnes et al, 2014; 
Mease et al, 2015; Hueber et al, 2010; Genovese et al, 2010). Taken together, these data suggest 
that inhibition of both IL-17A and IL-17F could be therapeutically effective in subjects with 
PSO, PsA, and axial spondyloarthritis. 
2.1.1 
Psoriatic arthritis epidemiology 
Psoriatic arthritis is usually diagnosed years after PSO appears. A substantial proportion of 
subjects have polyarthritis (Gladman 2015; McHugh et al, 2003). More than 50% of patients 
with PsA experience progressive, erosive arthritis that is often accompanied by pain, fatigue, and 
functional impairment. The combination of joint and skin manifestations of PsA can have a 
profound impact on patient function, well-being, and Health-Related Quality of Life (HRQoL). 
The functional impairments are also associated with significant direct health care costs and 
substantial work-related disability, including a lower rate of employment (Lee et al, 2010; 
Salaffi et al, 2009). 
2.1.2 
Current treatments for psoriatic arthritis 
Disease-modifying antirheumatic drugs (DMARDs) and biological agents targeting tumor 
necrosis factor alpha (TNFα), IL-17, and IL-12/23 are effective for the treatment of PsA 
(Kavanaugh et al, 2012; Kavanaugh et al, 2009; Gottlieb et al, 2009; Gladman et al, 2007; 


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Genovese et al, 2007; Kavanaugh et al, 2006; Antoni et al, 2005a; Antoni et al, 2005b; 
Mease et al, 2005; Mease et al, 2004; McInnes et al, 2015; Mease et al, 2015). Current treatments 
include DMARDs (hydroxychloroquine, azathioprine, cyclosporine, cyclophosphamide, 
mycophenolic acid, mycophenolate mofetil, sulfasalazine [SSZ], tofacitinib, apremilast, 
abatacept, methotrexate [MTX], and leflunomide [LEF]), IL-17A inhibitor (secukinumab, and 
ixekizumab) and TNFα inhibitors (infliximab, adalimumab, etanercept, golimumab, and 
certolizumab pegol [CZP]). However, some subjects are not responsive to these treatments 
(defined as achieving ACR20 response criteria), do not maintain a clinical response, or have 
contraindications or intolerance to these agents. The long-term goals of therapy include 
improvement in symptoms of the disease, psoriatic plaque clearance, inhibition of disease 
progression, and prevention of bone destruction. 
2.2 
Bimekizumab 
Bimekizumab (UCB4940) is an engineered, humanized full-length monoclonal antibody of 
immunoglobin G1 (IgG1) subclass of approximately 150,000 Dalton, which is expressed in a 
genetically engineered Chinese Hamster Ovarian (CHO) cell line. Bimekizumab has high affinity 
for human IL-17A and human IL-17F, and selectively and potently inhibits the activity of both 
isoforms in vitro. Interleukin-17A and IL-17F are key proinflammatory cytokines believed to 
play important roles in autoimmune and inflammatory diseases. Interleukin-17A has been shown 
to have a role in pathogenesis of several autoimmune disorders and IL-17F has been increasingly 
recognized to contribute to the pathogenesis of a number of inflammatory diseases, including 
PSO, ulcerative colitis, asthma, AS, PsA, and RA (Raychaudhuri et al, 2012; 
Fujishima et al, 2010; Watanabe et al, 2009).  
While anti-IL-17A antibodies have demonstrated efficacy in subjects with PSO, PsA, and AS, 
there is currently no therapeutic approach available that fully inhibits the activity of IL-17F. 
Bimekizumab selectively and potently inhibits the activity of both IL-17A and IL-17F isoforms 
in vitro. Therefore, it permits an evaluation of the potential for additional efficacy, which may be 
conferred by dual inhibition of both cytokines in patients with diseases in which both cytokines 
are active. Furthermore, a proof-of-concept study (PA0007) with bimekizumab in subjects with 
moderate to severe PsA demonstrated a strong efficacy signal that warrants further exploration of 
bimekizumab in this indication. A Phase 2b, dose-ranging study (PA0008) was designed to 
investigate the efficacy and safety of various bimekizumab dose regimens in subjects with active 
PsA. The current Phase 3, randomized, double-blind, placebo-controlled, and active-controlled 
confirmatory study (PA0010) is designed to investigate the efficacy and safety of bimekizumab 
in subjects with active PsA. 
2.2.1 
Nonclinical 
There is increasing evidence of the role of IL-17F in various inflammatory diseases. 
Simultaneous inhibition of IL-17A and IL-17F has been shown to be more efficacious than 
inhibition of IL-17A alone in in vitro models. Intravenously or sc administered bimekizumab 
was well tolerated in repeat-dose toxicology studies in Cynomolgus monkeys with dosing up to 
200mg/kg/week for up to 26 weeks. The findings of note varied from study to study but were all 
compatible with decreased muco-epidermal immunity induced by the inhibition of IL-17A and F 
signaling. They consisted of diarrhea-related to infectious enteritis, asymptomatic proliferation of 
a protozoan commonly found in the Cynomolgus monkey, Balantidium coli, superficial 


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dermatitis associated with increased bacterial load on the skin (mainly gram-positive cocci, 
including Staphylococcus aureus), and abscesses.  
Infection-related safety findings in a nonhuman primate can be highly variable from study to 
study and have limited ability to accurately predict the incidence and type of infection that can be 
expected in humans, especially because nonhuman primates bear different commensal flora and 
show different sensitivity to different pathogens. Immunomodulators can increase the 
susceptibility of monkeys to potential pathogens that are endemic in nonhuman primate 
populations and usually remain clinically undetectable or are mild and self-limiting in 
immunocompetent animals. Moreover, infections associated with the gastrointestinal (GI) tract 
that result in chronic enterocolitis are a persistent and widespread colony problem in nonhuman 
primates, often multifactorial in origin.  
The nonclinical studies have highlighted the already known risk of infection linked to decreased 
muco-epidermal immunity that needs to be carefully monitored in the clinic but are unlikely to 
predict the risk of infection in humans based on dose and exposure for the aforementioned 
reasons. To date, similar findings have not been seen in studies in humans. 
Results from the embryofetal and postnatal study conducted in the Cynomolgus monkey indicate 
no effects of bimekizumab on the gestation, gestation duration, or the parturition of pregnant 
females. No bimekizumab-related effects were noted in infants at birth, during postnatal 
development, or on infant survival rate. Toxicokinetic data confirmed dose-related exposure of 
maternal animals during the pregnancy and the lactation phase, and of infants at birth and during 
the postnatal phase. 
Additional information on the nonclinical data for bimekizumab is available in the current 
version of the Investigator’s Brochure (IB). 
2.2.2 
Clinical 
2.2.2.1 
Completed studies 
In the overall bimekizumab development program, the following clinical studies in healthy 
volunteers and subjects with PSO, RA, PsA, AS, ulcerative colitis (UC), and hidradenitis 
suppurativa (HS) have been completed: 
• UP0008 was a Phase 1, first-in-human study in subjects with mild to moderate PSO.  
• RA0124 and UP0031 were 2 Phase 1, bioavailability studies in healthy subjects. 
• UP0033 was a Phase 1, open-label, multicenter, randomized, parallel-group, 3-arm, single-
dose bioequivalence study of bimekizumab injected sc either by a prefilled syringe (PFS) or 
by an auto-injector in adult healthy subjects. 
• UP0034 is a Phase 1, open-label, randomized, parallel-group, single-dose study to evaluate 
the antibody response of influenza vaccination following concomitant exposure to 
bimekizumab in adult healthy subjects. 
• UP0074 was a Phase 1, open-label, randomized, parallel-group, single-dose study to evaluate 
the PK, safety, and tolerability of bimekizumab given as 2x1mL or 1x2mL sc administration 
in healthy subjects. 
• PA0007 was a Phase 1b study in subjects with moderate to severe PsA. 


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• UP0042 was a Phase 1, PK study in healthy Japanese and Caucasian subjects. 
• RA0123 was a Phase 2a study evaluating safety, PK, PD, and efficacy in subjects with 
moderate to severe RA who received bimekizumab as an add-on therapy to CZP. 
• UC0011 was a Phase 2a, multinational, multicenter, subject- and Investigator-blind, 
randomized, placebo-controlled study to evaluate the efficacy, safety, tolerability, and PK of 
bimekizumab in adult subjects with moderate to severe active UC (discontinued study). 
• PS0016 was a Phase 2a study evaluating the time course of Psoriasis Area and Severity Index 
(PASI) response, safety, and PK in subjects with moderate to severe chronic plaque PSO. 
PS0018 was the corresponding Phase 2 extension study. 
• PS0018 was a Phase 2 OLE study evaluating the long-term safety, tolerability, and efficacy 
of bimekizumab in subjects who completed PS0016. 
• PS0010 was a Phase 2b placebo-controlled dose-ranging study evaluating safety, efficacy, 
PK, and PD in subjects with moderate to severe PSO. 
• PS0011 was a Phase 2b, multicenter, 48-week, double-blind, parallel-group, extension study 
to assess the long-term safety, tolerability, and efficacy of bimekizumab in adult subjects 
with moderate to severe chronic plaque PSO who completed PS0010. 
• PS0008 is a Phase 3, multicenter, randomized, double-blind, parallel-group, active-
comparator-controlled study to evaluate the efficacy and safety of bimekizumab in adult 
subjects with moderate to severe chronic plaque PSO. 
• PS0009 is a Phase 3 randomized, double-blind, placebo- and active comparator-controlled 
study to evaluate the efficacy and safety of bimekizumab administered sc to adult subjects 
with moderate to severe plaque PSO. 
• PS0013 is a Phase 3, multicenter, randomized withdrawal, double-blind, placebo-controlled 
study to evaluate the efficacy and safety of bimekizumab in adult subjects with moderate to 
severe chronic plaque PSO. 
• PA0008 was a Phase 2b study evaluating the efficacy and safety in subjects with active PsA. 
• AS0008 was a Phase 2b, placebo-controlled study evaluating the efficacy and safety of 
bimekizumab in subjects with active AS. 
• HS0001 was a Phase 2 study to evaluate the safety, efficacy, and PK of bimekizumab in 
subjects with moderate to severe HS. 
To evaluate treatment in subjects with PsA, bimekizumab has been investigated in a Phase 1b, 
proof-of-concept, randomized, placebo-controlled, multiple-dose study (PA0007). The primary 
objective of PA0007 was to assess the safety and PK of multiple dose administration of iv 
bimekizumab in subjects with PsA. Four active doses and a placebo were tested. Drug was 
administered as a loading dose at Week 1, and 2 additional doses were administered at Week 4 
and Week 7. In each treatment group, subjects received a total of 3 doses of bimekizumab, 
administered every 3 weeks as shown below: 
• 80mg loading dose followed by 40mg at Weeks 4 and 7 
• 160mg loading dose followed by 80mg at Weeks 4 and 7 


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• 240mg loading dose followed by 160mg at Weeks 4 and 7 
• 560mg loading dose followed by 320mg at Weeks 4 and 7 
The results of this study demonstrated that all doses of bimekizumab were well tolerated and 
there were no unexpected clinically relevant safety findings. 
Infections (mostly nasopharyngitis) were the most commonly reported events in both the active 
treatment and the placebo group. None of the infections were considered serious or required 
treatment with antibiotics. Two subjects in the active treatment group experienced one local 
candida infection each (oropharyngitis and vulvovaginitis, respectively) that were nonserious and 
resolved with topical therapy. There was a potential reduction in mean neutrophil count in the 
active treatment group, although this drop was not clinically relevant and a clear relationship 
with dose or time was not evident. Some increases in liver function tests were reported, but none 
had a clear relationship to exposure to IMP. The exploratory analysis showed clinically relevant 
improvement in activity of PsA and in skin involvement in those subjects with concomitant 
active psoriatic lesions. 
PA0008 was a Phase 2b, placebo-controlled study to evaluate the efficacy, safety, tolerability, 
PK, PD, and immunogenicity of bimekizumab in subjects with active PsA. The primary 
objective of PA0008 was to assess the dose response based on the efficacy of bimekizumab 
administered sc Q4W (monthly) for 12 weeks in the treatment of subjects with active PsA. 
During the 12-week Double-Blind Period, subjects were randomized 1:1:1:1:1 (stratified by 
region and prior tumor necrosis factor [TNF] inhibitor exposure) to receive the following blinded 
IMP regimens. The enrollment of TNF inhibitor-experienced subjects was planned to be limited 
to approximately 30% of the total study population (actual enrollment was 18.9% of all subjects). 
• Placebo 
• Bimekizumab 16mg administered sc Q4W 
• Bimekizumab 160mg administered sc Q4W 
• Bimekizumab 320mg administered sc Q4W 
• Bimekizumab 320mg loading dose followed by 160mg administered sc starting at Week 4 
and Q4W thereafter  
After the 12-week Double-Blind Period, subjects entered the 36-week Dose-Blind Period. At the 
Week 12 Visit, subjects were allocated to bimekizumab treatment regimens: 160mg Q4W or 
320mg Q4W. 
The results of this study demonstrated a statistically significant dose response in the primary 
efficacy variable (ACR50 response at Week 12), and the dose response was linear for 
bimekizumab doses up to 160mg. The results of all secondary efficacy endpoints (ACR20, 
ACR70, PASI75, and PASI90 response at Week 12) were consistent with and supported the 
findings of the primary endpoint. All bimekizumab doses were associated with a greater response 
compared with placebo. 
In PA0008, all doses of bimekizumab were well tolerated, and there were no unexpected 
clinically relevant safety findings. During the overall study, the most commonly reported adverse 
events (AEs) in subjects treated with bimekizumab were nasopharyngitis (12.3%), upper 


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respiratory tract infection (10.3%), respiratory tract infection (5.9%), and pharyngitis (5.4%); all 
other AEs were reported by <5.0% of subjects. There was no apparent relationship to 
bimekizumab dose with regard to the incidence of treatment-emergent adverse events (TEAEs). 
Eight participants (3.9%) had serious adverse events (SAEs) in bimekizumab arms, and no SAE 
(by preferred term) was reported by more than 1 subject. Eight participants (3.9%) discontinued 
due to a TEAE. 
Additional information on the clinical data for bimekizumab is available in the current version of 
the Investigator’s Brochure (IB). 
2.2.2.2 
Ongoing studies 
The following studies of bimekizumab are ongoing:  
• PS0014 is a Phase 3, long-term extension study for eligible subjects from the Phase 3 PSO 
feeder studies to assess the safety, tolerability, and efficacy of bimekizumab. 
− DV0002 and DV0006 are multicenter, randomized, open-label studies to evaluate the 
safe and effective use of the prefilled safety syringe or the auto-injector for the sc 
self-injection of bimekizumab solution by subjects with moderate to severe PSO. 
DV0002 and DV0006 are substudies of PS0014; DV0002 is being conducted in North 
America, and DV0006 is being conducted in the EU and Japan.  
• PS0015 is a Phase 3b, randomized, double-blind, secukinumab-controlled, parallel-group 
study to evaluate the efficacy and safety of bimekizumab administered sc to subjects with 
moderate to severe chronic plaque PSO. 
• PA0009 is a Phase 2b, long-term extension study for eligible subjects from PA0008 to assess 
the safety, tolerability, and efficacy of bimekizumab. 
• PA0011 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study 
evaluating the efficacy and safety of bimekizumab in the treatment of subjects with active 
PsA. 
• PA0012 is a Phase 3, multicenter, OLE study to assess the long-term safety, tolerability, and 
efficacy of bimekizumab in the treatment of subjects with active PsA who complete PA0010 
or PA0011. 
− DV0004 is a multicenter, randomized, open-label study to evaluate the safe and effective 
use of the prefilled safety syringe or auto-injector for the sc self-injection of 
bimekizumab solution by subjects with active PsA. DV0004 is a substudy of PA0012. 
• AS0009 is a Phase 2b, long-term extension study for eligible subjects from AS0008 to assess 
the safety, tolerability, and efficacy of bimekizumab.  
• AS0010 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study 
evaluating the efficacy and safety of bimekizumab in subjects with active nonradiographic 
axial spondyloarthritis. 
• AS0011 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study 
evaluating the efficacy and safety of bimekizumab in subjects with active AS. 


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• AS0014 is a Phase 3, multicenter, OLE study to assess the long-term safety, tolerability, and 
efficacy of bimekizumab in the treatment of subjects who complete AS0010 or AS0011. 
• AS0013 is a Phase 2a, active-controlled study evaluating the efficacy and safety of 
bimekizumab compared with CZP in subjects with active AS. 
• HS0003 and HS0004 are Phase 3, multicenter, randomized, double-blind, placebo-controlled 
studies evaluating the efficacy and safety of bimekizumab in subjects with moderate to 
severe HS. 
• HS0005 is a Phase 3, multicenter, OLE study to assess the long-term safety, tolerability, and 
efficacy of bimekizumab in the treatment of subjects who complete HS0003 or HS0004. 
Additional information on the clinical data for bimekizumab is available in the current version of 
the IB. 
2.3 
Adalimumab 
In this study, the efficacy of bimekizumab will be assessed with reference to the active-reference 
drug, adalimumab. Adalimumab’s mechanism of action occurs through TNFα inhibition 
compared with bimekizumab’s inhibition of IL-17A and IL-17F (HUMIRA®, 2016). 
Adalimumab has been approved for the treatment of several auto-immune diseases such as PsA, 
RA, AS, Crohn’s disease, HS, and plaque PSO in the US and EU, as well as in many other 
countries globally, and is among the first line standard of care biologic therapy for patients not 
responding to conventional disease-modifying antirheumatic drugs (cDMARDs).  
3 
STUDY OBJECTIVES 
3.1 
Primary objective 
The primary objective is to demonstrate the clinical efficacy of bimekizumab administered sc 
Q4W for 16 weeks compared with placebo in the treatment of subjects with active PsA, as 
assessed by the ACR50 response. 
3.2 
Secondary objectives 
The secondary objectives of the study are as follows: 
• To assess the efficacy of bimekizumab compared with placebo  
• To assess the safety and tolerability of bimekizumab 
• To assess the impact of bimekizumab on patient-reported quality of life 
• To assess the impact of bimekizumab on skin PSO in the subgroup of affected subjects at 
Baseline 
• To assess the impact of bimekizumab on functional improvement  
• To assess the impact of bimekizumab on radiographic changes in the hands and feet 
• To assess the impact of bimekizumab on extra-articular disease manifestations (dactylitis, 
enthesitis) 


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3.3 
Other objectives 
Other objectives are as follows: 
• To descriptively assess the efficacy of bimekizumab with reference to adalimumab  
• To assess the immunogenicity of bimekizumab  
• To assess the impact of bimekizumab treatment on axial disease 
• To assess the maintenance of treatment effect 
• To assess nail PSO in the subgroup of affected subjects at Baseline 
• To explore the exposure response relationship of bimekizumab 
• To assess the effect of bimekizumab on gene and protein expression, and explore the 
relationship between genomic, genetic, and proteomic biomarkers and disease biology, drug 
treatment and inflammatory and immune responses (from consenting subjects who agree to 
participate in the biomarker substudy) 
• To assess the impact of bimekizumab on social life and work productivity 
4 
STUDY VARIABLES 
4.1 
Efficacy variables 
4.1.1 
Primary efficacy variable 
The primary efficacy variable for this study is the ACR50 response at Week 16. 
4.2 
Secondary variables 
4.2.1 
Secondary efficacy variables 
The secondary efficacy variables for this study are as follows: 
• Change from Baseline in Health Assessment Questionnaire—Disability Index (HAQ-DI) at 
Week 16 
• PASI90 response at Week 4 and Week 16 in the subgroup of subjects with PSO involving at 
least 3% BSA at Baseline 
• Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical 
Component Summary (PCS) at Week 16 
• Minimal Disease Activity (MDA) response at Week 16 
• Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in subjects 
with elevated hs-CRP and/or at least 1 bone erosion at Baseline at Week 16  
• Enthesitis-free state in the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of 
subjects with enthesitis at Baseline in the pooled population of PA0010 and PA0011 
• Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of 
subjects with dactylitis at Baseline in the pooled population of PA0010 and PA0011 
• Change from Baseline in vdHmTSS in the overall population at Week 16 


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• ACR20 response at Week 16 
• ACR70 response at Week 16 
• Proportion of subjects with an Investigator Global Assessment (IGA) score of 0 (clear) or 
1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 4 and Week 16 in 
the subset of subjects with psoriatic skin lesions at Baseline  
• Change from Baseline in the Patient’s Assessment of Arthritis Pain (PtAAP) at Week 16 
• Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada 
(SPARCC) index at Week 16 in the subgroup of subjects with enthesitis at Baseline 
• Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at 
Week 16 
4.2.2 
Secondary safety variables 
Secondary safety variables to be assessed are as follows: 
• Incidence of TEAEs 
• Incidence of treatment-emergent SAEs 
• TEAEs leading to withdrawal from IMP  
4.3 
Other variables 
4.3.1 
Other efficacy variables 
Other efficacy variables will be assessed as specified in Table 5-1 (all time points not specified 
in Section 4.1.1 or Section 4.2.1 are exploratory): 
• Time to ACR20, ACR50, and ACR70 response from Baseline (Day 1)  
• ACR20, ACR50, and ACR70 response 
• PASI75, PASI90, and PASI100 response in the subgroup of subjects with PSO involving at 
least 3% BSA at Baseline 
• Composite endpoint composed of ACR50 and PASI90 response in subjects with PSO 
involving at least 3% BSA at Baseline 
• Composite endpoint composed of ACR50 and PASI100 response in subjects with PSO 
involving at least 3% BSA at Baseline 
• Proportion of Psoriatic Arthritis Response Criteria (PsARC) responders 
• Psoriatic Arthritis Disease Activity Score (PASDAS) categories 
• Change from Baseline in the PASDAS  
• The proportion of ACR50 responders at Week 16 and maintaining response at Week 52 
• MDA response 
• Very Low Disease Activity (VLDA) response 


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• Proportion of subjects with an IGA score of 0 (clear) or 1 (almost clear) AND at least a 
2-grade reduction from Baseline in the subset of subjects with psoriatic skin lesions at 
Baseline 
• Disease Activity Index for Psoriatic Arthritis (DAPSA) score categories 
• Change from Baseline in DAPSA score 
• Change from Baseline in the Disease Activity Score-28 based on C-reactive protein 
(DAS28[CRP]) 
• Change from Baseline in all individual ACR core components: 
− SJC 
− TJC 
− HAQ-DI  
− PtAAP  
− Physician’s Global Assessment of Psoriatic Arthritis (PhGA-PsA)  
− Patient’s Global Assessment of Psoriatic Arthritis (PGA-PsA) 
− hs-CRP  
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores) in subjects with elevated hs-CRP and/or with at least 1 bone erosion at Baseline 
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores) in the overall population 
• Proportion of subjects with no radiographic joint damage progression (change from Baseline 
vdHmTSS of ≤0.5)  
• Dactylitis-free state based on the LDI in the subgroup of subjects with dactylitis at Baseline 
in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Enthesitis-free state based on the LEI in the subgroup of subjects with enthesitis at Baseline 
in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Enthesitis-free state based on the SPARCC index in the subgroup of subjects with enthesitis 
at Baseline in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Proportion of subjects with a decrease of HAQ-DI from Baseline of at least 0.35 in those 
subjects with HAQ-DI>0.35 at Baseline 
• Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
in the subgroup of subjects with axial involvement defined by a score of ≥4 at Baseline 
• Change from Baseline in the modified Nail Psoriasis Severity Index (mNAPSI) score in the 
subgroup of subjects with psoriatic nail disease at Baseline 
• Change from Baseline in the LEI in the subgroup of subjects with enthesitis at Baseline in the 
pooled population of PA0010 and PA0011, as well as for PA0010 alone 


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• Change from Baseline in the SPARCC index in the subgroup of subjects with enthesitis at 
Baseline in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Change from Baseline in the LDI in the subgroup of subjects with dactylitis at Baseline in the 
pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Change from Baseline in PsAID-12 total score, as well as the individual domain scores 
• Proportion of subjects achieving PsAID-12 total score ≤4 
• Proportion of PsAID-12 responders (decrease from Baseline in PsAID-12 total score ≥3 in 
subjects with PsAID-12 total score >3 at Baseline) 
• Change from Baseline in the Psoriatic Arthritis Quality of Life (PsAQoL) total score 
• Change from Baseline in the SF-36 PCS and Mental Component Summary (MCS), as well as 
the 8 domain scores (Physical Functioning, Role Physical, Bodily Pain, General Health, 
Vitality, Social Functioning, Role Emotional, and Mental Health) 
• Change from Baseline in Functional Assessment of Chronic Illness Therapy 
(FACIT)-Fatigue subscale score 
• Proportion of FACIT-Fatigue subscale responders (subjects with a minimum clinically-
important difference for FACIT-Fatigue subscale score, defined as an increase of ≥4) 
• Change from Baseline in Work Productivity and Activity Impairment Questionnaire-Specific 
Health Problem (WPAI-SHP) v2.0 adapted to PsA scores  
• Responses to the EuroQol-5 Dimensions-3 Level (EQ-5D-3L)  
• Change from Baseline in EQ-5D-3L Visual Analog Scale (VAS) scores 
• Change from Baseline in Physician’s Global Assessment of Arthritis (PhGA-Arthritis) 
• Change from Baseline in Patient’s Global Assessment of Arthritis (PGA-Arthritis)  
4.3.2 
Other safety variables 
Other safety variables to be assessed are: 
• Change from Baseline in vital signs (blood pressure [BP], temperature, and pulse rate) 
• Standard 12-lead electrocardiogram (ECG) results 
• Change from Baseline in clinical laboratory values (hematology, biochemistry and 
urinalysis) 
• Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) 
Physical examination findings considered clinically significant changes since the physical 
examination at the Screening Visit will be recorded as AEs. 
4.3.3 
Pharmacokinetic variable 
The PK variable is the plasma concentration of bimekizumab. 


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4.3.4 
Pharmacogenomic variables 
Additional blood samples will be collected from subjects who consent to participate in the 
substudy at specific time points. If the collected samples are not used immediately, they will be 
stored at -80°C for up to 20 years until the completion of bimekizumab development program. 
Genomic, genetic, epigenetic, proteins, and metabolite biomarkers may be measured to evaluate 
the relationship with response to treatment with bimekizumab, psoriatic arthritis disease biology, 
and inflammatory and immune response processes. The nature and format of these tentative 
substudy analyses will be determined when the results of the main study are made available. 
The candidate exploratory variables are the blood or blood derivative (eg, serum) concentrations 
of cytokines and chemokines of relevance to IL-17A/F signaling pathway and psoriatic arthritis 
biology. Additional variables may include but will not be limited to serum complement 
concentrations. Where local regulations permit, additional blood samples will be collected at 
time points specified in Table 5-1. They may be used to allow for potential exploratory analyses 
of ribonucleic acid (RNA), proteins, lipids, and metabolite biomarkers relevant to disease 
biology and progression, response to therapy, the inflammatory and immune response processes, 
and cardiovascular risk in PsA. 
4.3.5 
Immunological variables 
The immunological variables are the anti-bimekizumab antibody status and the 
treatment-emergent antibody positivity derived from anti-drug antibody assays. 
5 
STUDY DESIGN 
5.1 
Study description 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, active-reference 
study to evaluate the efficacy and safety of bimekizumab in subjects with active PsA. To be 
eligible to participate in this study, subjects must be adults with a diagnosis of active PsA based 
on the CASPAR criteria and have active disease with TJC ≥3 and SJC ≥3. It is planned to enroll 
a minimum of 45% of subjects who are positive for elevated hs-CRP (hs-CRP ≥6mg/L) and/or 
who have at least 1 bone erosion at Screening. 
Subjects should not have previously been treated with any biologic drugs for PsA or PSO. 
Detailed inclusion and exclusion criteria are presented in Section 6.1 and Section 6.2, 
respectively. 
The study will include 3 periods: a Screening Period (≥14 days to ≤35 days), a Treatment Period 
(52 weeks), and a Safety Follow-up Period (20 weeks after the final dose of IMP). The 
Treatment Period will consist of a 16-week Double-Blind Treatment Period followed by a 
36-week Active Treatment-Blind Period. Permitted rescue therapy changes after Week 16 are 
described in Section 5.4. The maximum study duration per subject will be up to 73 weeks. 
Eligible subjects will be randomized 3:2:1 (stratified by region and bone erosion [0, ≥1]) to 
receive 1 of 3 blinded treatments (bimekizumab 160mg sc Q4W, placebo, or active-reference 
[adalimumab 40mg sc Q2W]) and will remain on their allowable background medication. Details 
of the Treatment Period are provided in Section 5.3. 


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Subjects completing Week 52 and meeting eligibility criteria are eligible for enrollment in an 
extension study to continue to receive bimekizumab.  
An interim analysis of all available data (including efficacy, safety, and PK) will be undertaken 
after all randomized subjects have completed 24 weeks of treatment or have withdrawn from 
IMP or the study. The purpose of this analysis is to perform a comprehensive evaluation of all 
available data for the 3 treatment arms to prepare a regulatory submission for a marketing 
authorization application based on this analysis.  
A second interim analysis of all available data will be undertaken after all randomized subjects 
have completed 52 weeks of treatment or have withdrawn from IMP or the study. The purpose of 
this analysis is to demonstrate the long-term efficacy and safety of bimekizumab. For subjects 
who are ineligible for the open-label extension study at Week 52, a final analysis will be 
undertaken after the SFU Visit. 
Additional details for the interim analyses and data monitoring in this study are provided in 
Section 14.8.1. A detailed schedule of study assessments is presented in Table 5-1 and a study 
schematic diagram is presented in Figure 5-1.  
5.2 
Screening Period/Baseline 
The Screening Period will last for a minimum duration of 14 days and a maximum duration of 
35 days and will involve obtaining laboratory data and verifying that the doses of nonsteroidal 
anti-inflammatory drugs (NSAIDs), or permitted DMARDs, if used to treat PsA, are stable. The 
Screening Period will also enable washout of any medications not permitted for use during the 
study.  
During the Screening Period, X-rays of hands and feet will be assessed for bone erosion and used 
for the stratification of subjects at Baseline (Day 1). 
5.2.1 
Within-study rescreening/retesting requirements 
Rules for rescreening or repetition of screening tests within the study are listed below: 
• Subjects who fail to meet the eligibility criteria for PHQ-9, electronic Columbia-Suicide 
Severity Rating Scale (eC-SSRS), or the tuberculosis (TB) questionnaire are not allowed to 
be rescreened. 
The Medical Monitor must be contacted for confirmation of rescreening/retesting in all other 
cases. 
• Subjects who initially fail to meet selected eligibility criteria (eg, documented completion of 
latent tuberculosis infection [LTBI] prophylactic therapy) may be rescreened. 
• Subjects for whom eligibility assessments could not be completed as planned (eg, for 
technical reasons) within the defined Screening Period of 35 days may be rescreened.  
• Subjects with individual laboratory screening tests for which the results are exclusionary, can 
be retested.  
Of note, repetition of laboratory screening tests within the Screening Period is permitted for 
technical reasons (eg, frozen sample, expired laboratory kit) without contacting the Medical 
Monitor. 


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5.3 
Treatment Period 
5.3.1 
Double-Blind Treatment Period 
During the Double-Blind Treatment Period, subjects will be randomized 3:2:1 (stratified by 
region and bone erosion [0, ≥1]) to 1 of 3 blinded treatments. 
Investigational medicinal product treatment details are provided in Section 7.2. Visit windows of 
±2 days are allowed for all visits through Week 16. The visit window is relative to the Day 1 
(Baseline) Visit. 
Bimekizumab, adalimumab, and placebo will be administered sc by unblinded study personnel at 
the clinical site. 
The time between IMP doses should be ≥12 days and ≤16 days during the Double-Blind 
Treatment Period. The Double-Blind Period is 16 weeks in duration. At Week 16, subjects will 
transition from the double-blind, placebo-controlled treatment into the 36-week Active 
Treatment-Blind Period, as discussed in Section 5.3.2. 
Subjects withdrawing early from the study will undergo the Early Termination (ET) 
Visit assessments and will enter the SFU Period. Subjects who withdraw from IMP during the 
Double-Blind Period will be encouraged to return for all scheduled visits up to Week 52 and for 
the SFU Visit (20 weeks after their final dose of IMP), as applicable. 
5.3.2 
Active Treatment-Blind Period 
After the 16-week Double-Blind Treatment Period, subjects will enter the 36-week 
Active Treatment-Blind Period. At the Week 16 Visit, subjects will be allocated to treatment 
regimens as follows:  
• Subjects in the bimekizumab 160mg sc Q4W group will continue to receive 
bimekizumab 160mg Q4W 
• Subjects in the adalimumab 40mg sc Q2W group will continue to receive 
adalimumab 40mg sc Q2W  
• Subjects in the placebo group will be reallocated to bimekizumab 160mg sc Q4W 
Bimekizumab and adalimumab will be administered sc by unblinded study personnel at the 
clinical site. The first dose in the Active Treatment-Blind Period will be administered at Week 16 
after all assessments have been completed. After Week 16, if the subjects are not responding 
adequately as per Investigators’ judgement, rescue therapy will be allowed as described in 
Section 5.4. 
Visit windows of ±3 days are allowed for all visits after Week 16. 
The time between doses during the Active Treatment-Blind Period should be ≥11 days and 
≤17 days. 
Subjects who withdraw early from the study will undergo the ET Visit assessments and will 
enter the SFU Period. Subjects who withdraw from IMP during the Active-Treatment-Blind 
Period will be encouraged to return for all remaining scheduled visits up to Week 52 and the 
SFU Visit (20 weeks after their final dose of IMP), as applicable. 


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At the completion of the Active Treatment-Blind Period, Investigators should discuss treatment 
options with the subject. Subjects who complete PA0010 will be given the opportunity to enter 
an extension study at Week 52. 
5.4 
Permitted rescue therapy after Week 16 
After Week 16, subjects may be rescued by changes to their permitted background medications, 
if the subject is not responding as per Investigator assessment. Permitted rescue therapy changes 
are listed below. Any other changes should be discussed with the Medical Monitor prior to the 
change. 
Subjects who are rescued will remain on IMP. Permitted rescue therapy for eligible subjects will 
be at the Investigator’s discretion, with the following options:  
• Nonsteroidal anti-inflammatory drugs, DMARDs (MTX, SSZ, LEF, hydroxychloroquine 
[HCQ], apremilast), and/or joint injections may be given as permitted rescue therapy if 
deemed appropriate by the Investigator as outlined below. Subjects may receive these add-on 
therapies while continuing to receive their randomized dose of IMP. 
− For subjects taking NSAID/cyclooxygenase 2 (COX-2) inhibitors at Baseline, a change 
can be made to a different NSAID/COX-2 inhibitor. Changes from an NSAID to a 
COX-2 inhibitor or from a COX-2 inhibitor to an NSAID are permitted up to the 
maximum approved or tolerated dose, whichever is lower. Only 1 NSAID/COX-2 
inhibitor may be taken at a given time. 
− For subjects not taking NSAID/COX-2 inhibitors at Baseline, either an NSAID or COX-2 
inhibitor can be initiated, up to the maximum approved or tolerated dose, whichever is 
lower. Only 1 NSAID/COX-2 inhibitor may be taken at a given time.  
− Methotrexate may be added or increased to a maximum dose of 25mg/week, or the 
maximum tolerated dose, whichever is lower. The route of administration may be 
changed from oral to sc.  
− Sulfasalazine may be given up to a maximum dose of 3g/day or 4g/day if in accordance 
with local standard of care, or the maximum tolerated dose, whichever is lower.  
− Leflunomide may be given at a maximum dose of 20mg/day (or an average of 20mg/day 
if not dosed daily), or the maximum tolerated dose, whichever is lower.  
− Hydroxychloroquine may be added or increased to a maximum dose of 400mg/day or the 
maximum tolerated dose, whichever is lower. 
− Apremilast may be given at a maximum dose of 30mg twice daily, or the maximum 
tolerated dose, whichever is lower. 
− Combination DMARDs are allowed except that LEF and MTX may not be given 
together. 
− Up to 2 joints (up to a total dose of 80mg methylprednisolone or equivalent) may be 
injected at or after Week 16; however, the same joint should not be injected more than 
once during the study. 


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• A decrease in dose or dosing frequency of any agent for the treatment of PsA is permitted for 
reasons of intolerance/AEs/side-effects at any time. 
• Any medication not listed in the protocol for rescue must be approved by the Medical 
Monitor prior to starting that medication. 
• If, in the judgment of the Investigator, the options outlined above are not considered 
appropriate for the subject, or the subject does not achieve sufficient response to these 
options, biologics may be considered. Subjects must discontinue IMP prior to use of another 
biologic therapy and follow the withdrawal criteria and follow-up as outlined in Section 6.3.  
• Permitted rescue therapy will be determined by the Investigator taking into account the 
half-life of bimekizumab (27.8 days). 
No other medication changes or additions are permitted for rescue therapy. 
Subjects may be withdrawn from IMP at any time if they are judged to be not responding and 
continue treatment per the Investigator’s discretion, as described in the Withdrawal Section 
(Section 6.3). 
5.5 
Safety Follow-Up Visit 
All subjects who complete the study and do not enter the extension study will have an 
SFU Visit, 20 weeks after their final dose of IMP. 
Any subjects who discontinue early, including those withdrawn from IMP, will be asked to 
attend all scheduled visits and will have an SFU Visit, 20 weeks after their final dose of IMP. 
5.6 
Study duration per subject 
For each subject, the study will last up to 73 weeks, as follows: 
• ≥14 days to ≤35 days in the Screening Period 
• 16 weeks in the placebo-controlled, Double-Blind Treatment Period 
• 36 weeks in the Active Treatment-Blind Period 
• An SFU Visit 20 weeks after the final dose of IMP (for subjects not entering the extension 
study or who discontinue early, including those withdrawn from IMP) 
The end of the study is defined as the date of the last visit of the last subject in the study. 
5.7 
Planned number of subjects and sites 
Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
bone erosion [0, ≥1]) to the following treatment groups: bimekizumab 160mg sc Q4W (420 
subjects), placebo (280 subjects), and adalimumab 40mg sc Q2W (140 subjects). The planned 
number of study sites is approximately 150. 
5.7.1 
Enrollment of hs-CRP/bone erosion positive subjects 
It is planned to enroll a minimum of 45% of subjects who are positive for elevated hs-CRP 
(hs-CRP ≥6mg/L) and/or who have at least 1 bone erosion at Screening. 


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5.8 
Anticipated regions and countries 
This will be a multicenter, international study. Enrollment will be competitive among study sites 
and may be capped at sites.  
5.9 
Schedule of study assessments 
The schedule of study assessments is presented in Table 5-1. 
 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
Written Informed 
consent 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
c 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriatic arthritis 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Significant past 
medical history 
and concomitant 
diseases 
X 
X d 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior medication 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PHQ-9 
X 
X 
  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
eC-SSRS 
X 
X 
  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Height e 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight e 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Vital signs f 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
ECG by central 
reader 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Hematology/ 
biochemistryg 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
hs-CRP h 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
Pregnancy testingi 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA-B27 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RF and anti-CCP 
antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for 
bimekizumab 
plasma 
concentrationsj 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Anti-
bimekizumab 
antibody 
detectionj 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Serum and plasma 
blood samples for 
exploratory 
biomarkersj 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RNA blood 
samples for 
exploratory 
biomarkersj 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
Blood samples for 
genetic/ 
epigenetic 
analysis j 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGRA 
tuberculosis test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Tuberculosis 
questionnaire 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Physical 
examinationk 
X 
X 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
BSA affected by 
PSO l 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
PASIm 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
IGAm 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
TJC and SJC 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
HAQ-DI 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
PtAAP 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
PhGA-PsA 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
PhGA-Arthritis 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
PGA-PsA 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
PGA-Arthritis 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
BASDAI 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
mNAPSIn  
 
X 
 
X 
 
X 
 
X  
 
X 
 
 
 
X 
 
 
 
 
 
X  
 
 
 
 
 
 
 
X  
X  
 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
LEI 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
SPARCC 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
LDIo 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
PsAQoL 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
PsAID-12 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
FACIT-Fatigue 
subscale 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
SF-36 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
EQ-5D-3L 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
WPAI-SHP 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Chest x-rayp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-ray of hands 
and feetq 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Adverse eventsr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IXRSs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMP 
administrationt,u 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BP=blood pressure; BSA=body surface area; CASPAR=Classification Criteria for Psoriatic 
Arthritis; CCP=cyclic citrullinated peptide; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; EQ-5D-3L=EuroQol-5-
Dimensions-3 Level; ET=Early Termination; FACIT=Functional Assessment of Chronic Illness Therapy; HAQ-DI=Health Assessment Questionnaire—
Disability Index; HDL=high density lipoprotein; HIV=human immunodeficiency virus; HLA-27=human leukocyte antigen B27; hs-CRP=high sensitivity C-
reactive protein; IGA=Investigator’s Global Assessment; IGRA=interferon gamma release assay; IMP=investigational medicinal product; IXRS=interactive 
voice or web response system; LDI=Leeds Dactylitis Index; LDL=low density lipoprotein; LEI=Leeds Enthesitis Index; mNAPSI=modified Nail Psoriasis 
Severity Index; PASI=Psoriasis Area and 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; PsA=psoriatic arthritis; PsAID-12=Psoriatic Arthritis Impact of Disease-12; PsAQoL=Psoriatic Arthritis Quality of Life; 
PSO=psoriasis; PtAAP=Patient’s Assessment of Arthritis Pain; Q2W=every 2 weeks; Q4W=every 4 weeks; RF=rheumatoid factor; RNA=ribonucleic acid; 
SF-36= Short-Form 36-item Health Survey; SFU=Safety Follow-Up; SJC=swollen joint count; SPARCC= Spondyloarthritis Research Consortium of Canada; 
TB=tuberculosis; TJC=tender joint count; vdHmTSS=Van der Heijde modified Total Sharp Score; V=Visit; WPAI-SHP=Work Productivity and Activity 
Impairment Questionnaire–Specific Health Problem 
a Visit windows of ±2 days are allowed for all visits up to Week 16 and ±3 days are allowed for all visits after Week 16. The time between study treatment doses 
should be ≥12 days and ≤16 days or ≥11 days and ≤17 days, respectively. For the SFU Visit, the visit should occur no more than 3 days prior to the scheduled 
visit date and within 7 days after the scheduled visit date (-3 days/+7 days). 
b Safety Follow-Up Visit occurs 20 weeks after the final dose of IMP for all subjects who complete the study and do not enter the extension study or who 
discontinue early, including those withdrawn from IMP. 
c A complete history of lifestyle (alcohol, drug, and nicotine consumption at the time of Screening) and infections (fungal skin infections within 12 months prior 
to Screening). 
d Confirm there are no significant changes in medical history that would exclude the subject based on the exclusion criteria. 
e The Investigator or designee will measure the height of the subject with shoes removed in meters and the weight of the subject in kilograms. 
f Collect vital signs (pulse, BP, and temperature) prior to IMP administration and then at approximately 30 minutes after administration and 1 hour after 
administration at Baseline and Week 16 only. At all other applicable visits, vital signs will be collected once prior to IMP administration. All other procedures 
are done prior to dosing. 
g Biochemistry testing will include triglycerides, cholesterol, HDL cholesterol, and LDL cholesterol at Baseline, Weeks 12 and 24, and at the ET Visit. 
h After Baseline, the hs-CRP data will not be sent to the Investigator to protect the blinded nature of the treatment assignments. 
i Pregnancy testing will consist of serum testing at Screening for all women of childbearing potential. The pregnancy test will be urine at all other visits.  
j At dosing visits, all blood samples are taken prior to dosing. Blood samples for bimekizumab and anti-bimekizumab antibody detection will be processed as per 
instructions in the laboratory manual. 


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Table 5-1: 
Schedule of study assessments 
     Visit a/ 
Week 
 
Protocol activity 
Screening (V1) 
Baseline (Day 1) 
(first dose) (V2) 
Double-Blind Treatment Period 
(weeks after first dose) 
Active Treatment-Blind Period 
(weeks after first dose) 
 
 
3/ 
2 
4/ 
4 
5/ 
6 
6/ 
8 
7/ 
10 
8/ 
12 
9/ 
14 
10/ 
16 
11/
18 
12/
20 
13/
22 
14/
24 
15/
26 
16/
28 
17/
30 
18/
32 
19/
34 
20/
36 
21/
38 
22/
40 
23/
42 
24/
44 
25/
46 
26/
48 
27/
50 
28/
52 
ET 
SFU b 
k Includes evaluation of signs and symptoms of active TB and risk for exposure to TB.  
l Any subject with PSO lesions at Baseline will have a BSA-PSO assessment (Section 9.8.1) at each scheduled visit.  
m Only subjects with a BSA of ≥3% at Baseline will be required to have the PASI and IGA assessed at selected visits post Baseline (Day 1). 
n Only for subjects who have nail PSO at Baseline. 
o Circumference measured in millimeters. 
p If a subject has had a radiograph of the chest within 3 months prior to the Screening Visit, it may be used as the Screening chest x-ray. 
q The x-ray at Screening will be used for CASPAR classification (for inclusion) and will serve as the Baseline x-ray for assessment of the degree of joint damage, 
which will be assessed using the vdHmTSS (Van der Heijde et al, 2005). 
r  Adverse events are to be collected beginning at the signing of the Informed Consent form. 
s The IXRS will be used to register subjects at Screening, to randomize eligible subjects to treatment groups at Baseline (Day 1), to reallocate subjects (at 
Week 16) in the placebo group, and to register visits. 
t Bimekizumab subjects will be administered bimekizumab at Baseline, Week 4, and Q4W thereafter. The subjects will also receive dummy treatments at 
Week 2, and Q4W thereafter, in order to preserve the blind. Adalimumab subjects will be administered with adalimumab at Baseline, Week 2, and Q2W 
thereafter. Placebo will be administered at Baseline, Week 2, and Q2W thereafter to preserve blinding and correspond to the dosing schedule for adalimumab. 
For details of bimekizumab and adalimumab doses, see Section 7.2. 
u At Week 16 after all assessments are complete, the Active Treatment-Blind Period dosing will start as detailed in Section 5.3.2, at which point no subjects will 
be in the placebo group, but will still be administered placebo to maintain blind. 
.


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5.10 
Schematic diagram 
The study schematic PA0010 is presented in Figure 5-1.  
Figure 5-1: Study schematic diagram 
 
ACR50=American College of Rheumatology 50% response criteria; BKZ=bimekizumab; PsA=psoriatic arthritis; 
Q2W=every 2 weeks; Q4W=every 4 weeks; sc=subcutaneous; SFU=Safety Follow-Up; W=week 
a Adalimumab dosing is presented in Section 7.2.  
b After 16 weeks of double-blind treatment, subjects will enter the Active Treatment-Blind Period. All subjects 
randomized to placebo will be reallocated to receive bimekizumab 160mg Q4W. Subjects randomized to 
bimekizumab 160mg Q4W will continue to receive their originally randomized dose. Subjects randomized to 
active-reference (adalimumab) will continue with their active treatment.  
c Permitted rescue therapy is defined in Section 5.4. 
5.11 
Rationale for study design and selection of dose 
Bimekizumab 
Bimekizumab doses of 16mg, 160mg, 160mg with an initial 320mg dose, and 320mg were 
evaluated in PA0008, a Phase 2b multicenter, randomized, double-blind, placebo-controlled, 
parallel group, dose-ranging study. In this study, doses up to 320mg were well tolerated by 
subjects and found to have acceptable safety profile.  
PA0010 will evaluate the efficacy and safety of bimekizumab 160mg sc Q4W in adult subjects 
with active PsA. The dose was selected based on the data from Phase 2b study. In PA0008, both 
ACR50 and PASI90 responder rates saturate at bimekizumab 160mg Q4W, further increase in 
dose does not provide a significant benefit on either ACR50 or PASI90 responder rates. This 


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plateau at bimekizumab 160mg was further confirmed based on the observed noncontrolled 
Week 48 data, which demonstrated a similar ACR50 and PASI90 response between 160mg and 
320mg Q4W at Week 48. An exposure-response analysis was performed on both endpoints 
which also indicated that bimekizumab 160mg Q4W is the optimal dose for these patients.  
There were no dose-related safety concerns or changes in laboratory values in the preliminary 
data review up to 48 weeks that preclude the use of any of the tested doses in PA0008 for the 
Phase 3 program in PsA. 
Adalimumab 
Adalimumab is approved and indicated for the treatment of active and progressive PsA in adults 
when the response to previous DMARD therapy has been inadequate. The recommended dose of 
adalimumab for patients with PsA is 40mg adalimumab administered Q2W as a single dose via 
sc injection. Available data suggest that the clinical response is usually achieved within 12 weeks 
of treatment. Adalimumab dosing schedules are provided in Section 7.2.  
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1 
Inclusion criteria 
To be eligible to participate in this study, all of the following criteria must be met at Screening 
and be reconfirmed at the Baseline Visit: 
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject. 
2a. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand 
and complete diaries), visit schedule, or medication intake according to the judgment of the 
Investigator. 
3. Subject is male or female at least 18 years of age. 
4. Female subjects must be: 
− postmenopausal (menopause is defined as 12 consecutive months of amenorrhea, for 
which there is no other obvious pathological or physiological cause),  
− permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy),  
− or, if of childbearing potential (and engaged in sexual activity that could result in 
procreation), must be willing to use a highly effective method of contraception 
throughout the duration of the study until 20 weeks after last administration of IMP, and 
have a negative pregnancy test at Screening and immediately prior to the first dose.  
The following methods are considered highly effective when used consistently and 
correctly: 
− combined (estrogen and progestogen) hormonal contraception associated with inhibition 
of ovulation (oral, intravaginal, or transdermal)  
− progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, or implantable) 
− intrauterine device  


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− intrauterine hormone-releasing system  
− vasectomized partner  
− Abstinence as a form of birth control is generally not allowed in the study unless 
abstinence is in accordance with a subject’s preferred and common lifestyle. Study 
personnel must confirm the continued use of abstinence is still in accordance with the 
subject’s lifestyle at regular intervals during the study.  
5. Subject has a documented diagnosis of adult-onset PsA classified and meets the CASPAR 
classification criteria (Table 18-1) for at least 6 months prior to Screening with active PsA 
and must have at Baseline TJC ≥3 out of 68 and SJC ≥3 out of 66 (dactylitis of a digit counts 
as 1 joint each).  
6. Subject must be negative for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) 
antibodies.  
7. Subject must have at least 1 active psoriatic lesion(s) and/or a documented history of PSO. 
8. Subject must be considered, in the opinion of the Investigator, to be a suitable candidate for 
treatment with adalimumab per regional labeling and has no contraindications to receive 
adalimumab as per the local label. 
9. Subjects who are regularly taking NSAIDs/COX-2 inhibitors or analgesics (including mild 
opioids) as part of their PsA therapy are required to be on a stable dose/dose regimen for at 
least 14 days before Baseline and should remain on a stable dose until Week 16. 
10. Subjects taking oral corticosteroids must be on an average daily dose of ≤10mg/day 
prednisone or equivalent for at least 14 days before Baseline and should remain on a stable 
dose until Week 16. 
11. Subjects taking MTX (≤25mg/week) are allowed to continue their medication if started at 
least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization. 
Dose, dosing schedule and route of administration (oral or sc) should remain stable until 
Week 16. It is strongly recommended that subjects taking MTX are also taking folic acid 
supplementation. 
12. Subjects taking LEF (≤20mg/day or an average of 20mg/day if not dosed daily) are allowed 
to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose 
for at least 8 weeks before randomization. Dose and dosing schedule should remain stable 
until Week 16. 
13. Subjects taking SSZ (up to 3g/day, for arthritis or 4g/day if in accordance with local standard 
of care, HCQ (up to 400mg/day), or apremilast (up to 60mg/day and dosed as per local label) 
are allowed to continue their medication if started 8 weeks prior Baseline, with a stable dose 
for at least 4 weeks before randomization. Dose and dosing schedule should remain stable 
until Week 16. 
6.2 
Exclusion criteria 
Subjects are not permitted to enroll in the study if any of the following criteria are met: 
1. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 20 weeks following last dose of IMP.  


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2. Subjects with current or prior exposure to any biologics for the treatment of PsA or PSO, 
including participation in a bimekizumab clinical study who received at least 1 dose of IMP 
(including placebo). 
3. Subject previously participated in another study of a medication (systemic) under 
investigation. Subject must be washed out of the medication for 12 weeks or at least 
5 half-lives prior to the Baseline Visit, whichever is greater, or is currently participating in 
another study of a medication (systemic) under investigation, with the exception of subjects 
who were screen failures in PA0011. 
4. Subject previously participated in another study of a medical device under investigation 
within the 4 weeks prior to the Screening Visit or is currently participating in another study 
of a medical device under investigation. 
5. Subject has a known hypersensitivity to any excipients of bimekizumab or adalimumab.  
6. Subject is taking or has taken prohibited PsA or PSO medications without meeting the 
mandatory wash-out period relative to the Baseline Visit (Table 7-2 and Table 7-3).  
7. Subject has an active infection or history of infections as follows: 
− Any active infection (except common cold) within 14 days prior to Baseline. 
− A serious infection, defined as requiring hospitalization or iv anti-infectives within 
2 months prior to Baseline. 
− A history of opportunistic, recurrent or chronic infections that, in the opinion of the 
Investigator, might cause this study to be detrimental to the subject. Opportunistic 
infections are infections caused by uncommon pathogens (eg, pneumocystis jirovicii, 
cryptococcosis) or unusually severe infections caused by common pathogens 
(eg, cytomegalovirus, herpes zoster). 
8. Subject has concurrent acute or chronic viral hepatitis B or C or human immunodeficiency 
virus (HIV) infection. Subjects who have evidence of or tested positive for hepatitis B or 
hepatitis C are excluded.  
A positive test for the hepatitis B virus is defined as:  
• positive for hepatitis B surface antigen; or,  
• positive for anti-hepatitis B core antibody  
A positive test for the hepatitis C virus (HCV) is defined as:  
• positive for hepatitis C antibody (anti-HCV antibody), and  
• positive via a confirmatory test for HCV (for example, HCV polymerase chain reaction) 
9. Subject has received any live (includes attenuated) vaccination within the 8 weeks prior to 
the Baseline (eg, inactivated influenza and pneumococcal vaccines are allowed, but nasal 
influenza vaccination is not permitted). 
10. Subject has received Bacillus Calmette-Guerin (BCG) vaccinations within 1 year prior to the 
Baseline Visit. 


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11. Subject has known tuberculosis (TB) infection, is at high risk of acquiring TB infection, or 
has current or history of nontuberculous mycobacterium (NTMB) infection. A subject with 
latent tuberculosis (LTB) (a positive interferon gamma release assay [IGRA] and diagnosis 
confirmed by TB specialist) may be rescreened once and enrolled after receiving at least 
4 weeks of appropriate LTB infection (LTBI) therapy and if no evidence of therapy-related 
hepatotoxicity has occurred prior to the first injection (alanine aminotransferase 
[ALT]/aspartate aminotransferase [AST] remain ≤3 times upper limit of normal [ULN]). 
Subject has a past history of active TB involving any organ system unless adequately treated 
according to World Health Organization/Center for Disease Control and Prevention 
therapeutic guidance and proven to be fully recovered upon consult with a TB specialist. 
Refer to Section 12.3.5 for details on determining full TB exclusion criteria. 
12. Subject has a history of a lymphoproliferative disorder including lymphoma and/or current 
signs and symptoms suggestive of lymphoproliferative disease. 
13. Subject has a diagnosis of inflammatory conditions other than PSO or PsA including, but not 
limited to RA, sarcoidosis, systemic lupus erythematosus, and reactive arthritis. Subjects 
with a diagnosis of Crohn’s disease, ulcerative colitis, or other inflammatory bowel disease 
(IBD) are allowed as long as they have no active symptomatic disease at Screening or 
Baseline. 
14. Subject had acute anterior uveitis within 6 weeks of Baseline. 
15. Subjects with fibromyalgia or osteoarthritis symptoms that in the Investigator’s opinion 
would have potential to interfere with efficacy assessments. 
16. Subject has any active malignancy or history of malignancy within 5 years prior to the 
Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell 
carcinoma, or in situ cervical cancer. 
17. Subject has a form of PSO other than chronic plaque-type (eg, pustular, erythrodermic and 
guttate PSO, or drug-induced PSO). 
18. Subject has had major surgery (including joint surgery) within the 3 months prior to 
Baseline, or planned surgery within 6 months after entering the study. 
19. Subject has any systemic disease (ie, cardiovascular, neurological, renal, liver, metabolic, GI, 
hematological, immunological, etc) considered by the Investigator to be uncontrolled, 
unstable or likely to progress to a clinically significant degree during the course of the study. 
20. Subject has had myocardial infarction or stroke within the 6 months prior to the Screening 
Visit. 
21. Subject has laboratory abnormalities at Screening, including any of the following: 
a. ≥3x ULN of any of the following: ALT, AST, alkaline phosphatase (ALP); or >ULN 
total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome) 
b. White blood cell count <3.0x103/μL 
c. Absolute neutrophil count <1.5x103/μL 
d. Lymphocyte count <500 cells/μL 


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e. Hemoglobin <8.5g/dL 
f. Creatinine >2mg/dL 
g. Any other laboratory abnormality, which, in the opinion of the Investigator, will prevent 
the subject from completing the study or will interfere with the interpretation of the study 
results. 
Individual screening tests for which the results are in error, borderline, or indeterminate for 
inclusion in the study, can be repeated once for confirmation during the Screening Period. 
Upon retesting, subjects whose results remain outside this threshold should not be 
randomized. 
22. Subject has any other condition including medical or psychiatric which, in the Investigator's 
judgment, would make the subject unsuitable for inclusion in the study. 
23. Presence of active suicidal ideation, or positive suicide behavior using the “Screening” 
version of the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) with either of 
the following criteria: 
− Subject has a history of a suicide attempt within the 5 years prior to the Screening Visit. 
Subjects with a history of a suicide attempt more than 5 years ago should be evaluated by 
a mental healthcare professional (eg, locally licensed psychiatrist, psychologist, or 
master’s level therapist) before enrolling into the study. 
− Subject has suicidal ideation in the past month prior to the Screening Visit as indicated by 
a positive response (“Yes”) to either Question 4 or Question 5 of the “Screening” version 
of the eC-SSRS  
24. Subject has presence of moderately severe major depression, or severe major depression, 
indicated by a Score ≥15 using the screening PHQ-9. Medication used to treat depression 
should be stable for 8 weeks prior to Baseline.  
25. Subjects taking PsA medications other than MTX, SSZ, apremilast, HCQ, LEF, 
NSAIDs/COX-2 inhibitors, and oral corticosteroids as outlined in the Inclusion criteria 
(Section 6.1). Stable doses/regimens of analgesics are also permitted. 
26. Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening 
evaluated by the Investigator based on medical history, site interview, and results of the 
specified urine drug screen. 
27. Subject is a member of Investigator site personnel directly affiliated with this study and/or 
their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, 
whether biological or legally adopted. 
28. Subject is a UCB employee or is an employee of third-party organizations involved in the 
study. 


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6.3 
Withdrawal criteria 
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care. Subjects who withdraw from the study should complete the Early Termination Visit (see 
Section 8.3).  
Subjects should be withdrawn from the study and will be asked to come back for the SFU Visit 
20 weeks after the final dose of IMP if the subject withdraws his/her consent. 
Subjects should be withdrawn from IMP and will be asked to come back for all scheduled visits 
(up to Week 52) and the SFU Visit 20 weeks after the final dose of IMP if any of the following 
events occur:   
1. The Sponsor or a regulatory agency requests withdrawal of the subject. 
2. Subject develops an illness that, in the opinion of the Investigator, would interfere with 
his/her continued participation, if the risk of continuing with IMP outweighs the potential 
benefit. 
3. Subject is noncompliant with the study procedures or medications, which may present a risk 
to the safety of the subject, in the opinion of the Investigator. 
4. Subject uses prohibited concomitant medications, as defined in Section 7.8.2, that may 
present a risk to the safety of the subject in the opinion of the Investigator and the Medical 
Monitor. 
5. Subject has a clinical laboratory value meeting any of the following criteria: 
a. Hepatotoxicity as described in Section 6.3.1. 
b. A laboratory value meeting any of the following criteria: 
− Absolute neutrophil count <1.0x103/μL 
− Absolute lymphocyte count <0.2x103/μL  
Subjects may remain on IMP if the result is transient. A retest is required within 1 to 2 weeks 
at a scheduled or unscheduled visit. If the repeat absolute neutrophil count or absolute 
lymphocyte count is still below the allowable values, the subject must be withdrawn from the 
IMP. If the repeat absolute neutrophil count or absolute lymphocyte count is above the 
allowable values, the subject may continue to receive IMP. 
6. The subject experiences a severe AE, SAE, or a clinically significant change in a laboratory 
value occurs that, in the opinion of the Investigator, merits the discontinuation of the IMP 
and appropriate measures being taken. 
7. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test (see Section 12.1.4 for more information regarding pregnancies). 
8. Subject develops erythrodermic, guttate or generalized pustular form of PSO. 
9. A subject considered as having either a suspected new LTBI or who develops active TB or 
NTMB infection during the study (including but not limited to, conversion demonstrated by 
IGRA or other diagnostic means) must be immediately discontinued from IMP, and an ET 
Visit must be scheduled as soon as possible, but not later than the next regular visit. 


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The subject must be permanently withdrawn if further examinations result in a diagnosis of 
active TB, or if the subject is diagnosed with LTBI with no initiation of prophylactic 
treatment, prematurely discontinues prophylactic treatment, or, in the opinion of the 
Investigator or Sponsor, is noncompliant with prophylactic TB therapy. 
Confirmed active TB is an SAE and must be captured in the electronic Case Report form 
(eCRF) in the SAE Report Form section. As with all SAEs, periodic follow-up reports should 
be completed as per protocol requirements until such time as the TB infection resolves. 
Additional information on TB policies is provided in Section 12.3.5. 
10. Subjects with newly diagnosed IBD or with IBD flares during the study must: 
− Be referred, as appropriate, to a health care professional treating IBD, such as a 
gastroenterologist 
− Discontinue IMP and be followed-up until resolution of active IBD symptoms 
If IBD flares increase in severity or frequency during the study, the Investigator should use 
clinical judgment in deciding whether the subject should continue on IMP and contact the 
Medical Monitor and UCB study physician to confirm the subject's suitability for continued 
participation in the study. 
11. Subjects must be referred immediately to a mental healthcare professional and may be 
withdrawn from the study based upon the Investigator’s judgment of benefit/risk for: 
a. Active suicidal ideation as indicated by a positive response (“Yes”) to Question 4 of the 
“Since Last Visit” version of the eC-SSRS.  
b. Moderately severe major depression as indicated by a PHQ-9 score of 15 to 19 if this 
represents an increase of 3 points compared to last visit. 
The mental health consultation must be recorded in the subject’s source documentation. 
12. Subjects must be referred immediately to a mental health care professional and must be 
withdrawn from the study: 
a. Active suicidal ideation as indicated by a positive response (“Yes”) to Question 5 of the 
“Since Last Visit” version of the eC-SSRS. 
b. Any suicidal behavior since the last visit.  
c. Severe major depression as indicated by a PHQ-9 score ≥20. 
The mental health consultation must be recorded in the subject’s source documentation. 
13. Any subject who develops a clinically important infection or recurrent infections not 
responsive to standard therapy during the study must discontinue IMP until resolution of the 
infection. The Investigator should use clinical judgement in deciding whether the subject 
should restart IMP and contact the Medical Monitor and UCB study physician to confirm the 
subject’s suitability for continued participation in the study. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject from IMP or from the study in advance. 


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Subjects withdrawing from the study who are not continuing for all scheduled visits, will 
undergo the ET Visit and the SFU Visit 20 weeks after their final dose of IMP. 
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow-up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject) and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The electronic Case Report Form (eCRF) must document the primary reason for 
withdrawal or discontinuation. 
6.3.1 
Potential drug-induced liver injury IMP discontinuation criteria 
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued.  
The PDILI criteria below require immediate discontinuation of IMP:  
• Subjects with either of the following: 
− ALT or AST ≥8xULN 
− ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN  
− Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without 
clear alternative cause), rash, or eosinophilia (ie, >5%). 
If a nondrug-related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with the responsible UCB physician, but only when the 
requirements for rechallenge with IMP as provided in Section 12.2.1.2.1 are followed. 
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator.  
• Subjects with ALT or AST ≥5xULN and <8xULN, total bilirubin <2xULN, and no 
eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness).  
Evaluation of PDILI must be initiated as described in Section 12.2.1 with repeat tests performed 
in 2 weeks. Upon retest, if ALT or AST values have reduced to <5xULN, the subject can 
continue with the study. However, if ALT or AST remains ≥5xULN <8xULN after retest, IMP 
should be temporarily withheld and subject should undergo a repeat test in 2 weeks. The subject 
will continue to be monitored at least twice per week until values normalize, stabilize, or return 
to within baseline values. If ALT or AST values remain ≥5xULN even after the second retest, 
then the subject should be permanently withdrawn from the study and should be followed for 
possible PDILI.  
If subjects are unable to comply with the applicable monitoring schedule, IMP must be 
discontinued immediately. 


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Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The eCRF must document the primary 
reason for IMP discontinuation. 
7 
STUDY TREATMENTS 
7.1 
Description of investigational medicinal products 
The IMPs used in this study are bimekizumab, adalimumab, and placebo. 
• Bimekizumab will be supplied in a 1mL PFS. Each single-use syringe contains bimekizumab 
drug substance at a nominal formulation of 160mg/mL in 
mM sodium acetate, 
mM 
glycine, and 
% polysorbate 80 at pH 
 for sc injection. 
• 
 
 
• Placebo will be supplied as 0.9% sodium chloride aqueous solution (physiological saline, 
preservative free) of pharmacopoeia (US Pharmacopoeia/European Pharmacopoeia) quality 
in a 1mL PFS for sc injection. 
Further details of the IMPs and their specifications will be provided in the IMP Handling 
Manual.  
7.2 
Treatments to be administered 
The IMPs are to be administered in the clinic by unblinded study site staff. At all visits, only a 
single sc injection would be administered. Suitable areas for sc injections are the lateral 
abdominal wall and upper outer thigh. Injection sites should be rotated and injections should not 
be given in areas where the skin is tender, bruised, red, or hard. 
An IMP Handling Manual will be provided to each site containing instructions regarding drug 
preparation and dosing. 
The IMP dosing scheme is presented in Table 7-1. 


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Table 7-1: 
Dosing scheme 
 
 
Week 
 
Protocol 
activity 
Baseline  
(first dose) 
Double-Blind Treatment Period 
Active Treatment-Blind Period 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
Bimekizumab 
160mg sc Q4W 
● 
 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
 
○a 
Adalimumab 
40mg 
▲ 
 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
▲
a 
Placebo 
○ 
 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
● b 
○ 
● 
○ 
●  
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
○ 
● 
 
○a 
Note: A bimekizumab 160mg Q4W dose injection is depicted by a black circle (●). A placebo injection is depicted by a white circle (○). An adalimumab 40mg 
injection is depicted by a black triangle (▲).  
a Subjects that continue to the extension study will receive their final dose of IMP. 
b Placebo subjects reallocated to bimekizumab 160mg sc Q4W (follow applicable schedules noted above). 
  
 


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7.3 
Packaging 
The IMPs are manufactured, packaged, and labeled according to Good Manufacturing Practice 
guidelines and applicable laws or regulations. Investigational medicinal products will be suitably 
packaged in such a way as to protect the IMPs from deterioration during transport and storage. 
7.4 
Labeling 
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and 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 
Investigational Medicinal Products must be stored under refrigerated conditions (2ºC to 8ºC) 
protected from light. The IMPs must not be frozen. 
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access according to the storage conditions mentioned on the label. 
Appropriate storage conditions must be ensured either by controlling the temperature (eg, room, 
refrigeration unit) or by completion of a temperature log in accordance with local requirements 
on a regular basis, showing actual and minimum/maximum temperatures reached over the time 
interval.  
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
7.6 
Drug accountability 
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the 
study site, or returned to the Sponsor or designee must also be recorded on the appropriate forms. 
All supplies and pharmacy documentation must be made available throughout the study for UCB 
(or designee) to review. 
The packaging identifies each kit by a unique number that does not correlate to the contents and, 
therefore, does not unblind study site staff. Unblinded study staff will be responsible for 
preparation (eg, breaking tamper proof sticker on kit) of the clinical trial material, including 
recording the administration information in the source document. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed. 
The Investigator must assign some of the Investigator’s duties for drug accountability at the 
study site to an appropriate pharmacist/designee. 
The Investigator must ensure that the IMP is used only in accordance with the protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired IMP must be reconciled and either 


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destroyed at the site according to local laws, regulations, and UCB standard operating procedures 
(SOPs), or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
7.7 
Procedures for monitoring subject compliance 
Bimekizumab, adalimumab, and placebo will be administered in the clinic and compliance will 
be determined at the visit by unblinded study personnel. Drug accountability must be recorded 
by unblinded study personnel on the Drug Accountability form. 
7.8 
Concomitant medications/treatments 
All concomitant medications, including over-the-counter products, herbal, traditional remedies, 
vitamin/mineral supplements, other dietary supplements, “nutraceuticals,” and hormones must be 
recorded in the subject’s source documentation (eg, clinical chart) and in 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. 
7.8.1 
Permitted concomitant treatments (medications and therapies) 
No medication increases or additions are permitted for medications taken for PsA until Week 16. 
However, a decrease in dose or dosing frequency of any agent is permitted for reasons of 
intolerance/AEs/side-effects at any time. 
After Week 16, background medication changes are permitted at the Investigator’s discretion if 
the subject is considered to be not responding adequately. Permitted rescue therapy is described 
in Section 5.4. 
Subjects are allowed to use acetaminophen/paracetamol and mild opioids as needed, except 
within 24 hours of a visit with disease activity assessment. 
Subjects who are already receiving an established antidepressant regimen should be on a stable 
dose of the antidepressant for 8 weeks prior to Baseline. 
Subjects are allowed to use any other medications, including biologics, after at least 28 days of 
last dose of the IMP. This is applicable for subjects who discontinue from IMP or the study 
early, including those permanently withdrawn from IMP, or subjects who have completed the 
study treatment without entering the extension study and are in the SFU Period. 
7.8.1.1 
Psoriasis treatments 
For treatment of PSO, subjects may continue to use topical moisturizers, emollients, salicylic 
acid preparations, bath oils, and oatmeal bath preparations for skin conditions during the study, 
as needed. Over-the-counter shampoos for the treatment of PSO of the scalp are also permitted. 
Additionally, mild topical steroids are permitted for use limited to the face, axillae, and/or 
genitalia, as needed. Subjects who use prohibited topical medications will be allowed to stay in 
the study but will counseled to not use them further. No other topical preparations are allowed in 
the 2 weeks prior to randomization or during the study unless medically required to treat an AE. 
See Table 7-3 for prohibited PSO medications. 
After the Week 16 Visit, the addition of topical retinoids, vitamin D analogues, coal tar 
preparations, and more potent topical steroids may be used as medically required to treat a flare 
but are not permitted to be used within 24 hours prior to a study visit. Use of psoralen and 


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ultraviolet A light (PUVA/UVA) therapy for the treatment of PSO is not permitted for the first 
16 weeks of the study and is discouraged through the duration of the study. 
7.8.2 
Prohibited concomitant treatments (medications and therapies) 
Prohibited and/or restricted medications are summarized in Table 7-2 and Table 7-3. 
Table 7-2: 
Prohibited or restricted medications and required wash-out 
periods 
Drug class 
Dose 
Exclusion/Washout 
Analgesics, including mild 
opioid analgesics, 
acetaminophen/paracetamol, 
etc. 
Any dose  
Any ad hoc use in the 24 hours prior to any study 
visit.  
 
Stable doses of analgesics are permitted. 
NSAIDs/COX-2 inhibitors 
Any dose 
regimen 
Any change in dose/dose regimen in the 14 days 
prior to the Baseline Visit 
Oral corticosteroids 
Any dose 
regimen 
Any change in dose/dose regimen in the 14 days 
prior to the Baseline Visit. 
Intramuscular/intravenous 
/intra-articular 
corticosteroids  
Any dose  
Use in the 28 days prior to the Baseline Visit and 
during the study. 
Intra-articular hyaluronic 
acid  
Any dose  
Use in the 6 months prior to the Baseline Visit. 
DMARDs: 
-azathioprine,  
-cyclosporine,  
-cyclophosphamide,  
-mycophenolic acid 
-mycophenolate mofetil 
-any other nonpermitted 
small molecule DMARDs 
(eg, tofacitinib) 
Any dose 
Use within 8 weeks prior to the Baseline Visit and 
during the study. 
-apremilast a 
Any dose 
Use within 8 weeks prior to the Baseline Visit 
unless Inclusion Criterion #13 is met.  
-hydroxychloroquine a 
Any dose 
Use within 8 weeks prior to the Baseline Visit 
unless Inclusion Criterion #13 is met.  
-sulfasalazine a 
Any dose 
Use within 8 weeks prior to the Baseline Visit 
unless Inclusion Criterion #13 is met.  


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Table 7-2: 
Prohibited or restricted medications and required wash-out 
periods 
Drug class 
Dose 
Exclusion/Washout 
-methotrexate a 
Any dose 
regimen 
Initiation less than 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met.  
Administration of LEF and MTX together is not 
permitted at any time during the study. 
-leflunomide a 
Any dose 
Use in the 6 months prior to the Baseline Visit, 
unless (1) a cholestyramine washout has been 
performed, in which case, use up to 28 days prior 
to the Baseline Visit is acceptable or (2) Inclusion 
Criterion #12 is met. 
Any bDMARDs 
Any dose 
Any exposure history. 
COX-2=cyclooxygenase-2; CZP=certolizumab pegol; bDMARD=biological disease modifying antirheumatic 
drug; DMARD=disease modifying antirheumatic drug; ETN=etanercept; GOL=golimumab; 
HCQ=hydroxychloroquine; IFX=infliximab; LEF=leflunomide; MTX=methotrexate; NSAID=nonsteroidal 
anti-inflammatory drug; SSZ=sulfasalazine 
a Permitted as per Section 5.4. 
 
Table 7-3 
Additional prohibited psoriasis treatments 
Drug class 
Dose 
Exclusion criteria 
Phototherapy 
Any dose 
Use within the 28 days prior to the 
Baseline Visit. 
Topical corticosteroids for dermatological 
use except as detailed in Section 7.8.1, 
vitamin D analogues, topical retinoids, 
keratolytics, coal tar, and fumaric acid 
esters 
Any dose 
Use within 14 days prior to the 
Baseline Visit. 
Systemic retinoids 
Any dose 
Use within 3 months prior to the 
Baseline Visit. 
7.8.3 
Vaccines 
Administration of live (including attenuated) vaccines is not allowed during the conduct of the 
study and for 20 weeks after the final dose IMP (see exclusion criteria, Section 6.2). 
Administration of inactivated vaccines is allowed during the study at the discretion of the 
Investigator.  
7.9 
Blinding 
Due to differences in presentation between the bimekizumab, adalimumab, and placebo 
treatments, special precautions will be taken to ensure study blinding and study sites will have 
blinded and unblinded personnel. 


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As per dosing schedule for adalimumab (see Section 7.2), all subjects must come to the study 
center for IMP administration at Baseline, Week 2, Week 4, and then Q2W thereafter. 
For subjects receiving bimekizumab, bimekizumab will be administered at Baseline and Q4W 
thereafter; dummy/placebo treatments at Week 2 and Q4W thereafter to preserve blinding and 
correspond to the dosing schedule for adalimumab. Adalimumab subjects will receive 
adalimumab at Baseline and Q2W thereafter. Details of the interim sensitivity analysis to 
examine any treatment biases are provided in Section 14.3.2. 
7.9.1 
Procedures for maintaining and breaking the treatment blind 
7.9.1.1 
Maintenance of study treatment blind 
All subject treatment details will be allocated and maintained by the interactive voice or web 
response system (IXRS) system. 
Additional information on procedures to maintain the treatment blind after the 24-week and 
52-week interim analyses is provided in Section 14.8.1. 
7.9.1.2 
Breaking the treatment blind in an emergency situation 
The integrity of this clinical study must be maintained by observing the treatment blind. In the 
event of an emergency for which the appropriate treatment for a subject cannot be made without 
knowing the treatment assignment, it will be possible to determine to which treatment and dose 
the subject has been allocated by contacting the IXRS. All sites will be provided with details of 
how to contact the system for code breaking at the start of the study. The Medical Monitor or 
equivalent should be consulted prior to unblinding, whenever possible. 
The Clinical Project Manager (CPM) will be informed immediately via the IXRS when a code is 
broken but will remain blinded to specific treatment information. Any unblinding of the IMP 
performed by the Investigator must be recorded in the source documents and on the Study 
Termination eCRF page. 
7.10 
Randomization and numbering of subjects 
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by UCB (or 
designee). The randomization schedule will be produced by the IXRS vendor. The IXRS will 
generate individual assignments for subject kits of IMP, as appropriate, according to the visit 
schedule. 
To enroll a subject, the Investigator or designee will contact the IXRS and provide brief details 
about the subject to be enrolled. Each subject will receive a 5-digit number assigned at Screening 
that serves as the subject identifier throughout the study. The subject number will be required in 
all communication between the Investigator or designee and the IXRS regarding a particular 
subject. Subject numbers and kit numbers will be tracked via the IXRS. 
Eligible subjects will be randomized to treatment groups at Baseline (Day 1). To randomize a 
subject, the Investigator or designee will contact the IXRS and provide brief details about the 
subject to be randomized. The IXRS will automatically inform the Investigator or designee of the 
subject’s randomization number. The IXRS will allocate kit numbers to the subject based on the 
subject number during the course of the study. The randomization number must be documented 
into the eCRF. 


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After 16 weeks of double-blind treatment, subjects who were randomized to placebo will be 
reallocated to bimekizumab 160mg sc Q4W. Subjects randomized to bimekizumab160mg sc 
Q4W will continue to receive their originally randomized dose. Subjects randomized to 
adalimumab 40mg Q2W will continue with their reference treatment. 
8 
STUDY PROCEDURES BY VISIT  
The schedule of study assessments (Table 5-1) provides an overview of study assessments. A list 
of procedures to be completed at each visit is described below. Visit windows of ±2 days are 
allowed from the first dose at all visits through to Week 16. During the 16-week Double-Blind 
Period, the time between doses should be ≥12 days and ≤16 days. Visit windows of ±3 days are 
allowed for all visits after Week 16. The time between doses during the Active Treatment-Blind 
Period should be ≥11 days and ≤17 days. For the SFU Visit (20 weeks after the final dose of 
IMP), the visit should occur no more than 3 days prior to the scheduled visit date and within 
7 days after the scheduled visit date (-3 days/+7 days).  
Where local regulations permit, subjects will also be given the option to participate in the 
genomics, genetics, and proteomics substudy. Subjects agreeing to participate in the substudy 
will be required to complete a separate Informed Consent form (ICF). The ICF must be signed 
prior to collecting any samples for the substudy. The substudy will only be conducted where 
ethically accepted and authorized by the regulatory agencies. Refusal to participate in the 
substudy will not affect a subject’s ability to participate in the main PA0010 study. 
8.1 
Screening Period/Baseline 
8.1.1 
Screening 
The Screening Period will last for a minimum of 14 days and up to a maximum of 35 days. 
Prior to any study-specific activities, subjects will be asked to read, sign, and date an Informed 
Consent form that has been approved by the Sponsor and an IRB/IEC, and that complies with 
regulatory requirements. Subjects will be given adequate time to consider any information 
concerning the study given to them by the Investigator or designee. As part of the informed 
consent procedure, subjects will be given the opportunity to ask the Investigator any questions 
regarding potential risks and benefits of participation in the study. 
The following procedures or assessments will be performed at the Screening Visit: 
• Obtain written informed consent 
• Assessment of inclusion and exclusion criteria 
• Collect demographic data 
• Collect PsA history 
• Collect significant past medical history and concomitant diseases 
• Record prior medications 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 


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• Vital signs 
• ECG by central reader 
• Collect samples for hematology and biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (serum) 
• Urinalysis  
• Urine drug screen 
• Collect samples for Hepatitis B and Hepatitis C testing  
• Collect samples for HIV testing 
• Collect samples for rheumatoid factor, anti-CCP antibodies 
• IGRA TB test 
• TB questionnaire 
• Physical examination 
• BSA affected by PSO 
• PASI (if the BSA affected by PSO is ≥3%) 
• Investigator’s Global Assessment (IGA)   
• Perform TJC and SJC 
• Chest x-ray 
• X-ray of hands and feet 
• AEs 
• IXRS 
8.1.2 
Baseline (Day 1) 
• Assessment of inclusion and exclusion criteria 
• Collect significant past medical history and concomitant diseases 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Height 
• Vital signs 
• Collect samples for hematology and biochemistry (including triglycerides, cholesterol, high 
density lipoprotein [HDL] cholesterol, and low-density lipoprotein [LDL] cholesterol) 


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• Collect samples for hs-CRP 
• Collect sample for HLA-B27 
• Pregnancy testing (urine) 
• Urinalysis  
• Blood sample for bimekizumab plasma concentrations  
• Blood sample for anti-bimekizumab antibody detection  
• Serum and plasma blood samples for exploratory biomarkers (participating subjects only) 
• RNA blood samples for exploratory biomarkers (participating subjects only) 
• Blood samples for genetic/epigenetic analysis (participating subjects only) 
• TB questionnaire 
• Physical examination 
• BSA affected by PSO using the BSA palm method 
• PASI (if the BSA affected by PSO is ≥3%) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI 
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 


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• WPAI-SHP  
• AEs 
• IXRS (randomization) 
• IMP administration 
8.2 
Treatment Period 
8.2.1 
Double-Blind Treatment Period 
8.2.1.1 
Week 2 
• Record concomitant medications 
• Vital signs 
• Collect samples for hematology and biochemistry 
• Collect samples for hs-CRP 
• Blood sample for bimekizumab plasma concentrations 
• BSA affected by PSO  
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• AEs 
• IXRS 
• IMP administration 
8.2.1.2 
Week 4  
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology and biochemistry 


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• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Blood sample for bimekizumab plasma concentrations  
• Blood sample for anti-bimekizumab antibody detection  
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI 
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• AEs 
• IXRS 
• IMP administration 


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8.2.1.3 
Weeks 6, 10, and 14 
• Record concomitant medications 
• IXRS 
• AEs  
• IMP administration 
8.2.1.4 
Week 8 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology and biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Blood sample for bimekizumab plasma concentrations 
• Blood sample for anti-bimekizumab antibody detection 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI 
• AEs 


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• IXRS 
• IMP administration 
8.2.1.5 
Week 12 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• Collect samples for hematology and biochemistry (including triglycerides, cholesterol, 
HDL cholesterol, and LDL cholesterol) 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Blood sample for bimekizumab plasma concentrations  
• Blood sample for anti-bimekizumab antibody detection  
• TB questionnaire 
• Physical examination 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI  
• AEs 


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• IXRS 
• IMP administration 
8.2.1.6 
Week 16 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• ECG by central reader 
• Collect samples for hematology and biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Urinalysis  
• Blood sample for bimekizumab plasma concentrations 
• Blood sample for anti-bimekizumab antibody detection 
• Serum and plasma blood samples for exploratory biomarkers (participating subjects only) 
• RNA blood samples for exploratory biomarkers (participating subjects only) 
• Blood samples for genetic/epigenetic analysis (participating subjects only) 
• Physical examination 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 


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• SPARCC 
• LDI  
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• WPAI-SHP  
• X-ray of hands and feet 
• AEs 
• IXRS 
• IMP administration 
8.2.2 
Active Treatment-Blind Period 
After 16 weeks of double-blind treatment, subjects will enter the Active Treatment-Blind Period. 
Subjects in the placebo group will be reallocated to bimekizumab 160mg sc Q4W. Subjects 
randomized to receive bimekizumab or adalimumab during the Double-Blind Treatment Period 
will continue their Double-Blind Treatment Period regimen in the Active Treatment-Blind 
Period. After Week 16, rescue therapy will be permitted for all subjects at the Investigator’s 
discretion if the subject is judged to be not responding adequately. 
8.2.2.1 
Weeks 18 and 22 
• Record concomitant medications 
• IXRS 
• AEs  
• IMP administration 
8.2.2.2 
Week 20 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology and biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Blood sample for bimekizumab plasma concentrations 


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• Blood sample for anti-bimekizumab antibody detection 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• LEI 
• SPARCC 
• LDI  
• AEs 
• IXRS 
• IMP administration 
8.2.2.3 
Week 24 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• Collect samples for hematology and biochemistry (including triglycerides, cholesterol, 
HDL cholesterol, and LDL cholesterol) 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Urinalysis 
• Blood sample for bimekizumab plasma concentrations  
• Blood sample for anti-bimekizumab antibody detection  
• TB questionnaire 
• Physical examination 


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• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC/SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI  
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• WPAI-SHP  
• AEs 
• IXRS 
• IMP administration 
8.2.2.4 
Weeks 26, 30, 34, 38, 42, 46, and 50 
• Record concomitant medications 
• IXRS 
• AEs 
• IMP administration 


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8.2.2.5 
Week 28 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• AEs 
• IXRS 
• IMP administration 
8.2.2.6 
Week 32 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Urinalysis 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 


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• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• AEs 
• IXRS 
• IMP administration 
8.2.2.7 
Week 36 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Blood sample for bimekizumab plasma concentrations 
• Blood sample for anti-bimekizumab antibody detection 
• TB questionnaire 
• Physical examination 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 


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• LEI 
• SPARCC 
• LDI  
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• AEs 
• IXRS 
• IMP administration 
8.2.2.8 
Week 40 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Pregnancy testing (urine) 
• Urinalysis 
• Perform TJC and SJC 
• AEs 
• IXRS 
• IMP administration 
8.2.2.9 
Week 44 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 


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• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• AEs 
• IXRS 
• IMP administration 
8.2.2.10 
Week 48 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Vital signs 
• Collect samples for hematology/biochemistry 
• Pregnancy testing (urine) 
• Urinalysis 
• IGRA TB test 
• AEs 
• IXRS 
• IMP administration 
8.2.2.11 
Week 52 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• ECG by central reader 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 


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• Pregnancy testing (urine) 
• Urinalysis 
• Blood sample for bimekizumab plasma concentrations  
• Blood sample for anti-bimekizumab antibody detection  
• TB questionnaire 
• Physical examination 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• mNAPSI 
• LEI 
• SPARCC 
• LDI  
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• WPAI-SHP  
• X-ray of hands and feet 
• AEs 
• IXRS 


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At the completion of the Active Treatment-Blind Period, Investigators should discuss treatment 
options with the subject. Subjects will be given the opportunity to enter an extension study at 
Week 52. 
8.3 
Early Termination Visit 
Subjects withdrawing early from the study will undergo the following ET Visit assessments and 
will enter the SFU Period: 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• ECG by central reader 
• Collect samples for hematology/biochemistry (including triglycerides, cholesterol, 
HDL cholesterol, and LDL cholesterol) 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Urinalysis 
• Blood sample for bimekizumab plasma concentrations 
• Blood sample for anti-bimekizumab antibody detection 
• TB questionnaire 
• Physical examination 
• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 


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• mNAPSI 
• LEI 
• SPARCC 
• LDI  
• PsAQoL 
• PsAID-12 
• FACIT-Fatigue subscale 
• SF-36 
• EQ-5D-3L 
• WPAI-SHP  
• X-ray of hands and feet 
• AEs 
• IXRS 
8.4 
Safety Follow-Up Visit (20 weeks [-3 days/+7 days] after the final 
dose) 
All subjects who complete the study and do not enter the extension study or who discontinue 
early, including those withdrawn from IMP, will have an SFU Visit 20 weeks after their final 
dose of IMP with the following assessments: 
• Record concomitant medications 
• PHQ-9 
• eC-SSRS 
• Weight 
• Vital signs 
• ECG by central reader 
• Collect samples for hematology/biochemistry 
• Collect samples for hs-CRP 
• Pregnancy testing (urine) 
• Urinalysis 
• Blood sample for bimekizumab plasma concentrations 
• Blood sample for anti-bimekizumab antibody detection 
• TB questionnaire 
• Physical examination 


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• BSA affected by PSO 
• PASI (if BSA affected by PSO is ≥3% at the Baseline [Day 1] visit) 
• IGA 
• Perform TJC and SJC 
• HAQ-DI 
• PtAAP 
• PhGA-PsA 
• PhGA-Arthritis 
• PGA-PsA 
• PGA-Arthritis  
• BASDAI 
• LEI 
• SPARCC 
• LDI  
• PsAQoL 
• SF-36 
• AEs 
• IXRS 
8.5 
Unscheduled Visits 
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 wellbeing.  
If an Unscheduled Visit is conducted due to safety or efficacy reasons, an eC-SSRS assessment 
will be performed with the subject during the visit. If an Unscheduled Visit is conducted for 
reasons other than safety or efficacy concerns (eg, replacement of lost medication, repeated 
collection of a laboratory specimen due to collection or analysis issues), an eC-SSRS will not be 
required at these visits. 
At this visit, any of the following assessments may be performed, depending on the reason for 
the visit: 
• Record concomitant medication 
• eC-SSRS 
• Vital signs 
• ECG  
• Obtain urine sample for urine pregnancy test 


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• If indicated, obtain blood sample(s) for: 
− Standard safety laboratory tests (hematology/biochemistry)  
− Bimekizumab plasma concentrations and anti-bimekizumab antibody detection 
• An IGRA TB test 
• Physical examination 
• AEs 
9 
ASSESSMENT OF EFFICACY 
The ACR50 response at Week 16 is the primary efficacy variable. In addition, the ACR20 and 
ACR70 responses are secondary or other efficacy variables. Several assessments must be 
completed in order to determine the ACR response. These include the TJC and SJC based on 
68 and 66 joints, respectively, PGA-PsA, PhGA-PsA, PtAAP, HAQ-DI and hs-CRP. The 
methods for the component measures will be described first, followed by ACR response and 
assessments used in secondary and other efficacy variables.  
The timing for all assessments is specified in the schedule of study assessments (Table 5-1).  
9.1 
Joint assessments 
9.1.1 
68/66 joint evaluation for ACR response and verification of Inclusion 
Criterion 5 
The TJC/SJC, as recommended by ACR in RA, is the 68/66 count and it has since also been used 
in PsA studies; therefore, it will be utilized in this study. 
All joint assessments will be performed by an experienced independent evaluator who has had 
documented training on how to perform these assessments correctly. Preferably, the same 
evaluator should perform these assessment at all visits, as indicated in Table 5-1. The 
independent evaluator will not be involved in any other assessments. The following joints will be 
assessed for tenderness:  
• Upper body (6) - bilateral temporomandibular, sternoclavicular, and acromioclavicular joints 
• Upper extremity (34) - bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal 
and carpometacarpal bones considered as a single unit), metacarpophalangeal (I, II, III, IV, 
and V), thumb interphalangeals, proximal interphalangeal (II, III, IV, and V), and distal 
interphalangeals (II, III, IV, and V). 
• Lower extremity (28) - bilateral hips, knees, ankles, tarsi (includes subtalar, transverse tarsal, 
and tarsometatarsal considered as a single unit), metatarsophalangeals (I, II, III, IV, and V), 
great toe interphalangeals, and proximal interphalangeals (II, III, IV, and V). 
All of these except for the hips are assessed for swelling.  
Artificial and ankylosed joints, as well as missing joints (ie, amputated joints), are excluded from 
both tenderness and swelling assessments.  
One dactylitic digit is to be counted as 1 swollen joint (instead of counting as 3 in the finger or 
2 in the toe). 


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Table 9-1 summarizes the swelling and tenderness grading criteria. 
Table 9-1: 
Swelling and tenderness grading 
Grade 
Tenderness response (68) 
Swelling response (66) 
0 
Not tender 
None 
1 
Tenderness present 
Detectable synovial thickening 
Data mapping from collected data to the grades listed in Table 9-1 will be described in the 
Statistical Analysis Plan (SAP). 
9.1.2 
28 joint evaluation for determination of DAS28(CRP) 
The following 28 joints will be used for calculation of the DAS28(CRP). 
• Upper extremity (26)-bilateral shoulders, elbows, wrists (includes radiocarpal, and carpal and 
carpometacarpal bones considered as a single unit), metacarpophalangeal joints I, II, III, IV, 
and V, thumb interphalangeals, proximal interphalangeal II, III, IV, and V  
• Lower extremity (2)-knees 
9.2 
ACR20, ACR50, and ACR70 response 
The ACR20, ACR50, and ACR70 response rates are based on a 20%, 50%, and 70% or greater 
improvement relative to Baseline in the following measures: 
• TJC based on 68 joints 
• SJC based on 66 joints 
• 3 of the 5 remaining core set measures: 
− PGA-PsA 
− PhGA-PsA 
− PtAAP 
− HAQ-DI 
− hs-CRP 
9.3 
Patient’s Global Assessments  
9.3.1 
Patient’s Global Assessment of Psoriatic Arthritis (PGA-PsA) 
The subject’s global assessment of PsA will be performed using a 100mm VAS scale where 0 is 
“very good, no symptoms” and 100 is “very poor, severe symptoms.” The subject will be asked 
the following question:  
“Considering all the ways your psoriatic arthritis affects you, please mark a vertical line on 
the scale below to show how well you are doing today.” 
The subject should be asked to consider all aspects of their disease (including joint and skin 
components) in their response to this question. 


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9.3.2 
Patient’s Global Assessment of Arthritis (PGA-arthritis) 
The subject’s global assessment of arthritis will be performed using a 100mm VAS scale where 
0 is “very good, no symptoms” and 100 is “very poor, severe symptoms.” The subject will be 
asked the following question: 
“Considering all the ways your arthritis affects you, please mark a vertical line on the scale 
below to show how you are feeling today.” 
The subject should be asked to consider their arthritis symptoms and functional capacity in their 
response to this question. 
9.4 
Physician’s Global Assessments 
These assessments will be performed by the Principal Investigator, another delegated physician 
or an appropriately trained medical professional (based on local requirements) who has 
documented training on how to perform these assessments correctly. The assessments should be 
made blind to the PGA-PsA and PGA-Arthritis assessments. 
9.4.1 
Physician’s Global Assessment of Psoriatic Arthritis (PhGA-PsA) 
The Investigator or delegate will assess the overall status of the subject with respect to their PsA, 
which may include any element of the disease and may include arthritis, PSO, enthesitis, 
dactylitis, or spondylitis. This will be assessed using a 100mm VAS scale where 0 is “very good, 
asymptomatic and no limitation of normal activities” and 100 is “very poor, very severe 
symptoms which are intolerable and inability to carry out all normal activities”. The Investigator 
or delegate will be asked the following question: 
“Considering all the ways the disease affects your patient, mark a vertical line on the scale 
for how well his or her condition is today.”  
9.4.2 
Physician’s Global Assessment of Arthritis (PhGA-Arthritis) 
The Physician or delegate will assess how the subject’s overall arthritis appears at the time of the 
visit. This is an evaluation based on the subject’s disease signs, functional capacity, and physical 
examination using a 100mm VAS scale where 0 is “very good” and 100 is “very poor”. The 
physician will be asked to mark the Patient’s arthritis:  
The Patient’s arthritis at this time is:  
“Please mark a vertical line on the scale below to assess the overall status of the subject’s 
arthritis signs and symptoms and the functional capacity of the subject.”  
Very Good--------------------------------------------------------Very Poor 
9.5 
Patient’s Assessment of Arthritis Pain (PtAAP) 
The PtAAP VAS or ‘Pain VAS’ is part of the ACR core set of measures in arthritis 
(Felson et al, 1993). Subjects will assess their arthritis pain using a VAS where 0 is “no pain” 
and 100 is “most severe pain.”  


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9.6 
Health Assessment Questionnaire-Disability Index score 
(HAQ-DI)  
The HAQ-DI contains 20 items divided into 8 domains that measure: dressing and grooming, 
arising, eating, walking, hygiene, reach, grip, and common daily activities. Subjects are required 
to indicate the degree of difficulty they have experienced in each domain in the past week on a 
4-point scale that ranges from 0 (without difficulty) to 3 (unable to do). Any individual score of 
less than 2 is adjusted to 2 if the activity requires assistance from another individual or the use of 
an assistive device. The highest score in each category is then summed (0 to 24) and divided by 
the number of categories scored to give a score that ranges from 0 to 3.  
9.7 
High sensitivity C-reactive protein levels (hs-CRP) 
High sensitivity CRP levels will be analyzed by the central laboratory according to Table 5-1. 
After Baseline, the hs-CRP data will not be sent to the Investigator in order to protect the blinded 
nature of the treatment assignments and response. 
9.8 
Evaluation of psoriasis 
9.8.1 
Body surface area-psoriasis (BSA-PSO) 
In the BSA-PSO assessment, the subject’s hand (including the palm, fingers, and thumb) is used 
as the reference point for measuring how much of their skin is affected by PSO, representing 
roughly 1% of the body’s surface.  
The BSA palm method will be used for the evaluation of BSA affected by PSO as follows: 
• Head and neck=10% (10 palms) 
• Upper extremities=20% (20 palms) 
• Trunk=30% (30 palms) 
• Lower extremities=40% (40 palms)  
• Total BSA=100% 
9.8.2 
Psoriasis Area and Severity Index (PASI) 
The PASI will be assessed in all subjects with Baseline/Day 1 BSA affected by PSO ≥3% 
determined by the method described in Section 9.8.1 (ie, the BSA palm method).  
The PASI is the most commonly used and validated assessment for grading the severity of PSO 
in clinical studies (Feldman, 2004). The PASI quantifies the severity and extent of the disease 
and weighs these with the percentage of BSA involvement.  
The percent area of involvement (BSA%) is estimated across 4 body areas (head, upper limbs, 
trunk, and lower limbs) and then transferred into a grade (Table 9-2).  
The Investigator assesses the average redness, thickness, and scaliness of lesions in each body 
area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked.  
The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity. 


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Table 9-2: 
Body areas for calculation of percent BSA for PASI 
Body area 
Details of area 
BSA 
Degree of 
involvement of 
body area a 
Head 
Face, back of head 
10% 
0 to 6 
Upper limbs  
Left, right, upper lower, flexor 
surface, extensor surface 
20% 
0 to 6 
Trunk 
Front, back, groin 
30% 
0 to 6 
Lower limbs  
Left, right, upper lower, flexor 
surface, extensor surface, including 
buttocks 
40% 
0 to 6 
Total 
 
100% 
 
BSA=body surface area; PASI=Psoriasis Area and Severity Index 
 a Where 0=none; 1=1% to <10% affected, 2=10% to <30% affected, 3=30% to <50% affected, 4=50% to <70% 
affected, 5=70% to <90% affected, 6=90% to 100% affected 
The PASI75, PASI90, and PASI100 responses are based on at least 75%, 90%, and 100% 
improvement in the PASI score. The PASI will be assessed at Screening and at Baseline/Day 1. 
Thereafter, the PASI will be assessed for the purposes of determining response only in subjects 
with PSO involving at ≥3% of BSA at Baseline/Day 1. 
9.8.3 
Investigator’s Global Assessment (IGA) 
A static IGA for PSO will be used to assess disease severity in all subjects during the study. The 
IGA will completed at the visits specified in Table 5-1.  
The Investigator will assess the overall severity of PSO using the following 5-point scale 
presented in Table 9-3. 
Table 9-3: 
Five-point IGA 
Score 
Short Descriptor 
Detailed Descriptor 
0 
Clear 
No signs of PSO; post-inflammatory hyperpigmentation may 
be present  
1 
Almost Clear 
No thickening; normal to pink coloration; no to minimal focal 
scaling 
2 
Mild 
Just detectable to mild thickening; pink to light red coloration; 
predominantly fine scaling 
3 
Moderate 
Clearly distinguishable to moderate thickening; dull to bright 
red, moderate scaling  
4 
Severe 
Severe thickening with hard edges; bright to deep dark red 
coloration severe/coarse scaling covering almost all or all 
lesions 
IGA=Investigator’s Global Assessment; PSO=psoriasis 
 


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The IGA response is defined as a clear [0] or almost clear [1] assessment with at least a 
2-category improvement from Baseline, meaning that this parameter will be evaluable only for 
subjects with psoriatic skin lesions (IGA score ≥2) at Baseline.    
In this study, only subjects with BSA ≥ 3% at Baseline will have IGA assessed at post-Baseline 
Visits. 
9.8.4 
Modified Nail Psoriasis Severity Index (mNAPSI) 
Subjects with psoriatic nail disease will have a target nail selected at the Baseline Visit for 
evaluation using the mNAPSI. The nail selected should be the most affected nail observed at 
Baseline and should be the only one assessed throughout the study. The target nail will be scored 
(0 to 3) for onycholysis/oil drop dyschromia, nail plate crumbling, and pitting and will be scored 
(0 for “no” or 1 for “yes”) for leukonychia, nail bed hyperkeratosis, splinter hemorrhages, and 
red spots in the lunula. 
9.9 
Minimal Disease Activity (MDA) and Very Low Disease Activity 
(VLDA) 
Minimal Disease Activity and VLDA are states of disease activity deemed useful targets of 
treatment by both the subject and physician, given current treatment possibilities and limitations. 
Criteria covering all domains of the disease have been developed to determine whether or not a 
subject has reached MDA or VLDA based on key outcome measures in PsA (Mease, 2011; 
Coates et al, 2010).  
A subject is considered as having MDA if 5 or more of the following 7 criteria are fulfilled: 
• Tender joint count ≤1 
• Swollen joint count ≤1 
• PASI ≤1 or BSA ≤3 
• Patients’ pain VAS ≤15 
• PGA-PsA VAS ≤20 
• HAQ-DI ≤0.5 
• Tender enthesial points ≤1 
A subject is considered as having VLDA if all 7 of the above criteria are fulfilled. 
9.10 
Disease Activity Index for Psoriatic Arthritis (DAPSA) 
Disease Activity Index for Psoriatic Arthritis (DAPSA) is a composite score of patient global and 
pain VAS, TJC/SJC, and hs-CRP that incorporates a pattern of peripheral arthritis that often is 
encountered in PsA, and is calculated as follows: 
DAPSA=SJC (range 0-66) + TJC (range 0-68) + PGA-Arthritis (VAS range 0-10cm; 0=best, 
10=worst) + PtAAP (VAS range 0-10cm) + hs-CRP. 


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9.11 
Van der Heijde modified Total Sharp Score (vdHmTSS) 
The degree of joint damage is to be assessed using the vdHmTSS as used in the evaluation of 
PsA (Van der Heijde et al, 2005). This methodology quantifies the extent of bone erosions and 
joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater 
damage. 
Radiographs of the hands and feet are to be taken using standardized imaging methodology, 
which is defined in the Hand and Foot Radiography Manual that will be provided as part of the 
Study Manual. 
All enrolled subjects are required to have radiographs taken of both hands and both feet (a single 
posteroanterior view of each hand and a single dorsoplantar of each foot). Radiographs are to be 
read centrally and independently by 2 experienced readers. Readers will be blind to treatment 
assignment and time course of the films.  
9.12 
Disease Activity Score-28 based on C-reactive protein 
(DAS28[CRP]) 
The components for DAS28(CRP) include the TJC and SJC based on 28 joints (Section 9.1.2), 
hs-CRP (Section 9.7) and the PGA-Arthritis (Section 9.5). The DAS28(CRP) is calculated as 
follows: 
𝐷𝐴𝑆28(𝐶𝑅𝑃) = 0.56  √𝑇𝐽𝐶+ 0.28  √𝑆𝐽𝐶+ 0.014   𝑃𝐺𝐴−𝐴𝑟𝑡ℎ𝑟𝑖𝑡𝑖𝑠+ 0.36  𝑙𝑛(𝐶𝑅𝑃+ 1) + 0.96 
 
9.13 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
The BASDAI is the most common instrument used to measure the disease activity of ankylosing 
spondylitis from the subject’s perspective (Garrett et al, 1994) and is considered useful for 
evaluating axial involvement in subjects with PsA (Fernandez-Sueiro et al, 2009). The BASDAI 
is a validated self-reported instrument which consists of six 10-unit horizontal numeric rating 
scales to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, 
and morning stiffness (both severity and duration, respectively) over the last week 
(van Tubergen et al, 2015). The final BASDAI score ranges from 0 to 10, with lower scores 
indicating lower disease activity.  
The BASDAI is calculated as follows:  
𝐵𝐴𝑆𝐷𝐴𝐼=
Q1 + Q2 + Q3 + Q4 + (𝑄5 + 𝑄6
2
)
5
 
 
9.14 
Leeds Enthesitis Index (LEI) 
Enthesitis, the inflammation at the bone insertion of tendon, ligament, or joint capsule, is 
common in PsA. The LEI is a new enthesitis index designed for use in PsA (Healy and Helliwell, 
2007) adopted for use in randomized controlled studies involving subjects with PsA. Enthesitis 
will be assessed by palpation on the lateral epicondyles of the humerus (elbows), medial femoral 
epicondyles (knees), and Achilles tendons (heels) bilaterally and scored as 0=no pain and 
1=painful. 


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9.15 
Spondyloarthritis Research Consortium of Canada (SPARCC) 
The SPARCC is an index that measures the severity of enthesitis through the assessment of 
16 sites (the greater trochanter (right/left [R/L]), quadriceps tendon insertion into the patella 
(R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon 
insertion (R/L), plantar fascia insertion (R/L), medial and lateral epicondyles (R/L) and the 
supraspinatus insertion [R/L]) (Maksymowych et al, 2009). Tenderness on examination is 
recorded as either present (1) or absent (0) for each of the 16 sites, for an overall score range of 
0 to 16. 
9.16 
Leeds Dactylitis Index (LDI) 
Dactylitis, the swelling of an entire digit related to articular and periarticular inflammation is a 
characteristic of inflammatory spondyloarthropathies, including PsA. Presence of dactylitis will 
be assessed using the LDI basic. It measures the ratio of the circumference of the affected digit to 
the circumference of the digit on the contralateral hand or foot (millimeters): a minimum 
difference of 10% is used to define a dactylitic digit (Healy and Helliwell, 2007; 
Helliwell et al, 2005). If the contralateral digit is also dactylitic, a table of normative values 
based on population averages is used to provide the comparison. The ratio is then multiplied by 
the tenderness score, using a simple grading system (0=absent, 1=present). The results from each 
digit with dactylitis are then summed to produce a final score. The digits involved and the 
matching contralateral digit will also be recorded at the same visits. 
9.17 
Psoriatic Arthritis Quality of Life (PsAQoL) 
The use of the PsAQoL is recommended by the health regulatory authorities as 1 of the 
disease-specific HRQoL measures in PsA (CHMP/EWP/438/04). The PsAQoL comprises 
20 items so that the score ranges from 0 to 20 with higher scores indicating worse HRQoL. 
9.18 
Psoriatic Arthritis Impact of Disease-12 (PsAID-12) 
The PsAID-12 is a patient-reported outcome measure for assessing the impact of PsA in 
12 physical and psychological domains, including pain, fatigue, skin problems, work and/or 
leisure activities, functional capacity, discomfort, sleep disturbance, coping, 
anxiety/fear/uncertainty, embarrassment and/or shame, social participation, and depression. Each 
domain is assessed with a single question using a 0 to 10 numerical rating scale. Each domain 
score is multiplied by a weighting factor and the results are then summed to provide the total 
score. The total score ranges from 0 to 10, with higher scores indicating a worse status. The 
PsAID-12 demonstrated satisfactory psychometric properties in an international validation study; 
however, further validation is needed (Gossec et al, 2014). A score below 4 out of 10 is 
considered a patient-acceptable status. A change of 3 or more points is considered relevant 
absolute change.  
9.19 
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue 
subscale 
The FACIT-Fatigue is a 40-item measure that assesses self-reported fatigue and its impact upon 
daily activities and function over the past 7 days (FACIT.org). The scale consists of 5 subscales 
(physical well-being, social/family well-being, emotional well-being, functional well-being, and 
fatigue). The fatigue subscale is the only one used in this study . It is composed of 13 items, all 
scored from 0 (Not at all) to 4 (Very much). The FACIT-Fatigue subscale score ranges from 0 to 


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52 with 0 being the worst possible score and 52 being the best possible score. To obtain a score 
from 0 to 52, all negatively worded questions have to be recoded, so that responses range from 
worst (0) to the best (4) outcome. 
The FACIT-Fatigue subscale has been validated in patients with PsA. The minimum clinically 
important difference for FACIT-Fatigue subscale in patients with PsA was determined to be a 4-
point change (Cella et al, 2019). 
9.20 
Short-Form 36-item Health Survey (SF-36) 
The SF-36 (version 2, standard recall) is a 36-item generic HRQoL instrument that uses a recall 
period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), 
Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), 
Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and 1 item 
 
. The concepts 
represented by these domains contribute to physical, mental, and social aspects of HRQoL. 
In addition to domain scores, the PCS and MCS scores are calculated from the 8 domains 
(excluding the Health Transition item). Component scores reflect the impact of each domain on 
physical and mental health status. The norm-based T-scores for the 2 SF-36 component summary 
(PCS and MCS) and the 8 domains are standardized with a mean of 50 and a standard deviation 
(SD) of 10 in the general US population (Maruish, 2011). An individual respondent’s score that 
falls outside the T-score range of 45 to 55 should be considered outside the average range for the 
US general population. When considering group-level data, a score below 47 should be 
considered indicative of impaired functioning within that health domain or dimension. Similar to 
individual respondent data, group mean scores of 47 or greater should be considered average or 
above average as compared to the general US population. Higher scores indicate a better health 
status.  
9.21 
Euro Quality of life 5-Dimensions-3 Level (EQ-5D-3L) 
The EQ-5D-3L is comprised of a 5-item health status dimension and a VAS. The response to 
each of the 5 health status dimensions is divided into 3 levels (no problem, some or moderate 
problems, or extreme problems) and is scored as 1, 2, and 3, respectively. The EQ-5D-3L VAS 
records the respondent’s self-rated health status on a vertical 20cm scale, 0 to 100 graduated 
(0=worst imaginable health status, 100=best imaginable health status). 
9.22 
Work Productivity and Activity Impairment Questionnaire–
Specific Health Problem (WPAI-SHP) 
The WPAI-SHP v2.0 is a patient-reported questionnaire that assesses subject’s employment 
status, work absenteeism, work impairment while working (presenteeism), overall work, and 
daily activity impairment attributable to a specific health problem (Reilly et al, 1993).  
Five out of 6 items of the WPAI-SHP are regrouped into the 4 dimensions, with scores expressed 
as percentage, where higher numbers indicate greater impairment and less productivity (ie, worse 
outcomes) as described in the WPAI-SHP scoring rules. 
9.23 
Psoriatic Arthritis Response Criteria (PsARC) 
The PsARC is based on the TJC (68 joints) and SJC (66 joints), the PGA-PsA and PhGA-PsA 
VAS.  


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The PsARC response is defined as improvement from Baseline in at least 2 of the 4 measures 
(TJC, SJC, PGA-PsA, PhGA-PsA) 1 of which must be TJC or SJC and no worsening from 
Baseline in any of the 4 measures. Improvement for TJC and SJC is defined as a reduction of 
≥30% and worsening is defined as an increase of ≥30%. Improvement of PGA-PsA and 
PhGA-PsA is defined as a reduction of the 100-point VAS of ≥20 points and worsening is 
defined as an increase of the 100-point VAS of ≥20. 
9.24 
Psoriatic Arthritis Disease Activity Score (PASDAS) 
The PASDAS (Coates et al, 2014) is a composite score that includes patient and physician global 
scores of skin and joint disease, SJC, TJC, LEI, tender dactylitis count, the physical component 
of the SF-36 Health Survey, and level of CRP. It was developed by the Group for Research and 
Assessment of Psoriasis and Psoriatic Arthritis and the European League Against Rheumatism. 
PASDAS is calculated using the following equation: 
PASDAS = (((0.18 × √Physician global VAS) + (0.159 × √Patient global VAS) − 
(0.253 × √SF36 − PCS) + (0.101 × LN (SJC + 1)) + (0.048 × LN (TJC + 1)) + (0.23 × 
LN (LEI + 1)) + (0.377 LN (tender Dactylitis count + 1)) + (0.102 × LN (CRPmg/dL 
+ 1)) +2)*1.5. 
Note: LN=natural logarithm 
The following categories are used to define the level of disease activity (Coates et al, 2018): 
• Remission: PASDAS ≤1.9 
• Low disease activity: PASDAS 1.9 to <3.2 
• Moderate disease activity: PASDAS 3.2 to <5.4 
• High disease activity: PASDAS ≥5.4 
10 
ASSESSMENT OF PHARMACOKINETIC AND 
PHARMACOGENOMIC VARIABLES 
10.1 
Pharmacokinetic variable 
The PK variable is the plasma concentrations of bimekizumab.   
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5-1. When these samples are required at a visit during which the subject is 
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. Detailed information on 
sample analysis will be provided in a bioanalytical report. 
10.2 
Pharmacogenomic variables 
A separate ICF will be required for those subjects who agree to participate in the genomics, 
genetics, and proteomics substudy, and must be signed prior to collection of any samples for the 
substudy. The substudy will only be conducted where ethically accepted and authorized by the 
regulatory agencies. Refusal to participate in the substudy will not affect a subject’s ability to 
participate in the main study. 


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These analyses will enable evaluation of biomarkers relative to disease biology and progression, 
drug treatment, and inflammatory and immune response processes. The nature and format of 
these tentative analyses will be determined at a later date. 
For individuals consenting to the genomics, genetics, and proteomics substudy, blood samples 
will be drawn for exploratory genetic/epigenetic, genomic, proteomic, and metabolomics 
analysis and for candidate exploratory biomarker analyses. Candidate exploratory biomarker 
evaluations may include, but are not limited to, IL 17A/IL-17F pathway signaling and PsA 
biology (eg, IL-17A, IL-17F, IL-23, IL-6, tumor necrosis factor, dendritic cell-specific 
transmembrane protein, and circulating osteoclast precursors). 
Collection of these samples will occur at the time points specified in the schedule of study 
assessments (Table 5-1). At dosing visits, blood samples will be drawn prior to dosing, and will 
be drawn at the same time of the sampling for clinical laboratory tests. The time and date of 
collection will be recorded in the eCRF. The samples will be stored at -80°C at the central 
biorepository for up to 20 years. 
Detailed information on the collection, storage, preparation, and shipping of samples for 
potential RNA, proteins, lipids, and metabolites analysis will be presented in a Laboratory 
Manual. 
The nature and format of these tentative analyses will be determined at a later date. 
Results for the exploratory parameters obtained from potential RNA, lipids, proteins and 
metabolites analysis will be described in a separate report. 
11 
ASSESSMENT OF IMMUNOLOGICAL VARIABLES 
Immunological variables are the anti-bimekizumab antibody status, and the treatment-emergent 
antibody positivity derived from anti-drug antibody assays.  
The Investigator or designee will obtain blood samples for these measurements at the time points 
specified in Table 5-1. When these samples are required at a visit during which the subject is 
dosed with IMP, the blood samples will be drawn prior to dosing. Samples should be drawn at 
the same time of the sampling for clinical laboratory tests. The time and date of collection will be 
recorded in the eCRF. Instructions pertaining to sample collection, processing, storage, labeling, 
and shipping are provided in the laboratory manual for this study. The presence of antibodies to 
bimekizumab will be determined using a validated bioanalytical method. Detailed information on 
sample analysis will be provided in a bioanalytical report. 
The presence of anti-bimekizumab antibodies will be determined using a tiered approach of 
screening, confirmatory, and titer assays. Where applicable, a neutralizing-antibody assay will be 
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12 
ASSESSMENT OF SAFETY 
12.1 
Adverse events 
12.1.1 
Definitions 
12.1.1.1 
Adverse event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and post-treatment 
periods required by the protocol, must be reported in the eCRF even if no IMP was taken but 
specific study procedures were conducted. This includes all AEs not present prior to the initial 
visit and all AEs that recurred or worsened after the initial visit. 
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period. 
12.1.1.2 
Serious adverse event 
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria: 
• Death 
• Life-threatening 
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.) 
• Significant or persistent disability/incapacity 
• Congenital anomaly/birth defect (including that occurring in a fetus) 
• Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious 
(Important medical events may include, but are not limited to, potential Hy’s Law [see 
Section 12.1.1.3], allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.) 
• Initial inpatient hospitalization or prolongation of hospitalization 
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 


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admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event]. 
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.) 
Note: Confirmed active TB is an SAE and must be captured on an SAE Report Form and 
provided to the Sponsor in accordance with SAE reporting requirements. 
12.1.1.2.1 
Anticipated serious adverse events 
The following anticipated SAEs are anticipated to occur in the population studied in this protocol 
at some frequency that is independent of drug exposure. Note that listed events will not be 
regarded as anticipated SAEs if they are life threatening or if they result in the death of the study 
subject. 
This list does not change the Investigator’s obligation to report all SAEs (including anticipated 
SAEs) as detailed in Section 12.1.2.3. 


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Table 12-1: Anticipated SAEs for the population of subjects with PsA 
MedDRA system organ class 
MedDRA preferred terms 
Eye disorders 
Uveitis 
Cardiac disorders 
Myocardial infarction 
Atrial fibrillation 
Gastrointestinal disorders 
Crohn's disease 
Hepatobiliary disorders 
Non-alcoholic steatohepatitis 
Metabolism and Nutrition disorders 
Metabolic syndrome 
Diabetes mellitus 
Musculoskeletal and connective tissue disorders 
Psoriatic arthropathy 
Neoplasms benign, malignant and unspecified 
(including cysts and polyps) 
Basal cell carcinoma 
Squamous cell carcinoma 
Nervous system disorders 
Embolic Stroke 
Ischaemic Stroke 
Psychiatric disorders 
Anxiety 
Depression 
Skin and subcutaneous tissue disorders 
Psoriasis 
MedDRA=Medical Dictionary for Regulatory Activities; PsA=psoriatic arthritis; SAE=serious adverse event 
Note: Exception: Listed events will not be regarded as anticipated SAEs if they are life threatening or if they 
result in the death of the study subject. 
 
12.1.1.3 
Adverse events of special interest 
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. 
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AE of special interest (ie, without waiting for any 
additional etiologic investigations to have been concluded). Follow-up information should then 
be reported if an alternative etiology is identified during investigation and monitoring of the 
subject. 
12.1.1.4 
Other safety topics of interest 
Prespecified safety topics of interest for the study are: infections (serious, opportunistic, fungal 
and TB), neutropenia, hypersensitivity, suicidal ideation and behavior, major cardiovascular 
events, liver function test changes/enzyme elevations, malignancies, and inflammatory bowel 
diseases (with gastroenterology referral, as appropriate).  
This is based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or findings from other medicines with a related 


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mechanism of action. There are no specific AE reporting requirements for these topics; however, 
special monitoring, additional data collection activities, and/or enhanced signal detection 
activities (within UCB) are in place. 
12.1.2 
Procedures for reporting and recording adverse events 
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example: 
“Did you notice anything unusual about your health (since your last visit)?” 
In addition, the Investigator should review any self-assessment procedures employed in the 
study. 
12.1.2.1 
Description of adverse events 
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records and the corresponding medical terminology should be clarified in the 
source documentation. 
When recording the intensity of an AE in the CRF (ie, mild, moderate, or severe), the 
Investigator should use the following criteria: 
• Mild: the subject is aware of the sign or symptom (syndrome), but it does not interfere with 
his/her usual activities and/or is of no clinical consequence 
• Moderate: the AE interferes with the usual activities of the subject or it is of some clinical 
consequence 
• Severe: the subject is unable to work normally or to carry out his/her usual activities, or the 
AE is of definite clinical consequence 
Details for completion of the AE eCRF (including judgment of relationship to IMP) are 
described in the eCRF Completion Guidelines. 
12.1.2.2 
Rule for repetition of an adverse event 
An increase in the intensity of an AE should lead to the repetition of the AE being reported with: 
• The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening” 
• The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one 
12.1.2.3 
Additional procedures for reporting serious adverse events 
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site. The Investigator must enter the information regarding the SAE into the appropriate 
eCRFs and transmit to UCB via the clinical database, even if the data are incomplete, or if it is 
obvious that more data will be needed in order to draw any conclusions. This information will be 
received by UCB and entered into the global safety database. Any ancillary documentation (eg, 
autopsy or other documentation) that is valid for the SAE can be sent to UCB using the contact 


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information (fax/email) for SAE reporting listed in the Serious Adverse Event Reporting section 
at the front of the protocol. 
It is important for the Investigator, when entering the SAE data into the eCRF, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner. 
Additional information 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 eCRF and transmitted to 
UCB via the clinical database. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study. 
Upon receipt of the electronic transmission of the SAE, UCB will perform as assessment of 
expectedness of the reported SAE. The assessment of expectedness of the SAE is based on the 
IB. 
12.1.3 
Follow-up of adverse events 
An AE should be followed until it has resolved, has stable sequelae, the Investigator determines 
that it is no longer clinically significant, or the subject is lost to follow-up. This follow-up 
requirement applies to AEs, SAEs, and AEs of special interest; AESMs, further details regarding 
follow-up of PDILI events is provided in Section 12.2.1.4. 
If an AE is ongoing at the end of the study for a subject, follow-up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow-up. If no follow-up is provided, the 
Investigator must provide a justification. The follow-up will usually be continued for 20 weeks 
after the subject has discontinued his/her IMP. 
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time. 


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12.1.4 
Pregnancy 
If the Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately (within 24 hours) notify UCB’s PS department by entering all 
pregnancy information into the eCRF. An automatic notification will be sent to UCB PS. The 
subject should be permanently withdrawn from IMP as soon as pregnancy is known (by positive 
pregnancy test), and the following should be completed: 
• The subject should immediately stop the intake of the IMP. 
• The subject should return for an early ad-hoc study visit. 
• A Safety Follow-Up Visit should be scheduled 20 weeks after the final dose of IMP. 
The Investigator should discuss with the subject the possibility to continue the study by attending 
the scheduled visits for assessments without IMP administration. The tests or assessments, which 
are considered contraindicated during the pregnancy should not be performed. The early ad-hoc 
study visit will be considered as the ET Visit if the subject does not wish to pursue the study 
investigations. 
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives. 
The pregnancy will be documented in the eCRF provided to the Investigator. The progression of 
the pregnancy and the eventual birth (if applicable) must be followed up using the eCRF in 
which the Investigator must report on the health of the mother and of the child. Every reasonable 
attempt should be made to follow the health of the child for 30 days after birth for any significant 
medical issues. In certain circumstances, UCB may request that follow-up is continued for a 
period longer than 30 days. If the subject is lost to follow-up and/or refuses to give information, 
written documentation of attempts to contact the subject needs to be provided by the Investigator 
and filed at the site. UCB’s PS department is the primary contact for any questions related to the 
data collection for the pregnancy, eventual birth, and follow-up. 
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/contract research organization (CRO) contract monitor for the 
study. The Investigator will complete the information in the eCRF only after the partner has 
agreed that additional information can be captured and has provided the signed Partner 
Pregnancy Consent Form. UCB’s PS department is also the primary contact for any questions 
related to the data collection for partner pregnancy, eventual birth, and follow-up. 
A pregnancy becomes an SAE in the following circumstances: miscarriage, elective abortion, 
medically indicated abortion (eg, when the pregnancy is endangering life or health of woman, or 
when fetus will be born with severe abnormalities), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally 
reported using the eCRF. 


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12.1.5 
Suspected transmission of an infectious agent via a medicinal 
product 
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent. 
12.1.6 
Overdose of investigational medicinal product 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if 
there are associated clinical signs and symptoms or if the act of taking the excess medicine itself 
is an AE or SAE (eg, suicide attempt). 
12.1.7 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative. 
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory, or ECG results) for which data will be periodically reviewed during the course 
of the study. 
In addition, an independent Data Monitoring Committee (DMC) will periodically review and 
monitor the safety data from this study and advise UCB. The DMC membership includes 
clinicians knowledgeable about the disease or the treatment. All members have experience and 
expertise in clinical studies. Board members may not participate in the study as principal or 
co-Investigators, or as study subject care physicians. The duration of membership for the DMC 
will be inclusive of planned analyses for PA0010. The DMC may also be asked to provide a 
review of final study results, as deemed appropriate. The DMC procedures will ensure that data 
remain blind to the study team and Investigators at all times throughout the conduct of the study. 
The detailed role, scope, responsibilities, and complete procedures, as well as the identity of the 
DMC members, will be described in a separate charter document. A Cardiovascular Adjudication 
Committee and a Neuropsychiatric Adjudication Committee will be in place for this study. 
Specific procedures will be outlined in the charters, which will be developed by the committee 
members. 
12.2 
Laboratory measurements 
Clinical laboratory assessments consist of serum biochemistry, hematology, urinalysis, and 
pregnancy tests (serum or urine) (Table 5-1). A centralized laboratory will be used to supply all 
laboratory test supplies and analyze all blood and urine samples for hematology and 
biochemistry. Any unscheduled laboratory testing should also be collected using the central 


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laboratory (with the exception of urgent safety laboratory measurements which should be 
performed locally and centrally simultaneously). Testing to rule out hepatitis B, hepatitis C, and 
HIV will be performed at Screening. Rheumatoid factor and anti-CCP testing will also be 
performed at Screening. Testing of HLA-B27 will be performed at Baseline. 
Specific details regarding the handling and processing of serum biochemistry, hematology and 
urinalysis samples are provided in the study laboratory manuals. 
Laboratory parameters to be measured are presented in Table 12-2. 
Table 12-2: Laboratory measurements 
 
Hematology 
Biochemistry 
Urinalysis  
Basophils 
Calcium 
pH 
Eosinophils 
Chloride 
Albumin (protein) 
Lymphocytes 
Magnesium 
Glucose 
Monocytes 
Potassium 
Blood 
Neutrophils 
Sodium 
Leukocyte esterase 
Hematocrit 
Glucose 
Nitrite 
Hemoglobin 
BUN 
Urine dipstick for pregnancy testing b 
MCH 
Creatinine 
Urine drug screenc 
MCHC 
hs-CRP 
 
MCV 
AST 
 
Platelet count 
ALT 
 
RBC count 
GGT 
 
WBC count 
ALP 
 
 
Total bilirubin 
 
 
Triglyceridesa 
 
 
Cholesterola 
 
 
HDL cholesterola 
 
 
LDL cholesterola 
 
 
LDH 
 
 
Serum pregnancy testingb 
 


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Table 12-2: Laboratory measurements 
 
Hematology 
Biochemistry 
Urinalysis  
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood 
urea nitrogen; ET=early termination; GGT=gamma-glutamyltransferase; HDL=high density lipoprotein; 
hs-CRP=high sensitivity C-reactive protein; IMP=investigational medicinal product; IMS=International 
Menopause Society; LDH=lactate dehydrogenase; LDL=low density lipoprotein; MCH=mean corpuscular 
hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; 
RBC=red blood cell; SFU=Safety Follow-up; WBC=white blood cell 
a Biochemistry will include triglycerides, cholesterol, HDL cholesterol, and LDL cholesterol at Baseline, 
Weeks 12 and 24, and at the ET Visit. 
b Pregnancy testing will consist of serum testing at the Screening Visit for all women of childbearing potential. 
The pregnancy test will be urine at all other visits.  
c Urine drug screen will be performed at Screening Visit. 
 
12.2.1 
Evaluation of potential drug-induced liver injury 
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as AEs and PDILI events meeting SAE criteria should be reported to the 
Sponsor within 24 hours of learning of their occurrence. Any PDILI event that meets the 
criterion for potential Hy’s Law must be reported within 24 hours of learning of their occurrence 
as an AE of special interest (see Section 12.1.1.3), and, if applicable, also reported as an SAE 
(see Section 12.1.1.2).  
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.2.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 12.2.1.4).  
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor. 
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result. 
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages. 
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 


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any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative. 
When IMP is stopped due to PDILI (as described in Section 6.3.1), IMP must be permanently 
discontinued unless a subsequent alternative diagnosis fully explains the hepatic findings. If a 
subsequent alternative diagnosis fully explains the hepatic findings, and the requirements 
provided in Section 12.2.1.2.1 are met, rechallenge with IMP may be appropriate. 
The approach to investigate PDILI is summarized in Table 12‒3. 
 


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Table 12‒3: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥3xULN 
≥2xULNb NA 
Hepatology consultc 
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor 
ASAP. 
Immediate IMP 
discontinuation.d 
 
 
 
Essential: Must have 
repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 12.2.1.3); 
recommended to 
occur at the site with 
HCP. 
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within baseline values.e 
≥3xULN 
NA 
Yes 
≥8xULN 
NA 
NA 


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Table 12‒3: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥5xULN 
(and ≥2x 
baseline) 
and 
<8xULN  
<2xULN 
No 
Discussion with 
Medical Monitor 
required. 
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow 
up requirements).c 
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 12.2.1.2). 
 
IMP discontinuation 
required if any of the 
following occur: 
• Subject cannot 
comply with 
monitoring 
schedule. 
• Liver chemistry 
values continue to 
increase. 
• Liver chemistry 
values remain 
≥5xULN (and 
≥2x baseline) after 
4 weeks of 
monitoring without 
evidence of 
resolution. 
Essential: Every 
attempt must be 
made to have repeat 
liver chemistry 
values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.2.1.3). 
Monitoring of liver 
chemistry values at least 
twice per week for 2 
weeks.e 
• 
Immediate IMP 
discontinuation 
required if liver 
chemistry values 
continue to increase. 
After 2 weeks of 
monitoring liver 
chemistry values: 
• 
ALT or AST remains 
≥5xULN <8xULN, 
IMP should be 
temporarily withheld 
and subject should 
undergo repeat test in 
2 weeks. 
• 
Continue IMP if ALT 
or AST values 
<5xULN; continue to 
monitor at least twice 
per week until values 
normalize, stabilize, 
or return to within 
baseline values. 


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Table 12‒3: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
• 
If ALT or AST 
remains ≥5xULN 
after second re-test, 
immediate IMP 
discontinuation 
required. 
Continue to monitor until 
values normalize, 
stabilize, or return to 
within baseline values.e 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause). 
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor. 
c Details provided in Section 12.2.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist but may be a gastroenterologist. 
d Details are provided in Section 12.2.1.2.1.  
e Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
 


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12.2.1.1 
Consultation with Medical Monitor and local hepatologist  
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 12.2.1.3) and SAE report (if applicable). 
12.2.1.2 
Immediate action: determination of IMP discontinuation 
All PDILI events require immediate action, testing, and monitoring.  
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 12‒3 for details). 
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative. 
12.2.1.2.1 
IMP restart/rechallenge 
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 12‒3), but for whom an alternative diagnosis is 
confirmed, ie, drug-induced liver injury is excluded, can rarely restart IMP. Rechallenge with 
IMP can occur only if ALL of the following requirements are met at the time of the rechallenge: 
• The results of additional testing and monitoring described in Section 12.2.1.3 and 
Section 12.2.1.4 confirm a nondrug-related cause for the abnormal hepatic laboratory 
parameters and any associated symptoms (ie, a subsequent alternative diagnosis fully 
explains the hepatic findings).  
• No alternative treatment options are available to the subject. 
• The subject has shown clear therapeutic benefit from the IMP. 
• Subject’s ALT or AST elevations do not exceed ≥3xULN. 
• Subject’s total bilirubin is <1.5xULN. 
• Subject has no signs or symptoms of hypersensitivity.  
• The rechallenge is approved by the UCB responsible physician and a hepatologist. The 
hepatologist must be external to UCB. It is recommended that the hepatologist be a local 
hepatology expert or the hepatologist treating the subject. 
• Subject agrees to the investigator-recommended monitoring plan and understands their 
individual benefit risk for restarting IMP and this is adequately documented.  


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12.2.1.3 
Testing: identification/exclusion of alternative etiology 
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are detailed in 
Table 12-4 (laboratory measurements) and Table 12-5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the Sponsor on the 
corresponding eCRF. If the medical history of the subject indicates a requirement for other 
assessments not included below, these additional assessments should be completed and 
submitted, as applicable. 
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory. 


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The following measurements are to be assessed: 
Table 12-4: PDILI laboratory measurements 
Virology-
related 
Hepatitis A IgM antibody 
HBsAg 
Hepatitis E IgM antibody 
HBcAb-IgM 
Hepatitis C RNA 
Cytomegalovirus IgM antibody 
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophile 
antibody or monospot testing) 
Immunology 
Anti-nuclear antibody (qualitative and quantitative) 
Anti-smooth muscle antibody (qualitative and quantitative) 
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative) 
Hematology 
Eosinophil count 
Urinalysis 
Toxicology screen a 
Chemistry 
Amylase 
Sodium, potassium, chloride, glucose, BUN, creatinine 
Total bilirubin, ALP, AST, ALT, GGT, total cholesterol, albumin 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin 
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation  
Additional 
Prothrombin time/INRb 
Serum pregnancy test 
PK sample 
ALP= alkaline phosphatase; ALT=alanine aminotransferase; AST= aspartate aminotransferase; BUN=blood urea 
nitrogen; CPK=creatine phosphokinase; GGT=gamma-glutamyltransferase; HBcAb-IgM=hepatitis B core 
antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; 
LDH=lactate dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic 
acid; ULN=upper limit of normal 
a For detecting substances (ie, amphetamines, benzodiazepines, opioids, marijuana, cocaine, phencyclidine, and 
tricyclic antidepressants), additional tests may be performed based on the Investigator’s medical judgment and 
subject’s history.  
b Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause). 


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Additional information to be collected is presented in Table 12-5.  
Table 12-5: PDILI information to be collected 
New or updated information 
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included. 
Pertinent medical history, including the following: 
• 
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”) 
• 
Adverse reactions to drugs 
• 
Allergies 
• 
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency) 
• 
Recent travel  
• 
Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, 
should not be used as an explanation for significant AST and/or ALT elevations.) 
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash) 
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function 
Alcohol and illicit drug use 
Results of liver imaging or liver biopsy, if done 
Results of any specialist or hepatology consult, if done 
Any postmortem/pathology reports 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury 
12.2.1.4 
Follow-up evaluation 
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 12‒3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to baseline. Determination of stabilization is at the discretion of the Investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
12.3 
Other safety measurements 
12.3.1 
Vital signs 
The Investigator or designee should measure all vital signs (BP, temperature [oral, axillary, or 
otic], and pulse rate) after the subject has been sitting for at least 5 minutes, and the subject 
should remain seated during the measurements. At Baseline and at Week 16, vital signs will be 
measured prior to IMP administration and then at approximately 30 minutes and 1 hour after 
dosing. At all other visits, vital signs will be measured only once prior to dosing. 


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12.3.2 
Body weight and height 
The Investigator or designee will measure the height of the subject with shoes removed in meters 
and the weight of the subject in kilograms. The same scale should be utilized throughout the 
study where possible. 
12.3.3 
Physical examination 
The physical examination should be conducted by the Investigator or designee at the time points 
listed in Table 5-1 and will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; gastrointestinal; musculoskeletal; hepatic; neurological 
(including limb reflexes); and mental status. Findings considered clinically significant changes 
since the physical examination at the Screening Visit will be recorded as AEs. 
12.3.4 
12-lead electrocardiogram 
The Investigator or designee will perform the ECGs which will be read centrally. Full details of 
ECG recording will be provided in the ECG Manual. 
12.3.5 
Assessment and management of TB and TB risk factors 
All subjects will be assessed for TB at Screening and at the time points specified in the schedule 
of study assessments (Table 5-1) through physical examination for signs and symptoms of TB, 
chest x-ray (Section 12.3.5.2), laboratory testing (Section 12.3.5.1), and subject questionnaire 
(Section 12.3.5.3). 
At Screening, all subjects will have an IGRA test (QuantiFERON TB Test is recommended), a 
chest x-ray (unless already performed within 3 months of Screening) and examination for signs 
and symptoms of TB. In addition, each subject will complete a TB questionnaire directed at 
potential exposure to TB and symptoms of TB.  
For the purposes of this study, TB definitions are as follows: 
a. Known TB infection: 
− Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra-pulmonary). 
− History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection, unless adequately treated and proven to be fully 
recovered upon consult with a TB specialist. 
− Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject’s medical history. 
b. High risk of acquiring TB infection: 
− Known close exposure to another person with active TB infection within the 3 months 
prior to Screening. 
− Time spent in a healthcare delivery setting or institution where individuals infected with 
TB are housed and where the risk of transmission of infection is high. 


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c. Latent TB infection (unless appropriate prophylaxis is initiated at least 4 weeks prior to IMP 
dosing and continued to completion of prophylaxis): 
− The absence of signs, symptoms, or physical findings suggestive of TB infection with a 
positive IGRA test (or 2 indeterminate IGRA test results) and a chest x-ray (or other 
imaging) without evidence of TB infection. If the result of the IGRA test is 
indeterminate, the particular IGRA test previously performed may be repeated once; if 
positive or indeterminate on retest, the subject may not be randomized to IMP without 
further evaluation by a TB specialist and discussion with the Study Physician, if LTBI is 
identified. The retest must be done during the protocol-defined Screening window. 
− Note: If available, respiratory or other specimens must also be smear and culture negative 
for TB (Center for Disease Control diagnosis of LTB infection; 
http://www.cdc.gov/TB/topic /testing/default.htm). 
d. NTMB infection is defined as a clinical infection caused by mycobacterial species other than 
those belonging to the Mycobacterium tuberculosis complex. 
e. Tuberculosis test conversion: 
− A positive IGRA result for the current test when previous IGRA test results were 
negative. All subjects with TB test conversion must immediately stop IMP administration 
and be referred to a TB specialist for further evaluation. Confirmed TB test conversions 
should be classified as due to LTBI, active TB infection, or NTMB, and reported to the 
UCB PS function. 
Subject eligibility, retesting requirements, and treatment requirements are presented in 
Figure 12-1. A schematic diagram of TB test results during the study is presented in Figure 12‒2. 


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Figure 12-1: Schematic diagram of TB test results and study eligibility 
 
CDC=Center for Disease Control; IGRA=interferon-gamma release assay; LTBI= latent tuberculosis infection; 
TB=tuberculosis; WHO=World Health Organization 
a IGRA retest must be done during the protocol-defined Screening window. 
b Subject has a past history of active TB involving any organ system unless adequately treated according to 
WHO/CDC therapeutic guidance and proven to be fully recovered upon consult with a TB specialist. Subjects who 
have recently (no more than 12 months prior to Screening) completed full treatment course of prophylaxis for 
LTBI are allowed. Prophylaxis should be in accordance with WHO/CDC guidelines and TB specialist judgment 
based on the origin of infection.  
c Subjects with LTBI may enter the study only after they have completed at least 4 weeks of appropriate 
prophylactic therapy and thereafter, will continue and complete the entire regimen. 


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Figure 12‒2: Schematic diagram of TB test results during the study 
 
ASAP=as soon as possible; IGRA-interferon-gamma release assay; LTBI=latent tuberculosis infection; 
TB=tuberculosis 
a IGRA retest must be done ASAP and prior to the next dose. 
b Subjects with LTBI may continue the study only after they have completed at least 4 weeks of appropriate 
prophylactic therapy and thereafter, will continue and complete the entire regimen.  


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12.3.5.1 
Tuberculosis assessment by IGRA 
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB Test is 
recommended) will be performed as described in Table 5-1 for all subjects. The test results will 
be reported as positive, negative, or indeterminate. Positive and indeterminate TB test results that 
occur during the course of the study must be reported as an AE and appropriately updated once 
the final diagnosis is known (eg, active TB, latent TB, or false positive TB test). UCB also 
recommends that a TB specialist be consulted where TB (latent or active) is suspected or if there 
are doubts regarding test results. If latent or active TB is identified, subject must undergo 
appropriate study-specified withdrawal procedures. The retest during Screening must be done 
during the protocol-defined Screening window. 
12.3.5.2 
Chest x-ray for tuberculosis 
A plain posteroanterior chest x-ray must be performed in the Screening Period unless one has 
been performed within 3 months prior to the Screening Visit. The chest x-ray (or, if done, 
Computed Axial Tomography [CAT] of the chest) must be clear of signs of TB infection 
(previous or current) before first IMP administration. All chest imaging (particularly x-rays) 
should be available for review by the Investigator before randomization of the subject. The chest 
x-ray reading should be repeated if the TB test was confirmed positive. If the second read of the 
pretreatment chest x-ray is confirmed to be clear, the subject may be included in the study 
4 weeks after the start of the TB prophylactic treatment. If the pretreatment chest x-ray is not 
available for a re-read, it should be repeated after notification to the radiologist that this subject 
is IGRA positive and confirmed to be clear for signs of TB. 
The chest imaging must be negative for any old or recent TB infection as determined by a 
qualified radiologist and/or pulmonary physician. Any new clinically significant findings post 
Baseline on chest x-ray must be documented in the source documents and the eCRF as an AE. 
12.3.5.3 
Tuberculosis questionnaire 
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will be completed as described in Table 5-1. The 
questionnaire will assist with the identification of subjects who may require therapy for TB. A 
subject who answers “Yes” to the question 
 
 at Screening 
is excluded. A “Yes” response to any of the other questions within the questionnaire at Screening 
should trigger further careful assessment to determine if subject has LTB or active TB (see 
Exclusion Criterion #10 in Section 6.2). A “Yes” response to any of the questions during the 
study should trigger further assessments to determine if the subject has either LTB or active TB 
infection.  
12.3.5.4 
Tuberculosis management 
LTB infection and active TB identified during study 
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of IMP and will be referred to an appropriate TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Evidence of 
LTB infection is defined as subject’s IGRA test converts to positive or indeterminate (and 
confirmed indeterminate on repeat), or the subject’s questionnaire or history and physical 


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indicates that TB infection or exposure may have occurred. Evidence of active TB includes, in 
addition to the aforementioned tests, signs and symptoms of organ involvement. In either 
situation, the subject should be carefully assessed by a TB specialist for active TB. Subjects 
diagnosed with active TB should be withdrawn from the study and receive appropriate TB or 
prophylaxis therapy.  
If a TB specialist excludes an active TB infection, the subject can proceed with the IMP no 
earlier than 4 weeks after the start of an appropriate prophylactic therapy. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Confirmed active 
TB must be reported as an SAE. The Investigator is to complete and submit the TB follow-up 
form provided. 
The subject should be transferred to the care of his/her physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the ET Visit as soon as possible but no later 
than the next scheduled study visit and complete all ET Visit assessments.  
The subject should be encouraged to complete a SFU Visit (20 weeks after the final dose of 
IMP). 
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed. 
12.3.6 
Pregnancy testing 
Pregnancy testing will consist of serum testing at Screening for all women of childbearing 
potential. The pregnancy test will be urine at all other visits. 
The Screening Visit serum pregnancy test results must be negative and received and reviewed 
prior to randomization. A negative urine pregnancy test result should be obtained immediately 
prior to each administration of IMP at the visits specified in Table 5-1. Pregnancy tests should be 
administered to all female subjects of childbearing potential, regardless of their use of birth 
control. 
12.3.7 
Assessment of suicidal ideation and behavior 
Suicidal ideation and behavior will be assessed by trained study personnel using the eC-SSRS. 
This scale will be used to assess suicidal ideation and behavior that may occur during the study. 
The visits at which the eC-SSRS assessments will be performed are specified in the schedule of 
study assessments (Table 5-1). 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Posner et al, 2011; Mundt et al, 2010). 
Subjects respond to standardized clinical questions that are presented in a uniform fashion. The 
eC-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to self-injurious 
behavior with no suicidal intent. The eC-SSRS takes approximately 3 to 10 minutes to complete. 
Refer to Section 6.3 for eC-SSRS-related withdrawal criteria. 
12.3.8 
Patient Health Questionnaire-9 (PHQ-9) 
The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring, and measuring 
the severity of depression. The PHQ-9 scores for depression range from 0 to 27 with higher 


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scores indicating worse state. A score of 5 to 9 is considered to be minimal symptoms of 
depression. A score of 10 to 14 is considered minor depression, dysthymia, or mild major 
depression. A score of 15 to 19 is considered to indicate moderately severe major depression, 
and a score ≥20 is considered to be severe major depression. 
The PHQ-9 will be assessed at the visits specified in Table 5-1.  
Refer to Section 6.3 for PHQ-9-related withdrawal criteria. 
13 
STUDY MANAGEMENT AND ADMINISTRATION  
13.1 
Adherence to protocol 
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor. 
After implementation of such measure, the Investigator must notify the CPM of the Sponsor 
within 24 hours and follow any local regulatory requirements. 
13.2 
Monitoring 
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring SOPs, ICH-GCP 
guideline, and applicable regulatory requirements, and to ensure that study initiation, conduct, 
and closure are adequate. Monitoring of the study may be delegated by UCB to a CRO or a 
contract monitor. 
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s). 
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each subject). 
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). Photocopies and/or printouts of eCRFs are not considered 
acceptable source documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 


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pharmacy records, care records, ECG or other printouts, completed scales, or Quality of Life 
questionnaires, for example. Source documents should be kept in a secure, limited access area. 
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). 
Electronic Patient-Reported Outcome (ePRO) measures (eg, EQ-5D-3L, FACT-F, HAQ-DI, 
PGA-PsA and, PGA-arthritis) will be completed by each subject and will be collected 
electronically. 
The data collection and database management system will be supplied by a vendor and will be 
compliant with the relevant regulations. The data collected on the ePROs will be uploaded to a 
central server database and will be sent electronically to UCB (or a designated CRO). 
13.2.2 
Source data verification 
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 13.2.1. 
13.3 
Data handling 
13.3.1 
Case Report form completion 
This study will use electronic data capture (EDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRFs and in all required reports. 
Any change or correction to the eCRF should be dated, initialed, and explained (if necessary) 
and should not obscure the original entry.  
Corrections made after the Investigator’s review and signature of the completed eCRF will be 
resigned and dated by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. The 
Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
electronic eCRFs and in all required reports.  
Detailed instructions on the use of the EDC will be provided in the eCRF Completion 
Guidelines. 
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. 


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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. Case Report form data are entered into the clinical database using independent, 
double-data entry, with the exception of comment fields, which are verified by a second person. 
The data are entered into the eCRFs once and are subsequently verified if the study is performed 
using electronic data capture. 
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. 
13.3.3 
Subject Screening and Enrollment log/Subject Identification Code list 
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log. 
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject. 
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation. 
13.4 
Termination of the study 
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity. 
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study. 
13.5 
Archiving and data retention 
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data. 
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 


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UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
trial master file. 
13.6 
Audit and inspection 
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities. 
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and applicable regulatory 
requirements. 
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee). 
13.7 
Good Clinical Practice 
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study. 
14 
STATISTICS 
A description of statistical methods follows and will be described in more detail in the SAP. 
14.1 
Definition of analysis sets 
The following analysis sets were defined: 
• The Enrolled Set (ES) consists of all subjects who have given informed consent. 
• The Randomized Set (RS) consists of all randomized subjects.  
• The Safety Set (SS) consists of all randomized subjects who received at least 1 dose of the 
IMP. 
• The Full Analysis Set (FAS) consists of all randomized subjects who received at least 1 dose 
of IMP and have valid measurement of all the components of the primary efficacy variable at 
Baseline. 
• The Per-Protocol Set (PPS) will consist of all subjects in the RS who had no important 
protocol deviations affecting the primary efficacy variable. Important protocol deviations 
will be predefined and subjects with important protocol deviations will be evaluated during 
ongoing data cleaning meetings prior to unblinding of the data. Exclusions from the FAS will 
be considered important protocol deviations that also result in exclusion from the PPS. 


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• The Pharmacokinetic Per-Protocol Set (PK-PPS) consists of all randomized subjects who 
received at least one dose of the IMP and provided at least one quantifiable plasma 
concentration post-dose without important protocol deviations that would affect the 
concentration. Exclusions from the FAS will be considered important protocol deviations that 
also result in exclusion from the PK-PPS. 
• The Radiographic Set will consist of all subjects in the RS who received at least 1 dose of the 
IMP and have a valid radiographic image of the hands and feet at Baseline. 
• The COVID-19-free Set will consist of all subjects in the RS who had no COVID-19 impact 
up to the primary efficacy endpoint. This will be defined as subjects not having a COVID-19 
related important protocol deviation, nor having an impact based on the COVID-19 eCRF 
nor having an AE related to COVID-19 nor discontinuing due to COVID-19 up to the time of 
the primary endpoint. 
14.2 
General statistical considerations 
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, summary statistics will consist of number of available observations, arithmetic mean, 
SD, median, minimum, and maximum unless stated otherwise. 
All statistical tests will be performed 2-sided at a 5% level of significance unless stated 
otherwise. 
14.3 
Planned efficacy analyses 
14.3.1 
Analysis of the primary and secondary efficacy variables 
A fixed sequence testing procedure will be applied for the primary and selected secondary 
variables. The testing procedure will control the family-wise type-I-error and will account for 
multiplicity. The family-wise error will be set to α=0.05 (2-sided).  
For each test, on each binary efficacy endpoint, the null hypothesis is that the conditional odds 
ratio is equal to one.   
H0: ORT1T2 = 1 
The alternative hypothesis is that the conditional odds ratio is not equal to one. 
HA: ORT1T2 ≠ 1 
For each test on each continuous efficacy endpoint, the null hypothesis is that there is no 
difference between treatment groups.   
H0: T1 – T2 = 0 
The alternative hypothesis is that there is a difference between treatment groups. 
HA: T1 – T2 ≠ 0 
For the primary and secondary variables, the primary comparison is the bimekizumab 160mg sc 
Q4W vs placebo. Point estimates and 95% confidence intervals (CI) will be calculated.   
No formal statistical comparisons will be made with the adalimumab 40mg sc Q2W treatment 
group. 


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The testing starts with H1. If H1 can be rejected at α=0.05 (2-sided), the corresponding α will be 
passed on to the next test in the sequence and testing will continue. The testing will be stopped if 
a hypothesis cannot be rejected at α=0.05 (2-sided). 
The fixed sequence testing procedure of primary and secondary efficacy endpoints is shown in 
Figure 14-1. 
Figure 14-1: Sequential testing procedure of primary/secondary efficacy 
endpoints (fixed sequence testing procedure)  
 
ACR=American College of Rheumatology; BKZ=bimekizumab; CfB=change from Baseline; H=hypothesis; 
HAQ-DI=Health Assessment Questionnaire—Disability Index; hs-CRP=high sensitivity C-reactive protein; 
MDA=Minimal Disease Activity; PASI=Psoriasis Area and Severity Index; PCS=Physical Component Summary; 
Q4W=every 4 weeks; SF-36=Short-Form 36-item Health Survey; vdHmTSS=Van der Heijde modified Total 
Sharp Score; W=Week 
* It is planned to enroll a minimum of 45% of subjects who are positive for elevated hs-CRP (hs-CRP ≥6mg/L) 
and/or who have at least 1 bone erosion at Screening. 
** Based on the overall population 
14.3.1.1 
Analysis of the primary efficacy variable 
The primary efficacy variable will be analyzed for all subjects in the RS. 


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The primary endpoint is the ACR50 response at Week 16. The primary efficacy analysis will 
evaluate the composite estimand in the RS. The composite estimand combines the clinically 
meaningful improvement from Baseline in ACR50 response and not discontinuing treatment 
early. This composite estimand is similar to nonresponder imputation (NRI). 
The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for the primary efficacy analysis: 
1. Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
2. Subject-level outcome = ACR50 at Week 16. 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment prior to Week 16. A composite strategy will be implemented in which a positive 
clinical outcome is defined as achieving ACR50 at Week 16 and not discontinuing study 
treatment through Week 16.  
4. Population-level summary measure = Conditional odds ratio comparing bimekizumab to 
placebo. 
As the ACR response is based on 7 different component scores, it is necessary to consider 
various data scenarios that could impact the calculation of response. The rules described here are 
applicable in the context of the calculation of ACR response and may differ from the rules 
applied for calculating and summarizing the components individually (some values may need to 
be imputed for component analysis but are not required here to evaluate ACR response).  
The following rules will be applied prior to invoking any imputation analysis at the variable 
level: 
• If a subject has a component value that is equal to 0 at Baseline and the post-Baseline 
value is greater than or equal to 0, then the percent improvement for that component will 
be treated as 0 for purposes of ACR response calculations. 
• If a subject has component values that are missing at Baseline, then the percent 
improvement for that component will be treated as missing for purposes of ACR response 
calculations. 
Observed data will be used to calculate ACR response where possible. In case of partial missing 
data where an observed response may be calculated, imputed data will not change the result. 
Missing data at Week 16 that are not preceded by an intercurrent event, and any data after an 
intercurrent event will be imputed as non-responders. 
The statistical hypothesis for the ACR50 response at Week 16 is that the conditional odds ratio 
for ACR50 response in the bimekizumab treatment compared with placebo treatment is equal 
to 1.  
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including the 
randomization stratification variables, region and bone erosion at Baseline will be assessed and 
will be added to the model if appropriate. Comparisons will be made using the 2-sided Wald test 
at a significance level of α=0.05 (ie, H1 in Figure 14-1). The odds ratio versus placebo, p-value, 
and the 95% CI will be calculated. 


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Any use of prohibited or rescue medications through Week 16 would constitute an important 
protocol deviation which would be accounted for when the sensitivity analysis based on the PPS 
is performed (see Section 14.3.1.1.1). 
14.3.1.1.1 
Supportive analyses 
Supportive analyses for the primary efficacy variable will be conducted: 
1. The analysis will be repeated based on the PPS to evaluate the effect of important protocol 
deviations on the analysis.  
2. The analyses will be repeated for all subjects in the FAS to evaluate the consistency between 
the RS and the more restrictive FAS. This analysis will only be performed if the number of 
subjects in RS and FAS are different.  
3. The primary comparison will also be repeated for all individual components of the ACR50 
response to explore the effect of the signs and symptoms of the individual components on the 
composite endpoint. Since all ACR components are continuous variables (eg, change from 
Baseline in TJC), an analysis of covariance (ANCOVA) with treatment, region, and bone 
erosion at Baseline as fixed effects and the Baseline value as a covariate will be used for the 
analysis. Note as outlined above, some additional values may need to be imputed for 
component analysis which are not required to evaluate the overall ACR response. 
4. The analysis will be repeated using a modified composite estimand where intercurrent events 
are defined only as discontinuation due to AE or lack of efficacy. 
5. The analysis will be repeated using a treatment policy approach. 
6. The analysis will be repeated using observed cases only. 
7. The analysis will be repeated using the COVID-19-free Set. 
Additional sensitivity and supportive analyses to evaluate varying assumptions related to the 
handling of missing data will also be performed and are described in Section 14.7. 
14.3.1.2 
Analysis of the secondary efficacy variables 
The secondary efficacy variables will be analyzed for all subjects in the RS.  
All binary variables that are part of the testing hierarchy are given below: 
• PASI90 responders at Week 16 will be analyzed to evaluate the composite estimand. The 
composite estimand combines the clinically meaningful improvement from Baseline in 
PASI90 response and not discontinuing treatment early. 
• The proportion of subjects achieving MDA status at Week 16 will be analyzed to evaluate 
the composite estimand. The composite estimand combines (1) achieving the MDA status 
with (2) not discontinuing treatment early. 
• The proportion of subjects with enthesitis at Baseline achieving enthesitis-free status at 
Week 16 will be analyzed to evaluate the composite estimand. The composite estimand 
combines (1) achieving the enthesitis-free status with (2) not discontinuing treatment early. 
For this analysis, the PA0010 and PA0011 data will be pooled. 


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• The proportion of subjects with dactylitis at Baseline achieving dactylitis-free status at 
Week 16 will be analyzed to evaluate the composite estimand. The composite estimand 
combines (1) achieving the dactylitis-free status with (2) not discontinuing treatment early. 
For this analysis, the PA0010 and PA0011 data will be pooled. 
The statistical hypothesis for the binary variables at Week 16 is that the conditional odds ratio for 
binary variables in the bimekizumab treatment compared with placebo treatment groups is equal 
to 1. 
The binary variables will be analyzed using the same analysis methods and estimand approach as 
used for the primary variable (Section 14.3.1.1). 
If appropriate ie, where the outcome variable (eg, PASI90 response) is an assessment of 
skin/dermatological manifestations of PsA the fitted model will exclude the fixed term bone 
erosion at Baseline. 
All continuous variables that are part of the testing hierarchy are given below: 
• Change from Baseline in HAQ-DI at Week 16 
• Change from Baseline in the SF-36 PCS score at Week 16  
• Change from Baseline in vdHmTSS at Week 16  
Continuous variables will be analyzed to evaluate the hypothetical estimand as defined below: 
1. Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
2. Subject level outcome = variable as stated in Section 4.2.1  
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment prior to Week 16. A hypothetical strategy for addressing intercurrent events will be 
implemented. This estimand targets the treatment difference in a scenario where withdrawal 
from study treatment does not occur, such that outcomes for subjects without an intercurrent 
event are as observed, and outcomes for subjects with an intercurrent event are treated as 
though they had completed the randomized study treatment through Week 16. A multiple 
imputation strategy will be used to impute data following an intercurrent event. 
4. Population-level summary measure = the difference in the adjusted means between 
bimekizumab 160mg Q4W and placebo. 
Any missing data at Week 16 that are not preceded by an intercurrent event (ie, discontinuation 
of study medication) will also be imputed based on a predefined MI model. In MI, the missing 
value is replaced by a set of plausible values, where each value is a Bayesian draw from the 
conditional distribution of the missing data given the observed data. Intermittent missing data 
will be imputed using the MCMC method, followed by monotone regression for monotone 
missing data.  
In the case of vdHmTSS missing data, as vdHmTSS is only collected at Baseline prior to 
Week 16; missing data at Week 16 will be imputed using monotone regression. 
The statistical model for continuous endpoints for the comparison of bimekizumab and placebo 
will be an ANCOVA model with treatment, bone erosion, and region as fixed effects and the 


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Baseline value as covariate. The statistical hypothesis for the continuous variables at Week 16 is 
that the treatment difference between the bimekizumab treatment group and placebo is equal to 
0. 
All secondary efficacy variables will also be summarized based on observed case data as well as 
multiple imputation using the modified composite estimand for binary variables. 
Variables that are included in the hierarchy will additionally be rerun  using the COVID-19-free 
Set. 
14.3.2 
Analysis of the other efficacy variables 
All other efficacy variables will be analyzed for all subjects in the RS.  
Binary variables will be summarized using frequency tables by each visit. Generally, the 
estimand structure for binary other efficacy variables is as described below. Note that further 
details will be provided in the SAP. 
1. Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
2. Subject-level outcome = The given variable and time point being summarized (eg, ACR50 at 
Week 24) 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment prior to the time point being summarized. A composite strategy will be 
implemented in which a positive clinical outcome is defined as achieving the given variable 
at the specified time point and not discontinuing study treatment through that time point.  
4. Population-level summary measure = Unadjusted proportion of responders 
Any missing data that is not preceded by an intercurrent event as described above will be 
imputed based on NRI as described for the primary and secondary efficacy variables. 
Continuous variables will be summarized using descriptive statistics by each visit. Generally, the 
estimand structure for continuous other efficacy variables is as described below. Note that further 
details will be provided in the SAP. 
1. Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
2. Subject-level outcome = The given variable and time point being summarized (eg, change 
from Baseline in HAQ-DI at Week 36) 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment prior to the time point being summarized. A hypothetical strategy will be 
implemented in which outcomes for subjects without an intercurrent event are as observed at 
the given time point, and outcomes for subjects with an intercurrent event are treated as 
though they had completed the randomized study treatment through the time point being 
summarized. A multiple imputation strategy will be used to impute data following an 
intercurrent event.  
4. Population-level summary measure = Unadjusted mean 


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Any missing data that are not preceded by an intercurrent event as described above will be 
imputed based on a predefined multiple imputation model as described for continuous secondary 
efficacy variables. 
Other binary and continuous efficacy variables will also be summarized based on observed case 
data (ie, subjects with missing data or who have prematurely discontinued study treatment are 
treated as missing). Further, binary outcomes will be summarized using the modified composite 
estimand. 
Time to ACR20/50/70 response will be estimated and presented using the Kaplan-Meier 
product-limit method for each treatment. Time to a given response will be defined as the length 
in days from Baseline until the first date when the response is achieved. Subjects who 
discontinue study treatment prior to achieving a response will be censored at the date of study 
treatment discontinuation. Subjects in the placebo group who are rerandomized at Week 16 
without achieving response will be censored at the date of the Week 16 Visit. The median time to 
response, including the 2-sided 95% CI, will be calculated for each treatment. Between group 
differences will be analyzed with a log-rank statistic. 
The time to ACR20/50/70 endpoints with missing data that are not preceded by an intercurrent 
event as described above will be imputed based on a predefined multiple imputation model as 
described for the primary efficacy variable. 
The time to ACR20/50/70 endpoints will also be analyzed using observed case (OC) data. 
14.3.3 
Subgroup analyses 
Subgroup analyses will be performed on the ACR50 response and the PASI90 response at 
Week 16. The following variables for subgroup analyses will be defined:   
• Age (<45 years of age, ≥45 years of age) 
• Gender (male, female) 
• Disease duration (<1 year, ≥1 year) 
• Region (eg, Asia, Eastern Europe, North America, Western Europe) 
• Race  
• Weight at Baseline (≤100kg, >100kg) 
• Bone erosion (≥1) at Baseline (Yes, No) 
• hs-CRP at Baseline (<6mg/L, ≥6mg/L) 
• Bone erosion (≥1) and/or hs-CRP ≥6mg/L at Baseline (Yes, No) 
• Prior cDMARDs (0, 1, ≥2) 
• Concomitantly receiving cDMARDs versus no concomitant cDMARDs 
• Concomitantly receiving MTX versus no concomitant MTX 
• PSO affected BSA at Baseline (<3%, ≥3% to 10%, >10%) 
• BASDAI at Baseline (≤4, >4) 


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• Anti-bimekizumab antibody status (positive, negative) 
• HLA-B27 (positive, negative) 
14.4 
Planned safety analyses 
14.4.1 
Safety analyses 
Safety variables will be analyzed for all subjects in the SS. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA® 19.0). Adverse events with an onset date on or after the date of first IMP 
administration and up to 20 weeks after the last (most recent) dose of IMP will be defined as 
TEAEs. Treatment-emergent AEs will be summarized descriptively by treatment group, primary 
system organ class, high-level term, and preferred term. Additional tables will summarize 
TEAEs leading to withdrawal from IMP, TEAEs by intensity and relationship to IMP. 
Treatment-emergent AEs leading to withdrawal from both IMP or the study, serious TEAEs, 
TEAEs of special interest, TEAEs of special monitoring and deaths will be also be tabulated and 
listed. TEAEs adjusted for exposure will also be presented. 
When analyzing categorical data, the number and percentage of subjects in each category will be 
presented by treatment group. In addition, shift tables may be used to evaluate the number and 
percentage of subjects having a different post-Baseline status when compared to their baseline 
status. 
Laboratory value (including markedly abnormal values), urinary values, vital signs, ECGs, 
eC-SSRS, and extent of exposure will be presented descriptively by treatment group. Definitions 
for markedly abnormal laboratory values will be provided in the SAP. 
14.5 
Other planned analyses 
14.5.1 
Pharmacokinetics analyses 
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS.  
Bimekizumab plasma concentrations will be summarized for each treatment at each scheduled 
visit. 
The relationship between bimekizumab plasma concentrations and efficacy response (for 
example ACR20/50/70) and/or safety endpoints may be explored via a graphical and/or a model 
based (PK-PD) approach. The data may also be combined with that from other bimekizumab 
trials. The details of such analysis will be described separately in a data analysis plan, and the 
analysis itself will be reported separately from the CSR.  
14.5.2 
Immunological analyses 
Anti-bimekizumab antibodies will be assessed using a tiered approach: screening, confirmatory, 
and titer assays will be used. Anti-bimekizumab antibodies (including positivity) will be 
summarized by treatment at each scheduled visit at which samples are collected.  
14.6 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol, which potentially could have a 
meaningful impact on study conduct or on the primary efficacy, key safety, or PK outcomes for 


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an individual subject. The criteria for identifying important protocol deviations will be defined 
within the appropriate protocol-specific document. Important protocol deviations will be 
reviewed as part of the ongoing data cleaning process and all important deviations will be 
identified and documented prior to unblinding to confirm exclusion from analysis sets. 
14.7 
Handling of dropouts or missing data 
The primary method for assessing the efficacy variables will be the composite estimand 
approach to handling missing data that is similar to NRI. The sensitivity of results to the 
approach for handling missing data will be evaluated via supportive analyses using different 
missing data mechanisms.  
In instances where MI is used, the missing value is replaced by a set of plausible values, where 
each value is a Bayesian draw from the conditional distribution of the missing data given the 
observed data. Intermittent missing data will be imputed using the MCMC method, followed by 
regression for monotone missing data. The multiple imputation procedures planned for efficacy 
analyses are based on an assumption of data missing at random (MAR).  
Missing data will be evaluated as sensitivity analyses using different missing data mechanisms. 
The following sensitivity analyses for the primary efficacy variable will be conducted: 
1. Multiple imputation as described above will be performed using the modified composite 
estimand. The definition of an intercurrent event is changed from all treatment 
discontinuation, to discontinuation of treatment due to AE or lack of efficacy.  
2. A tipping point analysis will be performed to evaluate missingness assumptions. The tipping 
point analysis will be performed on the monotone missing data and only if the primary 
analysis is significant at α=0.05. Various delta adjustments will be made to the assumed 
responses on the monotone missing data in each treatment group independently with various 
degrees of plausibility. It will include scenarios where subjects who have missing data and 
are randomized to bimekizumab have a lower probability of response compared to subjects 
who have missing data and were randomized to placebo. For binary variables, this includes 
the worst-case scenario where subjects who have missing data and are randomized to 
bimekizumab are considered nonresponders, while subjects who have missing data and were 
randomized to placebo are considered responders. The goal of the tipping point analysis is to 
systematically vary assumptions until there is no evidence of a treatment effect (if possible). 
The plausibility of such required delta adjustment will then be assessed. Details will be 
provided in the SAP.  
3. The treatment policy strategy for addressing intercurrent events will be considered. This will 
be based on an analysis in which all available data at Week 16 regardless of the occurrence 
of intercurrent events will be considered. This analysis will use the same models specified for 
the primary and secondary analyses where subjects are analyzed according to their 
randomized treatment, even if they discontinued study treatment for any reason prior to 
Week 16 and were no longer on the randomized study treatment when the assessment was 
performed at Week 16. Even though efforts will be made to collect the primary outcome data 
for all subjects at Week 16, there may still be some subjects for whom Week 16 efficacy data 
cannot be obtained. In this case, missing data will be imputed using MI under the assumption 
of MAR. Results will be combined into a single inference using Rubin's rule. It should be 
noted that this measures something different from the primary analysis and could be 


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confounded by placebo subjects who withdraw and are subsequently on another active 
medication at the time of the Week 16 assessment. Therefore, the results of this analysis 
should be interpreted in the appropriate context. 
4. An additional sensitivity analysis will be based on observed data only for subjects who are 
still on the initially randomized treatment at Week 16. Subjects with missing data or who 
have prematurely discontinued study treatment will be treated as missing. The same 
procedure described as in the main efficacy analysis will be used. 
Additional details on these sensitivity analyses will be provided in the SAP. 
14.8 
Planned interim analyses and data monitoring 
14.8.1 
Interim analyses 
Two interim analyses will be performed: one after all randomized subjects have completed the 
Double-Blind Treatment Period and the Week 24 assessments, and one after all subjects have 
completed Week 52.  
The purpose of the Week 24 interim analysis is to perform a comprehensive evaluation of all 
available double-blind data for the 3 treatment arms and to prepare a regulatory submission for a 
marketing authorization application based on this analysis. 
For the Week 24 interim analysis, the database will be locked and the treatment codes will be 
made available to UCB personnel with exception of operational staff working on the study. An 
interim report will be written. The Investigators and subjects will remain blind to the assigned 
bimekizumab dosing regimen until the final analysis is completed. 
The Week 24 interim analysis will evaluate the primary and secondary efficacy variables, as well 
as all other efficacy, safety, and PK variables up to Week 24 according to the statistical methods 
specified in the SAP. No formal alterations to the further study conduct (eg, stopping rules, 
sample size re-estimation, or changes to eligibility criteria) are planned for this interim analysis. 
To ensure blinding of Investigators and subjects, a blinding plan will be written to evaluate the 
potential bias of the Active Treatment-Blind period, define blinded and unblinded teams, and 
describe the process of interim results generation and dissemination. The plan will be finalized 
prior to the lock of the database at the interim analysis. 
The purpose of the Week 52 interim analysis is to perform a comprehensive evaluation of all 
available data for the study and to supplement the regulatory submission based on the Week 24 
interim analysis. 
The Week 52 interim analysis will evaluate all efficacy, safety, and PK variables up to Week 52 
according to the statistical methods specified in the SAP. Only data from the SFU visits for 
subjects who discontinued and did not enter the extension study will not be included. 
Additional data cuts may be prepared following regulatory requests or for publication purposes. 
14.8.2 
Data monitoring 
A Data Monitoring Committee (DMC) will be reviewing safety data on an ongoing basis. The 
DMC membership includes experienced clinicians and a statistician, all of whom have expertise 
in clinical studies. Further details are specified in the DMC Charter.  


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Cardiovascular and Neuropsychiatric Adjudication Committees will also periodically review 
data from this study. Details are provided in the Cardiovascular Adjudication Committee and 
Neuropsychiatric Adjudication Committee charters. 
Other adjudication committees may be added as necessary.  
Both Data Monitoring and Adjudication Committee members may not participate in the study as 
principal or co-Investigators, or as study subject care physicians and must not be members of the 
study team at UCB or the conducting CRO. The duration of membership for the committees will 
be inclusive of planned analyses for PA0010. 
14.9 
Determination of sample size 
Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio to the following treatment 
groups: bimekizumab 160mg sc Q4W (420 subjects), placebo (280 subjects), 
adalimumab 40mg sc Q2W (140 subjects).  
The primary efficacy analysis is based on the bimekizumab dose versus placebo for 
ACR50 response at Week 16. It is planned that only descriptive summaries will be provided for 
the adalimumab reference arm. No statistical comparisons will be made between adalimumab 
and the other treatment groups.  
All sample size and power calculations were done at a significance level of 0.05. 
All sample size and power calculations were performed using the software nQuery Advisor® 7.0. 
14.9.1 
Power calculation for primary endpoint 
The sample size assumptions for bimekizumab versus placebo are based on the ACR50 response 
data from the Phase 2b bimekizumab study in subjects with moderate to severe PsA (PA0008). 
The median ACR50 responses of the top three dose groups (bimekizumab 160mg, 320mg, and 
320mg [initial dose] plus 160mg) at Week 12 in the TNF-naïve population are conservatively 
assumed for the Week 16 endpoint. The observed median ACR50 response rate of the top three 
bimekizumab doses in the TNF-naïve population in study PA0008 was 43.8%.  
The placebo ACR50 response at Week 16 is based on the TNFα-naïve population in PA0008 
(6.1% at Week 12, n=33); Mease et al, 2015), FUTURE 2 study in the subgroup of TNFα-naïve 
subjects (15.9%, n=63; McInnes et al, 2015), FUTURE 3 study (11.8%, n=93; Nash and Mease, 
2018), and FUTURE 5 study in a mixed TNFα exposure population (8.1% at Week 16, n=332; 
Mease et al, 2018). Therefore, the estimated ACR50 response at Week 16 in the placebo group is 
assumed to be 16%. 
The sample size for showing statistical superiority of bimekizumab vs placebo was calculated 
using a 2-sided 2-sample Chi-square test with continuity correction (Fleiss et al, 1980). 
Assuming 420 subjects in the bimekizumab group and 280 subjects in the placebo group, the test 
for detecting statistical superiority of bimekizumab 160mg Q4W vs placebo based on 
ACR50 response at Week 16 has >99% power to detect a true treatment difference of 27.8% 
(odds ratio 4.09).  
14.9.2 
Power calculations for secondary endpoints 
The assumptions for power calculations of the secondary endpoints included in the hierarchy, 
and for which supporting data exists, are based on the interim results of the Phase 2b 


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bimekizumab study PA0008 and the FUTURE 1, FUTURE 2, FUTURE 5, and SPIRIT P1 
studies. All power calculations for binary endpoints were performed using a 2-sided 2-sample 
Chi-square test with continuity correction (Fleiss et al, 1980). All power calculations for 
continuous endpoints were performed using a 2-sided 2-group Satterthwaite t-test 
(Moser et al, 1989). 
For the PASI90 response at Week 16, the bimekizumab 160mg Q4W treatment response at 
Week 12 is 45% (n=20) in the TNFα-naïve population of PA0008 at Week 12 and 46% (n=28) at 
Week 12 in the mixed TNFα exposure population. The placebo PASI90 response at Week 16 is 
based on the subgroup analyses of TNFα therapy-naïve subjects in PA0008 (9.1% at Week 12; 
n=22), FUTURE 2 study (9.7% at Week 24; n=63), and SPIRIT P1 study (1.5% at Week 12; 
n=67). Therefore, a placebo PASI90 response rate of 10% is assumed. With those assumptions, 
the study has >99% power to detect a true treatment difference at an assumed 60% of subjects 
with BSA ≥3% of the planned sample size. 
For change from Baseline in HAQ-DI at Week 16, the between treatment differences of the 
change from Baseline in HAQ-DI of in the mixed TNFα exposure population of the PA0008 at 
Week 12 were used. The bimekizumab 160mg Q4W treatment group mean change from 
Baseline in HAQ-DI at Week 12 of -0.37, SD=0.47 (n=41) versus placebo mean change from 
Baseline in HAQ-DI at Week 12 of -0.13, SD=0.50 (n=42). With those assumptions, the study 
has >99% power to detect a true treatment difference of -0.24 at the planned sample size. 
For change from Baseline in PCS of SF-36 at Week 16, the between treatment differences of the 
change from Baseline in PCS of SF-36 of the TNFα-naïve population of FUTURE 2 study 
(Kavanaugh et al, 2016) at Week 24 were used. The bimekizumab 160mg Q4W treatment group 
assumes the secukinumab 150mg treatment group mean change from Baseline in SF-36 PCS at 
Week 24 of 7.91, SD 7.38 (N=63) versus placebo mean change from Baseline in SF-36 PCS at 
Week 24 of 2.08, SD 9.51 (N=63). With those assumptions, the study has >99% power to detect 
a true treatment difference of 5.83 at the planned sample size. 
For MDA at Week 16, the bimekizumab 160mg Q4W treatment response at Week 12 in PA0008 
is 46.3% (N=41) in the mixed TNFα exposure population of PA0008. In the placebo group, 
14.3% of subjects achieved MDA at Week 12 (n=42). With those assumptions, the study has 
>99% power to detect a true treatment difference of 32% (odds ratio 5.17) at the planned sample 
size. 
For change from Baseline in vdHmTSS at Week 16, the between treatment differences of the 
change from Baseline in vdHmTSS at Week 16 of the SPIRIT P1 study in a TNFα-naive 
population (Mease et al, 2017) were used. The SPIRIT P1 study ixekizumab 80mg sc Q2W 
treatment group least square (LS) mean change from Baseline at Week 16 0.06 and SD 0.720; 
and LS mean change from Baseline 0.36 and SD 0.710 for placebo are assumed. With those 
assumptions, the study has a 95% power to detect a true treatment difference of -0.30, assuming 
45% of subjects with elevated hs-CRP and/or bone erosion, in the planned sample size. 
There is uncertainty in the final percentage of subjects with elevated hs-CRP and/or bone erosion 
at Baseline that will be recruited to the study and the variability in the subgroup. To demonstrate 
the sensitivity of the sample size calculation for this study, Table 14‒1 shows the power function 
for a fixed total sample size of 840 subjects in the RS population for this secondary efficacy 
analysis, varying the percentage of subjects with elevated hs-CRP and/or bone erosion at 


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Baseline and the treatment difference and estimated standard deviation on the change from 
Baseline in vdHmTSS at Week 16. 
Table 14‒1: Treatment effect by elevated hs-CRP and/or bone erosion at 
Baseline for secondary efficacy analyses 
Subjects with elevated hs-CRP and/or 
bone erosion at Baseline 
Treatment difference/standard deviation 
 
Treatment effect = -0.3 
SD=0.72 vs 0.71 
Treatment effect = -0.35 
SD=0.81 vs 0.93 
20% 
67 
62 
25% 
76 
72 
30% 
84 
79 
35% 
89 
85 
40% 
92 
89 
45% 
95 
92 
50% 
96 
95 
hs-CRP=high sensitivity C-reactive protein; SD=standard deviation 
 
For enthesis free-state at Week 16, enthesis resolution data from the FUTURE 5 study at 
Week 16 were used to estimate the bimekizumab 160mg Q4W treatment and placebo groups. In 
FUTURE 5 The treatment effect estimate from the secukinumab 150mg treatment group at 
Week 16 was 55% (n=141) and the placebo group estimate was 36% (n=192). Assuming a BKZ 
response of 55% and a placebo rate of 39% and having 25% of subjects with Baseline enthesis 
the pooled PA0010/PA0011 the studies have a 69% power to detect a true treatment difference 
of 16% (odds ratio 1.91). 
For dactylitis-free state at Week 16, dactylitis resolution data of the FUTURE 5 study (Mease et 
al, 2018) at Week 16 were used to estimate the bimekizumab 160mg Q4W treatment and placebo 
groups. The treatment effect estimate from the secukinumab 150mg treatment group at Week 16 
of 56% (n=103) is assumed versus a placebo group estimate of 32% (n=124). With those 
assumptions and having 11% of subjects with Baseline dactylitis, the pooled PA0010/PA0011 
studies have a 66% power to detect a true treatment difference of 24% (odds ratio 2.71). 
Treatment difference in change from Baseline in vdHmTSS at Week 16 in the overall population 
is estimated using the data from the FUTURE 5 study in a mixed TNFα exposure population. 
The bimekizumab 160mg Q4W group treatment difference compared to placebo is estimated to 
be the same as the difference in change from Baseline in vdHmTSS at Week 16 between the 
secukinumab 150mg group and placebo which is 0.42, assuming a SD of 1.13 for bimekizumab 
and SD=2.44 for placebo. With these assumptions the study has 76% power to detect a treatment 
difference of 0.42 in the planned sample size. 


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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 Informed Consent form should be signed and personally 
dated by the subject and by the person who conducted the informed consent discussion 
(Investigator or designee). The subject must receive a copy of the signed and dated Informed 
Consent form. As part of the consent process, each subject must consent to direct access to 
his/her medical records for study-related monitoring, auditing, IRB/IEC review, and regulatory 
inspection. 
If the Informed Consent form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent form by the IRB/IEC and use of the amended form. 
All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form. 
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. An eCRF 
must not be started, nor may any study specific procedure be performed for a given subject, 
without having obtained his/her written consent to participate in the study. 
15.2 
Subject identification cards 
Upon signing the Informed Consent form, 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, Informed 
Consent form, IB, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), 


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and all other subject-related documents to be used for the study to the IRB/IEC for its review and 
approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects. 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
15.4 
Subject privacy 
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study). 
15.5 
Protocol amendments 
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective. 
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented. 


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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 
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Secukinumab inhibition of Interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 
2015;373:1329-39. 
Mease P, van der Heijde D, Landewé R, Mpofu S, Rahman P, Tahir H, et al. Secukinumab 
improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary 
results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 
2018;77(6):890-7. 
Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, et al and 
SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the 
treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week 
randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the 
phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. 
Moser BK, Stevens GR, Watts CL. The Two-Sample T Test Versus Satterthwaite's Approximate 
F Test Article. Communication in Statistics-Theory and Methods 1989(11):3963-3975. 
Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG. Feasibility and 
Validation of a Computer-Automated Columbia-Suicide severity Rating Scale Using Interactive 
Voice Response Technology. J Psychiatr Res. 2010;44(16):1224-8. 
Nash P, Mease PJ, McInnes IB, Rahman P, Ritchlin CT, Blanco R, et al and FUTURE 3 study 
group. Efficacy and safety of secukinumab administration by autoinjector in patients with 
psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3). Arthritis Res 
Ther. 2018;15;20(1):47. 
Ogdie A, Weiss P. The epidemiology of psoriatic arthritis. Rheum Dis Clin North Am. 
2015;41(4):545-68. 
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, et al. Brodalumab, an 
anti–interleukin-17–receptor antibody for psoriasis. N Engl J Med. 2012;366:1181-9. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The 
Columbia-Suicide Severity Rating Scale: Initial validity and internal consistency findings from 
three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266-77. 
Raychaudhuri SP, Raychaudhuri SK, Genovese MC. IL-17 receptor and its functional 
significance in psoriatic arthritis. Mol Cell Biochem. 2012;359:419–29. 
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Salaffi F, Carotti M, Gasparini S, INtorcia M, Grassi W. The health-related quality of life in 
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sample of healthy people. Health Qual Life Outcomes. 2009;7:25. 
Van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of 
scoring methods. Ann Rheum Dis. 2005;64;ii61-ii64. 


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Van der Heijde D, Landewé RB, Mease PJ, McInnes IB, Conaghan PG, Pricop L, et al. Brief 
Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage 
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2009;129:650-6. 


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18 
APPENDICES 
18.1 
Classification Criteria for Psoriatic Arthritis  
Inflammatory articular disease (joint, spine, or entheseal) AND at least 3 points of the following 
5 categories: 
Table 18-1: CASPAR Criteria 
Category 
Definition 
Points 
1) Evidence of psoriasis:  
(Score for 1 of the following a) 
 
 
Current psoriasis 
Psoriatic skin or scalp disease present today as 
judged by a dermatologist or rheumatologist 
2 points 
Personal history of psoriasis 
A history of psoriasis that may be obtained from the 
subject, family physician, dermatologist, 
rheumatologist, or other qualified health care 
provider 
1 point 
Family history of psoriasis 
A history of psoriasis in a first- or second-degree 
relative according to subject report 
1 point 
2) Psoriatic nail dystrophy 
Typical psoriatic nail dystrophy, including 
onycholysis, pitting, and hyperkeratosis, observed on 
current physical examination 
1 point 
3) A negative test for rheumatoid 
factor 
By any method except latex, but preferably by 
enzyme-linked immunosorbent assay (ELISA) or 
nephelometry, according to the local laboratory 
reference range 
1 point 
4) Dactylitis:  
(Score for 1 of the following) 
 
 
Current dactylitis 
Swelling of an entire digit 
1 point 
History of dactylitis 
A history of dactylitis recorded by a rheumatologist 
1 point 
5) Radiologic evidence of 
juxta-articular new bone 
formation 
Ill-defined ossification near joint margins (but 
excluding osteophyte formation) on plain radiographs 
of the hand or foot 
1 point 
CASPAR=Classification Criteria for Psoriatic Arthritis  
 a “Score for 1 of the following” means that only 1 of the 3 criteria is applicable (either current psoriasis 
[scores 2 points], personal history [scores 1 point], or family history [scores 1 point]). 
 


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18.2 
Protocol Amendment 1 
Rationale for the amendment 
This protocol has been amended to update the completed and ongoing studies information, 
clarify study procedures, update the description of the IMP, and to apply a minimum percentage 
for enrollment of subjects who are positive for elevated hs-CRP and/or have at least 1 bone 
erosion at Screening. 
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 PA0010 
• “joint erosion” was changed to “bone erosion” 
• Minor spelling, editorial, and formatting changes were made throughout the document  
Specific changes: 
Change #1  
Study Contact Information 
Sponsor 
UCB Biopharma SPRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Sponsor Study Physician 
Name: 
 
Address: 
208 Bath Road 
Slough SL1 3WE 
Phone: 
 


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Clinical Project Manager 
Name: 
 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
 
Address: 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Strasse 10 
40789 Monheim am Rhein 
GERMANY 
Phone: 
 
 
Has been changed to: 
Sponsor 
UCB Biopharma SPRL SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Sponsor Study Physician 
Name: 
 
Address: 
UCB Celltech Ltd 
208 Bath Road 
Slough SL1 3WE 
UNITED KINGDOM 
Phone: 
 


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Clinical Project Manager 
Name: 
 
Address: 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
Phone: 
 
Clinical Trial Biostatistician 
Name: 
 
Address: 
UCB BIOSCIENCES GmbH 
Alfred Nobel Strasse 10 208 Bath Road 
40789 Monheim am Rhein Slough SL1 3WE 
GERMANY UNITED KINGDOM 
Phone: 
 
 
Change #2 
List of Abbreviations 
The following abbreviations were added:  
HS 
hidradenitis suppurativa 
OS 
observed case 
TNF 
tumor necrosis factor  
TNFα 
tumor necrosis factor alpha 
UC 
ulcerative colitis 
 
Change #3 
Section 1 Summary, paragraphs 7 through 10 (last paragraph) 
It is planned to enroll a minimum of 35% of subjects with elevated high sensitivity C-reactive 
protein (hs-CRP) and/or with at least one bone erosion (hs-CRP ≥6mg/L and/or 
erosion-positive). 
During the Double-Blind Treatment and Active Treatment-Blind Periods, permitted rescue 
therapy after Week 16 is described in Section 5.4. Subjects’ permitted background medications 
may be changed if the subject is not responding as per Investigator assessment. 
Subjects completing Week 52 are eligible for enrollment in an extension study where all subjects 
will receive bimekizumab. 


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Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
joint erosion [≥1]) to the following treatment groups: bimekizumab 160mg sc Q4W 
(420 subjects), placebo (280 subjects), and adalimumab sc 40mg every 2 weeks (Q2W) 
(140 subjects). The planned number of study sites is approximately 150. 
Has been changed to: 
It is planned to enroll a minimum of 3545% of subjects who are positive for with elevated high 
sensitivity C-reactive protein (hs-CRP ≥6mg/L) and/or withwho have at least one1 bone erosion 
at Screening(hs CRP ≥6mg/L and/or erosion positive). 
During the Double-Blind Treatment and Active Treatment-Blind Periods, permitted rescue 
therapy after Week 16 is described in Section 5.4. Subjects’ permitted background medications 
may be changed if the subject is not responding as per Investigator assessment. 
Subjects completing Week 52 are eligible for enrollment in an extension study where all subjects 
will receive bimekizumab. 
Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
joint bone erosion [0, ≥1]) to the following treatment groups: bimekizumab 160mg sc Q4W 
(420 subjects), placebo (280 subjects), and adalimumab sc 40mg every 2 weeks (Q2W) 
(140 subjects). The planned number of study sites is approximately 150. 
 
Change #4 
Section 2.2 Bimekizumab, paragraph 2 
While anti-IL-17A antibodies have demonstrated efficacy in subjects with PSO, PsA, and AS, 
there is currently no therapeutic approach available that fully inhibits the activity of IL-17F. 
Bimekizumab selectively and potently inhibits the activity of both IL-17A and IL-17F isoforms 
in vitro. Therefore, it permits an evaluation of the potential for additional efficacy, which may be 
conferred by dual inhibition of both cytokines in patients with diseases in which both cytokines 
are active. Furthermore, a proof-of-concept study with bimekizumab in subjects with moderate to 
severe PsA demonstrated a strong efficacy signal that warrants further exploration of 
bimekizumab in this indication. A Phase 2b, dose-ranging study (PA0008) is an ongoing study 
that was designed to investigate the efficacy and safety of various bimekizumab dose regimens in 
subjects with active PsA. The current Phase 3, randomized, double-blind, placebo-controlled, 
and active controlled confirmatory study (PA0010) is designed to investigate the efficacy and 
safety of bimekizumab in subjects with active PsA. 
Has been changed to: 
While anti-IL-17A antibodies have demonstrated efficacy in subjects with PSO, PsA, and AS, 
there is currently no therapeutic approach available that fully inhibits the activity of IL-17F. 
Bimekizumab selectively and potently inhibits the activity of both IL-17A and IL-17F isoforms 
in vitro. Therefore, it permits an evaluation of the potential for additional efficacy, which may be 
conferred by dual inhibition of both cytokines in patients with diseases in which both cytokines 
are active. Furthermore, a proof-of-concept study (PA0007) with bimekizumab in subjects with 
moderate to severe PsA demonstrated a strong efficacy signal that warrants further exploration of 
bimekizumab in this indication. A Phase 2b, dose-ranging study (PA0008) is an ongoing study 


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that was designed to investigate the efficacy and safety of various bimekizumab dose regimens in 
subjects with active PsA. The current Phase 3, randomized, double-blind, placebo-controlled, 
and active controlled confirmatory study (PA0010) is designed to investigate the efficacy and 
safety of bimekizumab in subjects with active PsA. 
 
Change #5 
Section 2.2.1 Nonclinical, paragraph 4 
Preliminary results from the embryofetal and postnatal study conducted in the Cynomolgus 
monkey indicate no effects of bimekizumab on the gestation, gestation duration, or the 
parturition of pregnant females. No bimekizumab-related effects were noted in infants at birth, 
during postnatal development, or on infant survival rate. Toxicokinetic data confirmed dose-
related exposure of maternal animals during the pregnancy and the lactation phase, and of infants 
at birth and during the postnatal phase. 
Has been changed to: 
Preliminary rResults from the embryofetal and postnatal study conducted in the Cynomolgus 
monkey indicate no effects of bimekizumab on the gestation, gestation duration, or the 
parturition of pregnant females. No bimekizumab-related effects were noted in infants at birth, 
during postnatal development, or on infant survival rate. Toxicokinetic data confirmed dose-
related exposure of maternal animals during the pregnancy and the lactation phase, and of infants 
at birth and during the postnatal phase. 
 
Change #6 
Section 2.2.2.1 Completed studies 
This section was updated to reflect the studies that have completed since the original protocol 
was written. Study descriptions for non-PsA studies were deleted and cross-reference to the 
bimekizumab IB was added for detail of these studies. PA0007 summary remains, and a 
summary of the recently completed PA0008 study was added. 
 
Change #7 
Section 2.2.2.2 Ongoing studies 
This section was updated to reflect studies that are ongoing as of 02 Dec 2019. 
 
Change #8 
Section 4.2.1 Secondary efficacy variables 
The secondary efficacy variables for this study are as follows: 
• PASI90 response at Week 4 and Week 16 in the subgroup of subjects with PSO involving at 
least 3% BSA at Baseline 


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• Change from Baseline in Health Assessment Questionnaire—Disability Index (HAQ-DI) at 
Week 16 
• Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical 
Component Summary (PCS) at Week 16 
• Minimal Disease Activity (MDA) response at Week 16 
• Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) at 
Week 16  
• Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of 
subjects with dactylitis at Baseline 
• Enthesitis-free state based on the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of 
subjects with enthesitis at Baseline 
• ACR20 response at Week 16 
• ACR70 response at Week 16 
• Proportion of subjects with an Investigator Global Assessment (IGA) score of 0 (clear) or 
1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 4 and Week 16 in 
the subset of subjects with psoriatic skin lesions at Baseline  
• Change from Baseline in the Patient’s Assessment of Arthritis Pain (PtAAP) at Week 16 
• Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada 
(SPARCC) index at Week 16 in the subgroup of subjects with enthesitis at Baseline 
• Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) at Week 16 
Has been changed to: 
The secondary efficacy variables for this study are as follows: 
• Change from Baseline in Health Assessment Questionnaire—Disability Index (HAQ-DI) at 
Week 16 
• PASI90 response at Week 4 and Week 16 in the subgroup of subjects with PSO involving at 
least 3% BSA at Baseline 
• Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical 
Component Summary (PCS) at Week 16 
• Minimal Disease Activity (MDA) response at Week 16 
• Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in 
subjects with elevated hs-CRP and/or at least 1 bone erosion at Baseline at Week 16  
• Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of 
subjects with dactylitis at Baseline 
• Change from Baseline in Enthesitis free state based on the Leeds Enthesitis Index (LEI) at 
Week 16 in the subgroup of subjects with enthesitis at Baseline 
• Change from Baseline in vdHmTSS in the overall population at Week 16 


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• ACR20 response at Week 16 
• ACR70 response at Week 16 
• Proportion of subjects with an Investigator Global Assessment (IGA) score of 0 (clear) or 
1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 4 and Week 16 in 
the subset of subjects with psoriatic skin lesions at Baseline  
• Change from Baseline in the Patient’s Assessment of Arthritis Pain (PtAAP) at Week 16 
• Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada 
(SPARCC) index at Week 16 in the subgroup of subjects with enthesitis at Baseline 
• Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) at Week 16 
 
Change #9 
Section 4.2.2 Secondary safety variables 
Secondary safety variables to be assessed are as follows: 
• Incidence of treatment-emergent adverse events (TEAEs) 
• Incidence of SAEs 
• Adverse events (AEs) leading to withdrawal from IMP  
Has been changed to:  
Secondary safety variables to be assessed are as follows: 
• Incidence of treatment emergent adverse events (TEAEs) 
• Incidence of treatment-emergent SAEs 
• Adverse events (AEs) TEAEs leading to withdrawal from IMP  
 
Change #10 
Section 4.3.1 Other efficacy variables, the following variables had changes and/or clarifications 
• The percentage of ACR50 responders at Week 16 and maintaining response at Week 52 
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores)  
• Percentage of subjects with no radiographic joint damage progression (Change from Baseline 
vdHmTSS of ≤0.5)  
• Change from Baseline in PsAID-12 
• Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) 
• Change from Baseline in the EQ-5D-3L utility score 


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Has been changed to: 
• The percentageproportion of ACR50 responders at Week 16 and maintaining response at 
Week 52 
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores) in subjects with elevated hs-CRP and/or with at least 1 bone erosion at 
Baseline 
• PercentageProportion of subjects with no radiographic joint damage progression (change 
from Baseline vdHmTSS of ≤0.5)  
• Change from Baseline in PsAID-12, in the individual domains of PsAID-12 
• Change from Baseline in the Patient Health Questionnaire 9 (PHQ 9) 
• Change from Baseline in the EQ 5D 3L utility score 
 
Change #11 
Section 4.3.1 Other efficacy variables, the following new variables were added:  
• Change from Baseline in vdHmTSS total score and in erosion and joint space 
narrowing (subscores) in the overall population 
• Subjects achieving PsAID-Score ≤4 
• Change from Baseline in Physician’s Global Assessment of Arthritis (PhGA-Arthritis) 
• Change from Baseline in Patient’s Global Assessment of Arthritis (PGA-Arthritis) 
 
Change #12 
Section 4.3.2 Other safety variables, PHQ-9 variable added (was removed from Section 4.3.1 
Other efficacy variables)  
• Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) 
 
Change #13 
Section 5.1 Study description, paragraphs 1 through 5 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, active-reference 
study to evaluate the efficacy and safety of bimekizumab in subjects with active PsA. To be 
eligible to participate in this study, subjects must be adults with a diagnosis of active PsA based 
on the CASPAR criteria and have active disease with TJC ≥3 and SJC ≥3. It is planned to enroll 
a minimum of 35% of subjects with elevated hs-CRP and/or with at least one bone erosion 
(hs-CRP ≥6mg/L and/or erosion-positive). 
Subjects should not have previously been treated with any biologic drugs for PsA or PSO. 
Detailed inclusion and exclusion criteria are presented in Section 6.1 and Section 6.2, 
respectively. 


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The study will include 3 periods: a Screening Period (≥14 days to ≤35 days), a Treatment Period 
(52 weeks), and a Safety Follow-up Period (20 weeks after the final dose of IMP). The 
Treatment Period will consist of a 16-week Double-Blind Treatment Period followed by a 
36-week Active Treatment-Blind Period. Permitted rescue therapy changes after Week 16 are 
described in Section 5.4. The maximum study duration per subject will be up to 73 weeks. 
Eligible subjects will be randomized 3:2:1 (stratified by region and joint erosion [≥1]) to receive 
1 of 3 blinded treatments (bimekizumab 160mg sc Q4W, placebo, or active-reference 
[adalimumab 40mg sc Q2W]), and will remain on their allowable background medication. 
Details of the Treatment Period are provided in Section 5.3. 
Subjects completing Week 52 are eligible for enrollment in an extension study to continue to 
receive bimekizumab.  
Has been changed to: 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, active-reference 
study to evaluate the efficacy and safety of bimekizumab in subjects with active PsA. To be 
eligible to participate in this study, subjects must be adults with a diagnosis of active PsA based 
on the CASPAR criteria and have active disease with TJC ≥3 and SJC ≥3. It is planned to enroll 
a minimum of 3545% of subjects withwho are positive for elevated hs-CRP (hs-CRP ≥6mg/L) 
and/or withwho have at least one1 bone erosion at Screening (hs CRP ≥6mg/L and/or erosion
positive). 
Subjects should not have previously been treated with any biologic drugs for PsA or PSO. 
Detailed inclusion and exclusion criteria are presented in Section 6.1 and Section 6.2, 
respectively. 
The study will include 3 periods: a Screening Period (≥14 days to ≤35 days), a Treatment Period 
(52 weeks), and a Safety Follow-up Period (20 weeks after the final dose of IMP). The 
Treatment Period will consist of a 16-week Double-Blind Treatment Period followed by a 
36-week Active Treatment-Blind Period. Permitted rescue therapy changes after Week 16 are 
described in Section 5.4. The maximum study duration per subject will be up to 73 weeks. 
Eligible subjects will be randomized 3:2:1 (stratified by region and jointbone erosion [0, ≥1]) to 
receive 1 of 3 blinded treatments (bimekizumab 160mg sc Q4W, placebo, or active-reference 
[adalimumab 40mg sc Q2W]), and will remain on their allowable background medication. 
Details of the Treatment Period are provided in Section 5.3. 
Subjects completing Week 52 and meeting eligibility criteria are eligible for enrollment in an 
extension study to continue to receive bimekizumab.  
 
Change #14 
New Section 5.2.1 Within-study rescreening/retesting requirements 
Rules for rescreening or repetition of screening tests within the study are listed below: 
• Subjects who fail to meet the eligibility criteria for PHQ-9, electronic Columbia-Suicide 
Severity Rating Scale (eC-SSRS), or the tuberculosis (TB) questionnaire are not allowed 
to be rescreened. 


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The Medical Monitor must be contacted for confirmation of rescreening/retesting in all 
other cases. 
• Subjects who initially fail to meet selected eligibility criteria (eg, documented 
completion of latent tuberculosis infection [LTBI] prophylactic therapy) may be 
rescreened. 
• Subjects for whom eligibility assessments could not be completed as planned (eg, for 
technical reasons) within the defined Screening Period of 35 days may be rescreened.  
• Subjects with individual laboratory screening tests for which the results are 
exclusionary, can be retested.  
Of note, repetition of laboratory screening tests within the Screening Period is permitted 
for technical reasons (eg, frozen sample, expired laboratory kit) without contacting the 
Medical Monitor. 
 
Change #15 
Section 5.3.1 Double-Blind Treatment Period, paragraph 1 
During the Double-Blind Treatment Period, subjects will be randomized 3:2:1 (stratified by 
region and joint erosion [≥1]) to 1 of 3 blinded treatments. 
Has been changed to: 
During the Double-Blind Treatment Period, subjects will be randomized 3:2:1 (stratified by 
region and jointbone erosion [0, ≥1]) to 1 of 3 blinded treatments. 
 
Change #16 
Section 5.7 Planned number of subjects and sites 
Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
joint erosion) to the following treatment groups: bimekizumab 160mg sc Q4W (420 subjects), 
placebo (280 subjects), and adalimumab 40mg sc Q2W (140 subjects). The planned number of 
study sites is approximately 150. 
Has been changed to:  
Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio (stratified by region and 
jointbone erosion [0, ≥1]) to the following treatment groups: bimekizumab 160mg sc Q4W (420 
subjects), placebo (280 subjects), and adalimumab 40mg sc Q2W (140 subjects). The planned 
number of study sites is approximately 150. 
 
Change #17 
Section 5.7.1 Enrollment of hs-CRP/bone erosion positive subjects 
It is planned to enroll a minimum of 35% of subjects with elevated hs-CRP and/or with at least 
one bone erosion (hs-CRP ≥6mg/L and/or erosion-positive). 


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Has been changed to: 
It is planned to enroll a minimum of 3545% of subjects withwho are positive for elevated hs-
CRP (hs-CRP ≥6mg/L) and/or withwho have at least one1 bone erosion at Screening (hs CRP 
≥6mg/L and/or erosion positive). 
 
Change #18 
Table 5-1: Schedule of study assessments footnote a 
a Visit windows of ±2 days are allowed for all visits up to Week 16 and ±3 days are allowed for all visits after Week 
16. The time between study treatment doses should be ≥12 days and ≤16 days or ≥11 days and ≤17 days, 
respectively. The Safety Follow-Up Visit window is scheduled -3 and +7 days from the final dose. 
Has been changed to: 
a Visit windows of ±2 days are allowed for all visits up to Week 16 and ±3 days are allowed for all visits after Week 
16. The time between study treatment doses should be ≥12 days and ≤16 days or ≥11 days and ≤17 days, 
respectively. The Safety Follow UpFor the SFU Visit window is, the visit should occur no more than 3 days 
prior to the scheduled 3visit date and +within 7 days from the final dose.after the scheduled visit date (-3 
days/+7 days). 
 
Change #19 
Table 5-1: Schedule of study assessments footnote o 
o Circumference measured in millimeters. 
Has been changed to: 
o Circumference measured in millimeters. The LDI assessment of dactylitis will be obtained for all subjects at 
the Baseline visit. Subsequent to the Baseline visit, the LDI assessment will be obtained only for those 
subjects who had dactylitis at Baseline (as per the LDI assessment performed at Baseline). 
 
Change #20 
Section 6.1 Inclusion criteria, #1 and #2 
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or legal representative.  
2. Subject/legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete diaries), visit schedule, or medication intake according 
to the judgment of the Investigator. 


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Has been changed to: 
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or legal representative.  
2a. Subject/legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete diaries), visit schedule, or medication intake according 
to the judgment of the Investigator. 
 
Change #21 
Section 6.3.1 Potential drug-induced liver injury IMP discontinuation criteria, paragraph 2 
The PDILI criteria below require immediate and permanent discontinuation of IMP:   
• Subjects with either of the following: 
− ALT or AST ≥8xULN 
− ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN  
The PDILI criterion below requires immediate discontinuation of IMP for: 
• Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%). 
Has been changed to: 
The PDILI criteria below require immediate and permanent discontinuation of IMP:   
• Subjects with either of the following: 
− ALT or AST ≥8xULN 
− ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN  
The PDILI criterion below requires immediate discontinuation of IMP for: 
− Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without 
clear alternative cause), rash, or eosinophilia (ie, >5%). 
 
Change #22 
Section 7.1 Description of investigational medicinal products, first bullet 
• 
 
 
 


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Has been changed to: 
• 
 
 
 
. 
 
Change #23 
Table 7-2: Prohibited or restricted medications and required wash-out periods, third row 
Oral corticosteroids 
Any dose 
regimen 
Any change in dose/dose regimen in the 28 days 
prior to the Baseline Visit. 
Has been changed to: 
Oral corticosteroids 
Any dose 
regimen 
Any change in dose/dose regimen in the 2814 days 
prior to the Baseline Visit. 
 
Change #24 
Table 7-2: Prohibited or restricted medications and required wash-out periods, 10th row 
-methotrexate a 
Any dose 
regimen 
Initiation within 12 weeks prior to the Baseline 
Visit unless Inclusion Criterion #11 is met.  
Administration of LEF and MTX together is not 
permitted at any time during the study. 
Has been changed to: 
-methotrexate a 
Any dose 
regimen 
Initiation withinless than 12 weeks prior to the 
Baseline Visit unless Inclusion Criterion #11 is 
met.  
Administration of LEF and MTX together is not 
permitted at any time during the study. 
 
Change #25 
Section 8 Study Procedures By Visit, paragraph 1 
The schedule of study assessments (Table 5-1) provides an overview of study assessments. A list 
of procedures to be completed at each visit is described below. Visit windows of ±2 days are 
allowed from the first dose at all visits through to Week 16. During the 16-week Double-Blind 
Period, the time between doses should be ≥12 days and ≤16 days. Visit windows of ±3 days are 
allowed for all visits after Week 16. The time between doses during the Active Treatment-Blind 
Period should be ≥11 days and ≤17 days. For the SFU Visit (20 weeks after the final dose), the 
visit should occur no more than 3 days prior to the scheduled visit date and within 7 days after 
the scheduled visit date (-3 days/+7 days). 


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Has been changed to: 
The schedule of study assessments (Table 5-1) provides an overview of study assessments. A list 
of procedures to be completed at each visit is described below. Visit windows of ±2 days are 
allowed from the first dose at all visits through to Week 16. During the 16-week Double-Blind 
Period, the time between doses should be ≥12 days and ≤16 days. Visit windows of ±3 days are 
allowed for all visits after Week 16. The time between doses during the Active Treatment-Blind 
Period should be ≥11 days and ≤17 days. For the SFU Visit (20 weeks after the final dose of 
IMP), the visit should occur no more than 3 days prior to the scheduled visit date and within 
7 days after the scheduled visit date (-3 days/+7 days). 
 
Change #26 
Section 9.8.1 Body surface area-psoriasis (BSA-PSO), paragraph 2 
The BSA palm method will be used for the evaluation of BSA affected by PSO as follows: 
• Subject’s palm=1% 
• Head and neck=10% (10 palms) 
• Upper extremities=20% (20 palms) 
• Trunk=30% (30 palms) 
• Lower extremities=40% (40 palms)  
• Total BSA=100% 
Has been changed to: 
The BSA palm method will be used for the evaluation of BSA affected by PSO as follows: 
• Subject’s palm=1% 
• Head and neck=10% (10 palms) 
• Upper extremities=20% (20 palms) 
• Trunk=30% (30 palms) 
• Lower extremities=40% (40 palms)  
• Total BSA=100% 
 
Change #27 
Section 9.8.3 Investigator’s Global Assessment (IGA) – new paragraphs added after Table 9-3 
The IGA response is defined as a clear [0] or almost clear [1] assessment with at least a 
2-category improvement from Baseline, meaning that this parameter will be evaluable only 
for subjects with psoriatic skin lesions (IGA score ≥2) at Baseline.    
In this study, only subjects with BSA ≥ 3% at Baseline will have IGA assessed at 
post-Baseline Visits. 


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Change #28 
Section 9.10 Disease Activity Index for Psoriatic Arthritis (DAPSA), formula 
SJC (range 0-66) + TJC (range 0-68) + PGA-Arthritis and patient’s pain assessment (VAS 
range 0-10; 0=best, 10=worst) + hs-CRP. 
Has been changed to: 
DAPSA=SJC (range 0-66) + TJC (range 0-68) + PGA-Arthritis and patient’s pain assessment 
(VAS range 0-10cm; 0=best, 10=worst) + PtAAP (VAS range 0-10cm) + hs-CRP. 
 
Change #29 
Section 12.1.4 Pregnancy, paragraph 1 
If the Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by entering all pregnancy 
information into the eCRF. An automatic notification will be sent to UCB PS. The subject should 
be withdrawn from the study as soon as pregnancy is known (by positive pregnancy test), and the 
following should be completed: 
• The subject should return for the ET Visit. 
• The subject should immediately stop the intake of the IMP. 
• A Safety Follow-Up Visit should be scheduled 20 weeks after the final dose of IMP. 
Has been changed to: 
If the Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately (within 24 hours) notify UCB’s PS department by entering 
all pregnancy information into the eCRF. An automatic notification will be sent to UCB PS. The 
subject should be permanently withdrawn from the studyIMP as soon as pregnancy is known 
(by positive pregnancy test), and the following should be completed: 
• The subject should immediately stop the intake of the IMP. 
• The subject should return for the ET Visitan early ad-hoc study visit. 
• A Safety Follow-Up Visit should be scheduled 20 weeks after the final dose of IMP. 
The Investigator should discuss with the subject the possibility to continue the study by 
attending the scheduled visits for assessments without IMP administration. The tests or 
assessments, which are considered contraindicated during the pregnancy should not be 
performed. The early ad-hoc study visit will be considered as the ET Visit if the subject 
does not wish to pursue the study investigations. 
 


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Change #30 
Section 12.1.4 Pregnancy, last paragraph of section was deleted 
Should a subject become pregnant while participating in the study, the subject may be offered the 
option to enroll in a separate observational pregnancy follow up study sponsored by UCB and 
conducted independently from study PA0010. If the study is available locally, the PA0010 
Investigator will be provided with locally approved information about the observational 
pregnancy follow up study to inform the subject at the time the pregnancy is reported. 
Participation in this separate study will be voluntary and will not impact the therapeutic 
management of the subject nor interfere with termination and follow up procedures as described 
in protocol PA0010. 
 
Change #31 
Table 12-2: Laboratory measurements, footnote c 
c Urine drug screen will be performed at Screening Visit and ET Visit 
Has been changed to: 
c Urine drug screen will be performed at Screening Visit and ET Visit. 
 


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Change #32 
Table 12-3: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥3xULN 
≥2xULNb NA 
Hepatology consultc 
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor 
ASAP. 
Immediate, 
permanent IMP 
discontinuation. 
 
 
 
Essential: Must have 
repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 12.2.1.3); 
recommended to 
occur at the site with 
HCP. 
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within baseline values.d 
≥3xULN 
NA 
Yes 
≥8xULN 
NA 
NA 
Need for hepatology 
consult to be discussed 
(required if ALT or 
AST ≥8xULN). 
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor 
ASAP. 
Immediate, 
permanent IMP 
discontinuation. 
 
 
 


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Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥5xULN 
(and ≥2x 
baseline) 
and 
<8xULN  
<2xULN 
No 
Discussion with 
Medical Monitor 
required. 
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow 
up requirements).c 
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 12.2.1.2). 
 
IMP discontinuation 
required if any of the 
following occur: 
• Subject cannot 
comply with 
monitoring 
schedule. 
• Liver chemistry 
values continue to 
increase. 
• Liver chemistry 
values remain 
≥5xULN (and 
≥2x baseline) after 
4 weeks of 
monitoring without 
evidence of 
resolution. 
Essential: Every 
attempt must be 
made to have repeat 
liver chemistry 
values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.2.1.3). 
Monitoring of liver 
chemistry values at least 
twice per week for 2 
weeks.d 
• 
Immediate IMP 
discontinuation 
required if liver 
chemistry values 
continue to increase. 
After 2 weeks of 
monitoring liver 
chemistry values: 
• 
ALT or AST remains 
≥5xULN <8xULN, 
IMP should be 
temporarily withheld 
and subject should 
undergo repeat test in 
2 weeks. 
• 
Continue IMP if ALT 
or AST values 
<5xULN; continue to 
monitor at least twice 
per week until values 
normalize, stabilize, 
or return to within 
baseline values. 
• 
If ALT or AST 
remains ≥5xULN 
after second re-test, 
immediate, 


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Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
permanent IMP 
discontinuation 
required. 
Continue to monitor until 
values normalize, 
stabilize, or return to 
within baseline values.d 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause). 
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor. 
c Details provided in Section 12.2.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist. 
d Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
Has been changed to: 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥3xULN 
≥2xULNb NA 
Hepatology consultc 
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor 
ASAP. 
Immediate, 
permanent IMP 
discontinuation.d 
 
 
 
Essential: Must have 
repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 12.2.1.3); 
recommended to 
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within baseline values.de 
≥3xULN 
NA 
Yes 


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Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥8xULN 
NA 
NA 
Need for hepatology 
consult to be discussed 
(required if ALT or 
AST ≥8xULN). 
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor 
ASAP. 
Immediate, 
permanent IMP 
discontinuation. 
 
 
 
occur at the site with 
HCP. 


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Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥5xULN 
(and ≥2x 
baseline) 
and 
<8xULN  
<2xULN 
No 
Discussion with 
Medical Monitor 
required. 
Consider need for 
hepatology consult if 
there is no evidence of 
resolution (see Follow 
up requirements).c 
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 12.2.1.2). 
 
IMP discontinuation 
required if any of the 
following occur: 
• Subject cannot 
comply with 
monitoring 
schedule. 
• Liver chemistry 
values continue to 
increase. 
• Liver chemistry 
values remain 
≥5xULN (and 
≥2x baseline) after 
4 weeks of 
monitoring without 
evidence of 
resolution. 
Essential: Every 
attempt must be 
made to have repeat 
liver chemistry 
values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.2.1.3). 
Monitoring of liver 
chemistry values at least 
twice per week for 2 
weeks.de 
• 
Immediate IMP 
discontinuation 
required if liver 
chemistry values 
continue to increase. 
After 2 weeks of 
monitoring liver 
chemistry values: 
• 
ALT or AST remains 
≥5xULN <8xULN, 
IMP should be 
temporarily withheld 
and subject should 
undergo repeat test in 
2 weeks. 
• 
Continue IMP if ALT 
or AST values 
<5xULN; continue to 
monitor at least twice 
per week until values 
normalize, stabilize, 
or return to within 
baseline values. 
• 
If ALT or AST 
remains ≥5xULN 
after second re-test, 
immediate, 


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Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis of 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
permanent IMP 
discontinuation 
required. 
Continue to monitor until 
values normalize, 
stabilize, or return to 
within baseline values.de 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause). 
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor. 
c Details provided in Section 12.2.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist. 
d Details are provided in Section 12.2.1.2.1. 
e Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
 


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Change #33 
Section 12.2.1.2 Immediate action: determination of IMP discontinuation, paragraph 2 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 12-3 for details). 
Has been changed to: 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 12-3 for details). 
 
Change #34 
Section 12.2.1.2.1 IMP restart/rechallenge, paragraph 1 
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 12-3), but for whom an alternative diagnosis is 
confirmed, ie, drug-induced liver injury is excluded, can rarely restart IMP. Rechallenge with 
IMP can occur only if ALL of the following requirements are met: 
Has been changed to: 
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 12-3), but for whom an alternative diagnosis is 
confirmed, ie, drug-induced liver injury is excluded, can rarely restart IMP. Rechallenge with 
IMP can occur only if ALL of the following requirements are met at the time of the 
rechallenge: 
 


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Change #35 
Figure 14-1: Sequential testing procedure of primary/secondary efficacy endpoints (fixed 
sequence testing procedure)  
 
ACR=American College of Rheumatology; BKZ=bimekizumab; CfB=change from Baseline; H=hypothesis; 
HAQ-DI=Health Assessment Questionnaire—Disability Index; hs-CRP=high sensitivity C-reactive protein; 
LEI=Leeds Enthesitis Index; MDA=Minimal Disease Activity; PASI=Psoriasis Area and Severity Index; 
PCS=Physical Component Summary; Q4W=every 4 weeks; SF-36=Short-Form 36-item Health Survey; 
vdHmTSS=Van der Heijde modified Total Sharp Score; W=Week 
* It is planned to enroll a minimum of 35% of subjects with elevated hs-CRP and/or with at least one bone erosion 
(hs-CRP ≥6mg/L and/or erosion-positive).  
** Based on the overall population 


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Has been changed to: 
(in the revised figure [below], the “CfB HAQ-DI at W16 superior to placebo” has moved to the 
H2 position from the H3 position and the “PASI90 response at W16 superior to placebo” has 
moved to the H3 position from the H2 position.) 
 
ACR=American College of Rheumatology; BKZ=bimekizumab; CfB=change from Baseline; H=hypothesis; 
HAQ-DI=Health Assessment Questionnaire—Disability Index; hs-CRP=high sensitivity C-reactive protein; 
LEI=Leeds Enthesitis Index; MDA=Minimal Disease Activity; PASI=Psoriasis Area and Severity Index; 
PCS=Physical Component Summary; Q4W=every 4 weeks; SF-36=Short-Form 36-item Health Survey; 
vdHmTSS=Van der Heijde modified Total Sharp Score; W=Week 
* It is planned to enroll a minimum of 3545% of subjects withwho are positive for elevated hs-CRP (hs-CRP 
≥6mg/L) and/or withwho have at least one1 bone erosion at Screening(hs CRP ≥6mg/L and/or erosion positive).  
** Based on the overall population 
 
Change #36 
Section 14.3.1.1 Analysis of the primary efficacy variable   
The primary efficacy variable will be analyzed for all subjects in the RS. 
The primary endpoint is the ACR50 response at Week 16. The primary efficacy analysis will 
evaluate the composite estimand in the RS. The composite estimand combines the clinically 
meaningful improvement from Baseline in ACR50 response and not discontinuing treatment 
early due to an AE or lack of efficacy.  
The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for the primary efficacy analysis: 


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1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria. 
2. Subject-level outcome = ACR50 at Week 16. 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to Week 16. A composite strategy will be 
implemented in which a positive clinical outcome is defined as achieving ACR50 at Week 16 
and not discontinuing study treatment due to an AE or lack of efficacy through Week 16.  
4. Population-level summary measure = Conditional odds ratio comparing bimekizumab to 
placebo. 
Any missing data at Week 16 that is not preceded by an intercurrent event (ie, discontinuation of 
study medication due to an AE or lack of efficacy) will be imputed based on a predefined 
multiple imputation model (MI). In MI, the missing value is replaced by a set of plausible values, 
where each value is a Bayesian draw from the conditional distribution of the missing data given 
the observed data. Intermittent missing data will be imputed using the Markov-Chain Monte 
Carlo (MCMC) method followed by logistic regression for monotone missing data. 
Any use of prohibited or rescue medications through Week 16 would constitute an important 
protocol deviation which would be accounted for when the sensitivity analysis based on the PPS 
is performed (see Section 14.3.1.1.1). 
The statistical hypothesis for the ACR50 response at Week 16 is that the conditional odds ratio 
for ACR50 response in the bimekizumab treatment compared with placebo treatment is equal 
to 1.  
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including the 
randomization stratification variables, region and joint erosion at Baseline will be assessed, and 
will be added to the model if appropriate. Comparisons will be made using the 2-sided Wald test 
at a significance level of α=0.05 (ie, H1 in Figure 14-1). The odds ratio versus placebo, p-value, 
and the 95% CI will be calculated. 
Has been changed to: 
The primary efficacy variable will be analyzed for all subjects in the RS. 
The primary endpoint is the ACR50 response at Week 16. The primary efficacy analysis will 
evaluate the composite estimand in the RS. The composite estimand combines the clinically 
meaningful improvement from Baseline in ACR50 response and not discontinuing treatment 
early due to an AE or lack of efficacy.  
The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for the primary efficacy analysis: 
1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria. 
2. Subject-level outcome = ACR50 at Week 16. 


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3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to Week 16. A composite strategy will be 
implemented in which a positive clinical outcome is defined as achieving ACR50 at Week 16 
and not discontinuing study treatment due to an AE or lack of efficacy through Week 16.  
4. Population-level summary measure = Conditional odds ratio comparing bimekizumab to 
placebo. 
Any missing data at Week 16 that is not preceded by an intercurrent event (ie, discontinuation of 
study medication due to an AE or lack of efficacy) will be imputed based on a predefined 
multiple imputation model (MI).  
As the ACR response is based on 7 different component scores, it is necessary to consider 
various data scenarios that could impact the calculation of response. The rules described 
here are applicable in the context of the calculation of ACR response and may differ from 
the rules applied for calculating and summarizing the components individually (some 
values may need to be imputed for component analysis but are not required here to 
evaluate ACR response).  
The following rules will be applied prior to invoking any imputation analysis at the 
variable level: 
• If a subject has a component value that is equal to 0 at Baseline and the post-
Baseline value is greater than or equal to 0, then the absolute and percent 
improvement for that component will be treated as 0 for purposes of ACR response 
calculations. 
• If a subject has a single component value that is missing at Baseline, then the 
absolute and percent improvement for that component will be treated as 0 across all 
visits for purposes of ACR response calculations. 
After these rules have been implemented, the following rules will be applied to complete the 
derivation of ACR response based on the composite estimand definition: 
• If a given visit has been preceded by an intercurrent event: 
o The endpoint at all subsequent visits (whether the data were observed or not) 
will be set to “non-response” as the subject has not met the criteria for response. 
• If a given visit has not been preceded by an intercurrent event: 
o If both the TJC and SJC are available and at least 3 of the other 5 components 
have observed data collected, the ACR response will be calculated based on 
observed data.  
o If either the TJC and SJC are missing or there are fewer than 3 of the other 
5 components with observed data at Week 16, then imputation methods will be 
applied, consistent with the predefined approach for handling intercurrent 
events. Multiple imputation will be applied, where each of the components will 
be imputed separately before deriving the response based on imputed 
components. Note: In the case where there is partial missing data at a visit 
(missing data for some components), the available observed values and the 
imputed values will be used to derive the response. 


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In MI, the missing value is replaced by a set of plausible values, where each value is a Bayesian 
draw from the conditional distribution of the missing data given the observed data. Intermittent 
missing data will be imputed using the Markov-Chain Monte Carlo (MCMC) method followed 
by logistic regression for monotone missing data. 
Any use of prohibited or rescue medications through Week 16 would constitute an important 
protocol deviation which would be accounted for when the sensitivity analysis based on the PPS 
is performed (see Section 14.3.1.1.1). 
The statistical hypothesis for the ACR50 response at Week 16 is that the conditional odds ratio 
for ACR50 response in the bimekizumab treatment compared with placebo treatment is equal 
to 1.  
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including the 
randomization stratification variables, region and jointbone erosion at Baseline will be assessed, 
and will be added to the model if appropriate. Comparisons will be made using the 2-sided Wald 
test at a significance level of α=0.05 (ie, H1 in Figure 14-1). The odds ratio versus placebo, 
p-value, and the 95% CI will be calculated. 
Any use of prohibited or rescue medications through Week 16 would constitute an 
important protocol deviation which would be accounted for when the sensitivity analysis 
based on the PPS is performed (see Section 14.3.1.1.1). 
 
Change #37 
Section 14.3.1.1.1 Sensitivity analyses, #3   
3. The primary comparison will also be repeated for all individual components of the ACR50 
response to explore the effect of the signs and symptoms of the individual components on the 
composite endpoint. Since all ACR components are continuous variables (eg, change from 
Baseline in TJC), an analysis of covariance (ANCOVA) with treatment, region, and joint 
erosion at Baseline as fixed effects and the Baseline values as covariate will be used for the 
analysis.  
Has been changed to:  
3. The primary comparison will also be repeated for all individual components of the ACR50 
response to explore the effect of the signs and symptoms of the individual components on the 
composite endpoint. Since all ACR components are continuous variables (eg, change from 
Baseline in TJC), an analysis of covariance (ANCOVA) with treatment, region, and 
jointbone erosion at Baseline as fixed effects and the Baseline valuesvalue as a covariate 
will be used for the analysis. Note as outlined above, some additional values may need to 
be imputed for component analysis which are not required to evaluate the overall ACR 
response. 
 


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Change #38 
Section 14.3.1.2 Analysis of the secondary efficacy variables 
The secondary efficacy variables will be analyzed for all subjects in the RS.  
All binary variables that are part of the testing hierarchy are given below: 
PASI90 responders at Week 16 will be analyzed to evaluate the composite estimand. The 
composite estimand combines the clinically meaningful improvement from Baseline in 
PASI90 response and not discontinuing treatment early due to an AE or lack of efficacy. 
The proportion of subjects achieving MDA status at Week 16 will be analyzed to evaluate the 
composite estimand. The composite estimand combines (1) achieving the MDA status with 
(2) not discontinuing treatment early due to an AE or lack of efficacy. 
The proportion of subjects with dactylitis at Baseline achieving dactylitis-free status at Week 16 
will be analyzed to evaluate the composite estimand. The composite estimand combines 
(1) achieving the dactylitis-free status with (2) not discontinuing treatment early due to an AE or 
lack of efficacy. 
The statistical hypothesis for the binary variables at Week 16 is that the conditional odds ratio for 
binary variables in the bimekizumab treatment compared with placebo treatment groups is equal 
to 1. 
The binary variables will be analyzed using the same analysis methods and estimand approach as 
used for the primary variable (Section 14.3.1.1). 
If appropriate ie, where the outcome variable (eg, PASI90 response) is an assessment of 
skin/dermatological manifestations of PsA the fitted model will exclude the fixed term joint 
erosion at Baseline. 
All continuous variables that are part of the testing hierarchy are given below: 
• Change from Baseline in HAQ-DI at Week 16 
• Change from Baseline in the SF-36 PCS score at Week 16  
• Change from Baseline in vdHmTSS at Week 16  
• Change from Baseline in LEI at Week 16 in the subgroup of subjects with enthesitis at 
Baseline 
Continuous variables will be analyzed to evaluate the hypothetical estimand as defined below: 
1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria 
2. Subject level outcome = variable as stated in Section 4.2.1  
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to Week 16. A hypothetical strategy for 
addressing intercurrent events will be implemented. This estimand targets the treatment 
difference in a scenario where withdrawal from study treatment due to an AE or lack of 
efficacy does not occur, such that outcomes for subjects without an intercurrent event are as 
observed, and outcomes for subjects with an intercurrent event are treated as though they had 


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completed the randomized study treatment through Week 16. A multiple imputation strategy 
will be used to impute data following an intercurrent event. 
4. Population-level summary measure = the difference in the adjusted means between 
bimekizumab 160mg Q4W and placebo. 
Any missing data at Week 16 that are not preceded by an intercurrent event (ie, discontinuation 
of study medication due to an AE or lack of efficacy) will be imputed based on a predefined 
MI model. In MI, the missing value is replaced by a set of plausible values, where each value is a 
Bayesian draw from the conditional distribution of the missing data given the observed data. 
Intermittent missing data will be imputed using the MCMC method, followed by monotone 
regression for monotone missing data. In the case of vdHmTSS missing data, where there are 
only 2 timepoints; missing data at Week 16 will be imputed using the MCMC method. 
The statistical model for the comparison of bimekizumab and placebo will be an ANCOVA 
model with treatment, joint erosion, and region as fixed effects and the Baseline value as 
covariate. The statistical hypothesis for the continuous variables at Week 16 is that the treatment 
difference between the bimekizumab treatment group and placebo is equal to 0. 
All secondary efficacy variables will also be summarized based on observed case data. 
Has been changed to: 
The secondary efficacy variables will be analyzed for all subjects in the RS.  
All binary variables that are part of the testing hierarchy are given below: 
• PASI90 responders at Week 16 will be analyzed to evaluate the composite estimand. The 
composite estimand combines the clinically meaningful improvement from Baseline in 
PASI90 response and not discontinuing treatment early due to an AE or lack of efficacy. 
• The proportion of subjects achieving MDA status at Week 16 will be analyzed to evaluate 
the composite estimand. The composite estimand combines (1) achieving the MDA status 
with (2) not discontinuing treatment early due to an AE or lack of efficacy. 
• The proportion of subjects with dactylitis at Baseline achieving dactylitis-free status at 
Week 16 will be analyzed to evaluate the composite estimand. The composite estimand 
combines (1) achieving the dactylitis-free status with (2) not discontinuing treatment early 
due to an AE or lack of efficacy. 
The statistical hypothesis for the binary variables at Week 16 is that the conditional odds ratio for 
binary variables in the bimekizumab treatment compared with placebo treatment groups is equal 
to 1. 
Any missing data at Week 16 which are not preceded by an intercurrent event (ie, 
discontinuation of study medication due to an AE or lack of efficacy) will be imputed based 
on a predefined MI model. In MI, the missing value is replaced by a set of plausible values, 
where each value is a Bayesian draw from the conditional distribution of the missing data 
given the observed data. Intermittent missing data will be imputed using the MCMC 
method followed by logistic regression for monotone missing data.  
In the case of MDA as the response is based on 7 different component scores, it is necessary 
to consider various data scenarios that could impact the calculation of response. The rules 


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described here are applicable in the context of the calculation of MDA response and may 
differ from the rules applied for calculating and summarizing the components individually 
(some values may need to be imputed for component analysis but are not required here to 
evaluate MDA response).  
The following rules will be applied to complete the derivation of MDA response based on 
the composite estimand definition: 
• If a given visit has been preceded by an intercurrent event: 
o The endpoint at all subsequent visits (whether the data were observed or not) 
will be set to “non-response” as the subject has not met the criteria for 
response. 
• If a given visit has not been preceded by an intercurrent event: 
o If at least 5 of the 7 components have observed data collected, the MDA 
response will be calculated based on observed data.  
o If there are fewer than 5 of the 7 components with observed data at Week 16, 
then imputation methods will be applied, consistent with the predefined 
approach for handling intercurrent events. Multiple imputation will be applied, 
where each of the components will be imputed separately before deriving the 
response based on imputed components. Note: In the case where there is partial 
missing data at a visit (missing data for some components), the available 
observed values and the imputed values will be used to derive the response. 
The binary variables will be analyzed using the same analysis methods and estimand approach as 
used for the primary variable (Section 14.3.1.1). 
If appropriate ie, where the outcome variable (eg, PASI90 response) is an assessment of 
skin/dermatological manifestations of PsA the fitted model will exclude the fixed term jointbone 
erosion at Baseline. 
All continuous variables that are part of the testing hierarchy are given below: 
• Change from Baseline in HAQ-DI at Week 16 
• Change from Baseline in the SF-36 PCS score at Week 16  
• Change from Baseline in vdHmTSS at Week 16  
• Change from Baseline in LEI at Week 16 in the subgroup of subjects with enthesitis at 
Baseline 
Continuous variables will be analyzed to evaluate the hypothetical estimand as defined below: 
1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria 
2. Subject level outcome = variable as stated in Section 4.2.1  
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to Week 16. A hypothetical strategy for 
addressing intercurrent events will be implemented. This estimand targets the treatment 
difference in a scenario where withdrawal from study treatment due to an AE or lack of 


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efficacy does not occur, such that outcomes for subjects without an intercurrent event are as 
observed, and outcomes for subjects with an intercurrent event are treated as though they had 
completed the randomized study treatment through Week 16. A multiple imputation strategy 
will be used to impute data following an intercurrent event. 
4. Population-level summary measure = the difference in the adjusted means between 
bimekizumab 160mg Q4W and placebo. 
Any missing data at Week 16 that are not preceded by an intercurrent event (ie, discontinuation 
of study medication due to an AE or lack of efficacy) will be imputed based on a predefined 
MI model. In MI, the missing value is replaced by a set of plausible values, where each value is a 
Bayesian draw from the conditional distribution of the missing data given the observed data. 
Intermittent missing data will be imputed using the MCMC method, followed by monotone 
regression for monotone missing data. In the case of vdHmTSS missing data, where there are 
only 2 timepoints; missing data at Week 16 will be imputed using the MCMC method. 
In the case of vdHmTSS missing data, where there are only 2 timepoints; missing data at 
Week 16 will be imputed using the MCMC method. 
The statistical model for continuous endpoints for the comparison of bimekizumab and placebo 
will be an ANCOVA model with treatment, jointbone erosion, and region as fixed effects and 
the Baseline value as covariate. The statistical hypothesis for the continuous variables at Week 
16 is that the treatment difference between the bimekizumab treatment group and placebo is 
equal to 0. 
All secondary efficacy variables will also be summarized based on observed case data as well as 
nonresponder imputation (NRI) for binary variables. 
 
Change #39 
Section 14.3.2 Analysis of the other efficacy variables, paragraph 3 through end 
Any missing data that is not preceded by an intercurrent event as described above will be 
imputed based on a predefined multiple imputation model as described for the primary efficacy 
variable. 
Continuous variables will be summarized using descriptive statistics by each visit. Generally, the 
estimand structure for continuous other efficacy variables is as described below. Note that further 
details will be provided in the SAP. 
1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria 
2. Subject-level outcome = The given variable and time point being summarized (eg, change 
from Baseline in HAQ-DI at Week 36) 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to the time point being summarized. A 
hypothetical strategy will be implemented in which outcomes for subjects without an 
intercurrent event are as observed at the given time point, and outcomes for subjects with an 
intercurrent event are treated as though they had completed the randomized study treatment 


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through the time point being summarized. A multiple imputation strategy will be used to 
impute data following an intercurrent event.  
4. Population-level summary measure = Unadjusted mean 
Any missing data that are not preceded by an intercurrent event as described above will be 
imputed based on a predefined multiple imputation model as described for continuous secondary 
efficacy variables. 
In some cases, other efficacy variables may also be summarized based on observed case data (ie, 
subjects with missing data or who have prematurely discontinued study treatment are treated as 
missing). 
Time to ACR20/50/70 response will be estimated and presented using the Kaplan-Meier 
product-limit method for each treatment. Time to a given response will be defined as the length 
in days from Baseline until the first date when the response is achieved. Subjects who 
discontinue study treatment prior to achieving a response will be censored at the date of study 
treatment discontinuation. Subjects in the placebo group who are rerandomized at Week 16 
without achieving response will be censored at the date of the Week 16 Visit. The median time to 
response, including the 2-sided 95% CI, will be calculated for each treatment. Between group 
differences will be analyzed with a log-rank statistic. 
Has been changed to: 
Any missing data that is not preceded by an intercurrent event as described above will be 
imputed based on a predefined multiple imputation model as described for the primary and 
secondary efficacy variables. 
Continuous variables will be summarized using descriptive statistics by each visit. Generally, the 
estimand structure for continuous other efficacy variables is as described below. Note that further 
details will be provided in the SAP. 
1. Population = Subjects meeting the protocol-specified inclusion/exclusion criteria 
2. Subject-level outcome = The given variable and time point being summarized (eg, change 
from Baseline in HAQ-DI at Week 36) 
3. Intercurrent event handling = An intercurrent event is defined as discontinuation of study 
treatment due to an AE or lack of efficacy prior to the time point being summarized. A 
hypothetical strategy will be implemented in which outcomes for subjects without an 
intercurrent event are as observed at the given time point, and outcomes for subjects with an 
intercurrent event are treated as though they had completed the randomized study treatment 
through the time point being summarized. A multiple imputation strategy will be used to 
impute data following an intercurrent event.  
4. Population-level summary measure = Unadjusted mean 
Any missing data that are not preceded by an intercurrent event as described above will be 
imputed based on a predefined multiple imputation model as described for continuous secondary 
efficacy variables. 


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In some cases, other Other binary and continuous efficacy variables willmay also be 
summarized based on observed case data (ie, subjects with missing data or who have 
prematurely discontinued study treatment are treated as missing). 
Time to ACR20/50/70 response will be estimated and presented using the Kaplan-Meier 
product-limit method for each treatment. Time to a given response will be defined as the length 
in days from Baseline until the first date when the response is achieved. Subjects who 
discontinue study treatment prior to achieving a response will be censored at the date of study 
treatment discontinuation. Subjects in the placebo group who are rerandomized at Week 16 
without achieving response will be censored at the date of the Week 16 Visit. The median time to 
response, including the 2-sided 95% CI, will be calculated for each treatment. Between group 
differences will be analyzed with a log-rank statistic. 
The time to ACR20/50/70 endpoints with missing data that are not preceded by an 
intercurrent event as described above will be imputed based on a predefined multiple 
imputation model as described for the primary efficacy variable. 
The time to ACR20/50/70 endpoints will also be analyzed using observed case (OC) data. 
 
Change #40 
Section 14.3.3 Subgroup analyses—the following subgroup analysis added: 
• Concomitantly receiving MTX versus no concomitant MTX 
 
Change #41 
Section 14.7 Handling of dropouts or missing data, paragraph 2  
Missing data will be evaluated as sensitivity analyses using different missing data mechanisms. 
The following sensitivity analyses for the primary efficacy variable and for those secondary 
efficacy variables that are part of the hierarchical testing will be conducted: 
Has been changed to: 
Missing data will be evaluated as sensitivity analyses using different missing data mechanisms. 
The following sensitivity analyses for the primary efficacy variable and for those secondary 
efficacy variables that are part of the hierarchical testing will be conducted: 
 
Change #42 
Section 14.7 Handling of dropouts or missing data, last paragraph (new text added before 
paragraph)  
Additional details on these sensitivity analyses will be provided in the SAP. 
Has been changed to: 
5. Nonresponder imputation analysis will also be performed where subjects will be 
considered “nonresponders” at the timepoint of interest if: 


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− Subjects are missing data at the time point of interest. 
− Subjects remained in the study but have discontinued study treatment due to an AE 
or lack of efficacy before the time point of interest. 
For the secondary efficacy variables, the binary endpoints will be analyzed using both NRI 
and OC and for continuous endpoints OC will be performed. 
For the other efficacy endpoints, OC analysis will be conducted for both binary and 
continuous variables. 
Additional details on these sensitivity analyses will be provided in the SAP. 
 
Change #43 
Section 14.8.1 Interim analyses—new sentence added to end of section 
Additional data cuts may be prepared following regulatory requests or for publication 
purposes. 
 
Change #44 
Section 14.8.2 Data monitoring—new sentence added after paragraph 2  
Other adjudication committees may be added as necessary. 
 
Change #45 
Section 14.9.2 Power calculations for secondary endpoints, paragraph 6, paragraph 7, and 
Table 14-1 
For change from Baseline in vdHmTSS at Week 16, the between treatment differences of the 
change from Baseline in vdHmTSS at Week 16 of the SPIRIT P1 study in a TNFα-naive 
population (Mease et al, 2017) were used. The SPIRIT P1 study ixekizumab 80mg sc Q2W 
treatment group least square (LS) mean change from Baseline at Week 16 0.06 and SD 0.720; 
and LS mean change from Baseline 0.36 and SD 0.710 for placebo are assumed. With those 
assumptions, the study has a 84% power to detect a true treatment difference of -0.30, assuming 
30% of subjects with joint erosion, in the planned sample size. 
There is uncertainty in the final percentage of subjects with joint erosion at Baseline that will be 
recruited to the study and the variability in the subgroup. To demonstrate the sensitivity of the 
sample size calculation for this study, Table 14-1 shows the power function for a fixed total 
sample size of 840 subjects in the RS population for this secondary efficacy analysis, varying the 
percentage of subjects with joint erosion at Baseline and the treatment difference and estimated 
standard deviation on the change from Baseline in vdHmTSS at Week 16. 


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Table 14-1: Treatment effect by joint erosion at Baseline for secondary efficacy 
analyses 
Subjects with joint erosion at Baseline 
Treatment difference/standard deviation 
 
Treatment effect = -0.3 
SD=0.72 vs 0.71 
Treatment effect = -0.35 
SD=0.81 vs 0.93 
20% 
67 
62 
25% 
76 
72 
30% 
84 
79 
35% 
89 
85 
40% 
92 
89 
45% 
95 
92 
50% 
96 
95 
SD=standard deviation 
Has been changed to: 
For change from Baseline in vdHmTSS at Week 16, the between treatment differences of the 
change from Baseline in vdHmTSS at Week 16 of the SPIRIT P1 study in a TNFα-naive 
population (Mease et al, 2017) were used. The SPIRIT P1 study ixekizumab 80mg sc Q2W 
treatment group least square (LS) mean change from Baseline at Week 16 0.06 and SD 0.720; 
and LS mean change from Baseline 0.36 and SD 0.710 for placebo are assumed. With those 
assumptions, the study has a 8495% power to detect a true treatment difference of -0.30, 
assuming 3045% of subjects with jointelevated hs-CRP and/or bone erosion, in the planned 
sample size. 
There is uncertainty in the final percentage of subjects with jointelevated hs-CRP and/or bone 
erosion at Baseline that will be recruited to the study and the variability in the subgroup. To 
demonstrate the sensitivity of the sample size calculation for this study, Table 14-1 shows the 
power function for a fixed total sample size of 840 subjects in the RS population for this 
secondary efficacy analysis, varying the percentage of subjects with jointelevated hs-CRP 
and/or bone erosion at Baseline and the treatment difference and estimated standard deviation 
on the change from Baseline in vdHmTSS at Week 16. 


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Table 14-1: Treatment effect by jointelevated hs-CRP and/or bone erosion at 
Baseline for secondary efficacy analyses 
Subjects with jointelevated hs-CRP 
and/or bone erosion at Baseline 
Treatment difference/standard deviation 
 
Treatment effect = -0.3 
SD=0.72 vs 0.71 
Treatment effect = -0.35 
SD=0.81 vs 0.93 
20% 
67 
62 
25% 
76 
72 
30% 
84 
79 
35% 
89 
85 
40% 
92 
89 
45% 
95 
92 
50% 
96 
95 
hs-CRP=high sensitivity C-reactive protein; SD=standard deviation 
 
 


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18.3 
Protocol Amendment 2 
The main purpose of this protocol amendment was to modify the secondary variables and fixed 
sequence testing procedure, update the statistical section, and make other procedural 
clarifications. 
Modifications and changes 
Global changes: 
Throughout the protocol, FACIT-F has been corrected to FACIT-Fatigue subscale, as it is the 
fatigue subscale that is being assessed in this study. In addition, minor spelling, editorial, and 
formatting changes were made throughout the protocol. These global changes are not included in 
specific changes table that follows.  
 


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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 
 
 
 
UCB Celltech Ltd 
208 Bath Road 
Slough SL1 3WE 
 
The Sponsor Study Physician has 
changed. 
 
UCB BIOSCIENCES Inc. 
8010 Arco Corporate Drive 
Raleigh, NC 27617 
UNITED STATES 
 
 
UCB BIOSCIENCES GmbH 
Alfred-Nobel-Str. 10 
40789 Monheim 
GERMANY 
 
The Clinical Project Manager has 
changed.  
Change 2: Abbreviation added 
List of abbreviations 
Abbreviations and definitions added for the following: LN, PsARC, PASDAS 
Abbreviations used in text. 
Change 3: Updated text in clinical studies section 
Section 2.2.2.1 
The list of completed studies was updated consistent with the current 
bimekizumab IB.  
More studies have completed, and 
additional studies have started, 
since the last protocol amendment. 
Section 2.2.2.2 
The list of ongoing studies was updated consistent with the current bimekizumab 
IB. 


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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Change 4: Updated 2 secondary efficacy variables 
Section 4.2.1 
• 
Dactylitis-free state based on the 
Leeds Dactylitis Index (LDI) at 
Week 16 in the subgroup of 
subjects with dactylitis at Baseline  
• 
Change from Baseline in the Leeds 
Enthesitis Index (LEI) at Week 16 
in the subgroup of subjects with 
enthesitis at Baseline 
• 
Change from Baseline Enthesitis-
free state in the Leeds Enthesitis 
Index (LEI) at Week 16 in the 
subgroup of subjects with 
enthesitis at Baseline in the 
pooled population of PA0010 
and PA0011 
• 
Dactylitis-free state based on the 
Leeds Dactylitis Index (LDI) at 
Week 16 in the subgroup of 
subjects with dactylitis at Baseline 
in the pooled population of 
PA0010 and PA0011 
In order to provide more clinically 
interpretable results for dactylitis 
and enthesitis endpoints across a 
more robust mixed population 
(TNF-inadequate responders and 
bDMARD-naïve), the endpoints of 
dactylitis free-state and enthesitis 
free-state will be analyzed using a 
pooled PA0010 and PA0011 
population. 
Given similar power between 
dactylitis and enthesitis, the 
enthesitis endpoint was moved up 
in the statistical testing hierarchy as 
it is considered a more relevant 
clinical endpoint.  
Section 14.3.1 
Figure 14-1 
In Figure 14-1 Sequential testing procedure of primary/secondary efficacy 
endpoints (fixed sequence testing procedure), the enthesitis and dactylitis 
variables were updated to be based on the pooled population of PA0010 and 
PA0011, and the enthesitis-free state variable was moved above the dactylitis-
free state variable in the figure. 


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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Change 5: Added 7 new Other efficacy variables 
Section 4.3.1 
Added the following variables:  
• 
Composite endpoint composed of ACR50 and PASI100 response in 
subjects with PSO involving at least 3% BSA at Baseline 
• 
Proportion of Psoriatic Arthritis Response Criteria (PsARC) responders 
• 
Psoriatic Arthritis Disease Activity Score (PASDAS) categories 
• 
Change from Baseline in the PASDAS  
• 
Proportion of subjects with a decrease of HAQ-DI from Baseline of at 
least 0.35 in those subjects with HAQ-DI >0.35 at Baseline 
• 
Proportion of PSAID-12 responders (decrease from Baseline in 
PsAID-12 total score ≥3 in subjects with PsAID-12 total score >3 at 
Baseline 
• 
Proportion of FACIT-Fatigue subscale responders (minimum 
clinically important difference for FACIT-Fatigue subscale score, 
defined as an increase of ≥4 
Updated to be consistent with 
variables added to the SAP 
Change 6: Updated wording in other efficacy variables 
Section 4.3.1 
• 
Dactylitis-free state based on the 
LDI in the subgroup of subjects 
with dactylitis at Baseline 
• 
Dactylitis-free state based on the 
LDI in the subgroup of subjects 
with dactylitis at Baseline in the 
pooled population of PA0010 
and PA0011, as well as PA0010 
alone 
Updated to be consistent with 
changes made to the dactylitis and 
enthesitis secondary efficacy 
variables and to specify that the 
PA0010-only population will also 
be analyzed. 
• 
Enthesitis-free state based on the 
LEI in the subgroup of subjects 
with enthesitis at Baseline 
• 
Enthesitis-free state based on the 
LEI in the subgroup of subjects 
with enthesitis at Baseline in the 
pooled population of PA0010 
and PA0011, as well as PA0010 
alone 


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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Section 4.3.1 
• 
Enthesitis-free state based on the 
SPARCC index in the subgroup of 
subjects with enthesitis at Baseline 
• 
Enthesitis-free state based on the 
SPARCC index in the subgroup of 
subjects with enthesitis at Baseline 
in the pooled population of 
PA0010 and PA0011, as well as 
PA0010 alone 
Updated to be consistent with 
changes made to the dactylitis and 
enthesitis secondary efficacy 
variables and to specify that the 
PA0010-only population will also 
be analyzed. 
• 
Change from Baseline in the LEI 
in the subgroup of subjects with 
enthesitis at Baseline 
• 
Change from Baseline in the LEI 
in the subgroup of subjects with 
enthesitis at Baseline in the 
pooled population of PA0010 
and PA0011, as well as for 
PA0010 alone 
• 
Change from Baseline in the 
SPARCC index in the subgroup of 
subjects with enthesitis at Baseline 
• 
Change from Baseline in the 
SPARCC index in the subgroup of 
subjects with enthesitis at Baseline 
in the pooled population of 
PA0010 and PA0011, as well as 
for PA0010 alone  
• 
Change from Baseline in the LDI 
in the subgroup of subjects with 
dactylitis at Baseline 
• 
Change from Baseline in the LDI 
in the subgroup of subjects with 
dactylitis at Baseline in the pooled 
population of PA0010 and 
PA0011, as well as for PA0010 
alone 


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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
Section 4.3.1 
• 
Disease Activity Index for 
Psoriatic Arthritis (DAPSA) 
• 
Disease Activity Index for 
Psoriatic Arthritis (DAPSA) score 
categories 
Corrected wording  
• 
Change from Baseline in 
PsAID-12, in the individual 
domains of PsAID-12 
• 
Change from Baseline in 
PsAID-12 total score, as well as 
in the individual domain scores 
• 
Change from Baseline in the 
Psoriatic Arthritis Quality of Life 
(PsAQoL) 
• 
Change from Baseline in the 
Psoriatic Arthritis Quality of Life 
(PsAQoL) total score 
• 
Change from Baseline in 
Functional Assessment of Chronic 
Illness Therapy—Fatigue 
(FACIT-F) 
• 
Change from Baseline in 
Functional Assessment of Chronic 
Illness Therapy—Fatigue 
(FACIT F) subscale score 
Change 7: Made minor updates to Double-Blind Treatment Period section and Active Treatment Period section text 
Section 5.3.1 
2nd paragraph: Investigational 
medicinal product treatment details are 
provided in Section 7.2. Visit windows 
of ±2 days are allowed for all visits up 
to Week 16. The visit window is 
relative to the Day 1 (Baseline) Visit. 
5th paragraph: Subjects withdrawing 
early from the study will undergo the 
Early Termination (ET) Visit 
assessments and will enter the SFU 
Period. Subjects who withdraw from 
IMP during the Double-Blind Period 
will return for all scheduled visits up to 
Week 52 and for the SFU Visit (20 
weeks after their final dose of IMP). 
2nd paragraph: Investigational 
medicinal product treatment details are 
provided in Section 7.2. Visit windows 
of ±2 days are allowed for all visits up 
tothrough Week 16. The visit window 
is relative to the Day 1 (Baseline) 
Visit. 
5th paragraph: Subjects withdrawing 
early from the study will undergo the 
Early Termination (ET) Visit 
assessments and will enter the SFU 
Period. Subjects who withdraw from 
IMP during the Double-Blind Period 
will be encouraged to return for all 
scheduled visits up to Week 52 and for 
Clarification of text. 


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Protocol section 
impacted 
Key components of previous 
protocol text 
Key components of revised protocol 
text 
Rationale 
the SFU Visit (20 weeks after their 
final dose of IMP), as applicable. 
Section 5.3.2 
5th paragraph: Subjects who withdraw 
early from the study will undergo the 
ET Visit assessments and will enter the 
SFU Period. Subjects who withdraw 
from IMP during the Active-
Treatment-Blind Period will return for 
all remaining scheduled visits up to 
Week 52 and the SFU Visit (20 weeks 
after their final dose of IMP). 
5th paragraph: Subjects who withdraw 
early from the study will undergo the 
ET Visit assessments and will enter the 
SFU Period. Subjects who withdraw 
from IMP during the Active-
Treatment-Blind Period will be 
encouraged to return for all remaining 
scheduled visits up to Week 52 and the 
SFU Visit (20 weeks after their final 
dose of IMP), as applicable. 
Clarification of text. 
Change 8: Made minor updates to Schedule of study assessments footnote o 
Table 5-1 
o 
Circumference measured in 
millimeters. The LDI assessment of 
dactylitis will be obtained for all 
subjects at the Baseline visit. 
Subsequent to the Baseline visit, 
the LDI assessment will be 
obtained only for those subjects 
who had dactylitis at Baseline (as 
per the LDI assessment performed 
at Baseline). 
o Circumference measured in 
millimeters. The LDI assessment of 
dactylitis will be obtained for all 
subjects at the Baseline visit. 
Subsequent to the Baseline visit, the 
LDI assessment will be obtained 
only for those subjects who had 
dactylitis at Baseline (as per the LDI 
assessment performed at Baseline). 
Correction of footnote ‘o,’ as the 
LDI assessment is being done at 
every visit. 
Change 9: Added a withdrawal criterion 
Section 6.3 
Added the following to the list of withdrawal criteria: 
13. Any subject who develops a clinically important infection or recurrent 
infections not responsive to standard therapy during the study must 
discontinue IMP until resolution of the infection. The Investigator should 
use clinical judgement in deciding whether the subject should restart IMP 
In line with the exclusion 
criterion 11 regarding infections, a 
specific infection-related 
withdrawal criterion was added to 
clarify that patients with serious or 
recurrent infections not responding 


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and contact the Medical Monitor and UCB study physician to confirm the 
subject’s suitability for continued participation in the study. 
to standard therapies are not 
exposed to immunomodulatory 
therapies until their infection is 
resolved. This is in line with most 
biologic therapies, including other 
anti-IL17s. 
Change 10: Updated the permitted concomitant treatments section 
Section 7.8.1 
Added the following paragraph to the section:  
Subjects are allowed to use any other medications, including biologics, after at 
least 28 days of last dose of the IMP. This is applicable for subjects who 
discontinue from IMP or the study early, including those permanently withdrawn 
from IMP, or subjects who have completed the study treatment without entering 
the extension study and are in the SFU period.  
Clarification of permitted 
concomitant medications. 
Change 11: Updated FACIT-F assessment section 
Section 9.19 
The FACIT–F scale (Cella et al, 2005) 
will be used to assess fatigue in PsA 
patients. The FACIT-F has been 
validated in the general population, in 
patients with RA, and in patients with 
PsA. The minimum clinically 
important difference for FACIT-F in 
patients with RA was determined to be 
a 3 to 4-point change; this minimum 
clinically important difference will be 
used in evaluating clinically 
meaningful changes in fatigue for 
patients with PsA. 
The FACIT F scale (Cella et al, 2005) 
will be used to assess fatigue in PsA 
patients. The FACIT-Fatigue is a 
40-item measure that assesses 
self-reported fatigue and its impact 
upon daily activities and function 
over the past 7 days (FACIT.org). 
The scale consists of 5 subscales 
(physical well-being, social/family 
well-being, emotional well-being, 
functional well-being, and fatigue). 
The fatigue subscale is the only one 
used in this study. It is composed of 
13 items, all scored from 0 (Not at 
all) to 4 (Very much). The 
FACIT-Fatigue subscale score 
ranges from 0 to 52 with 0 being the 
Added a reference for FACIT-
Fatigue subscale use in PsA. 
Wording changes implemented for 
consistency with the user manuals 
and to reflect precise description of 
the PRO tools and scoring (change 
in terminology but no change in the 
method). 


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worst possible score and 52 being 
the best possible score. To obtain a 
score from 0 to 52, all negatively 
worded questions have to be 
recoded, so that responses range 
from worst (0) to the best (4) 
outcome. 
The FACIT-Fatigue subscale has been 
validated in the general population, in 
patients with RA, and in patients with 
PsA. The minimum clinically 
important difference for 
FACIT-Fatigue subscale in patients 
with RAPsA was determined to be a 3   
to 4-point change (Cella et al, 2019); 
this minimum clinically important 
difference will be used in evaluating 
clinically meaningful changes in 
fatigue for patients with PsA. 
Change 12: Updated SF-36 assessment section 
Section 9.20 
In addition to domain scores, the PCS 
and MCS scores are calculated from 
the 8 domains (excluding the Health 
Transition item). Component scores 
appreciate the impact of each domain 
on physical and mental health status 
(Maruish, 2011). Each of the 8 domain 
scores and the component summary 
scores range from 0 to 100, with a 
higher score indicating a better health 
status. The 2 component summary 
scores are standardized with a mean of 
In addition to domain scores, the PCS 
and MCS scores are calculated from 
the 8 domains (excluding the Health 
Transition item). Component scores 
appreciate reflect the impact of each 
domain on physical and mental health 
status (Maruish, 2011). Each of the 8 
domain scores and the component 
summary scores range from 0 to 100, 
with a higher score indicating a better 
health status. The norm-based T-
scores for the 2 SF-36 component 
summary scores (PCS and MCS) and 
Wording changes implemented for 
consistency with the user manuals 
and to reflect precise description of 
the PRO tools and scoring (change 
in terminology but no change in the 
method). 


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50 and a standard deviation (SD) of 10 
in the general US population. 
the 8 domains are standardized with a 
mean of 50 and a standard deviation 
(SD) of 10 in the general US 
population (Maruish, 2011). .An 
individual respondent’s score that 
falls outside the T-score range of 45 
to 55 should be considered outside 
the average range for the US general 
population. When considering 
group-level data, a score below 47 
should be considered indicative of 
impaired functioning within that 
health domain or dimension. Similar 
to individual respondent data, group 
mean scores of 47 or greater should 
be considered average or above 
average as compared to the general 
US population. Higher scores 
indicate a better health status. 
Change 13: Added 2 new sections to describe the PsARC and PASDAS efficacy assessments added in new Other efficacy variables 
New Section 9.23 
Section 9.23 Psoriatic Arthritis Response Criteria (PsARC) added to describe the 
PsARC efficacy assessment 
The PsARC was added in a new 
Other efficacy variable 
New Section 9.24 
Section 9.24 Psoriatic Arthritis Disease Activity Score (PASDAS) added to 
describe the PASDAS efficacy assessment 
The PASDAS was added in 2 new 
Other efficacy variables. 


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Change 14: Moved PHQ-9 assessment section from efficacy assessments to safety assessments  
Old Section 9.23 
moved to  
New Section 12.3.8 
12.3.5 Assessment and management of 
TB and TB risk factors 
12.3.6 Pregnancy testing 
12.3.7 Assessment of suicidal ideation 
and behavior  
12.3.5 Assessment and management of 
TB and TB risk factors 
12.3.6 Pregnancy testing 
12.3.7 Assessment of suicidal ideation 
and behavior  
12.3.8 Patient Health 
Questionnaire-9 (PHQ-9) 
In PA0010 Protocol Amendment 1, 
the PHQ-9 was moved to Other 
safety variables from Other efficacy 
variables, but the assessment 
description section was not moved. 
In the current amendment (#2), the 
PHQ-9 assessment description 
section was moved to align with the 
variables. 
Change 15: Updated Other safety topics of interest section 
Section 12.1.1.4 
Prespecified safety topics of interest 
for the study are: infections (serious, 
opportunistic, fungal and TB), 
neutropenia, hypersensitivity, suicidal 
ideation and behavior, depression, 
major cardiovascular events, liver 
function test changes/enzyme 
elevations, malignancies, and 
inflammatory bowel diseases (with 
gastroenterology referral, as 
appropriate). 
Prespecified safety topics of interest 
for the study are: infections (serious, 
opportunistic, fungal and TB), 
neutropenia, hypersensitivity, suicidal 
ideation and behavior, depression, 
major cardiovascular events, liver 
function test changes/enzyme 
elevations, malignancies, and 
inflammatory bowel diseases (with 
gastroenterology referral, as 
appropriate). 
With progressive development of 
bimekizumab and based on the 
ongoing review of emerging safety 
data, depression has been removed 
as a safety topic of interest. 
Nevertheless, depression will 
continue to be monitored as a safety 
parameter by the PHQ-9 and will 
be captured via routine AE 
reporting during the study. This 
update is considered a procedural 
change. 


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Change 16: Updated Evaluation of PDILI section 
Section 12.2.1 
The PDILI IMP discontinuation 
criteria for this study are provided in 
Section 6.3.1, with the accompanying 
required follow-up investigation and 
monitoring detailed below. All PDILI 
events must be reported as AEs and 
reported to the study site and Sponsor 
within 24 hours of learning of their 
occurrence. Any PDILI event that 
meets the criterion for potential Hy’s 
Law must be reported as an AE of 
special interest (see Section 12.1.1.3), 
and, if applicable, also reported as an 
SAE (see Section 12.1.1.2). 
All PDILI events must be reported as 
an AE and reported to the study site 
PDILI events meeting SAE criteria 
should be reported to the Sponsor 
within 24 hours of learning of their 
occurrence. Any PDILI event that 
meets the criterion for potential Hy’s 
Law must be reported within 24 hours 
of learning of their occurrence as an 
AE of special interest (see 
Section 12.1.1.3), and, if applicable, 
also reported as an SAE (see 
Section 12.1.1.2). 
Clarified PDILI event reporting 
procedure. 
Section 12.2.1.2 
The immediate action is dependent on 
the laboratory values and symptoms of 
hepatitis or hypersensitivity and ranges 
from continuation of IMP (followed by 
immediate investigation) to immediate 
discontinuation (see Section 6.3.1 and 
Table 12‒3 for details). 
The immediate action is dependent on 
the laboratory values and symptoms of 
hepatitis or hypersensitivity and ranges 
from continuation of IMP (followed by 
immediate investigation) to immediate 
and permanent discontinuation (see 
Section 6.3.1 and Table 12‒3 for 
details). 
Clarify the range of potential 
actions. 
Change 17: Updated the analysis set definition section 
Section 14.1 
• 
The Per-Protocol Set (PPS) will 
consist of all subjects in the RS 
who had no important protocol 
deviations affecting the primary 
efficacy variable. Important 
protocol deviations will be 
predefined and subjects with 
important protocol deviations will 
• 
The Per-Protocol Set (PPS) will 
consist of all subjects in the RS 
who had no important protocol 
deviations affecting the primary 
efficacy variable. Important 
protocol deviations will be 
predefined and subjects with 
important protocol deviations will 
Clarified PPS and PK-PPS 
definitions. 
Added COVID-19-free analysis set 
to determine if COVID-19 has an 
impact on analyses. 


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be evaluated during ongoing data 
cleaning meetings prior to 
unblinding of the data. 
• 
The Pharmacokinetic Per-Protocol 
Set (PK-PPS) consists of all 
randomized subjects who received 
at least one dose of the IMP and 
provided at least one quantifiable 
plasma concentration post-dose 
without important protocol 
deviations that would affect the 
concentration.  
 
be evaluated during ongoing data 
cleaning meetings prior to 
unblinding of the data. Exclusions 
from the FAS will be considered 
important protocol deviations 
that also result in exclusion from 
the PPS. 
• 
The Pharmacokinetic Per-Protocol 
Set (PK-PPS) consists of all 
randomized subjects who received 
at least one dose of the IMP and 
provided at least one quantifiable 
plasma concentration post-dose 
without important protocol 
deviations that would affect the 
concentration. Exclusions from 
the FAS will be considered 
important protocol deviations 
that also result in exclusion from 
the PK-PPS. 
• 
The COVID-19-free Set will 
consist of all subjects in the RS 
who had no COVID-19 impact 
up to the primary efficacy 
endpoint. This will be defined as 
subjects not having a COVID-19 
related important protocol 
deviation, nor having an impact 
based on the COVID-19 eCRF, 
nor having an AE related to 
COVID-19, nor discontinuing 
due to COVID-19 up to the time 
of the primary endpoint. 


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Change 18: Updated text in analysis of the primary efficacy variables section 
Section 14.3.1.1 
Updated text regarding the statistical approach to be used for analyzing primary 
efficacy variable. 
Updated statistical methods based 
on feedback from the FDA. 
Change 19: Updated title and text in former Sensitivity analyses section 
Section 14.3.1.1.1 
Updated title of this section from Sensitivity analyses to SensitivitySupportive 
Analyses. Also, updated text regarding the statistical approach to be used for the 
supportive analyses. 
Updated statistical methods based 
on feedback from the FDA. 
Change 20: Updated text in analysis of the secondary efficacy variables section 
Section 14.3.1.2 
Updated text regarding the statistical approach to be used for analyzing 
secondary efficacy variables. 
Updated statistical methods based 
on feedback from the FDA. 
Change 21: Updated text in analysis of the other efficacy variables section 
Section 14.3.2 
Updated text regarding the statistical approach to be used for analyzing the other 
efficacy variables. 
Updated statistical methods based 
on feedback from the FDA. 
Change 22: Updated text in handling of dropouts or missing data section 
Section 14.7 
Updated the statistical approach to be used for missing data. 
Updated statistical methods based 
on feedback from the FDA. 
Change 23: Updated the power calculation text for enthesitis-free state and dactylitis-free state 
Section 14.9.2 
For dactylitis-free state at Week 16, it 
has been assumed that 25% of all 
subjects have dactylitis symptoms at 
Baseline. Dactylitis resolution data of 
the FUTURE 5 study (Mease et al, 
2018) at Week 16 were used to 
estimate the bimekizumab 160mg 
Q4W treatment and placebo groups. 
The treatment effect estimate from the 
secukinumab 150mg treatment group 
at Week 16 of 56% (n=103) is assumed 
For dactylitis-free state at Week 16, it 
has been assumed that 25% of all 
subjects have dactylitis symptoms at 
Baseline. Dactylitis resolution data of 
the FUTURE 5 study (Mease et al, 
2018) at Week 16 were used to 
estimate the bimekizumab 160mg 
Q4W treatment and placebo groups. 
The treatment effect estimate from the 
secukinumab 150mg treatment group 
at Week 16 of 56% (n=103) is 
Updated the power calculation 
based on pooled population of 
PA0010 and PA0011. 


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versus a placebo group estimate of 
32% (n=124). With those assumptions, 
the study has an 85% power to detect a 
true treatment difference of 24% (odds 
ratio 2.71), assuming 25% of subjects 
at Baseline with dactylitis of the 
planned sample size. 
assumed versus a placebo group 
estimate of 32% (n=124). With those 
assumptions and having 11% of 
subjects with Baseline dactylitis, the 
study has an 85 pooled 
PA0010/PA0011 studies have a 66% 
power to detect a true treatment 
difference of 24% (odds ratio 2.71), 
assuming 25% of subjects at Baseline 
with dactylitis of the planned sample 
size. 
For change from Baseline in LEI 
Week 16, it has been assumed that 
50% of all subjects have enthesitis 
symptoms at Baseline. Enthesitis 
change from Baseline in LEI data at 
Week 16 of the FUTURE 2 study in 
the mixed TNFα exposure population 
(McInnes et al, 2015) were used to 
estimate the bimekizumab 160mg 
Q4W treatment and placebo groups. 
The FUTURE 2 treatment effect 
estimate from the secukinumab 150mg 
treatment group at Week 16 of -1.5 
(SD=2.0) is assumed versus a placebo 
group estimate of -0.9 (SD=2.1). With 
those assumptions, the study has 76% 
power of detecting a true treatment 
difference of 0.6 assuming 50% of 
subjects with enthesitis at Baseline of 
the planned sample size. 
For change from Baseline in LEI 
Week 16, it has been assumed that 
50% of all subjects have enthesitis 
symptoms at Baseline. Enthesitis 
change from Baseline in LEI data at 
Week 16 of the FUTURE 2 study in 
the mixed TNFα exposure population 
(McInnes et al, 2015) were used to 
estimate the bimekizumab 160mg 
Q4W treatment and placebo groups. 
The FUTURE 2 treatment effect 
estimate from the secukinumab 150mg 
treatment group at Week 16 of 1.5 
(SD=2.0) is assumed versus a placebo 
group estimate of 0.9 (SD=2.1). With 
those assumptions, the study has 76% 
power of detecting a true treatment 
difference of 0.6 assuming 50% of 
subjects with enthesitis at Baseline of 
the planned sample size. 
For enthesis free-state at Week 16, 
enthesis resolution data from the 
The secondary endpoint for 
enthesitis was updated to enthesitis-
free state from change from 
Baseline in LEI, and the power 
calculation was updated based on 
pooled population of PA0010 and 
PA0011 


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FUTURE 5 study at Week 16 were 
used to estimate the bimekizumab 
160mg Q4W treatment and placebo 
groups. In FUTURE 5 The 
treatment effect estimate from the 
secukinumab 150mg treatment 
group at Week 16 was 55% (n=141) 
and the placebo group estimate was 
36% (n=192). Assuming a BKZ 
response of 55% and a placebo rate 
of 39% and having 25% of subjects 
with Baseline enthesis the pooled 
PA0010/PA0011 the studies have a 
69% power to detect a true 
treatment difference of 16% (odds 
ratio 1.91). 
Change 24: Updated reference list 
References 
Deleted the following 2 references due to updates made in Section 14.7 Handling 
of dropouts or missing data: 
Mallinckrodt CH, Lin Q, Lipkovich I, Molenberghs G. A structured approach 
to choosing estimands and estimators in longitudinal clinical trials. Pharm 
Stat. 2012;11:456 61. 
Mallinckrodt CH. Preventing and Treating Missing Data in Longitudinal 
Clinical Trials: A Practical Guide. New York, NY: Cambridge University 
Press; 2013. 
Added the following 3 references, 1 for FACIT-Fatigue subscale and 2 for 
PASDAS: 
Cella D, Wilson H, Shalhoub H, Revicki DA, Cappelleri JC, Bushmakin AG, 
et al. Content validity and psychometric evaluation of Functional Assessment 
of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis. J 
Patient Rep Outcomes. 2019;3(1):5. 
Deleted Mallinckrodt references, as 
they are no longer applicable due to 
statistical updates. 
Additional references were 
deleted/added to support the 
assessments of FACIT-Fatigue 
subscale and PASDAS. 


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Coates LC, FitzGerald O, Mease PJ, Gladman DD, Strand V, Goel N, 
Campbell I, et al. Development of a disease activity and responder index for 
psoriatic arthritis – Report of the Psoriatic Arthrits Module at OMERACT 11. 
J Rheumatol 2014;41:782-91. 
Coates LC, Gladman DD, Nash P, FitzGerald O, Kavanaugh A, Kvien TK, et 
al. Secukinumab provides sustained PASDAS-defined remission in psoriatic 
arthritis and improves health-related quality of life in patients achieving 
remission: 2-year results from the Phase III FUTURE 2 study. Arthritis Res 
Ther. 2018;20(1):272. doi: 10.1186/s13075-018-1773-y. 
Deleted the following FACIT reference because it was superseded by the Cella 
et al, 2019 reference: 
Cella D, Yount S, Sorensen M, Chartash E, Sengupta N, Grober J. Validation 
of the Functional Assessment of Chronic Illness Therapy Fatigue Scale 
relative to other instrumentation in patients with rheumatoid arthritis. J 
Rheumatol. 2005;32:811 19. 
 


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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 GCP. 
 



SAP_001.pdf: 
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Statistical Analysis Plan 
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STATISTICAL ANALYSIS PLAN 
Study: PA0010 
Product: Bimekizumab 
A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, ACTIVE REFERENCE (ADALIMUMAB) STUDY EVALUATING THE 
EFFICACY AND SAFETY OF BIMEKIZUMAB IN THE TREATMENT OF SUBJECTS 
WITH ACTIVE PSORIATIC ARTHRITIS 
SAP/Amendment 
Number 
Date 
Final SAP 
27 MAY 2019 
Amendment 1 
06 JUL 2021 
Amendment 2 
22 OCT 2021 
Amendment 3 
06 MAY 2022 
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. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................. 11 
1 
INTRODUCTION ........................................................................................................... 17 
2 
PROTOCOL SUMMARY ............................................................................................... 17 
2.1 
Study objectives ........................................................................................................... 17 
2.1.1 
Primary objective ................................................................................................. 17 
2.1.2 
Secondary objectives ........................................................................................... 17 
2.1.3 
Other objectives ................................................................................................... 17 
2.2 
Study variables ............................................................................................................. 18 
2.2.1 
Efficacy variables ................................................................................................ 18 
2.2.1.1 
Primary efficacy variable .......................................................................... 18 
2.2.1.2 
Secondary efficacy variables ..................................................................... 18 
2.2.1.3 
Other efficacy variables ............................................................................. 19 
2.2.2 
Pharmacokinetic variable ..................................................................................... 21 
2.2.3 
Pharmacogenomic variables ................................................................................ 21 
2.2.4 
Immunological variables ..................................................................................... 22 
2.2.5 
Safety variables .................................................................................................... 22 
2.2.5.1 
Secondary safety variables ........................................................................ 22 
2.2.5.2 
Other safety variables ................................................................................ 22 
2.3 
Study design and conduct ............................................................................................ 22 
2.3.1 
Study description ................................................................................................. 22 
2.3.2 
Study Periods ....................................................................................................... 24 
2.3.2.1 
Screening Period ........................................................................................ 24 
2.3.2.2 
Double-Blind Treatment Period ................................................................ 25 
2.3.2.3 
Active Treatment-Blind Period ................................................................. 25 
2.3.2.4 
Safety Follow-up ....................................................................................... 26 
2.4 
Determination of sample size ....................................................................................... 26 
2.4.1 
Power calculations for the primary endpoint ....................................................... 26 
2.4.2 
Power calculations for secondary endpoints ........................................................ 26 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 28 
3.1 
General presentation of summaries and analyses ........................................................ 28 
3.2 
General study level definitions .................................................................................... 33 
3.2.1 
Relative day ......................................................................................................... 33 
3.2.2 
Mapping of assessments performed at Early Discontinuation Visit .................... 33 
3.3 
Definition of Baseline values ....................................................................................... 34 
3.4 
Study treatment discontinuation and intercurrent event .............................................. 34 
3.5 
Protocol deviations....................................................................................................... 35 
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3.6 
Analysis sets................................................................................................................. 35 
3.6.1 
Enrolled Set ......................................................................................................... 35 
3.6.2 
Randomized Set ................................................................................................... 35 
3.6.3 
Safety Set ............................................................................................................. 35 
3.6.4 
Full Analysis Set .................................................................................................. 36 
3.6.5 
Active Medication Set ......................................................................................... 36 
3.6.6 
Active Treatment-Blind Set ................................................................................. 36 
3.6.7 
Per Protocol Set ................................................................................................... 37 
3.6.8 
Pharmacokinetic Per-Protocol Set ....................................................................... 37 
3.6.9 
Radiographic Set .................................................................................................. 37 
3.6.10 
COVID-19-free Set .............................................................................................. 37 
3.7 
Treatment assignment and treatment groups ............................................................... 37 
3.8 
Center pooling strategy ................................................................................................ 38 
3.9 
Coding dictionaries ...................................................................................................... 38 
3.10 
Changes to protocol-defined analyses ......................................................................... 38 
3.11 
Changes related to COVID-19 ..................................................................................... 39 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 40 
4.1 
Adjustments for covariates .......................................................................................... 40 
4.2 
Handling of dropouts or missing data .......................................................................... 40 
4.2.1 
Strategy for handling missing data for efficacy analyses .................................... 40 
4.2.1.1 
Primary analysis of binary endpoints that are part of the testing hierarchy 
(primary and secondary endpoints) ........................................................... 42 
4.2.1.2 
Primary analysis of continuous endpoints that are part of the testing 
hierarchy (secondary endpoints) ............................................................... 42 
4.2.1.3 
Supportive analyses of primary efficacy endpoint .................................... 42 
4.2.1.4 
Supportive analyses of endpoints that are part of the testing hierarchy 
(secondary endpoints) ................................................................................ 43 
4.2.1.5 
Analyses of secondary endpoints that are not part of the testing hierarchy 
and other efficacy endpoints ...................................................................... 43 
4.2.1.6 
Summary table of missing data handling approaches for efficacy analyses44 
4.2.2 
Methods for handling missing data for efficacy analyses.................................... 44 
4.2.2.1 
Non-responder imputation ......................................................................... 45 
4.2.2.2 
MI – MCMC/Monotone Regression ......................................................... 45 
4.2.2.3 
MI – MCMC/Reference-based imputation ................................................ 51 
4.2.2.4 
Tipping Point analysis ............................................................................... 52 
4.2.2.5 
Treatment Policy Strategy ......................................................................... 54 
4.2.3 
Handling of missing data for AEs ....................................................................... 55 
4.2.4 
Handling of missing data for prior and concomitant medications ....................... 56 
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4.3 
Planned analyses and data monitoring ......................................................................... 58 
4.3.1 
Interim analyses & final analysis ......................................................................... 58 
4.3.2 
Data Monitoring Committee ................................................................................ 61 
4.4 
Multicenter studies ....................................................................................................... 61 
4.5 
Multiple comparisons/multiplicity ............................................................................... 61 
4.6 
Use of an efficacy subset of subjects ........................................................................... 62 
4.7 
Active-control studies intended to show equivalence .................................................. 62 
4.8 
Examination of subgroups ........................................................................................... 62 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 63 
5.1 
Subject disposition ....................................................................................................... 63 
5.2 
Impact of COVID-19 ................................................................................................... 64 
5.3 
Protocol deviations....................................................................................................... 65 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 65 
6.1 
Demographics .............................................................................................................. 65 
6.2 
Baseline characteristics ................................................................................................ 66 
6.2.1 
Baseline values for components of the primary efficacy variable ....................... 66 
6.2.2 
Other Baseline characteristics .............................................................................. 67 
6.2.3 
History of psoriatic arthritis ................................................................................. 67 
6.3 
Medical history and concomitant diseases ................................................................... 68 
6.4 
Prior and concomitant medications .............................................................................. 68 
6.5 
Prohibited medications and permitted rescue therapy after Week 16 .......................... 70 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 70 
8 
EFFICACY ANALYSES ................................................................................................ 71 
8.1 
Statistical analysis of the primary efficacy variable .................................................... 71 
8.1.1 
Derivation of ACR50 response ............................................................................ 71 
8.1.1.1 
Derivation of tender joint count (TJC) and swollen joint count (SJC)...... 72 
8.1.1.2 
Patient and physician reported clinical outcomes on psoriatic arthritis .... 74 
8.1.1.3 
Derivation of Health Assessment Questionnaire-Disability index (HAQ-
DI) score .................................................................................................... 74 
8.1.1.4 
High sensitivity C-reactive protein levels (hs-CRP) ................................. 76 
8.1.2 
Primary analysis of the primary efficacy variable ............................................... 76 
8.1.3 
Subgroup analyses of the primary efficacy variable ............................................ 77 
8.1.4 
Supportive analyses of the primary efficacy variable .......................................... 79 
8.1.4.1 
Analysis on the PPS .................................................................................. 79 
8.1.4.2 
Analysis on the FAS .................................................................................. 79 
8.1.4.3 
Analysis using a modified composite estimand where intercurrent events 
are defined as discontinuation due to AE or lack of efficacy .................... 79 
8.1.4.4 
Analysis of individual components of the ACR ........................................ 80 
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8.1.4.5 
Analyses using treatment policy strategy imputation for missing data ..... 81 
8.1.4.6 
Analysis on Observed cases ...................................................................... 81 
8.1.4.7 
Tipping point analysis ............................................................................... 82 
8.1.4.8 
Analyses including COVID-19 impact ..................................................... 82 
8.2 
Statistical analysis of secondary efficacy variables ..................................................... 82 
8.2.1 
Derivation of secondary efficacy variables ......................................................... 82 
8.2.1.1 
HAQ-DI: Change from Baseline at Week 16 ............................................ 82 
8.2.1.2 
Psoriasis Area Severity Index 90 (PASI90) at Week 16 (in subjects with 
PSO involving at least 3% of BSA at Baseline) ........................................ 83 
8.2.1.3 
SF-36 PCS: Change from Baseline at Week 16 ........................................ 84 
8.2.1.4 
MDA at Week 16 ...................................................................................... 85 
8.2.1.5 
Van der Heijde modified Total Sharp Score (vdHmTSS): Change from 
Baseline at Week 16 .................................................................................. 85 
8.2.1.6 
Enthesitis-free state at Week 16 in the subgroup of subjects with enthesitis 
at Baseline ................................................................................................. 89 
8.2.1.7 
Dactylitis-free state at Week 16 in the subgroup of subjects with dactylitis 
at Baseline ................................................................................................. 90 
8.2.1.8 
Psoriasis Area Severity index 90 (PASI90) at Week 4 (in subjects with 
PSO involving at least 3% of BSA at Baseline) ........................................ 91 
8.2.1.9 
ACR20 and ACR70 response at Week 16 ................................................. 91 
8.2.1.10 
Proportion of subjects with an Investigator Global Assessment (IGA) 
score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction 
from Baseline at Week 4 and Week 16 in the subset of subjects with 
psoriatic skin lesions at Baseline ............................................................... 92 
8.2.1.11 
Change from Baseline in the Patient’s Assessment of Arthritis Pain 
(PtAAP) at Week 16 .................................................................................. 92 
8.2.1.12 
Enthesitis-Free state based on Spondyloarthritis Research Consortium of 
Canada (SPARCC) index at Week 16 ....................................................... 93 
8.2.1.13 
Change from Baseline in PsAID-12 total score at Week 16 ..................... 93 
8.2.2 
Primary analysis of secondary efficacy variables ................................................ 93 
8.2.3 
Supportive analyses of the secondary efficacy variables..................................... 95 
8.3 
Statistical analysis of other efficacy variables ............................................................. 96 
8.3.1 
Derivation of other efficacy variables ................................................................. 96 
8.3.1.1 
Time to ACR20, ACR50, ACR70 response from Baseline ...................... 96 
8.3.1.2 
ACR20, ACR50 and ACR70 ..................................................................... 96 
8.3.1.3 
PASI75, PASI90 and PASI100 response (in subjects with PSO involving 
at least 3% of BSA at Baseline) ................................................................ 97 
8.3.1.4 
Composite endpoints composed of ACR50 and PASI90 and ACR50 and 
PASI100 responses (subjects with PSO involving at least 3% of BSA at 
Baseline) .................................................................................................... 97 
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8.3.1.5 
Proportion of Psoriatic Arthritis Response Criteria (PsARC) responders. 97 
8.3.1.6 
Psoriatic Arthritis Disease Activity Score (PASDAS) categories and 
change from baseline in PASDAS ............................................................ 98 
8.3.1.7 
ACR50 responders at Week 16 and maintaining response at post-Week 16 
visits up to Week 52 .................................................................................. 98 
8.3.1.8 
MDA response ........................................................................................... 98 
8.3.1.9 
Very Low disease activity (VLDA) response ........................................... 99 
8.3.1.10 
Proportion of Subjects with an IGA score of 0 (clear) or 1 (almost clear) 
AND at least a 2-grade reduction from Baseline in the subset of subjects 
with psoriatic skin lesions at Baseline ....................................................... 99 
8.3.1.11 
Disease Activity Index for Psoriatic Arthritis (DAPSA) score, state and 
change from Baseline in DAPSA score .................................................... 99 
8.3.1.12 
Change from Baseline in the Disease Activity Score-28 based on C-
reactive protein (DAS28[CRP]) .............................................................. 100 
8.3.1.13 
Change from Baseline in all individual ACR core components.............. 100 
8.3.1.14 
Change from Baseline in vdHmTSS total score and in erosion and joint 
space narrowing (sub-scores) .................................................................. 101 
8.3.1.15 
Percentage of subjects with no radiographic joint damage progression 
(Change from Baseline vdHmTSS of ≤0.5) ............................................ 101 
8.3.1.16 
Dactylitis-free state based on the LDI and change in LDI from Baseline in 
the subgroup of subjects with dactylitis at Baseline ................................ 101 
8.3.1.17 
Enthesitis-free state based on the LEI and change in LEI from Baseline in 
the subgroup of subjects with enthesitis at Baseline ............................... 101 
8.3.1.18 
Enthesitis-free state based on the SPARCC index and change in SPARCC 
from Baseline in the subgroup of subjects with enthesitis at Baseline ... 102 
8.3.1.19 
Proportion of subjects with a decrease of HAQ-DI from Baseline of at 
least 0.35 in the subgroup of subjects with Baseline HAQ-DI≥0.35 ...... 102 
8.3.1.20 
Change from Baseline in the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) in the subgroup of subjects with axial 
involvement defined by a score of ≥4 at Baseline ................................... 102 
8.3.1.21 
Change from Baseline in the modified Nail Psoriasis Severity Index 
(mNAPSI) score in the subgroup of subjects with psoriatic nail disease at 
Baseline ................................................................................................... 103 
8.3.1.22 
Change from Baseline in PsAID-12 total score ...................................... 103 
8.3.1.23 
Change from Baseline in the Psoriatic Arthritis Quality of Life (PsAQoL) 
total score ................................................................................................ 103 
8.3.1.24 
Change from Baseline in the SF-36 PCS and MCS scores, as well as the 8 
domain scores (Physical Functioning, Role Physical, Bodily Pain, General 
Health, Vitality, Social Functioning, Role Emotional, and Mental Health)104 
8.3.1.25 
Change from Baseline in Functional Assessment of Chronic Illness 
Therapy (FACIT)—Fatigue subscale score............................................. 104 
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8.3.1.26 
Change from Baseline in Work Productivity and Activity Impairment 
Questionnaire–Specific Health Problem (WPAI-SHP) v2.0 adapted to 
PsA scores ............................................................................................... 104 
8.3.1.27 
Responses to the EuroQol-5 Dimensions-3 Level (EQ-5D-3L), change 
from Baseline in VAS score .................................................................... 106 
8.3.1.28 
Change from Baseline in Patient’s Global Assessment of Arthritis (PGA-
arthritis) and Physician’s Global Assessment of Arthritis (PhGA-Arthritis)107 
8.3.2 
Analyses of other efficacy endpoints ................................................................. 107 
8.3.2.1 
Time to ACR20/50/70 response .............................................................. 107 
8.3.2.2 
Other endpoints (excluding time to ACR20/50/70 response) ................. 108 
8.3.2.3 
Additional statistical analysis for other efficacy endpoints ..................... 110 
9 
PHARMACOKINETICS AND IMMUNOLOGICAL (IMMUNOGENICITY) 
ANALYSES ................................................................................................................... 112 
9.1 
Pharmacokinetics ....................................................................................................... 112 
9.2 
Immunological (Immunogenicity) analyses .............................................................. 114 
9.2.1 
Anti-bimekizumab antibody .............................................................................. 114 
9.2.2 
Neutralizing anti-bimekizumab antibodies ........................................................ 120 
10 SAFETY ANALYSES ................................................................................................... 122 
10.1 
Extent of exposure ..................................................................................................... 122 
10.1.1 
Double-Blind Treatment Period ........................................................................ 123 
10.1.1.1 
Study medication duration (days) ............................................................ 123 
10.1.1.2 
Time at risk (days) ................................................................................... 123 
10.1.2 
Active Treatment-blind Period .......................................................................... 124 
10.1.2.1 
Study medication duration (days) ............................................................ 124 
10.1.2.2 
Time at risk (days) ................................................................................... 124 
10.1.3 
Double-blind and the Active Treatment-blind Periods (combined) .................. 124 
10.1.3.1 
Study medication duration (days) ............................................................ 124 
10.1.3.2 
Time at risk (days) ................................................................................... 125 
10.1.4 
Exposure and time at risk in subject-years ........................................................ 125 
10.1.5 
Time at risk in subject-years by COVID-19 pandemic period .......................... 126 
10.1.5.1 
Time at Risk in the pre-COVID-19 pandemic period ............................. 126 
10.1.5.2 
Time at Risk in the COVID-19 pandemic period .................................... 126 
10.1.5.3 
Time at Risk in the post-COVID-19 pandemic period ............................ 127 
10.2 
Adverse events ........................................................................................................... 127 
10.2.1 
Standard AE summaries .................................................................................... 128 
10.2.2 
Exposure duration of AEs .................................................................................. 130 
10.2.3 
Exposure adjusted incidence rate (EAIR) and exposed adjusted event rate 
(EAER) .............................................................................................................. 130 
10.2.4 
Other safety topics of interest ............................................................................ 131 
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10.2.4.1 
Infections (serious, opportunistic, fungal and TB) .................................. 131 
10.2.4.2 
Malignancies ........................................................................................... 132 
10.2.4.3 
Major adverse cardiac events (MACE) ................................................... 132 
10.2.4.4 
Neutropenia ............................................................................................. 133 
10.2.4.5 
Suicidal Ideation and Behavior Neuropsychiatric events ........................ 133 
10.2.4.6 
Inflammatory bowel disease .................................................................... 134 
10.2.4.7 
Hypersensitivity (including Anaphylaxis) ............................................... 135 
10.2.4.8 
Hepatic events and DILI .......................................................................... 135 
10.2.4.9 
Summary table and figure ....................................................................... 136 
10.2.5 
Special considerations for interim data snapshots ............................................. 137 
10.2.6 
COVID-19 impact ............................................................................................. 137 
10.3 
Clinical laboratory evaluations .................................................................................. 138 
10.4 
Vital signs, physical examination findings, and other observations related to safety 142 
10.4.1 
Vital signs and physical examination findings .................................................. 142 
10.4.2 
Electrocardiograms ............................................................................................ 143 
10.5 
Other safety variables ................................................................................................ 144 
10.5.1 
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) ....................... 144 
10.5.2 
Assessment of tuberculosis ................................................................................ 145 
10.5.3 
Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) ............ 145 
11 REFERENCES .............................................................................................................. 146 
12 APPENDICES ............................................................................................................... 147 
12.1 
Appendix 1: MedDRA algorithmic approach to anaphylaxis (MedDRA V19.0) ..... 147 
12.2 
Appendix 2: UCB-DEFINED SEARCH CRITERIA FOR IDENTIFYING 
OPPORTUNISTIC INFECTIONS ............................................................................ 150 
13 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) (IF 
APPLICABLE) .............................................................................................................. 151 
13.1 
AMENDMENT 1....................................................................................................... 151 
13.1.1 
Efficacy variables (Section 2.2.1) ...................................................................... 151 
13.1.2 
Immunological variables (Section 2.2.4) ........................................................... 152 
13.1.3 
Safety Variables (Section 2.2.5) ........................................................................ 152 
13.1.4 
Protocol deviation (Section 3.5) ........................................................................ 152 
13.1.5 
Analysis sets (Section 3.6) ................................................................................. 152 
13.1.6 
Strategy for handling missing data for efficacy analyses (Section 4.2.1) ......... 153 
13.1.7 
Data reported in interim analysis 1 (Section 4.3) .............................................. 153 
13.1.8 
Testing hierarchy (Section 4.5) .......................................................................... 154 
13.1.9 
Changes related to COVID-19 (Section 5.2) ..................................................... 154 
13.1.10 
Statistical analysis of the primary efficacy variables (Section 8.1) ................... 154 
13.1.11 
Statistical analysis of the secondary efficacy variables (Section 8.2) ............... 154 
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13.1.12 
Statistical analysis of the other efficacy variables (Section 8.3) ....................... 154 
13.1.13 
Extent of exposure (Section 10) ........................................................................ 155 
13.1.14 
Safety topic of interest (Section 10.2.4) ............................................................ 155 
13.2 
AMENDMENT 2....................................................................................................... 155 
13.3 
AMENDMENT 3....................................................................................................... 174 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................... 188 
 
 
 
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LIST OF TABLES 
Table 2‒1: 
Treatment effect elevated hs-CRP and/or bone erosion at Baseline for 
secondary efficacy analyses ............................................................................. 28 
Table 3‒1: 
List of decimals for continuous efficacy endpoints ......................................... 30 
Table 4‒1: 
List of non-composite continuous efficacy endpoints ..................................... 41 
Table 4‒2: 
Missing data handling approaches for efficacy endpoints ............................... 44 
Table 4‒3: 
Tipping point analysis: Delta parameter for each ACR component ................ 54 
Table 4‒4: 
Type of efficacy and safety tables provided for the interim analyses .............. 59 
Table 4‒5: 
Sequential testing procedure of primary/secondary efficacy endpoints 
(fixed sequence testing procedure) (All efficacy endpoints at Week 16) ........ 61 
Table 8‒1: 
Swelling and Tenderness grading .................................................................... 73 
Table 8‒2: 
Aid and device associated with HAQ-DI category .......................................... 75 
Table 8‒3: 
Normative values for LDI ................................................................................ 90 
Table 8‒4: 
Five-point IGA ................................................................................................. 92 
Table 10‒1: 
Type of Extended MACE events ................................................................... 132 
Table 10‒2: 
Laboratory measurements .............................................................................. 138 
Table 10‒3: 
Definitions of markedly abnormal biochemistry values ................................ 139 
Table 10‒4: 
Definitions of markedly abnormal hematology values .................................. 140 
Table 10‒5: 
Definitions of markedly abnormal liver enzyme elevation values ................ 140 
Table 10‒6: 
Definitions of markedly abnormal blood pressure values ............................. 142 
 
LIST OF FIGURES 
Figure 2‒1: 
Study schematic diagram ................................................................................. 24 
 
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LIST OF ABBREVIATIONS 
ACR 
American College of Rheumatology 
ACR20,50,70 
American College of Rheumatology 20, 50, 70% response criteria 
ADA 
adalimumab 
ADAb 
antidrug antibody 
ADR 
adverse drug reaction 
AE 
adverse event  
AMP 
Active Medication Periods 
AMS 
Active Medication Set 
ANCOVA 
analysis of covariance  
ATC 
anatomic therapeutic class 
ATP 
Active Treatment-Blind Period 
ATS 
Active Treatment-Blind Set 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
bDMARD 
biologic disease modifying antirheumatic drug 
BKZ 
bimekizumab 
BLQ 
below the limit of quantification  
BMI 
body mass index 
BP 
blood pressure 
BSA 
body surface area 
CASPAR 
Classification Criteria for Psoriatic Arthritis  
CCP 
cyclic citrullinated peptide 
cDMARD 
conventional disease modifying antirheumatic drug 
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CI 
confidence interval 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRP 
C-reactive protein 
CV 
coefficient of variation 
DAPSA 
Disease Activity Index for Psoriatic Arthritis  
DAS28[CRP] 
Disease Activity Score-28 based on C-reactive protein 
DBP 
Double-Blind Treatment Period 
DILI 
drug-induced liver injury 
DMARDs 
disease modifying antirheumatic drugs 
DMC 
data monitoring committee 
eC-SSRS 
electronic Columbia Suicide Severity Rating Scale 
ECG 
electrocardiogram 
EQ-5D-3L 
Euro-Quality of Life 5-Dimensions 3 Level version 
ES 
erosion score 
ET 
Early Termination 
EAER 
exposure adjusted event rate 
EAIR 
exposure adjusted incidence rate 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
Full Analysis Set 
FDA  
Food and Drug Administration 
HAQ-DI 
Health Assessment Questionnaire - Disability Index  
HLA-B27 
human leukocyte antigen B27 
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HLT 
high level term 
hs-CRP 
high sensitivity C-reactive protein 
ICH 
International Council for Harmonisation  
IE 
intercurrent event 
IGA 
Investigator’s Global Assessment 
IMP 
investigational medicinal product 
IPD 
important protocol deviation 
IWRS 
interactive web response system 
JSN 
joint space narrowing 
KM 
Kaplan-Meier 
LCL 
lower confidence limit 
LDI 
Leeds Dactylitis Index 
LEI 
Leeds Enthesitis Index 
LLOQ 
lower limit of quantification 
LLT 
lowest level term 
LN 
natural logarithm 
LSM 
least square means 
MACE 
major adverse cardiac events 
MAR 
missing at random 
MCMC 
Markov-Chain Monte Carlo 
MCS 
Mental Component Summary 
MDA 
Minimal Disease Activity 
MedDRA 
Medical Dictionary for Regulatory Activities  
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MI 
multiple imputation 
mNAPSI 
modified Nail Psoriasis Severity Index 
NAb 
neutralizing anti-bimekizumab antibodies 
NRI 
non-responder imputation 
NSAID 
nonsteroidal anti-inflammatory drug 
OC 
observed case 
OLE 
open label extension 
OR 
odds-ratio 
PASDAS 
Psoriatic Arthritis Disease Activity Score 
PASI 
Psoriasis Area and Severity Index  
PASI75, PASI90, 
PASI100 
Psoriasis Area and Severity Index 75%, 90%, 100% 
PASS 
Patient acceptable symptom state 
PCS 
Physical Component Summary  
PD 
Protocol Deviation 
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  
PK-PPS 
Pharmacokinetics Per-Protocol Set 
PPS 
Per-Protocol Set 
PsA  
psoriatic arthritis 
PsAID-12 
Psoriatic Arthritis Impact of Disease-12 
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PsAQoL 
Psoriatic Arthritis Quality of Life  
PsARC 
Psoriatic Arthritis Response Criteria 
PSO 
psoriasis 
PT 
preferred term 
PtAAP 
Patient’s Assessment of Arthritis Pain 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
RAS 
Radiographic Set 
RS 
Randomized Set 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly)  
SD 
standard deviation 
SFU 
Safety Follow-up 
SJC 
swollen joint count 
SF-36 
Short-Form 36-item Health Survey  
SMQ 
standardized MedDRA query 
SOC 
system organ class 
SPARCC 
Spondyloarthritis Research Consortium of Canada 
SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
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TFLs 
tables, figures, and listings 
TJC 
tender joint count 
TNF 
tumor necrosis factor 
TNFα 
tumor necrosis factor alpha 
UCL 
upper confidence limit 
ULN 
upper limit of normal  
VAS 
Visual Analog Scale 
vdHmTSS 
van der Heijde modified Total Sharp Score 
VLDA 
Very Low Disease Activity 
WHO-DD 
World Health Organization drug dictionary 
WPAI-SHP 
Work Productivity and Activity Impairment Questionnaire – 
Specific Health Problem  
 
 
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1 
INTRODUCTION 
This statistical analysis plan (SAP) provides the necessary information to perform the interim 
(Week 24 and Week 52 analyses) and the final statistical analyses for study PA0010. It also 
defines the summary tables, figures, and listings (TFLs) to be generated for the Clinical Study 
Report. 
The SAP is based on Protocol amendment 2 (22 February 2021). All references to study protocol 
hereafter refer to this version of the protocol, and unless otherwise specified, the study will be 
analyzed as described in this version of the protocol. If a future protocol amendment necessitates 
a substantial change to the statistical analysis of the study data, or if analysis definitions must be 
modified or updated, this SAP will be amended accordingly.  
The content of this SAP is compatible with the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH)/Food and Drug 
Administration (FDA) E9 Guidance documents (ICH E9, 1998). 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective is to demonstrate the clinical efficacy of bimekizumab (BKZ) 
administered subcutaneously (sc) every 4 weeks (Q4W) for 16 weeks compared with placebo in 
the treatment of subjects with active psoriatic arthritis (PsA), as assessed by the American 
College of Rheumatology 50% response criteria (ACR50). 
2.1.2 
Secondary objectives 
The secondary objectives are as follows: 
• To assess the efficacy of BKZ compared with placebo  
• To assess the safety and tolerability of BKZ 
• To assess the impact of BKZ on patient-reported quality of life 
• To assess the impact of BKZ on skin psoriasis (PSO) in the subgroup of affected subjects at 
Baseline 
• To assess the impact of BKZ on functional improvement  
• To assess the impact of BKZ on radiographic changes in the hands and feet 
• To assess the impact of BKZ on extra-articular disease manifestations (dactylitis, enthesitis). 
2.1.3 
Other objectives 
Other objectives are as follows: 
• To descriptively assess the efficacy of BKZ with reference to adalimumab (ADA)  
• To assess the immunogenicity of BKZ  
• To assess the impact of BKZ treatment on axial disease 
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• To assess the maintenance of treatment effect 
• To assess nail PSO in the subgroup of affected subjects at Baseline 
• To explore the exposure response relationship of BKZ  
• To assess the effect of BKZ on gene and protein expression, and explore the relationship 
between genomic, genetic, and proteomic biomarkers and disease biology, drug treatment 
and inflammatory and immune responses (from consenting subjects who agree to participate 
in the biomarker substudy) 
• To assess the impact of BKZ on social life and work productivity. 
2.2 
Study variables 
2.2.1 
Efficacy variables 
2.2.1.1 
Primary efficacy variable 
The primary efficacy variable is the ACR50 response at Week 16. 
2.2.1.2 
Secondary efficacy variables 
The secondary efficacy variables are as follows: 
• Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at 
Week 16 
• Reduction of 90% from Baseline in Psoriasis Area and Severity index (PASI90 response) at 
Week 4 and Week 16 in the subgroup of subjects with PSO involving at least 3% of Body 
Surface Area (BSA) at Baseline 
• Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical 
Component Summary (PCS) at Week 16 
• Minimal Disease Activity (MDA) response at Week 16 
• Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) at Week 
16 on subjects with elevated high sensitivity C-reactive protein (hs-CRP) and/or at least 1 
bone erosion at Baseline  
• Enthesitis-free state based on the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of 
subjects with enthesitis at Baseline in the pooled population of PA0010 and PA0011 
• Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of 
subjects with dactylitis at Baseline in the pooled population of PA0010 and PA0011 
• Change from Baseline in vdHmTSS at Week 16 
• ACR20 response at Week 16 
• ACR70 response at Week 16 
• Proportion of subjects with an Investigator Global Assessment (IGA) score of 0 (clear) or 1 
(almost clear) and at least a 2-grade reduction from Baseline at Week 4 and Week 16 in the 
subset of subjects with psoriatic skin lesions at Baseline  
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• Change from Baseline in the Patient’s Assessment of Arthritis Pain (PtAAP) at Week 16 
• Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada 
(SPARCC) index at Week 16 in the subgroup of subjects with enthesitis at Baseline 
• Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at 
Week 16. 
2.2.1.3 
Other efficacy variables 
Change from Baseline variables evaluated during the Double-Blind Treatment Period (DBP) are 
relative to the Baseline (first dose) visit. For subjects randomized to placebo who switch to BKZ 
160mg Q4W at the Week 16 visit, change from Baseline variables during the Active Treatment-
Blind Period (ATP) may be evaluated relative to both the Baseline (first dose) visit and to the 
Week 16 visit (first dose of BKZ). 
For simplicity, “change from Baseline” is used below for all such variables. More details will be 
provided below in Section 3.3.   
The other efficacy variables listed below will be summarized for all timepoints except for the 
previously defined primary and secondary efficacy variables which will be also summarized 
separately at Week 16 (and at Week 4 and 16 for PASI90). 
The following other efficacy variables will be assessed (all timepoints not specified in 
Section 2.2.1.1 and 2.2.1.2 are exploratory): 
• Time to ACR20, ACR50, and ACR70 response from Baseline (Day 1)  
• ACR20, ACR50, and ACR70 response 
• PASI75, PASI90, and PASI100 response in the subgroup of subjects with PSO involving at 
least 3% BSA at Baseline 
• Composite endpoint composed of ACR50 and PASI90 in subjects with PSO involving at 
least 3% BSA at Baseline 
• Composite endpoint composed of ACR50 and PASI100 in subjects with PSO involving at 
least 3% BSA at Baseline 
• Proportion of Psoriatic Arthritis Response Criteria (PsARC) responders  
• Psoriatic Arthritis Disease Activity Score (PASDAS) categories  
• Change from Baseline in the PASDAS 
• Proportion of ACR50 responders at Week 16 and maintaining response at Week 52 
• MDA response 
• Very Low Disease Activity (VLDA) response 
• Proportion of subjects with an IGA score of 0 (clear) or 1 (almost clear) and at least a 2-grade 
reduction from Baseline in the subset of subjects with psoriatic skin lesions at Baseline 
• Disease Activity Index for Psoriatic Arthritis (DAPSA) score categories 
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• Change from Baseline in DAPSA score 
• Change from Baseline in the Disease Activity Score-28 based on C-reactive protein 
(DAS28[CRP]) 
• Change from Baseline in all individual ACR core components: 
− Swollen Joint Count (SJC) 
− Tender Joint Count (TJC) 
− HAQ-DI  
− PtAAP  
− Physician’s Global Assessment of Psoriatic Arthritis (PhGA-PsA)  
− Patient’s Global Assessment of Psoriatic Arthritis (PGA-PsA) 
− hs-CRP  
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores) in subjects with elevated hs-CRP and/or with at least 1 bone erosion at Baseline 
• Change from Baseline in vdHmTSS total score and in erosion and joint space narrowing 
(subscores) in the overall population 
• Proportion of subjects with no radiographic joint damage progression (change from Baseline 
vdHmTSS of ≤0.5)   
• Dactylitis-free state based on the LDI in the subgroup of subjects with dactylitis at Baseline 
in the pooled population of PA0010 and PA0011, as well as for PA0010 alone  
• Enthesitis-free state based on the LEI in the subgroup of subjects with enthesitis at Baseline 
in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Enthesitis-free state based on the SPARCC index in the subgroup of subjects with enthesitis 
at Baseline in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Proportion of subjects with a decrease of HAQ-DI from Baseline of at least 0.35 in the 
subgroup of subjects with Baseline HAQ-DI≥0.35  
• Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
in the subgroup of subjects with axial involvement defined by a score of ≥4 at Baseline 
• Change from Baseline in the modified Nail Psoriasis Severity Index (mNAPSI) score in the 
subgroup of subjects with psoriatic nail disease at Baseline (mNAPSI score>0) 
• Change from Baseline in the LEI in the subgroup of subjects with enthesitis at Baseline in the 
pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Change from Baseline in the SPARCC index in the subgroup of subjects with enthesitis at 
Baseline in the pooled population of PA0010 and PA0011, as well as for PA0010 alone 
• Change from Baseline in the LDI in the subgroup of subjects with dactylitis at Baseline in the 
pooled population of PA0010 and PA0011, as well as for PA0010 alone 
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• Change from Baseline in PsAID-12 total score, as well as the individual domain scores 
• Proportion of subjects achieving PsAID-12 total score ≤4 
• Proportion of PsAID-12 responders (decrease from Baseline in PsAID-12 total score ≥3) in 
subjects with PsAID-12 total score>3 at Baseline   
• Change from Baseline in the Psoriatic Arthritis Quality of Life (PsAQoL) total score 
• Change from Baseline in the SF-36 PCS and Mental Component Summary (MCS), as well as 
the 8 domain scores (Physical Functioning, Role Physical, Bodily Pain, General Health, 
Vitality, Social Functioning, Role Emotional, and Mental Health) 
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-Fatigue) subscale score 
• Proportion of FACIT-Fatigue subscale responders (subjects with a minimum clinically 
important difference for FACIT-Fatigue subscale score, defined as an increase of ≥4) in 
subjects with FACIT-Fatigue subscale score ≤48 at Baseline 
• Change from Baseline in Work Productivity and Activity Impairment Questionnaire-Specific 
Health Problem (WPAI-SHP) v2.0 adapted to PsA scores  
• Responses to the EuroQol-5 Dimensions-3 Level (EQ-5D-3L)  
• Change from Baseline in EQ-5D-3L Visual Analog Scale (VAS) scores 
• Change from Baseline in Physician’s Global Assessment of Arthritis (PhGA-Arthritis)  
• Change from Baseline in Patient’s Global Assessment of Arthritis (PGA-Arthritis).  
2.2.2 
Pharmacokinetic variable 
The pharmacokinetic (PK) variable is the plasma concentration of BKZ. Subjects are asked to 
provide blood samples for these measurements at Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24, 36, 
52, end of treatment and SFU visit. 
2.2.3 
Pharmacogenomic variables 
Genomic, genetic, epigenetic, proteins, and metabolite biomarkers may be measured to evaluate 
the relationship with response to treatment with BKZ, psoriatic arthritis disease biology, and 
inflammatory and immune response processes. The nature and format of these tentative substudy 
analyses will be determined when the results of the main study are made available. 
The candidate exploratory variables are the blood or blood derivative (eg, serum), concentrations 
of cytokines and chemokines of relevance to IL-17A/F signaling pathway and psoriatic arthritis 
biology. Additional variables may include but will not be limited to serum complement 
concentrations. Where local regulations permit, additional blood samples will be collected at 
Baseline and at Week 16. They may be used to allow for potential exploratory analyses of 
ribonucleic acid, proteins, lipids, and metabolite biomarkers relevant to disease biology and 
progression, response to therapy, the inflammatory and immune response processes, and 
cardiovascular risk in PsA. 
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A specific SAP will be written to describe the analysis methods for those variables. The nature 
and format of these analyses will be determined later.   
2.2.4 
Immunological variables 
The immunological variables allow evaluation of immunogenicity as following: 
• The anti-bimekizumab antibody status  
• The treatment-emergent antibody status derived from antidrug antibody (ADAb) assays  
• The neutralizing antidrug antibody (NAb) status. 
These 3 variables will be assessed at Baseline, Week 4, 8, 12, 16, 20, 24, 36, 52, end of treatment 
and at SFU visit. 
2.2.5 
Safety variables 
2.2.5.1 
Secondary safety variables 
Main safety variables to be assessed are as follows: 
• Incidence of treatment-emergent adverse events (TEAEs) 
• Incidence of treatment-emergent serious adverse events (TESAEs) 
• TEAEs leading to withdrawal from investigational medicinal product (IMP). 
2.2.5.2 
Other safety variables 
Other safety variables to be assessed are: 
• Change from Baseline in vital signs (blood pressure [BP], temperature and pulse rate) 
• Standard 12-lead electrocardiogram (ECG) results 
• Change from Baseline in clinical laboratory values (hematology, biochemistry, and 
urinalysis) 
• Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9). 
Physical examination findings considered clinically significant changes since the physical 
examination at the Screening visit will be recorded as AEs. 
2.3 
Study design and conduct 
2.3.1 
Study description 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, noninferential 
active reference study to evaluate the efficacy and safety of BKZ in subjects with active PsA 
who are biologic disease-modifying antirheumatic drug (bDMARD) naive. To be eligible to 
participate in this study, subjects must be adults with a diagnosis of active PsA based on the 
Classification Criteria for Psoriatic Arthritis (CASPAR) and have disease with TJC ≥3 and SJC 
≥3. In addition, subjects should not have been previously exposed to any bDMARD for PsA or 
PSO to be eligible for the study.  
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Approximately 840 subjects will be randomly assigned in a 3:2:1 ratio, stratified by region 
(North America, Western Europe, Eastern Europe, and Asia/Australia) and bone erosion (0, ≥1) 
to 1 of the 3 following blinded treatment groups:  
• Bimekizumab 160mg sc Q4W (420 subjects),  
• Placebo (280 subjects),  
• Adalimumab sc 40mg every 2 weeks (Q2W) (140 subjects).  
It is planned to enroll a minimum of 45% of subjects who have elevated hs-CRP (≥6mg/L) 
and/or who have at least 1 bone erosion at Screening. 
The overall study design consists of: 
• a Screening Period (≥14 days to ≤35 days)  
• a 16-week placebo controlled Double-Blind Treatment Period (DBP)  
• a 36-week Active Treatment-Blind Period (ATP) (Week 16 to week 52)  
• a Safety Follow Up (SFU) visit, 20 weeks after the final dose of IMP (for subjects not 
entering the open label extension (OLE) study or who discontinue early, including those 
withdrawn from IMP, as applicable).  
The maximum study duration per subject will be up to 73 weeks.   
The study schematic diagram for the study is presented in .  
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Figure 2‒1: Study schematic diagram 
 
ACR50=American College of Rheumatology 50% response criteria, BKZ=bimekizumab, PsA=psoriatic arthritis; 
Q2W=every 2 weeks, Q4W=every 4 weeks, sc=subcutaneous, SFU=Safety Follow-Up, W=week 
a Adalimumab dosing is performed every 2 weeks from Baseline to Week 50.  
b After 16 weeks of double-blind treatment, subjects will enter the Active Treatment-Blind Period. All subjects 
randomized to placebo will be reallocated to receive BKZ 160mg Q4W. Subjects randomized to BKZ 160mg 
Q4W will continue to receive their originally randomized dose. Subjects randomized to active reference (ADA) 
will continue with their active treatment.  
c Permitted rescue therapy is defined in Protocol Section 5.4. 
2.3.2 
Study Periods 
2.3.2.1 
Screening Period 
Subjects will enter a Screening Period (starting with a Screening visit  - Visit 1) that will last for 
a minimum duration of 14 days and a maximum duration of 35 days and will involve obtaining 
laboratory data and verifying that the doses of nonsteroidal anti-inflammatory drugs (NSAIDs), 
or permitted DMARDs, if used to treat PsA, are stable. The Screening Period will also enable 
washout of any medications not permitted for use during the study.  
During the Screening Period, X-rays of hands and feet will be assessed for bone erosion and used 
for the stratification of subjects at Baseline (Day 1). 
This period starts at time of the informed consent date (Screening visit -Visit 1) and ends the day 
prior to the day of the first dose of study drug (Baseline visit – Visit 2).  
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2.3.2.2 
Double-Blind Treatment Period 
After the Screening Period, subjects will attend a Baseline visit (Visit 2, Day 1). 
At the end of the Baseline visit, subjects will be randomized according to a 3:2:1 ratio (stratified 
by region and bone erosion [0, ≥1] at Screening) to receive 1 of the 3 following blinded 
treatments during the 16 weeks of the DBP: 
• Bimekizumab 160mg sc Q4W 
• Placebo 
• Adalimumab 40mg sc Q2W. 
The first administration of IMP will be delivered at the Baseline visit (Visit 2, Day 1). 
During the 16 weeks of the DBP, IMP administration will be performed by unblinded study 
personnel every 2 weeks (allowed visit window between 12 to 16 days) from Day 1 through 
Week 16 (Visits 2 to 10).  
For the BKZ group, active treatment will be administered every 4 weeks and placebo in between, 
to maintain the blind and still have an injection every 2 weeks. 
Visit 10 (Week 16) ends the DBP, and the last assessments for that period are collected during 
that visit. 
This period starts on the day of first dose administration of study drug (Visit 2) and ends at Week 
16 (Visit 10) or at the Early Termination visit (ET Visit) for subjects withdrawn from the study 
before Week 16. This period should last 16 weeks maximum.  
2.3.2.3 
Active Treatment-Blind Period  
After the 16-week DBP, subjects will enter the 36-week ATP. At Week 16 (Visit 10), subjects 
will be allocated to treatment regimens as follows:  
• Subjects in the BKZ 160mg sc Q4W group will continue to receive BKZ 160mg sc Q4W 
• Subjects in the placebo group will be reallocated to BKZ 160mg sc Q4WSubjects in the 
ADA 40mg sc Q2W group will continue to receive ADA 40mg sc Q2W.  
As for the DBP, BKZ and ADA will be administered sc by unblinded study personnel at the 
clinical site. The first dose in the ATP will be administered at Week 16 after all assessments have 
been completed.  
During the 36 weeks of the ATP, IMP administration will be performed every 2 weeks (allowed 
visit window between 11 and 17 days) at Study visits (from Visit 10 – Week 16 through Visit 27 
- Week 50). 
Visit 28 (Week 52) ends the ATP, and the last assessments for that period are collected during 
that visit. 
Subjects who withdraw early from the study will undergo the ET visit assessments and will enter 
the SFU Period, as applicable. Subjects who withdraw from IMP during the ATP will be 
encouraged to return for all remaining scheduled visits up to Week 52 and the SFU visit (20 
weeks after their final dose of IMP). 
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At the completion of the ATP, investigators should discuss treatment options with the subject. 
Subjects who complete PA0010 (ie who performed all visits up to Week 52 and not having 
permanently discontinued IMP and who did not meet any of the withdrawal criteria) will be 
given the opportunity to enter the OLE study at Week 52.  
The ATP starts on the day of dose administration at Week 16 and ends at Week 52 (Visit 28) or 
at the Early Termination visit (ET Visit) for subjects withdrawn from the study after Week 16 
and before Week 52. This period should last 36 weeks maximum.  
2.3.2.4 
Safety Follow-up 
All subjects who complete the study and do not enter the OLE study, or who discontinue early, 
including those withdrawn from IMP, will have a SFU visit 20 weeks after their final dose of 
IMP, as applicable. 
2.4 
Determination of sample size 
2.4.1 
Power calculations for the primary endpoint 
The sample size assumptions for BKZ versus placebo are based on the ACR50 response data 
from the Phase 2b BKZ study in subjects with moderate-to-severe PsA (PA0008). The median 
ACR50 responses of the top 3 dose groups (BKZ 160mg, 320mg, and 320mg [initial dose] plus 
160mg) at Week 12 in the Tumor necrosis factor-naïve (TNF-naïve) population are 
conservatively assumed for the Week 16 endpoint. The observed median ACR50 response rate of 
the top 3 BKZ doses in the TNF-naïve population in study PA0008 was 43.8%.  
The placebo ACR50 response at Week 16 is based on the TNFα-naïve population in PA0008 
(6.1% at Week 12, subjects with available measurement (n)=33); Mease et al, 2015), FUTURE 2 
study in the subgroup of TNFα-naïve subjects (15.9%, n=63; McInnes et al, 2015), FUTURE 3 
study (11.8%, n=93; Nash and Mease, 2018), and FUTURE 5 study in a mixed tumor necrosis 
factor alpha (TNFα) exposure population (8.1% at Week 16, n=332; Mease et al, 2018). 
Therefore, the estimated ACR50 response at Week 16 in the placebo group is assumed to be 
16%. 
The sample size for showing statistical superiority of BKZ vs placebo was calculated using a 
2-sided 2-sample Chi-square test with continuity correction (Fleiss et al, 1980). Assuming 420 
subjects in the BKZ group and 280 subjects in the placebo group, the test for detecting statistical 
superiority of BKZ 160mg Q4W vs placebo based on ACR50 response at Week 16 has >99% 
power to detect a true treatment difference of 27.8% (odds ratio (OR) 4.09).  
2.4.2 
Power calculations for secondary endpoints 
The assumptions for power calculations of the secondary endpoints included in the hierarchy, 
and for which supporting data exists, are based on the interim results of the Phase 2b BKZ study 
PA0008 and the FUTURE 1, FUTURE 2, FUTURE 5, and SPIRIT P1 studies. All power 
calculations for binary endpoints were performed using a 2-sided 2-sample Chi-square test with 
continuity correction (Fleiss et al, 1980). All power calculations for continuous endpoints were 
performed using a 2-sided 2-group Satterthwaite t-test (Moser et al, 1989). 
For the PASI90 response at Week 16, the BKZ 160mg Q4W treatment response at Week 12 is 
45% (n=20) in the TNFα-naïve population of PA0008 at Week 12 and 46% (n=28) at Week 12 
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in the mixed TNFα exposure population. The placebo PASI90 response at Week 16 is based on 
the subgroup analyses of TNFα therapy-naïve subjects in PA0008 (9.1% at Week 12; n=22), 
FUTURE 2 study (9.7% at Week 24; n=63), and SPIRIT P1 study (1.5% at Week 12; n=67). 
Therefore, a placebo PASI90 response rate of 10% is assumed. With those assumptions, the 
study has >99% power to detect a true treatment difference at an assumed 60% of subjects with 
BSA ≥3% of the planned sample size. 
For change from Baseline in HAQ-DI at Week 16, the between treatment differences of the 
change from Baseline in HAQ-DI of in the mixed TNFα exposure population of the PA0008 at 
Week 12 were used. The BKZ 160mg Q4W treatment group mean change from Baseline in 
HAQ-DI at Week 12 of -0.37, Standard deviation (SD)=0.47 (n=41) versus placebo mean change 
from Baseline in HAQ-DI at Week 12 of -0.13, SD=0.50 (n=42). With those assumptions, the 
study has >99% power to detect a true treatment difference of -0.24 at the planned sample size. 
For change from Baseline in PCS of SF-36 at Week 16, the between treatment differences of the 
change from Baseline in PCS of SF-36 of the TNFα-naïve population of FUTURE 2 study 
(Kavanaugh et al, 2016) at Week 24 were used. The BKZ 160mg Q4W treatment group assumes 
the secukinumab 150mg treatment group mean change from Baseline in SF-36 PCS at Week 24 
of 7.91, SD 7.38 (n=63) versus placebo mean change from Baseline in SF-36 PCS at Week 24 of 
2.08, SD 9.51 (n=63). With those assumptions, the study has >99% power to detect a true 
treatment difference of 5.83 at the planned sample size. 
For MDA at Week 16, the BKZ 160mg Q4W treatment response at Week 12 in PA0008 is 
46.3% (N=41) in the mixed TNFα exposure population of PA0008. In the placebo group, 14.3% 
of subjects achieved MDA at Week 12 (n=42). With those assumptions, the study has >99% 
power to detect a true treatment difference of 32% (OR=5.17) at the planned sample size. 
For change from Baseline in vdHmTSS at Week 16, the between treatment differences of the 
change from Baseline in vdHmTSS at Week 16 of the SPIRIT P1 study in a TNFα-naive 
population (Mease et al, 2017) were used. The SPIRIT P1 study ixekizumab 80mg sc Q2W 
treatment group least square mean (LSM) change from Baseline at Week 16 0.06 and SD 0.720; 
and LSM change from Baseline 0.36 and SD 0.710 for placebo are assumed. With those 
assumptions, the study has a 95% power to detect a true treatment difference of -0.30, assuming 
45% of subjects with elevated hs-CRP and/or bone erosion, in the planned sample size. 
There is uncertainty in the final percentage of subjects with elevated hs-CRP and/or bone erosion 
at Baseline that will be recruited to the study and the variability in the subgroup. To demonstrate 
the sensitivity of the sample size calculation for this study, Table 2‒1 shows the power function 
for a fixed total sample size of 840 subjects in the Randomized Set (RS) population for this 
secondary efficacy analysis, varying the percentage of subjects with elevated hs-CRP and/or 
bone erosion at Baseline and the treatment difference and estimated standard deviation on the 
change from Baseline in vdHmTSS at Week 16. 
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Table 2‒1: 
Treatment effect elevated hs-CRP and/or bone erosion at Baseline 
for secondary efficacy analyses 
Subjects with elevated hs-CRP 
and/or bone erosion at 
Baseline 
Treatment difference/standard deviation 
 
Treatment effect = -0.3  
SD = 0.72 vs. 0.71 
Treatment effect = -0.35  
SD = 0.81 vs. 0.93 
20% 
67 
62 
25% 
76 
72 
30% 
84 
79 
35% 
89 
85 
40% 
92 
89 
45% 
95 
92 
50% 
96 
95 
hs-CRP=high-sensitivity C-reactive protein ; SD=standard deviation 
For dactylitis-free state at Week 16, dactylitis resolution data of the FUTURE 5 study (Mease et 
al, 2018) at Week 16 were used to estimate the BKZ 160mg Q4W treatment and placebo groups. 
The treatment effect estimate from the secukinumab 150mg treatment group at Week 16 of 56% 
(n=103) is assumed versus a placebo group estimate of 32% (n=124). With those assumptions 
and having 11% of subjects with Baseline dactylitis, the pooled PA0010/PA0011 studies have a 
66% power to detect a true treatment difference of 24% (OR= 2.71). 
For enthesis-free state at Week 16, enthesis resolution data from the FUTURE 5 study at Week 
16 were used to estimate the BKZ 160mg Q4W treatment and placebo groups. In FUTURE 5 
The treatment effect estimate from the secukinumab 150mg treatment group at Week 16 was 
55% (n=141) and the placebo group estimate was 36% (n=192). Assuming a BKZ response of 
55% and a placebo rate of 39% and having 25% of subjects with Baseline enthesis the pooled 
PA0010/PA0011 the studies have a 69% power to detect a true treatment difference of 16% 
(odds ratio 1.91). Treatment difference in change from Baseline in vdHmTSS at Week 16 in the 
overall population is estimated using the data from the FUTURE 5 study in a mixed TNFα 
exposure population. The BKZ 160mg Q4W group treatment difference compared to placebo is 
estimated to be the same as the difference in change from Baseline in vdHmTSS at Week 16 
between the secukinumab 150mg group and placebo which is 0.42, assuming a SD of 1.13 for 
BKZ and SD=2.44 for placebo. With these assumptions the study has 76% power to detect a 
treatment difference of 0.42 in the planned sample size. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of TFLs and statistical outputs will be performed using SAS® 
Version 9.3 or higher unless otherwise specified. All tables and listings will use Courier New 
font size 9. 
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Descriptive statistics will be displayed to provide an overview of the study results.  
For categorical parameters, the number and percentage of subjects in each category will be 
presented. Unless otherwise noted, the denominator for percentages will be based on the number 
of subjects included in the respective analysis set. Subjects with missing data can generally be 
accounted for using one of the 2 following approaches:  
• Percentages will be summarized based on all subjects in the analysis set and a “Missing” 
category (corresponding to subjects with missing data for the variable being summarized) 
will be included as the last row in the list of categories being summarized. This approach will 
be used when reporting demography, Baseline characteristics, some NAb tables and some 
shift tables from Baseline for laboratory data. 
• Percentages will be 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 noted, all percentages will be displayed to 1 decimal place. No percentage will 
be displayed for zero counts, and no decimal will be presented when the percentage is 100%.  
For continuous parameters, descriptive statistics will include number of subjects with available 
measurements (n), arithmetic mean, standard deviation (SD), median, minimum, and maximum 
(unless otherwise stated).  
For hs-CRP variable, the summary statistics should contain arithmetic mean, geometric mean, 
geometric coefficient of variation (CV), median, first and third quartile (Q1 and Q3), minimum 
and maximum (for the value and the ratio to Baseline). The geometric CV (%) will be calculated 
using the following formula: 
𝐶𝑉= √𝑒𝑆𝐷𝑙𝑛
2 −1 
Where 𝑆𝐷𝑙𝑛 represents the SD of the ln-transformed hs-CRP value. 
For BKZ PK concentrations, geometric mean, geometric CV, 95% confidence intervals (CIs) for 
geometric mean (assuming log-normally distributed data) will be calculated if at least ⅔ of the 
values of interest are above the lower limit of quantification (LLOQ). If this is not the case, only 
median, minimum, and maximum will be presented.  
Decimal places for descriptive statistics will always apply the following rules: 
• “n” will be an integer 
• Mean, SD, SE, and median (Q1 and Q3 when applicable) will use 1 additional decimal place 
compared to the original data (for a derived score, number of decimals of the original data 
considered is the one obtained where deriving the score in the absence of missing data) 
• CV (%) will be presented with 1 decimal place 
• Minimum and maximum will have the same number of decimal places as the original value. 
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If the number of decimal places reported in the original data is varied then either the maximum 
raw number of reported decimal places or 3 will be used, whichever is the lowest, as a guide for 
the descriptive statistics. 
The table below provides the number of decimals to be reported for each continuous efficacy 
endpoint: 
Table 3‒1: 
List of decimals for continuous efficacy endpoints 
Continuous efficacy endpoint 
Decimal place used for 
minimum and maximum 
Decimal places used for Mean, 
SD (or SE) and median 
BASDAI 
1 
2 
DAPSA  
1 
2 
DAS28[CRP]  
2 
3 
EQ-5D-3L dimension scores  
0 
1 
EQ-5D-3L (VAS)  
0 
1 
FACIT-Fatigue subscale score  
1 
2 
HAQ-DI  
3 
4 
hs-CRP  
2 
3 
LDI  
1 
2 
LEI  
1 
2 
mNAPSI  
0 
1 
PASDAS  
1 
2 
PASI  
1 
2 
PGA-Arthritis /PhGA-Arthritis  
0 
1 
PGA-PsA / PhGA-PsA  
0 
1 
PsAID-12  
1 
2 
PsAQoL  
1 
2 
PsARC  
1 
2 
PtAAP  
0 
1 
SF-36  
2 
3 
SPARCC  
1 
2 
TJC / SJC  
1 
2 
vdHmTSS,  
Erosion score  
Joint space narrowing score  
1 
2 
WPAI-SHP  
1 
2 
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BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; DAPSA=disease activity index for psoriatic 
arthritis; DAS28[CRP]=disease activity score-28 based on C-reactive protein; EQ-5D-3L=Euro-Quality of Life 5-
Dimensions 3 Level version; FACIT-Fatigue=Functional assessment of chronic illness therapy - Fatigue; HAQ-
DI=Health assessment questionnaire – Disability index; hs-CRP=High sensitivity C-reactive protein; LDI=Leeds 
Dactylitis Index; LEI=Leeds Enthesitis Index; mNAPSI=Modified Nail Psoriasis Severity Index; PASDAS= 
Psoriatic Arthritis Disease Activity Score; PASI=Psoriasis Area and 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-12=Psoriatic Arthritis impact of disease-12; PsAQoL=Psoriatic Arthritis Quality of 
Life; PsARC= Psoriatic Arthritis Response Criteria; PtAAP=Patient’s assessment of Arthritis Pain;  SF-36=Short-
Form 36-item Health Survey; SJC= Swollen Joint Count; SPARCC= Spondyloarthritis Research Consortium of 
Canada ; TJC=Tender Joint Count; vdHmTSS=Van der Heijde modified Total Sharp Score; WPAI-SHP=work 
productivity and activity impairment questionnaire – specific health problem  
Unless stated otherwise, continuous endpoints will be expressed as a change from Baseline 
which will be calculated as the value at a specific timepoint minus the value at Baseline. 
Unless stated otherwise, statistical tests of efficacy variables will be presented as 2-sided p-
values rounded to 3 decimal places. P-values less than 0.001 will be presented as “<0.001” and 
p-values greater than 0.999 will be presented as “>0.999.” Statistical comparisons will be 
performed by 2-sided statistical tests at the 0.05 level of significance. Least square means 
(LSM), OR and corresponding CI will be presented using 3 decimals. 
UCB uses SAS in a 64-bit Windows environment, and it is well-documented that in this 
environment the maximum accuracy of any numeric value is 15 significant digits. However, SAS 
by default does not limit the accuracy of numeric values to 15 significant digits which, in certain 
instances, may result in inaccurate representation of the data and cause errors when used in 
subsequent calculations, particularly when comparing a value to a chosen threshold. This, in 
turn, could potentially result in a change in classification of a subject from a responder to a non-
responder (and vice versa) if these values occur on a threshold used in the evaluation of response 
(or a critical laboratory value for example). 
Therefore, in order to avoid issues caused by inaccurate floating point representation of numeric 
values, temporary variables are created (ie, for absolute values, change and percentage change 
from Baseline) during programming which are rounded to 12 decimal places prior to comparison 
to a specific threshold in the derivation of a response parameter. This does not imply inherent 
rounding on the analysis variables for absolute value, change or percentage of change which are 
retained unrounded in the final analysis dataset. Thus, rounding is applied exclusively during the 
derivation of new response parameters or critical value variables, and the rounded values are 
created on a temporary basis only.  
The SAS® outputs supportive of any inferential statistics that are part of the hierarchical testing 
procedure (ie, all inferential statistics associated with the endpoints in Table 4‒5) will be 
provided as a separate PDF document in addition to TFLs. These outputs will be included in the 
‘Documentation of Statistical Methods’ section of the clinical study report 
Unless specified differently in this SAP, the order of treatment groups presented in tables from 
left to right will be: 
• Placebo 
• Bimekizumab 160mg Q4W  
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• Adalimumab 40mg Q2W. 
Selected tables may also include columns for all subjects (regardless of study treatment) and/or 
all subjects on BKZ (regardless of whether they shifted from placebo after the DBP or not). 
The abbreviation for bimekizumab is BKZ, and ADA for adalimumab and will be used in table 
and listing headers. No abbreviation will be used for Placebo. 
In the TFLs, subjects randomized to BKZ 160mg Q4W will be labeled as “BKZ 160mg Q4W” , 
subjects randomized to ADA 40mg Q2W will be labeled as “ADA 40mg Q2W” and subjects 
randomized to Placebo will be labeled as “Placebo / BKZ 160mg Q4W” ( or “Placebo” when the 
TFLs report data from the DBP only).  
For the ATP, all subjects on BKZ 160mg Q4W (that includes the subjects switching from 
Placebo at Week 16) will be labeled as “BKZ 160mg Q4W Total” in the TFLs. 
Per protocol, visit windows of ±2 days from the first dose at all visits through Week 16 and ±3 
days after Week 16 are permissible. For the SFU visit, the visit should occur no more than 3 days 
prior to the scheduled visit date and within 7 days after the scheduled visit date. 
For the medical imaging collection date (at Week 16 and 52), the allowed visit window will be 
extended to ±14 days around the scheduled visit date.    
All by-visit tables will contain nominal (ie scheduled) visits only. Unscheduled visits will not be 
mapped to scheduled visits except for some assessments that may occur within the above visit 
window of a scheduled visit. In that case, the assessment will be mapped to the corresponding 
scheduled visit and will be used for the analysis unless data are present for that scheduled visit.   
Only data collected/mapped at the scheduled visits will be included in the analysis. The only 
deviation may concern unscheduled vendor data collected (Section 10.5). 
Assessments collected at unscheduled and repeated visits will only be listed, except in the case of 
determining treatment-emergent markedly abnormal criteria for laboratory and vital sign 
parameters where all post-Baseline (scheduled and unscheduled) values will be used.  
For by-visit tables summarizing efficacy data, the SFU visit will not be included but SFU 
efficacy data will be listed. By-visit tables summarizing safety data will however include the 
SFU visit.  For PK, immunological and immunogenicity analyses, SFU data will be part of the 
data reported in some tables (Section 9).   
A complete set of data listings containing all documented data and all derived data (eg, change 
from Baseline) will be generated. 
Unless otherwise stated, listings will be sorted by treatment group, subject number within each 
treatment group (not randomization number), variable (if applicable) and visit (if applicable, 
including timing relative to dosing if applicable). For listings including non-randomized subjects, 
the non-randomized subjects will be shown first in the listing, ordered by subject number. All 
listings will include repeated and unscheduled measurements. Such measurements will appear in 
chronological order together with the scheduled visits (ie: a repeated measurement will appear 
directly after the visit and time relative to dosing for which the repeat measurement was 
performed). In all the listings dates will be presented in the format ‘YYYY-MM-DD’ and times 
will be presented in 24h clock format as ‘hh:mm’. 
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3.2 
General study level definitions 
3.2.1 
Relative day 
The relative day will be included in some listings. The way that relative day is calculated 
depends on when the given event occurs relative to the date of first IMP administration. 
• If the event occurred on or after the date of first IMP administration (but before the last IMP 
administration), then the following calculation is used: Relative Day=Date of event - Date of 
first IMP administration + 1.  
• If the event occurred before the date of first IMP administration, then the following 
calculation is used: Relative Day=Date of event - Date of first IMP administration. Relative 
days that occur before the date of first IMP administration should be preceded by a “-”.  
• If the event occurred after the date of last IMP administration, then the following calculation 
is used: Relative Day=Date of event - Date of last IMP administration. Relative days that 
occur after the date of last IMP administration should be preceded by a “+”. 
Relative day will only be computed for fully completed dates and will be missing for partial 
dates. 
For AEs, relative days for start and stop dates will be calculated as the number of days since the 
date of first IMP administration.  
For subjects in the placebo group that switch to BKZ at Week 16, for events occurring after 
Week 16, an additional relative day will be calculated using the same rules as above but based on 
the date of first injection of BKZ. This additional relative day will be provided in listings for 
concomitant medications and safety data. 
For non-treatment-emergent AEs, relative day of onset will be negative if the event started 
before the date of first IMP administration. A complete date must be established to correctly 
identify the AEs. Section 4.2.3 describes imputation rules in case of missing data for AEs. 
3.2.2 
Mapping of assessments performed at Early Discontinuation Visit 
Study assessments at an early termination visit where visit date matches the visit date of a 
scheduled visit will be summarized at the scheduled visit with the same visit date. Premature 
study termination visit assessments that do not have a scheduled visit with a matching date will 
be assigned a visit based on the protocol-defined visit windows (±2 days up to and including 
Week 16, and ±3 days from Week 20 up to and including Week 52).  For early discontinuation 
visits that fall between protocol defined visit windows and not within them, the later of the 2 
visits is assigned.  
If there is an existing scheduled site visit in the window, then the assessments at the ET visit will 
be mapped to the next scheduled site visit.  
The ADAb assessments, PK and the vdHmTSS are exceptions to this rule:  
• ADAb levels, PK from an early termination visit will be mapped to the next visit where they 
are measured. 
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• VdHmTSS from an early termination visit will be mapped to the Week 16 assessment (if the 
early termination is before Week 16) or to the Week 52 assessment (if the early termination 
is between Week 16 and Week 52).    
3.3 
Definition of Baseline values 
A Baseline value for a subject is defined as the latest measurement for that subject up to and 
including the day of first administration of IMP (Visit 2 by default), unless otherwise stated.  
By default, for randomized subjects for whom no start date of treatment is available, the Baseline 
value will be considered as the last available value prior to the randomization date.   
If a Baseline assessment is taken on the same day as first administration of IMP, it is eligible to 
be used as the Baseline value, even in the case that the time of the assessment is recorded as 
taking place after the time of first administration of IMP. This is considered acceptable as this 
measurement is still the best representation of the Baseline value of the given assessment since it 
is highly unlikely that the IMP could have an impact on any measurement in such a short period 
of time. However, such cases should be rare as study center personnel are instructed to do all 
assessments at the Baseline visit prior to administering IMP. One exception to this rule is plasma 
concentration. If Baseline plasma concentration is measured at a time after the first 
administration of IMP, then it should not be eligible to be considered as a Baseline plasma 
concentration. Such cases should be discussed with the quantitative clinical pharmacologist.  
If a Baseline measurement is missing or not collected, and a Screening value is available, the 
Screening value will be utilized as Baseline instead. If no measurement is available prior to 
receiving IMP, then the Baseline value is treated as missing.  
Baseline values for component scores should be computed using components from the same visit 
where the relevant measurements were recorded prior to dosing. For example, if the Screening 
visit has all the components, but the Baseline visit is missing one or more components, the 
Baseline value for the component score should be calculated using the Screening visit values. 
When the time of first dose is derived, it should be based on the first injection of IMP, regardless 
of whether it is an active treatment. 
Chest x-ray performed within 3 months before the Screening visit is considered as Baseline 
measurement.  
For subjects who switch treatment from placebo to BKZ at Week 16 (Visit 10), an additional 
Baseline value (called Week 16 Baseline) will be defined for efficacy variables. The Week 16 
value will be considered as the Baseline value regardless of whether the Placebo subjects 
switched to BKZ on a later visit.  
The variables listed below will be analyzed relative to the Week 16 Baseline value for the ATP, 
for timepoints after Week 16: 
• PASI90 response 
• ACR50 response. 
3.4 
Study treatment discontinuation and intercurrent event 
The concept of intercurrent event (IE) is one of the estimand attributes. 
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Unless otherwise noted, treatment discontinuation due to any reason will be considered an IE. 
Since there is no treatment discontinuation date collected, the treatment discontinuation date is 
defined as:  
• Treatment end date + 31 days.    
3.5 
Protocol deviations 
An important protocol deviation (IPD) is defined as a protocol deviation (PD) likely to have a 
meaningful impact on the study conduct, the primary efficacy outcome, the key safety or the PK 
outcomes for an individual subject. The IPDs will be identified and classified by the deviation 
types defined in the appropriate protocol-specific document. All PDs will be reviewed as part of 
the ongoing data cleaning and data evaluation process and IPD will be identified and 
documented prior to unblinding to confirm exclusion from Per Protocol Set (PPS) and the 
Pharmacokinetics Per Protocol Set (PK-PPS).  
An IPD will not always necessitate the removal of a subject from the PPS. Depending on the 
type of PD, the subject may remain in the PPS. The IPD document developed by the clinical 
study team should clearly state which PD will result in a removal from the PPS.  
In addition to IPDs resulting in the exclusion from the PPS, subjects who reduce the dose or 
dosing frequency of certain medications due to intolerance, AE, side-effects or receive new 
prohibited medication for AE will be removed from the PPS. While this is not an IPD, as it is 
allowed per protocol for safety reasons, these subjects will be removed from the PPS as this non-
PD could have an effect on the primary efficacy outcome in the same way as flagged IPDs 
resulting in exclusion from the PPS. 
Since the PPS will be used for a supportive analysis of the primary endpoint, which is assessed at 
Week 16, the exclusion from PPS is limited to the DBP, ie only subjects with IPD (or the non-
PD above) observed prior to or at Week 16 (Visit 10) will be excluded from the PPS. Subjects 
with IPD after Week 16 will not be excluded from the PPS. 
A specific category of PD as a consequence of the Coronavirus Disease 2019 (COVID-19) 
pandemic (called COVID-19 related PD) will be assessed based especially on the information 
collected on a dedicated electronic case report form (eCRF) page (and other sources).  
3.6 
Analysis sets 
3.6.1 
Enrolled Set 
The Enrolled Set consists of all subjects who have given informed consent. 
Subject dispositions will be summarized on the Enrolled Set. 
3.6.2 
Randomized Set 
The Randomized Set (RS) consists of enrolled subjects that have been randomized. 
Demographic tables, primary, secondary (except VdHmTSS) and other efficacy variables will be 
presented on the RS.  
3.6.3 
Safety Set 
The Safety Set (SS) consists of all subjects who received at least 1 dose of the IMP. 
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Demographic tables, study treatment compliance, exposure and safety variables will be presented 
on the SS.  
3.6.4 
Full Analysis Set 
The Full Analysis Set (FAS) consists of all randomized subjects who received at least 1 dose of 
IMP and have valid measurements of all the components of the primary efficacy variable at 
Baseline. 
Supportive analysis of the primary efficacy variable will be performed in the FAS. 
3.6.5 
Active Medication Set 
The Active Medication Set (AMS) will consist of all subjects who have received at least 1 dose 
of active IMP (BKZ or ADA). The AMS will cover the analysis of data collected during the 
Active Medication Periods (AMP), ie: 
• The ATP for subjects randomized to placebo,  
• The DBP and the ATP for subjects randomized to BKZ or ADA.  
The AMS will be used for summaries of safety during the AMP. 
The anti-BKZ antibody will also be analyzed on the AMS for subjects receiving BKZ. 
In this analysis set, the order of the treatment groups presented in tables from left to right will be: 
• BKZ Total (all BKZ treated subjects)  
• ADA 40mg Q2W. 
For the analysis of the compliance, study medication and time at risk, the order of the treatment 
groups to be presented in tables from left to right will be:  
• Placebo / BKZ 160mg Q4W 
• BKZ 160mg Q4W 
• BKZ 160mg Q4W Total (all BKZ treated subjects)  
• ADA 40mg Q2W. 
3.6.6 
Active Treatment-Blind Set 
The Active Treatment-Blind Set (ATS) consists of all subjects who received at least 1 dose of 
active treatment (BKZ or ADA) during the ATP (Week 16 and after). 
Disposition, demographics, and Baseline characteristics will be reported on the ATS. The ATS 
will also be used to report data from the ATP such as study treatment compliance and exposure, 
adverse events, treatment-emergent markedly abnormal (TEMA) data for vital signs and 
laboratory data and selected efficacy analyses. 
In this analysis set, the order of treatment groups presented in tables from left to right will be: 
• Placebo / BKZ 160mg Q4W  
• BKZ 160mg Q4W 
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• ADA 40mg Q2W.  
For safety data, the first 2 groups will also be summarized as “BKZ 160mg Q4W Total”. 
3.6.7 
Per Protocol Set 
The Per-Protocol Set (PPS) will consist of all subjects in the RS who had no IPD or non-PD 
related to prohibited medications affecting the primary efficacy variable (only IPD/non-PD 
related to prohibited medications observed prior to Week 16 are considered for exclusion from 
the PPS). The deviations will be predefined and subjects with deviations will be evaluated during 
ongoing data cleaning and data evaluation meetings prior to unblinding of the data (Section 3.5). 
Exclusion from the FAS will be considered as an IPD that also results in exclusion from the PPS. 
Supportive analysis of the primary efficacy variable will be performed on the PPS. 
3.6.8 
Pharmacokinetic Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) consists of all randomized subjects who 
received at least one dose of the BKZ and provided at least one quantifiable plasma 
concentration post-dose (ie: after first BKZ dose) without IPD that would affect the 
concentration.  
PK variables will be analyzed for all subjects in the PK-PPS. 
3.6.9 
Radiographic Set 
The Radiographic Set (RAS) will consist of all subjects in the RS who received at least 1 dose of 
IMP and have a valid radiographic image of the hands and feet (with an assessment performed 
by at least the 2 reviewers) at Screening. 
The analysis of vdHmTSS will be performed on the RAS. 
3.6.10 
COVID-19-free Set 
The COVID-19-free Set will consist of all subjects in the RS who had no COVID-19 impact up 
to the primary efficacy endpoint. This will be defined as subjects (up to Week 16): 
• not having a COVID-19 related IPD  
• not having an impact based on the COVID-19 eCRF 
• not having an AE related to COVID-19 (Section 10.2.6)  
• not discontinuing due to COVID-19. 
The disposition data, the primary efficacy endpoint and the secondary efficacy endpoints 
included in the testing hierarchy will be analyzed on the COVID-19-free Set. 
3.7 
Treatment assignment and treatment groups 
It is expected that subjects receive treatment as randomized and hence safety analyses will be 
based on the SS, as randomized. However, after unblinding, study treatment received might be in 
some cases different from the randomized treatment. If subjects randomized to placebo received 
BKZ at any time during the DBP, then for safety analyses these subjects will be reallocated to 
the BKZ treatment group. If subjects randomized to placebo received ADA at any time during 
the DBP (but no BKZ), then for safety analyses these subjects will be reallocated to the ADA 
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treatment group. Subjects randomized to BKZ will only be reallocated to the placebo treatment 
group if they never received BKZ. Subjects randomized to ADA will only be reallocated to the 
placebo treatment group if they never received ADA. 
Efficacy analyses will be performed according to randomization and not actual treatment 
received. Data collected after study treatment discontinuation will be listed only and not reported 
in table except in the context of the treatment policy analysis performed on the primary efficacy 
endpoint (Section 8.1.4.5).  
3.8 
Center pooling strategy 
The 4 geographic regions considered for the study are the ones used for randomization 
stratification:   
• North America (Canada, USA)  
• Western Europe (Belgium, France, Germany, Italy, Spain, United Kingdom)  
• Eastern Europe (Czech Republic, Hungary, Poland, Russia)  
• Asia (Australia, Japan) identified as “Asia” in all analyses.   
The above regions will be the ones used when considering the region as factor in the efficacy 
analyses. 
3.9 
Coding dictionaries 
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) version 19.0. Medications will be coded using the World Health Organization 
Drug Dictionary (WHO-DD) version March-2021. Medical procedures will not be coded. 
To maintain consistency across studies in the BKZ development program, the dictionary versions 
will be held constant to support consistency of coding in the regulatory submissions. 
3.10 
Changes to protocol-defined analyses 
The following changes from the protocol will be considered: 
• An additional supportive analysis for primary endpoint based on the analysis of the 
individual components of ACR will be performed using the Reference-Based imputation 
method. 
• The main analyses of the secondary continuous variables included in the testing hierarchy  
will be performed using the Reference-Based imputation method. 
• Proportion of subjects with a decrease of HAQ-DI from Baseline of at least 0.35 (HAQ-DI 
responders) in those subjects with HAQ-DI ≥0.35 instead of >0.35. 
• An additional subgroup based on the combination of concomitant methotrexate (MTX) and 
Baseline  conventional disease modifying antirheumatic drug (cDMARD). 
• Additional subgroup analyses will be performed on HAQ-DI responders at Week 16. 
• Proportion of PsAID-12 responders (decrease from Baseline in PsAID-12 total score ≥3) in 
subjects with PsAID-12 total score ≥3 at Baseline instead of >3 at Baseline 
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• The subgroup analysis on BASDAI will be performed on the categories: <4 vs. ≥4 rather than 
≤4 vs. >4. 
• The analysis of the proportion of responding subjects at Week 52 among those who 
responded at Week 16 will be extended to all post Week 16 visits (and not only at Week 52). 
• The analysis of the proportion of FACIT-Fatigue subscale responders (subjects with a 
minimum clinically important difference for FACIT-Fatigue subscale score defined as an 
increase of ≥4) will be performed in subjects with FACIT-Fatigue subscale score ≤48 at 
Baseline.  
• The time to ACR20/50/70 will be exclusively analyzed using observed cases data. 
• The AMS is an analysis set that has been added for the analysis of safety variables. 
• The ATS is an analysis set that has been added for the analysis of data collected during the 
ATP.  
3.11 
Changes related to COVID-19 
The impact of the COVID-19 pandemic on study procedures/conduct as well as the efficacy and 
safety endpoints will be investigated, and additional analysis outputs will be provided as 
appropriate. These additional analyses were not planned as part of the original protocol as the 
pandemic was not ongoing at the time of protocol finalization. These additional analyses will 
include analyses by period of the COVID-19 pandemic (pre/during/post) as defined below: 
• Pre-COVID-19 pandemic period: period prior to COVID-19 pandemic start date defined 
as 11-Mar-2020 
• COVID-19 pandemic period: period from 11-Mar-2020 though the COVID-19 pandemic 
end date which is currently not defined at the time of approval of the SAP 
• Post-COVID-19 pandemic period: period after the declaration of the end of the 
pandemic. 
The additional analyses are described in the following sections: 
• Subject disposition (Section 5.1) 
• Demographics and other baseline characteristics (Section 6) 
• Details of impacted visits and effects on collection and reporting of efficacy data  
(Section 5.2) 
• Protocol deviations (Section 5.3) 
• Efficacy analyses related to the hierarchy endpoints (Section 8.1.4.8  and 8.2.3) 
• Adverse events (Section 10.2.6). 
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4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
The primary efficacy analysis will investigate the treatment effect, adjusting on the 2 
randomization stratification variables: 
• Region:  
− North America, Western Europe, Eastern Europe, Asia  
or 
− North America, Eastern Europe, Western Europe + Asia if the percentage of randomized 
subjects is < 10% in either of the Asia or Western Europe regions  
• Bone erosion (0, ≥1) at Baseline. 
When adjusting on these 2 variables, a statistical model might not converge (ie:  the likelihood 
maximization algorithm fails to converge). In that case, the statistical model will be run after 
dropping successively region and bone erosion at Baseline.   
If a subject is stratified in the incorrect stratum (ie: the stratum recorded in the Interactive voice 
or web Response System differs from the actual stratum the subject belongs to), the actual 
stratum will be used for the analysis.  
The secondary analyses will be adjusted on the same categorical factors as retained for the 
primary analysis. For continuous variables, Baseline value (of the variable of interest) will be 
also included as covariate where appropriate.  
4.2 
Handling of dropouts or missing data 
4.2.1 
Strategy for handling missing data for efficacy analyses 
Different approaches will be used to handle missing data including how the IE will be considered 
(Section 3.4). 
In this section, 3 terms will be used to define binary and continuous endpoints:  
• Non-composite binary endpoint: Binary endpoint derived based on one continuous 
measurement (eg, PASI90) 
• Composite binary endpoint: Binary endpoint derived based on several continuous 
measurements (eg, ACR50) 
• Composite continuous endpoint: Continuous endpoint derived based on several continuous 
measurements (eg, PASDAS). 
Below is a table summarizing for all continuous endpoints (excluding composite continuous 
endpoints) observed ranges and whether they are represented by an integer value. These 
endpoints will be analyzed and/or used in the derivation of composite or non-composite 
endpoints: 
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Table 4‒1: 
List of non-composite continuous efficacy endpoints 
Efficacy endpoint 
Minimum 
Maximum 
Integer value 
BASDAI 
0 
10 
 
EQ-5D-3L dimension scores 
1 
3 
Yes 
EQ-5D-3L (VAS) 
0 
100 
Yes 
FACIT-Fatigue subscale score 
0 
52 
 
HAQ-DI 
0 
3 
 
hs-CRP 
LLOQ/2 where 
LLOQ=0.10 
mg/L 
No maximum 
 
IGA 
0 
4 
Yes 
LDI 
0 
No maximum 
 
LEI 
0 
6 
 
mNAPSI 
0 
13 
Yes 
PASI 
0 
72 
 
PGA-Arthritis /PhGA-Arthritis 
0 
100 
Yes 
PGA-PsA / PhGA-PsA 
0 
100 
Yes 
PsAID-12 
0 
10 
 
PsAQoL 
0 
20 
 
PtAAP 
0 
100 
Yes 
SF-36a  
Physical Functioning (PF) 
Role Physical (RP) 
Bodily Pain (BP) 
General Health (GH) 
Vitaly (VT) 
Social Functioning (SF) 
Role Emotional (RE) 
Mental Health (MH) 
Physical component summary (PCS) 
Mental component summary (MCS) 
 
19.26 
21.23 
21.68 
18.95 
22.89 
17.23 
14.39 
11.63 
5.02 
-3.33 
 
57.54 
57.16 
62.00 
66.50 
70.42 
57.34 
56.17 
63.95 
79.78 
80.09 
 
SPARCC 
0 
16 
 
Tender Dactylitis Count 
0 
20 
Yes 
TJC / SJC 
0 
68/66 
 
vdHmTSS 
Erosion score 
Joint space narrowing score 
0 
528 
320 
208 
 
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Efficacy endpoint 
Minimum 
Maximum 
Integer value 
WPAI-SHP 
0 
100 
 
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; EQ-5D-3L=Euro-Quality of Life 5-Dimensions 3 
Level version; FACIT=Functional Assessment of Chronic Illness Therapy; HAQ-DI=Health Assessment 
Questionnaire – Disability index; hs-CRP=High sensitivity C-reactive protein; IGA=Investigator Global 
Assessment; LDI=Leeds Dactylitis Index; LEI=Leeds Enthesitis Index; LLOQ=lower limit of quantification; 
mNAPSI=Modified Nail Psoriasis Severity Index; PASI=Psoriasis Area and 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-12=Psoriatic Arthritis Impact of Disease-12; 
PsAQoL=Psoriatic Arthritis Quality of Life; PtAAP=Patient’s Assessment of Arthritis Pain;  SF-36=Short-Form 36-
Item Health Survey; SJC= swollen joint count; SPARCC= Spondyloarthritis Research Consortium of Canada ; 
TJC=tender joint count; vdHmTSS=van der Heijde Modified Total Sharp Score; WPAI-SHP=Work Productivity 
and Activity Impairment Questionnaire – Specific Health Problem 
a minimum and maximum of the norm-based scores – Normal range for SF-36 scores is 0-100 
4.2.1.1 
Primary analysis of binary endpoints that are part of the testing 
hierarchy (primary and secondary endpoints) 
All binary endpoints (composite & non-composite) are based on continuous component 
variables. 
The primary analysis of binary efficacy endpoints that are part of the testing hierarchy is 
considered under an estimand framework in which missing data (due to study treatment 
discontinuation) is considered indicative of failed treatment and imputed to non-response. 
Further missing data for subjects on treatment, or data observed while not on treatment is also 
imputed to non-response. 
This composite estimand approach to handling missing data which is the primary analysis 
method for binary efficacy endpoints is similar to the non-responder imputation (NRI) method.  
4.2.1.2 
Primary analysis of continuous endpoints that are part of the testing 
hierarchy (secondary endpoints) 
For continuous efficacy endpoints that are part of the testing hierarchy, the primary analysis 
method is based on the hypothetical estimand approach as follows:  
• If subjects have missing data regardless of whether the missing data is preceded by an IE, 
then missing data will be imputed based on the MI-Markov-Chain Monte Carlo (MI-MCMC) 
/Reference-Based imputation method (Section 4.2.2.3). 
• If subjects have non missing data after IE, then such data will be set to missing prior to 
running MI. 
4.2.1.3 
Supportive analyses of primary efficacy endpoint 
For the primary endpoint (which is a composite binary endpoint) several supportive analyses 
assuming different missing data mechanisms will be conducted: 
• The modified composite estimand approach: the IE is changed from all treatment 
discontinuation to treatment discontinuation due to AE or lack of efficacy. The same as the 
primary method will be used with the difference that only data after discontinuation due to 
AE or lack of efficacy is set to non-response. All other imputed data will be used. 
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• For the analysis of individual components of ACR, under the hypothetical estimand approach 
using the reference-based imputation methods (Section 4.2.2.3).   
• The tipping point approach implemented within the MI framework, but only if the primary 
endpoint analysis result is statistically significant at alpha=0.05. (Section 4.2.2.4).  
• The treatment policy strategy (Section 4.2.2.5). 
• The observed case (OC) analysis that will only include observed data while on treatment. For 
subjects who had treatment discontinuation, only observed data up to treatment 
discontinuation date will be analyzed.  For visits with missing data without treatment 
discontinuation, the data will remain missing.  For observed data after treatment 
discontinuation, the corresponding visit data and subsequent visit data will be treated as 
missing. 
4.2.1.4 
Supportive analyses of endpoints that are part of the testing 
hierarchy (secondary endpoints) 
The following supportive analysis methods will be performed for the secondary efficacy 
variables that are part of the testing hierarchy:  
For binary endpoints:  
• The modified composite estimand approach: the IE is changed from all treatment 
discontinuation to discontinuation of treatment due to AE or lack of efficacy. For composite 
or non-composite binary endpoints, the standard MI approach will be implemented (similarly 
as in Section 4.2.1.3) on the raw continuous score(s) (eg: PASI for the PASI90 endpoint) 
before deriving the binary endpoint based on the imputed score(s).  
• The OC analysis. 
For continuous endpoints: 
• The hypothetical estimand approach:  
− If subjects have missing data regardless of whether the missing data is preceded by an IE, 
then missing data will be imputed based on the MI-MCMC/Monotone regression method 
(Section 4.2.2.2). 
− If subjects have non missing data after IE, then such data will be set to missing prior to 
running MI. 
• The OC analysis.  
4.2.1.5 
Analyses of secondary endpoints that are not part of the testing 
hierarchy and other efficacy endpoints 
The other efficacy endpoints and the secondary efficacy endpoints that are not part of the testing 
hierarchy will be analyzed as the secondary efficacy endpoints (with the exclusion of the MI-
MCMC/referenced based imputation method for continuous variables) but with no designated 
priority.  
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For a combined binary endpoint based on the combination of a non-composite and a composite 
binary endpoint (as with the ACR50 and PASI90 combined endpoint), each binary endpoint will 
be derived independently, before deriving the combined endpoint.  
4.2.1.6 
Summary table of missing data handling approaches for efficacy 
analyses 
The below table summarizes which missing data handling approaches will be used for each type 
of efficacy endpoint.  
Table 4‒2: 
Missing data handling approaches for efficacy endpoints 
Efficacy Endpoint 
Priority 
Variable 
Type 
Missing data handling approach 
Composite 
estimand 
(NRI) 
Hypothetical  
estimand 
(RB-MI) 
Modified 
Composite 
estimand 
(MI) 
Hypothetical 
estimand 
(MI) 
OC  
Tipping 
Point 
Analysis 
( MI)  
Treatment 
Policy 
(MI)  
Primary endpoint 
Composite 
Binary 
P 
 
Sa 
 
S  
Sa 
Sa  
Secondary 
endpoints included 
in the testing 
hierarchy 
Binary  
P 
 
Sa 
 
S 
 
 
Continuous 
 
P 
 
S 
S 
 
 
Other Secondary 
endpoints 
(endpoints not 
included in the 
testing hierarchy) 
Binary 
X 
 
Xa 
 
X 
 
 
Continuous 
 
 
 
X 
X 
 
 
Other endpoints 
 
Binary  
X 
 
Xa,b 
 
X 
 
 
Continuous 
 
Xd 
 
Xb  
X 
 
 
Categorical 
Xc 
 
Xc 
 
X 
 
 
P=Primary analysis method, RB=Referenced Based, MI=multiple imputation, NRI=non-responder imputation, OC=observed 
cases, S=Supportive analysis method, X=Method to be used (no priority designated) 
Note: Composite estimand (NRI) refers to the approach in which data preceded by the intercurrent event of study treatment 
discontinuation are imputed as non-response, and other missing data are also imputed as non-response. 
Note : Referenced Based imputation  refers to the approach in which it is assumed that the statistical behavior of the 
bimekizumab and placebo-treated subjects after discontinuing study medication becomes that of the placebo-treated subjects that 
remain in the study. 
Note: Modified Composite Estimand (MI) refers to the approach in which data preceded by the intercurrent event of study 
treatment discontinuation due to AE or lack of efficacy are imputed as non-response (or worst category for categorical variable), 
and other missing data are imputed via a multiple imputation model.  
Note: Hypothetical Estimand (MI) refers to the approach where outcomes for subjects without an intercurrent event of study 
treatment discontinuation are as observed, and outcomes for subjects with the intercurrent event are imputed via a multiple 
imputation model. 
a Imputation method is applied on continuous data, and binary variable is derived from the continuous variable based on complete 
imputed dataset. 
b MI will be used to provide point estimates at each timepoint only 
c Missing data to be imputed to the worst category 
d for ACR components analysis at Week 16 
4.2.2 
Methods for handling missing data for efficacy analyses 
The sections below describe the method to be used for missing efficacy data handling. 
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For a specific endpoint, if analyzed subjects in a one or several treatment group(s) have no 
missing data, then analysis of observed cases will be performed in the concerned treatment 
group(s). 
4.2.2.1 
Non-responder imputation 
For binary endpoints, the non-responder imputation (NRI) analysis, also described above as the 
composite estimand, will consider the following subjects as “non-responders” for the timepoint 
of interest:  
• Subjects with missing data at the time point of interest. In the case of ACR50, non-response 
is imputed if ACR50 cannot be derived (ie: derived as “missing”) based on available ACR 
components (Section 8.1.1)  
• Subjects who remained in the study at the timepoint of interest but discontinuing study 
treatment before the timepoint of interest (data after IE) 
• Subjects with missing Baseline value (for composite or non-composite binary variables based 
on change(s) from Baseline of continuous endpoint(s)). 
4.2.2.2 
MI – MCMC/Monotone Regression 
In instances where MI is used, the missing value is replaced by a set of plausible values, where 
each value is a Bayesian draw from the conditional distribution of the missing data given the 
observed data. Intermittent missing data will be imputed using the MCMC method, followed by 
regression for monotone missing data (called “MI-MCMC/Monotone regression” method in this 
SAP). The MI procedures planned for efficacy analyses are based on an assumption of data 
missing at random (MAR). 
This section describes the algorithms to be implemented for the MI – MCMC/Monotone 
Regression procedures for non-composite binary endpoints, composite binary endpoints, and 
continuous endpoints. These descriptions focus on the MI procedure itself and do not specifically 
account for dealing with IE (Section 4.2.1). 
Non-composite binary endpoints 
For non-composite binary endpoints, the MI method will be applied as follows: 
• Step 1 - Imputation of missing data using MI 
Create datasets, one for each treatment group, of subjects with observed values and missing 
values (needing estimation by MI). For the imputation step, missing values will be separated 
into 2 categories: intermittent missing values (ie, missing values for a given subject that has 
available data before and after the missing timepoint, including missing value at Baseline) 
and monotone missing values (ie, where all subject data is missing after a given time point). 
Datasets should be designed in a horizontal structure meaning that each subject should be 
presented in a single observation, with a set of values, one for each scheduled visit where the 
endpoint is scheduled to be collected according to the protocol (this exclude the unscheduled 
visits). For the Week 24 analysis, this will include visits up to Visit 14 (Week 24) and for the 
Week 52 analysis, visits up to Visit 28 (Week 52). Datasets should also be sorted by subject 
number before proceeding with the MI process.  
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For the intermittent missing values, the missing value in each dataset will be filled in using 
the MCMC method with multiple chains, monotone missing data imputing pattern, and non-
informative priors for all parameters. Unless specified differently, the first 200 iterations will 
not be used (the ‘burn-in’ option).  A total of 100 sets of imputations will be performed. The 
seed used for these imputations will be 2017 and all other MI procedures described in this 
SAP will use this same seed as well. The procedure will be performed for each treatment 
group separately. The resulting 100 imputed datasets will have a monotone missing pattern 
and will be imputed using a method for monotone missingness. 
For monotone missing data, one monotone regression will be used to impute missing data. 
A separate regression model is estimated for each variable with missing values (ie, 
measurement at each time point). Based on the resulting model, a new regression model is 
then drawn and is used to impute the missing values for the variable. Since the dataset has a 
monotone missing data pattern, the process is repeated sequentially for variables with 
missing values. The procedure will be based on the 100 imputed datasets generated from the 
MCMC procedure and will be performed for each treatment group separately by imputation.  
The SAS® PROC MI procedure will be used for the imputation. 
In both cases, the imputation model will include the randomization strata as stratification 
variables (region and bone erosion at Baseline),  the value at Baseline and at each post-
Baseline visit (up to the week of interest). The imputation model based on the MCMC 
method will only allow joint multivariate normal variables. For the MCMC method (when 
imputing intermittent missing values), randomization strata will be re-coded as indicator 
variables and will always be specified in the following order: North America region (1 for 
North America, 0 otherwise), Western Europe region (1 for Western Europe,0 otherwise), 
Eastern Europe region (1 for Eastern Europe, 0 otherwise), For each imputation model, Bone 
erosion at Baseline (0 if bone erosion at Baseline =0 ; 1 if bone erosion at Baseline≥1). 
Bone erosions will be read for all visits at both at the Week 24 analysis and the Week 52 / 
final analyses to ensure that unnecessary bias is not introduced. Given there may be 
differences at Baseline for a subject between the two sets of reads, the following rules will be 
applied for the MI process: 
• For the Week 24 analysis,  the first set of reads will be used.  
• For the Week 52 and final analyses, Week 16 specific outputs will continue to use the 
first set of reads. Outputs involving over time data up to Week 52 will use the second set 
of reads.     
For each imputation model, the randomization strata (region and bone erosion at Baseline) 
may be dropped to facilitate convergence if required as described below: If the MI fails to 
converge when adjusting on the stratification variables specified above, or if the percentage 
of randomized subjects is < 10% in either of the Asia or Western Europe regions, then the 
Western Europe and Asia region will be combined  and the binary variables for region that 
will be left in the MI will then be for North America and Eastern Europe regions. 
If after doing that, the MI still fails to converge then all region factors will be removed from 
the MI. if the MI still does not converge after dropping the regions, the remaining 
stratification variable (bone erosion at Baseline) will also be removed. 
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If a variable is dropped in order to allow convergence for one model in the study, that 
variable does not have to be dropped from other models in the study of the model converges 
without dropping the variable. That is, model convergence should be evaluated for each 
efficacy table independently.  
The post-Baseline values will need to be specified in chronological order after the Baseline 
value in the imputation model so that the SAS® PROC MI imputes variables from left to 
right (ie, Week 2 value will be first imputed using regression based on Baseline value, and 
then Week 4 value will be imputed using regression based on Baseline and Week 2 value, 
etc.). The resulting datasets for each treatment arm will be combined into one complete 
dataset containing 100 times the number of subjects analyzed. 
When imputing  missing hs-CRP values, values below LLOQ (0.10 mg/L) will be replaced 
by the midpoint value between 0 and LLOQ prior to running MI. 
• Step 2: If an imputed value falls outside of the range for the given variable (as listed in 
Table 4‒1) the value will be updated to be within the predefined range. For example, the 
imputed value for PASI will be updated to 0 or 72 in the case of an imputed value < 0 or > 
72, respectively. For endpoints that can take only integer values (eg: IGA as listed in 
Table 4‒1), the imputed values will be rounded to the closest integer after each SAS® PROC 
MI.  
Note: For hs-CRP, the lower limit used the midpoint value between 0 and LLOQ. For some 
parameters, there is not a fixed upper limit to the imputed value (ie: LDI). 
• Step 3: On the dataset obtained from Step 2, the binary responder variable will be derived. In 
practice, the value at the week of interest (eg, Week 16) in the imputed datasets will be used 
to categorize the subject as a responder or not. If subjects have an IE, then the endpoint at all 
subsequent visits will be set to “non-response”. This will be performed: 
− When date of visit is available: by comparing the IE date vs. the date of visit 
− When a visit date is missing in case of fully imputed data at a visit: by comparing the  
next visit number after the visit where the last study medication occurs vs. the visit 
number where data are imputed.  
• Step 4: At each timepoint the (unadjusted) proportion of responders will be calculated by 
treatment group from the imputed datasets using SAS® PROC FREQ. 
• Step 5 (For primary and secondary efficacy endpoints only): For each value of the imputation 
number from 1 to 100, the adjusted proportion of responders will be analyzed using a logistic 
regression model with a fixed effect for treatment. The suitability of including region, and 
bone erosion at Baseline as fixed effects will be assessed using goodness-of-fit tests 
(Deviance and Pearson’s and Hosmer-Lemeshow) and added if appropriate, if it allows 
model convergence. Covariates kept in the modelling should also be the same as the ones 
previously used for the MI. Comparisons will be made using 2-sided Wald test at a 
significance level of 5%. The results obtained from the 100 logistic regression analyses (ie, 
the adjusted proportion of responders for each treatment group, the OR and the difference of 
proportions for the BKZ-placebo comparison and corresponding 95% CI) will be combined 
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for overall inference using Rubin’s rules, which account for the uncertainty associated with 
the imputed values (Rubin, 1987). This will be done using SAS® PROC MIANALYZE. 
Composite binary endpoints 
For composite binary endpoints, the MI method will be applied as follow:  
• Step 1: The MCMC/monotone regression approach described above in Step 1 for non-
composite binary endpoints will be performed separately for each individual component 
variable.  
• Step 2: The same rounding rules described in step 2 above for non-composite binary 
endpoints will be performed for each component.   
• Step 3: Based on the multiply imputed datasets obtained for each component, the binary 
response will be derived as follows: 
− The dataset obtained for each component will be merged by imputation number and 
subject number. 
− On the dataset obtained, the binary endpoint will be derived for each subject/visit based 
on the component values.  
− If subjects have an IE, then the endpoint at all subsequent visits (from the day after the IE 
date, whether the data were observed or not) will be set to “non-response”. 
• Step 4 and 5: Same as step 4 and 5 above for non-composite binary endpoints. 
For the primary endpoint, the ‘burn-in’ option in SAS® PROC MI may be set higher than the 
default value. The goodness-of-fit tests to assess convergence of the MCMC will be provided in 
a SAS® output.  
Calculation of adjusted responder rates, odds ratio, and CIs for binary endpoints. 
Estimates of the adjusted responder rates for each treatment group and the associated standard 
errors (SEs) are obtained from the logistic regression in Step 5 on the logit scale and as such are 
assumed to follow a normal distribution. These estimates will be combined using Rubin’s rules 
and the combined estimates and associated SEs will be used to construct 95% CIs on the logit 
scale.  The combined estimates and 95% CIs on the logit scale will be back transformed using 
the inverse logit link function to obtain the adjusted responder rates (%) and associated 95% CIs. 
Some key points need to be considered relative to the calculation of the OR and corresponding 
CIs. As the estimates of the odds ratios from the logistic regression models obtained in Step 5 
follow a lognormal distribution, a log transformation is needed to normalize these 100 odds ratio 
estimates. This is because the procedures for combining results from multiple imputed datasets 
assume that the statistics estimated from each imputed dataset are normally distributed. 
Therefore, the log of the OR estimates from the logistic regression model are used when 
combining into a single inference (Step 5). Additionally, the SE for the OR are transformed as 
follows: 
𝑆𝐸= log(𝑈𝐶𝐿) −log(𝐿𝐶𝐿)
2𝑍𝛼/2
 
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where UCL and LCL are the upper and lower confidence limit, respectively, for the CI of the 
odds ratio from the logistic regression model, and 𝑍𝛼/2 is the relevant critical value from the 
standard normal distribution (1.96 for a 95% CI). The estimates of the log odds ratio for BKZ 
relative to placebo and the corresponding upper and LCLs will be provided. The OR will be then 
estimated by exponentiating the estimate of the log odds ratio. The OR and the confidence limits 
of the OR will be estimated as follows: 
𝑂𝑅= exp(𝐿𝑜𝑔 𝑜𝑑𝑑𝑠 𝑟𝑎𝑡𝑖𝑜 𝑒𝑠𝑡𝑖𝑚𝑎𝑡𝑒 ) 
𝐿𝐶𝐿= 𝑂𝑅∗exp(−𝑆𝐸∗𝑍𝛼/2 ) 
𝑈𝐶𝐿= 𝑂𝑅∗exp(𝑆𝐸∗𝑍𝛼/2 ) 
where OR is the back-transformed estimate of the odds ratio just described, SE is the SE of the 
log odds ratio and 𝑍𝛼/2 is the relevant critical value from the standard normal distribution (1.96 
for a 95% CI). These calculations will be done such that OR and corresponding CIs are 
calculated for the OR of BKZ vs. placebo. 
In addition to calculating the OR, associated CIs, and p-values for the comparisons of BKZ vs. 
placebo, the estimated proportion of responders (ie, estimated responder rate) and the difference 
in the proportion of responders between BKZ and placebo will be estimated, along with 2-sided 
95% CIs. The creation of the estimates of this difference will be completed using the process 
detailed below: 
• Use the logistic regression model to calculate: 
LSM estimates of the log odds of BKZ (GB) and placebo (GP), as well as their corresponding 
standard errors (SB and SP, respectively). 
Standard error of the LSM estimate of the log odds ratio (SR). 
• Compute estimates for predicted proportions using the following transformations: 
PB = exp (GB)/(1 + exp(GB)) 
PP = exp (GP)/(1 + exp(GP)) 
The difference in proportions is then given by: 
D = PB – PP 
• Estimate the standard error of D by: 
SD = sqrt [PB2(1-PB)2SB2 + PP2(1-PP)2SP2 + PB(1-PB)PP(1-PP)SR2 – PB(1-PB)PP(1-PP)(SB2 + 
SP2]) 
The MI/MCMC monotone regression method, as previously outlined, will be used to account for 
missing values. The calculation steps described above will be based on the results provided from 
the logistic regression model of the multiple imputed datasets. An estimate for the difference in 
proportions, D, and corresponding standard error, SD, will be computed for each of these 
datasets. The results from these analyses will be combined into a single estimate of the difference 
in predicted proportion of response and a 2-sided 95% CI interval using SAS® PROC 
MIANALYZE. 
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Continuous efficacy endpoints 
For continuous efficacy endpoints, the MI method will be applied as follows based on the values 
at the timepoint(s) of interest:  
• Step 1: The same imputation procedure as the described in step 1 for the non-composite 
binary endpoints will be used.  
• Step 2: The same rounding rules described in step 2 above for non-composite binary 
endpoints will be performed.   
• Step 3: On the dataset obtained with the imputation number from 1 to 100; change from 
Baseline will be derived. Simple means and SEs will be calculated using Rubin’s rules (via 
SAS® PROC MIANALYZE) for each timepoints of interest. For calculation of other 
descriptive statistics such as the median, min and max, Rubin's rules do not apply. MI 
estimates will be computed by simply averaging the estimates from the multiple repetitions 
of the imputation algorithm. For CRP data (that will be presented using the geometric mean 
and corresponding 95% CI, arithmetic mean, median, Q1, Q3, minimum and maximum). The 
change from Baseline will be expressed as the ratio to Baseline (value at the visit divided by 
the value at Baseline) in the by-visit summaries. The following approach will be applied: 
− Following the MI procedure, the ratio to Baseline will be calculated for any of the 
imputed values  
− The natural logarithm of the absolute values and of the ratios to Baseline will be 
calculated 
− The logged values will be summarized by treatment, visit and imputation  
− The datasets will be combined using SAS® PROC MIANALYZE in order to get the 
mean from the absolute values and ratios to Baseline across imputations 
− The estimates of the mean will be back transformed to obtain the geometric mean on the 
original scale 
− For the median, Q1, Q3, minimum and maximum the procedure outlined above for the 
other endpoints will be followed. 
• Step 4 (for primary and secondary efficacy variables):  For each value of the imputation 
number from 1 to 100, the change from Baseline will be analyzed using and ANCOVA 
model with treatment group, region and bone erosion as fixed effects and the Baseline value 
as covariate. The results obtained from the 100 ANCOVA analyses (ie: the LSM for the 
treatment difference and the 95% CI for the contrasts) will be combined using Rubin’s rules 
(via SAS® PROC MIANALYZE).  
For composite continuous endpoints, the MI will be applied on each component the same way as 
for composite binary endpoint. The datasets obtained for each component will be merged by 
imputation number and subject number. On the dataset obtained, the endpoint will be derived for 
each subject/visit based on the component values. The endpoint obtained will be analyzed as 
above.  
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Ordinal efficacy endpoints 
For ordinal efficacy endpoints, the MI method will be applied as for the continuous efficacy 
endpoints with the following exceptions:  
• After the imputation of the intermittent and monotone missing data, the rounding rules will 
be performed to align the data with the possible responses for the respective endpoint (eg: If 
the variable can take the value 1, 2 or 3, the imputed values will be rounded to the closest 
possible value).   
• If the ordinal efficacy endpoint is used to derive a binary endpoint, the same analysis strategy 
as described above for the binary endpoints will be used. 
• If the ordinal efficacy endpoint is not used to derive a binary endpoint, the unadjusted 
proportions of subject by categories will be presented.  
• If subjects have an IE, then the ordinal endpoint at all subsequent visits (from the day after 
the IE date, whether the data were observed or not) will be set to the value used for the worst 
category. 
4.2.2.3 
MI – MCMC/Reference-based imputation 
For the primary analysis of the secondary continuous efficacy variables included in the testing 
hierarchy and the individual components of the ACR response, the referenced-based multiple 
imputation method will be used. In this imputation method, the missing data will be imputed 
based on data from the placebo group only (Mallinckrodt, 2013). This analysis will be performed 
only for the subjects randomized to Placebo and BKZ. 
Reference-based MI assumes that the statistical behavior of the BKZ and placebo randomized 
subjects after discontinuing study medication becomes that of the placebo-treated subjects. All 
time points after study treatment discontinuation for BKZ and placebo groups will be considered 
missing. MIs are used to replace missing outcomes for BKZ and placebo-treated subjects who 
discontinued using multiple draws from the posterior predictive distribution estimated from the 
placebo arm.  
Note : SAS 9.4 may be used for this analysis where equivalent steps to those outlined below will 
be used  to perform the imputation.  
In the case of continuous endpoints, the procedure will be implemented as follows on the raw 
values: 
1. Data will be processed sequentially, one timepoint (visit) at a time, by repeatedly calling 
SAS® PROC MI to impute missing outcome data at visits t=1 (Baseline), …, Week 16 (Week 
16 being the time point of interest) using data from the placebo-treated subjects only. 
a. Initialization. Set t=1 (Baseline visit). Create a dataset combining all records from BKZ and 
placebo subjects with columns for covariates (bone erosion and region) and outcome at 
Baseline. Impute missing values at Baseline using bone erosion at Baseline, and region. Note 
that both placebo and BKZ data will be used to estimate the imputation model. 
b. Iteration. Set t=t+1. Create a dataset combining records from BKZ subjects with missing data 
at visit t and all placebo subjects with columns for covariates (bone erosion and region) and 
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outcomes at visits 1 to t. In this dataset, outcomes for all BKZ randomized subjects are 
missing at visit t and observed or previously imputed values at visits 1 to t-1. Outcomes for 
placebo-treated subjects are observed or missing at visit t or observed or previously imputed 
values at visits 1 to t-1. The outcomes should be sorted in chronological order in the model. 
c. Imputation. Impute missing values for visit t using previous outcomes for visits 1 to t-1, bone 
erosion at Baseline, and region. Note that only placebo data will be used to estimate the 
imputation model since no outcome is available for BKZ-treated subjects at visit t. As a 
consequence, the input dataset should include all subjects from Placebo but only subjects 
from the BKZ arm that have values at timepoint t missing.  
d. Repeat steps 2a-2d for all timepoints after Baseline up to Week16, 100 times with different 
seed values (seeds ranging from 201 to 300) to create 100 imputed complete datasets. 
Subjects whose missing values were imputed in the last SAS® PROC MI call will be 
included in the input dataset for the next SAS® PROC MI call. Standard rounding rules will 
be applied to the imputed values. If the MI procedure yields a value outside of the pre-
defined range for the given variable, the value will be updated to be within the predefined 
range of values for the endpoint of interest. For example, the imputed value for TJC will be 
updated to 0 or 68 in the case of an imputed value less than 0 or greater than 68, respectively. 
2. The analysis will be done on the change from Baseline, and the model will be an ANCOVA 
model with treatment group, region, and bone erosion classification as fixed effects and the 
Baseline value as covariate.  
For generation of summary statistics, the 100 imputed datasets will be combined, and simple 
means and standard errors will be calculated using Rubin’s rules (via SAS® PROC 
MIANALYZE). For calculation of other descriptive statistics (median, Q1, Q3, minimum 
and maximum), Rubin’s rules do not apply. MI estimates will be computed by calculating 
arithmetic means of the estimates from the multiple repetitions of the imputation algorithm. 
Thus, for median, Q1, Q3, minimum and maximum the following approach will apply: 
• The data will be summarized by treatment, visit and imputation and the summary 
statistics will be computed.  
• Results will be summarized by taking the mean value of each summary statistic at 
each visit across all imputations.  
• The number of decimal places will remain the same as the original for display 
purposes (ie, if the mean was presented to 1 decimal place, the mean of the means 
will also be presented to 1 decimal place). 
3. The results obtained from the 100 ANCOVA analyses in Step 4 (i.e. LSM for the treatment 
difference and the 95% CI for the contrasts) will be combined with Rubin’s rules.  
4.2.2.4 
Tipping Point analysis 
Tipping point analyses will also be implemented as a supportive analysis for the primary efficacy 
endpoint. This analysis will be performed only for the subjects randomized to Placebo and BKZ.   
The objective of the tipping point analyses is to identify assumptions about the missing data 
under which the conclusions from the main analysis change (ie: under which there is no longer 
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evidence of a treatment effect). These tipping point analyses will only be performed if the 
primary efficacy analysis results in a statistically significant treatment effect (p<0.05). 
As a first step, the worst-case scenario will be evaluated. Specifically, all BKZ randomized 
subjects with a missing ACR50 at Week 16 (or non-missing ACR50 after study treatment 
discontinuation) will be imputed as non-responders, while all placebo-randomized subjects with 
a missing ACR50 at Week 16 will be imputed as responders. While there is little justification for 
such an approach, it makes the most putative assumption possible against a BKZ treatment 
effect. After applying this imputation approach, a logistic regression model consistent with the 
one described for the primary analysis will be applied. If the p-value for the OR of BKZ versus 
placebo is < 0.05, then no further tipping point analyses are needed. 
If this analysis based on the worst-case scenario results in a p-value > 0.05, then additional 
tipping point analyses will be performed. In practice, it implies different delta adjustments will 
be made to the assumed responses on the missing data (where missing values include 
observations after the IE date and any other missing values) in each treatment group 
independently with various degrees of plausibility with the goal to find for each treatment group 
the “tipping point” that will significantly reverse the primary result which yielded a p-value < 
0.05. These delta adjustments will be done on each component of ACR50 as follows: 
• Step 1: The same MCMC method described in Section 4.2.2.2 will be implemented for non-
monotone (intermittent) missing pattern values, using the same imputation model. This will 
be based on 100 imputations. 
• Step 2: Based on the datasets obtained in Step 1, a monotone regression model will be 
applied (using the same imputation model as in Step 1) and as described in Section 4.2.2.2. 
This will be based on 1 imputation. 
• Step 3: Imputed values will be shifted using a delta adjustment independently in each 
treatment group. 
Once defined, the same delta adjustment value will be applied on the imputed values for the 
Week 16 visit only. The selected scenario will assume that subjects randomized to BKZ and 
who have missing data have a lower probability of response compared to subjects 
randomized to placebo with missing data.  
− For ACR components for which high scores are associated with a less favorable outcome, 
it will mean that:  
▪ A positive shift is applied to the imputed value for subjects randomized to BKZ to 
increase the imputed value. 
▪ A negative shift is applied to the imputed value for subjects randomized to 
placebo to decrease the imputed value. 
A set of possible values will be first pre-defined for the delta parameter as below: 
− For all ACR component, the value of the initial delta parameter will be equivalent to a 
specific percentage of the possible range of each component (i.e. 5%). For hs-CRP, the 
range will be based on the log-transformed values at Week 16. The delta parameters for 
each endpoint are listed in the table below:  
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Table 4‒3: 
Tipping point analysis: Delta parameter for each ACR component 
ACR component1 
Range 
Delta 
SJC 
0-66 
3.3 
TJC 
0-68 
3.4 
HAQ-DI 
0-3 
0.15 
PtAAP, PhGA-PsA, PGA-PsA 
0-100 
5 
hs-CRP2 
Observed range  
of the loge transformed values 
for all BKZ and Placebo 
subjects (at Week 16) 
5% of the observed range 
1The shifted imputed value should not exceed the range for the ACR component. 
2The delta adjustment will be applied on the loge transformed imputed and observed values which will then be 
exponentiated prior to deriving endpoint.   
• Step 4: Standard rounding rules will be applied to the imputed values. If the SAS® PROC 
MI yields a value outside of the range for the given component, the value will be updated 
after the imputation has been performed to be within the predefined range.  
• Step 5: Repeat Steps 1 to 4 for each ACR component. The composite binary endpoint 
(ACR50) will then be derived based on the multiply shifted imputed datasets obtained for 
each component.  
• Step 6: Additionally, as the primary endpoint is derived using NRI, subjects randomized to 
BKZ with missing data (where missing values include observations after the IE date and any 
other missing values) should be set to non-response, after applying the delta adjustment 
outlined in Step 3 above. This ensures subjects randomized to BKZ do not have a higher 
probability of response in the tipping point analyses compared to the primary analysis (i.e. a 
subjects randomized to BKZ who is non-responder in the primary analysis cannot become a 
responder in the tipping point analyses). 
• Step 7:  In the data obtained, for each value of the imputation number, ACR50 will be 
analyzed using a logistic regression model with factors of treatment group, regions, and bone 
erosion at Baseline as fixed effects.  
• Step 8: The results obtained from the 100 logistic regression analyses in Step 6 will be 
combined for overall inference using Rubin’s rules, and the results obtained for each shift 
parameter will be presented in a single table.  
• Step 9: Step 3 to 8 will be repeated so that, at each iteration, missing values are adjusted with 
a larger shift than at the previous iteration. Depending on the results obtained, delta 
parameters with more granularity (eg, 2 times, 3 times the initial delta, etc.) will be 
investigated. The process will go on until the p-value for the OR between BKZ and placebo 
is no longer statistically significant (ie ≥ 0.05). The OR, 95% CI, and p-values obtained for 
each value of delta will be combined in one single table.  
4.2.2.5 
Treatment Policy Strategy  
Another supportive analysis will be performed on the primary efficacy endpoint to address IE.  
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The treatment policy strategy will include all available data observed at the week of interest 
(Week 16) regardless of the occurrence of IE. This means the analysis includes on- and off-
treatment values collected after subjects prematurely discontinued study treatment but agreed to 
remain on the study and continued to attend visits and provide assessments at those visits. Those 
observed values will be analyzed according to the subject’s randomized treatment. Subjects for 
whom efficacy data cannot be obtained at the week of interest, despite attempts to retain them in 
the study, will have their data imputed using MI-MCMC / monotone regression (Section 4.2.2.2) 
based on non missing data collected up to Week 16.   
4.2.3 
Handling of missing data for AEs 
For analyses of AEs, a complete date must be established to correctly identify the AE as 
occurring during treatment or not. For purposes of imputing missing components of partially 
reported start and stop dates for AEs, the algorithms listed below will be followed. In the event 
of ambiguity or incomplete data which makes it impossible to determine whether the AE was 
treatment-emergent, the AE will be considered treatment-emergent. 
Although the algorithms for treatment-emergence depend on the start date, imputation rules are 
provided for stop date as well, as these may be needed for certain statistical analyses, such as an 
analyses of AE prevalence or AE duration. 
Start and stop dates of AEs will be displayed as reported in the subject data listings (ie, no 
imputed values will be displayed in data listings). 
Imputation of partial AE start dates  
• If only the month and year are specified: 
− if the month and year of first dose of IMP is not the same as the month and year of the 
start date, then use the 1st of the month 
− if the month and year of first dose of IMP is the same as the month and year of the start 
date, then use the date of first dose of IMP 
− if the subject did switch treatment during that month and year from placebo to BKZ at 
Week 16, then use the date of treatment switch. 
• If only the year is specified:  
− if the year of first dose is not the same as the year of the start date, and if the subjects did 
not switch from placebo to BKZ at Week 16 during that year then use January 1 of the 
year of the start date 
− if the year of first dose is not the same as the year of the start date, and if the subjects did 
switch from placebo to BKZ at Week 16 during that year then use the date of treatment 
switch 
− if the year of first dose is the same as the year of the start date and the same as the year 
the subject did switch from placebo to BKZ at Week 16, then use the date of first dose. 
• If the date is completely unknown: 
− use the date of first dose of IMP if the stop date is unknown or not prior to the onset date  
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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 an 
AE is treatment-emergent, the AE will be considered as treatment emergent. 
Other imputations 
In addition, the following imputations will be applied when presenting AE in summary tables: 
• if the intensity of an AE is unknown, it will be considered as severe  
• If the relationship to study drug is missing, it will be considered as related  
No imputation rule will be applied for missing seriousness. 
4.2.4 
Handling of missing data for prior and concomitant medications 
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days. In the event of ambiguity or incomplete data which makes it impossible to determine 
whether a medication was concomitant or not, the medication will be considered as concomitant. 
Such imputations will only be performed for these classifications and calculations; in the listings 
all data will be shown as recorded on the eCRF. 
Imputation of partial start dates 
• If only the month and year are specified: 
− if the month and year of first dose of IMP is not the same as the month and year of the 
start date and the subject did not switch from placebo to BKZ at Week 16 during that 
month and year, then use the 1st of the month. 
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− if the month and year of first dose of IMP is the same as the month and year of the start, 
then use the date of first dose of IMP. 
− if the subject did switch from placebo to BKZ at Week 16 during that month and year, 
then use the date of treatment switch. 
• If only the year is specified: 
− If the year of first dose of IMP is not the same as the year of the start date and the subject 
did not switch from placebo to BKZ at Week 16 during that year, then use the 1st of 
January of the year of the start date. 
− If the year of first dose of IMP is the same as the year of the start date, then use the date 
of first dose of IMP. 
− if the year of first dose of IMP is the same as the year the subject did switch treatment 
from placebo to BKZ at Week 16, then use the date of treatment switch. 
− if the year of first dose of IMP is the same as the year of the start date and the same as the 
year the subject did switch from placebo to BKZ at Week 16, then use the date of first 
dose of IMP. 
• If the start date is completely unknown: 
− if the stop date is unknown or not prior to the date of first dose of IMP, then use the date 
of first dose of IMP. 
− if the stop date is prior to the date of first dose of IMP, then set the start date to the 1st of 
January of the year of the end date. 
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. There will be no 
imputation of any other missing data. 
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 
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− 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, the medication will be considered as concomitant. 
4.3 
Planned analyses and data monitoring 
4.3.1 
Interim analyses & final analysis 
Two interim analyses will be performed:  
• Interim analysis 1: Week 24 analysis.  
The Week 24 analysis is the first interim analysis after all randomized subjects have completed 
the DBP and the ATP up to Week 24 or have withdrawn from the IMP or the study before Week 
24. The purpose of this analysis is to perform a comprehensive evaluation of all available data 
for the 3 treatment arms to prepare a regulatory submission for a marketing authorization 
application based on this analysis.  This interim analysis will cover the analysis of all efficacy 
and non-safety by visit tables on data collected up to Week 24 and the analysis of safety in tables 
on data collected up to the cut-off date (defined as Week 24 visit) for the last subject (all 
available data will be reported in listings). The type of efficacy and safety tables provided for the 
first interim analysis is detailed in Table 4‒4. 
For this analysis, the database will be cleaned and locked, and the treatment codes will be made 
available to the independent unblinded UCB and PAREXEL personnel. The database will 
include all data available at the time of the lock including available SFU data (for subjects 
having completed the SFU Period). An interim report will be written. The investigators and the 
subjects will remain blinded until the final analysis is completed. A blinding plan will be written 
to ensure blinding of investigators and subjects, define blinded and unblinded teams at UCB and 
PAREXEL and describe the process of generation and dissemination of the results of this first 
interim analysis. This plan will be finalized prior to the lock of the database for this analysis. 
• Interim analysis 2: Week 52 analysis.  
The Week 52 analysis is the second interim analysis after all subjects have completed Week 52 
or have withdrawn from the IMP or the study. The purpose of this analysis is to demonstrate the 
long-term efficacy and safety of BKZ, perform a comprehensive evaluation of all available data 
for the study and to supplement the regulatory submission based on the Week 24 interim 
analysis. This analysis will comprise the results of the 16 weeks of the DBP, the 36-weeks of the 
ATP and the available SFU data at the time of this analysis (for subjects having completed the 
SFU Period). The type of efficacy and safety tables provided for the second interim analysis is 
detailed in Table 4‒4.  
No formal alterations to the further study conduct (eg, stopping rules, sample size re-estimation, 
or changes to eligibility criteria) are planned for the 2 interim analyses. 
No separate SAP for the interim analyses will be provided. The TFL shells for the interim and 
the final analyses will be provided in the same document and appropriately identified. 
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The below table summarize the type of efficacy and safety analyses to be performed for the 2 
interim analyses.  
Table 4‒4: 
Type of efficacy and safety tables provided for the interim analyses 
Variable 
Type of tables 
Period or 
Timepoint 
(Analysis set) 
Treatment  
groups 
Provided for 
Interim 
Analysis 1 
(Week 24 analysis) 
Provided for  
Interim 
Analysis 2 
(Week 52 analysis) 
Tables of primary 
efficacy variable 
Week 16 
(RS FAS PPS) 
 
• 
Placebo  
• 
BKZ 160mg Q4W 
• 
ADA 40mg Q2W  
Yes 
Yes, rerun of tables 
provided for interim 
analysis 1 
Tables of secondary 
efficacy variables. 
Week 4 and 16 
(RS*)  
 
• 
Placebo  
• 
BKZ 160mg Q4W 
• 
ADA 40mg Q2W 
Yes 
Yes, rerun of tables 
provided for interim 
analysis 1 
Tables / Graphs of 
time to ACR response   
DBP 
(RS) 
 
• 
Placebo  
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes, subjects not 
achieving response 
at Week 16 are 
censored at Week 
16. 
Yes, rerun of tables 
provided for interim 
analysis 1 
Overall Study 
Period 
(RS) 
 
• 
Placebo/BKZ 160 mg 
Q4W 
• 
BKZ 160mg Q4W 
• 
ADA 40mg Q2W 
Yes, subjects not 
achieving response 
at Week 24 are 
censored at Week 
24. 
Yes, subjects not 
achieving response 
at Week 52 are 
censored at Week 
52. 
By-visit tables of other 
efficacy endpoints 
Overall Study 
Period  
(RS*) 
• 
Placebo / BKZ 160 
mg Q4W 
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes, from Baseline 
to Week 24  
Yes, from Week 0 
until Week 52.  
Extra by-visit tables 
for ACR50 and 
PASI90 using 
Baseline Week 16  
ATP 
(ATS) 
• 
Placebo / BKZ 
160mg Q4W 
Yes, from Week 20 
until Week 24 
Yes, from Week 16 
until Week 52. 
Extent of exposure and 
time at risk  
DBP (SS) 
• 
Placebo  
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes 
Yes 
ATP (ATS) 
• 
Placebo / BKZ 
160mg Q4W  
• 
BKZ 160mg Q4W 
• 
BKZ 160mg Q4W 
Total   
• 
ADA 40mg Q2W 
Yes, until Week 24 
Yes 
AMP 
(AMS) 
• 
Placebo / BKZ 
160mg Q4W  
• 
BKZ 160mg Q4W 
• 
BKZ 160mg Q4W 
Total   
• 
ADA 40mg Q2W 
Yes, until Week 24 
Yes 
Cumulative study 
medication duration 
Overall Study 
Period (SS) 
• 
Placebo / BKZ 
160mg Q4W  
• 
BKZ 160mg Q4W 
• 
ADA 40mg Q2W 
Yes, until Week 24 
Yes 
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Variable 
Type of tables 
Period or 
Timepoint 
(Analysis set) 
Treatment  
groups 
Provided for 
Interim 
Analysis 1 
(Week 24 analysis) 
Provided for  
Interim 
Analysis 2 
(Week 52 analysis) 
Tables of AEs or 
Tables of AEs of 
Special Interest or 
Tables of Other Safety 
Topics of Interest.  
DBP (SS) 
• 
Placebo  
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes  
Yes 
ATP (ATS) 
• 
Placebo / BKZ 160 
mg Q4W 
• 
BKZ 160 mg Q4W 
• 
BKZ 160mg Q4W 
Total  
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this analysis 
Yes 
AMP 
(AMS) 
• 
BKZ 160mg Q4W 
Total 
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this analysis 
Yes, for treatment-
emergent events 
until Week 52 and 
including available 
SFU data 
By-visit and shift 
tables of laboratory 
data or vital signs 
Overall Study 
Period 
(SS) 
• 
Placebo / BKZ 
160mg Q4W  
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this analysis 
Yes, for all visits 
until Week 52  
Tables of markedly 
abnormal laboratory 
values or vital signs 
DBP (SS) 
• 
Placebo  
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes 
Yes 
ATP (ATS) 
• 
Placebo / BKZ 
160mg Q4W  
• 
BKZ 160mg Q4W  
• 
BKZ 160mg Q4W 
Total  
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this analysis 
Yes  
AMP 
(AMS) 
• 
BKZ 160mg Q4W 
Total 
• 
ADA 40mg Q2W 
Yes 
Yes 
By-visit tables of 
ECG, table of ECG 
abnormalities  
Overall study 
period 
(SS) 
• 
Placebo / BKZ 
160mg Q4W 
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this 
analysis. 
Yes, for all visits 
until Week 52. 
Table of eC-SSRS 
events. 
Overall Study 
Period 
(SS) 
• 
Placebo / BKZ 
160mg Q4W 
• 
BKZ 160mg Q4W  
• 
ADA 40mg Q2W 
Yes, until cut-off 
date for this analysis 
Yes 
Table of tuberculosis 
testing.  
Screening and 
W48 
(SS) 
• 
Placebo / BKZ 
160mg Q4W 
• 
BKZ 160mg Q4W 
• 
ADA 40mg Q2W 
Yes, Screening and 
Week 48 values (if 
observed prior to 
cut-off date). 
Yes, Screening and 
Week 48 value.  
 
ACR= American College of Rheumatology, ADA=Adalimumab, AE=adverse events, ATP=Active Treatment-Blind 
Period, ATS=Active Treatment-Blind Set, AMP=Active Medication Periods, AMS=Active Medication Set,  
BKZ=Bimekizumab, DBP=Double-Blind Treatment Period, eC-SSRS=electronic Columbia Suicide Severity Rating 
Scale, ECG=electrocardiogram, FAS=Full Analysis Set, PASI= Psoriasis Area and Severity Index, RS=Randomized 
Set, SS=Safety Set  
*For subjects in the Radiographic Set for vdHmTSS  
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Note: Subjects in the Placebo/ BKZ 160mg Q4W treatment group are taking BKZ 160 mg Q4W treatment after 
Week 16.  
• The final analysis. 
The final analysis will consist of a rerun of all analyses provided during the preceding Week 52 
analysis. This includes new SFU data that were not available for the Week 52 analysis.  If there 
is no SFU data ongoing, the final analysis will be identical to the Week 52 analysis. 
Prior to the final analysis, additional data cuts may be prepared following regulatory requests or 
for publication purposes. 
4.3.2 
Data Monitoring Committee  
A Data Monitoring Committee (DMC) will be reviewing safety data on an ongoing basis. The 
DMC membership includes experienced clinicians and a statistician, all of whom have expertise 
in clinical studies. Further details are specified in the DMC Charter. The presentation and 
analysis of data for the DMC meetings will be described in a separate DMC SAP. 
4.4 
Multicenter studies 
In general, the data from all centers will be pooled for the purposes of the analysis. However, the 
effect of center (using a pooling of centers by region) on results will be evaluated as mentioned 
in Section 3.8. 
4.5 
Multiple comparisons/multiplicity 
A step-down closed testing procedure will be applied for the primary endpoint and some 
secondary endpoints. The testing procedure will account for multiplicity and control the family-
wise type I error rate at alpha=0.05 (2-sided).  
For each test, on each binary efficacy endpoint, the null hypothesis is that the conditional odds 
ratio is equal to one (H0: ORT1T2 = 1). The alternative hypothesis is that the conditional odds ratio 
is not equal to one (HA: ORT1T2≠ 1). 
For each test, on each continuous efficacy endpoint, the null hypothesis is that there is no 
difference between treatment groups (H0: T1 – T2 = 0). The alternative hypothesis is that there is 
a difference between treatment groups (HA: T1 – T2 ≠0). 
T1 refers to BKZ and T2 to placebo.  
According to this strategy, the statistical testing of an endpoint can be investigated only if the 
null hypothesis for the previous endpoint has been rejected (i.e., if p<0.05). Table 4‒5 shows the 
testing order for these endpoints. 
Table 4‒5: 
Sequential testing procedure of primary/secondary efficacy 
endpoints (fixed sequence testing procedure) (All efficacy endpoints 
at Week 16) 
BKZ 160mg Q4W 
H1 
ACR50 Response superior to Placebo 
H2 
Change from Baseline HAQ-DI superior to Placebo  
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BKZ 160mg Q4W 
H3 
PASI90 Response superior to Placebo  
H4 
Change from Baseline SF-36 PCS superior to Placebo 
H5 
MDA superior to Placebo 
H6 
Change from Baseline vdHmTSS* superior to Placebo on subjects with elevated hs-CRP 
and/or with at least one bone erosion (hs-CRP ≥6mg/L and/or erosion-positive) 
H7 
Enthesitis-free state superior to Placebo (based on pooled PA0010 and PA0011 W16 
data) 
H8 
Dactylitis-free state superior to Placebo (based on pooled PA0010 and PA0011 W16 
data) 
H9 
Change from Baseline vdHmTSS** superior to Placebo 
ACR=American College of Rheumatology; BKZ=bimekizumab; CfB=change from Baseline; H=hypothesis; 
HAQ-DI=Health Assessment Questionnaire - Disability Index; hs-CRP=high sensitivity C-reactive protein; 
LEI=Leeds Enthesitis Index; MDA=Minimal Disease Activity; PASI=Psoriasis Area and Severity Index. 
PCS=Physical Component Summary; Q4W=every 4 weeks; SF-36=Short-Form 36-item Health Survey; 
vdHmTSS=Van der Heijde modified Total Sharp Score.  
* It is planned to enroll a minimum of 45% of subjects who are positive for elevated hs-CRP (hs-CRP ≥6mg/L) 
and/or who have at least 1 bone erosion at Screening.  
** Based on the overall population 
4.6 
Use of an efficacy subset of subjects 
The RS will be the primary analysis set for efficacy analyses, but analyses will also be repeated 
on the FAS and the PPS for the primary efficacy endpoint. The FAS analysis will evaluate 
whether there are differences in the efficacy analysis between randomized subjects and 
randomized subjects with a Baseline assessment, while the PPS analysis will evaluate the effect 
of IPD on the analysis. 
4.7 
Active-control studies intended to show equivalence 
Efficacy outcomes are based on superiority comparisons of the Bimekizumab 160mg sc Q4W to 
placebo, this section is then not applicable for this study. 
4.8 
Examination of subgroups 
Subgroup analyses will be performed on the variables below. They are all assessed at Baseline 
except concomitant cDMARDs, concomitant MTX and ADAb status which will be assessed 
during the 16-week DBP. Subgroup analyses will be performed on the ACR50 response, the 
PASI90 response and the HAQ-DI response (subjects with a decrease of HAQ-DI from Baseline 
of at least 0.35) at Week 16. ADAb status will also be used for subgroup analysis for the PK 
endpoints. The variables for subgroup analyses will be:   
• Age (<45 years of age, ≥45 years of age) 
• Gender (male, female) 
• Disease duration (<1 year, ≥1 year) 
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• Region (eg, North America, Western Europe, Eastern Europe, Asia. Western Europe will be 
combined with Asia if any of these 2 regions have less than 10% of the randomized subjects) 
• Race (White, Black and Other) 
• Body weight at Baseline (≤100kg, >100kg) 
• Bone erosion (≥1) at Baseline (Yes, No) 
• hs-CRP at Baseline (<6mg/L, ≥6mg/L) 
• Bone erosion (≥1) and/or hs-CRP ≥6mg/L at Baseline (Yes, No) 
• Prior cDMARDs (0, 1, ≥2) (taken prior to Baseline,). Such medications will be classified 
using the adjudicated spreadsheet.  
• Concomitantly receiving cDMARDs versus no concomitant cDMARDs  
• Concomitantly receiving MTX versus no concomitant MTX  
• Concomitantly receiving MTX at Baseline vs. other cDMARDs at Baseline (MTX at 
Baseline, no MTX at Baseline and cDMARDs at Baseline, no MTX at Baseline and no 
cDMARDs at Baseline)  
• PSO affected BSA at Baseline (<3%, ≥3% to 10%, >10%) 
• BASDAI at Baseline (<4, ≥4) 
• ADAb status (positive, negative) (Section 9.2) (for the BKZ 160mg Q4W group only) 
• Human leukocyte antigen B27 (HLA-B27) (positive, negative). 
In the context of submission to Japanese health authorities, a subset of tables and figures will be 
provided in the subgroup of subjects randomized in Japan(when MI is used, data for subjects 
randomized in Japan will be extracted from the MI datasets generated for the full population). 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
Subject disposition will be summarized for all subjects screened overall, by region and by site. In 
this summary, the dates of first subject screened and dates of last subject last visit (end of the 
study), number of screened subjects, and the number of subjects included in each analysis set 
(RS, SS, FAS, AMS, ATS, PPS, RAS, PK-PPS, COVID-19-free Set) will be presented.  
The disposition of subjects into treatment groups and analysis sets will also be summarized on 
the RS. 
Reasons for screen failures (as collected on the Study Termination Screen Failure CRF page) 
will be listed for all screened subjects who failed to be randomized.  
The number and percentage of randomized subjects who completed the study, completed the 
study not on randomized treatment, who discontinued IMP overall and by reason and who 
discontinued the study, with the primary reason for study discontinuation (as collected on the 
Study Termination CRF page), by study treatment period (DBP and ATP) will be tabulated 
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overall and by treatment group. The numbers and percentages of randomized subjects entering 
the SFU Period will additionally be presented. The numbers and percentages of these subjects 
who either complete the SFU visit or not will additionally be presented.  
The numbers and percentages of randomized subjects entering the Open Label Extension (OLE) 
study and those not entering the OLE study will be presented. Of the randomized subjects not 
entering the OLE study.  
A subject will be said to have completed the study if she/he had completed the last scheduled 
study visit, not including SFU visit (the SFU visit is typically 140 days after the last dose of IMP, 
which is roughly equivalent to 5 half-lives of BKZ). 
A subject will be considered to have completed a period if she/he completes the last scheduled 
study visit for that period. 
Subjects who previously discontinued IMP and are continuing for all scheduled visits through 
the end of each period (DBP or ATP) will also be considered as completing the period.  A 
separate summary of subjects who discontinue IMP will be provided. 
Finally, the number of randomized subjects who discontinued the study due to AEs (during the 
DBP and the ATP separately) by type of AEs (serious fatal, non-fatal, other) will be summarized. 
Study disposition and termination details will be listed for all screened subjects. Additional 
listings will be created on study discontinuation, subject analysis sets and visit dates (both actual 
visit and visit remapped for analysis). A listing will also be provided for subjects who did not 
meet the study eligibility criteria. 
To assess subject disposition (entry and periods in the study) during the COVID-19 pandemic, 
subject disposition will be assessed by period of the COVID-19 pandemic (pre – during) (Section 
3.11), by comparing the dates of visits (or events) to the dates of the COVID-19 pandemic 
period. 
5.2 
Impact of COVID-19 
A listing of visits affected by COVID-19 will be presented based on the Enrolled Set including 
the visit, dates of visit, relationship to COVID-19, impact category and a narrative (short 
description) of the event. These data will be summarized by treatment group and overall, for 
randomized subjects. 
A summary of study visits by COVID-19 pandemic period (pre – during) will be presented for 
subjects enrolled prior or during the pandemic.  
In addition, in order to assess the potential impact of COVID-19 on the collection and reporting 
of efficacy data, a separate summary based on the RS will be presented to display missing data as 
well as data collected via an alternative modality (eg: phone, video call) for efficacy endpoints 
included in the hierarchy (Table 4‒5). For these displays, missing data will be presented only for 
visits affected by COVID-19, as reported on the dedicated eCRF page. Missing data at other 
visits and for other reasons will not be included. 
For visits conducted remotely, it was not possible to assess some endpoints (eg, TJC, SJC, LDI, 
LEI, PASI, etc.) and therefore these assessments will be missing for those visits. In addition, for 
any missed visit or visit conducted remotely, the CRP assessment will also be missing. Such 
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assessments will be considered missing because of the COVID-19 pandemic. For these visits, it 
will therefore not be possible to assess composite endpoints like ACR response. For this 
summary table based on the RS, only visits at which efficacy assessments are scheduled will be 
included. 
5.3 
Protocol deviations 
The definition of an IPD is given in Section 3.5.  
A summary displaying the number and percentage of subjects with an IPD will be provided by 
treatment group separately for the DBP on the RS and on the ATP on the ATS. This will include 
a summary of subjects excluded from the PPS (DBP only) and the PK-PPS. The summary will 
be provided overall and by type of deviation (inclusion criteria deviation, exclusion criteria 
deviation, withdrawal criteria deviation, prohibited concomitant medication, incorrect treatment 
or dose, treatment non-compliance, procedural non-compliance, COVID-19 related IPD) as well 
as the number and percentage of subjects excluded from the PPS due to reason other than PD.  
Criteria for exclusion of subjects from the PPS or PK-PPS will be defined in a separate 
document.  
A by-subject listing of IPDs will be provided for all subjects in the RS. 
A by-subject listing of COVID-19 related PDs will be provided for all subjects in the RS. 
A by-subject listing of subjects excluded from the PPS for reasons other than IPD will be 
provided. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
Unless otherwise specified, all summaries will be based on the SS and repeated on the RS 
(unless the SS and RS analysis sets are identical) and on the ATS. 
6.1 
Demographics 
The following demographic variables measured at Baseline will be summarized overall and by 
treatment group: age (years), gender, country, geographic region, country, race, ethnicity, height 
(cm), body weight (kg) and Body Mass Index (BMI) (kg/m2).  
Age, body weight and BMI will be summarized as continuous variables and as categorical 
variables based on the categories specified below.  
For age, 3 sets categories will be defined: 
• ≤18, 19 to <65, ≥65 years (clinicaltrials.gov requirement),  
• 18 to <65, 65 to <85, ≥85 years (EudraCT requirement),  
• 18 to <45, ≥45 to <65, ≥65 years.  
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For body weight, categories will be: ≤100 kg, >100 kg. 
BMI (in kg/m2) will be recalculated during analysis based on height (in meter) and weight (in 
kg). The formula for BMI (kg/m2) calculation is: 
𝐵𝑀𝐼 = 𝐵𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
(𝐻𝑒𝑖𝑔ℎ𝑡(𝑚))2
 
For BMI, categories will be: <25, 25 to <30, 30 to <35, ≥35 kg/m2.  
A separate frequency table will summarize the subject’s lifestyle on the SS. 
By-subject listings on demographics, female subject’s childbearing potential data will be 
provided for all screened subjects. Listing on lifestyle will be provided on the RS. 
To understand the study population during the different periods of the COVID-19 pandemic, the 
reporting of Baseline demographics will be repeated by COVID-19 pandemic period (pre or 
during as determined by the Baseline visit date) on the SS. 
6.2 
Baseline characteristics 
6.2.1 
Baseline values for components of the primary efficacy variable 
Baseline values for the 7 components of the primary efficacy variable will be summarized by 
treatment group and overall. The following variables will be summarized: 
• TJC  
• SJC  
• PGA-PsA 
• PhGA-PsA 
• PtAAP 
• HAQ-DI 
• hs-CRP (mg/L).  
For hs-CRP, SJC and TJC, the following rule will be applied: if the Baseline value is missing, 
then the most recent value (taken at previous unscheduled visit or at Screening) will be 
considered. If the value is still missing, the Baseline value will be considered missing.  
The hs-CRP variable will be summarized using descriptive statistics and in classes (≥6mg/L, 
<6mg/L).  
Efficacy variables not listed above will not be presented in the Baseline characteristics section. 
They will be presented in by-visit tables in the context of the analysis of secondary and other 
efficacy variables. 
To understand the study population during the different periods of the COVID-19 pandemic, the 
reporting of Baseline characteristics will be repeated by COVID-19 pandemic period (pre or 
during as determined by the Baseline visit date) on the SS. 
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6.2.2 
Other Baseline characteristics 
The following variables will be summarized by treatment group and overall: 
• Bone erosion (0, ≥1) – based on IXRS randomization strata 
• Bone erosion (0, ≥1) – based on actual randomization strata (as per imaging data) 
• Bone erosion (≥1) and/or hs-CRP ≥6mg/L at Screening (Yes, No). To determine this, bone 
erosion will be derived from imaging data and corresponds to actual randomization strata 
• % of BSA affected by PSO (<3%, ≥3% to ≤10%, >10%)  
• PASI score at Baseline (for subjects with PSO involving at least 3% of BSA at Baseline). 
This variable will be summarized as a continuous variable and in classes (<10, 10 to 20,>20)  
• BASDAI (<4, ≥4) 
• Rheumatoid factor (positive, negative). A rheumatoid factor value <30IU/mL is defined as 
negative and a value ≥30IU/mL is defined as positive  
• Anti-cyclic citrullinated peptide (CCP) antibodies (positive, negative). Anti-CCP antibodies 
negative is a value <20U/mL and a value ≥20U/mL is defined as positive 
• Nail psoriasis (yes, no) 
• Dactylitis (“yes” if LDI score>0, “no” if LDI score=0, missing) 
• Enthesitis based on LEI (“yes” if LEI score>0, “no” if LEI score=0, missing) 
• Enthesitis based on SPARCC (“yes” if SPARCC>0, “no” if SPARCC=0, missing) 
• Prior NSAID (yes, no)  
• NSAID at Baseline (yes, no) 
• Past cDMARDs therapy (yes, no)  
• Prior cDMARDs (0, 1, ≥2) (Section 4.8) 
• cDMARDs at Baseline (yes, no) 
• HLA-B27 (positive, negative) 
• Methotrexate at Baseline (yes, no) (Section 4.8) 
• Prior oral corticosteroids (yes, no) 
• Oral corticosteroids at Baseline (yes, no). 
To understand the study population during the different periods of the COVID-19 pandemic, the 
reporting of other Baseline characteristics will be repeated by COVID-19 period (pre or during 
as determined by the Baseline visit date) on the SS. 
6.2.3 
History of psoriatic arthritis 
The following PsA history variables will be summarized overall and by treatment group:  
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• The time since first diagnosis of PsA (years). Time since first diagnosis will be summarized 
as a continuous variable and as categorical variables based on following categories: <1, 1-<2, 
≥2 years 
• The time since first diagnosis of PSO (years), calculated as : 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑖𝑛𝑓𝑜𝑟𝑚𝑒𝑑 𝑐𝑜𝑛𝑠𝑒𝑛𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠 
365.25
 
If the date of diagnosis is partial, it should be imputed to the most recent feasible date (ie, last 
day of the month if only day is missing, or the last day of the year if day and month are 
missing). 
• The age at first diagnosis date of PsA (years), calculated as:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑃𝑠𝐴 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑖𝑠−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑏𝑖𝑟𝑡ℎ
365.25
 
If the date of PsA diagnosis is partial, it should be imputed to the most recent feasible date 
(ie: the last day of the month if only day is missing, or the last day of the year if day and 
month are missing. Partial date should not be imputed later than the subject’s screening date).   
For subjects enrolled at German sites, only the year of birth may be entered into the eCRF for 
this study. For these subjects age will be calculated after imputing their date of birth to be on 
January 1st. 
• The PsA subtype (polyarticular – symmetric arthritis, oligoarticular – asymmetric arthritis, 
distal interphalangeal, joint predominant, spondylitis predominant, arthritis mutilans)  
The data on history of psoriasis and psoriatic arthritis will be listed for all screened subjects. 
6.3 
Medical history and concomitant diseases 
Medical history conditions are defined as conditions that have resolved prior to study entry.  
Ongoing medical conditions are defined as conditions that are ongoing at the time of study entry. 
• Medical history and ongoing medical conditions will be summarized on the SS by MedDRA 
System Organ Class (SOC) and Preferred Term (PT), by treatment and overall including the 
number and percentage of subjects with each condition. The denominator of the percentages 
will be the number of subjects in the population considered. The tables will be ordered 
alphabetically for SOC and in terms of decreasing frequency for PT within SOC in the BKZ 
treatment group. In the event of ties, PT will be ordered alphabetically. 
Medical history and ongoing medical conditions will be listed by treatment and subject including 
the reported term, PT, and SOC on the RS. The start date (month and year only) and the end date 
(or ongoing if applicable) will be included in the listing. Partial dates will not be imputed. A 
glossary of all medical history conditions will be presented including the reported term, PT and 
SOC. Concomitant medical procedures will be listed on the RS. 
6.4 
Prior and concomitant medications 
Prior medications include any medications that started prior to the date of the first IMP 
administration.  
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Concomitant medications are medications taken at least one day in common with the IMP dosing 
period.   
The IMP dosing period corresponding to the combined DBP and ATP will be calculated as 
follows: 
The study medication dosing period start date is defined as the date of first dose. 
The study medication dosing period stop date is defined as follows: 
• For subjects who are ongoing at the time of the clinical data cut (not including participants 
who are in SFU) use date of last clinical contact 
• For subjects who died prior to last visit (not including those who died during SFU), use the 
minimum of the following: 
− Date of death 
− Date of last dose of any study medication + 28 days 
• For subjects who complete the study as planned, the dosing period ends at the later of the 
following 2 dates: 
− Date of last administration of IMP + 14 days 
− The last scheduled visit date not including SFU 
• For all other subjects, use the maximum of the following: 
− Date of last dose of any study medication + 28 days 
− Date of last visit (not including SFU). 
In the case of missing data, the classification of medications as prior or concomitant will be 
performed as described in Section 4.2.4. Imputations of missing data will be performed before 
calculation of relative study days. 
The number and percentage of subjects taking prior medications (excluding past psoriasis 
medications) will be summarized on the SS by treatment group, overall and by ATC class, 
presenting Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC level 3) 
and PT.  
The table summary will be ordered alphabetically for the ATC class and in terms of decreasing 
frequency for PT within ATC class in the BKZ treatment group. In the event of ties, PT will be 
ordered alphabetically.  
The number and percentage of subjects taking concomitant medications will be summarized 
similarly on the SS by treatment group (for the Week 24 analysis on the period from Baseline to 
Week 24, for the Week 52 analysis on the overall study treatment period).  
A by-subject listing of all prior (on the RS) and concomitant medications (on the RS) as well as 
glossary of all medical medications will be provided. 
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6.5 
Prohibited medications and permitted rescue therapy after 
Week 16 
Prohibited or restricted medications are defined in the protocol (section 7.8.2). Prohibited 
medications will be listed on the SS. 
Some permitted rescue therapies are allowed after Week 16 as defined in Section 5.4 of the 
protocol. 
The number and percentage of subjects who used permitted rescue medications after Week 16 
will be summarized by ATC class, presenting ATC Level 1, ATC level 3, and PT. This table will 
be produced on the ATS.  
Permitted rescue therapies will be listed on the SS. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Treatment compliance summaries will be provided: 
• On the SS for the DBP, by randomized treatment and for all subjects. 
• On the ATS for the ATP, by randomized treatment, for all BKZ treated subjects and for all 
subjects 
• On the AMS for the AMP, by randomized treatment, for all BKZ treated subjects and for all 
subjects.  
Due to the method of IMP administration, compliance will be examined in terms of completed 
injections. Treatment compliance will be calculated as: 
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑎𝑐𝑡𝑢𝑎𝑙 (𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒𝑑) 𝑖𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛𝑠 
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑖𝑛𝑗𝑒𝑐𝑡𝑖𝑜𝑛𝑠
 x 100 % 
The total number of expected injections is derived relative to when the subject finishes treatment:  
• If a subject completes the DBP, 8 injections are expected (every 2 weeks from Baseline to 
Week 16) 
• If a subject completes treatment over the entire study, 26 injections are expected (every 2 
weeks from Baseline to Week 50) 
• If a subject discontinues early, then the number of expected injections is based on the time of 
early discontinuation relative to the dosing visits. This number will be calculated by 
determining the number of expected dosing visits prior to the date of early discontinuation. If 
the early discontinuation coincides with an expected dosing visit, this visit will used to 
determine the number of expected injections. 
A summary of percent treatment compliance categorized as <75% and ≥75% will be provided by 
treatment group, as well as a by-subject listing of treatment compliance. 
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8 
EFFICACY ANALYSES 
8.1 
Statistical analysis of the primary efficacy variable 
8.1.1 
Derivation of ACR50 response 
The ACR50 response at Week 16 is the primary efficacy variable.  
This is a composite endpoint that represents at least 50% improvement from Baseline at Week 16 
for each of the following: 
• TJC (based on 68 joints), 
• SJC (based on 66 joints), 
• At least 3 of the 5 remaining core set measures: 
− PGA-PsA 
− PhGA-PsA 
− PtAAP 
− HAQ-DI 
− hs-CRP.  
Prior to deriving ACR50, the percent of change for each component will be calculated as: 
Percent improvement from Baseline = 100 × Baseline Value −Week 16 value 
Baseline Value
 
As the ACR response is based on 7 different component scores, it is necessary to consider 
various data scenarios that could impact the calculation of ACR response. The rules described 
here are applicable in the context of the calculation of ACR response and may differ from the 
rules applied for calculating and summarizing the components individually (some values may 
need to be imputed for component analysis but are not required here to evaluate the ACR 
response) 
The following rules will be applied prior to invoking any imputation analysis at the variable 
level: 
• If a subject has a component value that is equal to 0 at Baseline and the post-Baseline value 
is ≥ 0, then the percent improvement for that component will be treated as 0 for purposes of 
ACR response calculations. 
• If a subject has a component value that is missing at Baseline, then the percentage of 
improvement for that component will be treated as missing for purposes of ACR response 
calculations.   
Observed data will be used to calculate ACR response where possible. In case of partial missing 
data where an observed response may be calculated, imputed data will not change the result. 
To address possible missing data in ACR components, ACR50 will be derived as below:  
• Positive response on ACR50: 
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o Improvement at Week 16 of at least 50% from Baseline on SJC and TJC and at least 
3 out of the 5 remaining ACR components (regardless of whether the 2 remaining 
components are missing or not). 
• Negative response on ACR50: 
o No improvement at Week 16 of at least 50% from Baseline on SJC (regardless of 
whether the remaining components are missing or not). 
o No improvement at Week 16 of at least 50% from Baseline on TJC (regardless of 
whether the remaining components are missing or not). 
o No improvement for at least 3 out of the 5 following ACR components (PGA-PsA, 
PhGA-PsA, PtAAP, HAQ-DI, hs-CRP) regardless of whether the remaining 
components are missing or not. 
• Missing ACR50 response: 
o For all other situations that are not specified above. 
For the OC analysis (Section 8.1.4.6): if a given visit date falls after the treatment 
discontinuation date, the endpoint at this visit and all subsequent visits (whether the data were 
observed or not) will be derived but reported as missing. 
For the MI analysis (Section 8.1.4.3): If a given visit date falls after the treatment discontinuation 
date, the endpoint at this visit and all subsequent visits (whether the data were observed or not) 
will be imputed. Responses falling after an IE (defined as treatment discontinuation due to AE or 
lack of efficacy for the modified composite estimand) will be set to non-response. 
8.1.1.1 
Derivation of tender joint count (TJC) and swollen joint count (SJC) 
Tender and swollen joints are assessed based on the 68 and 66 joints for tenderness and swelling, 
respectively. The 68/66 joints that are assessed are: 
• Upper body (6): bilateral temporomandibular, sternoclavicular, and acromioclavicular joints 
• Upper extremity (34): bilateral shoulders, elbows, wrists (includes radiocarpal, carpal and 
carpometacarpal joints considered as 1 unit), metacarpophalangeals (I, II, III, IV, V), thumb 
interphalangeals, proximal interphalangeals (II, III, IV, V), distal interphalangeals (II, III, IV, 
V) 
• Lower extremity (28): bilateral hips, knees, ankles, tarsi (includes subtalar, transverse tarsal, 
and tarsometastarsal joints considered as 1 unit), metarsalphalangeals (I, II, III, IV, V), great 
toe interphalangeals, and proximal interphalangeals (II, III, IV, V). 
The assessments on swelling exclude the hips.  
Each of the joints can be graded as follows by the assessor:  
• Permanently not assessable 
• Temporarily not assessable 
• Asymptomatic 
• Tender only 
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• Swollen only 
• Tender and swollen 
Permanently non-evaluable joints will be considered missing for both tender and swollen joint 
counts at the visit at which the grading was recorded and all subsequent visits. The asymptomatic 
joints will be included in the joint count analysis with scores of 0. 
For the statistical analysis, swelling and tenderness are each graded on a 2-point scale as 
described below: 
Table 8‒1: 
Swelling and Tenderness grading 
Present 
Tenderness response (68) 
Swelling response (66) 
No (0) 
Not tender 
None 
Yes (1) 
Positive response to questioning 
(tender), spontaneous response 
elicited (tender and winced) or 
withdrawal by subject on 
examination (tender, winced, 
and withdrew). 
Detectable synovial thickening 
with or without loss of bony 
contours, or bulging synovial 
proliferation with or without 
cystic characteristics. 
The joint graded by the assessor will then have its grade mapped as follows: 
• The “Tender only” joints will correspond to a tenderness response of 1, and a swollen 
response of 0.  
• The “Swollen only” joints will correspond to a swollen response of 1, and a tenderness 
response of 0. 
• The “Tender and swollen” joints will correspond to a swelling and tenderness response of 1. 
In addition, injected joints will be counted as swollen and tender (ie, swelling and tenderness 
response of 1) from and including the date of injection up to 52 weeks after injection.  
Injected joints are allowed after Week 16 as part of rescue medications.  
Dactylitic digits will be identified as follows and the joints will be counted as follows: 
• Fingers 2-5: Swelling Distal Interphalangeal Joint x (side), Swelling Proximal 
Interphalangeal Joint x (side), Swelling Metacarpophalangeal Joint x (side) – if they are in 
any of the gradings ‘swollen only’ or ‘tender and swelling’ or ‘injected’ then only 1 finger 
will be added to the swollen joint count. 
• Toes 1-5: Swelling Interphalangeal Joint x (side), Swelling Metatarsophalangeal Joint x 
(side) – if they were in any of gradings ‘swollen’ or ‘tender and swollen’ or ‘injected’ then 
only 1 toe will be added to the swollen joint count. 
The tender joint count (TJC) and swollen joint count (SJC) are weighted joint counts. If there are 
missing observations in the tender or swollen joint assessments (TJ and SJ, respectively), then 
the remaining observations will be assessed and weighted by the number of the assessed 
joints (AJ) as shown below: 
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𝑇𝐽𝐶= 𝑛× ∑
𝑇𝐽
𝑛
𝑖=1
∑
𝐴𝐽
𝑛
𝑖=1
 
𝑆𝐽𝐶= 𝑛× ∑
𝑆𝐽
𝑛
𝑖=1
∑
𝐴𝐽
𝑛
𝑖=1
 
Where n represents the number of total joints.  
If a joint is missing at Baseline, then that joint is set to missing throughout the study. If more 
than 50% of the planned tender joint assessments (ie more than 34) or 50% of the planned 
swollen joint assessments (ie more than 33) are missing at the time of a given assessment any 
post-Baseline visit, then no imputation will be done and the total TJC or SJC will be set to 
missing for that visit.  
8.1.1.2 
Patient and physician reported clinical outcomes on psoriatic 
arthritis 
The physician’s global assessment of psoriatic arthritis (PhGA-PsA), the patient’s global 
assessment of psoriatic arthritis (PGA-PsA) and the patient’s assessment of arthritis pain 
(PtAAP) are clinical outcomes based on visual analog scales (VAS) ranged from 0 to 100 (in 
mm).  
• PhGA-PsA: The investigator will assess the overall status of the subjects with respect to their 
PsA signs and symptoms using a numerical rating scale where 0 is “very good, asymptomatic 
and no limitation of normal activities” and 100 is “very poor, very severe symptoms which 
are intolerable and inability to carry out all normal activities”. This assessment will be based 
through the following question “Considering all the ways the disease affects your patient, 
mark a vertical line on the scale for how well his or her condition is today.”  
• PGA-PsA: Subjects will assess the impact of PsA in answering the following question 
“Considering all the ways your psoriatic arthritis affects you, please mark a vertical line on 
the scale below to show how well you are doing today.” The subjects should be asked to 
consider all aspects of their disease (including joint and skin components) in their response to 
this question. Subjects will score PGA-PsA in using a VAS where 0 is “very good, no 
symptoms” and 100 is “very poor, severe symptoms.” 
• PtAAP: Subjects will assess their arthritis pain through the PtAAP using a VAS where 0 is 
“no pain” and 100 is “most severe pain.” 
8.1.1.3 
Derivation of Health Assessment Questionnaire-Disability index 
(HAQ-DI) score 
The HAQ-DI contains 20 items that measure the degree of difficulty experienced in the 
following 8 categories of the daily living activities: dressing and grooming (2 items), arising (2 
items), eating (3 items), walking (2 items), hygiene (3 items), reach (2 items), grip (3 items), and 
common daily activities (3 items). 
For each question/item, subjects should indicate the level of difficulty (ranged from 0 to 3) in the 
past week as follows: 
• 0: ‘without any difficulty’ 
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• 1: ‘with some difficulty’ 
• 2: ‘with much difficulty’ 
• 3: ‘unable to do’ 
Each category is given a score by taking the maximum value for each question. 
For each question related to a specific daily living activity, subjects can specify whether an aid or 
devices is usually used.  
If a category score equals 0 or 1, but a device related to that category is used, or help from 
another person is provided for that category, then the category score is increased to 2.  
If a category score already equals 2, and a device related to that category is used, or help from 
another person is provided for that category, the score for that category remains 2.  
Table 8‒2 details how each aid and device is associated with the category scores. Aid or device 
considered as ‘other’ than the ones listed will not be considered in the analysis.  
Table 8‒2: 
Aid and device associated with HAQ-DI category 
 
Will be associated with category score 
  
Walking  
 
Dressing and grooming 
 
Eating 
 
Arising 
 
Hygiene 
 
Hygiene 
 
Grip 
 
Hygiene 
 
Reach  
 
Hygiene 
If all questions within a given category are unanswered, no score will be provided for that 
category (this rule applies even if aids and devices are non-missing).  
The HAQ-DI score will be calculated by dividing the sum of the highest score in each category 
(0 to 24) by the number of categories with at least 1 question answered. If fewer than 6 
categories have responses, no HAQ-DI score will be calculated (ie HAQ-DI score will be 
considered as missing). 
The HAQ-DI score ranges from 0 to 3. A lower HAQ-DI score indicates an improvement in 
function.  
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8.1.1.4 
 High sensitivity C-reactive protein levels (hs-CRP) 
High sensitivity C-reactive protein values which are below the lower limit of quantification 
(LLOQ) should be set to the midpoint between 0 and the LLOQ prior to the analysis. Listing will 
show values below the LLOQ. The LLOQ for hs-CRP is 0.10 mg/L. 
8.1.2 
Primary analysis of the primary efficacy variable 
The primary efficacy variable will be analyzed for all subjects in the RS. 
The primary endpoint is the ACR50 response at Week 16. The primary efficacy analysis will 
evaluate the composite estimand in the RS. The composite estimand combines the clinically 
meaningful improvement from Baseline in ACR50 response and not discontinuing study 
treatment early.  
The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for the primary efficacy analysis: 
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = ACR50 at Week 16.  
• IE handling = An IE is defined as discontinuation of study treatment prior to Week 16. A 
composite strategy will be implemented in which a positive clinical outcome is defined as 
achieving ACR50 at Week 16 and not discontinuing study treatment through Week 16.  
• Population-level summary measure = Conditional OR comparing BKZ to placebo. 
Missing data at Week 16 that are not preceded by an IE, and any data after an IE will be imputed 
as non-responders. This results in a more traditional NRI approach and will be labeled as such 
throughout the SAP.  
The statistical hypothesis for the ACR50 response at Week 16 is that the conditional OR for 
ACR50 response in the BKZ treatment compared to placebo treatment is equal to 1.  
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including 
randomization stratification variables (bone erosion at Baseline and region) will be assessed 
using Pearson and Deviance and The Hosmer-Lemeshow Goodness-of-Fit Tests (Hosmer and 
Lemeshow, 2000).  
In the context of the Week 24 analysis, actual bone erosion at Baseline as a covariate will be 
based on data from the first set of reads. For Week 52 analysis, data from the second set of reads 
will be used. 
P-values below 0.05 would lead to a reconsideration of the model to be used and if the logistic 
regression model is unable to converge the stratification variables will be dropped (Section 4.1). 
In that case, all supportive analyses as well as imputation models conducted for the primary 
endpoint will disregard these factors from their models. 
The country-specific analyses performed on subjects randomized in Japan will not consider the 
region factor as a covariate for the modelling.   
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Considering that the number of subjects randomized in Japan is low (less than 10% of the 
Randomized Set), statistical models might not converge. If a model (Logistic Model or Mixed 
model) is not converging, all related adjusted statistics and p-value will not be presented : “NE” 
for “Not Evaluable” will be displayed instead. 
The SAS® PROC LOGISTIC will be used to run the logistic regression. 
The summary table results will present the adjusted responder rates and the associated 95% CIs 
for the 3 treatment groups, the adjusted OR and the corresponding 95% CI for the comparison of 
BKZ versus placebo, the p-value that the OR=1 and the difference of response rate between BKZ 
and placebo and associated 95% CI. Comparisons of BKZ vs. placebo will be made using the 2-
sided Wald test at a significance level of α=0.05 (ie, H1 in Table 4‒5 ).  
Any use of prohibited or rescue medications through Week 16 would constitute an important 
protocol deviation which would be accounted for when the sensitivity analysis based on the PPS 
is performed (Section 8.1.4.1). 
8.1.3 
Subgroup analyses of the primary efficacy variable 
Subgroup analyses will be performed on the primary efficacy variable on the RS.  
The variables for subgroup analyses are defined in Section 4.8. 
In the context of the Week 24 analysis, actual bone erosion at Baseline used as a covariate and/or 
a subgroup will be based on data from the first set of reads. For the Week 52/final analyses, data 
from the second set of reads will be used. 
For each subgroup analysis (except for the analysis by region, by bone erosion at Baseline, by 
hs-CRP value combined with bone erosion at Baseline and by ADAb status), a logistic 
regression will be fitted involving the same terms that were retained when running the primary 
analysis model, plus a term for the subgroup and the subgroup by treatment interaction as 
detailed below :  
• Fixed effect for treatment  
• Bone erosion at Baseline (0 if bone erosion at Baseline=0; 1 if bone erosion at Baseline≥1)   
• Region  
• Subgroup  
• Subgroup by treatment interaction.  
For subgroup analyses by bone erosion, the terms that will be retained will be:  
• Fixed effect for treatment  
• Bone erosion at Baseline   
• Region  
• Bone erosion at Baseline by treatment interaction.  
For subgroup analyses by region, the terms that will be retained will be:  
• Fixed effect for treatment  
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• Bone erosion at Baseline   
• Region  
• Region by treatment interaction. 
For subgroup analyses by bone erosion (≥1) and/or hs-CRP ≥6mg/L at Baseline (Yes, No), the 
terms that will be retained will be:  
• Fixed effect for treatment  
• Bone erosion (≥1) and/or hs-CRP ≥6mg/L at Baseline (Yes, No) 
• Region  
• Bone erosion (≥1) and/or hs-CRP ≥6mg/L at Baseline by treatment interaction. 
For subgroup analyses by ADAb status, the terms that will be retained will be:  
• Bone erosion at Baseline   
• Region  
• ADAb Status (Positive, Negative). 
For all subgroup analyses, the term for the subgroups will coded as below: 
• For Yes/No or positive /negative variables, the category “yes” or “positive” will be coded 
“1”. 
• For continuous variables in 2 classes, the highest category will be coded “1”. 
• For continuous variables in 3 classes (or more), the coding categories will start from 1 for the 
lowest value. 
• For gender, “male” will be the category coded “1”.     
The same estimand approach as the one used for the primary analysis will be used to handle 
missing data (NRI).  
For each subgroup category and each of the 3 treatment groups (for the BKZ group only for the 
subgroup analysis on the ADAb status), the mean proportion of responders on imputed datasets, 
the adjusted responder rates with associated 95% CI, will be provided. The adjusted OR (for the 
comparison of BKZ vs. placebo), the corresponding 95% CI, the difference in response rates 
between BKZ and placebo and the corresponding 95% CI will also be presented (except for the 
subgroup analysis on the ADAb status). The results obtained for each subgroup will be presented 
in one single table.  
The observed rates of responses by subgroup categories will be also provided along with the 
results obtained on imputed data. 
For each subgroup category, the ORs and the associated 95% CIs will also be displayed on a 
single forest-plot. 
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In addition, the mean proportion of ACR50 responders at Week 16 separated by the 6 pre-
defined ADAb subcategories (as defined in Section 9.2) will be presented graphically for the 
BKZ randomized subjects.  
8.1.4 
Supportive analyses of the primary efficacy variable 
The following supportive analyses for the primary efficacy variable will be conducted on the RS 
(except analyses described in Section 8.1.4.1 , 8.1.4.2 and 8.1.4.8). For the below analyses, 
unless specified: 
• The same model as run for the primary analysis will be used. 
• The same statistics will be provided: the mean proportion of responders (on imputed datasets 
when applicable), the adjusted responder rates for each treatment group, the adjusted ORs for 
the comparison BKZ versus placebo and its 95% CI , the p-value for the comparison between 
BKZ and placebo and the difference of response rates between BKZ and placebo and its 
corresponding 95% CI.  
The adjusted OR and 95% CI for the comparison of BKZ vs. placebo obtained for the primary 
analysis and the supportive analyses described below (except for Section 8.1.4.4) will be 
displayed in a forest plot. 
8.1.4.1 
Analysis on the PPS 
The analysis described in Section 8.1.2 will be repeated based on the PPS to evaluate the effect 
of IPD on the analysis.  
8.1.4.2 
Analysis on the FAS 
The analyses described in Section 8.1.2 will be repeated for all subjects in the FAS to evaluate 
the consistency between the RS and the more restrictive FAS. This analysis will only be 
performed if the number of subjects in RS and FAS are different.  
8.1.4.3 
Analysis using a modified composite estimand where intercurrent 
events are defined as discontinuation due to AE or lack of efficacy  
The modified composite estimand is detailed below:  
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = ACR50 at Week 16. 
• IE handling = An IE is defined as discontinuation due to AE or lack of efficacy. A composite 
strategy will be implemented in which a positive clinical outcome is defined as achieving 
ACR50 at Week 16 and not discontinuing study treatment due to AE or lack of efficacy 
through Week 16.  
• Population-level summary measure = Conditional OR comparing BKZ to placebo. 
Any missing data at Week 16 that is not preceded by an IE will be imputed based on a 
predefined MI model (MI/MCMC - Monotone Regression) (Section 4.2.2).  
The following categories of subjects will enter the MI/MCMC – Monotone regression process 
for each ACR component:  
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• Subjects with all post-baseline values missing  
• Subjects withdrawn from the study treatment (data collected prior to the treatment 
withdrawal will be retained) - Those subjects will have values imputed for missing 
assessments and non missing assessment falling after study treatment discontinuation (falling 
after or before the study withdrawal) 
• Subjects with missing value at Baseline. MI will be applied for each of the components 
separately before deriving the response.  
In the case of partial missing data, ACR will be derived as in Section 8.1.1. 
If an IE occurred prior to Week 16, the subjects will be considered as “non-responders”. 
In MI, the missing value is replaced by a set of plausible values, where each value is a Bayesian 
draw from the conditional distribution of the missing data given the observed data.  
8.1.4.4 
Analysis of individual components of the ACR 
The primary comparison (BKZ vs. placebo) will also be repeated for all individual components 
of the ACR response to explore the effect of the signs and symptoms of the individual 
components on the composite endpoint. Since all ACR components are continuous variables (eg, 
change from Baseline in TJC), an analysis of covariance (ANCOVA) with treatment, region, and 
bone erosion at Baseline as fixed effects and the Baseline value as covariate will be used for the 
analysis. Missing data imputation described in Section 4.2.2.2 and 4.2.2.3 will be successively 
applied for each component. 
The following 4 attributes describe the hypothetical estimand that will be used to define the 
treatment effect of interest for each of the 7 ACR components: 
• Population = Subjects meeting the protocol-specified inclusion/exclusion criteria and 
randomized to IMP. 
• Subject level outcome = Change from Baseline in ACR components at Week 16. 
• IE handling =An IE is defined as discontinuation of study treatment prior to Week 16. This 
estimand targets the treatment difference in a scenario where withdrawal from study 
treatment does not occur, such that outcomes for subjects without an IE are as observed, and 
outcomes for subjects with an IE are treated successively according to the two following 
hypothetical strategies: 
− (a) as they had completed treatment through Week 16. In that strategy, missing data and 
non missing data after IE (reset as missing) will be imputed using MI. 
− (b) as they had completed the randomized study treatment through Week 16 but on 
Placebo. In that strategy, missing data and non missing data after IE (reset as missing) 
will be imputed using reference-based MI, in which the MI model is based on data from 
the Placebo group. 
• Population-level summary measure = The difference in the adjusted means between BKZ 
160mg Q4W and placebo.  
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For the results obtained using the MI method, the SAS® PROC MIXED will be used to run the 
ANCOVA models. 
The inferential statistics obtained from each model will be displayed in a single table. For all 
variables, the following statistics will be presented: 
• The LSM and SE by treatment group 
• For the comparison between BKZ and placebo: the difference between the LSM, the 
associated 95% CI for the contrasts, and the corresponding p-value. 
An additional table will present the descriptive statistics for the 3 treatment groups for each ACR 
component variable at Week 16. Those statistics will be the mean, SE, median, minimum and 
maximum obtained after MI. 
8.1.4.5 
Analyses using treatment policy strategy imputation for missing data 
The treatment policy strategy for addressing IE will be considered. This will be based on an 
analysis in which all available data at Week 16 regardless of the occurrence of IE will be kept in 
the analysis. This analysis will use the same models specified for the primary analyses where 
subjects are analyzed according to their randomized treatment, even if they discontinued study 
treatment for any reason prior to Week 16 and were no longer on the randomized study treatment 
when the assessment was performed at Week 16.  
In the context of this analysis, in addition to the statistics provided in the context of MI, the 
number of observed ACR50 responses regardless of the occurrence of IE will be also reported. 
The estimand for the treatment policy strategy analysis is detailed below:  
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = ACR50 at Week 16.  
• IE handling = Discontinuation of study medication for any reason will be handled by using 
the data as observed irrespective of the IE occurring. 
• Population-level summary measure = Conditional OR comparing ‘BKZ and other medication 
as needed’ to ‘placebo and other medication as needed’.  
8.1.4.6 
Analysis on Observed cases  
An OC analysis will additionally be conducted, where only observed data for subjects who are 
still on the randomized treatment at Week 16 are included. Subjects with missing data at Week 
16 or who have prematurely discontinued study treatment prior to Week 16 will be treated as 
missing and missing data will not be replaced.  
The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for the OC analysis: 
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = ACR50 at Week 16 while on randomized treatment. 
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• IE handling = A ”while on randomized treatment” strategy will be implemented.  
• Population-level summary measure = Conditional OR comparing BKZ to placebo. 
The same analysis model as used for the primary efficacy analysis will be conducted on the RS. 
8.1.4.7 
Tipping point analysis 
The degree of the departure from the MAR assumption to overturn conclusions from the primary 
analysis will be investigated in a tipping point analysis. This analysis will be performed on the 
monotone missing data and only if the primary analysis is significant at α=0.05. Intermittent 
missing data will be imputed using the MCMC method. In this analysis, it will be assumed that 
subjects who have missing data and are randomized to BKZ have a lower probability of response 
compared to subjects who have missing data and are randomized to placebo.  
The analysis will be primarily conducted on the binary response endpoint itself in considering 
the worst-case scenario that subjects who have missing ACR50 response will be set as non-
responders if they are randomized to BKZ and as responders if they are randomized to Placebo. 
If the result tips, then the tipping point analysis will be reconducted on the ACR50 endpoint after 
having delta-adjusted each individual component of the ACR50 endpoint. For both analyses, the 
same model as used for the primary efficacy analysis will be conducted on the RS. If the delta 
parameter value for which the study conclusion under MAR is reversed is plausible, the 
conclusion under MAR will then be questionable. Refer to Section 4.2.2.4 for more details on the 
methodology.  
8.1.4.8 
Analyses including COVID-19 impact 
To assess the impact of the COVID-19 pandemic on the primary efficacy endpoint, 2 sensitivity 
analyses will be conducted using the same analysis method as the primary analysis: 
• on the COVID-19-free Set  
• by COVID-19 period (pre or during as determined by the Week 16 date). 
8.2 
Statistical analysis of secondary efficacy variables  
8.2.1 
Derivation of secondary efficacy variables  
The primary and supportive analysis methods of secondary efficacy variables for which the 
derivation method is provided below are described in Section 8.2.2 and 8.2.3. For the other 
secondary variables (which are not part of the testing hierarchy), there is no priority designated 
between methods.   
8.2.1.1 
HAQ-DI: Change from Baseline at Week 16 
The derivation for HAQ-DI is described in Section 8.1.1.3 (The analysis of this variable is 
already covered in Section 8.1.4.3). 
Change from Baseline at Week 16 in HAQ-DI is the 2nd endpoint in the sequential testing 
hierarchy (Table 4‒5). 
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8.2.1.2 
Psoriasis Area Severity Index 90 (PASI90) at Week 16 (in subjects 
with PSO involving at least 3% of BSA at Baseline) 
PASI scoring of psoriatic plaques is based on 3 criteria:  
• redness (R)  
• thickness (T)  
• scaliness (S).  
Severity is rated for each index (R, S, T) on a 0-4 scale (0=none, 1=slight, 2=moderate, 
3=marked, and 4=very marked).  
The body is divided into 4 areas comprising: 
• head (h)  
• upper extremities (u)  
• trunk (t)  
• lower extremities (l).  
In each of these areas, the fraction of total surface area affected is graded on a 0-6 scale (where 
0=0% [clear], 1=>0% to <10%, 2=10% to <30%, 3=30% to <50%, 4=50% to <70%, 5=70% to 
<90%, and 6=90% to 100%). 
The various body regions are weighted to reflect their respective proportion of BSA. The 
composite PASI score is then calculated by multiplying the sum of the individual-severity scores 
for each area by the weighted area-of-involvement score for that respective area, and then 
summing the 4 resulting quantities as follows:  
𝑃𝐴𝑆𝐼= (0.1 × (𝑅ℎ + 𝑇ℎ + 𝑆ℎ ) × 𝐴ℎ) 
+ (0.2 × (𝑅𝑢 + 𝑇𝑢 + 𝑆𝑢 ) × 𝐴𝑢) 
  +(0.3 × (𝑅𝑡 + 𝑇𝑡 + 𝑆𝑡 ) × 𝐴𝑡)  
  +(0.4 × (𝑅𝑙 + 𝑇𝑙 + 𝑆𝑙 ) × 𝐴𝑙)  
Where:  
Rh, Ru, Rt, Rl = redness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively  
Th, Tu, Tt, Tl = thickness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively  
Sh, Su, St, Sl = scaliness score of plaques on the head, upper extremities, trunk, and lower 
extremities, scored 0-4 respectively  
Ah, Au, At, Al = numerical value translation of % area of psoriatic involvement score for the 
head, upper extremities, trunk, and lower extremities, scored 0-6 respectively.  
The highest potential PASI score is 72 for severe disease and the lowest is 0 for no psoriasis 
lesions. PASI scores are treated as continuous.  
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If a subject is missing 1 or 2 severity measurements for a certain region, the average of the 
remaining non-missing severity measurement(s) within that region will be utilized to substitute 
for the missing severity measurement(s) in that region. If the area of affected skin and/or all 
severity measurements for up to 2 regions are missing, then the missing (R+T+S) x A for a 
region will be substituted by the average of the available (R+T+S) x A. Otherwise, the PASI will 
be set to missing. 
The percent improvement in PASI scores from Baseline will be computed as:  
Percent improvement from Baseline = 100 × Baseline PASI −PostBaseline PASI 
Baseline PASI
 
If a subject has experienced an improvement, this measure will be positive. If a subject has 
experienced a worsening in their condition, this measure will be negative.  
PASI90 is a binary variable equal to 1 if the percentage improvement from Baseline in the PASI 
scores is ≥ 90% and 0 if the percentage improvement from Baseline is < 90%. 
PASI90 is the 3rd endpoint in the sequential testing hierarchy (Table 4‒5). 
8.2.1.3 
SF-36 PCS: Change from Baseline at Week 16 
The SF-36 (Version 2, standard recall) is a 36-item generic health-related quality of life 
instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows:  
• Physical Functioning (10 items) 
• Role Physical (4 items) 
• Bodily Pain (2 items) 
• General Health (5 items) 
• Vitality (4 items) 
• Social Functioning (2 items) 
• Role Emotional (3 items) 
• Mental Health (5 items). 
 
 The concepts represented by these domains contribute to 
physical, mental, and social aspects of health-related quality of life. 
In addition to domain scores, the PCS and MCS scores are calculated from the 8 domains 
(excluding the Health Transition item). Component scores reflect the impact of each domain on 
physical and mental health status.  
The norm-based T-scores for the 2 SF-36 component summary (PCS and MCS) and the 8 
domains are standardized with a mean of 50 and a standard deviation (SD) of 10 in the general 
US population (Maruish, 2011). An individual respondent’s score that falls outside the T-score 
range of 45 to 55 should be considered outside the average range for the US general population. 
When considering group-level data, a score below 47 should be considered indicative of 
impaired functioning within that health domain or dimension. Similar to individual respondent 
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data, group mean scores of 47 or greater should be considered average or above average as 
compared to the general US population. Higher scores indicate a better health status. 
For the calculation of the SF-36 norm-based T-scores for the 8 domains and the PCS and MCS, 
the scoring software Optum’s PRO CoRE (version 1.4) will be used. The software uses updated 
2009 U.S. population norms and applies a Full Missing Score Estimation method as follows: 
• A health domain score (except the Physical Functioning domain) will be estimated provided 
that at least 1 non-missing response is available within that domain.  
• For the Physical Functioning domain, item response theory will be used to develop a model 
for estimates of the missing score. 
• Regression methods will then be applied to estimate the PCS and MCS on the basis of the 
available domains. 
Change from Baseline at Week 16 in SF-36 PCS score is the 4th endpoint in the sequential testing 
hierarchy (Table 4‒5). 
8.2.1.4 
MDA at Week 16 
MDA is a state of disease activity deemed a useful target of treatment by both the subject and 
physician, given current treatment possibilities and limitations. The criteria that need to be met 
are based on key outcome measures in PsA and are shown below: 
• Tender joint count ≤1 
• Swollen joint count ≤1 
• PASI ≤1(for subjects with PSO involving at least 3% of BSA at Baseline) or BSA ≤3 
• PtAAP (VAS) ≤15 mm 
• PGA-PsA (VAS) ≤20 mm 
• HAQ-DI ≤0.5 
• Tender enthesial points ≤1 (LEI≤1). 
A subject has achieved MDA if 5 or more of the 7 above criteria are fulfilled.  
The enthesitis instrument of the study (ie: LEI) will be used to determine whether a subject has 
≤1 tender enthesial point. 
The following rule will be applied for subjects with BSA <3 at Baseline: Subjects with BSA <3 
at Baseline will always meet the criteria PASI ≤1 or BSA ≤3 except in the cases where a BSA 
score >3 is observed.  
MDA at Week 16 is the 5th endpoint in the sequential testing hierarchy (Table 4‒5). 
8.2.1.5 
Van der Heijde modified Total Sharp Score (vdHmTSS): Change from 
Baseline at Week 16 
The degree of joint damage is to be assessed using the vdHmTSS as used in the evaluation of 
PsA (Van der Heijde et al, 2005). This methodology quantifies the extent of joint erosions (52 
joints) and joint space narrowing (52 joints), with higher scores representing greater damage. 
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Radiographs of the hands and feet are to be taken using standardized imaging methodology, 
which is defined in the Hand and Foot Radiography Manual that will be provided as part of the 
Study Manual. 
All enrolled subjects are required to have radiographs taken of both hands and both feet (a single 
posteroanterior view of each hand and a single dorsoplantar of each foot). Radiographs are to be 
read centrally and independently by 2 experienced readers. If the 2 primary readers disagree, 
adjudication will be performed by a third reviewer. Readers will be blind to treatment 
assignment and time course of the films. Additional details on radiograph reading, assessment, 
and adjudication should be given in the imaging charter. 
The scoring methodology is outlined below. 
Scoring of Erosions: 
Bone erosions in the hands and feet will be scored in the following locations according to the 
following grading scheme: 
Erosion Scoring Locations: 
• 20 locations in each hand and wrist (left and right): 40 locations overall: 
− 4 Distal inter-phalangeal joints (2-5) 
− 4 Proximal Inter-Phalangeal Joints (2-5) 
− 5 Metacarpo-Phalangeal Joints (1-5) 
− Inter-Phalangeal Joint of the thumb 
− Proximal first Metacarpal Bone 
− Radius Bone 
− Ulnar Bone 
− Trapezium and Trapezoid (as one unit; multangular) 
− Navicular Bone 
− Lunate Bone. 
• 6 joints in each foot (left and right), 12 locations overall for the 2 feet: 
− 5 Metatarso-phalangeal joints (1-5) 
− Inter-phalangeal joint of the first toe. 
Erosion Grading Scheme: 
• Scores will be based on the number and size of discrete erosions in each location as follows:  
− 0=Normal (no erosion) 
− 1=Discrete small erosion 
− 2=Either 2 discrete erosions or 1 larger erosion that do not cross the joint middle line 
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− 3=Combination of the above or 1 large erosion that cross the joint middle line of the bone 
− 4=Combination of above adding up to 4 
− 5=Combination of above adding up to 5 or more. 
The maximum score for erosion is 5 per joint in the hand and 10 per joint in the feet. 
A score of  ”N” will be assigned in the case that the location is non-evaluable due to advanced 
subluxation, interfering osteoarthritis, or poor radiographic depiction. A score of  ”S” will be 
assigned in the case that the location had joint replacement, amputation, or other surgery. 
Exported score will be from 0 to 5 for hand and 0 to 10 for foot. Score of “S” and “N” will not be 
exported as a score but in an additional text field (“Reason”). 
Scoring of Joint Space Narrowing: 
Joint space narrowing (JSN) in the hands and feet will be scored in the following locations 
according to the following grading scheme: 
Joint Space Narrowing Scoring Locations: 
• 20 locations in each hand and wrist (40 locations overall): 
− 4 Distal inter-phalangeal joints (2-5) 
− 5 Metacarpo-phalangeal joints (1-5) 
− 4 Proximal inter-phalangeal joints (2-5) 
− Interphalangeal Joint of thumb (IP) 
− 3 Carpo-metacarpal joints (3-5) 
− Radio-carpal joint 
− Multangular-navicular joint 
− Capitate-navicular-lunate joint. 
• 6 locations in each foot (12 locations overall): 
− 5 Metatarso-phalangeal joints 
− Inter-phalangeal joint of first toe. 
Joint Space Narrowing Grading Scheme: 
• The joints mentioned above will be scored using a 5-point scale from 0 to 4 as follows: 
− 0=normal 
− 1=asymmetrical or minimal narrowing up to a maximum of 25% 
− 2=definite narrowing with loss of up to 50% of the normal space 
− 3=definite narrowing with loss of 50–99% of the normal space or subluxation 
− 4=absence of a joint space, presumptive evidence of ankylosis, or complete luxation. 
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A score of ”N” will be assigned in the case that the location is non-evaluable due to advanced 
subluxation, interfering osteoarthritis, or poor radiographic depiction. A score of  “S” will be 
assigned in the case that the location had joint replacement, amputation, or other surgery.  
Exported score will be from 0 to 5 for hand and 0 to 10 for foot. Score of  “S” and “N” will not 
be exported as a score but in an additional text field (“Reason”). 
Total Scores: 
The individual joint scores will be summed separately to create a total erosion score (ES) and a 
total JSN score for the hands/wrists.  
• The maximum total ES for both hands/wrists is 200 (20 locations × 5 maximum per joint × 
2).  
• The maximum total JSN score for both hands/wrists is 160 (20 locations × 4 maximum per 
joint × 2. 
In the feet as for the hands/wrists the individual joint scores will be summed separately to create 
a total ES and a total JSN score for the feet.  
• The maximum total ES for both feet is 120 (12 locations × 10 per joint)  
• The maximum total JSN score for both feet is 48 (6 locations × 4 maximum per joint × 2). 
Thus, the maximum possible scores are:  
• 320 for erosions  
• 208 for joint space narrowing  
• 528 for the total score. 
The total score is the sum of the ES and JSN score.  
Radiographic assessments should be conducted using a standardized imaging methodology as 
defined in an imaging charter. Subjects reaching Week 52 will have 2 sets of reads for Baseline 
and Week 16 as x-rays for these subjects are read more than once in different sessions to reduce 
within subject variability by each of the independent reviewers.  
Bone erosions will be read for all visits at both at the Week 24 analysis and the Week 52/final 
analyses to ensure that unnecessary bias is not introduced. Given there may be differences at a 
visit for the two sets of reads, the following rules will be applied for the derivation: 
• For the  analysis involving data up to Week 16 only (Week 24 analysis),  the first set of 
reads  will be used for all subjects.  
• For the analyses involving data up to Week 52, the second set of reads will be used for all 
subjects.     
For the analysis, the average of the scores (ES, JSN score and total score) from the 2 independent 
reviewers will be utilized. They will be calculated as: 
• (Score from Reviewer 1 + Score from Reviewer 2)/2 
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When a third reviewer will perform adjudication, the following average will be used for the 
scores: 
• (Sum of the adjudicated score + score closest to the adjudicated score)/2 
If the 2 scores are equidistant to the adjudicated score, then the highest score will be taken.  
For the assessment of an individual reviewer, the following imputation rules will be applied: 
• If at least 1 score for a particular joint used to calculate JSN score or ES at a visit is available, 
the remaining score will be imputed:  
− For Baseline, missing scores for a particular joint will be set to 0   
− At post-Baseline visits, missing score for a particular joint (ie, the assigned score is ”N” 
or “S”), the joint score from the previous visit will be carried forward to compute the 
total score.   
• If the total score is missing at a post-Baseline visit (ie, only ”N” or “S” is recorded for all 
joints) or if JSN or ES score is missing then the missing total score will be imputed using MI 
imputation. 
For the change from Baseline analyses, subjects who withdraw early and have radiographs taken 
at their early withdrawal visit should be included in the analysis. In such cases, one or more 
imputation methods may be applied for the subjects with less than 2 radiographs. In addition to 
any such imputation approach that is selected, an analysis excluding subjects with less than 2 
radiographs from the analysis should be performed. 
In the testing hierarchy (Table 4‒5), 2 endpoints are defined based on the vdHmTSS:   
• Change at Week 16 from Baseline in vdHmTSS for subjects with elevated hs-CRP and/or 
with at least one bone erosion at Baseline (planned to be approximately 45% of the overall 
population). This is the 6th endpoint in the sequential testing hierarchy. 
• Change at Week 16 from Baseline in vdHmTSS for all subjects. This is the 9th endpoint in 
the sequential testing hierarchy. 
The 2 endpoints will be analyzed in the radiographic set. 
At Week 16, imaging data collected outside ±14 days of the expected visit date will be excluded 
from the analysis. 
For the Week 24 interim analysis only, in the primary analysis of these 2 endpoints, missing data 
at Week 16 will be imputed based on value at Screening (as there is no value collected in 
between) using MI-MCMC / Monotone regression. Since VdHmTSS is only collected at 
Baseline prior to Week 16, only the second MI step to address monotone missing pattern and 
generating 100 imputations will be processed (Section 4.2.2.2).  
8.2.1.6 
Enthesitis-free state at Week 16 in the subgroup of subjects with 
enthesitis at Baseline 
The Leeds Enthesitis Index (LEI) consists of 6 items, 3 for the right part and 3 for the left part of 
the body. The body parts are Lateral epicondyles of the humerus, Medial femoral condyle, and 
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Achilles tendons. Each item is scored for tenderness with either 1 or 0 (tenderness, no 
tenderness, respectively). The total score ranges from 0 (no enthesitis) to 6 (severe enthesitis).  
Note that LEI is collected for all subjects regardless of their Baseline score. 
In case 4 items are missing, the LEI will be set to missing. If at least 3 items are available, the 
available items will be assessed and scored and then weighted by the number of the assessed 
items (AI) as shown in the formula below: 
𝐿𝐸𝐼= 𝑛× ∑
𝑠𝑐𝑜𝑟𝑒
𝑛
𝑖=1
∑
𝐴𝐼
𝑛
𝑖=1
 
Note that n here refers to the number of total items. 
Enthesitis-free state is based on a LEI response of 0 at Week 16, for subjects with enthesitis at 
Baseline (LEI>0). 
Enthesitis-free state at Week 16 (pooled between PA0010 and PA0011) is the 7th endpoint in the 
sequential testing hierarchy (Table 4‒5) and will be based on pooled data from PA0010 and 
PA0011 (for subjects in the BKZ160mg Q4W and the Placebo groups). The analysis will also be 
repeated using PA0010 data alone and the p-value for this analysis will only be considered 
nominal. 
8.2.1.7 
Dactylitis-free state at Week 16 in the subgroup of subjects with 
dactylitis at Baseline 
The LDI measures the percent difference between the circumference of the affected digit and the 
circumference of the digit on the opposite hand or foot (referred to as the contralateral digit), 
where circumference is measured in millimeters. A minimum difference of 10% and the 
assessment of the investigator that the digit was affected by dactylitis will be used to define a 
dactylitis digit.  
The percent difference between circumferences will be multiplied by a tenderness score (0 for 
non-tender, 1 for tender). The score using the binary tenderness score is referred to as the LDI 
basic. The results from each digit with dactylitis will then be summed to produce a final LDI 
score. 
Table 8‒3 is a table of normative values, which will be used to provide the comparison, if 
matching digits are thought to be involved. 
Table 8‒3: 
Normative values for LDI 
 
Digit 
Men 
Women 
Hand 
Thumb 
70 
58 
Index 
63 
54 
Middle 
63 
54 
Ring 
59 
50 
Little 
52 
44 
Foot 
Great toe 
82 
72 
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Digit 
Men 
Women 
Second 
52 
46 
Middle 
50 
44 
Fourth 
50 
44 
Little 
52 
45 
The following rules will be applied for the LDI calculation in case of unclear data.  
• Circumferences of 0 will be considered as missing. Circumferences <15 will be assumed to 
be in cm instead of mm and will be multiplied by 10 before being used in 
summaries/analyses. 
• If both digits of a given pair are recorded as affected, then each digit will be compared to the 
normative value (shown in the above table). Note that if both comparisons result in a 
difference ≥10%, then both digits will contribute to the final LDI score. 
• If the circumference of the affected digit is smaller than the unaffected digit, then the LDI 
will be calculated by comparing the smaller digit to the normative value. 
• If a digit is recorded as affected and the circumference of the contralateral digit is missing, 
the normative value will be used for comparison with the affected digit. 
• If a digit is selected but recorded as ‘not affected’ but has circumference and contralateral 
circumferences collected, a missing tenderness score will be considered as 1. 
• If the investigator did not complete the LDI questionnaire at Baseline, it will be assumed that 
no digits were affected (ie, a LDI score of 0 will be assigned).  
Dactylitis-free state is based on a Leeds Dactylitis Index (LDI) at Week 16 of 0, for subjects with 
dactylitis at Baseline (LDI>0). 
Dactylitis-free state at Week 16 (pooled between PA0010 and PA0011) is the 8th endpoint in the 
sequential testing hierarchy (Table 4‒5) and will be based on pooled data from PA0010 and 
PA0011 (for subjects in the BKZ160mg Q4W and the Placebo groups). The analysis will also be 
repeated using PA0010 data alone and the p-value will only be considered nominal. 
A tender dactylitis count will be calculated as the sum of the tenderness scores for all digits and 
will be used for the PASDAS score calculation (Section 8.3.1.6). 
8.2.1.8 
Psoriasis Area Severity index 90 (PASI90) at Week 4 (in subjects with 
PSO involving at least 3% of BSA at Baseline) 
This variable will be derived as described in Section 8.2.1.2.   
8.2.1.9 
ACR20 and ACR70 response at Week 16 
The ACR20 and ACR70 responses are defined based on respectively 20% and 70% or greater 
improvement from Baseline in the same measures than the primary endpoint (Section 8.1.1).  
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8.2.1.10 
Proportion of subjects with an Investigator Global Assessment (IGA) 
score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction 
from Baseline at Week 4 and Week 16 in the subset of subjects with 
psoriatic skin lesions at Baseline 
A static IGA for PSO will be used to assess disease severity in all subjects during the study. The 
Investigator will assess the overall severity of PSO using the following 5-point scale presented in 
Table 8‒4. 
Table 8‒4: 
Five-point IGA 
Score 
Short Descriptor 
Detailed Descriptor 
0 
Clear 
No signs of PSO; post-
inflammatory 
hyperpigmentation may be 
present  
1 
Almost Clear 
No thickening; normal to pink 
coloration; no to minimal focal 
scaling 
2 
Mild 
Just detectable to mild 
thickening; pink to light red 
coloration; predominantly fine 
scaling 
3 
Moderate 
Clearly distinguishable to 
moderate thickening; dull to 
bright red, moderate scaling  
4 
Severe 
Severe thickening with hard 
edges; bright to deep dark red 
coloration severe/coarse scaling 
covering almost all or all lesions 
IGA=Investigator’s Global Assessment; PSO=psoriasis 
The IGA response is defined as clear [0] or almost clear [1] assessment with at least a 2-category 
improvement from Baseline, meaning that this parameter will be only evaluable for subjects with 
psoriatic skin lesions (IGA score ≥2) at Baseline. 
Note that per protocol and device setting, only subjects with BSA ≥ 3% at Baseline will have 
IGA assessed at post-Baseline visits. 
For some subjects with BSA ≥ 3% at Baseline, IGA data have not been captured at Week 4 and 
Week 16 visits when BSA<3% at those visits. To address that, an additional supportive analysis 
will be performed in which these subjects will be considered as IGA responders at the respective 
visit.  
8.2.1.11 
Change from Baseline in the Patient’s Assessment of Arthritis Pain 
(PtAAP) at Week 16 
The change from Baseline at Week 16 in PtAAP will be analyzed as described in Section 8.1.4.4. 
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8.2.1.12 
Enthesitis-Free state based on Spondyloarthritis Research 
Consortium of Canada (SPARCC) index at Week 16 
The SPARCC index  measures the severity of enthesitis through the assessment of 16 sites, 8 for 
the right part and 8 for the left part of the body: the greater trochanter (right/left), quadriceps 
tendon insertion into the patella (right/left), patellar ligament insertion into the patella and tibial 
tuberosity (right/left), achilles tendon insertion (right/left), plantar fascia insertion (right/left), 
medial and lateral epicondyles (right/left), and the supraspinatus insertion (right/left). Tenderness 
on examination is recorded as either present (1) or absent (0) for each of the 16 sites, for an 
overall score range of 0 (no enthesitis) to 16 (severe enthesitis). 
In case 9 or more are missing, the SPARCC index will be set to missing. If at least 8 items are 
available, the available items will be assessed and scored and then weighted by the number of the 
assessed items as shown in the formula below: 
𝑆𝑃𝐴𝑅𝐶𝐶 𝑖𝑛𝑑𝑒𝑥= 𝑛×
∑
𝑠𝑐𝑜𝑟𝑒
𝑛
𝑖=1
∑
𝐴𝐼
𝑛
𝑖=1
 
where n refers to the number of total items and AI the number of assessed items. 
The analysis of enthesitis-free state based on SPARCC index at Week 16 from Baseline will be 
restricted to the subset of subjects with enthesitis at Baseline (defined as SPARCC>0). 
8.2.1.13 
Change from Baseline in PsAID-12 total score at Week 16 
The PsAID questionnaires measure the impact of disease on the subject. The impact of PsA is 
measured by weighting 12 different domains of health to derive a weighted summary score. The 
domains are pain, fatigue, skin problems, work and/or leisure activities, functional capacity, 
discomfort, sleep disturbance, coping, anxiety/fear/uncertainty, embarrassment and/or shame, 
social participation, and depression. The PsAID score is based on the relative importance of each 
of the domains. Each domain is answered based on a numeric rating scale ranging from 0 to 10. 
The equation for the PsAID-12 score is as follows: 
𝑃𝑠𝐴𝐼𝐷−12 = 1
20 (3 × 𝑃𝑎𝑖𝑛+ 2 × 𝐹𝑎𝑡𝑖𝑔𝑢𝑒+ 2 × 𝑆𝑘𝑖𝑛 𝑃𝑟𝑜𝑏𝑙𝑒𝑚𝑠+ 2 × 𝑊𝑜𝑟𝑘𝐿𝑒𝑖𝑠𝑢𝑟𝑒
⁄
+ 2 × 𝐹𝑢𝑛𝑐𝑡𝑖𝑜𝑛𝑎𝑙 𝐶𝑎𝑝𝑎𝑐𝑖𝑡𝑦+ 2 × 𝐷𝑖𝑠𝑐𝑜𝑚𝑓𝑜𝑟𝑡+ 2 × 𝑆𝑙𝑒𝑒𝑝 𝐷𝑖𝑠𝑡𝑢𝑟𝑏𝑎𝑛𝑐𝑒
+ 𝐶𝑜𝑝𝑖𝑛𝑔+ 𝐴𝑛𝑥𝑖𝑒𝑡𝑦/𝐹𝑒𝑎𝑟+ 𝐸𝑚𝑏𝑎𝑟𝑟𝑎𝑠𝑠𝑚𝑒𝑛𝑡/𝑆ℎ𝑎𝑚𝑒
+ 𝑆𝑜𝑐𝑖𝑎𝑙 𝑃𝑎𝑟𝑡𝑖𝑐𝑖𝑝𝑎𝑡𝑖𝑜𝑛+ 𝐷𝑒𝑝𝑟𝑒𝑠𝑠𝑖𝑜𝑛) 
The total score also ranges from 0 to 10 with higher scores indicating a worse impact of the 
disease. A score below 4 out of 10 is considered a subject-acceptable status. A change of 3 or 
more points is considered relevant absolute change. 
If a value (from the 12 domains) is missing, the missing value will be imputed in taking the mean 
value of the remaining (non-missing) domains, and the imputed value will be used to calculate 
the PsAID with the formula above. If 2 or more of the domains are missing, the PsAID score will 
be set to missing. 
8.2.2 
Primary analysis of secondary efficacy variables 
The secondary efficacy variables will be analyzed for all subjects in the RS by treatment group 
(except for vdHmTSS for which the analysis will be performed on the RAS). 
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As indicated in Table 4‒5, there are 8 secondary endpoints included in the testing hierarchy that 
will be tested in a chronological order until one is failed to be statistically significant.  
For the other secondary endpoints (secondary endpoints which are not part of the testing 
hierarchy), the p-values produced by the statistical models will be considered nominal since 
these endpoints are not controlled for multiplicity. 
For the secondary composite and non-composite binary endpoints, the same estimand structure 
(composite estimand) as the one defined for the primary efficacy analysis of the primary efficacy 
endpoint (Section 8.1.2) will be used. The NRI approach for handling missing data and the same 
analysis model will be considered, and the analysis results will be presented similarly, with the 
exceptions that the analyses performed on pooled data from PA0010 and PA0011 subjects will 
consider the region and the study-id factor as possible covariates for the modelling. 
The statistical hypothesis for the binary variables at Week 16 is that the conditional odds ratio in 
the BKZ group compared with placebo treatment group is equal to 1. 
For the secondary continuous endpoints, the analysis will evaluate the hypothetical estimand as 
defined below: 
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP.  
• Subject level outcome = variable as stated in Section 2.2.1.2  
• IE handling = An IE is defined as discontinuation of study treatment prior to Week 16. A 
hypothetical strategy for addressing IE will be implemented. This estimand targets the 
treatment difference in a scenario where withdrawal from study treatment does not occur, 
such that outcomes for subjects without an IE are as observed, and outcomes for subjects 
with an IE are treated as though they had completed treatment through Week 16 but on 
Placebo. A MI strategy will be used to impute any missing data and observed data after IE 
which will be set to missing prior to running MI. Such data will be imputed using reference-
based MI, in which the MI model is based on data from the Placebo group. 
• Population-level summary measure = the difference in the adjusted means between BKZ 
160mg Q4W and placebo. 
The same analysis model and imputation strategy for handling missing data as in Section 8.1.4.4 
will also be considered. The analysis results will be presented similarly as for this analysis on the 
individual ACR components.  
For vdHmTSS, a similar estimand structure as the one defined above for continuous endpoints 
will be used with the following exception for population:  
• When analyzing change at Week 16 from Baseline in vdHmTSS for subjects with elevated 
hs-CRP or with at least one bone erosion at Baseline: Population=Subjects enrolled 
according to the protocol-specified inclusion/exclusion criteria, randomized to IMP, who 
have a valid radiographic image of the hands and feet at Baseline in the subgroup of patients 
with elevated CRP and with at least one bone erosion at Baseline. 
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• When analyzing change at Week 16 from Baseline in vdHmTSS for all subjects: 
Population=Subjects enrolled according to the protocol-specified inclusion/exclusion criteria, 
randomized to IMP, who have a valid radiographic image of the hands and feet at Baseline.  
In the case of MDA as the response is based on 7 different component scores, it is necessary to 
consider various data scenarios that could impact the calculation of response. The rules described 
here are applicable in the context of the calculation of MDA response and may differ from the 
rules applied for calculating and summarizing the components individually (some values may 
need to be imputed for component analysis but are not required here to evaluate MDA response).  
The following rules will be applied to complete the derivation of MDA response based on the 
composite estimand definition: 
• If a given visit has been preceded by an IE (treatment discontinuation): 
− The endpoint at all subsequent visits (whether the data were observed or not) will be set 
to “non-response” as the subject has not met the criteria for response. 
• If a given visit has not been preceded by an IE: 
− If a subject is satisfying at least 5 of the 7 MDA criteria, the subject will be considered as 
MDA responder 
− If a subject is not satisfying at least 3 MDA criteria, the subject will be considered as 
MDA non-responder 
− In all other cases, the NRI approach will be applied. 
An overview table will combine the results of the primary analysis for the primary and secondary 
efficacy endpoints included in the testing hierarchy. 
For the country specific analyses performed on subjects randomized in Japan, the region factor 
will not be considered as a covariate for the modelling.  
Considering that the number of subjects randomized in Japan is low (less of 10% of the 
Randomized Set), statistical models might not converge. If a model (Logistic Model or Mixed 
model) is not converging, all related adjusted statistics and p-value will not be presented, “NE” 
for “Not Evaluable” will be displayed instead. 
8.2.3 
Supportive analyses of the secondary efficacy variables  
As mentioned in Table 4‒2, the supportive analyses for all secondary variables will be performed 
using the modified composite estimand for binary variables (using MI-MCMC/monotone 
regression as in Section 8.1.4.3), the hypothetical estimand for continuous variables (using MI-
MCMC/monotone regression as in Section 8.1.4.4) and OC.  
For PASI90, the MI will be run on the PASI score on subjects involving at least 3% of BSA at 
Baseline. 
For the MDA (and VLDA) MI analysis, subjects with BSA <3 at Baseline will always meet the 
criteria PASI ≤1 or BSA ≤3 except in the cases where a BSA score >3 is observed.  Subjects 
involving at least 3% of BSA at Baseline will have their BSA values imputed using MI when 
deriving MDA (VLDA). 
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For enthesitis and dactylitis free-state based on the pooled data of PA0010 and PA0011 subjects 
(in the BKZ160mg Q4W and the Placebo group), the MI will be performed on the pooled dataset 
(using data from Baseline, Week 4, 8, 12 and 16) the same way as described in Section 4.2.2.2:  
• with the following covariates in that order for each SAS® PROC MI: region (North America, 
Western Europe and Eastern Europe) and study-id ( “1” for PA0011 and “0” for PA0010) 
• For MI on LDI : on subjects with LDI>0 at Baseline 
• For MI on LEI : on all subjects (but the results will be reported for subjects with LEI>0 at 
Baseline). 
In addition, subgroup analyses will be performed on the PASI90 response at Week 16 (in 
subjects with PSO involving at least 3% of BSA at Baseline) (Refer to Section 4.8 for the list of 
subgroups of interest). The same analysis method used for the subgroup analysis of the primary 
endpoint will be performed, and the results will be presented similarly.  
Enthesitis and dactylitis free state will be analyzed as supportive analyses in the PA0010 data 
only (successively using the NRI, the modified composite estimand and the OC strategies) .  
To assess the impact of the COVID-19 pandemic, the analysis of secondary efficacy endpoints 
included in the hierarchy with be repeated on the COVID-19-Free Set (on subjects from the 
Radiographic Set included in the COVID-19-Free-Set for the analysis of VdHmTSS) using the 
primary analysis method. 
8.3 
Statistical analysis of other efficacy variables 
8.3.1 
Derivation of other efficacy variables 
8.3.1.1 
Time to ACR20, ACR50, ACR70 response from Baseline 
Time to a given response will be defined as the length in days from Baseline until the first date 
when the response is achieved.  
Time from Baseline to censoring will be considered for the following subjects:  
• Subjects who discontinue study treatment prior to achieving a response will be censored at 
the date of study treatment discontinuation.  
• Subjects in the placebo group who fail to achieve a response prior to Week 16 visit will be 
censored at the date of the Week 16 visit.  
• Subjects who reach the end of treatment without achieving the given response will be 
censored at the date of the end of treatment visit (for the Week 24 analysis, subjects who 
reached Week 24 without achieving the given response will be censored at that visit).   
8.3.1.2 
ACR20, ACR50 and ACR70 
Method for derivation of ACR50 can be found in Section 8.1.1. ACR20 and ACR70 will be 
derived similarly except that they will be based on a 20% and on 70% improvement from 
Baseline.  
ACR20, ACR50 and ACR70 responses will be analyzed at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 
36, 44, 52. 
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For the placebo group, ACR50 response will be presented both based on the Day 1 Baseline and 
on the Week 16 Baseline (on the ATS, for the ATP, for subjects switching to BKZ at Week 16).   
8.3.1.3 
PASI75, PASI90 and PASI100 response (in subjects with PSO 
involving at least 3% of BSA at Baseline) 
Method for derivation of PASI score can be found in Section 8.2.1.2. 
PASI75, PASI90, PASI100 are binary variables equal to 1 if the percentage improvement from 
Baseline in the PASI scores is ≥ 75%, ≥90%, 100% and 0 if the percentage improvement from 
Baseline is < 75%, 90%, 100%. 
PASI75, PASI90, PASI100 as well as the PASI score and the change from Baseline for subjects 
with PSO involving at least 3% of BSA at Baseline will be analyzed at Week 2, 4, 8, 12, 16, 20, 
24, 28, 32, 36, 52. 
For the placebo group, PASI90 responses will be determined both based on the Day 0 Baseline 
and on Week 16 Baseline (on the ATS, for the ATP, for subjects switching to BKZ at Week 16).   
8.3.1.4 
Composite endpoints composed of ACR50 and PASI90 and ACR50 
and PASI100 responses (subjects with PSO involving at least 3% of 
BSA at Baseline) 
The composite endpoint composed of ACR50 and PASI90 is a binary variable equal to 1 for 
subjects responding to ACR50 (ACR50=1) and PASI90 (PASI90=1). 
The composite endpoint will be equal to 0 if ACR50=0 or PASI90=0 regardless of whether any 
of the 2 endpoints is missing. 
The same rules as above will be applicable for the composite endpoint on ACR50 and PASI100. 
The composite endpoints will be missing if both endpoints are missing or if any of the 2 is 
missing and the other one equal to 1.    
Each endpoint (ACR50 and PASI90 or PASI100) will be imputed separately before deriving the 
composite endpoint. 
The composite endpoints for subjects with PSO involving at least 3% BSA at Baseline will be 
analyzed at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 52. 
8.3.1.5 
Proportion of Psoriatic Arthritis Response Criteria (PsARC) 
responders 
The PsARC is based on the TJC (68 joints) and SJC (66 joints), the PGA-PsA and PhGA-PsA. 
The PsARC response is defined as improvement from Baseline in at least 2 of the 4 measures 
(TJC, SJC, PGA-PsA, PhGA-PsA) 1 of which must be TJC or SJC and no worsening from 
Baseline in any of the 4 measures:  
• Improvement for TJC and SJC is defined as a reduction of ≥30%. Improvement for PGA-
PsA and PhGA-PsA is defined as a reduction of the 100-point VAS of ≥20 points 
• Worsening for TJC and SJC is defined as an increase of ≥30%. Worsening for PGA-PsA and 
PhGA-PsA is defined as an increase of the 100-point VAS of ≥20. 
PsARC response will be analyzed at Week 2, 4, 8, 12, 16, 20, 24, 36, 52. 
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8.3.1.6 
Psoriatic Arthritis Disease Activity Score (PASDAS) categories and 
change from baseline in PASDAS 
The PASDAS is a composite score that includes patient and physician global scores of skin and 
joint disease, SJC, TJC, LEI, tender dactylitis count (sum of tenderness scores), the physical 
component of the SF-36 Health Survey, and level of hs-CRP. PASDAS is calculated using the 
following equation:  
𝑃𝐴𝑆𝐷𝐴𝑆= ((0.18 × √Physician global VAS) + (0.159 × √Patient global VAS )
− (0.253 × √SF36 PCS ) + (0.101 × LN(SJC + 1)) + (0.048 × LN(TJC + 1))
+ (0.23 × LN(LEI + 1)) + (0.377 × LN (Tender dactylitis count + 1))
+ (0.102 x LN(hs −CRP + 1) + 2)) ∗1.5 
Note: LN=natural logarithm  
If Tender Dactylitis count is missing because LDI=0 at Baseline, Tender Dactylitis count will be 
replaced by 0 in the formula. 
If for any other reason a PASDAS component is missing, PASDAS will be set to missing. 
The following categories are used to define the level of disease activity:  
• Remission: PASDAS ≤1.9  
• Low disease activity: PASDAS >1.9 to <3.2 
• Moderate disease activity: PASDAS 3.2 to <5.4 
• High disease activity: PASDAS ≥5.4. 
The PASDAS categories and the change from Baseline in PASDAS score will be analyzed at 
Week 4, 16, 24, 36, 52. 
8.3.1.7 
ACR50 responders at Week 16 and maintaining response at post-
Week 16 visits up to Week 52 
For subjects who have an observed ACR50 response at Week 16, the ACR50 responders at 
Week 52 will be presented.  
This summary will be presented on the ATS by randomized treatment for responder subjects at 
Week 16.  
ACR50 responses for subjects responding at Week 16 will be analyzed at Week 20, 24, 28, 32, 
36, 44, 52. 
8.3.1.8 
MDA response 
Method for derivation of the MDA response can be found in Section 8.2.1.4.    
MDA response will be analyzed at Week 4, 8, 12, 16, 20, 24, 36, 52.  
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8.3.1.9 
Very Low disease activity (VLDA) response 
Like MDA, VLDA is a state of disease activity deemed a useful target of treatment by both the 
subject and physician, given current treatment possibilities and limitations.  
A subject is considered as having VLDA if all 7 of the criteria used for MDA and listed in 
Section 8.2.1.4 are fulfilled.  
If any of the 7 MDA criteria is not met, then the subject will be considered as non-responder. 
VLDA response will be analyzed at Week 4, 8, 12, 16, 20, 24, 36, 52.  
8.3.1.10 
Proportion of Subjects with an IGA score of 0 (clear) or 1 (almost 
clear) AND at least a 2-grade reduction from Baseline in the subset of 
subjects with psoriatic skin lesions at Baseline 
Method for derivation of this variable can be found in Section 8.2.1.10. 
The proportion of subjects with an IGA score of 0 (clear) or 1 (almost clear) AND at least a 2-
grade reduction from Baseline in the subset of subjects with psoriatic skin lesions at Baseline 
will be analyzed at Week 4, 8, 12, 16, 20, 24, 36, 52. 
For some subjects with BSA ≥ 3% at Baseline, IGA data have not been captured at some post-
Baseline visits when BSA<3% at those visits. To address that, an additional supportive analysis 
will be performed in which these subjects will be considered as IGA responders at the respective 
visit.  
In the context of this analysis, observed data for % of BSA affected by PSO will be also 
analyzed by visit using descriptive statistics. 
8.3.1.11 
Disease Activity Index for Psoriatic Arthritis (DAPSA) score, state 
and change from Baseline in DAPSA score 
Disease Activity Index for Psoriatic Arthritis (DAPSA) is a composite score of patient global and 
pain VAS, TJC, SJC and hs-CRP (mg/L) that incorporates a pattern of peripheral arthritis that 
often is encountered in PsA. DAPSA score will be calculated as follows:  
𝐷𝐴𝑃𝑆𝐴= 𝑆𝐽𝐶+ 𝑇𝐽𝐶+ 𝑃𝐺𝐴– 𝐴𝑟𝑡ℎ𝑟𝑖𝑠𝑡𝑖𝑠
+ 𝑃𝑡𝐴𝐴𝑃+ ℎ𝑠– 𝐶𝑅𝑃  
where:  
• SJC range from 0 to 66  
• TJC ranges from 0 to 68  
• PGA-Arthritis represents the patient’s global assessment of arthritis ranging from 0 to 10 ;  
0=best, 10=worst  (using the unrounded VAS value that ranges from 0 to 100 mm and 
dividing this value by 10) (Section 8.3.1.28) 
• PtAAP ranging from 0 to 10, 0=best, 10=worst, (unrounded, by dividing the original value 
by 10)  
• hs-CRP in mg/L (no upper limit applied). 
DAPSA values will be categorized in the following disease activity states: 
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• Remission (REM) (DAPSA≤4) 
• Low Disease Activity (LDA) (DAPSA >4 and ≤14)  
• Medium Disease Activity (MDA) (DAPSA >14 and ≤28)  
• High Disease Activity (HDA) (DAPSA>28). 
For analyses with imputation of missing data, the imputed value for DAPSA will be based on the 
imputed values for the individual components. 
For the OC analyses, if any individual component score is missing, the DAPSA score will be set 
to missing.  
DAPSA state, DAPSA scores and changes in scores from Baseline will be analyzed at Week 2, 
4, 8, 12, 16, 20, 24, 28, 32, 36, 44, 52. 
8.3.1.12 
Change from Baseline in the Disease Activity Score-28 based on C-
reactive protein (DAS28[CRP]) 
The components for DAS28[CRP] include: 
• the TJC and SJC based on 28 joints (Section 8.1.1.1): 
− Upper extremity (26) - bilateral shoulders, elbows, wrists (includes radiocarpal, and 
carpal and carpometacarpal bones considered as a single unit), metacarpophalangeal 
joints I, II, III, IV, and V, thumb interphalangeals, proximal interphalangeal II, III, IV, 
and V. 
− Lower extremity (2) - knees. 
• the PGA-Arthritis (ranging from 0 to 10 by dividing the original value by 10)  
• the hs-CRP (in mg/L). 
The DAS28[CRP] is calculated as follows: 
𝐷𝐴𝑆28[𝐶𝑅𝑃] = 0.56 × √𝑇𝐽𝐶+ 0.28 × √𝑆𝐽𝐶+ 0.014 × PGA– Arthritis
+ 0.36 × ln(ℎ𝑠– 𝐶𝑅𝑃+ 1) + 0.96 
For analyses with imputation of missing data, the imputed value for DAS28[CRP] will be based 
on the imputed values for the individual components. 
For OC analyses, if any individual component score is missing, the DAS28[CRP] score will be 
set to missing.  
The changes from Baseline in DAS28[CRP] will be analyzed at Week 2, 4, 8, 12, 16, 20, 24, 28, 
32, 36, 44, 52. 
8.3.1.13 
Change from Baseline in all individual ACR core components 
Individual ACR components (as listed in Section 8.1.1) are:  
 
• SJC 
• TJC 
• HAQ-DI  
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• PtAAP 
• PhGA-PsA  
• PGA-PsA 
• hs-CRP. 
The change from Baseline (ratio from Baseline for hs-CRP) for each of the ACR components 
will be summarized at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 (for SJC, TJC and hs-CRP), 
44, 48 (for hs-CRP only), 52. 
8.3.1.14 
Change from Baseline in vdHmTSS total score and in erosion and 
joint space narrowing (sub-scores)  
Scoring of vdHmTSS can be found in Section 8.2.1.5.  
The change from Baseline in vdHmTSS total score, erosion sub-score and joint space narrowing 
sub-score will be analyzed at Week 16, 52, on the radiographic set (successively on the overall 
population , on subjects with elevated hs-CRP and/or with at least one bone erosion at Baseline 
and on subjects without elevated hs-CRP and without bone erosion at Baseline). 
At Week 16 and 52, imaging data collected outside ±14 days around the expected visit date will 
be excluded from the analysis. 
8.3.1.15 
Percentage of subjects with no radiographic joint damage 
progression (Change from Baseline vdHmTSS of ≤0.5) 
The higher the vdHmTSS score is the more radiographic damage the Subject will have. 
The absence of joint damage progression (ie, stabilization or improvement in radiographic 
damage from Baseline) is then considered is the change of score from Baseline is ≤0.5.   
The percentage of subjects with no joint damage progression will be analyzed at Week 16 and 52 
on the radiographic set (successively on the overall population and on subjects with elevated hs-
CRP and/or with at least one bone erosion at Baseline). 
8.3.1.16 
Dactylitis-free state based on the LDI and change in LDI from 
Baseline in the subgroup of subjects with dactylitis at Baseline 
Dactylitis-free state is based on a Leeds Dactylitis Index (LDI) of 0, for subjects with dactylitis 
at Baseline (LDI>0) (Section 8.2.1.7).  
The percentage of subjects with dactylitis free-state and the change from Baseline in LDI (on the 
subgroup of subjects with dactylitis at Baseline) will be analyzed at Week 4, 8, 12, 16 on the 
pooled Sample of PA0010 and PA0011 subjects (for subjects in the BKZ 160mg Q4W and the 
Placebo groups) and at Week 4, 8,12, 16, 20, 24, 36, 52 on PA0010 subjects. 
8.3.1.17 
Enthesitis-free state based on the LEI and change in LEI from 
Baseline in the subgroup of subjects with enthesitis at Baseline 
Enthesitis-free state is based on a Leeds Enthesitis Index (LEI) of 0, for subjects with enthesitis 
at Baseline (LEI>0) (Section 8.2.1.6).  
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The percentage of subjects with enthesitis-free state and the change from Baseline in LEI (on the 
subgroup of subjects with enthesitis at Baseline) will be analyzed at Week 4, 8, 12, 16 on the 
pooled Sample of PA0010 and PA0011 subjects (for subjects in the BKZ160mg Q4W and the 
Placebo groups) and at Week 4, 8,12, 16, 20, 24, 36, 52 on PA0010 subjects. 
8.3.1.18 
Enthesitis-free state based on the SPARCC index and change in 
SPARCC from Baseline in the subgroup of subjects with enthesitis at 
Baseline 
Enthesitis-free state is based on a SPARCC index of 0, for subjects with enthesitis at Baseline 
(SPARCC>0) (Section 8.2.1.12).  
The percentage of subjects with enthesitis-free state and the change from Baseline in the 
SPARCC index (on the subgroup of subjects with enthesitis at Baseline) will be analyzed at 
Week 4, 8, 12, 16 on the pooled Sample of PA0010 and PA0011 subjects (for subjects in the 
BKZ160mg Q4W and the Placebo group) and at Week 4, 8,12, 16, 20, 24, 36, 52 on PA0010 
subjects. 
8.3.1.19 
Proportion of subjects with a decrease of HAQ-DI from Baseline of at 
least 0.35 in the subgroup of subjects with Baseline HAQ-DI≥0.35  
The proportion of HAQ-DI responders (subjects with a decrease of HAQ-DI from Baseline of at 
least 0.35 for subjects with HAQ-DI≥0.35 at Baseline) will be analyzed at Week 2, 4, 8, 12, 16, 
20, 24, 28, 32, 36, 44, 52. 
In addition, subgroup analyses will be performed on the HAQ-DI response at Week 16. Refer to 
Section 4.8 for the list of subgroups of interest. The same analysis method used for the subgroup 
analysis of the primary endpoint will be performed and the results will be presented similarly.  
8.3.1.20 
Change from Baseline in the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) in the subgroup of subjects with axial 
involvement defined by a score of ≥4 at Baseline 
The BASDAI measure the disease activity of ankylosing spondylitis. The BASDAI is a validated 
self-reported instrument which consists of 6 horizontal Numeric Rating Scales, each with 10 
units to measure the severity of the 5 major symptoms: fatigue, spinal pain, peripheral joint pain 
and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. 
To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness 
is taken. The resulting 0 to 50 sum score is divided by 5 to give a final BASDAI score between 0 
and 10, with lower scores indicating lower disease activity. 
The BASDAI is calculated as follows: 
𝐵𝐴𝑆𝐷𝐴𝐼=
𝑄1 + 𝑄2 + 𝑄3 + 𝑄4 + (𝑄5 + 𝑄6
2
)
5
 
where Q1 – Q6 are the 6 questions from the BASDAI questionnaire. 
If 1 of the 2 morning stiffness measurements (ie, questions: “How would you describe the overall 
level of morning stiffness you have had from the time you wake up?” and “How long does your 
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morning stiffness last from the time you wake up?”) is missing, the other one will be used for the 
morning stiffness calculation.  
If 1 major symptom of the BASDAI is missing, the total score of the remaining symptoms will 
be divided by the number of symptoms assessed. If more than 1 major symptom is missing, the 
total BASDAI score will be set to missing. 
Change from Baseline in BASDAI will be analyzed for subjects with axial involvement at 
Baseline (BASDAI≥4) at Week 4, 8, 12, 16, 24, 36, 52.  
8.3.1.21 
Change from Baseline in the modified Nail Psoriasis Severity Index 
(mNAPSI) score in the subgroup of subjects with psoriatic nail 
disease at Baseline 
Subjects with psoriatic nail disease will have a target nail selected at the Baseline visit for 
evaluation using the mNAPSI. The nail selected should be the most affected nail observed at 
Baseline and should be the only one assessed throughout the study. The target nail will be scored 
(0 to 3) for onycholysis/oil drop dyschromia, nail plate crumbling, and pitting and will be scored 
(0 for “no” or 1 for “yes”) for leukonychia, nail bed hyperkeratosis, splinter hemorrhages, and 
red spots in the lunula. The total score (also called the mNAPSI score) will then range from 0 to 
13 with higher scores indicative of more severe nail disease. 
If any of the 7 response items that contribute to mNAPSI is present, while other items are 
missing (ie partial mNAPSI data), then the missing items are assumed to be 0 for the mNAPSI 
calculation. In some cases, the data may be captured in such a way that only non-zero component 
scores are present in the database. Again, those components that are not present are simply 
assumed to be 0 for the mNAPSI calculation.   
Change from Baseline in mNAPSI and mNAPSI resolution (mNAPSI=0 at post-baseline 
assessments) will be analyzed for subjects with psoriatic nail disease at Baseline (mNAPSI 
score>0) at Week 4, 8, 12, 16, 24, 36, 52. 
8.3.1.22 
Change from Baseline in PsAID-12 total score 
Method for derivation of PsAID-12 can be found in Section 8.2.1.13. 
The proportion of subjects achieving a total score of PsAID-12 ≤ 4 - Patient acceptable symptom 
state (PASS), the proportion of subjects achieving a decrease of 3 or more points from Baseline 
on the total score (for subjects with minimal score of 3 at Baseline), the change from Baseline in 
the total score and in the individual scores for each PsAID-12 domain, will be analyzed at Week 
4, 16, 24, 36, 52 (the proportions of subjects achieving PASS will also be analyzed at Baseline).  
8.3.1.23 
Change from Baseline in the Psoriatic Arthritis Quality of Life 
(PsAQoL) total score 
PsAQoL is a disease specific Health-Related Quality of Life questionnaire comprised of 20 
items. Each item is scored as 0 for “not true” or 1 for “true”, so that the score ranges from 0 to 20 
with higher scores indicating worse health-related quality of life.  
If 6 or less item responses are missing, the missing responses will be imputed with the mean of 
available responses to calculate a total score. If more than 6 items responses are missing, the total 
score will be left missing. 
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Change from Baseline in PsAQoL total score will be analyzed at Week 4, 16, 24, 36, 52. 
8.3.1.24 
Change from Baseline in the SF-36 PCS and MCS scores, as well as 
the 8 domain scores (Physical Functioning, Role Physical, Bodily 
Pain, General Health, Vitality, Social Functioning, Role Emotional, 
and Mental Health) 
Scoring instructions of SF-36 norm-based T-scores for the 8 domains and the SF-36 PCS and 
MCS are described in Section 8.2.1.3. 
Change from Baseline in SF-36 individual domain scores, MCS and PCS scores will be analyzed 
at Week 4, 16, 24, 36, 52.  
8.3.1.25 
Change from Baseline in Functional Assessment of Chronic Illness 
Therapy (FACIT)—Fatigue subscale score 
The FACIT-Fatigue is a 40-item measure that assesses self-reported fatigue and its impact upon 
daily activities and function over the past 7 days. The scale consists of 5 subscales (physical 
well-being, social/family well-being, emotional well-being, functional well-being, and fatigue). 
The fatigue subscale is the only one used in this study. It is composed of 13 items, all scored 
from 0 (Not at all) to 4 (Very much). The FACIT-Fatigue subscale score ranges from 0 to 52 
with 0 being the worst possible score and 52 being the best possible score. To obtain a score 
from 0 to 52, all negatively worded questions must be recoded, so that responses range from 
worst (0) to the best (4) outcome.  
Items 1 to 6 and 9 to 13 are negatively framed questions for which the coding needs to be 
reversed before deriving the score.  
The FACIT-Fatigue subscale score is obtained by summing up the responses of all reversed / non 
reversed items with equal weight. In cases where some answers are missing, a total score is re-
scaled from the score of the answered items, so long as more than 50% of the items (ie, at least 7 
of 13) were answered. 
The formula to derive the FACIT-Fatigue subscale score is then: 
𝐹𝐴𝐶𝐼𝑇−𝐹𝑎𝑡𝑖𝑔𝑢𝑒 𝑠𝑢𝑏𝑠𝑐𝑎𝑙𝑒 𝑠𝑐𝑜𝑟𝑒= 13 𝑥 
∑𝑆𝑐𝑜𝑟𝑒 𝑜𝑓 𝑖𝑡𝑒𝑚𝑠
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑖𝑡𝑒𝑚 𝑎𝑛𝑠𝑤𝑒𝑟𝑒𝑑  
The minimum clinically important difference for FACIT-Fatigue subscale score in patients with 
PsA was determined to be a 4-point positive change.  
Change from Baseline in FACIT-Fatigue subscale score, as well as the proportion of subjects 
with minimum clinically important difference for FACIT-Fatigue subscale score in subjects with 
FACIT-Fatigue subscale score ≤48 at Baseline, will be analyzed at Week 4, 16, 24, 36, 52.   
8.3.1.26 
Change from Baseline in Work Productivity and Activity Impairment 
Questionnaire–Specific Health Problem (WPAI-SHP) v2.0 adapted to 
PsA scores  
The WPAI-SHP is a subject-reported questionnaire that assesses subject’s employment status, 
work absenteeism, work impairment while working (presenteeism), overall work and daily 
activity impairment attributable to a specific health problem.  
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Five out of 6 items of the WPAI-SHP are regrouped into the 4 dimensions (absenteeism, 
presenteeism, work productivity and activity impairment) with scores expressed as percentage, 
where higher numbers indicate greater impairment and less productivity, ie, worse outcomes, as 
described in the WPAI-SHP scoring rules. 
The scoring rules for the WPAI-SHP are as follows: 
Questions: 
• 
 
• 
 
• 
 
• 
 
• 
 
 
• 
 
 
Scores:  
• Percent work time missed due to problem from the target disease:  
 
100 ×
𝑄2 ℎ𝑜𝑢𝑟𝑠 
(𝑄2 ℎ𝑜𝑢𝑟𝑠+ 𝑄4 ℎ𝑜𝑢𝑟𝑠) 
• Percent impairment while working due to problem from the target disease:  
 
100 × 𝑄5 𝑆𝑐𝑜𝑟𝑒
10
 
• Percent overall work impairment due to problem from the target disease:  
 
100 × [
𝑄2 ℎ𝑜𝑢𝑟𝑠
(𝑄2 ℎ𝑜𝑢𝑟𝑠+ 𝑄4 ℎ𝑜𝑢𝑟𝑠) + ((1 −
𝑄2 ℎ𝑜𝑢𝑟𝑠
(𝑄2 ℎ𝑜𝑢𝑟𝑠+ 𝑄4 ℎ𝑜𝑢𝑟𝑠)) × 𝑄5 𝑠𝑐𝑜𝑟𝑒
10
) ] 
 
• Percent activity impairment due to problem from the target disease:  
 
100 × 𝑄6 𝑆𝑐𝑜𝑟𝑒
10
 
To make data consistent and amenable to statistical analysis, the following counting rules will be 
applied to handle out of range and ambiguous answers of the WPAI-SHP. These rules will be 
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applied prior to conducting any type of statistical analysis of the data. Due to the inter-relation 
between certain questions of the WPAI-SHP, the priority order for implementing these specific 
counting rules is as in the listed order below. 
• Employment status: 
− If (Q1=missing) and (Q2>0 or Q3>0 or Q4>0), then Q1=YES. 
• Hours missed due to psoriatic arthritis: 
− If Q1 = NO, then Q2 = missing. 
− If (Q2 =0 or missing) and Q1 = missing, then Q2=missing. 
• Hours missed due to other reasons: 
− If Q1 = NO, then Q3 = missing. 
− If (Q3 =0 or missing) and Q1 = missing, then Q3=missing.  
• Hours actually worked: 
− If Q1 = NO, then Q4 = missing. 
− If (Q4 =0 or missing) and Q1 = missing, then Q4=missing. 
• Work productivity: 
− If Q1 = NO, then Q5 = missing. 
− If (Q5 =0 or missing) and Q1 = missing, then Q5=missing. 
− If Q4=0, then Q5 = missing. 
In the listings, the original values will be kept and displayed. 
 
The WPAI-SHP scores are based on 1-item (presenteeism, activity impairment), 2-items 
(absenteeism) and multiple items (overall work productivity). A score cannot be calculated if 
there is a missing response to the corresponding item.   
A negative number will indicate a reduction in the score/improvement for subjects. 
The change from Baseline score is derived as post Baseline score minus Baseline score.  A 
negative change score indicates a reduction in the score/improvement for the subject. 
The change from Baseline in scores will be analyzed at Week 16, 24, 52. 
The analysis of WPAI-SHP scores will be performed on observed cases only. 
8.3.1.27 
Responses to the EuroQol-5 Dimensions-3 Level (EQ-5D-3L), change 
from Baseline in VAS score  
The Euro-Quality of Life 5-Dimensions 3 Level version (EQ-5D-3L) health questionnaire 
provides a descriptive profile and a single index value for health status (using a VAS).  
The instrument is composed of a 5-item health status measure (mobility, self-care, usual 
activities, pain/discomfort, anxiety/depression) and a VAS. Each of the 5 health states is divided 
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into 3 levels (no problem, some or moderate problems, and extreme problems) and is scored as 1, 
2, and 3, respectively. These scores are referred as “utility scores”. 
The EQ-5D VAS records the respondent’s self-rated health status on a vertical 20cm scale, 0 to 
100 graduated (0=worst imaginable health status, 100=best imaginable health status). 
The response in each of the 5 items of the EQ-5D-3L and the values and the changes in VAS 
from Baseline will be presented at Week 4, 16, 24, 36, 52.    
8.3.1.28 
Change from Baseline in Patient’s Global Assessment of Arthritis 
(PGA-arthritis) and Physician’s Global Assessment of Arthritis 
(PhGA-Arthritis) 
The physician’s global assessment of arthritis (PhGA-arthritis) and the patient’s global 
assessment of arthritis (PGA-arthritis) are clinical outcomes based on visual analog scales (VAS) 
ranged from 0 to100 (in mm).  
• PGA-Arthritis: Subjects will assess the impact of their arthritis pain in answering the 
following question “Considering all the ways your arthritis affects you, please mark a vertical 
line on the scale below to show how you are feeling today.” The subject should be asked to 
consider their arthritis symptoms and functional capacity in their response to this question. 
Subjects will score PGA-Arthritis in using a VAS where 0 is “very good, no symptoms” and 
100 is “very poor, severe symptoms.” 
• PhGA-Arthritis: The investigator will assess how the subject’s overall arthritis appears at the 
time of the visit using a numerical rating scale where 0 is “very good” and 100 is “very 
poor”. This assessment will be based through the following question: “The Patient’s arthritis 
at this time is: “Please mark a vertical line on the scale below to assess the overall status of 
the subject's arthritis signs and symptoms and the functional capacity of the subject.” 
Values and changes from Baseline in PhGA-Arthritis and PGA-Arthritis will be analyzed at 
Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 44, 52.  
8.3.2 
Analyses of other efficacy endpoints 
Unless specified above, all other efficacy variables will be analyzed for all subjects: 
• In by-visit tables, for the following treatment groups: Placebo/BKZ160 mg Q4W, BKZ 
160mg Q4W, ADA 40mg Q2W.  
• on the RS, for the overall study period (until Week 24 for the Week 24 analysis). 
8.3.2.1 
Time to ACR20/50/70 response  
The time to ACR20/50/70 response will be successively analyzed: 
• For the DBP, on the 3 treatment groups (for the Week 24 analysis). 
• For the overall study period, on the 3 treatment groups (for the Week 52 analysis) They will 
be estimated and presented using the Kaplan Meier (KM) product limit method for each of 
treatment groups.  
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The KM plots of time to ACR20,50,70 response will be presented by treatment group. The line 
will start at 0 and will increase over time, representing time to achieving the response (reversed 
KM estimates). 
The median time to response, including the 2 sided 95% CI, will be calculated for each treatment 
group.  
For the analysis on the DBP, the hazard ratio of BKZ vs. placebo as well as the corresponding 
95% CI and p-value will be displayed (using SAS® PROC PHREG stratified by region and bone 
erosion at Baseline) 
Comparisons of BKZ vs. placebo will be analyzed based on a log-rank test stratified by region 
and bone erosion at Baseline (0, ≥1) (considering that the same stratification factors have been 
retained for the primary efficacy analysis). This comparison will be performed using SAS® 
PROC LIFETEST on subjects from both treatment groups. 
The time to ACR20/50/70 endpoints will be analyzed using OC data. 
8.3.2.2 
Other endpoints (excluding time to ACR20/50/70 response) 
For the binary variables, the following estimand structure (composite estimand) will be defined: 
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = The given variable and time point being summarized.  
• IE handling = An IE is defined as discontinuation of study treatment prior to the time point 
being summarized. A composite strategy will be implemented in which a positive clinical 
outcome is defined as achieving the given variable at the specified time point and not 
discontinuing study treatment through that time point. 
• Population-level summary measure = Unadjusted proportion of responder. 
Subjects who have an IE, which will be considered associated to a treatment failure, will be 
considered as non-responders. Any missing data will also be considered as non-responders (NRI 
approach). For categorical variables, the worst-category will be imputed similarly instead of non-
response.   
For the continuous variables, the following estimand (hypothetical estimand) will be defined: 
• Population = Subjects enrolled according to the protocol-specified inclusion/exclusion 
criteria and randomized to IMP. 
• Subject-level outcome = The given variable and time point being summarized. 
• IE handling = An IE is defined as discontinuation of study treatment prior to the time point 
being summarized. A hypothetical strategy will be implemented in which outcomes for 
subjects without an IE are as observed at the given time point, and outcomes for subjects 
with an IE are treated as though they had completed the randomized study treatment through 
the time point being summarized. A MI strategy will be used to impute data following an IE.  
• Population-level summary measure = Unadjusted mean. 
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The analysis of other continuous efficacy variables will be performed according to the above 
estimand, using MI-MCMC/ monotone regression as imputation method for missing data for all 
visits up to Week 24 for the Week 24 analysis and all visits up to Week 52 for the Week 52 
analysis (similarly as in Section 8.2.2). 
The other efficacy variables will also be summarized based on OC and the modified composite 
estimand (for binary variables) and summarized by visit for all treatment groups as detailed 
below: 
For binary endpoints using:  
• The number and proportion of responders using the NRI approach.  
• The mean proportion of responders in the multiple imputed datasets and the 95% CI 
(modified composite estimand). For ACR50 response at post-Week 16 visits for subjects 
responding at Week 16, the same imputed data as generated in the context of the analysis of 
the primary efficacy endpoint will be used.  
− For enthesitis and dactylitis free-state based on the pooled data of PA0010 and PA0011 
subjects (for subjects in the BKZ 160mg Q4W and the Placebo group), the MI will be 
performed on the pooled dataset (using data from Baseline, Week 4, 8, 12 and 16) the 
same way as described in Section 4.2.2.2, but with the following covariates in that order 
for each SAS® PROC MI: region (North America, Western Europe and Eastern Europe 
in that order) and study-id ( “1” for PA0011 and “0” for PA0010). 
− For enthesitis based on LEI, the MI will be run on all subjects and results reported for 
subjects with LEI>0 at Baseline ; for other binary variables derived from continuous 
value(s), the MI will be run on the subset of subjects (if applicable) for which the variable 
will be reported (ie: for LDI and Tender dactylitis count in the context of PASDAS 
calculation, on subjects with LDI>0 at Baseline)  
− For ACR50 based on Week 16 Baseline, the MI will be run on Week 16 and post-week 
16 values, on the ATBS for the Placebo group. Week 16 value will be considered as the 
Baseline value regardless of whether the Placebo subjects switched to BKZ on a later 
visit. 
− For PASI90 based on Week 16 Baseline, the MI will be run on W16 and post-week 16 
values, on the ATBS for the Placebo group on subjects with PSO involving at least 3% of 
BSA at Week 16. Week 16 value will be considered as the Baseline value regardless of 
whether the Placebo subjects switched to BKZ on a later visit.        
•     The observed number and proportion of responders on subjects with observed data  
For categorical endpoints (ie, EQ-5D-3L dimensions score, DAPSA state, PASDAS categories) 
using:  
• The number and percentage by endpoint category using the NRI approach (as performed for 
the primary analysis of the primary endpoint with the exception that the NRI is replaced by 
the worst category imputation) 
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• The mean percentage and corresponding 95% CI by endpoint category in the multiple 
imputed datasets (modified composite estimand). Regardless of imputed values, the value of 
the categorical endpoint after IE are by default set to the worst category (ie:  High Disease 
Activity for DAPSA state)   
• The observed number and percentage by category on subjects with observed data.  
For continuous endpoints, on absolute values and changes from Baseline (or ratio from Baseline 
for hs-CRP) using: 
• The mean (with geometric mean for hs-CRP and its 95% CI), SE, median, minimum, and 
maximum in the multiple imputed datasets (hypothetical estimand) (except for WPAI-SHP 
scores).  
− For the change from baseline in LDI, LEI and SPARCC based on the pooled data of 
PA0010 and PA0011 subjects (for subjects in the BKZ 160mg Q4W and the Placebo 
group), the MI will be performed on the pooled dataset (using data from Baseline, Week 
4, 8, 12 and 16) the same way as described in Section 4.2.2.2, but with the following 
covariates in that order for each SAS® PROC MI: region (North America, Western 
Europe and Eastern Europe in that order) and study-id ( “1” for PA0011 and “0” for 
PA0010). 
− For LEI, the MI will be run on all subjects and results reported for subjects with LEI>0 at 
Baseline ; for other continuous variables derived from continuous value(s), the MI will be 
run on the subset of subjects (if applicable) for which the variable will be reported (ie: for 
LDI, on subjects with LDI>0 at Baseline) 
− For Tender dactylitis count in the context of PASDAS calculation, if the MI does not 
converge, a conservative approach will be used by first imputing a value of 1 for all joints 
with missing tenderness score.       
• The observed number of observations (n), the mean (with the geometric mean for hs-CRP), 
SD, median, CV (geometric CV for hs-CRP), minimum, and maximum. 
For ACR20, ACR50, ACR70, PASI75, PASI90, and PASI100 responders over time, a line plot 
by treatment group will be produced.  
8.3.2.3 
Additional statistical analysis for other efficacy endpoints 
Although statistical testing is not planned for other efficacy variables as per protocol, for selected 
other efficacy variables, it is of interest to perform statistical testing and calculate inferential 
statistics. The associated p-values will be considered nominal and not controlled for multiplicity. 
For continuous variables, the MI-MCMC/monotone regression approach will be applied for the 
imputation model on the change from Baseline (hypothetical estimand). The analysis model will 
be based on ANCOVA with fixed effect of treatment, region, bone erosion at Baseline and 
Baseline value as covariates. 
For responder variables, the analysis will follow the NRI approach (composite estimand). The 
analysis model will be based on a logistic model with fixed effect for treatment and bone erosion 
at Baseline and region as stratification variables.    
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Below is a list of other secondary efficacy variables for which these nominal p-values (with the 
timepoints in parentheses) will be calculated.  
The results of these inferential tests (LSM differences for continuous variables, OR for binary 
variables, 95% CI and p-value) will be presented in a single table:  
For the following endpoints, the p-value provided (based on the change from Baseline for 
continuous variables) will be based on the comparison of BKZ 160mg Q4W and placebo groups   
using the same statistical methods for binary variables as used for the primary analysis of 
ACR50 (Section 8.1.2) and for the continuous variables as used for the analysis of the ACR 
components (Section 8.1.4.4): 
• ACR20/50/70 (Week 2, 4, 8, 12, 16) 
• PASI75/90/100 (Week 2, 4, 8, 12, 16) 
• ACR50/PASI90 composite (Week 2, 4, 8, 12, 16) 
• ACR50/PASI100 composite (Week 2, 4, 8, 12, 16) 
• TJC (Week 2, 4, 8, 12, 16)  
• SJC (Week 2, 4, 8, 12, 16) 
• MDA (Week 4, 8, 12, 16) 
• PtAAP (Week 2, 4, 8, 12, 16) 
• PsAQoL (Week  4,16) 
• PsAID-12 (Week 4, 16) 
• FACIT-Fatigue subscale (Week  4, 16) 
• WPAI-SHP (Week 16) (on observed data) 
• VdHmTSS (Week 16) 
• DAPSA (Low disease activity or better) “response” (Week 2, 4, 8, 12, 16) 
• PsARC (Week 2, 4, 8, 12, 16). 
For the following endpoints, 2 p-values will be provided one for the comparison of BKZ 160mg 
Q4W and Placebo / BKZ 160mg Q4W groups and one for the comparison of BKZ 160mg Q4W 
and ADA 40mg Q2W groups:  
• ACR20/50/70 (Week 16, 24, 52) 
• PASI75/90/100 (Week 16, 24, 52) 
• ACR50/PASI90 composite (Week 16, 24, 52) 
• ACR50/PASI100 composite (Week 16, 24, 52) 
• MDA (Week 16, 24, 52) 
• PsARC (Week 16, 24, 52). 
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9 
PHARMACOKINETICS AND IMMUNOLOGICAL 
(IMMUNOGENICITY) ANALYSES 
9.1 
Pharmacokinetics 
Pharmacokinetic variables will be analyzed for all subjects in the PK-PPS.  
Only subjects treated with BKZ will be included in the PK analyses. The Baseline observation 
for the Placebo group will be the Week 16 pre-dose observation. PK variables will be 
summarized at each scheduled visit by treatment group (Placebo / BKZ 160mg Q4W and BKZ 
160mg Q4W). 
• BKZ concentrations will be summarized by treatment group, globally and on subjects 
randomized in Japan. 
No imputation will be used for missing samples. However, if plasma concentration 
measurements are below the limit of quantification (BLQ), then for the calculation of the derived 
statistics, the result will be set to ½ of LLOQ (ie, 1/2*0.250 = 0.125 µg/mL). Descriptive 
statistics including number of values, geometric mean, its 95% CI, geometric coefficient of 
variation, mean, SD, median, minimum, and maximum. Geometric mean and its 95% CI, 
geometric CV, mean and SD will be calculated if at least ⅔ of the values of interest is above the 
LLOQ and number of values ≥3 at the respective timepoint; otherwise, only number of values, 
median, minimum, and maximum will be presented. 
• In addition, geometric mean of BKZ plasma concentration (with 95% CI) time curves will be 
plotted on linear and semi-logarithmic scales:  
− by treatment group (2 lines per graph, one line for each treatment), 
• The table summary and figures will be primarily repeated by anti-BKZ antibody status 
(positive, negative, missing) by treatment group (3 lines per graph, one line for each anti-
BKZ antibody status, one graph per treatment group). The missing group will not be 
displayed if ≥95% of subjects are categorized in the non-missing groups.  
The ADAb status (positive, negative, or missing) will be considered in a cumulative manner 
at each time point:  
− a subject will be counted as positive from the first visit at which the subject achieved a 
positive ADAb sample result to the end of the treatment period (regardless of any 
missing/inconclusive or negative ADAb sample result).  
− If a subject has only negative ADAb samples or only one missing/inconclusive sample 
with negative ADAb samples up to that timepoint, the subject will be classified as 
negative. An exception remains for the Baseline Visit where only one sample would be 
available. If the sample is missing/inconclusive, then the sample will be classified as 
being negative for the cumulative ADAb status. 
− Otherwise, the subject will be classified in the missing ADAb category.  
• The table summaries and figures will also be repeated by neutralizing anti-bimekizumab 
antibodies (NAb) status (ADAb negative, NAb positive, ADAb positive / NAb negative, 
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NAb missing) (Section 9.2.2) and treatment groups. Separate tables and figures will be 
generated for concentration data up to Week 16, 24 and 52. 
For the concentration summary tables and figures by NAb status, 2 sets of summary tables 
and figures will be produced: 
− For the DBP (up to Week 16), a table and figure summarizing the BKZ concentration for 
the BKZ 160 mg Q4W group. For these tables and figures, the NAb status will be 
determined on a subject-level basis (ie, not on a visit level) according to the categories in 
Section 9.2.2. The NAb status will be determined based on data from the Baseline visit 
(pre-dose sample on study Day 1) up to Week 16 NAb sample (eg, if a subject has no 
positive samples for IL17AA or IL17FF from Baseline up to Week 16, that subject will 
be assigned a NAb negative status for all visit of the DBP). 
− For the DBP and the ATP (up to Week 24), tables and figures summarizing the BKZ 
concentration by treatment group and NAb status. For the Placebo / BKZ 160mg Q4W 
group, the NAb status will be determined based on data from sample at baseline visit 
(pre-dose sample on Week 16) up to Week 24. For the BKZ 160 mg Q4W group, the 
NAb status will be determined based on data from sample at Baseline visit (pre-dose 
sample on study Day 1) up to the NAb sample on Week 24 (eg, if a subject has no 
positive samples for IL17AA or IL17FF from Baseline up to Week 24, that subject will 
be assigned a NAb negative status for all visit of the DBP and ATP up to Week 24). The 
NAb status will be re-derived with updated data for the Week 52 analysis, followed by an 
update to the relevant tables and figures.  
PK samples collected at scheduled visits and meeting the following requirements will be 
included in summaries and corresponding figures. Samples not meeting the following 
requirements will be excluded: 
− For PK samples associated with Visit 3 (Week 2):  include samples collected ≥1 week 
and ≤ 3 weeks after the first BKZ dose and before the subsequent BKZ dose. 
− For PK samples associated with Visit 28 (Week 52) or the ET visit: include samples 
collected >14 days and < 42 days after the last/previous dose received. 
− For PK samples associated with all other visits (Week 4, 8, 12, 16, 20, 24, 36):  include 
samples collected >14 days after the preceding dose, <42 days after the preceding dose, 
and no later than 1 hour after the current visit dose including unscheduled assessments as 
described in Section 3.1.  
− For the SFU visit, all concentrations obtained at the SFU visit will be included in the 
summary tables but will not be included in the figures. 
When multiple samples meeting the criteria above are associated with the same visit (either 
because multiple samples were collected or due to remapping or unscheduled visits), only results 
from 1 valid sample will be included in summaries and figures using the following rules. All 
others will be excluded and only listed:  
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− For PK samples with different dates, the sample that is closest to the target visit date will 
be included.  For samples with different dates that are the same distance to the target visit 
date, the sample collected prior to IMP dosing will be included. 
− For PK samples with the same date, the first sample as provided in the raw data will be 
included. 
• The BKZ concentrations will also be listed for all subjects in the SS (for BKZ treated 
subjects). All concentrations will be listed as received, prior to substitution of any BLQ 
values. The listing will include flags for concentrations that were excluded from the summary 
statistics where the reason for exclusion will be one or more of the following: 
− Sample collected out of window relative to current dose: for PK samples associated with 
Week 2:  includes samples collected <1 week or > 3 weeks after the first BKZ dose. For 
PK samples associated with visits other than week 2, 52, ET, or SFU: includes samples 
>1 hour after the current visit dose. 
− Sample collected out of window relative to previous dose: For PK samples associated 
with all visits except the Week 2 or SFU visit: includes samples collected <14 days or 
>42 days after the previous dose received 
− More than 1 sample obtained at the same visit: Includes all samples excluded due to 
multiple valid samples associated with a visit. 
All plasma concentration data will be reported in ug/mL in the tables, figures, and listings. 
If more than 10% of the PK concentration results have been excluded from the table summaries, 
the PK excluded results will be listed in a separate listing. 
9.2 
Immunological (Immunogenicity) analyses 
9.2.1 
Anti-bimekizumab antibody 
The ADAb will be assessed using a 3-tiered assay approach: Screening, confirmatory, and 
titration assays. Samples confirmed as positive within the confirmatory assay will be further 
evaluated for the presence of NAb specific to binding of BKZ to IL-17AA, IL-17FF or both. 
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 ADAb samples are analyzed on the SS but are not analyzed when subjects are on a treatment 
other than BKZ. For subjects who switch from placebo to BKZ, samples are analyzed at Baseline 
visit (prior to any dosing) and at the visit (Week 16) when the switch to BKZ occurs. The sample 
at the visit when the switch occurs will act as the Baseline for that treatment group. 
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).  
The ADAb status for each visit will be derived as following: 
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− Sample values 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 of 
availability of a titer value) 
− Missing if it does not go into one of the above categories. 
PI samples will be titrated, and the ADAb titer (reciprocal dilution factor including MRD) 
reported. The PI samples will also be subject to a neutralizing assay to evaluate whether the anti-
BKZ antibody neutralizes the target binding of BKZ (IL17A or IL17F or both) in-vitro. 
The following rule will be implemented for by-visit ADAb summaries where applicable: 
− From Baseline through Week 24 visit, if the ADAb sample is collected within ±14 days 
relative to the visit date at which the drug was administered (or ±14 days from a 
scheduled visit at which dosing was not performed), the ADAb result for that sample will 
be associated with the scheduled visit and summarized accordingly. 
− From Week 24 visit, if the ADAb sample is collected within ±21 days relative to the visit 
date at which the drug was administered (or ±21 days from a scheduled visit at which 
dosing was not performed), the ADAb result for that sample will be associated with the 
scheduled visit and summarized accordingly. 
− In all cases, this will include unscheduled assessments as described in Section 3.1 (if a 
dose was administered at an unscheduled visit). Samples collected outside this window 
will be excluded from the ADAb summaries and will be listed only. 
The rules above will apply to by-visit summaries only. This rule will not apply for the Week 52, 
ET or SFU visits. Thus, all ADAb data obtained at these visits will be included in the by-visit 
summaries. 
All other summaries of ADAb status will use all available data (scheduled and unscheduled).  
In addition, the anti-BKZ antibody status will be further classified according to the ADAb 
categories outlined below: 
− Category 1: Pre ADAb negative – treatment-emergent ADAb negative: Includes 
subjects who are negative at Baseline and antibody negative at all sampling points post 
treatment (including SFU), one post-baseline missing/inconclusive sample is allowed for 
subjects with pre-ADAb negative sample. This group also includes subjects who have 
missing/inconclusive pre-treatment sample (eg either missing/inconclusive or insufficient 
volume) at baseline with all post-baseline samples as ADAb negative.  
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive: Includes 
subjects who are negative at Baseline and antibody positive at any sampling point post 
treatment (including SFU). This group also includes subjects who have a missing pre-
treatment sample (either missing or insufficient volume) at Baseline with one or more 
ADAb positive post-treatment samples. 
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− Category 3: Pre ADAb positive – treatment reduced ADAb: Includes subjects who are 
positive at Baseline, and antibody negative at all sampling points post treatment 
(including SFU). 
− Category 4: Pre ADAb positive – treatment unaffected ADAb positive: Includes 
subjects who are positive at Baseline and are positive at any sampling point post 
treatment (including SFU) with titer values of the same magnitude as Baseline (ie less 
than a predefined fold difference from the Baseline value). For the purposes of this study, 
this is set at an increase of less than the validated Minimum Significant Ratio (MSR) of 
2.07-fold from baseline.  
− Category 5: Pre ADAb positive – treatment boosted ADAb positive: Includes subjects 
who are positive at Baseline and are positive at any sampling point post treatment 
(including SFU) with increased titer values compared to Baseline (greater than or equal 
to a predefined fold difference increase from Baseline value which is defined within the 
validation of the assay). For the purposes of this study, this is set at an increase greater 
than or equal to the validated Minimum Significant Ratio (MSR) of 2.07-fold from 
Baseline. 
Note: For any subject who is positive at Baseline and positive at a post-Baseline time 
point, but for whom titers are not available to determine treatment unaffected or treatment 
boosted status, the subject will be considered as treatment boosted (ie, Category 5), 
assuming no other samples are available.  
− Category 6: Inconclusive: Includes subjects who have a positive pre-treatment sample 
and some post-treatment samples are missing, while other post-treatment samples are 
ADAb negative or missing. 
− Category 7: Total treatment-emergent: Category 2 and 5 combined: Includes subjects 
who are pre ADAb negative – treatment emergent ADAb positive (Category 2) and pre 
ADAb positive – treatment boosted ADAb positive (Category 5). 
− Category 8: Total prevalence of pre-ADAb positivity: (Categories 3, 4, 5 and 6 
combined): Subjects that are tested ADAb positive at Baseline. 
− Category 9: Missing: Includes subjects who have a negative or a missing/inconclusive 
pre-treatment sample and some post-treatment samples are missing/inconclusive, while 
other post-treatment samples are ADAb negative or missing. 
For the subjects randomized to placebo group, the Baseline will be the Week 16 pre-dose 
observation. 
All the following analyses will be prepared on the SS on BKZ treated subjects by treatment 
group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W): 
• A summary table displaying the number and percentage of subjects with ADAb status - 
positive, negative, total of positive and negative , missing - at each visit (including SFU) and 
overall will be provided. For the overall summary at any visit, 2 summaries will be 
presented:  
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− Including any visit during the treatment period (as defined in Section 3.1). Thus, this 
summary will exclude data obtained at the SFU visit and will include data obtained at 
Baseline. This summary will display the overall ADAb status up to Week 16 (for the 
BKZ 160 mg Q4W group), and to Week 24 and 52 by treatment group (BKZ 160 mg 
Q4W, Placebo / BKZ 160 mg Q4W). 
− Including any visit during the study. Thus, this summary will include data obtained at 
both the SFU visit and at Baseline. Subjects who rolled over to the OLE study will not 
have a SFU visit per study protocol. For these subjects, the ‘overall ADAb status 
including SFU’ will then be considered as being identical to the ‘overall ADAb status up 
to Week 52’. 
For the overall ADAb status, a subject will be classified as: 
− Positive if the subject has at least one positive sample at any time in the treatment period 
(regardless of having missing /inconclusive data) 
− Negative if the subject has all the samples negative or only one missing/inconclusive 
sample with negative ADAb samples up to the timepoint of interest 
− Missing if the subject has missed more than one sample result for ADAb assessment (or 
have more than one inconclusive sample) and all other available ADAb samples are 
negative during the period of interest (If there are ≥95% of subjects included in the non-
missing groups, the missing group will not be displayed on the table). 
• The above summary table displaying the number and percentage of subjects in each of the 
ADAb status (positive, negative, total of positive and negative, missing) will be repeated for 
the subjects randomized in Japan for Placebo / BKZ 160 mg Q4W and BKZ 160 mg Q4W 
groups (overall summaries only). The overall summary excluding SFU will be generated for 
up to Week 16, 24 and 52. 
• A summary table displaying the number and percentage of subjects in each of the ADAb 
status (positive, negative, total of positive and negative, missing) by concomitant medications 
(use of cDMARDs at entry, use of MTX at entry, use of oral/systemic corticosteroids at 
entry) will be provided (overall summaries only, including summaries up to Week 16, 24, 52 
and SFU). 
• A table displaying the number (%) of subjects with the first occurrence of any ADAb 
positivity (ie: including Baseline visit) or ADAb treatment-emergent positivity during the 
study will be summarized by treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg 
Q4W). This summary will include the following categories: 
− Any ADAb+: ADA positive sample regardless of category during the treatment period, 
− ADAb Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− ADAb Category 5: Pre ADAb positive – treatment-boosted ADAb positive (if this 
category represents at least 10% of the subjects, otherwise results are to be merged with 
category 2). For this category, the first occurrence of a boosted result is considered.  
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The table will include the number and percentage of subjects with first occurrence of any 
ADAb+ sample, and also subjects who are either treatment-emergent ADAb positive or 
treatment-boosted ADAb positive for the first time at the specified time point in the study 
and will include the cumulative number and percentage of subjects with any ADAb+ sample 
and treatment-emergent ADAb positive results at each time point. 
• A boxplot of the ADAb titer by time of occurrence of ADAb positivity will be created for 
each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W). The ADAb titer 
results will be presented on the log-scale. The time to occurrence is defined as the time in 
weeks from Baseline until the visit of interest when a sample is ADAb positive. Subjects who 
do not have any ADAb positivity will be excluded from the plot. 
• A summary table of the number and percentage of subjects in each of the 9 ADAb categories 
will be tabulated.  
• Some figures summarizing the time to achieve any ADAb positivity and treatment emergent 
ADAb positivity on a cumulative basis will be presented by treatment group (4 lines per plot: 
i.e. 2 lines for each treatment group, one line for time to achieve any ADAb positivity and 
one line for time to achieve treatment emergent ADAb positivity). Subjects will be 
considered to have an event at the timepoint at which an ADAb+ result or treatment 
emergent ADAb positivity is first achieved. Treatment-emergent ADAb+ in this plot will be 
based on ADAb category 7 (total treatment-emergent ADAb).  
If ≥10% subjects are classified as ADAb category 5, the treatment emergent ADAb+  line 
will be further split by the following categories (thus the plot by treatment group will include 
3 lines):  
− ADAb category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− ADAb category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
• Individual plots (one plot by subject) of BKZ concentrations/ADAb titer and ACR50 
response (based on NRI) will be created. All 3 endpoints will be plotted on the Y-axis by 
visit (x-axis) for the full treatment period, including SFU when a subject has not progressed 
into the OLE. Plots should be labeled and grouped into the 9 ADAb categories and display 
vertical lines on the x-axis corresponding to the dosing incidences/visits.  
For the Week 24 analysis, the ADAb categories will be based on data up to Week 24. 
• Individual plots (1 plot by subject) of BKZ concentrations/ADAb titer and PASI90 (on 
subjects with PSO involving at least 3% of BSA at Baseline) will also be created similarly as 
described above.  
• Spaghetti plots of ADAb titer (y-axis) will be reported on the log-scale by visit (x-axis) by 
treatment group for all ADAb positive subjects. This plot will include the following ADAb 
categories: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
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The 3 plots described above will present ADAb titers using a semi-logarithmic (ADAb negative 
samples will therefore be excluded from the plots). Furthermore, all ADAb titer values<100 will 
be represented as 1 in these plots. 
• Figures will summarize efficacy response (ACR50, ACR20 and PASI90 responders based on 
NRI, for PASI90 in the subgroup of subjects with PSO involving at least 3% BSA at 
Baseline) versus ADAb titer quartiles. The x-axis will display the ADAb titer quartiles at 
Week 16 (categorized as negative, Q1, Q2, Q3 and Q4) and the y-axis will display 
percentage of ACR50 (ACR20 or PASI90) responders at Week 16. The plot will therefore 
display the percentage of ACR50 (ACR20 or PASI90) responders as a function of the 
number of subjects within each ADAb and titer categories. Subjects with negative ADAb 
results at Week 16 will be included in the ‘negative’ category on the x‑axis. This plot will 
include data only from subjects randomized to BKZ 160 mg Q4W.  
The figure will be repeated using Week 24 and 52 ACR50,  ACR20 and PASI90 responder 
rates and Week 24 and 52 ADAb titer quartiles, respectively, and will include all subjects 
receiving BKZ. The figure for Week 24 and 52 data will be split by treatment group. Thus, 2 
figures per efficacy variable and time point will be presented. 
• Two figures (side by side) summarizing time course of efficacy response (ACR50 responders 
based on NRI) for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg 
Q4W) by the following ADAb categories considered for the efficacy sub-group analysis (3 
lines per plot) will be created: 
− ADAb positive - Defined as subjects having at least 2 ADAb positive samples during the 
study (including baseline and SFU up to the timepoint of interest) regardless of other 
ADAb negative samples and/or missing or inconclusive samples 
− ADAb negative - Defined as subjects for whom either (1) all samples (including baseline 
and SFU up to the timepoint of interest) are ADAb negative and there are no missing or 
inconclusive samples, (2) only 1 sample is ADAb positive and all other samples 
(including baseline and SFU up to the timepoint of interest) are ADAb negative or 
missing/inconclusive or (3) only one sample is missing/inconclusive and the remaining 
ADAb samples are negative. 
− ADAb Missing - Defined as subjects who do not fulfil the criteria for one of the 2 groups 
listed above. 
Separate figures will be presented for data up to Week 16 (for the BKZ 160mg Q4W group) 
and side by side by treatment group for data up to Week 24 and Week 52. The data will also 
be presented in a tabular format. The analyses will be repeated for ACR20 and PASI90 (for 
PASI90, in the subgroup of subjects with PSO involving at least 3% BSA at Baseline). 
If ≥95% of subjects are included in the non-missing groups, the missing group will not be 
tabulated and thus not displayed on the figure.  
Note: for efficacy by ADAb status summary up to a particular timepoint (Week 16, 24 and 
52), only ADAb data up to the timepoint of interest will be utilized in deriving the overall 
ADAb status during that period. The percent of subjects in each of the ADAb categories 
considered for efficacy sub-group analyses will be summarized. 
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• All individual subject-level ADAb results will be listed including the Screening assay, 
confirmatory assay, ADAb status, and titers if applicable. Note, that titer results will only be 
available, if the confirmatory assay is positive. The listing will also include flags for ADAb 
measurements that were excluded from the by-visit summaries. The reason for exclusion will 
be one of the following: 
− Sample collected out of window relative to current dose (or visit), 
− More than one sample obtained at the same visit. 
• Finally, if more than 10% of the ADAb results have been excluded from the table summaries, 
the ADAb excluded results will be listed in the same listing as the one mentioned in 
Section 9.1 for excluded PK results.  
9.2.2 
Neutralizing anti-bimekizumab antibodies 
NAb will be assessed using IL-17AA- and IL-17FF-specific assay methods, respectively. NAb 
results will be positive or negative to each specific NAb assay or both. 
Any NAb results derived from samples with drug concentrations > the drug tolerance limits of 
the NAb assays (100μg/mL) will be labeled 'inconclusive'. All inconclusive results will be 
regarded as missing. 
Subjects will be assigned an overall Neutralizing anti-BKZ antibodies (NAb) classification, 
inclusive of Baseline and post-Baseline results from NAb assay: 
• NAb negative: No NAb positive samples for IL-17AA and IL-17FF at Baseline or post-
Baseline. This group will also include subjects who have only 1 missing sample and all other 
available samples during the period of interest are negative. Study participants who are NAb 
negative will be classified as follows: 
− ADAb positive / NAb negative: ADAb positive subjects who are 1) NAb negative for all 
available ADAb positive samples or 2) with only one missing NAb sample and all other 
evaluated ADAb positive samples are NAb negative. 
− ADAb negative: if the subject has all the samples as ADAb negative or only one 
missing/inconclusive sample with all other available samples as negative ADAb. Note 
that ADAb negative samples are not subject to the neutralizing assay.  
• NAb positive: One or more positive samples (IL-17AA positive, IL-17FF positive, or both) 
at Baseline or post-Baseline (regardless of missing samples). Study participants who are NAb 
positive will be further classified as follows: 
− Positive for IL-17AA only: one or more positive samples for IL-17AA at baseline or 
post-baseline. No positive samples for IL-17FF 
− Positive for IL-17FF only: one or more positive samples for IL-17 FF at baseline or post-
baseline. No positive samples for IL-17AA 
− Positive for both IL-17AA and IL-17FF: one or more positive samples for both IL-17AA 
and IL-17FF at baseline or post-baseline 
• NAb Missing:  
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− >1 relevant NAb samples are missing/inconclusive and other available NAb samples 
during the period of interest are negative, eg, missing or insufficient sample left for NAb 
testing. 
Note: For PK and efficacy analyses up to a certain timepoint (Week 16, 24 and 52) by NAb 
status, only data up to the timepoint of interest will be utilized in deriving the subject’s overall 
NAb status during that period (eg for the ACR50 by NAb up to Week 16, only NAb data from 
baseline up to Week 16 will be used to derive subject’s overall NAb status during the DBP). 
• A listing will be produced to summarize the NAb status overall in the study. The listing will 
be sorted by treatment group (Placebo/ BKZ 160mg Q4W vs. BKZ 160mg Q4W), subject 
identifier and visit and will summarize the following information for each subject assessed 
for NAb: 
− Visit 
− Study week  
− Laboratory sampling date and time 
− Time since previous dose (weeks) 
− The corresponding BKZ plasma concentration level at each visit (ug/mL) 
− Anti-BKZ anti-body titer at each visit 
− IL-17AA NAb status and corresponding IL-17AA signal/negative control result 
− IL-17FF NAb status and corresponding IL-17FF signal/negative control result 
• A summary table will provide the following overall summary statistics by treatment group 
(Placebo/ BKZ 160mg Q4W vs. BKZ 160mg Q4W) (based on the total number of 
randomized subjects): 
− The number and percentage of subjects confirmed as anti-BKZ antibody positive and 
anti-BKZ antibody negative up to Week 16, 24, 52 (excluding SFU), 52 (including SFU)  
− The number and percentage of subjects who are NAb positive, NAb negative and missing 
up to Week 16, 24, 52 (excluding SFU) and 52 (including SFU).   
The NAb summary tables will be repeated with percentages calculated on a denominator 
based on the number of ADAb positive subjects during the above periods. 
In addition, the following analyses will be performed to assess the impact of NAb status on 
efficacy variables: 
• Two figures (side by side) summarizing efficacy response (ACR50 based on NRI) versus 
time for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W) by NAb 
status (ADAb negative, NAb positive, ADAb positive / NAb negative, missing) will be 
created. If ≥95% of subjects are included in the non-missing groups, the missing group will 
not be displayed in the figure. Separate figures will be presented for data up to Week 16 (for 
the BKZ 160mg Q4Wgroup), and to Week 24 and 52 by treatment group (BKZ 160mg Q4W 
vs. Placebo / BKZ 160mg Q4W). The analyses will be repeated for ACR20 and PASI90 (for 
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PASI90, in the subgroup of subjects with PSO involving at least 3% BSA at Baseline). The 
data will be also presented in a tabular format. 
10 
SAFETY ANALYSES 
All safety summaries will be done on all subjects in the SS.  
10.1 
Extent of exposure 
The extent of exposure will be evaluated based on the duration of exposure to study drug and the 
time at risk. 
Summaries for exposure will be presented: 
• For the DBP on the SS by treatment group, 
• For the ATP on the ATS by treatment group and for all BKZ treated subjects  
• For the AMP on the AMS by treatment group and for all BKZ treated subjects. 
The following results will be presented:    
• A descriptive summary of duration of study treatment exposure in days,   
• A total study medication duration in subject-years, 
• The number of subjects exposed to the following duration of study treatment (for the DBP 
and ATP together):  
− > 0 week 
− ≥ 16 weeks 
− ≥ 24 weeks 
− ≥ 36 weeks 
− ≥ 48 weeks 
− ≥ 52 weeks 
• A descriptive summary of time at risk in days,  
• A total time at risk in subject-years. 
A by-subject listing of date of first and last dose, the duration of exposure and the time at risk 
will be performed. 
Throughout the below sections, date of last clinical contact for each subject is defined as the 
maximum of the following dates:  
• Date of last visit including SFU visit,  
• Last imputed AE start date,  
• Date of study termination/completion,  
• Last date of study drug administration. 
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• Or any other collected date. 
In calculation of exposure detailed below, 14 days refers to the time between 2 consecutive study 
treatment administrations. 
10.1.1 
Double-Blind Treatment Period 
10.1.1.1 
Study medication duration (days) 
The study medication duration will be calculated as: 
• For subjects with a date of last dose in the DBP +14 days beyond the date of first dose in the 
ATP (excluding SFU): 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
• For subjects with a date of last dose in the DBP +14 days before or on the same day as the 
date of first dose in the ATP (excluding SFU): 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 14 
• For subjects who have died during the DBP: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
• For other subjects: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 14 
• For other subjects who withdrew from study or ongoing in the study during DBP, the 
minimum between: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 14 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑡ℎ𝑒 𝑓𝑖𝑛𝑎𝑙 𝑣𝑖𝑠𝑖𝑡 (𝑒𝑥𝑐𝑙𝑢𝑑𝑖𝑛𝑔 𝑆𝐹𝑈) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
10.1.1.2 
Time at risk (days) 
The time at risk will be calculated as: 
• For subjects who completed the DBP and continue in the ATP:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
• For subjects who have died prior to the final visit of the DBP: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃 𝑃𝑒𝑟𝑖𝑜𝑑) + 1 
• For all other subjects (who discontinue on or prior to the final visit of the DBP), the 
minimum between:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑜𝑛𝑡𝑎𝑐𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 141 
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑖𝑛 𝑡ℎ𝑒 𝐷𝐵𝑃 (112 𝑑𝑎𝑦𝑠) 
Note: 140 days refer to 5 times the half-life of BKZ. 
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10.1.2 
Active Treatment-blind Period 
The exposure will be calculated for subjects in the ATS only.  
10.1.2.1 
Study medication duration (days) 
The study medication duration will be calculated as:  
• For subjects who completed the study, with a date of last dose +14 days beyond the date of 
final visit of the ATP (excluding SFU): 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑛𝑎𝑙 𝑣𝑖𝑠𝑖𝑡 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒(𝐴𝑇𝑃) + 1 
• For subjects who have died during the ATP: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) + 1 
For other subjects𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒(𝐴𝑇𝑃) + 14 
10.1.2.2 
Time at risk (days) 
The time at risk will be calculated as: 
• For subjects who completed the study (and continue into the OLE study):  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑛𝑎𝑙 𝑣𝑖𝑠𝑖𝑡 (𝐴𝑇𝑃) − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) + 1 
• For subjects who have died prior to the final visit of the ATP: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) + 1 
• For all other subjects (subjects who discontinue early from the study, subjects who complete 
study as planned but chose not to continue into the OLE study, or subjects who are ongoing 
in the SFU period at the time of the data snapshot), the minimum between:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑜𝑛𝑡𝑎𝑐𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) + 1 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) + 141 
Note: 140 days refer to 5 times the half-life of BKZ. 
10.1.3 
Double-blind and the Active Treatment-blind Periods (combined) 
10.1.3.1 
Study medication duration (days) 
The study medication duration (in days) for subjects who do not switch study treatment at Week 
16 will be calculated as:  
• For subjects who completed the study with a date of last dose +14 days beyond the date of 
final visit date (excluding SFU): 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑛𝑎𝑙 𝑣𝑖𝑠𝑖𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 1 
• For subjects who have died: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 1 
• For other subjects: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 14 
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The study medication duration (in days) for Placebo subjects who switch study treatment at 
Week 16 will be calculated as: 
For the DBP (attributed to the Placebo treatment):  
• For subjects with a date of last dose +14 days beyond the date of final visit date (excluding 
SFU): 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
• For other subjects: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 14 
For the ATP (attributed to the BKZ treatment):  
• Use the algorithm specified for the ATP.  
10.1.3.2 
Time at risk (days) 
The time at risk (days) for subjects who do not switch study treatment at Week 16 will be 
calculated as: 
• For subjects who completed the study (and continue into the OLE study):  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑛𝑎𝑙 𝑣𝑖𝑠𝑖𝑡 − 𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 1 
• For subjects who have died prior to scheduled final visit date of the ATP: 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 1 
• For all other subjects (subjects who discontinue early from the study, subjects who complete 
study as planned but chose not to continue into the OLE study, or subjects who are ongoing 
in the SFU period at the time of the data snapshot), the minimum between:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑜𝑛𝑡𝑎𝑐𝑡−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒  + 1 
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑙𝑎𝑠𝑡 𝑑𝑜𝑠𝑒 −𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 + 141 
The time at risk (days) for Placebo subjects who switch study treatment at Week 16 will be 
calculated as: 
For the DBP (attributed to the Placebo treatment):  
• For all subjects:  
𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐴𝑇𝑃) −𝑑𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝐷𝐵𝑃) + 1 
For the ATP (attributed to the BKZ treatment):  
• Use the algorithm specified for the ATP.  
10.1.4 
Exposure and time at risk in subject-years 
The sum of all durations of exposure (in subject-years) will be calculated as: 
∑
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 (𝑑𝑎𝑦𝑠)
𝑆𝑢𝑏𝑗𝑒𝑐𝑡𝑠
365.25
 
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The sum of all times at risk (in subject-years) will be calculated as: 
∑
𝑇𝑖𝑚𝑒𝑠 𝑎𝑡 𝑟𝑖𝑠𝑘 (𝑑𝑎𝑦𝑠)
𝑆𝑢𝑏𝑗𝑒𝑐𝑡𝑠
365.25
 
10.1.5 
Time at risk in subject-years by COVID-19 pandemic period 
The time at risk will be determined by COVID-19 pandemic period as defined in Section 3.11. 
10.1.5.1 
Time at Risk in the pre-COVID-19 pandemic period  
Only subjects starting study drug during the pre-COVID-19 pandemic period will have a time at 
risk calculated during that period.  
• For subjects with date of last dose of study drug on or after 11mar2020: 
 10mar2020 – date of first dose + 1 
• For subjects who have died on or before 10mar2020: 
Date of death – date of first dose + 1 (If the date of death is later than 140 days 
following the last dose of BKZ, this rule does not apply). 
• For subjects with date of last dose of study drug on or before 10mar2020 but with the earliest 
date between (date of last dose + 141) and (date of last clinical contact) on or after 
11mar2020:  
10mar2020 – date of first dose + 1  
• For subjects with date of last dose of study drug on or before 10mar2020 but with the earliest 
date between (date of last dose + 141) and (date of last clinical contact) on or before 
10mar2020, minimum between:  
date of last dose + 141 – date of first dose 
date of last clinical contact – data of first dose +1 
10.1.5.2 
Time at Risk in the COVID-19 pandemic period  
Subjects with study drug period overlapping the COVID-19 pandemic periods will have a time at 
risk calculated during that period.  
• For subjects with date of last dose of study drug on or after 11mar2020, minimum between: 
Minimum(date of last dose + 141, COVID-19 pandemic end date) – maximum of 
(11mar2020, date of first dose) 
Minimum(date of last clinical contact, COVID-19 pandemic end date) – maximum of 
(11mar2020, date of first dose) +1 
• For subjects who have died on or after 11mar2020: 
Minimum(Date of death, COVID-19 pandemic end date) – maximum of (11mar2020, 
date of first dose) + 1 ( If the date of death is later than 140 days following the last dose 
of BKZ, this rule does not apply). 
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• For subjects with date of last dose of study drug on or before 10mar2020 but with the earliest 
date between (date of last dose + 141) and (date of last clinical contact) on or after 
11mar2020, minimum between:  
Minimum(date of last dose+ 141, COVID-19 pandemic end date) – 11mar2020 
Minimum(date of last clinical contact, COVID-19 pandemic end date) – 11mar2020+1 
10.1.5.3 
Time at Risk in the post-COVID-19 pandemic period  
Subjects with study drug period continuing after the COVID-19 pandemic periods will have a 
time at risk calculated during that period:  
• For subjects with date of last dose of study drug on or after the end date of the COVID-19 
pandemic period, minimum between: 
date of last dose + 141 – maximum of (COVID-19 pandemic end date, date of first dose) 
date of last clinical contact – maximum of (COVID-19 pandemic end date, date of first 
dose) +1 
• For subjects who have died on or after COVID-19 pandemic end date: 
Date of death – maximum of (COVID-19 pandemic end date, date of first dose) + 1 ( If 
the date of death is later than 140 days following the last dose of BKZ, this rule does not 
apply). 
• For subjects with date of last dose of study drug on or before COVID-19 pandemic end date 
but with the earliest date between (date of last dose + 141) and (date of last clinical contact) 
on or after COVID-19 pandemic end date, minimum between :  
date of last dose + 141 – COVID-19 pandemic end date 
date of last clinical contact – COVID-19 pandemic end date+1 
10.2 
Adverse events 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether related or not to the IMP. 
AEs (including SAEs) are characterized as either non-treatment or treatment-emergent according 
to the following criteria: 
• Non treatment-emergent are the events with onset date and time prior to the very first 
administration of study medication (BKZ or placebo) or after a 140-day period after the final 
drug administration. 
• Treatment-emergent AEs (TEAE) are those with onset date at or after the very first 
administration of study medication. The events that emerge within 140 days after the final 
drug administration, will also be considered as treatment-emergent (eg, in the case of 
premature discontinuation or during the SFU Period). 
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If an AE occurs on the same day as the treatment switch (Week 16, to BKZ for subjects 
randomized to Placebo) then the AE will be allocated to the Double-Blind Treatment. An 
exception from this general rule is made for the following types of AEs that will be allocated to 
the BKZ:  
• Events that fulfill the anaphylaxis criteria for acute events (refer to Appendix 1) 
• Events that fulfill the hypersensitivity reaction criteria (refer to Appendix 1) 
• Events with a high-level term (HLT) of “Administration site reactions NEC” 
• Events with an HLT of “Injection site reactions” 
The incidence of TEAEs will be summarized descriptively by treatment group, MedDRA 
primary system organ class (SOC), HLT, and preferred term (PT).  
AEs will be presented as “number of subjects (percentage of subjects) [number of events]”. In 
this style of output, “[number of events]” will include all cases of an AE including repeat 
occurrences in individual subjects, while “number of subjects” will count each subject only once. 
Adverse event summaries by SOC, HLT and PT will be ordered alphabetically for SOC and HLT 
within SOC and in terms of decreasing frequency for PT within HLT in the BKZ treatment group 
and then similarly by decreasing frequency in the placebo group. 
AE summaries by PT will be ordered in terms of decreasing frequency for PT within the BKZ 
treatment group, and in the event of ties, PT will be sorted alphabetically.  
TEAEs will be classified by period (DBP, ATP or AMP) according to their date of emergence. 
Summary tables of TEAEs will be provided on:  
• The DBP by treatment on the SS,  
• The ATP by treatment and for all BKZ-treated subjects in the ATS,  
• The AMP for all BKZ-treated subjects and the ADA group in the AMS. 
10.2.1 
Standard AE summaries 
Tables for incidence of the following categories of TEAES will be provided: 
• TEAEs (overview), 
• TEAEs by SOC, HLT, PT, 
• TEAEs by decreasing frequency of PT,  
• TEAEs above the reporting threshold of 5% by PT, by SOC and PT 
• TEAEs by maximum intensity,   
• TEAEs by relationship to IMP,  
• Related TEAEs by SOC, HLT, PT, 
• Related TEAEs above the reporting threshold of 5% by PT, by SOC and PT 
• TEAEs leading to study discontinuation, by SOC, HLT, PT, 
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• TEAEs leading to study drug discontinuation, by SOC, HLT, PT, 
• Treatment-emergent SAEs (TESAEs) by SOC, HLT, PT, 
• TESAEs by relationship by SOC, HLT, PT,  
• TEAEs leading to Death by SOC, HLT, PT - Deaths will also be tabulated and listed,  
• Non-serious TEAEs above the reporting threshold of 5% of subjects by relationship by PT. 
Some selected tables of incidence will include the exposure adjusted incidence rate (EAIR) with 
associated 95% CI and the exposure adjusted event rate (EAER) (Section 10.2.3). The categories 
of TEAES concerned are listed below:   
• TEAEs by SOC, HLT, PT,  
• TEAEs leading to study discontinuation by SOC, HLT, PT, 
• TEAEs leading to study drug discontinuation, 
• TEAEs by timing of onset relative to ADAb status by SOC, HLT, PT (on subjects treated 
with BKZ). This will include columns for the following: 
− TEAEs starting before the first ADAb positive result (includes ADAb categories 2 and 5) 
where TEAEs have occurred before the following events: a) the first positive ADAb 
result for subjects in category 2 and b) the first post-baseline boosted ADAb titer result 
for subjects with titer results and the first post-Baseline positive ADAb result for subjects 
with positive ADAb at Baseline with no other samples with titer available for subjects in 
category 5. 
− TEAEs starting on the same date or after the first ADAb positive result (includes ADAb 
Categories 2, 3, 4, 5 and 6) where TEAEs have occurred on or after the following events: 
a) the first positive ADAb results for subjects in categories 2, 3, 4 and 6, and b) the first 
post-baseline boosted ADAb titer result for subjects with titer results and the first post-
Baseline positive ADAb result for subjects with positive ADAb at Baseline with no other 
samples with titer available for subjects in category 5. 
− TEAEs for subjects who are ADAb negative at all timepoints (includes ADAb Category 
1). 
• TEAEs by NAb status (ADAb negative, NAb positive, ADAb positive / NAb, negative) on 
subjects treated with BKZ. TEAEs will be sorted by system organ class, high level term and 
preferred term. 
Note: for TEAE by onset relative to ADAb positivity and by NAb status, all available ADAb 
and NAb data at the time of IA cut-off, respectively, will be utilized to derive the subject-
level ADAb/NAb status categories.  
• TESAEs by SOC, HLT, PT.  
By-subject listings on all AEs and all deaths will be provided on the Enrolled Set. AEs leading to 
study discontinuation will also be listed on the SS. AE occurring at first study drug 
administration (including for subjects randomized to Placebo, at first administration of BKZ at 
Week 16) will also be listed. A glossary listing will also be created for all TEAEs.   
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10.2.2 
Exposure duration of AEs 
The duration of each AE will be calculated as: 
𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝐴𝐸 (𝑑𝑎𝑦𝑠) =  𝐸𝑛𝑑 𝑑𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸−𝑆𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸+ 1  
For the calculation of duration for AEs with missing start dates, the dates will be imputed as 
described in Section 4.2.3. 
The time since first dose of IMP for each AE will be calculated for all TEAEs as: 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒 (𝑑𝑎𝑦𝑠) =  𝑆𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑓𝑖𝑟𝑠𝑡 𝑑𝑜𝑠𝑒+ 1  
The time since the most recent dose of IMP for each AE will be calculated for all TEAEs as: 
𝑇𝑖𝑚𝑒 𝑠𝑖𝑛𝑐𝑒 𝑡ℎ𝑒 𝑚𝑜𝑠𝑡 𝑟𝑒𝑐𝑒𝑛𝑡 𝑑𝑜𝑠𝑒 (𝑑𝑎𝑦𝑠)
=  𝑆𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒 𝑜𝑓 𝐴𝐸−𝐷𝑎𝑡𝑒 𝑜𝑓 𝑚𝑜𝑠𝑡 𝑟𝑒𝑐𝑒𝑛𝑡 𝑑𝑜𝑠𝑒+ 1  
Time to first dose and time to most recent dose will not be calculated for pretreatment AEs. 
For the calculation of time to first BKZ and time to most recent BKZ dose the same formulas as 
above will be used but the date of first BKZ dose will be used instead of the date of first dose of 
IMP. The time to first dose and time to first BKZ dose differs only for those subjects who 
receive placebo at Baseline after the time they switch to BKZ. 
10.2.3 
Exposure adjusted incidence rate (EAIR) and exposed adjusted event 
rate (EAER) 
The EAIR is defined as the number of subjects (k) with a specific AE adjusted for the exposure 
and will be scaled to 100 patient-years: 
𝐸𝐴𝐼𝑅= 100 × 
𝑘
∑
(𝑇𝐸𝑥𝑝(𝑖))
𝑛
𝑖=1
 
where n is the total number of subjects and TExp(i) is the time of exposure for each subject defined 
as:  
• For subjects with the AE: years since first dose of IMP to the first occurrence for the AE of 
interest at the level of coding evaluated  
• For subjects without the AE: the time at risk in years.  
Exact Poisson 95% CIs for incidence rates are calculated using the relationship between the 
Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997): 
𝐿𝐶𝐿=
𝜒2𝑘,𝛼/2
2
2
 
𝑈𝐶𝐿=
𝜒2(𝑘+1),1− 𝛼/2
2
2
 
where k is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2. 
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The EAER will be the number of AEs (NAE)including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using: 
𝐸𝐴𝐸𝑅= 100 × 
𝑁𝐴𝐸
∑
(𝑇𝑅𝑖𝑠𝑘(𝑖))
𝑛
𝑖=1
 
where NAE is the number of AE occurrences, n is the total number of subjects and TRisk(i) is the 
time at risk in years for each subject.  
No CI will be computed for EAER. 
10.2.4 
Other safety topics of interest 
Other safety topics of interest for this study include: 
• Infections (serious, opportunistic, fungal and tuberculosis) 
• Malignancies 
• Major adverse cardiac events (MACE) 
• Neutropenia 
• Suicidal Ideation and Behavior (SIB)  
• Inflammatory bowel disease 
• Hypersensitivity (including Anaphylaxis) 
• Hepatic events and drug-induced liver injury (DILI) 
The analyses produced for the other safety topics of interest are based on the specifications 
described in the BKZ safety topic of interest document version from Apr-2021. 
The incidence of other safety topics of interest will be summarized by MedDRA SOC, HLT, and 
PT. The EAIR with associated 95% CI and the EAER will be included in the summary tables.  
Output tables will be produced for categories of other safety topics of interest as described below 
separately for the DBP in the SS, the ATP on the ATS and on the combined DBP and ATP in the 
AMS. 
10.2.4.1 
Infections (serious, opportunistic, fungal and TB)  
Serious infections will be identified based on MedDRA classification (SOC “Infections and 
infestations”) using the “Any SAE” table. A separate table does not need to be produced to 
summarize these events: 
• Fungal infections will be summarized in a stand-alone table. The table will include all 
TEAEs (serious and non-serious) which code into the High-Level Group Term (HLGT) 
“Fungal infectious disorders”. 
• Opportunistic infections (including tuberculosis) will be summarized in a stand-alone table. 
The table will include all opportunistic infection TEAEs identified using UCB-defined search 
criteria. The process for identifying opportunistic infections is outlined in a separate 
document located in Appendix 2. 
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10.2.4.2 
Malignancies  
Two tables will be produced for malignancies: 
• A table will be based on the criteria SMQ= “Malignant or unspecified tumours (SMQ)”.  
• A table will be based on the criteria SMQ=” Malignant tumours (SMQ)”.  
SMQ search should include all TEAEs which code to a PT included in the Scope=Narrow group 
within each SMQ.  
Note that the events included in the “Malignancies” table will be a subset of the events included 
in the “Malignancies (including unspecified)” table. While the “Malignant tumours (SMQ)” is 
most relevant, “Malignant or unspecified tumours (SMQ)” must be reviewed for potential 
malignancies. 
The output tables will include 2 different overall incidence rows: 
• The first overall incidence row will summarize “Any Malignancy” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table (using the appropriate 
SMQ depending on the table), regardless of the High Level Term (HLT) it codes to.  
• The second overall incidence row will summarize “Any Malignancy excluding non 
melanomic skin cancers HLT” and this row will summarize the incidence of AEs flagged for 
inclusion in the table (using the appropriate SMQ depending on the table), excluding those 
which code to an HLT of “skin neoplasms malignant and unspecified (excl melanoma)”.  
10.2.4.3 
Major adverse cardiac events (MACE) 
The classification of an event as MACE is determined by an external cardiovascular event 
adjudication committee.  
• Major adverse cardiac events will be presented in a table.  
• Extended MACE events will be presented in a separate table and listing. All events which are 
classified by the adjudication committee as any of the following event types will be 
considered an extended MACE event. 
Table 10‒1: Type of Extended MACE events 
Event Type Code 
Event Type 
1 
Non-Fatal Myocardial Infarction (MI) 
2 
Non-Fatal Stroke: hemorrhagic 
3 
Non-Fatal Stroke: ischemic 
4 
Non-Fatal Stroke: embolic 
5 
Non-Fatal Stroke: undeterminable 
6 
Hospitalization or ER for Unstable Angina with urgent revascularization 
8 
Hospitalization for Heart Failure 
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Event Type Code 
Event Type 
10 
Coronary Revascularization Procedures (eg percutaneous coronary 
intervention, coronary artery bypass grafting) 
11 
Urgent Revascularization Procedures (ie due to symptoms of brain 
ischemia or pending infarction) 
18 
Death due to Myocardial Infarction (MI) 
19 
Death due to Stroke 
20 
Sudden Cardiac Death 
21 
Other CV Death (eg heart failure, pulmonary embolism, cardiovascular 
procedure-related) 
22 
Cardiovascular: Undetermined Cause of Death (ie cause of death 
unknown) 
• A separate table and listing will present the adjudicated cardiovascular events by type. For 
each cardiovascular event type (24 in total, for the full list of adjudicated cardiovascular 
events refer to the Bimekizumab-Event-Adjudication-Committee-Analysis-Plan ), the 
individual PTs which fall within each event type will be summarized. 
• Additionally, a listing of all events identified for potential review by the cardiovascular event 
adjudication committee will be produced. This listing will indicate whether each event was 
escalated to the committee for formal review/adjudication.  
10.2.4.4 
Neutropenia 
A table will be created based on the following PTs (regardless of seriousness): 
• Autoimmune neutropenia 
• Band neutrophil count decreased 
• Cyclic neutropenia 
• Febrile neutropenia 
• Idiopathic neutropenia 
• Neutropenia 
• Neutropenic infection 
• Neutropenic sepsis 
• Neutrophil count decreased 
10.2.4.5 
Suicidal Ideation and Behavior Neuropsychiatric events  
An external neuropsychiatric adjudication committee will evaluate potential neuropsychiatric 
events and determine whether any of those events were associated with suicidal ideation and 
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behavior (SIB). If an event is adjudicated as SIB, further information will be provided. A table 
and listing for SIB events as determined by the adjudication committee will be produced. 
A separate table will present the adjudicated neuropsychiatric events by type. For each 
neuropsychiatric event type (6 total), the individual PTs which fall within each event type will be 
summarized. It will include events adjudicated as SIB and events adjudicated as non-suicidal. 
Note that the event type Suicidal ideation can be classified as either SIB or non-suicidal. 
Additionally, a listing of all events identified for potential review by the neuropsychiatric 
adjudication committee will be produced. This listing will indicate whether each event was 
escalated to the committee for formal review/adjudication. A separate listing will also be 
produced to summarize the adjudicated results of all events escalated to the full committee. 
10.2.4.6 
Inflammatory bowel disease 
An external inflammatory bowel disease (IBD) adjudication committee will evaluate potential 
IBD events and will classify each one as follows: 
• Event Type Code 1: Possible IBD – Crohn’s Disease 
• Event Type Code 2: Probable IBD – Crohn’s Disease 
• Event Type Code 3: Definite IBD – Crohn’s Disease 
• Event Type Code 4: Possible IBD – Ulcerative Colitis 
• Event Type Code 5: Probable IBD – Ulcerative Colitis 
• Event Type Code 6: Definite IBD – Ulcerative Colitis 
• Event Type Code 7: Possible IBD – Unclassified 
• Event Type Code 8: Probable IBD – Unclassified 
• Event Type Code 9: Definite IBD – Unclassified 
• Event Type Code 10: Symptoms not consistent with IBD 
• Event Type Code 11: Possible Inflammatory Bowel Disease – Microscopic Colitis 
• Event Type Code 12: Probable Inflammatory Bowel Disease – Microscopic Colitis 
• Event Type Code 13: Definite Inflammatory Bowel Disease – Microscopic Colitis 
• Event Type Code 14: Possible Inflammatory Bowel Disease – no further differentiation 
possible 
• Event Type Code 15: Probable Inflammatory Bowel Disease – no further differentiation 
possible 
• Event Type Code 16: Definite Inflammatory Bowel Disease – no further differentiation 
possible 
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• Event Type Code 99: Not enough information to adjudicate 
A table for adjudicated IBD events (event type codes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15 
and 16) as determined by the adjudication committee will be produced. It will summarize events 
determined by the adjudication committee as definite IBD (event type codes 3, 6, 9, 13, and 16), 
probable IBD (event type codes 2, 5, 8, 12, and 15) and possible IBD (event type codes 1, 4, 7, 
11, and 14). Definite and probable IBD will also be aggregated and summarized. This table will 
be stratified by subjects with or without a previous medical history of IBD. Previous medical 
history of IBD will be determined using the information recorded on the Extra-Articular 
Assessment at Screening CRF page ("Does subject have a history of IBD?”). 
A separate table will present the adjudicated gastrointestinal events by type. For each 
gastrointestinal event type (17 total), the individual PTs which fall within each event type will be 
summarized. It will include events determined by the adjudication committee as definite IBD 
probable IBD and possible IBD. It will also include events determined as Symptoms not 
consistent with IBD (event type code 10) and Not enough information to adjudicated (event type 
code 99). 
A listing of all events identified for potential review by the IBD adjudication committee will be 
produced. This listing will indicate whether each event was escalated to the committee for formal 
review/adjudication.  
A listing will present the adjudicated IBD events by type. For each IBD event type (event type 
codes 1 through 16 and 99; 17 total), the individual PTs which fall within each event type will be 
listed.  
A third listing will present the individual diagnostic criteria met for each adjudicated IBD event. 
10.2.4.7 
Hypersensitivity (including Anaphylaxis)   
A table will be prepared based on the MedDRA anaphylaxis Algorithm (see Appendix 1) for 
acute anaphylactic events (reported on the same day as when an injection was administered or 
one day after). An AE glossary table will also be produced to summarize the MedDRA coding 
for these events. The glossary table will include the following fields: reported term, PT, LLT, 
HLT, and SOC. 
A table will be prepared to summarize hypersensitivity events, identified using the SMQ 
“Hypersensitivity (SMQ)”. All TEAEs which code to a PT included in the Scope=Narrow search 
will be included in this table. In addition, a separate table will be prepared to summarize serious 
hypersensitivity events, identified using the SMQ “Hypersensitivity (SMQ)”. All serious TEAEs 
which code to a PT included in the Scope=Narrow search will be included in this table. An AE 
glossary table will also be produced to summarize the MedDRA coding for these events. The 
glossary table will include the following fields: reported term, PT, LLT, HLT, and SOC. 
Furthermore, a table will be prepared to summarize injection site reactions, identified using the 
HLTs: “Administration site reactions NEC” and “Injection site reactions”. 
10.2.4.8 
Hepatic events and DILI  
A table for hepatic events will be created based on the SMQ of “Drug related hepatic disorders - 
comprehensive search (SMQ)”. However, these 2 sub-SMQs are to be excluded: “Liver 
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neoplasms, benign (incl. cysts and polyps) (SMQ)” and “Liver neoplasms, malignant and 
unspecified (SMQ) “. For each of the above SMQs, include all TEAEs which code to a PT 
included in the Scope=Broad and/or Scope=Narrow. 
Note that all AEs meeting the above criteria are to be included. It should not be limited to events 
that the investigator determined to be related to study drug. 
Potential cases of Hy’s Law will be reported separately in a liver function test table 
(Section 10.3). 
10.2.4.9 
 Summary table and figure  
The incidence of the below safety topics of interest occurring during the Double-Blind Treatment 
Period will be reported in one summary table and displayed graphically.  
• Serious infection (Terms included in SOC “Infections and Infestations”)  
• Fungal infection 
• Opportunistic infection 
• Malignancy (Terms included in the SMQ “Malignant tumours (SMQ)”) 
• Adjudicated major adverse cardiac events (MACE) 
• Neutropenia 
• Adjudicated suicidal ideation and behavior (SIB)  
• Definite adjudicated IBD 
• Definite or probable adjudicated IBD 
• Anaphylactic reaction 
• Hypersensitivity reaction 
• Hepatic events and drug-induced liver injury 
For each of the above categories, the summary table and the graph will include the incidence, the 
EAIR by treatment group and the risk difference (BKZ minus placebo) with its 95% CI.  
The risk difference (RD) will be derived as follows: 
𝑅𝐷= Ab
Nb −Ap
Np 
The lower and upper CI bounds for RD will be calculated as follows:  
𝑅𝐷−𝑍𝛼/2 ∗𝑆𝐸 (𝑅𝐷), 𝑅𝐷+ 𝑍𝛼/2 ∗𝑆𝐸 (𝑅𝐷) 
Where: 
Ab / Ap = Number of subjects in the BKZ / Placebo group (Safety Set) affected by the event 
Nb / Np = Number of subjects in the BKZ / Placebo group (Safety Set) 
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𝑍𝛼/2 = Critical value from the standard normal distribution (1.96 for a 95% CI). 
10.2.5 
Special considerations for interim data snapshots 
As two interim analyses are planned, there will be 2 interim data snapshots before the final 
analysis: 
• One after the last subject completed Week 24 (visit 14), 
• One after the last subject completed Week 52 (visit 28).  
Some subjects will likely have pending safety outcome data at the time of the interim data 
snapshots. Despite this, safety tables for the interim data analyses will be based on all available 
data at the time of the snapshot.  
For the Week 24 analysis, AE summary tables and listings will only include AEs with an onset 
date prior to Week 24.  
For the Week 52 analysis, some AEs including the ones with onset date prior to Week 24 may 
have been updated. For this analysis, all TEAEs tables created for the Week 24 analysis will 
need to be rerun. 
Because of the long SFU Period (140 days from last dose), subjects who have completed the 
SFU visit (and do not, therefore, enroll into the OLE study) may have a longer period of 
exposure than subjects who complete the study and roll in to the OLE study. For those subjects, 
exposure ends at 20 weeks after the last dose of IMP. 
For a subject completing Week 52 and enrolled into the OLE study, exposure ends at Week 52 
(visit 28).  
This potential difference is acknowledged and is not considered to have a meaningful impact on 
the AE summaries. Furthermore, the exposure-adjusted AE summaries (which will be 
incorporated into many of the AE tables) would account for these differences with EAIRs and 
EAERs.  
After the last subject has completed the final SFU visit, the study database will be locked, and 
TFLs will be re-run including all subjects.  
10.2.6 
COVID-19 impact 
To assess the impact of the COVID-19 pandemic on safety, additional summaries and listings 
will be presented.  
For reporting purposes, AEs will be assigned to either Pre-COVID-19, COVID-19, or post-
COVID-19 pandemic period by comparing the AE start date (based on imputed date) to the 
COVID-19 pandemic period dates (AE allocated to a period if is starts during the period). 
The following categories of TEAEs will be summarized by MedDRA SOC, HLT and PT, 
including EAIR and EAER: 
• All TEAEs by time of onset relative to COVID-19 pandemic period (pre – during – post) by 
region and overall 
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• All TEAEs leading to study discontinuation and/or permanent withdrawal of study 
medication by time of onset relative to COVID-19 pandemic period (pre – during – post) by 
region and overall 
• All Serious TEAEs by time of onset relative to COVID-19 pandemic period (pre – during – 
post) by region and overall 
• All COVID-19 related TEAEs by treatment group, separately for the DBP, ATP, and the 
AMP, by region and overall - COVID-19 related TEAEs will be identified by the 2 preferred 
terms “Corona virus infection” and “coronavirus test positive” and will include confirmed or 
suspected COVID-19 infections. 
A listing of COVID-19 related AEs will be presented where these AEs are identified as 
described above. Additionally, the listing of AEs will include a column for COVID-19 
relatedness and the time of onset of each AE relative to the COVID-19 pandemic will be 
included in all AE listings. 
For the purpose of calculating EAIR and EAER by COVID-19 pandemic period, the calculation 
of exposure time at risk presented in Section 10.1.5 will be used. An individual subject may 
therefore be counted in the denominator for several COVID-19 pandemic periods dependent on 
whether the subject is still considered at risk on the COVID-19 pandemic start and stop dates. In 
this case time at risk will be calculated separately for each period.  
10.3 
Clinical laboratory evaluations 
The routine clinical laboratory evaluations specified below will be evaluated: 
Table 10‒2: Laboratory measurements 
Hematology 
Biochemistry 
Urinalysis 
Basophils 
Calcium 
pH 
Eosinophils 
Chloride 
Albumin (protein) 
Lymphocytes 
Magnesium 
Glucose 
Monocytes 
Potassium 
Blood 
Neutrophils 
Sodium 
Leukocyte esterase 
Hematocrit 
Glucose 
Nitrite 
Hemoglobin 
BUN 
Urine dipstick for pregnancy 
testing b 
MCH 
Creatinine 
Urine drug screenc 
MCHC 
hs-CRP 
 
MCV 
AST 
 
Platelet count 
ALT 
 
RBC count 
GGT 
 
WBC count 
ALP 
 
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Hematology 
Biochemistry 
Urinalysis 
 
Total bilirubin 
 
 
Triglyceridesa 
 
 
Cholesterola 
 
 
HDL cholesterola 
 
 
LDL cholesterola 
 
 
LDH 
 
 
Serum pregnancy testingb 
 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; ET=early termination; GGT=gamma-glutamyl transferase; HDL=high density lipoprotein; hs-CRP=high 
sensitivity C-reactive protein; IMP=investigational medicinal product; IMS=International Menopause Society; 
LDH=lactate dehydrogenase; LDL=low density lipoprotein; MCH=mean corpuscular hemoglobin; MCHC=mean 
corpuscular hemoglobin concentration; MCV=mean corpuscular volume; RBC=red blood cell; SFU=Safety Follow-
up; WBC=white blood cell 
a Biochemistry will include triglycerides, cholesterol, HDL cholesterol, and LDL cholesterol at Baseline, Weeks 12 
and 24, and at the ET visit. 
b Pregnancy testing will consist of serum testing at the Screening visit for all women of childbearing potential. The 
pregnancy test will be urine at all other visits.  
c Urine drug screen will be performed at Screening visit. 
Biochemistry and hematology values will be flagged based on their reference range:  
• Values that are below the lower limit of the reference range will be flagged as ‘L’ (low)  
• Values that are above the upper limit of the reference range will be flagged as ‘H’ (high) 
• All other values will be referenced as normal. 
Markedly abnormal values for blood chemistry and hematology will be defined as laboratory 
values graded 3 or 4 according to the Rheumatology Common Toxicity Criteria (RCTC). 
Definitions of the markedly abnormal values are given in Table 10‒3 and Table 10‒4 and are 
based on the RCTC units. All units in the tables below will be converted to the standard units 
based on Clinical Data Interchange Standards Consortium (CDISC) standards. 
Table 10‒3: Definitions of markedly abnormal biochemistry values 
Parameter name 
Unit 
Criteria 
Abnormal designation 
Creatinine 
mmol/L 
>3.0 x ULN or 
>3.0 x Baseline 
AH 
Glucose 
mmol/L 
<2.2 
>13.9 
AL 
AH 
Calcium 
mmol/L 
>3.1 
<1.75 
AH 
AL 
Magnesium 
mmol/L 
>1.23 
<0.4 
AH 
AL 
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Parameter name 
Unit 
Criteria 
Abnormal designation 
Potassium 
mmol/L 
>6.0 
<3.0 
AH 
AL 
Sodium 
mmol/L 
>155 
<130 
AH 
AL 
Triglyceride 
mmol/L 
>5.7 
AH 
Cholesterol 
mmol/L 
>10.34 
AH 
AH=abnormal high; AL=abnormal low; dL = deciliter; L = liter; mg = milligram; mmol = millimoles; ULN = upper 
limit of normal. 
Table 10‒4: Definitions of markedly abnormal hematology values 
Parameter name 
Unit 
Criteria 
Abnormal designation 
Hemoglobin 
g/L 
<80 
>40 above ULN or >40 
above Baseline if 
Baseline is above ULN 
AL 
AH 
Lymphocytes Absolute 
109/L 
<0.5 
>20.0 
AL 
AH 
Neutrophils Absolute 
109/L 
<1.0 
AL 
Platelets 
109/L 
<50 
AL 
WBC/ 
Leukocytes 
109/L 
<2.0 
>100 
AL 
AH 
Table 10‒5: Definitions of markedly abnormal liver enzyme elevation values 
Parameter name 
Unit 
Criteria 
Abnormal designation 
Alkaline Phosphatase 
 
>5.0 x ULN 
AH 
ALT 
U/L 
>5.0 x ULN 
AH 
AST 
U/L 
>5.0 x ULN 
AH 
Total Bilirubin 
umol/L 
>3.0 x ULN 
AH 
GGT 
U/L 
>5.0 x ULN 
AH 
ALT= alanine aminotransferase; AST = aspartate aminotransferase; GGT= gamma-glutamyltransferase 
Definitions of the markedly abnormal values for liver enzyme elevation are given in Table 10‒5.  
All laboratory summaries will be presented in standard international (SI) units and will be based 
on observed case values. In the case where laboratory values are below the LLOQ, then these 
will be set to the midpoint between 0 and the LLOQ for the purpose of summarizing the data. 
In the case where laboratory data are expressed as above a fixed value (ie,  “>xx.xx”), then the 
numeric portion of the value will be used (ie, xx.xx) to present and calculate statistics. 
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To define the minimum/maximum post-Baseline values, all post-Baseline assessments including 
those at unscheduled visits (but excluding any that occur more than 140 days after the last 
administration of study medication) will be used. 
The following additional rule will be also applied :  
Subjects who have completed PA0010 and have a PA0012 start date, only PA0010 results up to 
and including the PA0012 start date will be used to find the subjects minimum or maximum 
results. Additionally, subjects who are in PA0012 without a start date (date of first dose), only 
PA0010 results up to the Week 52 visit + 14 days will be used to find the subjects minimum or 
maximum results. 
Different summary tables for hematology, biochemistry variables (except hs-CRP which will be 
analyzed in the efficacy section) and urinalysis (pH, Albumin (protein), glucose, blood, 
leukocyte esterase and nitrite) will be provided in the SS. For shift tables, results for the DBP 
and the ATP will be presented together for the overall study period.  
As indicated in Section 3.1, for tables where data are summarized by visit only values occurring 
at scheduled visits will be included.  
For each laboratory parameter, the below results will be presented for the overall study period, 
by treatment (Placebo/BKZ 160mg Q4W, BKZ 160mg Q4W and ADA 40mg Q2W):  
• Observed values at Baseline and observed values and changes from Baseline at each 
scheduled post-Baseline visit  
• Number and percentage of subjects by CTCAE grade (version 4.03) (when applicable) based 
on minimum/maximum post Baseline value (for blood chemistry and hematology). Subjects 
who meet the decreased potassium criterion of 3.0-<LLN, which is specified as the decreased 
potassium lab criterion for both CTCAE Grade 1 and Grade 2, will be counted as Grade 2. 
• Shift in CTCAE grade from Baseline to minimum/maximum post-Baseline value (for blood 
chemistry and hematology)  
• Number and percentage of subjects meeting the below criteria at any time during the study: 
− AST: >2xULN, >3xULN, >5xULN, >10xULN, >20xULN 
− ALT: >2xULN, >3xULN, >5xULN, >10xULN, >20xULN 
− AST or ALT : >2xULN, >3xULN, >5xULN, >10xULN, >20xULN 
− Bilirubin: >1xULN, >1.5xULN 
− ALP: >2xULN 
• Number and percentage of subjects with potential Hy’s Law cases based on the 2 following 
definitions: 
− [AST ≥3xULN or ALT ≥3xULN] and Total Bilirubin ≥2xULN 
− [AST ≥3xULN or ALT ≥3xULN] and Total Bilirubin ≥2xULN in the absence of ALP 
≥2xULN  
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To meet either of the above criteria, a subject must experience the elevation in bilirubin and ALT 
or AST (and the absence of ALP elevation, if applicable) at the same visit.  
The below results will be presented on the SS (for the DBP), on the ATS (for the ATP by 
treatment and for all BKZ-treated subjects),  and on the AMS (for all the BKZ-treated subjects 
and on the ADA group). All values observed at any time while on treatment (ie, occurring at 
scheduled and unscheduled visits) will be included in the below tables. Baseline values and 
values observed more than 140 days after the last administration of study medication are not 
considered:  
• Number and percentage of subjects with treatment-emergent markedly abnormal laboratory 
data overall (for blood chemistry and hematology), All values observed at any time while on 
treatment (ie, occurring at scheduled and unscheduled visits) will be included in this table 
summarizing markedly abnormal values. For this summary, Baseline values and values 
observed more than 140 days after the last administration of study medication are not 
considered.  
• Number and percentage of subjects with markedly abnormal liver enzyme elevation tests 
(data beyond the CTCAE Grade 3 thresholds as outlined in Table 10‒5) 
All laboratory data will be listed by treatment, subject and visit including changes from Baseline 
for numeric variables, flags for measurements outside the normal ranges, the relative study day, a 
flag for whether the test was not done and a flag for whether the subject was fasting. 
The markedly abnormal laboratory data will also be listed separately.  
Listings will also include Hepatitis B and C, human immunodeficiency virus (HIV), genomic 
proteomic/metabolomics, and genetic/epigenetic tests.  
In addition, the laboratory results classified as Grade 3 or Grade 4 will be listed separately.  
Urinalysis laboratory results and hepatic events will be listed separately.   
10.4 
Vital signs, physical examination findings, and other 
observations related to safety 
10.4.1 
Vital signs and physical examination findings 
The vital signs (systolic BP (mmHg), diastolic BP (mmHg), and pulse rate (beats/min)) will be 
summarized as: 
• Absolute and change from Baseline at each scheduled visit on the SS for the full study period 
by randomized treatment 
• For systolic and diastolic blood pressure, number and percentage of subjects experiencing at 
least one markedly abnormal value as defined in Table 10‒6. 
Table 10‒6: Definitions of markedly abnormal blood pressure values 
Parameter (unit) 
Markedly abnormal low 
Markedly abnormal high 
Systolic blood pressure (mmHg) 
<90 and a decrease from 
Baseline of ≥20 
>180 and an increase from 
Baseline of ≥20 
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Parameter (unit) 
Markedly abnormal low 
Markedly abnormal high 
Diastolic blood pressure 
(mmHg) 
<50 and a decrease from 
Baseline of ≥15 
>105 and an increase from 
Baseline of ≥15 
For the Baseline visit where several BP assessments are taken, the individual observed data 
assessments as well as the mean of these assessments will be summarized and listed (pre-dose, 
30 min post-dose and 1-hour post-dose). 
Treatment-emergent markedly abnormal values will be analyzed on the SS (for the DBP, by 
treatment), on the ATS (for the ATP by treatment and for all BKZ-treated subjects), and on the 
AMS (for all BKZ-treated subjects and the ADA group). 
Vital signs measurements will also be listed by visit and timing relative to dosing including 
changes from Baseline. The listing will also include details of abnormal value based on flags as 
defined in Table 10‒6 (“L” for markedly abnormal low and “H” for markedly abnormal high).   
Similarly, physical examination findings together with the details of abnormalities (when 
applicable) will be listed by treatment group, subject and visit. 
Body weight will be only listed. 
10.4.2 
Electrocardiograms 
The following ECG variables will be assessed at Baseline (Screening visit), Week 16, Week 52 
and at the end of SFU: 
• Heart Rate (bpm) 
• PR interval (ms) 
• RR interval (ms) 
• QRS duration (ms) 
• QT interval (ms) 
• QTcF interval (ms) 
• QTcB interval (ms) 
The date and time of the ECG will be recorded in the eCRF together with the Investigator 
interpretation and details of any abnormalities. A summary of the number and percentage of 
subjects with normal, abnormal not clinically significant, and abnormal clinically significant 
ECG results will be presented for Baseline, Week 16, Week 52 timepoints and at end of SFU.  
Absolute values at Baseline, Week 16, Week 52 and end of SFU and change from Baseline at 
Week 16, Week 52 and at end of SFU of all ECG variable will also be summarized.   
QTc outliers are defined as QTcF/QTcB values following dosing that are > 450 ms or that have 
increased from Baseline > 30 ms. These outliers will be summarized in a dedicated table using 
the following categories: 
• Value >450 ms, >480 ms, >500 ms 
• Increase from Baseline >30 ms, >60 ms, >90 ms 
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• Value >450 ms and increase from Baseline >30 ms, value >500 ms and increase from 
Baseline >60 ms. 
Number and percentage of subjects who meet the ECG outlier criteria defined above at Week 16, 
Week 52 and end of treatment will be summarized. 
All ECG tables will be provided on the SS by randomized treatment. 
All 12-lead ECG data where QTcF and QTcB outliers are highlighted will also be listed. 
10.5 
Other safety variables 
10.5.1 
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) 
The eC-SSRS is an assessment tool that evaluates suicidal ideation and behavior. The eC-SSRS 
contains 9 categories with binary responses (yes/no): 
• 
 
• 
 
• 
 
• 
 
• 
 
• 
 
• 
 
• 
 
• 
 
Following composite endpoints based on the above categories are defined as: 
• Suicidal ideation: A “yes” answer at any time during treatment to any 1 of the 5 suicidal 
ideation questions (Categories 1-5). 
• Suicidal behavior: A “yes” answer at any time during treatment to any 1 of the 4 suicidal 
behavior questions (Categories 6-9). 
• Suicidal ideation or behavior: A “yes” answer at any time during treatment to any 1 of the 9 
suicidal ideation and behavior questions (Categories 1-9). 
Self-injurious behavior without suicidal intent is defined as event in the category non-suicidal 
self-injurious behavior (in category 9). 
The visit identification for each assessment of eC-SSRS will not be part of the data collected and 
the visit date in eCRF will then be used to assign a visit identification to the eC-SSRS data. 
For each subject, eC-SSRS assessment dates will be compared to eCRF visit dates.  
In the Study Data Tabulation Model:  
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• If an eC-SSRS assessment date is matching an eCRF scheduled visit date, then the eC-SSRS 
visit identification will be the one corresponding to eCRF visit date. Otherwise, the eC-SSRS 
visit identification will be considered as “unscheduled”.   
In the analysis datasets:  
• If an eC-SSRS assessment date is matching an eCRF scheduled visit date within a window of 
+/- 2 days, then the eC-SSRS visit identification will be the one corresponding to the eCRF 
visit date. Otherwise, the eC-SSRS visit identification will stay as “unscheduled”.   
The incidence of subjects with suicidal ideation, suicidal behavior, suicidal behavior or ideation, 
and self-injurious behavior without suicidal intent will be summarized by treatment and by visit 
for the SS during the DBP and the ATP. A by-subject listing of the eC-SSRS questionnaire data 
will be provided. 
10.5.2 
Assessment of tuberculosis 
The laboratory test results from the TB assessment performed by interferon gamma release assay 
(for non-Japanese subjects) and by T-Spot test (for Japanese subjects)  will be summarized by 
treatment group for Baseline (Screening) and Week 48. They will also be listed.  
The results from the ‘Evaluation of signs and symptoms of tuberculosis’ questionnaire data will 
be also listed.  
10.5.3 
Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) 
The PHQ-9 is a multipurpose instrument for Screening, diagnosing, monitoring, and measuring 
the severity of depression. The PHQ-9 score is based on 9 questions assessing the depression 
over the last 2 weeks through 9 criteria. Each criterion is scored from 0 (not at all) to 3 (nearly 
every day). The total score for the 9 questions is added up and provides the PHQ-9 score and can 
range from 0 to 27 with higher scores indicating worse state. If 1 of the 9 criteria is missing, the 
PHQ-9 score will be set to missing. 
The following depression states are defined based on the PHQ-9 score: 
• A score below 5 is considered to be none to minimal symptom of depression, 
• A score of 5 to 9 is considered to be mild symptoms of depression,  
• A score of 10 to 14 is considered to be moderate symptoms of depression,  
• A score of 15 to 19 is considered to indicate moderately severe depression,  
• A score ≥20 is considered to be severe depression.  
The change from Baseline in PHQ-9 will be analyzed as Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 
40, 44, 48, 52. 
The percentage of subjects with scores below 5, between 5 and 9, between 10 and 14, between 
15 and 19, and ≥20 in PHQ-9 will also be analyzed by visit. 
Only observed will be presented for PHQ-9. results 
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11 
REFERENCES 
Fleiss JL, Tytun A, Ury SHK. A simple approximation for calculating sample sizes for 
comparing independent proportions. Biometrics. (1980): 36:343-6. 
Moser, BK; Stevens, GR; Watts, CL. The Two-Sample T Test Versus Satterthwaite's 
Approximate F Test. Communication in Statistics- Theory and Methods 18(11):3963-3975 
Rubin, Donald B. "The calculation of posterior distributions by data augmentation: 
Comment: A noniterative sampling/importance resampling alternative to the data 
augmentation algorithm for creating a few imputations when fractions of missing information 
are modest: The SIR algorithm." Journal of the American Statistical Association 82, no. 398 
(1987): 543-546. 
Ulm K. A simple method to calculate the confidence interval of a standardized mortality 
ratio. American Journal of Epidemiology (1990);131(2):373-375.  
Hosmer, D. W., Jr., and Lemeshow, S. (2000). Applied Logistic Regression. 2nd ed. New 
York: John Wiley & Sons. 
Maruish M, Kosinki M, Bjorner J, Gandek B, Turner-Bowker D, Ware J. User’s manual for 
the SF36v2 Health Survey 
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12 
APPENDICES 
12.1 
Appendix 1: MedDRA algorithmic approach to anaphylaxis 
(MedDRA V19.0) 
The SMQ Anaphylactic reaction consists of 3 parts:   
• 
 A narrow search containing PTs that represent core anaphylactic reaction terms (Category 
A – core anaphylactic terms):  
− Anaphylactic reaction 
− Anaphylactic shock 
− Anaphylactic transfusion reaction 
− Anaphylactoid reaction 
− Anaphylactoid shock 
− Circulatory collapse 
− Dialysis membrane reaction 
− Kounis syndrome 
− Shock 
− Shock symptom 
− Type I hypersensitivity 
• A broad search that contains additional terms that are added to those included in the narrow 
search. These additional terms are signs and symptoms possibly indicative of anaphylactic 
reaction and categorized in B, C or D   
Category B (Upper Airway / Respiratory Terms) 
 
− Acute respiratory failure 
− Asthma 
− Bronchial oedema 
− Bronchospasm 
− Cardio-respiratory distress 
− Chest discomfort 
− Choking 
− Choking sensation 
− Circumoral oedema 
− Cough 
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− Cyanosis 
− Dyspnoea 
− Hyperventilation 
− Irregular breathing 
− Laryngeal dyspnoea 
− Laryngeal oedema 
− Laryngospasm 
− Laryngotracheal oedema 
− Mouth swelling 
− Nasal obstruction 
− Oedema mouth 
− Oropharyngeal spasm 
− Oropharyngeal swelling 
− Respiratory arrest 
− Respiratory distress 
− Respiratory failure 
− Reversible airways obstruction 
− Sensation of foreign body 
− Sneezing 
− Stridor 
− Swollen tongue 
− Tachypnoea 
− Throat tightness 
− Tongue oedema 
− Tracheal obstruction 
− Tracheal oedema 
− Upper airway obstruction 
− Wheezing 
 
Category C (Angioedema / Urticaria / Pruritus / Flush tems)  
  
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− Allergic oedema 
− Angioedema 
− Erythema 
− Eye oedema 
− Eye pruritus 
− Eye swelling 
− Eyelid oedema 
− Face oedema 
− Flushing 
− Generalised erythema 
− Injection site urticaria 
− Lip oedema 
− Lip swelling 
− Nodular rash 
− Ocular hyperaemia 
− Oedema 
− Periorbital oedema 
− Pruritus 
− Pruritus allergic 
− Pruritus generalised 
− Rash 
− Rash erythematous 
− Rash generalised 
− Rash pruritic 
− Skin swelling 
− Swelling 
− Swelling face 
− Urticaria 
− Urticaria papular 
−  
 
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Category D (Cardiovascular / Hypotension Terms) 
− Blood pressure decreased 
− Blood pressure diastolic decreased 
− Blood pressure systolic decreased 
− Cardiac arrest 
− Cardio-respiratory arrest 
− Cardiovascular insufficiency 
− Diastolic hypotension 
− Hypotension 
• 
 An algorithmic approach which combines a number of anaphylactic reaction symptoms in 
order to increase specificity. A case must include one of the following where both occur on 
either the same day as when an injection was administered or one day after, and for scenarios 
where two events must have been reported, both events must have occurred within one day of 
each other:   
− A narrow term or a term from Category A;   
− A term from Category B - (Upper Airway/Respiratory) AND a term from Category C - 
(Angioedema/Urticaria/Pruritus/Flush);   
− A term from Category D - (Cardiovascular/Hypotension) AND [a term from Category B - 
(Upper Airway/Respiratory) OR a term from Category C - (Angioedema/Urticaria/ 
Pruritus/Flush)]   
12.2 
Appendix 2: UCB-DEFINED SEARCH CRITERIA FOR 
IDENTIFYING OPPORTUNISTIC INFECTIONS 
Opportunistic infections are identified in two steps:  
Step 1: Refer to column B of the UCB Opportunistic infections document (Opportunistic 
infections MedDRA v 19.xlsx) which identifies the Preferred Terms (PTs) to be classified as 
opportunistic infections using either a single ‘x’ or a double ‘xx’. 
TEAEs which code to a PT flagged with a single ‘x’ need to also be serious to be considered an 
opportunistic infection. 
All TEAEs which code to a PT flagged with a double ‘xx’ are considered to be an opportunistic 
infection, regardless of seriousness.  
Step 2: Refer to column C of the spreadsheet which identifies the PTs that need to be evaluated 
on a case-by-case basis by the study physician to determine whether or not it is an opportunistic 
infection. If Column C has a single ‘x’, then the corresponding preferred term should be flagged 
for case-by-case review by the study physician. 
 
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13 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) (IF APPLICABLE) 
13.1 
AMENDMENT 1 
Rationale for the amendment 
The primary purpose of this amendment was to implement changes in response to protocol 
amendments, discussions and feedback provided at meetings between UCB and Parexel technical 
teams for procedural clarifications, COVID-19 global pandemic impact and updates in guidelines 
for BKZ AE of special monitoring conventions. The main changes are described below:  
13.1.1 
Efficacy variables (Section 2.2.1)  
Secondary efficacy variables : change of analysis population for the following endpoints:   
• “Enthesitis-free state based on the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup 
of subjects with enthesitis at Baseline” to be analyzed in the pooled population of PA0010 
and PA0011. 
• “Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup 
of subjects with dactylitis at Baseline” to be analyzed in the pooled population of PA0010 
and PA0011. 
Other efficacy variables : New variables  
• Composite endpoint composed of ACR50 and PASI100 in subjects with PSO involving at 
least 3% BSA at Baseline 
• Proportion of Psoriatic Arthritis Response Criteria (PsARC) responders 
• Psoriatic Arthritis Disease Activity Score (PASDAS) categories  
• Change from Baseline in the PASDAS 
• Proportion of subjects with a decrease of HAQ-DI from Baseline of at least 0.35 in the 
subgroup of subjects with Baseline HAQ-DI≥0.35 
• Proportion of FACIT-Fatigue subscale responders (subjects with a minimum clinically 
important difference for FACIT-Fatigue subscale score, defined as an increase of ≥4) in 
subjects with FACIT-Fatigue subscale score ≤48 at Baseline   
Other efficacy variables : change of analysis population for the following endpoints:   
• Dactylitis-free state based on the LDI in the subgroup of subjects with dactylitis at Baseline  
• Enthesitis-free state based on the LEI in the subgroup of subjects with enthesitis at Baseline 
• Enthesitis-free state based on the SPARCC index in the subgroup of subjects with enthesitis 
at Baseline 
• Change from Baseline in the LEI in the subgroup of subjects with enthesitis at Baseline  
• Change from Baseline in the SPARCC index in the subgroup of subjects with enthesitis at 
Baseline 
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• Change from Baseline in the LDI in the subgroup of subjects with dactylitis at Baseline 
Other efficacy variables : Additional detail provided as below: 
• Disease Activity Index for Psoriatic Arthritis (DAPSA) score categories 
• Change from Baseline in PsAID-12 total score, as well as the individual domain scores 
• PsAID-12 responders (decrease from Baseline in PsAID-12 total score ≥3) in subjects with 
PsAID-12 total score>3 at Baseline   
• Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-
Fatigue subscale score 
Other efficacy variable moved to the safety section: 
• Change from baseline in PHQ-9 
Other efficacy variable removed: 
• Change from Baseline in the EQ-5D-3L utility score 
Change of analysis method for the supportive analysis of primary endpoint, based on  the 
analysis of the individual components of the ACR: 
• Individual components of the ACR to be analyzed using the referenced based multiple 
imputation method.  
13.1.2 
Immunological variables (Section 2.2.4) 
New variable :  
• The neutralizing antidrug antibody (NAb) status 
13.1.3 
Safety Variables (Section 2.2.5) 
• Secondary safety variables now focused on treatment emergent events 
New other safety variable:  
• Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) 
13.1.4 
Protocol deviation (Section 3.5) 
New category of protocol deviation:  
• COVID-19 related IPD  
13.1.5 
Analysis sets (Section 3.6) 
Additional subjects to be excluded from the PPS and the PK-PPS:  
• Subject excluded from the FAS  
New analysis set:  
• COVID-19-free Set (subjects in the RS who had no COVID-19 impact up to the primary 
efficacy endpoint) 
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13.1.6 
Strategy for handling missing data for efficacy analyses (Section 
4.2.1) 
Definition of an addition type of endpoint: 
• Composite continuous endpoint 
New table of continuous endpoints :  
• New table listing for each non composite continuous endpoint, the minimum and maximum 
value and whether the endpoint should be integer. 
 Change in missing data handling approaches for efficacy endpoints :  
• MI - MCMC/ Logistic Regression method no longer used. 
Change of primary analysis method for variables in the testing hierarchy 
• Primary analysis for binary variables performed under the composite estimand approach 
(NRI) instead of MI. 
• Primary analysis for continuous endpoints to be analyzed using the referenced based multiple 
imputation method.  
Change of supportive analysis method for variables in the testing hierarchy 
• For binary variables, supportive analyses now include Modified Composite estimand 
approach (MI) (where IE are defined as study treatment discontinuation due to AE or Lack of 
efficacy) 
• For continuous variables (including ACR component at Week16), supportive analyses now 
performed under the Hypothetical estimand approach (MI). 
MI process 
• All MI now performed up to Week 24 for the interim analysis 1 and Week 52 for the interim 
analysis 2 
New statistics 
• New method added describing how to obtain the estimated proportion of responders (ie, 
estimated responder rate) and the difference in the proportion of responders between BKZ 
and along with 2-sided 95% CIs. 
Worst category imputation for categorical variables 
• Worst category imputation introduced for categorical variable as the equivalence of the NRI 
concept for binary variables. 
No order of priority in the analysis of other endpoints:  
• Other efficacy endpoints will be analyzed using the same method as for the secondary 
efficacy variables 
13.1.7 
Data reported in interim analysis 1 (Section 4.3) 
• For the efficacy analysis, only data collected up to W24 will be reported in tables. 
• For the safety analysis, all data collected up to the cut-off point fixed for this analysis will be 
reported. 
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13.1.8 
Testing hierarchy (Section 4.5)  
• H7 is now: Enthesitis-free state superior to Placebo (based on pooled PA0010 and PA0011 
W16 data) 
• H8 is now: Dactylitis-free state superior to Placebo (based on pooled PA0010 and PA0011 
W16 data)  
13.1.9 
Changes related to COVID-19 (Section 5.2) 
• Additional disposition, demographic and baseline characteristics, efficacy, and safety 
analyses to be performed by COVID-19 pandemic periods (pre COVID-19 pandemic period / 
COVID-19 pandemic period / Post COVID-19 pandemic period). 
• Now analyses on visits, endpoint collection impacted by the COVID-19 pandemic  
13.1.10 
Statistical analysis of the primary efficacy variables (Section 8.1) 
Additional details for subgroup analyses  
• NRI used instead of MI for subgroup analyses  
• Addition details provided for subgroup analyses based on Bone Erosion at Baseline, region 
and ADAb categories 
• Observed results to be provided in the context of subgroup analysis. 
13.1.11 
Statistical analysis of the secondary efficacy variables (Section 8.2) 
Two extra rules added for the LDI calculation:  
• Circumferences of 0 will be considered as missing. Circumferences ≤15 will be assumed to 
be in cm instead of mm and will be multiplied by 10 before being used in 
summaries/analyses. 
• If a digit is recorded as ‘not affected’ but has circumference and contralateral circumferences 
collected, the tenderness score will be considered as 1 if the percent of difference between 
circumference and contralateral circumference is ≥to 10%.    
• Introduction of the tenderness dactylitis count to be used for the PAS score calculation. 
IGA  
• New supportive analysis for subjects with missing IGA at some post-baseline visits when 
BSA<3% (to be considered as responders)  
• New Analysis of BSA by visit 
13.1.12 
Statistical analysis of the other efficacy variables (Section 8.3) 
ACR50 responders at Week 16 and maintaining response at post-Week 16 visits up to Week 52  
• Extension of this analysis to all post-W16 visits and not only W52 
WPAI-SHP  
• Analysis of WPAI-SHP to be performed on OC only. 
Additional analyses for other efficacy endpoints  
• Addition of some extra analyses of efficacy endpoint with statistical testing 
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13.1.13 
Extent of exposure (Section 10) 
• Now also calculated by COVID-19 pandemic period 
13.1.14 
Safety topic of interest (Section 10.2.4) 
• Hypersensitivity now includes injection site reactions in addition to anaphylaxis 
13.2 
AMENDMENT 2 
Rationale for the amendment 
The primary purpose of this amendment was to address discrepancies of the SAP amendment 1 
vs. the table shells that are going to be produced for the Week 24 analysis.  
 
Modifications and changes 
 
Global change  
Interim analysis 1 is now referenced as Week 24 analysis throughout the document. Interim 
analysis 2 is now referenced as Week 52 analysis throughout the document. 
 
Change #1 
Section 2.2.4: Immunological variables (last sentence) 
These 3 variables will be assessed at Baseline, Week 4, 6, 8, 12, 16, 20, 24, 36, 52, end of 
treatment and at SFU visit. 
Has been changed to: 
These 3 variables will be assessed at Baseline, Week 4, 8, 12, 16, 20, 24, 36, 52, end of treatment 
and at SFU visit. 
 
Change #2 
Section 3.3: Definition of Baseline value  (second paragraph from the end) 
For subjects who switch treatment from placebo to BKZ at Week 16 (Visit 10), an additional 
Baseline value (called Week 16 Baseline) will be defined for efficacy variables. This Baseline 
value will be the last value collected before and up to the date of treatment switch (planned at 
Week 16), which corresponds to the beginning of the ATP.  
Has been changed to: 
For subjects who switch treatment from placebo to BKZ at Week 16 (Visit 10), an additional 
Baseline value (called Week 16 Baseline) will be defined for efficacy variables. This Baseline 
value will be the last value collected before and up to the date of treatment switch (planned 
at Week 16), which corresponds to the beginning of the ATP. The Week 16 value will be 
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considered as the Baseline value regardless of whether the Placebo subjects switched to 
BKZ on a later visit.  
 
Change #3 
Section 3.5: Protocol deviations 
An important protocol deviation (IPD) is defined as a protocol deviation (PD) likely to have a 
meaningful impact on the study conduct, the primary efficacy outcome, the key safety or the PK 
outcomes for an individual subject. The IPDs will be identified and classified by the deviation 
types defined in the appropriate protocol-specific document. All PDs will be reviewed as part of 
the ongoing data cleaning and data evaluation process and IPD will be identified and 
documented prior to unblinding to confirm exclusion from Per Protocol Set (PPS) and the 
Pharmacokinetics Per Protocol Set (PK-PPS).  
An IPD will not always necessitate the removal of a subject from the PPS. Depending on the 
type of PD, the subject may remain in the PPS. The IPD document developed by the clinical 
study team should clearly state which PD will result in a removal from the PPS.  
Since the PPS will be used for a supportive analysis of the primary endpoint, which is assessed at 
Week 16, the exclusion from PPS is limited to the DBP, ie only subjects with IPD observed prior 
to or at Week 16 (Visit 10) will be excluded from the PPS. Subjects with IPD after Week 16 will 
not be excluded from the PPS. 
A specific category of PD as a consequence of the Coronavirus Disease 2019 (COVID-19) 
pandemic (called COVID-19 related PD) will be assessed based especially on the information 
collected on a dedicated electronic case report form (eCRF) page (and other sources).  
Has been changed to: 
An important protocol deviation (IPD) is defined as a protocol deviation (PD) likely to have a 
meaningful impact on the study conduct, the primary efficacy outcome, the key safety or the PK 
outcomes for an individual subject. The IPDs will be identified and classified by the deviation 
types defined in the appropriate protocol-specific document. All PDs will be reviewed as part of 
the ongoing data cleaning and data evaluation process and IPD will be identified and 
documented prior to unblinding to confirm exclusion from Per Protocol Set (PPS) and the 
Pharmacokinetics Per Protocol Set (PK-PPS).  
An IPD will not always necessitate the removal of a subject from the PPS. Depending on the 
type of PD, the subject may remain in the PPS. The IPD document developed by the clinical 
study team should clearly state which PD will result in a removal from the PPS.  
In addition to IPDs resulting in the exclusion from the PPS, subjects who reduce the dose  
or dosing frequency of certain medications due to intolerance, AE, side-effects or receive  
new prohibited medication for AE will be removed from the PPS. While this is not an IPD, 
as it is allowed per protocol for safety reasons, these subjects will be removed from the PPS 
as this non-PD could have an affect the primary efficacy outcome in the same way as 
flagged IPDs resulting in exclusion from the PPS. 
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Since the PPS will be used for a supportive analysis of the primary endpoint, which is assessed at 
Week 16, the exclusion from PPS is limited to the DBP, ie only subjects with IPD (or the non-
PD above) observed prior to or at Week 16 (Visit 10) will be excluded from the PPS. Subjects 
with IPD after Week 16 will not be excluded from the PPS. 
A specific category of PD as a consequence of the Coronavirus Disease 2019 (COVID-19) 
pandemic (called COVID-19 related PD) will be assessed based especially on the information 
collected on a dedicated electronic case report form (eCRF) page (and other sources).  
 
Change #4 
Section 3.6.7: Per Protocol Set 
The Per-Protocol Set (PPS) will consist of all subjects in the RS who had no IPD affecting the 
primary efficacy variable (only IPD observed prior to Week 16 are considered for exclusion from 
the PPS). The IPDs will be predefined and subjects with IPDs will be evaluated during ongoing 
data cleaning and data evaluation meetings prior to unblinding of the data (Section 3.5). 
Exclusion from the FAS will be considered as IPDs that also result in exclusion from the PPS. 
Supportive analysis of the primary efficacy variable will be performed on the PPS. 
Has been changed to: 
The Per-Protocol Set (PPS) will consist of all subjects in the RS who had no IPD or non-PD 
related to prohibited medications affecting the primary efficacy variable (only IPD/non-PD 
related to prohibited medications observed prior to Week 16 are considered for exclusion from 
the PPS). The IPDs deviations will be predefined and subjects with IPDs deviations will be 
evaluated during ongoing data cleaning and data evaluation meetings prior to unblinding of the 
data (Section 3.5). Exclusion from the FAS will be considered as an IPDs that also results in 
exclusion from the PPS. 
Supportive analysis of the primary efficacy variable will be performed on the PPS. 
 
Change #5 
Section 4.2.1: Strategy for handling missing data for efficacy analyses  
Added line to Table 4.1  
Efficacy endpoint 
Minimum  
Maximum 
Integer value 
Tender dactylitis 
count 
0 
20 
Yes 
 
Change #6  
Section 4.2.2.3: MI-MCMC / Reference-based imputation (steps of the procedure) 
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In the case of continuous endpoints, the procedure will be implemented as follows on the raw 
values:  
1. Data will be processed sequentially, one timepoint (visit) at a time, by repeatedly calling 
SAS® PROC MI to impute missing outcome data at visits t=1,…, Week 16 (Week 16 being 
the time point of interest) using data from the placebo-treated subjects only.  
a. Initialization. Set t=1 (Baseline visit).  
b. Iteration. Set t=t+1. Create a dataset combining records from BKZ and placebo subjects with 
columns for covariates (bone erosion and region) and outcomes at visits 1 to t. Outcomes for all 
BKZ randomized subjects are set to missing at visit t and set to observed or previously imputed 
values at visits 1 to t-1. Outcomes for placebo-treated subjects are set to observed at visit t or 
observed or previously imputed values at visits 1 to t-1. The outcomes should be sorted in 
chronological order in the model.  
c. Imputation. Impute missing values for visit t using previous outcomes for visits 1 to t-1, bone 
erosion at Baseline, and region. Note that only placebo data will be used to estimate the 
imputation model since no outcome is available for BKZ-treated subjects at visit t. As a 
consequence, the input dataset should include all subjects from Placebo but only subjects from 
the BKZ arm that have values at timepoint t missing.  
d. Repeat steps 2a-2d for all timepoints, (…) 
Has been changed to: 
In the case of continuous endpoints, the procedure will be implemented as follows on the raw 
values:  
1. Data will be processed sequentially, one timepoint (visit) at a time, by repeatedly calling 
SAS® PROC MI to impute missing outcome data at visits t=1 (Baseline),…, Week 16 
(Week 16 being the time point of interest) using data from the placebo-treated subjects only.  
a. Initialization. Set t=1 (Baseline visit).  
Create a dataset combining all records from BKZ and placebo subjects with columns for 
covariates (bone erosion and region) and outcome at Baseline.  
Impute missing values at Baseline using bone erosion at Baseline, and region. Note that 
both placebo and BKZ data will be used to estimate the imputation model. 
b. Iteration. Set t=t+1. Create a dataset combining records from BKZ subjects with missing 
data at visit t and all placebo subjects with columns for covariates (bone erosion and region) 
and outcomes at visits 1 to t. In this dataset, outcomes for all BKZ randomized subjects are set 
to missing at visit t and set to observed or previously imputed values at visits 1 to t-1. Outcomes 
for placebo-treated subjects are set to observed or missing at visit t or and observed or 
previously imputed values at visits 1 to t-1. The outcomes should be sorted in chronological 
order in the model.  
c. Imputation. Impute missing values for visit t using previous outcomes for visits 1 to t-1, bone 
erosion at Baseline, and region. Note that only placebo data will be used to estimate the 
imputation model since no outcome is available for BKZ-treated subjects at visit t. As a 
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consequence, the input dataset should include all subjects from Placebo but only subjects from 
the BKZ arm that have values at timepoint t missing.  
d. Repeat steps 1b-1c for all timepoints after Baseline up to Week 16, (…) 
 
Change #7 
Section 4.2.2.4: Tipping point analysis (Updated line to Table 4.3)  
ACR component 
Range  
Delta 
hs-CRP 
Observed range of the loge 
transformed values for all BKZ 
and Placebo subjects 
(at Week 16) 
5% of the observed range 
 
Change #8 
Section 4.3.1 Interim analyses and final analysis (first bullet) 
The Week 24 analysis is the first interim analysis after all randomized subjects have completed 
the DBP and the ATP up to Week 24 or have withdrawn from the IMP or the study before Week 
24. The purpose of this analysis is to perform a comprehensive evaluation of all available data 
for the 3 treatment arms to prepare a regulatory submission for a marketing authorization 
application based on this analysis.  This interim analysis will cover the analysis of all efficacy in 
tables on data collected up to Week 24 and the analysis of safety in tables on data collected up to 
the cut-off date (defined as Week 24 visit) for the last subject (all available data will be reported 
in listings). The type of efficacy and safety tables provided for the first interim analysis is 
detailed in Table 4-4.  
Has been changed to: 
The Week 24 analysis is the first interim analysis after all randomized subjects have completed 
the DBP and the ATP up to Week 24 or have withdrawn from the IMP or the study before Week 
24. The purpose of this analysis is to perform a comprehensive evaluation of all available data 
for the 3 treatment arms to prepare a regulatory submission for a marketing authorization 
application based on this analysis.  This interim analysis will cover the analysis of all efficacy in 
and non-safety by visit tables on data collected up to Week 24 and the analysis of safety in 
tables on data collected up to the cut-off date (defined as Week 24 visit) for the last subject (all 
available data will be reported in listings). The type of efficacy and safety tables provided for the 
first interim analysis is detailed in Table 4-4. 
 
Change #9 
Section 4.8 Examination of subgroups (5th bullet from the end) 
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• Concomitantly receiving MTX vs. cDMARDs at Baseline (concomitant MTX, no 
concomitant MTX and cDMARDs at Baseline, no concomitant MTX and no cDMARDs at 
Baseline)  
Has been changed to: 
• Concomitantly receiving MTX at Baseline vs. other cDMARDs at Baseline (concomitant 
MTX at Baseline, no concomitant MTX at Baseline and cDMARDs at Baseline, no 
concomitant MTX at Baseline and no cDMARDs at Baseline)  
 
Change #10 
Section 5.1 Subject Disposition (New text after paragraph 4). 
The numbers and percentages of these subjects who either complete the SFU visit or not 
will additionally be presented.  
The numbers and percentages of randomized subjects entering the Open Label Extension 
(OLE) study and those not entering the OLE study will be presented. Of the randomized 
subjects not entering the OLE study,  
 
Change #11 
Section 5.3 Protocol deviations. 
The definition of an IPD is given in Section 3.5 
A summary displaying the number and percentage of subjects with an IPD will be provided by 
treatment group separately for the DBP on the RS and on the ATP on the ATS. This will include 
a summary of subjects excluded from the PPS (DBP only) and the PK-PPS due to IPD. The 
summary will be provided overall (any IPD) and by type of deviation (inclusion criteria 
deviation, exclusion criteria deviation, withdrawal criteria deviation, prohibited concomitant 
medication, incorrect treatment or dose, treatment non-compliance, procedural non-compliance, 
COVID-19 related IPD).  
Criteria for exclusion of subjects from the PPS or PK-PPS will be defined in a separate 
document.  
A by-subject listing of IPDs will be provided for all subjects in the RS. 
A by-subject listing of COVID-19 related PDs will be provided for all subjects in the RS. 
Has been changed to: 
The definition of an IPD is given in Section 3.5 
A summary displaying the number and percentage of subjects with an IPD will be provided by 
treatment group separately for the DBP on the RS and on the ATP on the ATS. This will include 
a summary of subjects excluded from the PPS (DBP only) and the PK-PPS due to IPD. The 
summary will be provided overall (any IPD) and by type of deviation (inclusion criteria 
deviation, exclusion criteria deviation, withdrawal criteria deviation, prohibited concomitant 
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medication, incorrect treatment or dose, treatment non-compliance, procedural non-compliance, 
COVID-19 related IPD) as well as the number and percentage of subjects excluded from the 
PPS due to reason other than PD. 
Criteria for exclusion of subjects from the PPS or PK-PPS will be defined in a separate 
document.  
A by-subject listing of IPDs will be provided for all subjects in the RS. 
A by-subject listing of COVID-19 related PDs will be provided for all subjects in the RS. 
A by-subject listing of subjects excluded from the PPS for reasons other than IPD will be 
provided. 
 
Change #12 
Section 6.2.2 Other baseline characteristics (14th bullet) 
• NSAID at Baseline (Yes, No) 
• Prior cDMARDs (0,1, >=2) 
Has been changed to: 
• NSAID at Baseline (Yes, No) 
• Past cDMARDs Therapy (Yes, No) 
• Prior cDMARDs (0,1, >=2) 
 
Change #13 
Section 7 Measure of treatment compliance (last sentence) 
A summary of percent treatment compliance categorized as ≤75% and >75% will be provided by 
treatment group, as well as a by-subject listing of treatment compliance. 
Has been changed to: 
A summary of percent treatment compliance categorized as <75% and >=75% will be provided 
by treatment group, as well as a by-subject listing of treatment compliance. 
 
Change #14 
Section 8.1.2 Primary analysis of the primary efficacy variable (paragraph 8) and Section 8.2.2 
Primary analysis of secondary efficacy variables (last sentence) 
For the country specific analyses performed on subjects randomized in Japan, the region factor 
will not be considered as a covariate for the modelling.  
Has been changed to: 
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For the country specific analyses performed on subjects randomized in Japan, the region factor 
will not be considered as a covariate for the modelling.   
Considering that the number of subjects randomized in Japan is low (less than 10% of the 
Randomized Set), statistical models might not converge. If a model (Logistic Model or 
Mixed model) is not converging, all related adjusted statistics and p-value will not be 
presented : “NE” for “Not Evaluable” will be displayed instead.  
 
Change #15 
Section 8.2.1.4 MDA at Week 16 (last but one paragraph) 
The following rule will be applied for subjects with BSA <3 at Baseline: Subjects with BSA <3 
at Baseline will always meet the criteria PASI ≤1 or BSA ≤3 except in the cases where a BSA 
score ≥3 is observed.  
Has been changed to: 
The following rule will be applied for subjects with BSA <3 at Baseline: Subjects with BSA <3 
at Baseline will always meet the criteria PASI ≤1 or BSA ≤3 except in the cases where a BSA 
score >3 is observed.  
 
Change #16 
Section 8.2.1.5 Van den Hedje modified Total Sharp Score (vdHmTSS) : Change from Baseline 
at Week 16 (after the sixth bullet from the end). 
Radiographic assessments should be conducted using a standardized imaging methodology as 
defined in an imaging charter. For the analysis, the average of the scores (ES, JSN score and total 
score) from the 2 independent reviewers will be utilized.  
Has been changed to: 
Radiographic assessments should be conducted using a standardized imaging methodology as 
defined in an imaging charter. Subjects reaching Week 52 will have 2 sets of reads for 
Baseline and Week 16 as x-rays for these subjects are read more than once in different 
sessions to reduce within subject variability by each of the independent reviewers. For 
the interim analysis first set of reads (initial Baseline and Week 16 read)will be used for all 
subjects. For the analysis, the average of the scores (ES, JSN score and total score) from the 2 
independent reviewers will be utilized. They will be calculated as: 
 
Change #17 
Section 8.2.3 Supportive analyses of the secondary efficacy variables (second paragraph) 
For PASI90, the MI will be run on the PASI score on subjects involving at least 3% of BSA at 
Baseline.  
Has been changed to: 
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For PASI90, the MI will be run on the PASI score on subjects involving at least 3% of BSA at 
Baseline.  
For the MDA (and VLDA) MI analysis, subjects with BSA <3 at Baseline will always meet 
the criteria PASI ≤1 or BSA ≤3 except in the cases where a BSA score >3 is observed.  
Subjects involving at least 3% of BSA at Baseline will have their BSA values imputed using 
MI when deriving MDA (VLDA). 
 
Change #18 
Section 8.2.3 Supportive analyses of the secondary efficacy variables (last sentence) 
To assess the impact of the COVID-19 pandemic, the analysis of secondary efficacy endpoints 
included in the hierarchy with be repeated on the COVID-19-Free Set using the primary analysis 
method. 
Has been changed to: 
To assess the impact of the COVID-19 pandemic, the analysis of secondary efficacy endpoints 
included in the hierarchy with be repeated on the COVID-19-Free Set (On subjects from the 
Radiographic Set included in the COVID-19-Free-Set for the analysis of VdHmTSS) using 
the primary analysis method. 
 
Change #19 
Section 8.3.1.6 : Psoriatic Arthritis Disease Activity Score (PASDAS) categories and change 
from Baseline in PASDAS  
PASDAS= ((0.18 × √Physician global VAS) + (0.159 × √Patient global VAS ) 
− (0.253 × √SF36 PCS ) + (0.101 × LN(SJC + 1)) + (0.048 × LN(TJC + 1)) 
+ (0.23 × LN(LEI + 1)) + (0.377 × LN (Tender dactylitis count + 1)) 
+ (0.102 x LN(hs − CRP + 1) + 2)) 
Note: LN=natural logarithm. 
If any of the PASDAS component is missing, PASDAS will be set to missing.  
(…) 
The following categories are used to define the level of disease activity:  
• Remission: PASDAS <1.9 
• Low disease activity: PASDAS 1.9 to <3.2 
• Moderate disease activity: PASDAS 3.2 to <5.4 
• High disease activity: PASDAS ≥5.4. 
The PASDAS categories and the change from Baseline in PASDAS score will be analyzed at 
Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 52. 
Has been changed to: 
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PASDAS=((0.18 × √Physician global VAS) + (0.159 × √Patient global VAS ) 
− (0.253 × √SF36 PCS )  
+ (0.101 × LN(SJC + 1))  
+ (0.048 × LN(TJC + 1)) 
+ (0.23 × LN(LEI + 1))  
+ (0.377 × LN (Tender dactylitis count + 1)) 
+ (0.102 x LN(hs−CRP + 1) ) 
+ 2)*1.5 
Note: LN=natural logarithm. 
If Tender Dactylitis count is missing because LDI=0 at Baseline, Tender Dactylitis count 
will be replaced by 0 in the formula. 
If for any other reason a any of the PASDAS component is missing, PASDAS will be set to 
missing.  
(…) 
The following categories are used to define the level of disease activity:  
• Remission: PASDAS ≤1.9 
• Low disease activity: PASDAS >1.9 to <3.2 
• Moderate disease activity: PASDAS 3.2 to <5.4 
 • High disease activity: PASDAS ≥5.4.  
The PASDAS categories and the change from Baseline in PASDAS score will be analyzed at 
Baseline, Week 4, Week 16, 24, 36, 52. 
 
Change #20 
Section 8.3.2.2 : Other endpoints (excluding time to ACR20/50/70 response) 
(….) 
For binary endpoints using:  
• The number and proportion of responders using the NRI approach.  
• The mean proportion of responders in the multiple imputed datasets and the 95% CI 
(modified composite estimand). For ACR50 response at post-Week 16 visits for subjects 
responding at Week 16, the same imputed data as generated in the context of the analysis of 
the primary efficacy endpoint will be used.  
− For enthesitis and dactylitis free-state based on the pooled data of PA0010 and PA0011 
subjects (for subjects in the BKZ 160mg Q4W and the Placebo group), the MI will be 
performed on the pooled dataset (using data from Baseline, Week 4, 8, 12 and 16) the 
same way as described in 4.2.2.2, but with the following covariates in that order for each 
SAS® PROC MI: region (North America, Western Europe and Eastern Europe in that 
order) and study-id ( “1” for PA0011 and “0” for PA0010). 
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− For enthesitis based on LEI, the MI will be run on all subjects and results reported for 
subjects with LEI>0 at Baseline ; for other binary variables derived from continuous 
value(s), the MI will be run on the subset of subjects (if applicable) for which the variable 
will be reported (ie: for LDI, on subjects with LDI>0 at Baseline)      
• The observed number and proportion of responders on subjects with observed data.  
Has been changed to: 
For binary endpoints using:  
• The number and proportion of responders using the NRI approach.  
• The mean proportion of responders in the multiple imputed datasets and the 95% CI 
(modified composite estimand). For ACR50 response at post-Week 16 visits for subjects 
responding at Week 16, the same imputed data as generated in the context of the analysis of 
the primary efficacy endpoint will be used.  
− For enthesitis and dactylitis free-state based on the pooled data of PA0010 and PA0011 
subjects (for subjects in the BKZ 160mg Q4W and the Placebo group), the MI will be 
performed on the pooled dataset (using data from Baseline, Week 4, 8, 12 and 16) the 
same way as described in 4.2.2.2, but with the following covariates in that order for each 
SAS® PROC MI: region (North America, Western Europe and Eastern Europe in that 
order) and study-id ( “1” for PA0011 and “0” for PA0010). 
− For enthesitis based on LEI, the MI will be run on all subjects and results reported for 
subjects with LEI>0 at Baseline ; for other binary variables derived from continuous 
value(s), the MI will be run on the subset of subjects (if applicable) for which the variable 
will be reported (ie: for LDI, on subjects with LDI>0 at Baseline)  
− For ACR50 based on Week 16 Baseline, the MI will be run on Week 16 and post-
week 16 values, on the ATBS for the Placebo group. Week 16 value will be 
considered as the Baseline value regardless of whether the Placebo subjects switched 
to BKZ on a later visit. 
− For PASI90 based on Week 16 Baseline, the MI will be run on W16 and post-week 
16 values, on the ATBS for the Placebo group on subjects with PSO involving at 
least 3% of BSA at Week 16. Week 16 value will be considered as the Baseline value 
regardless of whether the Placebo subjects switched to BKZ on a later visit.        
• The observed number and proportion of responders on subjects with observed data.  
 
Change #21 
Section 8.3.2.2 Other endpoints (excluding time to ACR20/50/70 response) (paragraph about 
analysis of categorical endpoints) 
For categorical endpoints (ie, EQ-5D-3L dimensions score, DAPSA state) using:  
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• The number and percentage by endpoint category using the NRI approach (as performed for 
the primary analysis of the primary endpoint with the exception that the NRI is replaced by 
the worst category imputation) 
• The mean percentage by endpoint category in the multiple imputed datasets (modified 
composite estimand). Regardless of imputed values, the value of the categorical endpoint 
after IE are by default set to the worst category (ie:  High Disease Activity for DAPSA state)   
Has been changed to: 
For categorical endpoints (ie, EQ-5D-3L dimensions score, DAPSA state, PASDAS categories) 
using:  
• The number and percentage by endpoint category using the NRI approach (as performed for 
the primary analysis of the primary endpoint with the exception that the NRI is replaced by 
the worst category imputation) 
• The mean percentage and corresponding 95% CI by endpoint category in the multiple 
imputed datasets (modified composite estimand). Regardless of imputed values, the value of 
the categorical endpoint after IE are by default set to the worst category (ie:  High Disease 
Activity for DAPSA state)   
 
Change #22 
Section 8.3.2.3 : Additional statistical analysis for other efficacy endpoints (3rd and 4th bullet 
from the end) 
• ACR50/PASI90 composite (Week16, 20, 52) 
• ACR50/PASI100 composite (Week16, 20, 52) 
Has been changed to: 
• ACR50/PASI90 composite (Week16, 20 24, 52) 
• ACR50/PASI100 composite (Week16, 20 24, 52) 
 
Change #23 
Section 9.1 : Pharmacokinetics (paragraph 3) 
No imputation will be used for missing samples. However, if plasma concentration 
measurements are below the limit of quantification (BLQ), then for the calculation of the derived 
statistics, the result will be set to ½ of LLOQ (ie, 1/2*0.250 = 0.125 ug/mL). Descriptive 
statistics including number of values, geometric mean, its 95% CI, geometric coefficient of 
variation, mean, SD, median, minimum, and maximum. Geometric mean and its 95% CI, 
geometric CV, mean and SD will be calculated if at least ⅔ of the values of interest is above the 
LLOQ ; otherwise, only number of values, median, minimum, and maximum will be presented. 
Has been changed to: 
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No imputation will be used for missing samples. However, if plasma concentration 
measurements are below the limit of quantification (BLQ), then for the calculation of the derived 
statistics, the result will be set to ½ of LLOQ (ie, 1/2*0.250 = 0.125 ug/mL). Descriptive 
statistics including number of values, geometric mean, its 95% CI, geometric coefficient of 
variation, mean, SD, median, minimum, and maximum. Geometric mean and its 95% CI, 
geometric CV, mean and SD will be calculated if at least ⅔ of the values of interest is above the 
LLOQ and number of values>=3; otherwise, only number of values, median, minimum, and 
maximum will be presented. 
 
Change #24 
Section 9.1 : Pharmacokinetics (Third bullet) 
• The table summary and figures will be primarily repeated by anti-BKZ antibody status 
(positive, negative, missing) by treatment group (3 lines per graph, one graph per treatment 
group). The missing group will not be displayed if ≥95% of subjects are categorized in the 
non-missing groups.  
The ADAb status (positive, negative, or missing) will be considered in a cumulative manner 
at each time point:  
− a subject will be counted as positive from the first visit at which the subject achieved a 
positive ADAb sample result to the end of the treatment period (regardless of any 
missing/inconclusive or negative ADAb sample result).  
− If a subject has only negative ADAb samples or only one missing/inconclusive sample 
with negative ADAb samples up to that timepoint, the subject will be classified as 
negative.  
Has been changed to: 
• The table summary and figures will be primarily repeated by anti-BKZ antibody status 
(positive, negative, missing) by treatment group (3 lines per graph, one graph per treatment 
group). The missing group will not be displayed if ≥95% of subjects are categorized in the 
non-missing groups.  
The ADAb status (positive, negative, or missing) will be considered in a cumulative manner 
at each time point:  
− a subject will be counted as positive from the first visit at which the subject achieved a 
positive ADAb sample result to the end of the treatment period (regardless of any 
missing/inconclusive or negative ADAb sample result).  
− If a subject has only negative ADAb samples or only one missing/inconclusive sample 
with negative ADAb samples up to that timepoint, the subject will be classified as 
negative. An exception remains for the Baseline Visit where only one sample would 
be available. If the sample is missing/inconclusive, then the sample will be classified 
as being negative for the cumulative ADAb status. 
 
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Change #25 
Section 9.1 : Pharmacokinetics (last sentence) 
All plasma concentration data will be reported in ug/mL in the tables, figures, and listings. 
Has been changed to: 
All plasma concentration data will be reported in ug/mL in the tables, figures, and listings. 
If more than 10% of the PK concentration results have been excluded from the table 
summaries, the PK excluded results will be listed in a separate listing. 
 
Change #26 
Section 9.2.1 : Anti-bimekizumab antibody  (line before the description of the ADAb categories) 
Summaries of cumulative ADAb status and time to treatment-emergent positivity will use all 
available data.  
Has been changed to: 
All other Summaries of cumulative ADAb status and time to treatment-emergent positivity 
will use all available data (scheduled and unscheduled).  
 
Change #27 
Section 9.2.1 : Anti-bimekizumab antibody (ADAb categories) 
− Category 1: Pre ADAb negative – treatment-emergent ADAb negative: Includes 
subjects who are negative at Baseline and antibody negative at all sampling points post 
treatment (including SFU). This group also includes subjects who have 
missing/inconclusive pre-treatment sample (eg either missing/inconclusive or insufficient 
volume) at baseline with all post-baseline samples as ADAb negative.  
(…) 
− Category 6: Inconclusive: Includes subjects who have a positive pre-treatment sample 
and some post-treatment samples are missing, while other post-treatment samples are 
ADAb negative or missing. 
(…) 
− Category 9: Missing: Includes subjects who have a negative or a missing/inconclusive 
pre-treatment sample and some post-treatment samples are missing/inconclusive, while 
other post-treatment samples are ADAb negative. 
 
Has been changed to: 
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− Category 1: Pre ADAb negative – treatment-emergent ADAb negative: Includes 
subjects who are negative at Baseline and antibody negative at all sampling points post 
treatment (including SFU), one post-baseline missing/inconclusive sample is allowed 
for subjects with pre-ADAb negative sample. This group also includes subjects who 
have missing/inconclusive pre-treatment sample (eg either missing/inconclusive or 
insufficient volume) at baseline with all post-baseline samples as ADAb negative.  
(…) 
− Category 6: Inconclusive: Includes subjects who have a positive pre-treatment sample 
and some post-treatment samples are missing, while other post-treatment samples are 
ADAb negative or missing. 
(…) 
− Category 9: Missing: Includes subjects who have a negative or a missing/inconclusive 
pre-treatment sample and some post-treatment samples are missing/inconclusive, while 
other post-treatment samples are ADAb negative or missing. 
 
Change #28 
Section 9.2.1 : Anti-bimekizumab antibody (First Bullet) 
• A summary table displaying the number and percentage of subjects with ADAb status 
(positive, negative or missing) at each visit and overall will be provided. For the overall 
summary at any visit, 2 summaries will be presented:  
− Including any visit during the treatment period (as defined in Section 3.1). Thus, this 
summary will exclude data obtained at the SFU visit and will include data obtained at 
Baseline. This summary will display the overall ADAb status up to Week 16, 24 and 52 
by treatment group (BKZ 160 mg Q4W, Placebo / BKZ 160 mg Q4W). 
− Including any visit during the study. Thus, this summary will include data obtained at 
both the SFU visit and at Baseline. 
Has been changed to: 
• A summary table displaying the number and percentage of subjects with ADAb status 
(positive, negative or missing) at each visit and overall will be provided. For the overall 
summary at any visit, 2 summaries will be presented:  
− Including any visit during the treatment period (as defined in Section 3.1). Thus, this 
summary will exclude data obtained at the SFU visit and will include data obtained at 
Baseline. This summary will display the overall ADAb status up to Week 16, 24 and 52 
by treatment group (BKZ 160 mg Q4W, Placebo / BKZ 160 mg Q4W). 
− Including any visit during the study. Thus, this summary will include data obtained at 
both the SFU visit and at Baseline. Subjects who rolled over to the OLE study will not 
have a SFU visit per study protocol. For these subjects, the ‘overall ADAb status 
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including SFU’ will then be considered as being identical to the ‘overall ADAb 
status up to Week 52’. 
 
Change #29 
Section 9.2.1 : Anti-bimekizumab antibody (Second, third and fourth bullet) 
• The above summary table displaying the number and percentage of subjects in each of the 
ADAb status (positive, negative, missing) will be repeated by region for Placebo / BKZ 160 
mg Q4W and BKZ 160 mg Q4W groups. The overall summary excluding SFU will be 
generated for up to Week 16, 24 and 52. 
• A summary table displaying the number and percentage of subjects in each of the ADAb 
status (positive, negative, missing) by concomitant medications (use of cDMARDs at entry, 
use of MTX at entry, use of oral/systemic corticosteroids at entry) will be provided (overall 
summaries only, including summaries up to Week 16, 24 and 52). 
• A table displaying the number (%) of subjects with the first occurrence of ADAb treatment-
emergent positivity during the study (ie: including Baseline visit) will be summarized. This 
summary will include the following categories: 
− Any ADAb+: ADA positive sample regardless of category during the treatment period, 
− ADAb Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− ADAb Category 5: Pre ADAb positive – treatment-boosted ADAb positive (if this 
category represents at least 10% of the subjects, otherwise results are to be merged with 
category 2). For this category, the first occurrence of a boosted result is considered.  
Has been changed to: 
• The above summary table displaying the number and percentage of subjects in each of the 
ADAb status (positive, negative, total of positive and negative, missing) will be repeated by 
region for Placebo / BKZ 160 mg Q4W and BKZ 160 mg Q4W groups. The overall 
summary excluding SFU will be generated for up to Week 16, 24 and 52. 
• A summary table displaying the number and percentage of subjects in each of the ADAb 
status (positive, negative, total of positive and negative, missing) by concomitant 
medications (use of cDMARDs at entry, use of MTX at entry, use of oral/systemic 
corticosteroids at entry) will be provided (overall summaries only, including summaries up to 
Week 16, 24 and 52 and SFU). 
• A table displaying the number (%) of subjects with the first occurrence of any ADAb 
positivity (ie including Baseline visit) or ADAb treatment-emergent positivity during the 
study (ie: including Baseline visit) will be summarized. This summary will include the 
following categories: 
− Any ADAb+: ADA positive sample regardless of category during the treatment period, 
− ADAb Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
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− ADAb Category 5: Pre ADAb positive – treatment-boosted ADAb positive (if this 
category represents at least 10% of the subjects, otherwise results are to be merged with 
category 2). For this category, the first occurrence of a boosted result is considered.  
 
Change #30 
Section 9.2.1 : Anti-bimekizumab antibody (eighth, nineth, and tenth bullet) 
• Individual plots (one plot by subject) of BKZ concentrations/ADAb titer and ACR50 
response (based on NRI) will be created. All 3 endpoints will be plotted on the Y-axis by 
visit (x-axis) for the full treatment period, including SFU where a patient has not progressed 
into the OLE. Plots should be labeled and grouped into the 9 ADAb categories and display 
vertical lines on the x-axis corresponding to the dosing incidences/visits. 
For the Week 24 interim analysis, the ADAb categories will be based on data up to Week 24. 
• Individual plots (1 plot by subject) of BKZ concentrations/ADAb titer and PASI90 will also 
be created similarly as described above.  
• Spaghetti plots of ADAb titer (y-axis) will be reported on the log-scale by visit (x-axis) by 
treatment group for all ADAb positive subjects. This plot will include the following ADAb 
categories: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
Plots will be presented using a semi-logarithmic scale for the ADAb titers (ADAb negative 
samples will therefore be excluded from the plot). 
Has been changed to: 
• Individual plots (one plot by subject) of BKZ concentrations/ADAb titer and ACR50 
response (based on NRI) will be created. All 3 endpoints will be plotted on the Y-axis by 
visit (x-axis) for the full treatment period, including SFU where a patient has not progressed 
into the OLE. Plots should be labeled and grouped into the 9 ADAb categories and display 
vertical lines on the x-axis corresponding to the dosing incidences/visits. 
For the Week 24 interim analysis, the ADAb categories will be based on data up to Week 24. 
• Individual plots (1 plot by subject) of BKZ concentrations/ADAb titer and PASI90 will also 
be created similarly as described above.  
• Spaghetti plots of ADAb titer (y-axis) will be reported on the log-scale by visit (x-axis) by 
treatment group for all ADAb positive subjects. This plot will include the following ADAb 
categories: 
− Category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− Category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
The 3 plots described above  will be presented ADAb titers using a semi-logarithmic scale 
for the ADAb titers (ADAb negative samples will therefore be excluded from the plots). 
Furthermore, all ADAb titer values<100 will be represented as 1 in these plots. 
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Change #31 
Section 9.2.1 : Anti-bimekizumab antibody (last paragraph) 
• Finally, all individual subject-level ADAb results will be listed including the Screening 
assay, confirmatory assay, ADAb status, and titers if applicable. Note, that titer results will 
only be available, if the confirmatory assay is positive. The listing will also include flags for 
ADAb measurements that were excluded from the by-visit summaries. The reason for 
exclusion will be one of the following: 
− Sample collected out of window relative to current dose (or visit), 
− More than one sample obtained at the same visit. 
Has been changed to: 
• Finally, All individual subject-level ADAb results will be listed including the Screening 
assay, confirmatory assay, ADAb status, and titers if applicable. Note, that titer results will 
only be available, if the confirmatory assay is positive. The listing will also include flags for 
ADAb measurements that were excluded from the by-visit summaries. The reason for 
exclusion will be one of the following: 
− Sample collected out of window relative to current dose (or visit), 
− More than one sample obtained at the same visit. 
• Finally, if more than 10% of the ADAb results have been excluded from the table 
summaries, the ADAb excluded results will be listed in the same listing as the one 
mentioned in Section 9.1 for excluded PK results.  
 
Change #32 
Section 9.2.2 : Neutralizing anti-bimekizumab antibodies (first bullet) 
• NAb negative: No NAb positive samples for IL-17AA and IL-17FF at Baseline or post-
Baseline. This group will also include subjects who have only 1 missing sample and all other 
available samples during the period of interest are negative. Study participants who are NAb 
negative will be classified as follows: 
− ADAb positive / NAb negative: ADAb positive subjects who are 1) NAb negative for all 
available ADAb positive samples or 2) with only one missing NAb sample and all other 
evaluated ADAb positive samples are NAb negative. 
− ADAb negative: if the subject has all the samples as ADAb negative or only one 
missing/inconclusive sample with all other available samples as negative ADAb. 
Has been changed to: 
• NAb negative: No NAb positive samples for IL-17AA and IL-17FF at Baseline or post-
Baseline. This group will also include subjects who have only 1 missing sample and all other 
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available samples during the period of interest are negative. Study participants who are NAb 
negative will be classified as follows: 
− ADAb positive / NAb negative: ADAb positive subjects who are 1) NAb negative for all 
available ADAb positive samples or 2) with only one missing NAb sample and all other 
evaluated ADAb positive samples are NAb negative. 
− ADAb negative: if the subject has all the samples as ADAb negative or only one 
missing/inconclusive sample with all other available samples as negative ADAb. Note 
that ADAb negative samples are not subject to the neutralizing assay. 
 
Change #33 
Section 9.2.2 : Neutralizing anti-bimekizumab antibodies (Third bullet) 
• NAb Missing:  
− >1 relevant NAb samples are missing and other available NAb samples during the period 
of interest are negative, eg, missing or insufficient sample left for NAb testing. 
Has been changed to: 
• NAb Missing:  
− >1 relevant NAb samples are missing/inconclusive and other available NAb samples 
during the period of interest are negative, eg, missing or insufficient sample left for NAb 
testing. 
 
Change #34 
Section 10.2.1 : Standard AE summaries (18th bullet) 
• TEAEs by timing of onset relative to ADAb status by SOC, HLT, PT (on subjects treated 
with BKZ). This will include columns for the following: 
− TEAEs starting before the first ADAb positive result (includes ADAb categories 2, 4 and 
5) where TEAEs have occurred before the following events: a) the first positive ADAb 
result for subjects in category 2 and b) the first post-baseline boosted ADAb titer result 
for subjects with titer results and the first post-Baseline positive ADAb result for subjects 
with positive ADAb at Baseline with no other samples with titer available for subjects in 
category 5. 
Has been changed to: 
• TEAEs by timing of onset relative to ADAb status by SOC, HLT, PT (on subjects treated 
with BKZ). This will include columns for the following: 
− TEAEs starting before the first ADAb positive result (includes ADAb categories 2, 4 and 
5) where TEAEs have occurred before the following events: a) the first positive ADAb 
result for subjects in category 2 and b) the first post-baseline boosted ADAb titer result 
for subjects with titer results and the first post-Baseline positive ADAb result for subjects 
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with positive ADAb at Baseline with no other samples with titer available for subjects in 
category 5. 
 
Change #35 
Section 10.3 : Clinical laboratory evaluations (2nd bullet after Table 10-5) 
• Number and percentage of subjects by CTCAE grade (version 4.03) (when applicable) based 
on minimum/maximum post Baseline value (for blood chemistry and hematology).  
Has been changed to: 
• Number and percentage of subjects by CTCAE grade (version 4.03) (when applicable) based 
on minimum/maximum post Baseline value (for blood chemistry and hematology).  Subjects 
who meet the decreased potassium criterion of 3.0-<LLN, which is specified as the 
decreased potassium lab criterion for both CTCAE Grade 1 and Grade 2, will be 
counted as Grade 2. 
 
13.3 
AMENDMENT 3 
Rationale for the amendment 
The primary purpose of this amendment was to address discrepancies of the SAP amendment 2 
vs. the table shells that are going to be produced for the Week 52 analysis.  
Modifications and changes 
Change #1 
Section 4.2.2.2: MI – MCMC/Monotone Regression 
(…) For the MCMC method (when imputing intermittent missing values), randomization 
strata will be re-coded as indicator variables and will always be specified in the following 
order: North America region (1 for North America, 0 otherwise), Western Europe region (1 
for Western Europe,0 otherwise), Eastern Europe region (1 for Eastern Europe, 0 otherwise), 
For each imputation model, Bone erosion at Baseline (0 if bone erosion at Baseline =0 ; 1 if 
bone erosion at Baseline≥1). 
For each imputation model, the randomization strata (region and bone erosion at Baseline) 
may be dropped to facilitate convergence if required as described below: If the MI fails to 
converge when adjusting on the stratification variables specified above, or if the percentage 
of randomized subjects is < 10% in either of the Asia or Western Europe regions, then the 
Western Europe and Asia region will be combined  and the binary variables for region that 
will be left in the MI will then be for North America and Eastern Europe regions. 
Has been changed to: 
(…) For the MCMC method (when imputing intermittent missing values), randomization 
strata will be re-coded as indicator variables and will always be specified in the following 
order: North America region (1 for North America, 0 otherwise), Western Europe region (1 
for Western Europe,0 otherwise), Eastern Europe region (1 for Eastern Europe, 0 otherwise), 
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For each imputation model, Bone erosion at Baseline (0 if bone erosion at Baseline =0 ; 1 if 
bone erosion at Baseline≥1). 
Bone erosions will be read for all visits both at the Week 24 analysis and the Week 52 / 
final analyses to ensure that unnecessary bias is not introduced. Given there may be 
differences at Baseline for the two sets of reads, the following rules will be applied for 
the MI process: 
• For the Week 24 analysis,  the first set of reads will be used.  
• For the Week 52 and final analyses, Week 16 specific outputs will continue to use 
the first set of reads. Outputs involving over time data up to Week 52 will use the 
second set of reads.     
For each imputation model, the randomization strata (region and bone erosion at Baseline) 
may be dropped to facilitate convergence if required as described below: If the MI fails to 
converge when adjusting on the stratification variables specified above, or if the percentage 
of randomized subjects is < 10% in either of the Asia or Western Europe regions, then the 
Western Europe and Asia region will be combined  and the binary variables for region that 
will be left in the MI will then be for North America and Eastern Europe regions. 
 
Change #2 
Section 4.2.2.2: MI – MCMC/Monotone Regression 
If a variable is dropped in order to allow convergence for one model in the study, that 
variable does not have to be dropped from other models in the study of the model converges 
without dropping the variable. That is, model convergence should be evaluated for each 
efficacy table independently. Furthermore, this means that a table based on a single timepoint 
may have different variables in the imputation model than a separate by-visit table for the 
same variable. 
Has been changed to: 
If a variable is dropped in order to allow convergence for one model in the study, that 
variable does not have to be dropped from other models in the study of the model converges 
without dropping the variable. That is, model convergence should be evaluated for each 
efficacy table independently. Furthermore, this means that a table based on a single 
timepoint may have different variables in the imputation model than a separate by-visit 
table for the same variable. 
 
Change #3 
Section 4.2.2.2: MI – MCMC/Monotone Regression 
Step 2: Standard rounding rules will be applied to the imputed values after each SAS® PROC 
MI. If an imputed value falls outside of the range for the given variable (as listed in Table 4-1) 
the value will be updated to be within the predefined range. 
Has been changed to: 
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Step 2: Standard rounding rules will be applied to the imputed values after each SAS® 
PROC MI. If an imputed value falls outside of the range for the given variable (as listed in 
Table 4-1) the value will be updated to be within the predefined range. 
 
Change #4 
Section 4.2.2.5: Treatment Policy Strategy 
Subjects for whom efficacy data cannot be obtained at the week of interest, despite attempts to 
retain them in the study, will have their data imputed using MI-MCMC / monotone regression 
(Section 4.2.2.2 ).  
Has been changed to: 
Subjects for whom efficacy data cannot be obtained at the week of interest, despite attempts to 
retain them in the study, will have their data imputed using MI-MCMC / monotone regression 
(Section 4.2.2.2) based on non missing data collected up to Week 16.  
 
Change #5 
Section 4.8 Examination of subgroups 
In the context of submission to Japanese health authorities, a subset of tables and figures will be 
provided in the subgroup of subjects randomized in Japan.  
Has been changed to: 
In the context of submission to Japanese health authorities, a subset of tables and figures will be 
provided in the subgroup of subjects randomized in Japan (when MI is used, data for subjects 
randomized in Japan will be extracted from the MI datasets generated for the full 
population). 
 
Change #6 
Section 5.2 Impact of COVID-19 
A listing of visits affected by COVID-19 will be presented based on the Enrolled Set including 
the visit, dates of visit, relationship to COVID-19, impact category and a narrative (short 
description) of the event. These data will be summarized for non-randomized subjects and by 
treatment group and overall, for enrolled subjects. 
Has been changed to: 
A listing of visits affected by COVID-19 will be presented based on the Enrolled Set including 
the visit, dates of visit, relationship to COVID-19, impact category and a narrative (short 
description) of the event. These data will be summarized for non-randomized subjects and by 
treatment group and overall, for enrolled randomized subjects. 
 
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Change #7 
Section 8.1.2 Primary analysis of the primary efficacy variable 
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including 
randomization stratification variables (bone erosion at Baseline and region) will be assessed 
using Pearson and Deviance and The Hosmer-Lemeshow Goodness-of-Fit Tests (Hosmer and 
Lemeshow, 2000).  
Has been changed to: 
A logistic regression model will be used to assess the treatment effect on ACR50 response at 
Week 16. The model will include a fixed effect for treatment. The suitability of including 
randomization stratification variables (bone erosion at Baseline and region) will be assessed 
using Pearson and Deviance and The Hosmer-Lemeshow Goodness-of-Fit Tests (Hosmer and 
Lemeshow, 2000).  
In the context of the Week 24 analysis, actual bone erosion at Baseline as a covariate will be 
based on data from the first set of reads. For Week 52 analysis, data from the second set of 
reads will be used. 
 
Change #8 
Section 8.1.3 Subgroup analyses of the primary efficacy variable 
Subgroup analyses will be performed on the primary efficacy variable on the RS.  
The variables for subgroup analyses are defined in Section 4.8. 
Has been changed to: 
Subgroup analyses will be performed on the primary efficacy variable on the RS.  
The variables for subgroup analyses are defined in Section 4.8. 
In the context of the Week 24 analysis, actual bone erosion at Baseline used as a covariate 
and/or a subgroup will be based on data from the first set of reads. For the Week 52/final 
analyses, data from the second set of reads will be used. 
 
Change #9 
Section 8.2.1.5 Van der Heijde modified Total Sharp Score (vdHmTSS): Change from Baseline 
at Week 16. 
(…) 
Radiographic assessments should be conducted using a standardized imaging methodology as 
defined in an imaging charter. Subjects reaching Week 52 will have 2 sets of reads for Baseline 
and Week 16 as x-rays for these subjects are read more than once in different sessions to reduce 
within subject variability by each of the independent reviewers. For the Week 24 analysis first 
set of reads (initial Baseline and Week 16 read) will be used for all subjects. 
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(…) 
In the primary analysis of these 2 endpoints, missing data at Week 16 will be imputed based on 
value at Screening (as there is no value collected in between) using MI-MCMC / Monotone 
regression. Since VdHmTSS is only collected at Baseline prior to Week 16, only the second MI 
step to address monotone missing pattern and generating 100 imputations will be processed 
(Section 4.2.2.2).  
Has been changed to: 
(…)  
Radiographic assessments should be conducted using a standardized imaging methodology as 
defined in an imaging charter. Subjects reaching Week 52 will have 2 sets of reads for Baseline 
and Week 16 as x-rays for these subjects are read more than once in different sessions to reduce 
within subject variability by each of the independent reviewers.  
Bone erosions will be read for all visits both at the Week 24 analysis and the Week 52/final 
analyses to ensure that unnecessary bias is not introduced. Given there may be differences 
for the two sets of reads, the following rules will be applied for the derivation: 
• For the Week 24 analysis involving data up to Week 16 only (Week 24 analysis),  the 
first set of reads (initial Baseline and Week 16 read) will be used for all subjects.  
• For the analysis involving data up to Week 52, the second set of reads will be used 
for all subjects.  
(…) 
For the Week 24 interim analysis only, in the primary analysis of these 2 endpoints, missing 
data at Week 16 will be imputed based on value at Screening (as there is no value collected in 
between) using MI-MCMC / Monotone regression. Since VdHmTSS is only collected at 
Baseline prior to Week 16, only the second MI step to address monotone missing pattern and 
generating 100 imputations will be processed (Section 4.2.2.2).  
 
Change #10 
Section 8.3.2.2 Other endpoints (excluding time to ACR20/50/70 response) 
For binary endpoint: (…) 
− For enthesitis based on LEI, the MI will be run on all subjects and results reported for 
subjects with LEI>0 at Baseline ; for other binary variables derived from continuous 
value(s), the MI will be run on the subset of subjects (if applicable) for which the variable 
will be reported (ie: for LDI, on subjects with LDI>0 at Baseline)  
(…) 
For continuous endpoints, on absolute values and changes from Baseline (or ratio from Baseline 
for hs-CRP) using: (…) 
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− For LEI, the MI will be run on all subjects and results reported for subjects with LEI>0 at 
Baseline ; for other continuous variables derived from continuous value(s), the MI will be 
run on the subset of subjects (if applicable) for which the variable will be reported (ie: for 
LDI, on subjects with LDI>0 at Baseline) 
Has been changed to: 
For binary endpoint: (…) 
− For enthesitis based on LEI, the MI will be run on all subjects and results reported for 
subjects with LEI>0 at Baseline ; for other binary variables derived from continuous 
value(s), the MI will be run on the subset of subjects (if applicable) for which the variable 
will be reported (ie: for LDI and Tender dactylitis count in the context of PASDAS 
calculation, on subjects with LDI>0 at Baseline)  
(…) 
For continuous endpoints, on absolute values and changes from Baseline (or ratio from Baseline 
for hs-CRP) using: (…) 
− For LEI, the MI will be run on all subjects and results reported for subjects with LEI>0 at 
Baseline ; for other continuous variables derived from continuous value(s), the MI will be 
run on the subset of subjects (if applicable) for which the variable will be reported (ie: for 
LDI, on subjects with LDI>0 at Baseline) 
− For Tender dactylitis count in the context of PASDAS calculation, if the MI does not 
converge, a conservative approach will be used by first imputing a value of 1 for all 
joints with missing tenderness score.       
 
Change #11 
Section 8.3.2.3 Additional statistical analysis for other efficacy endpoints 
• MDA (Week 2, 4, 8, 12, 16) 
• PtAAP (Week 2, 4, 8, 12, 16) 
• PsAQoL (Week 2, 4,8,12,16) 
• PsAID-12 (Week 2, 4, 8, 12, 16) 
• FACIT-Fatigue subscale (Week 2, 4, 8, 12, 16) 
Has been changed to: 
• MDA (Week 2, 4, 8, 12, 16) 
• PtAAP (Week 2, 4, 8, 12, 16) 
• PsAQoL (Week 2, 4, 8, 12,16) 
• PsAID-12 (Week 2, 4, 8, 12,16) 
• FACIT-Fatigue subscale (Week 2, 4, 8, 12,16) 
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Change #12 
Section 9.1 Pharmacokinetics 
(…) 
• BKZ concentrations will be summarized by treatment group, globally and by region (Japan 
vs. rest of the world excluding Japan). 
No imputation will be used for missing samples. However, if plasma concentration 
measurements are below the limit of quantification (BLQ), then for the calculation of the derived 
statistics, the result will be set to ½ of LLOQ (ie, 1/2*0.250 = 0.125 ug/mL). Descriptive 
statistics including number of values, geometric mean, its 95% CI, geometric coefficient of 
variation, mean, SD, median, minimum, and maximum. Geometric mean and its 95% CI, 
geometric CV, mean and SD will be calculated if at least ⅔ of the values of interest is above the 
LLOQ and number of values ≥3 ; otherwise, only number of values, median, minimum, and 
maximum will be presented. 
• In addition, geometric mean of BKZ plasma concentration (with 95% CI) time curves will be 
plotted on linear and semi-logarithmic scales:  
− by treatment group (2 lines per graph, one for each treatment), 
− by treatment group and region (Japan vs. rest of the world excluding Japan) (for each 
treatment: 2 lines per graph, one for each region).  
• The table summary and figures will be primarily repeated by anti-BKZ antibody status 
(positive, negative, missing) by treatment group (3 lines per graph, one graph per treatment 
group). The missing group will not be displayed if ≥95% of subjects are categorized in the 
non-missing groups.  
(…) 
PK samples collected at scheduled visits (except the SFU visit) and meeting the following 
requirements will be included in summaries and corresponding figures. Samples not meeting the 
following requirements will be excluded: 
(…) 
• The BKZ concentrations will also be listed for all subjects in the SS. All concentrations will 
be listed as received, prior to substitution of any BLQ values. The listing will include flags 
for concentrations that were excluded from the summary statistics where the reason for 
exclusion will be one or more of the following: 
(…) 
Has been changed to: 
Section 9.1 Pharmacokinetics 
(…) 
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• BKZ concentrations will be summarized by treatment group, globally and on subjects 
randomized in Japan by region (Japan vs. rest of the world excluding Japan). 
No imputation will be used for missing samples. However, if plasma concentration 
measurements are below the limit of quantification (BLQ), then for the calculation of the derived 
statistics, the result will be set to ½ of LLOQ (ie, 1/2*0.250 = 0.125 µg/mL). Descriptive 
statistics including number of values, geometric mean, its 95% CI, geometric coefficient of 
variation, mean, SD, median, minimum, and maximum. Geometric mean and its 95% CI, 
geometric CV, mean and SD will be calculated if at least ⅔ of the values of interest is above the 
LLOQ and number of values ≥3 at the respective timepoint; otherwise, only number of values, 
median, minimum, and maximum will be presented. 
• In addition, geometric mean of BKZ plasma concentration (with 95% CI) time curves will be 
plotted on linear and semi-logarithmic scales:  
− by treatment group (2 lines per graph, one line for each treatment), 
− by treatment group and region (Japan vs. rest of the world excluding Japan) (for 
each treatment: 2 lines per graph, one for each region).  
• The table summary and figures will be primarily repeated by anti-BKZ antibody status 
(positive, negative, missing) by treatment group (3 lines per graph, one line for each anti-
BKZ antibody status, one graph per treatment group). The missing group will not be 
displayed if ≥95% of subjects are categorized in the non-missing groups.  
(…) 
PK samples collected at scheduled visits (except the SFU visit) and meeting the following 
requirements will be included in summaries and corresponding figures. Samples not meeting the 
following requirements will be excluded: 
(…) 
• The BKZ concentrations will also be listed for all subjects in the SS (for BKZ treated 
subjects). All concentrations will be listed as received, prior to substitution of any BLQ 
values. The listing will include flags for concentrations that were excluded from the summary 
statistics where the reason for exclusion will be one or more of the following: 
(…) 
 
Change #13 
Section 9.2.1 Anti-bimekizumab antibody 
• A summary table displaying the number and percentage of subjects with ADAb status 
(positive, negative or missing) at each visit and overall will be provided. For the overall 
summary at any visit, 2 summaries will be presented:  
− Including any visit during the treatment period (as defined in Section 3.1). Thus, this 
summary will exclude data obtained at the SFU visit and will include data obtained at 
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Baseline. This summary will display the overall ADAb status up to Week 16, 24 and 52 
by treatment group (BKZ 160 mg Q4W, Placebo / BKZ 160 mg Q4W). 
(…) 
• The above summary table displaying the number and percentage of subjects in each of the 
ADAb status (positive, negative, total of positive and negative, missing) will be repeated by 
region for Placebo / BKZ 160 mg Q4W and BKZ 160 mg Q4W groups. The overall 
summary excluding SFU will be generated for up to Week 16, 24 and 52. 
(…) 
• A table displaying the number (%) of subjects with the first occurrence of any ADAb 
positivity (ie: including Baseline visit) or ADAb treatment-emergent positivity during the 
study will be summarized.  
(…) 
• A boxplot of the ADAb titer by time of occurrence of ADAb positivity will be created for 
each dose group. The ADAb titer results will be presented on the log-scale. The time to 
occurrence is defined as the time in weeks from Baseline until the visit of interest when a 
sample is ADAb positive. Subjects who do not have any ADAb positivity will be excluded 
from the plot. 
(…) 
• Some figures summarizing the time to achieve any ADAb positivity and treatment emergent 
ADAb positivity on a cumulative basis will be presented by treatment group (2 lines per plot, 
one plot per treatment group  ). Subjects will be considered to have an event at the timepoint 
at which an ADAb+ result or treatment emergent ADAb positivity is first achieved. 
Treatment-emergent ADAb+ in this plot will be based on ADAb category 7 (total treatment-
emergent ADAb).  
If ≥10% subjects are classified as ADAb category 5, the lines will be further split by the 
following categories (thus the plot by treatment group will include 3 lines):  
− ADAb category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− ADAb category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
• Individual plots (one plot by subject) of BKZ concentrations/ADAb titer and ACR50 
response (based on NRI) will be created. All 3 endpoints will be plotted on the Y-axis by 
visit (x-axis) for the full treatment period, including SFU where a patient has not progressed 
into the OLE. Plots should be labeled and grouped into the 9 ADAb categories and display 
vertical lines on the x-axis corresponding to the dosing incidences/visits. 
For the Week 24 analysis, the ADAb categories will be based on data up to Week 24. 
• Individual plots (1 plot by subject) of BKZ concentrations/ADAb titer and PASI90 will also 
be created similarly as described above. 
(…)  
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• Figures will summarize efficacy response (ACR50, ACR20 and PASI90 responders based on 
NRI) versus ADAb titer quartiles. The x-axis will display the ADAb titer quartiles at Week 
16 (categorized as negative, Q1, Q2, Q3 and Q4) and the y-axis will display percentage of 
ACR50 (ACR20 or PASI90) responders at Week 16. The plot will therefore display the 
percentage of ACR50 (ACR20 or PASI90) responders as a function of the number of 
subjects within each ADAb and titer categories. Subjects with negative ADAb results at 
Week 16 will be included in the ‘negative’ category on the x‑axis. This plot will include data 
only from subjects randomized to BKZ 160 mg Q4W.  
The figure will be repeated using Week 24 and 52 data (ie Week 24 and 52 ACR50 (and 
ACR20, PASI90) responder rates and Week 24 and 52 ADAb titer quartiles, respectively) 
and will include all subjects receiving BKZ. The figure for Week 24 and 52 data will be split 
by treatment group. Thus, 2 figures per efficacy variable and time point will be presented. 
• Two figures (side by side) summarizing time course of efficacy response (ACR50 responders 
based on NRI) for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg 
Q4W) by the following ADAb groups (3 lines per plot) will be created: 
− ADAb positive - Defined as subjects having at least 2 ADAb positive samples during the 
study (including baseline and SFU) regardless of other ADAb negative samples and/or 
missing or inconclusive samples 
− ADAb negative - Defined as subjects for whom either (1) all samples (including baseline 
and SFU) are ADAb negative and there are no missing or inconclusive samples, (2) only 
1 sample is ADAb positive and all other samples (including baseline and SFU) are ADAb 
negative or missing/inconclusive or (3) only one sample is missing/inconclusive and the 
remaining ADAb samples are negative. 
− Missing - Defined as subjects who do not fulfil the criteria for one of the 2 groups listed 
above. 
If ≥95% of subjects are included in the non-missing groups, the missing group will not be 
displayed on the figure.  
Separate figures will be presented for data up to Week 16 (for the BKZ 160mg Q4W group) 
and side by side by treatment group for data up to Week 24 and Week 52. The data will also 
be presented in a tabular format. The analyses will be repeated for ACR20 and PASI90. 
Has been changed to: 
• A summary table displaying the number and percentage of subjects with ADAb status -( 
positive, negative, total of positive and negative or, missing) - at each visit (including 
SFU) and overall will be provided. For the overall summary at any visit, 2 summaries will be 
presented:  
− Including any visit during the treatment period (as defined in Section 3.1.1). Thus, this 
summary will exclude data obtained at the SFU visit and will include data obtained at 
Baseline. This summary will display the overall ADAb status up to Week 16 (for the 
BKZ 160 mg Q4W group), and to Week 24 and 52 by treatment group (BKZ 160 mg 
Q4W, Placebo / BKZ 160 mg Q4W). 
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(…) 
• The above summary table displaying the number and percentage of subjects in each of the 
ADAb status (positive, negative, total of positive and negative, missing) will be repeated by 
region for the subjects randomized in Japan for Placebo / BKZ 160 mg Q4W and BKZ 
160 mg Q4W groups (overall summaries only). The overall summary excluding SFU will 
be generated for up to Week 16, 24 and 52. 
(…) 
• A table displaying the number (%) of subjects with the first occurrence of any ADAb 
positivity (ie: including Baseline visit) or ADAb treatment-emergent positivity during the 
study will be summarized by treatment group (Placebo / BKZ 160mg Q4W and BKZ 
160mg Q4W).  
(…) 
• A boxplot of the ADAb titer by time of occurrence of ADAb positivity will be created for 
each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W) dose group. 
The ADAb titer results will be presented on the log-scale. The time to occurrence is defined 
as the time in weeks from Baseline until the visit of interest when a sample is ADAb positive. 
Subjects who do not have any ADAb positivity will be excluded from the plot. 
(…) 
• Some figures summarizing the time to achieve any ADAb positivity and treatment emergent 
ADAb positivity on a cumulative basis will be presented by treatment group (2 4 lines per 
plot, one plot per treatment group. e.g 2 lines for each treatment group, one line for 
time to achieve any ADAb positivity and one line for time to achieve treatment 
emergent ADAb positivity). Subjects will be considered to have an event at the timepoint at 
which an ADAb+ result or treatment emergent ADAb positivity is first achieved. Treatment-
emergent ADAb+ in this plot will be based on ADAb category 7 (total treatment-emergent 
ADAb).  
If ≥10% subjects are classified as ADAb category 5, the treatment-emergent ADAb+ the 
lines will be further split by the following categories (thus the plot by treatment group will 
include 3 lines):  
− ADAb category 2: Pre ADAb negative – treatment-emergent ADAb positive, 
− ADAb category 5: Pre ADAb positive – treatment-boosted ADAb positive. 
• Individual plots (one plot by subject) of BKZ concentrations/ADAb titer and ACR50 
response (based on NRI) will be created. All 3 endpoints will be plotted on the Y-axis by 
visit (x-axis) for the full treatment period, including SFU where when a patient subject has 
not progressed into the OLE. Plots should be labeled and grouped into the 9 ADAb 
categories and display vertical lines on the x-axis corresponding to the dosing 
incidences/visits.  
For the Week 24 analysis, the ADAb categories will be based on data up to Week 24. 
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• Individual plots (1 plot by subject) of BKZ concentrations/ADAb titer and PASI90 (on 
subjects with PSO involving at least 3% of BSA at Baseline) will also be created similarly 
as described above. 
(…)  
• Figures will summarize efficacy response (ACR50, ACR20 and PASI90 responders based on 
NRI, for PASI90 in the subgroup of subjects with PSO involving at least 3% BSA at 
Baseline) versus ADAb titer quartiles. The x-axis will display the ADAb titer quartiles at 
Week 16 (categorized as negative, Q1, Q2, Q3 and Q4) and the y-axis will display 
percentage of ACR50 (ACR20 or PASI90) responders at Week 16. The plot will therefore 
display the percentage of ACR50 (ACR20 or PASI90) responders as a function of the 
number of subjects within each ADAb and titer categories. Subjects with negative ADAb 
results at Week 16 will be included in the ‘negative’ category on the x‑axis. This plot will 
include data only from subjects randomized to BKZ 160 mg Q4W.  
The figure will be repeated using Week 24 and 52 data ie Week 24 and 52 ACR50, (and 
ACR20 and PASI90 responder rates and Week 24 and 52 ADAb titer quartiles, respectively,  
and will include all subjects receiving BKZ. The figure for Week 24 and 52 data will be split 
by treatment group. Thus, 2 figures per efficacy variable and time point will be presented. 
• Two figures (side by side) summarizing time course of efficacy response (ACR50 responders 
based on NRI) for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg 
Q4W) by the following ADAb groups categories considered for the efficacy sub-group 
analysis (3 lines per plot) will be created: 
− ADAb positive - Defined as subjects having at least 2 ADAb positive samples during the 
study (including baseline and SFU up to the timepoint of interest) regardless of other 
ADAb negative samples and/or missing or inconclusive samples 
− ADAb negative - Defined as subjects for whom either (1) all samples (including baseline 
and SFU up to the timepoint of interest) are ADAb negative and there are no missing or 
inconclusive samples, (2) only 1 sample is ADAb positive and all other samples 
(including baseline and SFU up to the timepoint of interest) are ADAb negative or 
missing/inconclusive or (3) only one sample is missing/inconclusive and the remaining 
ADAb samples are negative. 
− ADAb Missing - Defined as subjects who do not fulfil the criteria for one of the 2 groups 
listed above. 
If ≥95% of subjects are included in the non-missing groups, the missing group will not 
be displayed on the figure.  
Separate figures will be presented for data up to Week 16 (for the BKZ 160mg Q4W group) 
and side by side by treatment group for data up to Week 24 and Week 52. The data will also 
be presented in a tabular format. The analyses will be repeated for ACR20 and PASI90 (for 
PASI90, in the subgroup of subjects with PSO involving at least 3% BSA at Baseline). 
If ≥95% of subjects are included in the non-missing groups, the missing group will not 
be tabulated and thus not displayed on the figure.  
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Change #14 
Section 9.2.9 Neutralizing anti-bimekizumab antibodies  
• Two figures (side by side) summarizing efficacy response (ACR50 based on NRI) versus 
time for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W) by NAb 
status (ADAb negative, NAb positive, ADAb positive / NAb negative, missing) will be 
created. If ≥95% of subjects are included in the non-missing groups, the missing group will 
not be displayed in the figure. Separate figures will be presented for data up to Week 16 (for 
the BKZ 160mg Q4Wgroup), and to Week 24 and 52 by treatment group (BKZ 160mg Q4W 
vs. Placebo / BKZ 160mg Q4W). The data will also be presented in a tabular format. The 
analyses will be repeated for ACR20 and PASI90. The data will be also presented in a 
tabular format. 
Has been changed to: 
• Two figures (side by side) summarizing efficacy response (ACR50 based on NRI) versus 
time for each treatment group (Placebo / BKZ 160mg Q4W and BKZ 160mg Q4W) by NAb 
status (ADAb negative, NAb positive, ADAb positive / NAb negative, missing) will be 
created. If ≥95% of subjects are included in the non-missing groups, the missing group will 
not be displayed in the figure. Separate figures will be presented for data up to Week 16 (for 
the BKZ 160mg Q4Wgroup), and to Week 24 and 52 by treatment group (BKZ 160mg Q4W 
vs. Placebo / BKZ 160mg Q4W). The data will also be presented in a tabular format. The 
analyses will be repeated for ACR20 and PASI90 (for PASI90, in the subgroup of subjects 
with PSO involving at least 3% BSA at Baseline). The data will be also presented in a 
tabular format. 
 
Change #15 
Section 10.2.4 Other safety topics of interest 
New section : Section 10.2.4.9 Summary table and figure   
 
Change #16 
Section 10.2.5 Special considerations for interim data snapshots 
Because of the long SFU Period (140 days from last dose), subjects who have completed the 
SFU visit (and do not, therefore, enroll into the OLE study) may have a longer period of 
exposure than subjects who complete the study and roll in to the OLE study. For those subjects, 
exposure ends at 20 weeks after Week 48 (last dose of BKZ) making 68 weeks of exposure. 
Has been changed to: 
Because of the long SFU Period (140 days from last dose), subjects who have completed the 
SFU visit (and do not, therefore, enroll into the OLE study) may have a longer period of 
exposure than subjects who complete the study and roll in to the OLE study. For those subjects, 
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exposure ends at 20 weeks after Week 48 (last dose of BKZ) making 68 weeks of exposure the 
last dose of IMP. 
 
Change #17 
Section 10.3 Clinical laboratory evaluations 
(…) 
To define the minimum/maximum post-Baseline values, all post-Baseline assessments including 
those at unscheduled visits (but excluding any that occur more than 140 days after the last 
administration of study medication) will be used.  
Has been changed to: 
(…) 
To define the minimum/maximum post-Baseline values, all post-Baseline assessments including 
those at unscheduled visits (but excluding any that occur more than 140 days after the last 
administration of study medication) will be used. 
The following additional rule will be also applied :  
Subjects who have completed PA0010 and have a PA0012 start date, only PA0010 results 
up to and including the PA0012 start date will be used to find the subjects minimum or 
maximum results. Additionally, subjects who are in PA0012 without a start date (date of 
first dose), only PA0010 results up to the Week 52 visit + 14 days will be used to find the 
subjects minimum or maximum results. 
 
Change #18 
Section 10.5.2 Assessment of tuberculosis 
The laboratory test results from the TB assessment performed by interferon gamma release assay   
will be summarized by treatment group for Baseline (Screening) and Week 48. They will also be 
listed.  
The results from the ‘Evaluation of signs and symptoms of tuberculosis’ questionnaire data will 
be also listed.  
Has been changed to: 
The laboratory test results from the TB assessment performed by interferon gamma release assay 
(for non-Japanese subjects) and by T-Spot test (for Japanese subjects)  will be summarized 
by treatment group for Baseline (Screening) and Week 48. They will also be listed.  
The results from the ‘Evaluation of signs and symptoms of tuberculosis’ questionnaire data will 
be also listed.  
 
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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:
PA0010 SAP AMEND3.0 FINAL
Version:
1. 0
Document Number:
CLIN-000190125
Title:
pa0010-sap-amend-3
Approved Date:
06 May 2022
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Document Author
Date of Signature: 06-May-2022 14:58:17 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 06-May-2022 15:12:36 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 06-May-2022 15:44:31 GMT+0000
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