Conditions: Hidradenitis Suppurativa
Keywords: Bimekizumab UCB4940 HS Hidradenitis Suppurativa Acne inversa
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 509
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate the efficacy and safety of bimekizumab in study participants with moderate to severe hidradenitis suppurativa (HS)

Detailed description:

Arms:
arm 1: Subjects participating in the study will receive assigned bimekizumab dosing regimen 1 during the Treatment Period. arm 2: Subjects participating in the study will receive assigned bimekizumab dosing regimen 2 during the Treatment Period. arm 3: Subjects participating in the study will receive assigned bimekizumab dosing regimen 3 during the Treatment Period. arm 4: Subjects randomized to this arm will receive placebo during the Initial Treatment Period and bimekizumab during the Maintenance Treatment Period.

Interventions: intervention 1: Bimekizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects will receive bimekizumab at pre-specified time-points. intervention 2: Subjects will receive placebo at pre-specified time-points during the Initial Treatment Period.

Protocol document:
Prot_000.pdf: 
UCB 
 
06 May 2022 
Clinical Study Protocol Amendment 4 
Bimekizumab 
HS0004 
 
 
 
Confidential 
Page 1 of 121 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, MULTICENTER STUDY EVALUATING THE 
EFFICACY AND SAFETY OF BIMEKIZUMAB IN STUDY 
PARTICIPANTS WITH MODERATE TO SEVERE 
HIDRADENITIS SUPPURATIVA 
PROTOCOL HS0004 AMENDMENT 4 
PHASE 3 
SHORT TITLE: 
A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study Evaluating the 
Efficacy and Safety of Bimekizumab in Study Participants with Moderate to Severe Hidradenitis 
Suppurativa 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying numbers: 
Eudra CT Number: 
2019-002551-42 
Investigational New 
Drug (IND) Number: 
134700 
NCT Number: 
NCT04242498 
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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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
 
Document History 
Document 
Date of Issue 
Type of Amendment 
Amendment 4 
06 May 2022 
Substantial  
Amendment 3 
09 Feb 2021 
Substantial  
Amendment 2.1 (Japan) 
19 Dec 2019 
Not applicable 
Amendment 2 
16 Dec 2019 
Nonsubstantial 
Amendment 1.1 (Japan) 
10 Dec 2019 
Not applicable 
Amendment 1 
06 Dec 2019 
Nonsubstantial 
Original Protocol 
29 Oct 2019 
Not applicable 
 
 
 
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Amendment 4 (06 May 2022) 
Overall rationale for the amendment 
It is recommended that a threshold for within-patient clinically meaningful change to define 
treatment success be used in order to establish efficacy for skin pain in Phase 3 trials of patients 
with moderate to severe hidradenitis suppurativa. The Sponsor conducted analyses to estimate 
the threshold for within-patient clinically meaningful change that can be used for a responder 
definition based on the Hidradenitis Suppurativa Symptom Daily Diary worst skin pain item 
score using established guidelines and analytical methods. Pain response status at Week 16 using 
this definition has been added as a secondary endpoint to the study. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
3 Objectives and 
endpoints 
 
• An additional secondary efficacy 
endpoint was added to the protocol 
assessing pain response at Week 
16 using a threshold for within-
patient clinically meaningful 
change as recommended by the 
U.S. Food and Drug 
Administration. 
• Other pain endpoints clarified and 
updated accordingly. 
To align with FDA 
recommendations.  
9.3.2 Analysis of the 
secondary efficacy 
endpoints 
• 
Section updated to include the 
new pain response endpoint in 
the statistical hierarchy, and 
description of planned analysis  
• 
Figure 9-1 updated to include the 
new pain response endpoint. 
To accommodate the new pain 
response endpoint. 
9.8 Determination of 
sample size 
• Sample size assumptions updated 
based on additional secondary 
endpoint. 
The addition to the protocol of 
the HSSDD worst skin pain 
response as a ranked secondary 
endpoint resulted in an addition 
to the power calculation 
section, including assumptions 
for sample size, response rates, 
and statistical power. 
Throughout 
• Minor editorial and formatting 
revisions 
Minor edits and formatting 
revisions that do not impact 
content were made for 
readability and/or clarity 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ............................................................................................... 10 
1.1 
Synopsis ....................................................................................................................... 10 
1.2 
Schema ......................................................................................................................... 13 
1.3 
Schedule of activities ................................................................................................... 14 
2 
INTRODUCTION ........................................................................................................... 20 
2.1 
Study rationale ............................................................................................................. 20 
2.2 
Background .................................................................................................................. 20 
2.3 
Benefit/risk assessment ................................................................................................ 21 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 23 
4 
STUDY DESIGN ............................................................................................................. 26 
4.1 
Overall design .............................................................................................................. 26 
4.1.1 
Screening Period (Weeks -5 to 0) ........................................................................ 27 
4.1.2 
Initial Treatment Period (Weeks 0-16) and Maintenance Treatment Period 
(Weeks 16-48) ..................................................................................................... 27 
4.1.3 
Safety Follow-up Visit ......................................................................................... 27 
4.1.4 
Visit Windows ..................................................................................................... 27 
4.2 
Scientific rationale for study design ............................................................................ 27 
4.3 
Justification for dose .................................................................................................... 28 
4.4 
End of study definition................................................................................................. 29 
5 
STUDY POPULATION .................................................................................................. 29 
5.1 
Inclusion criteria .......................................................................................................... 29 
5.2 
Exclusion criteria ......................................................................................................... 30 
5.3 
Lifestyle restrictions..................................................................................................... 34 
5.4 
Screen failures .............................................................................................................. 34 
6 
STUDY TREATMENTS ................................................................................................. 35 
6.1 
Treatments administered .............................................................................................. 35 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 38 
6.2.1 
Drug accountability ............................................................................................. 38 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 38 
6.3.1 
Randomization and numbering of participants .................................................... 38 
6.3.2 
Procedures for maintaining and breaking the treatment blind ............................. 39 
6.3.2.1 
Maintenance of study treatment blind ....................................................... 39 
6.3.2.2 
Breaking the treatment blind in an emergency situation ........................... 39 
6.4 
Treatment compliance .................................................................................................. 40 
6.5 
Concomitant medications/treatments ........................................................................... 40 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 40 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 41 
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6.5.3 
Rescue medication ............................................................................................... 44 
6.5.3.1 
Antibiotic Rescue Medication/Antibiotics ................................................ 44 
6.5.3.2 
Rescue Medications/Lesion Intervention .................................................. 44 
6.6 
Dose modification ........................................................................................................ 45 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 45 
6.8 
Treatment after the end of the study ............................................................................ 45 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 46 
7.1 
Discontinuation of study medication ........................................................................... 46 
7.1.1 
Study participant does not achieve partial response ............................................ 46 
7.1.2 
Potential drug-induced liver injury IMP discontinuation criteria ........................ 46 
7.1.2.1 
PDILI Discontinuation Criteria ................................................................. 46 
7.1.3 
Treatment interruptions ....................................................................................... 47 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 48 
7.3 
Lost to follow up .......................................................................................................... 50 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 51 
8.1 
Efficacy assessments .................................................................................................... 52 
8.1.1 
Lesion count ......................................................................................................... 52 
8.1.1.1 
Hidradenitis Suppurativa Clinical Response (HiSCR) .............................. 52 
8.1.1.2 
Hidradenitis Suppurativa Physician’s Global Assessment ........................ 53 
8.1.1.3 
International Hidradenitis Suppurativa Severity Score System (IHS4) .... 53 
8.1.2 
Partial response .................................................................................................... 53 
8.1.3 
High-sensitivity C-reactive protein (hs-CRP) ..................................................... 54 
8.1.4 
Patient-reported outcomes ................................................................................... 54 
8.1.4.1 
HS symptom measures of skin pain, smell or odor, drainage or oozing 
from HS lesions, and itch .......................................................................... 54 
8.1.4.2 
Patient Global Impression of HS Severity (PGI-S-HS) and Change in HS 
Severity (PGI-C-HS) ................................................................................. 54 
8.1.4.3 
Patient Global Impression of Severity of Skin Pain (PGI-S-SP) and 
Change in Severity of Skin Pain (PGI-C-SP) ............................................ 54 
8.1.4.4 
Hidradenitis Suppurativa Quality of Life Questionnaire (HiSQOL) ........ 55 
8.1.4.5 
Dermatology Life Quality Index (DLQI) .................................................. 55 
8.1.4.6 
Euro-Quality of Life 5-Dimensions, 3 levels ............................................ 55 
8.1.4.7 
Workers Productivity and Activity Impairment Questionnaire: Specific 
Health Problem .......................................................................................... 55 
8.1.4.8 
Treatment Satisfaction Questionnaire for Medication .............................. 55 
8.1.5 
Hurley Stage ........................................................................................................ 56 
8.2 
Safety assessments ....................................................................................................... 56 
8.2.1 
Physical examination ........................................................................................... 56 
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8.2.2 
Vital signs ............................................................................................................ 56 
8.2.3 
Electrocardiograms .............................................................................................. 57 
8.2.4 
Clinical safety laboratory assessments ................................................................ 57 
8.2.5 
Depression and suicidal risk monitoring ............................................................. 57 
8.2.5.1 
PHQ-9 ........................................................................................................ 57 
8.2.5.2 
eC-SSRS .................................................................................................... 57 
8.2.6 
Assessment and management of tuberculosis and tuberculosis risk factors ........ 58 
8.2.6.1 
Assessments at Screening .......................................................................... 58 
8.2.6.2 
Definitions ................................................................................................. 58 
8.2.6.3 
Assessment and reporting of TB and TB risk factors during the study..... 59 
8.3 
Adverse events and serious adverse events ................................................................. 64 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 64 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 64 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 64 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 65 
8.3.5 
Pregnancy ............................................................................................................ 65 
8.3.6 
Adverse events of special interest ........................................................................ 65 
8.3.7 
Other safety topics of interest .............................................................................. 66 
8.3.8 
Anticipated serious adverse events ...................................................................... 66 
8.3.9 
Suspected transmission of an infectious agent .................................................... 67 
8.4 
Safety signal detection ................................................................................................. 67 
8.5 
Treatment of overdose ................................................................................................. 68 
8.6 
Pharmacokinetics ......................................................................................................... 68 
8.7 
Genetics........................................................................................................................ 68 
8.8 
Pharmacodynamics ...................................................................................................... 69 
8.9 
Biomarkers ................................................................................................................... 69 
8.9.1 
Immunogenicity assessments ............................................................................... 69 
8.10 
Medical resource utilization and health economics ..................................................... 70 
8.11 
Photography ................................................................................................................. 70 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 70 
9.1 
Definition of analysis sets ............................................................................................ 70 
9.1.1 
Enrolled Set ......................................................................................................... 70 
9.1.2 
Randomized Set ................................................................................................... 70 
9.1.3 
Safety Set ............................................................................................................. 70 
9.1.4 
Full Analysis Set .................................................................................................. 70 
9.1.5 
Per-Protocol Set ................................................................................................... 70 
9.1.6 
Pharmacokinetics Per-Protocol Set ...................................................................... 71 
9.1.7 
COVID-19 Free Set ............................................................................................. 71 
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9.2 
General statistical considerations ................................................................................. 71 
9.3 
Planned efficacy/outcome analyses ............................................................................. 71 
9.3.1 
Analysis of the primary efficacy endpoint ........................................................... 71 
9.3.2 
Analysis of the secondary efficacy endpoints ..................................................... 72 
9.3.3 
Other efficacy/other outcome analyses ................................................................ 74 
9.3.4 
COVID-19 impact analysis .................................................................................. 74 
9.4 
Planned safety and other analyses................................................................................ 75 
9.4.1 
Safety analyses ..................................................................................................... 75 
9.4.2 
PK and ADAb analyses ....................................................................................... 75 
9.5 
Handling of protocol deviations................................................................................... 75 
9.6 
Handling of dropouts or missing data .......................................................................... 76 
9.7 
Planned interim analysis and data monitoring ............................................................. 77 
9.7.1 
Data Monitoring Committee ................................................................................ 77 
9.7.2 
Interim Analysis ................................................................................................... 77 
9.8 
Determination of sample size ....................................................................................... 77 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 80 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 80 
10.1.1 
Regulatory and ethical considerations ................................................................. 80 
10.1.2 
Financial disclosure ............................................................................................. 80 
10.1.3 
Informed consent process .................................................................................... 81 
10.1.4 
Data protection ..................................................................................................... 81 
10.1.5 
Committees structure ........................................................................................... 82 
10.1.6 
Data quality assurance ......................................................................................... 82 
10.1.6.1 
Case report form completion ..................................................................... 83 
10.1.7 
Source documents ................................................................................................ 83 
10.1.8 
Study and Site Closure ......................................................................................... 83 
10.1.9 
Publication Policy ................................................................................................ 84 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 85 
10.3 
Appendix 3: Adverse events – definitions and procedures for recording, evaluating, 
follow-up, and reporting .............................................................................................. 87 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 93 
10.5 
Appendix 5: Genetics ................................................................................................... 96 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 97 
10.6.1 
Consultation with Medical Monitor and local hepatologist............................... 101 
10.6.2 
Immediate action: determination of IMP discontinuation ................................. 101 
10.6.2.1 
IMP restart/rechallenge ........................................................................... 101 
10.6.3 
Testing: identification/exclusion of alternative etiology ................................... 102 
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10.7 
Appendix 7: Medical device AEs, Adverse device effects, SAEs, and device 
deficiencies: definition and procedures for recording, evaluating, follow-up, and 
reporting ..................................................................................................................... 105 
10.8 
Appendix 8: Rapid alert procedures .......................................................................... 106 
10.9 
Appendix 9: Country-specific requirements .............................................................. 107 
10.10 Appendix 10: Abbreviations and trademarks ............................................................ 108 
10.11 Appendix 11: Protocol amendment history ............................................................... 111 
11 REFERENCES .............................................................................................................. 118 
SPONSOR DECLARATION ................................................................................................ 121 
 
LIST OF TABLES 
Table 1‒1: 
Schedule of activities ....................................................................................... 14 
Table 6‒1: 
Study medications administered ...................................................................... 36 
Table 6‒2: 
Dosing scheme ................................................................................................. 37 
Table 6‒3: 
Exclusions for prior medications ..................................................................... 42 
Table 8‒1: 
Anticipated SAEs for the Population of Participants with HS ........................ 67 
Table 9‒1: 
Power calculation assumptions and methods ................................................... 79 
Table 10‒1: 
Required investigations and follow-up for PDILI ........................................... 98 
Table 10‒2: 
PDILI laboratory measurements .................................................................... 103 
Table 10‒3: 
PDILI information to be collected ................................................................. 104 
 
LIST OF FIGURES 
Figure 1-1: 
Study Schematic............................................................................................... 13 
Figure 8-1: 
Decision tree for IGRA TB results at Screening ............................................. 62 
Figure 8-2: 
Decision tree for IGRA TB results during a study .......................................... 63 
Figure 9-1: 
Closed Testing Procedure ................................................................................ 74 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: 
A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study Evaluating the 
Efficacy and Safety of Bimekizumab in Study Participants with Moderate to Severe Hidradenitis 
Suppurativa 
Short Title: 
A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study Evaluating the 
Efficacy and Safety of Bimekizumab in Study Participants with Moderate to Severe Hidradenitis 
Suppurativa 
Rationale: 
UCB is investigating bimekizumab (a humanized, full-length immunoglobulin [Ig] G1 
monoclonal antibody [mAb] with high affinity for human interleukin [IL] 17 [IL-17A and IL 
17F]) for the treatment of hidradenitis suppurativa (HS). Antibodies targeting IL-17A are 
effective in treating patients with moderate to severe psoriasis (PSO) and other 
immuno-inflammatory conditions. Data from clinical studies with bimekizumab suggest that 
inhibition of both IL-17A and IL-17F could be beneficial to patients with such conditions, 
including HS. Based on results from a Phase 2a study in study participants with HS (HS0001); 
and a Phase 2b study in study participants with PSO (PS0010) and its 48 week extension study 
(PS0011), bimekizumab doses of 320mg every 2 weeks (Q2W) in HS and 320mg every 4 weeks 
(Q4W) in PSO appeared to have an acceptable safety profile, and achieved clinically meaningful 
efficacy in both primary and key secondary endpoints in their respective studies. Based on these 
data and considering the high unmet need for safe and effective therapies for HS, confirmatory 
studies are being conducted with bimekizumab for the treatment of moderate to severe HS. 
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Objectives and Endpoints 
The primary and secondary objectives and associated endpoints are as follows: 
Objectives 
Endpoints 
Primary 
Evaluate the efficacy of 
bimekizumab in study 
participants with moderate 
to severe HS 
• HiSCR50 at Week 16 
Secondary 
Evaluate the efficacy of 
bimekizumab on other 
measures of disease activity 
in study participants with 
moderate to severe HS 
• HiSCR75 at Week 16 
• Flare (defined as a ≥25% increase in AN count with an 
absolute increase in AN count of ≥2 relative to Baseline) by 
Week 16 
• Absolute change from Baseline in DLQI Total Score at 
Week 16 
• Absolute change from Baseline in the Worst HS Skin Pain 
score at Week 16, as assessed by the “worst pain” item 
(11-point numeric rating scale) in the HSSDD 
• Pain response (defined as a decrease from Baseline in 
HSSDD weekly worst skin pain score at or beyond the 
threshold for clinically meaningful change) at Week 16 
Evaluate the safety of 
bimekizumab in study 
participants with moderate 
to severe HS 
• Treatment-emergent AEs 
• Serious TEAEs 
• TEAEs leading to withdrawal from study 
AE=adverse event; AN=abscess and inflammatory nodule; DLQI=Dermatology Life Quality Index; HiSCR50=a 
50% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel count; 
HiSCR75=a 75% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel 
count; HS= hidradenitis suppurativa; HSSDD=Hidradenitis Suppurativa Symptom Daily Diary; 
TEAE=treatment-emergent adverse event 
Overall Design 
HS0004 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, pivotal study 
evaluating the efficacy and safety of bimekizumab in study participants with moderate to severe 
HS. 
Number of Participants 
Approximately 490 study participants will be randomly assigned to study treatment: 140 for 
bimekizumab 
, 140 for bimekizumab 
, 140 for 
bimekizumab 
, and 70 for placebo/
. The Randomized Set (ie, all 
randomized study participants) is the primary analysis set for efficacy analyses. 
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Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized to study treatment (Section 5.4). 
Treatment Groups and Duration 
Study participants meeting the inclusion criteria who do not meet any exclusion criteria will 
complete a Screening Period of 14 days to up to 5 weeks; a double-blind, 48-week Treatment 
Period comprising a 16-week Initial Treatment Period and 32-week Maintenance Treatment 
Period; and a 20-week Safety Follow-up (SFU) Period following the final injection of 
investigational medicinal product (IMP) if study participants do not enter a subsequent extension 
study (HS0005) or withdraw prematurely from treatment. The total duration of study 
participation in HS0004 will be 68 to 71 weeks for those who complete HS0004 and do not 
participate in the extension study HS0005 and 50 to 53 weeks for those who participate in 
HS0005 and, thus, do not participate in the 20-week SFU Period. 
Study participants will be randomized in a 2:2:2:1 ratio (stratified by Hurley Stage and current 
antibiotic use) to 1 of 3 dose regimens of bimekizumab or placebo as shown in the schematic 
(Figure 1-1). All doses of IMP will be administered by subcutaneous (sc) injection. The primary 
efficacy variable at Week 16 is HiSCR50 (a 50% reduction in the total AN count with no increase 
from Baseline in abscess or draining tunnel count). Study visits will occur at Screening; Baseline 
(Week 0); Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16; 
 from Week 16 through Week 48 
for assessments of efficacy, safety, and other measures of quality of life/health status/work 
productivity; and a SFU visit 20 weeks after the last dose of IMP for participants who do not 
enter the extension study. 
An independent Data Monitoring Committee (DMC) will periodically review unblinded efficacy 
and safety data to assess the benefit/risk of bimekizumab in study participants with moderate to 
severe HS. In addition, aggregated unblinded efficacy data is planned to be provided to the DMC 
when approximately 66% of study participants have reached the primary efficacy endpoint at 
Week 16. Efficacy data will be provided to the DMC to put the safety review in the context of 
risk/benefit. Measures to ensure that unblinded interim results are not disseminated beyond the 
DMC will be implemented. 
 
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1.2 
Schema 
A schematic diagram for the study is presented in Figure 1-1. 
Figure 1-1: Study Schematic 
 
HiSCR50=a 50% reduction in the total abscess and inflammatory nodule count with no increase from Baseline in abscess or draining tunnel count; 
IMP=investigational medicinal product; 
 
*Week 16 = primary endpoint (HiSCR50 bimekizumab versus placebo) 
a Study participants should discontinue from the study from Week 32 on if no partial response is achieved (partial response is defined as ≥25% improvement in 
abscess and inflammatory nodule count relative to Baseline [Week 0] lesion values,) 
b Study participants achieving an improvement of at least 25 % in abscess and inflammatory nodule count continue in HS0005 (Extension Study). 
c 20-week Safety Follow-up (from last IMP injection) for any study participant who discontinues from study prior to Week 48, or who does not continue in 
HS0005. 
 
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1.3 
Schedule of activities 
The Schedule of Activities is presented in Table 1‒1. 
Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
Study Visit 
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 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xd 
 
 
Study 
participant 
number 
assigned 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/excl
usion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic 
and Baseline 
disease 
characteristics 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hidradenitis 
suppurativa 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Significant 
past medical 
history/ 
concomitant 
diseasese 
X 
Xf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examinationg 
X 
X 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
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Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Vital signsh 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Hematology/ 
biochemistry 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
hs-CRP 
 
X 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
Urine drug 
screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Pregnancy 
testingi 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Hepatitis B 
and C testingj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV testingk 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest x-rayl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGRA TB 
testm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
TB 
questionnaire 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Lesion count 
(includes 
Hurley Stage)n 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
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Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
Photographyo 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
Blood sample 
– 
bimekizumab 
plasma 
concentrations
p 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Blood sample 
for anti-drug 
antibodiesp 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Blood sample 
for genomic/ 
proteomic/ 
metabolomics, 
and candidate 
biomarker 
analysesp, q 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Blood sample 
for genetic/ 
epigenetic 
analysesp, q 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Urine samples 
for biomarker 
research 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
DLQI 
 
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 
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Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
eC-SSRS 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
WPAI-SHP 
 
X 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
TSQM-9 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
HiSQOL 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
HSSDDr 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HSSQ 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PGI-S-HS 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
PGI-C-HS 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
PGI-S-SP 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
PGI-C-SP 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
EQ-5D-3L 
 
X 
 
 
X 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
X 
X 
 
Concomitant 
medications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse 
events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomizations 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRT 
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 
AN=abscess and inflammatory nodule; Bsl=Baseline; CAT=computed axial tomography; CRF=case report form; DLQI=Dermatology Life Quality Index; 
ECG=electrocardiogram; eC-SSRS=electronic Columbia-Suicide Severity Rating Scale; EQ-5D-3L=Euro-Quality of Life 5-Dimensions, 3 levels; 
HiSCR25=a 25% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel count; HiSCR50=a 50% reduction in the total 
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Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
AN count with no increase from Baseline in abscess or draining tunnel count; HiSCR75=a 75% reduction in the total AN count with no increase from 
Baseline in abscess or draining tunnel count; HiSCR90=a 90% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel 
count; HiSCR100=a 100% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel count; HiSQOL=Hidradenitis 
Suppurativa Quality of Life; HIV=human immunodeficiency virus; HS=hidradenitis suppurativa; hs-CRP=high sensitivity C-reactive protein; 
HSSDD=Hidradenitis Suppurativa Symptom Daily Diary; HSSQ=Hidradenitis Suppurativa Symptom Questionnaire; IGRA=interferon-gamma release 
assay; IMP=investigational medicinal product; IRT=interactive response technology; PEOT=Premature End of Treatment Visit; PGI-C-HS=Patient Global 
Impression of Change in HS Severity; PGI-C-SP=Patient Global Impression of Change in Severity of Skin Pain; PGI-S-HS=Patient Global Impression of 
HS Severity; PGI-S-SP=Patient Global Impression of Severity of Skin Pain; PHQ-9=Patient Health Questionnaire 9; SFU=Safety Follow-Up; 
TB=tuberculosis; TSQM=Treatment Satisfaction Questionnaire for Medication; WPAI-SHP=Work Productivity and Impairment Questionnaire-Specific 
Health Problem 
Note: Some study-specific assessments may be conducted remotely according to the study protocol during a pandemic or other exceptional circumstance (eg, 
hurricanes) due to the need to implement safety measures and guidance from regulatory authorities. Refer to Section 8 for additional information. 
a Visit windows are ±3 days (based on the date of the first dose). However, the minimum of 8 days between injection visits (eg, Visit 2 +3 days occurs on 
Day17; Visit 4 -3 days occurs on Day 25) may be used only 1 time in the Initial Treatment Period and 1 time in the Maintenance Treatment Period, if 
needed. The study participant should be dosed according to the administration schedule thereafter. The 20-week SFU Visit window is ±7 days (based on the 
date of the final dose). 
b The Screening Period will last a minimum of 14 days up to a maximum of 5 weeks prior to randomization. 
c All study participants not continuing in the extension study, including those withdrawn from IMP as well as those completing all study visits, will have an 
SFU Visit 20 weeks after his or her final dose of IMP. 
d A separate informed consent form will be required to be completed for participation in extension study HS0005. Study participants continuing in HS0005 
will receive first dose of bimekizumab in that study on Week 48. 
e Past medical history includes tobacco and alcohol use. 
f Ensure no significant changes from Baseline in medical history and concomitant disease. 
g The physical examination will be performed as detailed in Section 8.2.1. Includes evaluation of signs and symptoms of active TB and risk for exposure to 
TB. 
h Vital signs (sitting systolic and diastolic blood pressure, pulse rate, and body temperature) are to be measured prior to blood sampling and prior to dosing, 
where applicable. 
i Pregnancy testing will consist of serum testing at the Screening Visit. Urine pregnancy tests will be performed at all other visits where specified. 
j See Exclusion Criterion 9. 
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Table 1‒1: 
Schedule of activities 
Visit Name or 
Weeks After 
1st Dosea 
 
 
 
Protocol 
activity 
Screeningb 
Initial Treatment Period 
(weeks after first dose) 
Maintenance Treatment Period 
(weeks after first dose) 
PEOT 
SFUc 
Bsl 
1st 
dos
e 
0 
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
k The HIV test result will not be recorded in the eCRF. 
l A chest x-ray must be performed at the Screening Visit, or must occur within 2 months prior to Screening and results must be available at Baseline. A CAT 
scan of chest at Screening or within 2 months prior to Screening is acceptable, if available. The official report of the imaging must specifically indicate the 
absence of findings suggestive of current active TB or prior inactive TB. 
m Quantiferon Gold Plus will be used for this analysis. Details on IGRA assessment are provided in Section 8.2.6.3.4. 
n Lesion count will be performed at the specified study visits, and must address all relevant anatomical regions in each study participant; Hurley Stage is 
included as an assessment performed during the lesion count. The data collected from the lesion count will be used for the derivation of the HiSCR25, 
HiSCR50, HiSCR75, HiSCR90, HiSCR100, HS Physician’s Global Assessment, and International Hidradenitis Suppurativa Severity score system (IHS4). 
o At certain sites, where feasible, representative photographs of the changes in skin will be captured. Photographs will be anonymized. 
p All blood samples taken prior to dosing. 
q All genomic, proteomic, and metabolomic samples and the genetic/epigenetic samples will be stored at -80°C at the central biorepository for up to 20 years. 
r The HSSDD (pain, smell or odor, drainage or oozing from HS lesions, and itch) will be completed daily from Screening through Week 16. 
s Randomization occurs at the Baseline Visit for all study participants. 
t IMP administration is based on randomization at the Baseline Visit for all study participants. Double-dummy IMP administration will occur 
 
in all study participants to maintain the study blind. The dosing window is ±3 days relative to the scheduled dosing visit. 
 
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2 
INTRODUCTION 
2.1 
Study rationale 
UCB is investigating bimekizumab (a humanized, full-length immunoglobulin [Ig] G1 
monoclonal antibody [mAb] with high affinity for human interleukin [IL] 17 [IL-17A and IL 
17F]) for the treatment of hidradenitis suppurativa (HS). Antibodies targeting IL-17A are 
effective in treating patients with moderate to severe psoriasis (PSO) and other 
immuno-inflammatory conditions. Data from clinical studies with bimekizumab suggest that 
inhibition of both IL-17A and IL-17F could be beneficial to patients with such conditions, 
including HS. Based on results from a Phase 2a study in study participants with HS (HS0001; 
European Union Drug Regulating Authorities Clinical Trials [EudraCT] Number 
2017-000892-10, NCT03248531) and a Phase 2b study in study participants with PSO (PS0010) 
and its 48 week extension study (PS0011), bimekizumab doses of 320mg every 2 weeks (Q2W) 
in HS and 320mg every 4weeks (Q4W) in PSO, appeared to have an acceptable safety profile, 
and achieved clinically meaningful efficacy in both primary and key secondary endpoints in their 
respective studies. Based on these data and considering the high unmet need for safe and 
effective therapies for HS, confirmatory studies are being conducted with bimekizumab for the 
treatment of moderate to severe HS. 
2.2 
Background 
Hidradenitis suppurativa or acne inversa is a chronic, inflammatory, recurrent, debilitating skin 
disease that usually presents after puberty with painful, deep-seated, inflamed lesions in the 
apocrine gland-bearing areas of the body, most commonly the axillaries, inguinal, and anogenital 
regions (Dessau definition, First International Conference on HS, 30 Mar to 01 Apr 2006, 
Dessau, Germany). The nodules are often inflamed, can progress to abscess formation, and may 
rupture to form fistulas and subsequent scarring. Thus, many patients with HS develop 
permanent sequelae of past inflammation that are only remediable through surgical excision of 
the involved skin areas. Hidradenitis suppurativa is also associated with several complications 
(eg, the development of anal, urethral, and rectal strictures and fistulas), and the excessive 
scarring and fibrosis produced by HS lesions can lead to contractures and limitations in limb 
mobility (Alikhan, 2009; Danby, 2010). 
Hidradenitis suppurativa is estimated to affect about 1% of the adult European population, with a 
female to male ratio of approximately 3:1 (Revuz, 2008; Naldi, 2006). The prevalence of 
diagnosed HS in the US may be lower (<0.1%), although further research is needed to determine 
the prevalence of undiagnosed HS in the US (McMillan, 2014). Patients diagnosed with HS often 
experience a significant reduction in quality of life (QOL), equivalent to severe PSO (Sartorius, 
2009), due to the location of, and discharge from, the lesions that leads to an often persistent 
morbidity due to pain and sequelae from uncontrolled inflammation (von der Werth, 2001; 
Wolkenstein, 2007). The reduction in QOL and persistent morbidity result in functional 
impairment in patients with HS similar or greater to that of heart disease, diabetes, or asthma, 
when measured by the European Quality-of-Life 5 dimensions 3-level questionnaire (EQ-5D-3L) 
scale (Riis, 2016). 
Bimekizumab is a humanized full-length mAb of IgG1 subclass being developed for the 
treatment of patients with inflammatory diseases such as PSO, psoriatic arthritis, axial 
spondyloarthritis, and HS. Bimekizumab has high affinity for human IL-17A and human IL-17F, 
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and selectively and potently inhibits the activity of both isoforms in vitro. The key 
pro-inflammatory cytokine IL-17A has been demonstrated to, and IL-17F is believed to, play 
important roles in autoimmune and inflammatory diseases. Published data and 
immunohistochemistry studies performed by UCB have shown that expression of both IL-17A 
and IL-17F is present in HS lesions, and there are published reports highlighting the potential for 
IL-17A and IL-17F to drive HS disease pathology (UCB Research Report 40001864; Cho, 2012; 
Schlapbach, 2011). This supports the hypothesis that the IL-17 cytokine family is a potential 
therapeutic target in HS. Bimekizumab is hypothesized to demonstrate a treatment response in 
HS because it selectively and potently inhibits the activity of both IL-17A and IL-17F isoforms 
in vitro. 
2.3 
Benefit/risk assessment 
Overall, the Phase 2a POC study in HS (HS0001) demonstrated that the  safety profile (during 
10 weeks of dosing for a 12-week treatment period) for bimekizumab 320mg sc Q2W appears 
consistent with that of bimekizumab in other indications (PSO, psoriatic arthritis, axial 
spondyloarthritis) for which bimekizumab is being developed. 
Treatment-emergent adverse events (TEAEs) experienced by study participants with HS 
receiving repeated doses of bimekizumab occurred at incidences similar to those with placebo 
and adalimumab (range: 61.9% to 71.4%). In both the bimekizumab and adalimumab groups, the 
most frequently reported TEAEs were in the system organ classes of Infections and infestations 
(43.5% and 42.9%, respectively), Skin and subcutaneous tissue disorders (28.3% and 42.9%, 
respectively), and General disorders and administration site conditions (21.7% and 23.8%, 
respectively). The most frequently reported TEAEs in the placebo group were in the SOCs of 
Nervous system disorders (28.6%) and Infections and infestations and Skin and subcutaneous 
tissue disorders (19.0% each). The most frequently reported TEAEs (by preferred term ) were 
hidradenitis (17.4%) and fatigue (8.7%) in the bimekizumab group, hidradenitis (33.3%) and 
influenza (14.3%) in the adalimumab group, and headache and hidradenitis (14.3% each) and 
arthralgia (4.8%) in the placebo group. Events of hidradenitis were not unexpected in a 
population of study participants with moderate-to-severe HS. 
With regard to TEAEs of special interest and other safety topics of interest, there were no major 
adverse cardiovascular events, serious fungal/opportunistic infections (including tuberculosis 
[TB]), malignancies (including lymphoma), neuropsychiatric events, cases of inflammatory 
bowel disease (IBD), evidence of hepatotoxicity (per Hy’s Law criteria), or 
hypersensitivity/anaphylactic reactions reported with bimekizumab treatment. No new safety 
signals were identified in HS0001 compared with those observed with bimekizumab across other 
development programs to date. 
No clinically relevant patterns of changes were observed in any treatment group in hematology, 
clinical chemistry, vital signs, or electrocardiogram (ECG) findings. Few markedly abnormal 
post-Baseline liver function test values were reported during the study. 
With respect to benefit, the totality of the data from HS0001 demonstrated that bimekizumab 
results in clinically meaningful and consistent improvements versus placebo across all HS 
outcome measures assessed. Improvements began early after initiation of treatment, and 
persisted through the last assessment (Week 12). The efficacy data for the primary endpoint, 
HiSCR50 (ie, a 50% reduction in the total abscess and inflammatory nodule [AN] count with no 
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increase from Baseline in abscess or draining tunnel count) at Week 12, were comparable with 
that of adalimumab, and other efficacy measures suggested improved therapeutic outcomes 
(larger proportions of study participants achieving HiSCR75 [a 75% reduction in the total AN 
count with no increase from Baseline in abscess or draining tunnel count], HiSCR90 [a 90% 
reduction in the total AN count with no increase from Baseline in abscess or draining tunnel 
count], and Dermatology Life Quality Index [DLQI] total scores of 0 and 1). 
Overall, results of HS0001 show that bimekizumab appears to have an acceptable safety profile 
considering the anticipated benefit at a dose of 320mg Q2W for the treatment duration evaluated 
to date. No new safety concerns were raised in study participants with moderate to severe HS, 
and the benefit/risk remains positive and supports continued investigation of bimekizumab at 
320mg Q2W. 
More detailed information about the known and expected benefits and risks of bimekizumab may 
be found in the Investigator’s Brochure. 
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3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
Evaluate the efficacy of 
bimekizumab in study 
participants with moderate 
to severe HS 
• HiSCR50 at Week 16 
Secondary 
Evaluate the efficacy of 
bimekizumab on other 
measures of disease activity 
in study participants with 
moderate to severe HS 
• HiSCR75 at Week 16  
• Flare (defined as a ≥25% increase in AN count with an 
absolute increase in AN count of ≥2 relative to Baseline) by 
Week 16 
• Absolute change from Baseline in DLQI Total Score at 
Week 16 
• Absolute change from Baseline in Skin Pain score at 
Week 16, as assessed by the “worst pain” item (11-point 
numeric rating scale) in the HSSDD 
• Pain response (defined as a decrease from Baseline in 
HSSDD weekly worst skin pain score at or beyond the 
threshold for clinically meaningful change) at Week 16 
Evaluate the safety of 
bimekizumab in study 
participants with moderate 
to severe HS 
• Treatment-emergent AEs 
• Serious TEAEs 
• TEAEs leading to withdrawal from study 
Other 
Evaluate the efficacy of 
bimekizumab on HiSCR, 
other HS Scores, and other 
clinical measures of disease 
activity at various 
timepoints in study 
participants with moderate 
to severe HS 
• Time to response of HiSCR25, HiSCR50, HiSCR75, HiSCR90, 
and HiSCR100 
• HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100  
• Absolute change from Baseline in International Hidradenitis 
Suppurativa Severity Score System 
• Change from Baseline in the HS-Physician’s Global 
Assessment 6-point scale 
• Absolute and percentage change from Baseline in hs-CRP 
• Initiation of systemic antibiotic rescue therapy 
• HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 at 
both Weeks 16 and 48 
• Time to loss of response of HiSCR50, HiSCR75, HiSCR90, 
and HiSCR100 in Week 16 responders 
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Objectives 
Endpoints 
• Partial responders (defined as a ≥25% reduction in AN 
count from Baseline [Week 0]) at Week 16 who progress to 
HiSCR50 during the Maintenance Treatment Period 
• Partial responders (defined as a ≥25% reduction in AN 
count from Baseline [Week 0]) at Week 16 who progress to 
HiSCR75, HiSCR90, and HiSCR100 response during the 
Maintenance Treatment Period 
Evaluate the efficacy of 
bimekizumab on abscesses, 
nodules, and draining 
tunnels at various 
timepoints in study 
participants with moderate 
to severe HS 
• Change and percentage change from Baseline in lesion 
counts (abscess count, inflammatory nodule count, AN 
count, and draining tunnel count) 
• AN count of 0, 1, or 2 
• AN25, AN50, AN75, AN90, AN100 
• Flare (defined as a ≥25% increase in AN count with an 
absolute increase in AN count of ≥2 relative to Week 16) by 
Week 48 
• Time to flare from Weeks 0 to 16 
• Time to flare from Week 16 to 48 
Evaluate the efficacy of 
bimekizumab on 
patient-reported outcome 
measures at various 
timepoints in study 
participants with moderate 
to severe HS 
• Absolute and percentage change (worst and average pain) 
from Baseline in HS Skin Pain score (11-point numeric 
rating scale) 
• Pain response (defined as a decrease from Baseline in 
HSSDD weekly worst skin pain score at or beyond the 
threshold for clinically meaningful change)  
• Pain response (defined as a decrease from Baseline in 
HSSQ weekly worst skin pain score at or beyond the 
threshold for clinically meaningful change) 
• Pain response (at least a 30% reduction and at least a 1-unit 
reduction from Baseline in HSSDD weekly worst skin pain 
score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline  
• Pain response (at least a 30% reduction and at least a 1-unit 
reduction from Baseline in HSSDD weekly average skin 
pain score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline  
• Pain response (at least a 30% reduction and at least a 1-unit 
reduction from Baseline in HS Skin Pain score [11-point 
numeric rating scale]) assessed by the HSSQ among study 
participants with a score of ≥3 at Baseline 
• Absolute change from Baseline in DLQI Total Score 
• DLQI Total Score of 0 or 1 
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Objectives 
Endpoints 
• Minimum clinically important difference (improvement 
from Baseline of 4 or more) in the DLQI Total Score among 
study participants with a Baseline score of at least 4) 
• Absolute change from Baseline in HiSQOL domain scores 
(symptoms, psychosocial, activities, adaptations) 
• Absolute change from Baseline in Patient Global 
Impression of HS Severity 
• Absolute change from Baseline in Patient Global 
Impression of Severity of HS Skin Pain 
• Absolute change from Baseline in each of the other HS 
Symptoms - itch, drainage or oozing of HS lesions, and 
smell or odor. 
• Response on other HS Symptoms (11-point numeric rating 
scale) - itch, drainage or oozing of HS lesions, and smell or 
odor 
• Responses to the EQ-5D-3L, absolute and changes from 
Baseline in EQ-5D-3L visual analog scale scores 
• Absolute change from Baseline in Work Productivity and 
Activity Impairment Questionnaire-Specific Health 
Problem v2.0 adapted to HS scores 
• Domain Scores (effectiveness, convenience and global 
satisfaction) on the Treatment Satisfaction Questionnaire – 
Medication-9 
Evaluate the effect of 
bimekizumab on other 
safety measures at various 
timepoints in study 
participants with moderate 
to severe HS 
• Adverse events of special interest (Hy’s Law) 
• Other safety topics of interest: infections (serious, 
opportunistic, fungal, and TB), neutropenia, 
hypersensitivity (including anaphylaxis), suicidal ideation 
and behavior, , major adverse cardiovascular events, hepatic 
events and potential drug-induced liver injury (PDILI), 
malignancies, and inflammatory bowel disease. 
• Absolute change from Baseline in the PHQ-9 score 
• Absolute change from Baseline in vital signs 
• Absolute change from Baseline in clinical laboratory values 
(chemistry and hematology) 
• ECG results 
Evaluate the 
pharmacokinetics of 
bimekizumab in study 
participants with moderate 
to severe HS 
• Plasma bimekizumab concentrations over the study duration 
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Objectives 
Endpoints 
Evaluate the 
immunogenicity of 
bimekizumab (antidrug 
antibodies) in study 
participants with moderate 
to severe HS 
• Bimekizumab antidrug antibodies 
• Bimekizumab neutralizing antibodies 
Exploratory 
Evaluate biomarkers in 
study participants with 
moderate to severe HS.  
• Genomic, genetic, epigenetic, proteins, and metabolite 
biomarkers may be measured to evaluate the relationship 
with response to treatment with bimekizumab, HS disease 
biology, and inflammatory and immune response processes. 
The candidate exploratory biomarkers are the blood or 
blood derivative (eg, plasma) concentrations of cytokines 
and chemokines of relevance to the IL-17A/F signaling 
pathway and HS biology. Additional biomarkers may 
include, but will not be limited to, plasma complement 
concentrations. 
AE=adverse event; AN=abscess and inflammatory nodule; AN25=a 25% reduction in the total abscess and 
inflammatory nodule count relative to Baseline; AN50=a 50% reduction in the total abscess and inflammatory 
nodule count relative to Baseline; AN75=a 75% reduction in the total abscess and inflammatory nodule count 
relative to Baseline; AN90=a 90% reduction in the total abscess and inflammatory nodule count relative to 
Baseline; AN100=a 100% reduction in the total abscess and inflammatory nodule count relative to Baseline; 
DLQI=Dermatology Life Quality Index; ECG=electrocardiogram; eC-SSRS=electronic Columbia Suicide 
Severity Rating Scale; EQ-5D-3L=Euro-Quality of Life 5-Dimensions, 3 levels; HiSCR=Hidradenitis 
Suppurativa Clinical Response; HiSCR50=a 50% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count; HiSCR75=a 75% reduction in the total AN count with no increase from 
Baseline in abscess or draining tunnel count; HiSCR90=a 90% reduction in the total AN count with no increase 
from Baseline in abscess or draining tunnel count; HiSCR100=a 100% reduction in the total AN count with no 
increase from Baseline in abscess or draining tunnel count; HiSQOL=Hidradenitis Suppurativa Quality of Life; 
HS=hidradenitis suppurativa; hs-CRP=high-sensitivity C-reactive protein; HSSDD=Hidradenitis Suppurativa 
Symptom Daily Diary; HSSQ=Hidradenitis Suppurativa Symptom Questionnaire; PDILI=potential drug-
induced liver injury; PHQ-9=Patient Health Questionnaire Depression Module; QOL=quality of life; 
TB=tuberculosis; TEAE=treatment-emergent adverse event 
4 
STUDY DESIGN 
4.1 
Overall design 
HS0004 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, pivotal study 
evaluating the efficacy and safety of bimekizumab in study participants with moderate to severe 
HS. Study participants meeting the inclusion criteria who do not meet any exclusion criteria will 
complete a Screening Period of 14 days to up to 5 weeks; a double-blind, 48-week Treatment 
Period comprising a 16-week Initial Treatment Period and 32-week Maintenance Treatment 
Period; and a 20-week Safety Follow-up (SFU) Period following the final injection of 
investigational medicinal product (IMP) if study participants do not enter a subsequent extension 
study (HS0005) or withdraw prematurely from treatment. 
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Study participants will be randomized in a 2:2:2:1 ratio (stratified by Hurley Stage and current 
antibiotic use) to 1 of 3 dose regimens of bimekizumab or placebo as shown in the schematic 
(Figure 1-1). All doses of IMP will be administered by sc injection. The primary efficacy 
variable at Week 16 is HiSCR50. Study visits will occur at Screening; Baseline (Week 0); 
Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16; and 
 from Week 16 through Week 48 for 
assessments of efficacy, safety, and other measures of QOL/health status/work productivity. An 
SFU visit will be conducted 20 weeks after the last dose of IMP for participants who do not enter 
the extension study, or who are prematurely withdrawn from the study. 
4.1.1 
Screening Period (Weeks -5 to 0) 
The Screening Period will last a minimum of 14 days up to a maximum of 5 weeks prior to 
randomization. 
4.1.2 
Initial Treatment Period (Weeks 0-16) and Maintenance Treatment 
Period (Weeks 16-48) 
Eligible study participants will be randomized in a 2:2:2:1 ratio as noted in the Study Schema to: 
• Bimekizumab 
 from Weeks 0 to 48 
• Bimekizumab 
 from Weeks 0 to 48 
• Bimekizumab 
 to Week 16, continuing on 
 from Weeks 16 to 48 
• Placebo to Week 16, continuing on bimekizumab 
 from Weeks 16 to 48 
4.1.3 
Safety Follow-up Visit 
All study participants not continuing in the extension study, including those withdrawn from 
IMP as well as those completing all study visits, will have an SFU Visit 20 weeks after their final 
dose of IMP. 
4.1.4 
Visit Windows 
Visit windows are ±3 days (based on the date of the first dose). The minimum number of days 
between 2 consecutive injection visits is 8 days (eg, Visit 2 +3 days occurs on Day 17; Visit 
4 -3 days occurs on Day 25). However, the minimum of 8 days between injections may be used 
only 1 time in the Initial Treatment Period and 1 time in the Maintenance Treatment Period, if 
needed. The study participant should be dosed according to the administration schedule 
thereafter. The 20-week SFU Visit window is ±7 days (based on the date of the final dose). 
4.2 
Scientific rationale for study design 
A randomized, double-blind, placebo-controlled study design has been selected to demonstrate 
efficacy and safety of bimekizumab for regulatory approval. The study population will include 
adults with moderate to severe HS. The inclusion and exclusion criteria were designed to ensure 
the safety of study participants, and to enroll a broad HS study participant population 
representative of clinical practice in terms of disease severity and morbidity (physical disability 
and discomfort) that warrants therapy with a systemic agent. Considering that study participants 
with moderate to severe HS are treated with different antibiotics, systemic tetracyclines have 
been selected as the most appropriate class of antibiotics for the study based on the current 
therapeutic guidelines for HS.  
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The primary efficacy outcome measure (HiSCR50) is a validated clinical outcome measure for 
evaluating efficacy in study participants with moderate to severe HS. 
In addition, a core domain set for HS study outcome established for HS calls for the concurrent 
measurement of 5 core outcome domains agreed by both patients and health care providers: pain, 
physical signs, HS specific quality of life, global assessment and progression of course. A sixth 
domain, symptoms, has also been recommended by the Steering Group because it received 
strong support from the patient stakeholder group (Thorlacius, 2018). 
The Screening Period is included to ensure eligibility criteria are met, including collection of 
laboratory data, verification that the doses of concomitant and allowable medications are stable, 
and to enable washout of any medications not permitted for use during the study. 
The randomization allocation and sample sizes have been selected to (1) maximize exposures to 
bimekizumab test doses/regimens, (2) ensure adequate power to demonstrate superiority of 
bimekizumab to placebo for the primary endpoint (HiSCR50) at Week 16, and (3) have sufficient 
sample size to detect statistically significant differences between treatments as specified in the 
secondary endpoints at Week 16. 
An initial treatment period of 16 weeks will be used to demonstrate the efficacy of bimekizumab 
over placebo. The 32-week Maintenance Treatment Period will collect information on safety and 
efficacy beyond initial treatment. 
The Maintenance Treatment Period is designed to assess the durability of response of the study 
endpoints and to provide sufficient longer-term (up to 48 weeks, including the Initial Treatment 
Period) safety and exposure to bimekizumab for regulatory filings. Continuous (up to 48 weeks) 
exposure to both the 
 bimekizumab 
 and 
 bimekizumab 
 dose regimens 
allow for the following assessments: 
• Durability of response and longer-term safety 
• Optimal dosing interval for maintenance treatment 
This period will also allow study participants who received placebo in the Initial Treatment 
Period to begin receiving bimekizumab at Week 16 in the randomized, controlled Maintenance 
Treatment Period of the study. 
4.3 
Justification for dose 
The pathophysiology of HS is an active area of research, with investigations targeting 
identification of the cytokines and immune pathways in HS. Recent reviews on the subject 
indicate the potential diversity of these inflammatory pathways and mediators, and the impact on 
treatment response to various pharmacologic interventions. As concluded by Frew, Hawkes, and 
Krueger, no current schema accurately predicts treatment efficacy to date (Prens, 2015; Frew, 
2018). Furthermore, the inflammatory burden in HS seems greater than other autoinflammatory 
conditions affecting the skin (Van der Zee, 2011; Riis, 2015, Martorell, 2015). These data, and 
the current pharmacologic treatment of HS suggest that a more intensive dosing regimen (ie, 
dose level and/or frequency of administration) may be needed for the treatment of HS. 
Consistent with the above literature, a 
 dose regimen of bimekizumab is being 
evaluated in the Phase 3 program for HS. This dose regimen is higher than those used in other 
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indications currently in Phase 3 development for bimekizumab; however, HS0001 results 
revealed that bimekizumab 320mg Q2W demonstrated consistent, clinically meaningful efficacy 
in the treatment of HS when compared to placebo, with safety results consistent with those of 
studies of bimekizumab in other indications in development. In addition, pharmacokinetic (PK) 
data from HS0001 demonstrated that study participants with HS have a lower exposure to 
bimekizumab than study participants with PSO given the same dose and regimen, thus 
necessitating higher bimekizumab doses for HS (maximum monthly bimekizumab dose of 
640mg). 
In addition to the 320mg Q2W dose used in HS0001, the highest dose being used in other 
bimekizumab indications (PSO dose regimen of 
) is being used in this study. The 
assessment of both the
 and 
 dosing frequencies in this study will help determine the 
optimal monthly bimekizumab dose required to sustain efficacy with long-term (maintenance) 
treatment. 
4.4 
End of study definition 
A study participant will be considered to have completed the study if he or she completed the 
Week 48 visit. 
The end of the study is defined as the date of the last scheduled procedure shown in the Schedule 
of Activities (Table 1‒1) for the last study participant in the study globally, including the SFU, as 
applicable. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be at least 18 years of age, at the time of signing the informed consent. If a 
study participant is under the local age of consent and is at least 18 years of age, written 
informed consent will be obtained from both the study participant and the legal 
representative. 
Type of participant and disease characteristics 
2a. Study participants must have a diagnosis of HS based on clinical history and physical 
examination for at least 6 months prior to the Baseline visit; diagnosis must be verifiable 
through medical notes and documentation. 
3. Study participant must have HS lesions present in at least 2 distinct anatomic areas (eg, left 
and right axilla), 1 of which must be at least Hurley Stage II or Hurley Stage III at both the 
Screening and Baseline visits. 
4. Study participant must have moderate to severe HS defined as a total of ≥5 inflammatory 
lesions (ie, number of abscesses plus number of inflammatory nodules) at both the Screening 
and Baseline visits. 
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5a. Study participant must have had a history of inadequate response to a course of a systemic 
antibiotics for treatment of HS at the Screening Visit as assessed by the Investigator through 
study participant interview and review of medical history; inadequate response must be 
verifiable through medical notes and documentation. Study participants who meet any of the 
following are NOT automatically excluded from the study: 
− Demonstrated intolerance to (or during therapy became intolerant to) systemic antibiotics 
− Had a contraindication to systemic antibiotics 
− Responded to course(s) of systemic antibiotic(s) and subsequently exhibited recurrence 
after discontinuation of the antibiotic 
Sex 
6. Males and females may be study participants. 
− A female study participant is eligible to participate if she is not pregnant (see Appendix 4 
[Section 10.4]), not breastfeeding, and at least one of the following conditions applies: 
◦ 
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
OR 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the 
treatment period and for at least 20 weeks after the last dose of IMP. 
Informed consent 
7. Study participant was capable of giving signed informed consent as described in Appendix 1 
which includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
5.2 
Exclusion criteria 
Study participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Study participant has any medical or psychiatric condition that, in the opinion of the 
Investigator, could jeopardize or would compromise the study participant’s ability to 
participate in this study as determined by the Investigator based on protocol-required 
assessments. 
HS, Skin-Specific, and Other Inflammatory Disease 
2. Study participant has a draining tunnel count of >20 at the Baseline Visit. 
3. Study participant has any other active skin disease or condition (eg, bacterial cellulitis, 
candida intertrigo, extensive condyloma) that may, in the opinion of the Investigator, 
interfere with the assessment of HS. 
4. Study participant has a diagnosis of sarcoidosis, systemic lupus erythematosus, or active 
IBD. Note: Study participants with a diagnosis of Crohn’s disease or ulcerative colitis are 
allowed if they have no active symptomatic disease at Screening or Baseline. 
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5. Study participant has a primary immunosuppressive condition, including taking 
immunosuppressive therapy following an organ transplant, or has had a splenectomy. 
Other Medical Conditions 
6. Female study participant who is breastfeeding, pregnant, or plans to become pregnant during 
the study or within 20 weeks following the final dose of IMP. 
7. Study participant has an active infection or history of infection(s) as follows: 
− Any infection requiring systemic treatment within 14 days prior to Baseline 
− A serious infection, defined as requiring hospitalization or intravenous anti-infective(s) 
within 2 months prior to the Baseline Visit 
− A history of opportunistic, recurrent, or chronic infections that, in the opinion of the 
Investigator, might cause this study to be detrimental to the study participant. 
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. Study participant has any of the following: 
− Known active TB disease 
− History of active TB involving any organ system unless adequately treated according to 
World Health Organization/Centers for Disease Control and Prevention therapeutic 
guidance and proven to be fully recovered upon consult with a TB specialist 
− Latent TB infection (LTBI). Participants with LTBI diagnosed during Screening must 
have completed a course of prophylaxis prior to IMP dosing. Participants can be 
rescreened after completion of a full course of prophylaxis plus a wash-out of least 
5 half-lives of the prophylactic medication(s) prior to Baseline to avoid any interference 
with the study efficacy measurements (eg, concomitant antibiotics). Prophylaxis should 
be in accordance with applicable clinical guidelines and TB specialist judgment based on 
the origin of infection. 
− High risk of exposure to TB infection 
− Current pulmonary nontuberculous mycobacterial (NTM) infection or history of 
pulmonary NTM infection unless proven to be fully recovered 
Note: For further information relating to definitions of known active TB, past history of TB, 
LTBI, high risk of acquiring TB infection and NTM infection refer to Section 8.2.6. 
9. Study participant has an acute or chronic hepatitis B virus, hepatitis C virus (HCV), or 
human immunodeficiency virus (HIV) infection. Study participants who have evidence of, or 
tested positive for, hepatitis B or hepatitis C will be excluded. A positive test for hepatitis B 
virus is defined as: 1) positive for hepatitis B surface antigen, or 2) positive for anti-hepatitis 
B core antibody. A positive test for HCV is defined as: 1) positive for hepatitis C antibody, 
and 2) positive via a confirmatory test for HCV (for example, HCV polymerase chain 
reaction). 
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10. Study participants with concurrent malignancy are excluded. Study participants with a 
history of malignancy within the past 5 years prior to the Screening Visit are excluded, 
EXCEPT if the malignancy was a cutaneous squamous or basal cell carcinoma, or in situ 
cervical cancer that has been treated and is considered cured. 
11. Study participant has a history of a lymphoproliferative disorder including lymphoma or 
current signs and symptoms suggestive of lymphoproliferative disease. 
12. Study participant has had major surgery within the 3 months prior to the Baseline Visit, or 
has planned major surgery after entering the study. 
13. Study participant has any systemic disease (ie, cardiovascular, neurological, renal, liver, 
metabolic, gastrointestinal, 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. 
14. Study participant has had a myocardial infarction or stroke within the 6 months prior to the 
Screening Visit. 
15. Study participant has a history of chronic alcohol or drug abuse within 6 months prior to 
Screening as evaluated by the Investigator based on medical history, interview, and/or results 
of the Screening urine drug screen. 
16a. Study participant has the 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: 
− Study participant has a history of a suicide attempt within the 5 years prior to the 
Screening Visit. Study participants with a history of a suicide attempt more than 5 years 
ago should be evaluated by a mental healthcare practitioner before enrolling into the 
study. 
− 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. 
17. Study participant has presence of moderately severe major depression or severe major 
depression indicated by a score of ≥15 using the screening Patient Health Questionnaire 
Depression Module (PHQ-9). Medication used to treat depression should be stable for 
8 weeks prior to Baseline. 
18. Study participant has a known hypersensitivity to any components of bimekizumab or 
comparative drugs as stated in this protocol. 
Prior/Concomitant therapy 
19a. Study participant has had prior treatment with an IL-17 biologic response modifier or has 
participated in IL-17 biologic response modifier study unless an appropriate washout has 
been performed since the last dose of IMP (within 6 months prior to the Baseline Visit or 
5 half-lives [whichever is greater]). 
20. Study participant received prescription topical therapies for the treatment of HS within 
14 days prior to the Baseline Visit. 
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21. Study participant is currently receiving systemic nonbiologic or biologic therapies for HS 
with potential therapeutic impact for HS. Note: If study participant received systemic 
nonbiologic or biologic therapies for HS and stopped these treatments, washout periods 
should be applied as shown in Table 6‒3. Note: this does not apply to study participants who 
may be eligible for randomization into the antibiotic strata. 
22. If study participant is using concomitant, non-opioid analgesics for HS-related or 
non-HS-related pain as permitted by protocol, they should be on a stable (scheduled) dose for 
at least 14 days prior to the Baseline Visit and anticipate continuing that dose through 
Week 16 unless a decrease in dose is warranted based on symptoms. Opioid analgesics are 
excluded. Note: As needed (PRN) use is not considered a stable dose, but (for example) 
taking a nonsteroidal anti-inflammatory drug (NSAID) 3 times per week, every week is 
considered a stable dose. 
23. Study participant has received any live (including attenuated) vaccination within the 8 weeks 
prior to the Baseline Visit (eg, inactivated influenza and pneumococcal vaccines are allowed, 
but nasal influenza vaccination is not permitted). Live vaccines are not allowed during the 
study, including the SFU Period (20 weeks after the last dose of IMP). 
24. Study participant has received Bacillus Calmette-Guerin vaccination within 1 year prior to 
IMP administration. 
Prior/Concurrent clinical study experience 
25. Study participant has previously participated in this study or study participant has previously 
been assigned to treatment in a study of the medication under investigation in this study, and 
received at least 1 dose of IMP (including placebo). 
26. Study participant is currently participating in another study of a systemic medication under 
investigation, including SFU. Study participant must be washed out of the medication as 
indicated in Table 6‒3. 
27. Study participant is currently participating in another study of a topical medication under 
investigation, including SFU. Study participant must be washed out of the medication for 
4 weeks prior to the Baseline Visit. 
28. Study participant is currently, or was within the 4 weeks prior to the Baseline Visit, 
participating in another study of a medical device under investigation. 
Diagnostic assessments 
29. Study participant has laboratory abnormalities at Screening, including any of the following: 
− ≥3× the upper limit of normal (ULN) of any of the following: alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) 
− Bilirubin >1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
− White blood cell count <3.00×103/μL 
− Absolute neutrophil count <1.5×103/μL 
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− Lymphocyte count <500 cells/μL 
− Hemoglobin <8.5g/dL 
Note: 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, study participants whose results remain outside this 
threshold should not be randomized. 
30. Study participant has any other laboratory abnormality, which, in the opinion of the 
Investigator, will prevent the study participant from completing the study or will interfere 
with the interpretation of the study results. 
Other exclusions 
31. Study participant is a UCB employee or is an employee of third-party organizations involved 
in the study. 
32. Study participant and/or his or her immediate family member is an employee, volunteer, or 
other worker at the investigative site either affiliated or not affiliated with this study. 
Immediate family is defined as a spouse, parent, child, or sibling whether biological or 
legally adopted. 
5.3 
Lifestyle restrictions 
Not applicable to this study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized to study treatment. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse events (SAE). Individuals who do not meet the 
criteria for participation in this study (screen failure) may be rescreened, following discussion 
with the Medical Monitor or Sponsor’s study physician. 
Participants who are rescreened should be assigned a new participant number for rescreening. 
A study participant may be rescreened 1 time for reasons including, but not limited to, the 
following: 
• Individual laboratory screening tests for which the results are exclusionary can be retested 
(eg, tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be 
repeated once for confirmation. Test can also be repeated during rescreening.) 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. 
• Eligibility assessments that could not be completed as planned (eg, for technical reasons) 
within the defined Screening Period of 5 weeks without approval by Medical Monitor. 
• Abnormal ECG results. 
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• Did not meet the required washout period for concomitant medications. 
• Study participant needs to complete a full course of antibiotic therapy for LTBI plus a 
wash-out of least 5 half-lives of the prophylactic medication(s) prior to Baseline as described 
in Exclusion Criterion 8 (Section 5.2). 
• If the study participant requires an incision and drainage procedure for a HS lesion(s) during 
the Screening Period, the study participant should be screen failed. The participant can be 
rescreened when the lesion is considered healed. The study participant must have completed 
antibiotics/analgesic treatment if required for the procedure before rescreening as described 
in Table 6‒3. 
Study participants who fail to meet the eligibility criteria for PHQ-9, eC-SSRS, or the TB 
questionnaire are not allowed to be rescreened. 
The Medical Monitor must be contacted for confirmation of rescreening/retesting in all other 
cases. 
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment, marketed product, placebo, or 
medical device intended to be administered to a study participant according to the study protocol. 
6.1 
Treatments administered 
Eligible study participants will be randomized in a 2:2:2:1 ratio as noted in the Study Schema 
(Figure 1-1). 
A summary of the treatments administered is provided in Table 6‒1. 
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Table 6‒1: 
Study medications administered 
ARM Name 
Bimekizumab 
Placebo 
Intervention name 
Bimekizumab 
Placebo 
Type 
Biologic 
Drug 
Dose formulation 
Solution for injection (pre-filled 
1-mL syringe) 
Solution for injection (pre-filled 
1-mL syringe) 
Unit dose strengths 
160mg/mL 
0.9% sodium chloride aqueous 
solution (physiological saline, 
preservative free) of US 
Pharmacopoeia/European 
Pharmacopoeia quality 
appropriate for injection; same 
volume to maintain blinding to 
the study participant 
Dosage levels 
 
Not applicable 
Route of administration 
Subcutaneous injection 
Subcutaneous injection 
Use 
Experimental 
Placebo comparator 
Investigational Medicinal 
Product and 
Non-Investigational 
Medicinal Product 
Investigational Medicinal Product 
Investigational Medicinal Product 
Sourcing 
Provided centrally by the 
Sponsor. 
Provided centrally by the 
Sponsor. 
Packaging and labeling 
Study Intervention will be 
provided in a kit. Each kit will be 
labeled as required per country 
requirement 
Study Intervention will be 
provided in a kit. Each kit will be 
labeled as required per country 
requirement 
Current/Former names or 
aliases 
Bimekizumab 
Not applicable 
Because of differences in the dosing schedules and in order to maintain blinding, all study 
participants will receive 2 injections sc 
 from Week 0 to Week 46 as depicted in 
Table 6‒2. 
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6.2 
Preparation, handling, storage, and accountability requirements 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only study participants enrolled in the study may receive study treatment and only authorized 
site staff may supply or administer study treatment. All study treatments must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and authorized site 
staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
Further guidance and information for the final disposition of unused study treatment are provided 
in the IMP Handling Manual. 
6.2.1 
Drug accountability 
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-participant basis and will serve as source documentation during the course of the study. 
Details of any IMP lost, damaged (due to breakage or wastage), not used, partially used, 
disposed of at the study site, or returned to the Sponsor or designee must also be recorded on the 
appropriate forms. All supplies and pharmacy documentation must be made available throughout 
the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the IMP is used only in accordance with the protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired IMP must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB standard operating procedures 
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. 
6.3 
Measures to minimize bias: randomization and blinding 
6.3.1 
Randomization and numbering of participants 
An interactive response technology (IRT) system will be used for assigning eligible study 
participants to a treatment regimen (as applicable) based on a predetermined production 
randomization and/or packaging schedule provided by UCB (or designee). The randomization 
schedule will be produced by the IRT vendor. The IRT will generate individual assignments for 
kits of IMP, as appropriate, according to the visit schedule. 
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To enroll a study participant at Screening, the Investigator or designee will contact the IRT and 
provide brief details about the study participant to be enrolled. Each study participant will 
receive a unique number assigned at Screening that serves as the study participant identifier 
throughout the study. The study participant number will be required in all communication 
between the Investigator or designee and the IRT regarding a particular study participant. Study 
participant numbers and kit numbers will be tracked via the IRT. 
To randomize a study participant, the Investigator or designee will contact the IRT and provide 
brief details about the study participant to be randomized. The IRT will automatically inform the 
Investigator or designee of the study participant’s randomization number. The IRT will allocate 
kit numbers to the study participant based on the study participant number during the course of 
the study. The randomization number must be incorporated into the case report form (CRF). 
6.3.2 
Procedures for maintaining and breaking the treatment blind 
6.3.2.1 
Maintenance of study treatment blind 
All study participant treatment details will be allocated and maintained by the IRT system. 
The IRT provider will receive the randomization code at the start of the study. 
Due to differences in presentation between bimekizumab and placebo treatments, special 
precautions will be taken to ensure study blinding; study sites will have blinded and unblinded 
personnel. Bimekizumab and placebo injections will be administered at the investigational sites 
by unblinded, dedicated study personnel according to the site-specific blinding plan. Unblinded 
study personnel will be responsible for recording the administration information on source 
documents, and administration of the IMP as sc injections. Study site pharmacists or other 
suitably qualified site personnel who are responsible for preparation and administration of IMP 
treatments will have access to treatment allocations for individual study participants via the IRT. 
The unblinded pharmacy monitors from the Contract Research Organization (CRO), and the 
UCB Clinical Trial Supply representative will also have access to the treatment allocations and 
to the drug accountability records, if applicable. 
The following individuals may, as necessary, have access to the randomization code as indicated: 
• Members of the Data Monitoring Committee (DMC) who participate in unblinded sessions 
will be given information about the IMP allocation for those study participants for whom 
data are provided. 
• The unblinded, independent CRO staff supporting preparation of the data outputs for the 
DMC reviews. 
The unblinded study site personnel will not be involved in the study in any way other than 
assuring the IMP is taken from the correct kit and prepared according to the IMP-handling 
manual, and administering the IMP to the study participants. 
In addition, high-sensitivity C-reactive protein (hs-CRP) results will not be reported to any 
blinded study personnel as long as the study remains blinded. 
6.3.2.2 
Breaking the treatment blind in an emergency situation 
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the study participant has been allocated by contacting the IRT. The Investigator is responsible for 
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breaking the treatment blind in case of emergency. All sites will be provided with details of how 
to contact the system for code breaking at the start of the study. The Medical Monitor and/or 
UCB study physician or equivalent should be consulted prior to unblinding, whenever possible. 
The Clinical Project Manager will be informed immediately via the IRT when a code is broken, 
but will remain blinded to specific treatment information. Any unblinding of the IMP performed 
by the Investigator must be recorded in the source documents and on the Study Termination 
electronic CRF (eCRF) page. 
Inadvertent unblinding will be listed as a major protocol deviation. 
6.4 
Treatment compliance 
During the double-blind Initial Treatment and Maintenance Treatment Periods, IMP will be 
administered in the clinic and compliance will be recorded at the visit by study personnel in the 
eCRF. Drug accountability must be recorded on the Drug Accountability form. 
6.5 
Concomitant medications/treatments 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study: 
• Wound care: Concomitant use of wound care dressings on HS wounds is allowed; however, 
options are limited to alginates, hydrocolloids, and hydrogels and use of these will be 
recorded in the eCRF. 
• Lesion care: Concomitant use of saline, water, and/or Vaseline (petroleum jelly) is allowed 
for care of skin lesions and use of these will be recorded in the eCRF. 
• Analgesic therapy: 
− Study participants will be required to wash out of all analgesics for HS-related pain 
14 days prior to Baseline. However, if a study participant is on a stable (scheduled) dose 
of a non-opioid analgesic for HS-related pain, or for a non-HS medical condition (eg, 
osteoarthritis, neuropathic pain), the study participant may continue the analgesic. Opioid 
analgesics (including tramadol) are excluded for any indication. 
Notes: (1) Dose should be stable for 14 days prior to Baseline, and is anticipated to 
remain stable throughout study participation. (2) Dosing PRN is not considered stable, 
but (for example) taking an NSAID 2 or 3 times per week every week is considered a 
stable dose. 
− If a study participant’s pain (HS-related or non–HS-related) worsens after Baseline, the 
study participant may initiate analgesic therapy at any time and/or per local labeling as 
follows: For HS-related pain, permitted analgesics are limited to ibuprofen at a dose of up 
to 800mg orally every 6 hours, not to exceed 3.2g/24 hours; and/or 
acetaminophen/paracetamol as per local labeling. For non-HS-related pain, initiation of 
any new analgesic/treatment must not include exclusionary medications (eg, opioids and 
tramadol), and must be recorded on the eCRF. 
− All analgesic use (start dates, end dates, dose, reason) will be recorded on the eCRF. 
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• Antibiotic therapy: 
− For study participants entering the study in the antibiotic strata, they should be on a stable 
dose and regimen of doxycycline, minocycline, or an equivalent systemic tetracycline for 
28 days prior to Baseline (Visit 2). The dose and regimen should remain stable 
throughout study participation, but at least through Week 16. Antibiotics taken on a PRN 
basis are not considered as a stable dose. After Week 16, participants may receive an 
antibiotic if required in the judgement of the Investigator.  Also see Section 6.5.3.1 for 
details on systemic antibiotic rescue medication. 
− All antibiotic use (start dates, end dates, dose, reason) will be recorded on the eCRF. 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications and therapies are prohibited during the study (also see 
Table 6‒3): 
• All biologic therapy with a potential therapeutic impact on the disease being studied, 
including those listed in Table 6‒3. 
• Phototherapy (psoralen and ultraviolet A and/or ultraviolet B) or photochemotherapy. 
• Immunomodulatory therapy, including topical or systemic steroids except as noted in 
Section 6.5.3.1 (Rescue Medications/Lesion Intervention), and Table 6‒3. 
• Topical and systemic therapies for HS (see Table 6‒3). 
• Surgical or laser intervention for an HS lesion except as outlined in Section 6.5.3.1 (Rescue 
Medications/Lesion Intervention). 
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Table 6‒3: 
Exclusions for prior medications 
Drug class 
Exclusion criteria 
Systemic antibiotics 
Used within 2 weeks prior to the Baseline Visit. 
Note: See exception for permitted, stable doses of 
antibiotics in Section 6.5.1. 
Systemic retinoids 
Used within 4 weeks prior to the Baseline Visit 
Systemic treatment (non-biologic) 
• 
Apremilast 
• 
Systemic immunosuppressant agents (eg: 
methotrexate, cyclosporine, azathioprine, 
thioguanine) 
• 
Systemic fumarate 
• 
Systemic oral or injectable corticosteroids 
• 
Phototherapy and radiotherapy (eg, psoralen 
and ultraviolet A and/or ultraviolet B) or 
photoradio/chemotherapy 
Used within 4 weeks prior to the Baseline Visit. 
Note: See exception for permitted, stable doses of 
antibiotics in Section 6.5.1. 
Anti-tumor necrosis factors (including 
biosimilars) 
adalimumab, etanercept, certolizumab, 
golimumab, infliximab 
Used within 12 weeks prior to the Baseline Visit. 
Note: For etanercept, used within 1 month prior to 
the Baseline Visit. 
Other biologics 
   Abatacept 
   Anakinra 
   Natalizumab 
   Belimumab 
   Tocilizumab 
   Efalizumab 
Or other biologics approved by regulatory 
agencies after the protocol is approved 
Used within 12 weeks prior to the Baseline Visit 
Note: for other biologics approved by regulatory 
agencies after the protocol is approved: Washout 
of 6 months prior to the Baseline Visit or 5 
half-lives prior to the Baseline Visit, whichever is 
greater. 
Secukinumab, brodalumab, ixekizumab and other 
IL-17 inhibitors approved by regulatory agencies 
after the protocol is approved 
Washout of 6 months prior to the Baseline Visit or 
5 half-lives prior to the Baseline Visit, whichever 
is greater. 
IL-12, IL-23 inhibitors: 
   Ustekinumab 
   Risankizumab 
   Tildrakizumab 
   Guselkumab 
Or other biologics approved by regulatory 
agencies after the protocol is approved 
Used within 6 months prior to the Baseline Visit 
Note: for other biologics approved by regulatory 
agencies after the protocol is approved: Washout 
of 6 months prior to the Baseline Visit or 5 
half-lives prior to the Baseline Visit, whichever is 
greater. 
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Table 6‒3: 
Exclusions for prior medications 
Drug class 
Exclusion criteria 
Janus kinase inhibitors 
   Tofacitinib 
   Baricitinib 
   Filgotinib 
   Upadacitnib 
Or other janus kinase inhibitors approved by 
regulatory agencies after the protocol is approved 
Used within 12 weeks of the Baseline Visit or 5 
half-lives prior to the Baseline Visit, whichever is 
greater 
Any other systemic HS drug under investigation 
(or approved after the protocol is approved) 
Used within 12 weeks or 5 half-lives prior to the 
Baseline Visit, whichever is greater 
Rituximab 
Used within 2 years of the Baseline Visit 
 Topical drugs for HS (including intralesional 
corticosteroids, over-the-counter and prescription 
drugs, as well as disinfectants for skin lesions, eg, 
chlorhexidine, povidone iodine) 
Used within 14 days of the Baseline Visit 
Topical corticosteroids (in HS-affected areas) for 
dermatological use 
Used within 14 days of the Baseline Visit. Note: 
Topical steroids in non-HS affected areas are 
permitted. 
Herbal medications for HS 
Used within 14 days of the Baseline Visit 
Vaccines 
Administration of live (including attenuated) 
vaccines is not allowed within 8 weeks prior to 
Baseline, during the conduct of the study, and for 
20 weeks after the final dose of IMP (see 
Exclusion Criteria #23 and #24). Administration 
of inactivated vaccines is allowed during the study 
at the discretion of the Investigator. 
Administration of any other vaccine not 
mentioned above may be allowed following 
discussion with the Medical Monitor. 
Analgesics 
See Section 6.5.1. 
Spironolactone 
Permitted if indicated for non-HS-related 
condition (eg, polycystic ovary syndrome); and if 
study participant meets all other entry criteria. 
Study participant must be on a stable dose for at 
least 28 days prior to the Baseline visit. 
Metformin 
Permitted if indicated for non-HS-related 
condition (eg, diabetes mellitus); and if study 
participant meets all other entry criteria. Study 
participant must be on a stable dose for at least 
28 days prior to the Baseline visit. 
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Table 6‒3: 
Exclusions for prior medications 
Drug class 
Exclusion criteria 
Finasteride and other 5-reductase inhibitors 
Permitted if indicated for non-HS-related 
condition (eg, benign prostatic hypertrophy); and 
if study participant meets all other entry criteria. 
Study participant must be on a stable dose for at 
least 28 days prior to the Baseline visit. 
HS=hidradenitis suppurativa; IL=interleukin; IMP=investigational medicinal product 
6.5.3 
Rescue medication 
The Sponsor will not supply rescue medication. The following rescue medications may be used: 
6.5.3.1 
Antibiotic Rescue Medication/Antibiotics 
Any systemic antibiotic that is initiated (new antibiotic or change in the dose/type of current 
antibiotic) on or after Baseline (first day of study drug administration) will be considered rescue 
medication for both the Initial Treatment Period and Maintenance Treatment Period. If a newly 
initiated systemic antibiotic (or increase in dose/type of antibiotic) is required during the Initial 
Treatment Period based on disease flare or other extenuating circumstances, the Investigator 
should discuss the decision with the Medical Monitor. 
6.5.3.2 
Rescue Medications/Lesion Intervention 
There are no absolute restrictions on the use of rescue medications for study participants whose 
HS deteriorates during the study. While the objectives of the study should be protected as much 
as possible through observance of the restrictions detailed above in Section 6.5, the well-being of 
the study participant will always take priority; study participants should be managed as deemed 
appropriate by the Investigator. 
In the event an acutely painful lesion occurs that requires an immediate intervention, 
Investigators will have the option to perform interventions. Interventions can include analgesics 
for a limited period of time (see below), intralesional injections of triamcinolone, and/or incision 
and drainage of the abscess. Intralesional injections of triamcinolone (up to 20mg across all 
lesions at a given visit, and using a concentration of no more than 20mg/mL [suspension for 
injection]) must be consistent with the maximum number of interventions described below and 
clinical practice. Concomitant use of wound care dressings is permitted; however, options are 
limited to alginates, hydrocolloids, and hydrogels. Concomitant medications associated with the 
lesion intervention(s) must be captured in source documents and on the appropriate eCRF. 
Any analgesic that is initiated (new analgesic, new class of analgesic, increased dose of an 
analgesic stable since Baseline, regardless of duration of treatment) after Baseline (first day of 
study drug administration) will be considered rescue pain medication for the Initial Treatment 
Period and Maintenance Treatment Period (Weeks 0 to 48). 
A total of 2 protocol-allowed interventions are permissible during the Initial Treatment Period 
(from Baseline Visit to Week 16). Do not include analgesic rescue treatment in the number of 
protocol-allowed interventions. An intervention can occur on maximally 2 different lesions at the 
same visit, or on the same lesion at 2 different study visits. The same lesion cannot be treated 
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2 times at the same visit. If a study participant requires more than 2 interventions within the first 
16 weeks of the study, then the study participant should be discontinued from the study. 
During the Maintenance Treatment Period (Weeks 16 to 48), a maximum of 2 interventions 
every 4 weeks are permitted. Do not include analgesic rescue treatment in the number of 
protocol-allowed interventions. An intervention can occur on 2 different lesions at the same visit 
or on the same lesion at 2 different study visits. Within each 4-week period, the same type of 
intervention cannot be used 2 times on the same lesion. If a study participant requires more than 
2 interventions within a 4-week period, or has 2 of the same interventions on the same lesion 
within that period, then the study participant should be discontinued from the study. 
6.6 
Dose modification 
Dose modification is not applicable in this study. 
6.7 
Criteria for study hold or dosing stoppage 
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. See Section 9.7 for details on 
interim analyses to be evaluated by the DMC (ie, study may be stopped for futility but not for 
superior efficacy). 
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 Institutional Review Board (IRB)/ Independent Ethics Committee (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 or destruction of all unused 
IMP and other material in accordance with UCB procedures for the study. 
Detailed procedures for reporting SAEs and other safety events which may meet study hold 
criteria are provided in Appendix 8. 
6.8 
Treatment after the end of the study 
Study participants who complete HS0004 will have the option of enrolling in a Phase 3, 
multicenter, extension study (HS0005). 
Study participants who elect not to enroll in HS0005 at Week 48 will be scheduled to have the 
SFU Visit 20 weeks after the final injection of IMP. During the SFU, if study participants’ HS 
deteriorates, the Investigator may consider standard of care for HS treatment after discussion 
with the Medical Monitor or UCB study physician. Note that the half-life of bimekizumab must 
be considered in selection of appropriate HS treatments during the SFU period. All concomitant 
medications and HS interventions administered during the SFU will be recorded on the 
appropriate eCRF pages. 
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7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
Study medication will be stopped if the study participant develops a medical condition, adverse 
event (AE), or laboratory abnormality that, in the opinion of the Investigator, compromises the 
safety of the study participant or his or her ability to continue participation in the study. Study 
participants who are discontinued from IMP should be encouraged by the Investigator to return 
for all scheduled visits through Week 48, and the SFU Visit (if the Week 48 Visit is ≥20 weeks 
after the final dose of IMP, the SFU Visit is not required). Any study participant who 
discontinues IMP but continues in the study should be discussed with the Medical Monitor or 
UCB study physician. 
In all cases the study participant should be followed until the condition has resolved as agreed by 
the Investigator and the UCB study physician. Investigators should contact the Medical Monitor 
and/or UCB study physician, in advance whenever possible, to discuss the withdrawal of a study 
participant. 
Study medication will be stopped if the study participant has a confirmed positive coronavirus 
disease 2019 (COVID-19) test result or a suspected COVID-19 infection. Study medication can 
be resumed after the participant’s recovery from COVID-19, based on the Investigator’s clinical 
judgement. All such cases must be discussed with the Medical Monitor or UCB study physician. 
7.1.1 
Study participant does not achieve partial response 
If a study participant does not achieve a partial response (defined as a ≥25% reduction in AN 
count from Baseline [Week 0]) at any visit from Week 32 to 46, the Investigator should contact 
the Medical Monitor to discuss whether the study participant should continue on study. 
7.1.2 
Potential drug-induced liver injury IMP discontinuation criteria 
Study participants 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. 
7.1.2.1 
PDILI Discontinuation Criteria 
The PDILI criteria below require immediate discontinuation of IMP for study participants with 
either of the following (see Section 10.6.2.1): 
• ALT or AST ≥8×ULN 
• ALT or AST ≥3×ULN and coexisting total bilirubin ≥2×ULN 
Similarly, the PDILI criterion below requires immediate discontinuation of IMP for: 
• Study participants with ALT or AST ≥3×ULN 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%). 
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If a nondrug-related cause for the symptoms can be confirmed, these study participants may 
resume IMP administration after discussion with the Medical Monitor and/or UCB study 
physician, but only when the requirements for rechallenge with IMP as provided in 
Section 10.6.2.1 are followed. 
The PDILI criterion below allows for study participants to continue on IMP at the discretion of 
the Investigator. 
• Study participants with ALT or AST ≥5×ULN and <8×ULN, total bilirubin <2×ULN, 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 10.6 (Appendix 6) with repeat tests 
performed in 2 weeks. Upon retest, if ALT or AST values have reduced to <5×ULN, the study 
participant can continue with the study. However, if ALT or AST remains ≥5×ULN and 
<8×ULN after retest, IMP should be temporarily withheld and study participant should undergo 
a repeat test in 2 weeks. If ALT or AST values remain ≥5×ULN even after the second retest, then 
the study participant should be permanently withdrawn from IMP and should be followed for 
possible PDILI. 
If study participants are unable to comply with the applicable monitoring schedule, IMP must be 
discontinued immediately. 
Investigators should attempt to obtain information on study participants in the case of IMP 
discontinuation to complete the final evaluation. Study participants 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 study 
participant withdrawal (if applicable), must be recorded in the source documents. The eCRF 
must document the primary reason for IMP discontinuation. 
7.1.2.1.1 
Follow-up evaluation 
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 10‒1. 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 study physician, as needed. 
7.1.3 
Treatment interruptions 
If a study participant is found to be persistently noncompliant (for example, missing 2 or more of 
the doses in the Initial Treatment Period or 3 or more doses during Maintenance Treatment 
Period) the Sponsor, in conjunction with the Investigator, will make a decision as to whether the 
study participant should be withdrawn from the study. 
Note: Doses of IMP that were missed due to a reasonable interfering AE that does not allow 
administration of IMP due to safety reasons will not be considered for the evaluation of study 
participant discontinuation. Evaluation of the reasonability of the AE should be discussed 
immediately with the Medical Monitor. 
Any participant who develops a clinically important infection or recurrent infections not 
responsive to standard therapy during the study must discontinue IMP until resolution of the 
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infection. The Investigator should use clinical judgement in deciding whether the participant 
should restart IMP and contact the Medical Monitor and UCB study physician to confirm the 
participant’s suitability for continued participation in the study.  
7.2 
Participant discontinuation/withdrawal from the study 
Note: For female study participants, please see Section 8.3.5 for pregnancy that occurs during the 
study as evidenced by a positive pregnancy test. 
Study participants are free to withdraw from the study at any time, without prejudice to their 
continued care. 
A study participant may withdraw from the study at any time at his or her own request, or may 
be withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, 
or administrative reasons. 
If the study participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a study participant withdraws from the study, he or she may request destruction of any samples 
taken and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Activities (Table 1‒1) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
If a study participant does not achieve a partial response (defined as a ≥25% reduction in AN 
count from Baseline [Week 0]) at any visit from Week 32 to 46, the Investigator should contact 
the Medical Monitor to discuss whether the study participant should continue on study. 
Study participants will be withdrawn from the study, after being encouraged to complete the 
Premature End of Treatment (PEOT) and the SFU Visit if either of the following events occur: 
1. Study participant withdraws his or her consent. 
2. The Sponsor or a regulatory agency requests withdrawal of the study participant. 
Study participants should be withdrawn from IMP and encouraged by the Investigator to return 
for all scheduled visits through Week 48, and the SFU Visit (if the Week 48 Visit is ≥20 weeks 
after the final dose of IMP, the SFU Visit is not required) if any of the following events occur: 
1. Study participant develops an illness that would interfere with his or her continued 
participation. 
2. Study participant is noncompliant with the study procedures or medications in the opinion of 
the Investigator. 
3. Study participant takes prohibited concomitant medications as defined in this protocol 
(Section 6.5.2) that may present a risk to the safety of the participant or the integrity of the 
study data, in the opinion of the Investigator and/or the Medical Monitor and/or UCB study 
physician. 
4. Study participant requires more than the number of protocol-allowed lesion interventions 
(see Section 6.5.3.2). 
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5. Study participant has a clinical laboratory value meeting any of the following criteria: 
a. Hepatotoxicity as described in Section 7.1.2. 
b. A laboratory value meeting any of the following criteria: 
− Absolute neutrophil count <1.0 x103/μL 
− Absolute lymphocyte count <200 cells/μL 
Study participants 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 participant must be 
discontinued from the IMP. If the repeat absolute neutrophil count or absolute lymphocyte 
count is above the allowable values, the participant may continue to receive IMP. 
6. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test (see Section 8.3.5 for more information regarding pregnancies). 
7. A study participant considered as having either a suspected new LTBI or who develops 
active TB or an NTM infection during the study (including but not limited to, conversion 
demonstrated by interferon gamma release assay [IGRA] or other diagnostic means) must be 
immediately discontinued from IMP. 
− The study participant must immediately be permanently withdrawn from the study if 
further examinations result in a diagnosis of the following: 
− active TB or 
− an NTM infection, or 
− latent TB infection and study participant does not initiate TB prophylactic therapy, 
prematurely discontinues TB prophylactic therapy, or, in the opinion of the 
Investigator or Sponsor, is noncompliant with TB prophylactic therapy. 
The PEOT Visit must be scheduled as soon as possible, but not later than the next regular 
visit. 
− If the study participant is diagnosed with LTBI during the study and desires to continue 
in the study, he or she must immediately discontinue IMP and start TB prophylactic 
therapy. After at least 4 weeks of TB prophylaxis, the IMP can be restarted after 
discussion with the UCB study physician regarding results of laboratory assessments, 
physical examination, and TB questionnaire. The full course of TB prophylaxis treatment 
will be completed during the study. 
Confirmed active TB is an SAE and must be captured on an SAE Report Form and provided 
to the Sponsor in accordance with SAE reporting requirements. As with all SAEs, periodic 
follow-up reports should be completed as per protocol requirements until such time as the TB 
infection resolves. 
Additional information on TB policies is provided in Section 8.2.6. 
8. Study participants with newly diagnosed IBD or with IBD flares during the study must: 
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− Be referred, as appropriate, to a healthcare 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 judgement in deciding whether the study participant should continue on IMP and 
contact the Medical Monitor and UCB study physician to confirm the study participant’s 
suitability for continued participation in the study. 
9 Study participants 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: 
− Active suicidal ideation as indicated by a positive response (“Yes”) to Question 4 of the 
“Since Last Visit” version of the eC-SSRS 
− Moderately severe major depression as indicated by a PHQ-9 score of 15 to 19 if this 
represents an increase of at least 3 points compared to the last visit 
The mental health consultation must be recorded in the study participant’s source 
documentation. 
10. Study participants must be referred immediately to a mental healthcare professional and must 
be withdrawn from the study in case of: 
− Active suicidal ideation as indicated by a positive response (“Yes”) to Question 5 of the 
“Since Last Visit” version of the eC-SSRS. 
− Any suicidal behavior since last visit. 
− Severe major depression as indicated by a PHQ-9 score ≥20. 
The mental health consultation must be recorded in the study participant’s source 
documentation. 
Investigators should contact the Medical Monitor in advance, whenever possible, to discuss the 
withdrawal of a study participant from IMP or from the study. 
Study participants withdrawing from the study who are not continuing for all scheduled visits 
through Week 48, will undergo the PEOT Visit and the SFU Visit 20 weeks after their final dose 
of IMP, as applicable. 
The eCRF must document the primary reason for withdrawal or discontinuation. 
Investigators should contact the Medical Monitor and/or UCB study physician, whenever 
possible, to discuss the withdrawal of a study participant in advance. 
Withdrawn participants will not be replaced. 
7.3 
Lost to follow up 
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
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The following actions must be taken if a study participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the study participant and reschedule the missed visit as soon 
as possible and counsel the study participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the study participant wishes to and/or should 
continue in the study. 
• Before a study participant is deemed lost to follow up, the Investigator or designee must 
make every effort to regain contact with the study participant (at least 1 phone call and 
1 written message to the participant), and document his or her effort (date and summary of 
the phone call and copy of the written message in the source documents), to complete the 
final evaluation (PEOT and SFU, as applicable). All results of these evaluations and 
observations, together with a narrative description of the reason(s) for removing the study 
participant, must be recorded in the source documents. The CRF must document the primary 
reason for withdrawal. 
Should the study participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up documented in the eCRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Table 1‒1). 
Some study-specific assessments may be conducted remotely according to the study protocol 
during a pandemic or other exceptional circumstance (eg, hurricanes) due to the need to 
implement safety measures and guidance from regulatory authorities. In such a situation, which 
may be accompanied by local or global containment or other measures, sites may need to 
prohibit access to study participants and study-related personnel. Study participants’ visits to the 
study site may be replaced by contingency measures. These measures are primarily established to 
ensure the safety of study participants during the course of the study and to maintain the study 
participants’ treatment schedules, if the Investigator considers it appropriate. These measures 
include, but are not limited to, virtual visits or home-nursing visits replacing site visits, eg, 
telemedicine contacts or home-nursing visits when treatment and/or blood sampling is scheduled. 
Any study specific assessments not conducted due to such circumstances must be recorded 
appropriately in the source documents and eCRF. If it is related to the COVID-19 pandemic, 
then it must be captured in the COVID-19 impact eCRF page. The contingency measures are 
described in a contingency plan that will be maintained by UCB for the respective study. The 
contingency measures are shared with the Investigator and the respective study-related personnel 
as soon as there are indications that it is necessary to implement any of the measures. 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Medical Monitor and/or UCB study 
physician immediately upon occurrence or awareness to determine if the study participant should 
continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
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All screening evaluations must be completed and reviewed to confirm that potential study 
participants meet all eligibility criteria. The Investigator will maintain a screening log to record 
details of all study participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable. 
Procedures conducted as part of the study participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may not be utilized for screening or Baseline 
purposes. 
The maximum amount of blood collected from each study participant over the duration of the 
study, including any extra assessments that may be required, will not exceed the usual volume of 
blood taken for a blood donation. Repeat or unscheduled samples may be taken for safety 
reasons or for technical issues with the samples. 
8.1 
Efficacy assessments 
The timing for all assessments described below is specified in Table 1‒1. 
8.1.1 
Lesion count 
The lesion count is defined as an assessment of all the various skin “appearances” that are termed 
“lesions” in HS study participants. The lesion count will include the following: 
• Abscesses (circumscribed collection of purulent exudate frequently associated with swelling 
and other signs of inflammation, such as fluctuance, tenderness, and pain) 
• Draining tunnels (fistulas/sinus tracts) (pathologic passageway connecting to the skin surface 
from dermis or sc tissue/pathologic passageway that develops into a channel to the skin 
surface that drains serous or purulent fluid, either spontaneously or by gentle palpation) 
• Non-draining tunnels (fistulas/sinus tracts) (pathologic passageway connecting to the skin 
surface from dermis or sc tissue/pathologic passageway that develops into a channel to the 
skin surface that does not drain serous or purulent fluid) 
• Noninflammatory nodules (nontender or minimally tender, nonerythematous nodules) 
• Inflammatory nodules (a tender, erythematous, well-defined nodule. The lesion has no 
evidence of fluctuance. A pyogenic granuloma lesion is considered an inflammatory nodule; 
a papule or pustule is not considered an inflammatory nodule) 
• Scars of HS lesions (enlargement or overgrowth of a scar so that it extends above the 
surrounding skin surface) 
The data collected from the lesion count will be used for the derivation of study variables 
including, but not limited to HiSCR25 (a 25% reduction in the total AN count with no increase 
from Baseline in abscess or draining tunnel count), HiSCR50, HiSCR75, HiSCR90, HiSCR100 (a 
100% reduction in the total AN count with no increase from Baseline in abscess or draining 
tunnel count), HS Physician’s Global Assessment, AN count, and International HS Severity 
score system (IHS4). 
8.1.1.1 
Hidradenitis Suppurativa Clinical Response (HiSCR) 
The HiSCR; defined as at least a 50% reduction from Baseline in the total AN count, with no 
increase from Baseline in abscess or draining tunnel count; was developed to address issues with 
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available HS scoring systems. It is a validated endpoint that is responsive to improvement in 
disease activity, simplifies the scoring process, and increases the sensitivity to detect HS-specific 
lesions (Kimball, 2014; Kimball, 2016b). HiSCR has been labeled HiSCR50 in this protocol. 
The HiSCR75, HiSCR90, and HiSCR100 also will be evaluated in this study. These measures of 
clinical response differ from HiSCR50 only in the percent decrease in AN count from Baseline. 
The HiSCRxx is derived by the statistical programming group based on Investigator 
documentation of lesion count, and does not require calculation on the part of the Investigator 
from the lesion count. 
8.1.1.2 
Hidradenitis Suppurativa Physician’s Global Assessment 
The HS Physician’s Global Assessment is a validated 6-point scale that is used to measure 
improvement in inflammatory nodules, abscesses, and draining tunnels (Kimball, 2012; 
Zouboulis, 2015). The HS Physician’s Global Assessment scale is defined by the following: 
• Clear: No inflammatory or noninflammatory nodules 
• Minimal: Only the presence of noninflammatory nodules 
• Mild: ≥1 and ≤4  inflammatory nodules or 1 abscess or draining tunnel and no inflammatory 
nodules 
• Moderate: ≥5 inflammatory nodules or 1 abscess or draining tunnel and 1 or more 
inflammatory nodules or 2 to 5 abscesses or draining tunnels and ≤10 inflammatory nodules 
• Severe: 2 to 5 abscesses or draining tunnels and >10 inflammatory nodules 
• Very severe: >5 abscesses or draining tunnels 
This assessment (clear, minimal, mild, moderate, severe, or very severe) is derived based on 
totals across all affected body regions by the statistical programming group and does not require 
calculation on the part of the Investigator. 
8.1.1.3 
International Hidradenitis Suppurativa Severity Score System (IHS4) 
The IHS4 is a validated tool to dynamically assess HS severity to be used both in real-life and 
the clinical trials setting (Zouboulis, 2017). The IHS4 achieved consensus among European HS 
Foundation members. This IHS4 score is calculated as follows: (number of nodules multiplied by 
1) + (number of abscesses multiplied by 2) + [number of draining tunnels (ﬁstulae/sinuses) 
multiplied by 4]. A score of 3 or less signiﬁes mild HS, a score of 4–10 signiﬁes moderate HS 
and a score of 11 or higher signiﬁes severe HS. 
The determination of IHS4 requires counting the nodules, abscesses and draining tunnels/sinus 
tracts. 
The IHS4 score is derived by the statistical programming group, and does not require calculation 
on the part of the Investigator. 
8.1.2 
Partial response 
A partial response is defined as a ≥25% reduction in AN count from Baseline [Week 0]) at a 
particular timepoint. 
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The partial response is derived by the statistical programming group, and does not require 
calculation on the part of the Investigator. 
8.1.3 
High-sensitivity C-reactive protein (hs-CRP) 
Blood will be collected for measurement of hs-CRP. The hs-CRP data will not be sent to any 
blinded study personnel to protect the blinded nature of the treatment assignments and response. 
8.1.4 
Patient-reported outcomes 
The patient-reported outcome (PRO) instruments should be completed by the study participants 
themselves in a quiet place. The PRO instruments to be completed at the study site, should be 
completed prior to all other protocol-specified assessments at each visit (including dosing on 
dosing days). 
8.1.4.1 
HS symptom measures of skin pain, smell or odor, drainage or 
oozing from HS lesions, and itch 
8.1.4.1.1 
HS symptom daily diary (HSSDD) 
The 5 items on the HS Symptom Daily Diary (HSSDD) assesses patients’ perception of the core 
symptoms of HS experienced in the past 24 hours: pain, smell or odor, drainage or oozing from 
HS lesions, and itch on an 11-point numeric rating scale (NRS). Two items assess skin pain (ie, 
worst skin pain and average skin pain). The remaining 3 items assess smell or odor, itch at its 
worst, and amount of drainage or oozing from HS lesions. 
The HSSDD will be completed daily by the study participant, at the end of the day on an 
electronic hand-held device from the start of Screening  through the Week 16 visit. 
8.1.4.1.2 
HS symptom questionnaire (HSSQ) 
The 4 items on the HS Symptom Questionnaire (HSSQ) assesses patients’ perception of the core 
symptoms of HS experienced in the past 7 days - pain, smell or odor, drainage or oozing from 
HS lesions, and itch on an 11-point NRS. The HSSQ will be completed on an electronic device 
during study visits (ie, Baseline and Weeks 16-48/PEOT). 
8.1.4.2 
Patient Global Impression of HS Severity (PGI-S-HS) and Change in 
HS Severity (PGI-C-HS) 
The Patient Global Impression of HS Severity (PGI-S-HS) is a single item to assess study 
participants perceptions of the overall severity of HS over the past 7 days (none, mild, moderate, 
severe, very severe). The Patient Global Impression of Change in HS Severity (PGI-C-HS) is a 
single item to asses study participants perception of the change in HS since they started taking 
the study medication (much better, a little better, no change, a little worse, much worse). Data 
collected using the PGI-S-HS and PGI-C-HS will be used as anchors for interpreting change 
scores on the Hidradenitis Suppurativa Quality of Life (HiSQOL). 
8.1.4.3 
Patient Global Impression of Severity of Skin Pain (PGI-S-SP) and 
Change in Severity of Skin Pain (PGI-C-SP) 
The Patient Global Impression of Severity of Skin Pain (PGI-S-SP) is a single item to assess 
study participants’ perceptions of the severity of their skin pain from their HS lesions, over the 
past 7 days (none, mild, moderate, severe, very severe). The Patient Global Impression of 
Change in Severity of Skin Pain (PGI-C-SP) is a single item to assess study participants’ 
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perceptions of change in their skin pain from their HS lesions, since they started taking the study 
medication (much better, a little better, no change, a little worse, much worse). PGI-S-SP and 
PGI-C-SP will be used to evaluate outcomes related to Skin Pain. 
8.1.4.4 
Hidradenitis Suppurativa Quality of Life Questionnaire (HiSQOL) 
The 17 item HiSQOL questionnaire has a recall period of 7 days. The HiSQOL includes 
3 subscales: symptom status, psychosocial impact, and impact on physical activities. 
8.1.4.5 
Dermatology Life Quality Index (DLQI) 
The DLQI is a questionnaire designed for use in adult participants with inflammatory skin 
diseases and has been used in patients with HS (Finlay, 1998; Esmann, 2010; Basra, 2012). The 
DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and 
treatment affect participants’ health-related QOL. This instrument asks participants about 
symptoms and feelings, daily activities, leisure, work and school, personal relationships and 
treatment. The DLQI total score ranges from 0 to 30 with higher scores indicating lower health 
related QOL. In other dermatological/skin conditions, a 4-point change in the DLQI total score 
(DLQI response) has been reported to be meaningful for the participant (within participant 
minimal important difference); while a DLQI total absolute score of 0 or 1 indicates no or small 
impact of the disease on health related QOL. 
8.1.4.6 
Euro-Quality of Life 5-Dimensions, 3 levels 
The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and 
psychological status with 3 possible answers for each item (1=no problem, 2=moderate problem, 
3=severe problem). In addition, the questionnaire includes a visual analogue scale to indicate the 
general health status, with 100 indicating the best health status. 
8.1.4.7 
Workers Productivity and Activity Impairment Questionnaire: 
Specific Health Problem 
The Workers Productivity and Activity Impairment Questionnaire: Specific Health Problem 
(WPAI-SHP) V2.0 is a patient-reported questionnaire that assesses study participant’s 
employment status, work absenteeism, work impairment while working (presenteeism), overall 
work, and daily activity impairment attributable to a specific health problem (Reilly, 1993). It 
has been used in several clinical studies of biologic therapy in participants with plaque PSO 
(Kimball, 2012; Vender , 2012). 
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. 
8.1.4.8 
Treatment Satisfaction Questionnaire for Medication 
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is an abbreviated 9-item 
version of the TSQM, excluding the side effects of medication domain. The domains included in 
the TSQM-9 include effectiveness (3 items), convenience (3 items) and global satisfaction 
(3 items). The TSQM-9 domain scores range from 0 to 100 with higher scores representing 
higher satisfaction (Bharmal, 2009). 
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8.1.5 
Hurley Stage 
The Hurley Stage is a severity classification for HS that was developed in 1989 and is widely 
used for the determination of the severity of HS (Hurley, 1989). 
The Hurley Stage is defined by the following criteria: 
• Stage I: Abscess formation, single or multiple, without sinus tracts and cicatrization 
(scarring). 
• Stage II: Recurrent abscesses with tract formation and cicatrization, single or multiple, 
widely separated lesions. 
• Stage III: Diffuse or near-diffuse involvement, or multiple interconnected tracts and 
abscesses across the entire area. 
Hurley Stage is assigned to a given anatomic region. The overall worst Hurley Stage (ie, the 
highest Hurley Stage across all anatomic regions) for a given study participant at a given visit is 
then the study participant-level Hurley Stage. This study participant-level Hurley Stage is 
important for baseline stratification and disease severity assessment. 
Hurley stage is included as a stratification factor for randomization. 
8.2 
Safety assessments 
Planned timepoints for all safety assessments are provided in the Schedule of Activities 
(Table 1‒1). 
8.2.1 
Physical examination 
A complete physical examination will include, at a minimum, general appearance; ear, nose, and 
throat; eyes, hair, and skin; and assessments of the cardiovascular, respiratory, gastrointestinal 
musculoskeletal, and hepatic, neurological (including limb reflexes) systems, and mental status. 
Each physical examination also includes evaluation of signs and symptoms of active TB and risk 
for exposure to TB (Section 8.2.6). 
Height and weight will also be measured and recorded. The same scale for measuring body 
weight should be utilized throughout the study where possible. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings since the physical examination at 
the Screening Visit will be recorded as AEs. 
8.2.2 
Vital signs 
Vital signs will be measured in a sitting position after 5 minutes rest and will include body 
temperature (oral, axillary, otic or noncontact forehead), systolic and diastolic blood pressure, 
and pulse. Vital signs are to be measured prior to blood sampling, and prior to dosing, where 
applicable. 
Vital signs will consist of single pulse and blood pressure measurements. 
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8.2.3 
Electrocardiograms 
A single 12-lead ECG will be obtained using an ECG machine that automatically calculates the 
heart rate and measures PR, QRS, QT, and QT corrected for heart rate intervals. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 10 minutes before the recording and prior to taking blood samples or dosing. 
ECG machines will be provided to study centers, and ECGs will be read by a central ECG 
laboratory. Full details of ECG recordings will be provided in the ECG Manual. 
8.2.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed. 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the study participant’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 20 weeks after the last dose of IMP should be repeated until the values 
return to normal or Baseline or are no longer considered clinically significant by the Investigator 
or Medical Monitor. 
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the Schedule of Activities. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the CRF. 
8.2.5 
Depression and suicidal risk monitoring 
8.2.5.1 
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 
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. 
Refer to Section 7.2 for PHQ-9–related withdrawal criteria. 
8.2.5.2 
eC-SSRS 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior (Mundt, 2010; Posner, 2011). Study 
participants respond to standardized clinical questions that are presented in a uniform fashion. 
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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 7.2 for eC-SSRS-related withdrawal criteria. 
8.2.6 
Assessment and management of tuberculosis and tuberculosis risk 
factors 
All participants will be assessed for TB through physical examination for signs and symptoms of 
TB, laboratory testing (Section 8.2.4), chest x-ray (CXR)  (Section 8.2.6.3.2), and TB 
questionnaire (Section 8.2.6.3.3). 
8.2.6.1 
Assessments at Screening 
At Screening, all participants will have an IGRA test (QuantiFERON Gold Plus TB test is 
recommended), a CXR (unless already performed within 2 months of Screening; a computed 
axial tomography (CAT) scan of the chest at Screening or within 2 months prior to Screening is 
acceptable, if available), and examination for signs and symptoms of TB. In addition, the 
Investigator or designee will complete a TB questionnaire directed at the participants potential 
exposure to TB and symptoms of TB. 
Study participants diagnosed with active TB during Screening will be excluded from the study. 
Study participants with LTBI diagnosed during Screening must have completed a full course of 
prophylaxis prior to IMP dosing and can be rescreened after completion of a full course of 
prophylaxis plus a wash-out of least 5 half-lives of the prophylactic medication(s) prior to 
Baseline. (See also Section 8.2.6.3.5.) 
8.2.6.2 
Definitions 
Study participants with known active TB disease, at high risk of acquiring TB infection, or with 
untreated LTBI (ie, pending anti-TB prophylactic course) or current or history of NTM infection 
are excluded from the study. 
a. Known TB infection whether present or past is defined as: 
• Active TB disease or clinical signs and symptoms strongly suggestive of TB (pulmonary or 
extra pulmonary). 
• History of active TB disease involving any organ system or findings in other organ systems 
consistent with TB, 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 disease that is not reported in the study participant's medical history. 
b. High risk of acquiring TB infection is defined as: 
• Known close exposure (eg, sleeping in the same room) to another person with active TB 
infection within 3 months prior to Screening. 
• Time spent within 3 months prior to screening in a healthcare delivery setting or institution 
where individuals infected with TB are housed or where the risk of transmission of infection 
is high. 
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c. Latent TB infection is defined as an infection by Mycobacterium tuberculosis with: 
• A positive IGRA (or 2 indeterminate IGRAs) AND 
• Chest imaging (or other imaging) negative for TB infection, AND 
• Absence of signs, symptoms (eg, evidence of organ-specific involvement), or physical 
findings suggestive of TB infection. 
d. Pulmonary NTM infection is defined as a group of lung or extrapulmonary infections caused 
by mycobacteria different from M. tuberculosis infections. 
8.2.6.3 
Assessment and reporting of TB and TB risk factors during the study 
8.2.6.3.1 
Physical examination 
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the study participant’s medical or 
social history. 
The most common primary focus of TB is the lung. Other sites may include gastrointestinal 
system, bone/joints, lymph glands and meninges, etc. However, in immune-compromised 
patients, study participants, and/or patients treated with biologics, especially tumor necrosis 
factors inhibitors, extra-pulmonary manifestations of TB is common compared to normal 
population. 
Some common symptoms that the study participant may present are dependent on the primary 
focus of infection and may include cough, blood in sputum, night sweats, lymphadenitis, joint 
pain/swelling, spinal deformity, headache/confusion, abdominal pain (mimicking inflammatory 
bowel disease), etc. Unusual presentations should always be considered. 
8.2.6.3.2 
Chest x-ray for tuberculosis 
Chest radiographic imaging is performed at screening and results must be available at baseline 
before first drug administration unless a CXR or CAT scan is available from 2 months prior to 
screening. 
Additional CXR or other imaging test should be performed when positive signs and symptoms 
indicate pulmonary infection, including potential TB infection, or when close exposure to 
persons with TB is documented. 
8.2.6.3.3 
Tuberculosis questionnaire 
A questionnaire entitled “Evaluation of Signs and Symptoms of Tuberculosis” has been 
developed by UCB (document mod-000582) to help in identifying TB risk factors in study 
participants; it is administered by the Investigator or their designee. For the purpose of case 
reporting, this questionnaire also ensures appropriate follow-up with reporters when a case of 
either latent TB or active TB is diagnosed. Moreover, it ensures proactive and appropriate 
follow-up with Investigators and study participants on treatment course. 
8.2.6.3.4 
IGRA Test Conversion 
The IGRA is a whole-blood testing methodology for diagnosing M. tuberculosis infection. It has 
become the gold standard, but does not help in differentiating LTBI from active tuberculosis 
disease. 
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Tuberculosis test conversion is defined as a positive or indeterminate (and confirmed 
indeterminate on repeat) IGRA result for the current test when previous IGRA test results were 
negative. All study participants with positive or indeterminate IGRA test results must 
immediately stop IMP administration. In case of a IGRA test conversion, the study participant 
must be considered as having either a suspected new latent or an active TB infection and be 
promptly referred to an appropriate specialist (eg, pulmonologist, infectious disease specialist) 
for further evaluation. Additional assessments (eg, blood tests or IGRA, CXRs, or other imaging) 
should be performed where medically relevant and documented. Such conversions should be 
reported as AEs as described in the protocol. The AE term would need to be updated with final 
diagnosis once available. 
8.2.6.3.5 
Latent TB 
In case the evaluation by the appropriate specialist diagnoses a new LTBI, a TB prophylactic 
therapy in accordance with applicable clinical guidelines should be immediately initiated. 
Study participants who initiate treatment for LTBI during the Screening period must repeat 
initial screening laboratory parameters, all physical examinations, and questionnaires prior to 
randomization in the study, and must continue the full course of TB prophylactic therapy. 
Participants can be rescreened after completion of a full course of prophylaxis. Eligible study 
participants can be included after a wash-out of least 5 half-lives of the prophylactic 
medication(s) prior to Baseline. 
Study participants who initiate treatment for LTBI during the study must repeat study 
assessments after TB prophylactic therapy has been received for at least 4 weeks. The 
Investigator and Medical Monitor and/or UCB study physician will decide which investigations 
(safety laboratory parameters, physical exams and questionnaires) need to be performed after 
required LTBI prophylaxis period and before the IMP will be restarted. 
The IMP can be restarted no sooner than 4 weeks after the start of TB prophylactic therapy if it is 
deemed likely that the TB prophylactic therapy will be continued to full completion. If no TB 
prophylactic therapy is initiated for the newly diagnosed LTBI, the study participant must 
permanently stop IMP and be withdrawn from the study. Every related action should be 
discussed in advance with the Medical Monitor. 
Study participants who prematurely discontinue treatment for LTBI or who, in the opinion of the 
Investigator or Sponsor, are noncompliant with anti-TB therapy must discontinue further intake 
of IMP and be immediately withdrawn. Once withdrawn from study treatment, study participants 
should return for the PEOT visit, complete all assessments, and complete the SFU visit. LTBI 
must be reported as an AE. Follow-up reports should be completed as per protocol requirement 
until such time as the LTBI resolves. 
8.2.6.3.6 
Active TB or non-tuberculosis mycobacterium infection 
Study participants who develop active TB or NTM infection during the study must be withdrawn 
from the study. The study participant must be immediately permanently discontinued from study 
medication and a PEOT visit must be scheduled as soon as possible, but no later than the next 
scheduled visit. The study participant should be encouraged to keep the SFU visit as specified by 
the protocol. Treatment for active TB or NTMB should be started immediately. 
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Confirmed active TB is always considered an SAE. UCB’s process requires that these must be 
captured on an SAE report form and provided to the Sponsor in accordance with SAE reporting 
requirements. Follow-up reports should be completed as per protocol requirement until such time 
as the TB infection resolves. 
8.2.6.3.7 
Tuberculosis management of LTBI, active TB, or other NTB infection 
identified during study 
During the study, study participants who develop evidence of LTBI, active TB or NTB infection 
must immediately stop further administration of IMP and will be referred to a TB specialist 
(pulmonologist or infectious disease specialist) for further evaluation. Study participants 
diagnosed with active TB or LTBI should receive appropriate TB or prophylaxis therapy. If a TB 
specialist excludes active TB, the study participant can restart the IMP no earlier than 4 weeks 
after the start of an appropriate TB prophylactic therapy. The study participant should be 
transferred to the care of his or her physician and managed according to the standard of care. 
Study participants identified as having active TB during the study must be withdrawn and 
scheduled to return for the PEOT Visit as soon as possible but no later than the next scheduled 
study visit and complete all PEOT Visit assessments. The study participant should be encouraged 
to complete an SFU Visit after the last dose of study medication. 
If infection with NTM is identified during the study, the same procedure as for active TB 
acquired during the study and compliant TB treatment shall be followed. 
Study participant eligibility, retesting requirements, and treatment requirements are shown in 
Figure 8-1 (screening) and Figure 8-2 (during the study). Additional details on TB detection and 
management are provided in the UCB TB Detection Procedure Guideline. 
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Figure 8-1: Decision tree for IGRA TB results at Screening 
 
IGRA=interferon gamma release assay; IMP=investigational medicinal product; LTBI=latent tuberculosis infection; 
TB=tuberculosis 
a IGRA retest must be done during the protocol-defined Screening window 
b Study participants with LTBI diagnosed during Screening must have completed a course of prophylaxis prior to 
IMP dosing. Participants can be rescreened after completion of a course of prophylaxis plus a wash-out of least 
5 half-lives of the prophylactic medication(s) prior to Baseline. 
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Figure 8-2: Decision tree for IGRA TB results during a study 
 
ASAP=as soon as possible; IGRA=interferon-gamma release assay; IMP=investigational medicinal product; 
LTBI=latent tuberculosis infection; TB=tuberculosis 
a IGRA retest must be done ASAP and prior to the next IMP dose 
b Study participants with LTBI diagnosed during the study 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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8.3 
Adverse events and serious adverse events 
AE will be reported by the study participant (or, when appropriate, by a caregiver, surrogate, or 
the study participant’s legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
study participant to discontinue the study treatment or the study (see Section 7). 
Confirmed and suspected cases of COVID-19 infection will be recorded as AEs (or SAEs, as 
required). 
8.3.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the SFU visit (except for 
those study participants who enroll in extension study HS0005) or until the first dose 
administration in extension study HS0005 (for study participants enrolling in HS0005). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the CRF even if no IMP was taken but specific study procedures 
were conducted. This includes all AEs not present prior to the initial visit and all AEs that 
recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 3. The Investigator will submit any updated SAE data to the Sponsor within 
24 hours of it being available. 
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 
20 weeks from the last dose of IMP for each study participant, and to also inform study 
participants 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. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3. 
8.3.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each study 
participant at subsequent visits/contacts. All AEs and SAEs, will be followed until resolution, 
stabilization, the Investigator determines that it is no longer clinically significant, the event is 
otherwise explained, or the study participant is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is given in Section 10.3. 
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8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants who 
become pregnant will be collected after the start of study treatment and through the SFU visit (ie, 
20 weeks after last dose of IMP). 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
A female study participant should be withdrawn from the study as soon as pregnancy is known 
(by positive pregnancy test), and the following should be completed: 
• The study participant should return for an early discontinuation visit. 
• The study participant should immediately stop the intake of the IMP. 
• An SFU Visit should be scheduled 20 weeks after the study participant has received her last 
dose of IMP. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
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 cases, defined as ≥3×ULN ALT 
or AST with coexisting ≥2×ULN total bilirubin in the absence of ≥2×ULN 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 participant. 
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8.3.7 
Other safety topics of interest 
Prespecified safety topics of interest for the study are infections (serious, opportunistic, fungal, 
and TB), neutropenia, hypersensitivity (including anaphylaxis), suicidal ideation and behavior, 
major adverse cardiovascular events, hepatic events and PDILI, malignancies, and inflammatory 
bowel disease. 
These are based on findings from the IMP clinical program to date, potential risks generally 
associated with biologic immunomodulators, or findings from other medicines with a related 
mechanism of action. There are no specific AE reporting requirements for these topics, except 
those listed below for events relating to TB; however, special monitoring, additional data 
collection activities, and/or enhanced signal detection activities (within UCB) are in place. 
The reporting requirements for events relating to TB are as follows: 
• The IGRA test conversions defined as a positive or indeterminate (and confirmed 
indeterminate on repeat) should be reported as AEs. The AE term would need to be updated 
with final diagnosis once available. 
• Latent TB infection must be reported as an AE. Follow-up reports should be completed as 
per protocol requirement until the LTBI resolves. 
• Confirmed active TB is always considered an SAE and must be reported per SAE reporting 
instruction in the study protocol. Follow-up reports should be completed as per protocol 
requirement until TB infection resolves. 
8.3.8 
Anticipated serious adverse events 
The following list of Anticipated SAEs (Table 8‒1) is predicted to occur in the population 
studied in this protocol at some frequency that is independent of drug exposure. This original list 
will remain in effect for the duration of the protocol. Note that listed events will not be regarded 
as anticipated SAEs if they are life threatening or if they result in the death of the study 
participant. 
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 8.3.1 and Section 10.3. 
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Table 8‒1: 
Anticipated SAEs for the Population of Participants with HS 
MedDRA System Organ Class 
MedDRA Preferred Term 
Gastrointestinal disorders 
Crohn’s disease  
Colitis ulcerative 
Psychiatric disorders 
Depression 
Anxiety 
Musculoskeletal and connective tissue disorders 
Arthropathy 
Skin and subcutaneous tissue disorders 
Pyoderma gangrenosum 
Pilonidal cyst 
Acne conglobate 
Hidradenitis 
Neoplasms benign, malignant and unspecified 
(including cysts and polyps) 
Lymphoma 
Squamous cell carcinoma of skin 
Infections and infestations 
Cellulitis 
Metabolism and nutritional disorders 
Diabetes mellitus 
Dyslipidaemia 
Metabolic syndrome 
Endocrine disorders 
Thyroid disorder 
Polycystic ovaries 
HS=hidradenitis suppurativa; MedDRA=Medical Dictionary for Regulatory Activities; SAE=serious 
adverse event 
8.3.9 
Suspected transmission of an infectious agent 
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. 
8.4 
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 participants, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The UCB study physician or medically qualified designee/equivalent will conduct an ongoing 
review of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient 
Safety (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. 
An independent DMC will be used in this study; see Section 9.7 and Section 10.1.5 for details. 
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8.5 
Treatment of overdose 
For this study, any dose of IMP greater than that prescribed in the protocol will be considered an 
overdose. Overdose events are only considered AEs or SAEs if there are associated clinical signs 
and symptoms or if the act of taking the excess IMP itself is an AE or SAE (eg, suicide attempt). 
UCB does not recommend specific treatment for an overdose. Any signs or symptoms of adverse 
reactions should be treated symptomatically as per standard care by the Investigator. 
Bimekizumab will not be self-administered by the study participant. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the study participant for any AE/SAE and laboratory abnormalities until 
they have resolved, have a stable sequelae, the Investigator determines that it is no longer 
clinically significant, or the study participant is lost to follow up. 
3. Document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the study participant. 
8.6 
Pharmacokinetics 
Blood samples will be collected prior to dosing for measurement of plasma concentrations of 
bimekizumab at all timepoints described in Table 1‒1. A total of 9mL will be collected at 
timepoints for which PK, anti-drug antibodies (ADAb), and neutralizing antibodies are all 
measured and 3mL will be collected at timepoints for which only PK is measured. Instructions 
for the collection and handling of biological samples will be provided by the Sponsor. The actual 
date and time (24-hour clock time) of each sample will be recorded. 
Samples will be used to evaluate the PK of bimekizumab. Samples collected for analyses of 
bimekizumab plasma concentration may also be used to evaluate safety or efficacy aspects 
related to concerns arising during or after the study. 
Genetic analyses will not be performed on these samples. Study participant confidentiality will 
be maintained. At visits during which blood samples for the determination of plasma 
concentrations of bimekizumab will be taken, 1 sample of sufficient volume can be used. 
Drug concentration information that may unblind the study will not be reported to any blinded 
study personnel as long as the study remains blinded. 
8.7 
Genetics 
For individuals consenting to the pharmacogenetic substudy, blood samples will be drawn for 
exploratory genetic/epigenetic analyses at the timepoints specified in Table 1‒1. Collection of 
these samples will enable evaluation of genetics/epigenetics biomarkers relative to disease 
biology and progression, drug treatment and inflammatory and immune response processes. The 
nature and format of these tentative analyses will be determined when the results of the main 
study are made available. A separate ICF will be required for those study participants who agree 
to participate in the pharmacogenetics substudy. The substudy will be conducted only where 
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ethically accepted and authorized by the regulatory agencies. Refusal to participate in the 
substudy will not affect a study participant’s ability to participate in the main study. 
The samples will be stored at -80°C at the central biorepository for up to 20 years. 
In the event of deoxyribonucleic acid (DNA) extraction failure, a replacement genetic blood 
sample may be requested from the participant. Signed informed consent will be required to 
obtain a replacement sample unless it was included in the original consent. 
See Appendix 5 (Section 10.5) for information regarding genetic research. Details on processes 
for collection and shipment and destruction of these samples can be found in laboratory manual 
for this study. Detailed information on sample analysis will be provided in a bioanalytical report. 
8.8 
Pharmacodynamics 
See Section 8.9. 
8.9 
Biomarkers 
Where local regulations permit, blood samples will be drawn for exploratory ribonucleic acid, 
proteins and metabolites biomarker analysis at the timepoints specified in Table 1‒1. Where 
local regulations permit, urine samples will be drawn for exploratory proteins and metabolites 
biomarker analysis at the timepoints specified in Table 1‒1. Collection of these samples will 
enable evaluation of biomarkers relative to disease biology and progression, drug treatment and 
inflammatory and immune response processes. Candidate biomarker evaluations may include, 
but are not limited to, IL-17A/IL17-F pathway signaling and HS biology (eg, IL-17A, IL-17F). 
These samples may be used for additional analyses of other exploratory biomarkers. 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. The nature and format of these tentative 
analyses will be determined at a later stage. The samples will be stored at the secure long-term 
storage facility selected by UCB for up to 20 years. 
These samples will only be used to further our understanding of HS and/or how biomarkers, 
including genetic variation, may affect response or be affected by treatment with bimekizumab in 
HS. 
8.9.1 
Immunogenicity assessments 
Blood samples for the measurement of ADAb and neutralizing antibodies will be collected. A 
total of 9mL will be collected at timepoints for which PK, ADAb, and neutralizing antibodies are 
all measured. Immunogenicity data will not be sent to the Investigator to protect the blinded 
nature of the treatment assignments and response. 
Antibodies to bimekizumab will be evaluated in plasma samples collected from all participants 
according to the Schedule of Activities. Additionally, plasma samples should also be collected at 
the final visit from participants who discontinued IMP or were withdrawn from the study. These 
samples will be tested by the Sponsor or Sponsor’s designee. 
Plasma samples will be screened for antibodies binding to bimekizumab and the titer of 
confirmed positive samples will be reported. Other analyses may be performed to verify the 
stability of antibodies to bimekizumab and/or further characterize the immunogenicity of 
bimekizumab. 
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The detection and characterization of antibodies to bimekizumab will be performed using 
validated assay methods by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to bimekizumab will also be evaluated for bimekizumab plasma 
concentration to enable interpretation of the antibody data. Antibodies may be further 
characterized and/or evaluated for their ability to neutralize the activity of 
bimekizumab. Samples may be stored for a maximum of 20 years (or according to local 
regulations) following the last study participant’s last visit for the study at a facility selected by 
the Sponsor to enable further analysis of immune responses to bimekizumab. 
8.10 
Medical resource utilization and health economics 
Health-related outcomes and medical resource utilization will be collected as part of standard 
eCRF pages during the study (eg, concurrent medical procedures, concomitant medications, 
hospitalizations, WPAI-SHP). 
8.11 
Photography 
At certain sites, where feasible, representative photographs of the changes in skin will be 
captured. Photographs will be anonymized. This is optional for study participants and requires a 
separate informed consent. A decision not to consent does not exclude the study participant from 
the study. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP). 
9.1 
Definition of analysis sets 
9.1.1 
Enrolled Set 
The Enrolled Set will consist of all study participants who have given informed consent. 
9.1.2 
Randomized Set 
The Randomized Set (RS) will consist of all randomized study participants. 
9.1.3 
Safety Set 
The Safety Set will consist of all study participants who received at least 1 full or partial dose of 
IMP and will be used for the demographic, safety, and immunogenicity analyses. 
9.1.4 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all study participants who received at least 1 dose 
(full or partial) of IMP and had a valid Baseline measurement and a post-Baseline measurement 
for abscess, inflammatory nodules, and draining tunnel counts. 
9.1.5 
Per-Protocol Set 
The Per-Protocol Set will consist of all study participants in the FAS who had no important 
protocol deviations affecting the primary efficacy variable. Important protocol deviations will be 
predefined and study participants with important protocol deviations will be evaluated during 
ongoing data cleaning meetings prior to unblinding of the data. 
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9.1.6 
Pharmacokinetics Per-Protocol Set 
The Pharmacokinetics Per-Protocol Set will consist of study participants who received at least 
1 full dose of bimekizumab and provided at least 1 quantifiable plasma concentration post-dose 
without important protocol deviations that would affect the PK. The Pharmacokinetics 
Per-Protocol Set is defined separately for each of the treatment periods (ie, separately for the 
Initial Treatment Period and the Maintenance Treatment Period). 
9.1.7 
COVID-19 Free Set 
The COVID-19 Free Set will consist of all study participants randomized into the study and who 
have no COVID-19 impact through Week 16. This analysis set will be used for sensitivity 
analysis of the primary efficacy endpoint. 
9.2 
General statistical considerations 
All analyses will be performed using SAS® version 9.4 or later (SAS Institute, Cary, NC, US). 
Descriptive statistics will be used to provide an overview of the Baseline, efficacy, and safety 
results. For categorical parameters, the number and percentage of study participants in each 
category will be presented by treatment group. The denominator for the percentages will be 
based on the number of study participants appropriate for the purpose of analysis. Unless 
otherwise noted, all percentages will be expressed to 1 decimal place. For continuous parameters, 
descriptive statistics will include n, mean, standard deviation, median, minimum, and maximum. 
Two-sided 95% confidence intervals, geometric means, and coefficient of variation will be 
presented for selected variables as appropriate. 
Baseline for each assessment is defined as either the value obtained at Baseline or the last 
available value obtained prior to treatment administration (details to be specified in the SAP). 
Formal statistical testing will be conducted for this study for the primary and secondary efficacy 
variables. Other efficacy variables will be summarized descriptively by treatment arm. P-values 
and confidence intervals may be produced for other or exploratory variables but will be 
interpreted as non-inferential (ie, nominal). Additionally, other analyses will be conducted as 
deemed appropriate and described in the SAP. 
The primary treatment comparison for all formal statistical analyses of efficacy will be between 
bimekizumab and placebo. 
9.3 
Planned efficacy/outcome analyses 
9.3.1 
Analysis of the primary efficacy endpoint 
The primary objective of this randomized, double-blind, placebo-controlled, multicenter, pivotal 
study in study participants with moderate to severe HS is to compare the efficacy of 
bimekizumab 
 and bimekizumab 
 with placebo at Week 16. For the 
purposes of Week 16 analyses, the bimekizumab treatment arms of 
 and 
bimekizumab 
 treatment groups will be pooled. 
The primary and secondary efficacy analyses will be performed based on the RS. 
The primary endpoint is the HiSCR50 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 based on the HiSCR50 response and early receipt of 
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systemic antibiotic rescue medication, or discontinuation of IMP 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=Study participants meeting the protocol-specified inclusion/exclusion criteria. 
2. Study participant-level outcome=HiSCR50 at Week 16. 
3. Intercurrent event handling=An intercurrent event is defined as receipt of systemic antibiotic 
rescue medication or 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 HiSCR50 at Week 16 and not receiving systemic antibiotic 
rescue medication, and not discontinuing study treatment due to an AE or lack of efficacy 
through Week 16. Any missing data at Week 16 that are not preceded by an intercurrent 
event will be imputed using multiple imputation. 
4. Population-level summary measure=conditional odds ratio comparing bimekizumab to 
placebo adjusted for stratification factors used in the randomization. 
As a sensitivity analysis, any missing data at Week 16 that are not preceded by an intercurrent 
event (ie, receipt of systemic antibiotic rescue medication, or discontinuation of IMP due to an 
AE or lack of efficacy) will be imputed as non-response. 
The statistical hypothesis for the HiSCR50 response at Week 16 is that the conditional odds ratio 
for the HiSCR50 response in the bimekizumab treatment group relative to the placebo group is 
equal to 1. 
A logistic regression model will be used to assess the effect of bimekizumab vs placebo on 
HiSCR50 response. The model will include a fixed effect for treatment. The stratification 
variables of Hurley stage and prior antibiotic use will be added to the model unless inappropriate. 
The odds ratio versus placebo, p-value (from Wald test), and confidence interval will be 
calculated. 
To assess the impact of the COVID-19 pandemic on the primary efficacy endpoint analysis, 
additional sensitivity analyses will be performed as specified in Section 9.3.4. 
9.3.2 
Analysis of the secondary efficacy endpoints 
The secondary efficacy variables supporting the primary efficacy variable are listed below, and 
will be included in the multiplicity adjustment: 
1. Proportion of study participants who achieve HiSCR75 at Week 16. A similar analysis to the 
primary responder analysis will be performed. 
a. bimekizumab
 vs placebo 
b. bimekizumab 
 vs placebo 
2. Proportion of study participants who experience at least 1 flare by Week 16, with flare 
defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 relative 
to Baseline. A similar analysis to the primary responder analysis will be performed. 
a. bimekizumab
 vs placebo 
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b. bimekizumab 
 vs placebo 
3. Absolute change from Baseline in DLQI Total Score at Week 16. Analysis will be based on 
an analysis of covariance (ANCOVA) with treatment and stratification variables as fixed 
effects and the Baseline values as covariate. 
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
4. Absolute change from Baseline in Skin Pain Score at Week 16, as assessed by the “worst 
pain” item (11-point numeric rating scale) in the HSSDD. Analysis will be based on an 
ANCOVA with treatment and stratification variables as fixed effects and the Baseline values 
as covariate. 
a. bimekizumab 
 vs placebo 
b. bimekizumab
 vs placebo 
5. Pain response (defined as a decrease from Baseline in HSSDD weekly worst skin pain score 
at or beyond the threshold for clinically meaningful change) at Week 16. A similar analysis 
to the primary responder analysis will be performed.  
a. bimekizumab 
 vs placebo 
b. bimekizumab
 vs placebo 
To control the overall type I error rate at 0.05 for the multiple comparisons in the primary and 
secondary efficacy variables, a closed testing procedure under a parallel gatekeeping framework 
will be applied (Sun, 2018). 
Under this framework, each bimekizumab dose of 
 and 
 will be 
compared to placebo in the first instance at a familywise error rate of 0.025 (α/2). 
Simultaneously within each dose, closed testing for the primary and secondary efficacy 
endpoints will be performed as follows: 
1. Step 1: Test HiSCR50 at significance level 0.025. 
2. Steps 2 to 6 – If Step 1 is significant at 0.025 then test each secondary endpoint sequentially 
in the order shown below, moving to the next step only if significance achieved at 0.025. 
3. In the event that Step 6 is significant at 0.025 for a given dose, then Steps 1 to 6 will be 
repeated for the other dose using a significance level of 0.05. 
A schematic of the procedure is shown in Figure 9-1.  
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Figure 9-1: Closed Testing Procedure 
 
 
AN=abscess and inflammatory nodule; CFB=change from Baseline; DLQI=Dermatology Life Quality Index; 
HiSCR50=a 50% reduction in the total AN count with no increase from Baseline in abscess or draining tunnel 
count; HiSCR75=a 75% reduction in the total AN count with no increase from Baseline in abscess or draining 
tunnel count; HS=hidradenitis Suppurativa; 
 
9.3.3 
Other efficacy/other outcome analyses 
Analyses of the other efficacy measures will be detailed in the SAP. 
9.3.4 
COVID-19 impact analysis 
To assess the impact of the COVID‑19 pandemic on the primary efficacy endpoint analysis, the 
following additional sensitivity analyses will be performed: 
• Imputation as nonresponse for any missing data due to COVID‑19 at Week 16 and analyzed 
using the same analysis model as for the primary analysis 
• Separate inferential analysis of the primary and secondary efficacy endpoints based on the 
COVID‑19 Free Set 
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• Separate summary statistics for the primary efficacy endpoint at Week 16, based on the 
COVID-19 Free Set 
• Summary of the number of study participants with missing primary or secondary endpoint 
data, as applicable   
In addition, to assess the broader impact of the COVID-19 pandemic on the study, the following 
summaries will be presented: 
• Summary of study participant disposition based on enrollment before, during, and after 
COVID-19 pandemic onset 
• A summary of study visits impacted by the COVID-19 pandemic 
• A summary of protocol deviations related to COVID-19 
Any additional COVID-19 related analyses will be specified in the study SAP. Note: the date of 
COVID-19 pandemic onset is defined as 11 March 2020, the date that the World Health 
Organization declared the COVID-19 pandemic. The end date of the COVID-19 pandemic end 
will be defined in the study SAP, if applicable. 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
All TEAEs, SAEs, TEAEs leading to discontinuation, AEs of special interest (eg, cases meeting 
Hy’s Law criteria), and other safety topics of interest (Section 8.3.7) will be collected during the 
study and for up to 20 weeks after the last dose of IMP (for study participants who do not 
participate in the extension study, HS0005). Safety analyses will be carried out using the Safety 
Set (study participants who received at least 1 full or partial dose of IMP). Summaries of 
Confirmed and Suspected COVID-19 TEAEs, respectively, will be presented. The definition of 
Confirmed and Suspected COVID-19 TEAEs will be provided in the SAP. 
9.4.2 
PK and ADAb analyses 
Plasma concentrations of bimekizumab will be summarized by treatment group at each timepoint 
using descriptive statistics. In addition, PK model-based analyses may be performed. 
Antidrug antibody data will be evaluated for each study participant and each regimen, and rates 
and classification of ADAb-positive study participants will be calculated. 
9.5 
Handling of protocol deviations 
Important protocol deviations are identified as part of the data cleaning process as specified in 
the study-specific data cleaning schedule/plan. Ongoing, blinded data cleaning meetings will be 
held throughout the duration of the study. Objectives of these meetings include to review 
protocol deviations and to document potential impact that these deviations might have on the 
study objectives. Furthermore, overall trends in protocol deviations will be discussed at the Data 
Evaluation Meeting(s). Through this ongoing data cleaning and evaluation process, all decisions 
regarding important protocol deviations are made on an ongoing basis. Protocol deviations (eg, 
missing assessments or visits) related to COVID-19 will be listed and summarized separately. 
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9.6 
Handling of dropouts or missing data 
The analyses for the primary and secondary efficacy variables will include the use of multiple 
imputation. In multiple imputation, 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 method, 
followed by regression for monotone missing data. The multiple imputation procedures planned 
for the primary and secondary efficacy analyses are based on an assumption of data missing at 
random. 
The sensitivity of results to the approach for handling missing data will be evaluated via 
supportive analyses using different missing data mechanisms. The following supportive analyses 
for the primary efficacy variable will be conducted: 
1. Deviations from the missing at random pattern will be evaluated using a reference-based 
multiple imputation approach. Intermittent missing data will be imputed using the 
Markov-Chain Monte Carlo method. The remaining monotone missing data will be assumed 
to follow a missing not at random pattern. These data will be imputed using a 
reference-based approach in which the multiple imputation model is based on data from the 
placebo group, thereby assuming that monotone missing data follow a trajectory similar to 
the placebo group. 
2. Tipping point analyses will be performed to evaluate missingness assumptions. 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 study participants who have missing data and are randomized to bimekizumab have a 
lower probability of response compared to study participants who have missing data and 
were randomized to placebo. For binary variables, this includes the worst case scenario 
where study participants who have missing data and are randomized to bimekizumab are 
considered nonresponders, while study participants 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. 
3. The treatment policy strategy for addressing intercurrent events will be considered. This will 
be based on an analysis of all available data at Week 16 regardless of the occurrence of 
intercurrent events. This analysis will use the same models specified for the primary analysis, 
where study participants are analyzed according to their randomized treatment, even if they 
discontinued study treatment for any reason prior to Week 16. Even though efforts will be 
made to collect the primary outcome data for all study participants at Week 16, there may 
still be some study participants for whom Week 16 efficacy data cannot be obtained. In this 
case, missing data will be imputed using multiple imputation 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 confounded by 
placebo study participants 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. 
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4. An additional supportive analysis will be based on observed data only for study participants 
who are still on the randomized treatment at Week 16. Study participants with missing data 
or who have prematurely discontinued study treatment will be treated as missing. The same 
procedure described as in the primary efficacy analyses will be used. 
All imputation of other missing data will be detailed in the SAP. 
9.7 
Planned interim analysis and data monitoring 
9.7.1 
Data Monitoring Committee 
An independent DMC will periodically review unblinded efficacy and safety data to assess the 
benefit/risk of bimekizumab in study participants with moderate to severe HS. Individual study 
participant-level efficacy data listings may be provided to the DMC to put the safety review in 
the context of risk/benefit. Any data to be provided will be specified per the DMC charter. In 
addition, unblinded efficacy data analysis is planned to be provided to the DMC when 
approximately 66% of study participants have reached the primary efficacy endpoint at Week 16. 
At this analysis, formal primary endpoint comparisons between active treatment groups and 
placebo will be provided so that the DMC can make an assessment regarding the futility of each 
dose group. However, no early stopping of a treatment group or study will be made on the basis 
of superior efficacy. Therefore, no alpha adjustment is planned since the efficacy analyses will 
only be for futility. 
Measures to ensure that unblinded interim results are not disseminated beyond the DMC will be 
implemented. Details of futility stopping boundaries and decision rules will be detailed in the 
DMC Charter. 
9.7.2 
Interim Analysis 
After the last study participant has completed the Week 48 visit, or after the last study participant 
has prematurely discontinued prior to reaching Week 48, an unblinded interim analysis will be 
performed and a corresponding interim clinical study report (CSR) may be written. The purpose 
of this interim analysis is to perform a comprehensive evaluation of all available double-blind 
data to prepare regulatory submissions for approval of the HS indication. A final analysis and 
updated final CSR will be prepared once all data (through to the SFU visit) have been collected. 
9.8 
Determination of sample size 
A total of 490 study participants will be randomly assigned in a 2:2:2:1 ratio to the following 
treatment arms: 
• Bimekizumab 
 during Initial Treatment Period (Weeks 0-16) and Maintenance 
Treatment (Weeks 16-48) Periods, N=140 
• Bimekizumab 
 during Initial Treatment Period (Weeks 0-16), and Bimekizumab 
 during Maintenance Treatment Period (Weeks 16-48), N=140 
• Bimekizumab 
 during Initial Treatment (Weeks 0-16) and Maintenance 
Treatment Periods (Weeks 16-48), N=140 
• Placebo during Initial Treatment Period (Weeks 0-16), and Bimekizumab 
 
during Maintenance Treatment Period (Weeks 16-48), N=70 
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The analysis of the primary efficacy endpoint and secondary efficacy endpoints are based on a 
comparison of bimekizumab versus placebo at Week 16, with alpha adjustment strategy as 
indicated in Section 9.3.1 and Section 9.3.2. 
The power to detect a statistically significant difference for each of the endpoints are shown in 
Table 9‒1. Notably, with a 2-sided significance level of 0.025, the sample size of 140:70 
provides 73% power for detecting at least a difference of 1.5 (bimekizumab 
 vs placebo) for 
the Worst Pain change from Baseline (CFB) endpoint. 
Given the high level of power for each of the primary and key secondary endpoints at the 
0.025 significance level for the 
 comparison (power≥0.89), and per the alpha spending 
strategy, there is a high likelihood that the 
 comparison of Worst Pain CFB vs placebo will 
be allowed to be tested against the 0.05 level of significance. The power for this latter test is 
81%. The sample size is thus ultimately driven by the Worst Pain CFB endpoint. Furthermore, 
the randomization ratio of 2:2:2:1 has been chosen to provide study participants with a high 
probability (6/7 ~ 86%) of being randomized to active study drug. 
After randomization for this study was complete, an additional endpoint to assess Worst Pain 
response was included in the sequential testing procedure. This additional endpoint is defined as 
HSSDD weekly worst skin pain score at or beyond the threshold for clinically meaningful 
change at Week 16. Note that the power calculations reported in Table 9‒1 for this endpoint are 
based on the sample size that was initially driven by the Worst Pain CFB endpoint as described 
above. With a 2-sided significance level of 0.025, the sample size of 104:52 in the subset of 
participants reporting Baseline HSSDD worst skin pain score at or beyond the threshold for 
clinically meaningful change (ie, Baseline HSSDD ≥threshold value) provides 53% power for 
detecting a statistically significant difference between bimekizumab 
and placebo in the 
proportion of Worst Pain responders.  
Note that the power at the 0.025 level of significance associated with this endpoint for the 
comparison between bimekizumab 
 and placebo is 95%. The 
 comparison of Worst 
Pain response vs placebo against the 0.05 level of significance is therefore likely, and the power 
at this significance level is 65%. Given the strength of the power for the bimekizumab 
 arm 
vs placebo across endpoints, it is considered acceptable to have a relatively low  power for this 
final endpoint in the testing sequence for the bimekizumab 
 treatment arm vs placebo 
 
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Table 9‒1: 
Power calculation assumptions and methods 
Endpoint 
Power 
α = 0.025,  
2-sided 
Assumptions 
 
 
Week 16 Bimekizumab 
 
N=280a 
Week 16 Bimekizumab 
 
N=140 
Week 16 Placebo 
N=70 
HiSCR50 
0.99 
0.90 
Proportion responders=0.60 
Proportion responders=0.50 
Proportion responders=0.25 
HiSCR75 
0.99 
0.98 
Proportion responders=0.45 
Proportion responders=0.35 
Proportion responders=0.10 
Flare 
0.99 
0.99 
Proportion of participants with flare by 
Week 16=0.09 
Proportion of participants with flare by 
Week 16=0.19 
Proportion of participants with flare by 
Week 16=0.52 
DLQI 
0.99 
0.96 
Mean CFB=-5.4; 
SD=6.8 
Mean CFB=-4.8; 
SD=6.8 
Mean CFB=-0.8; 
SD=6.6 
Worst Pain 
CFBb 
0.89 
0.73 
Mean CFB=-2.2; 
SD=3.2 
Mean CFB=-2.0; 
SD=3.2 
Mean CFB=-0.5; 
SD=3.7 
Worst Pain 
Responsec 
0.95 
0.53 
Proportion responders=0.53 
Proportion responders=0.43 
Proportion responders=0.23 
CFB=change from Baseline; 
 SD=standard deviation 
Note: Estimates for HS0004 are based on Week 12 data from the HS0001 study. 
a Pooled 
 at Week 16 from 
 and 
 arms 
b 
Within-subject average of Worst Pain according to 24-hour recall. 
c 
Assumes N=208, 104, 52 in 
 and placebo, respectively, to account for Worst Pain score at or above the threshold for clinically meaningful 
change from Baseline 
 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)- Good Clinical Practice (GCP), and in 
accordance with the ethical principles that have their origin in the Declaration of Helsinki. 
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, 
Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), advertisement (if 
applicable), and all other participant-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 participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
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 participants. 
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 participant 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. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or CRO agreements, as applicable. 
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10.1.3 
Informed consent process 
Study participant’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 study participant in both oral and written form by the 
Investigator (or designee). Each study participant will have the opportunity to discuss the study 
and its alternatives with the Investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the 
participant, or his or her legal representative, and by the person who conducted the informed 
consent discussion (Investigator or designee). The study participant or his or her legal 
representative must receive a copy of the signed and dated ICF. As part of the consent process, 
each study participant must consent to direct access to his or her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection. 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF by 
the IRB/IEC and use of the amended form. 
All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form. 
The study participant may withdraw his or her consent to participate in the study at any time. A 
study participant is considered as enrolled in the study when he or she has signed the ICF. A 
CRF must not be started, nor may any study specific procedure be performed for a given study 
participant, without having obtained his or her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the study participant’s confidentiality. 
Throughout this study, all data forwarded to UCB (or designee) will be identified only by the 
study participant 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 
study participant’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 study participant’s study participation, and autopsy 
reports for deaths occurring during the study). 
The study participant must be informed that his or her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the study participant. 
The study participant must be informed that his or her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
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10.1.5 
Committees structure 
A DMC will be reviewing safety and efficacy data on an ongoing basis. The DMC membership 
includes experienced clinicians and a statistician, all of whom have expertise in clinical studies. 
Further details will be specified in the DMC Charter. 
Cardiovascular, Gastrointestinal, and Neuropsychiatric Adjudication Committees will also 
periodically review data from this study. Details will be provided in the Cardiovascular, 
Gastrointestinal, and Neuropsychiatric Adjudication Committee charters. 
Both DMC and Adjudication Committee members may not participate in the study as principal 
or co-Investigators, or as study participant 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 this study. 
10.1.6 
Data quality assurance 
All study participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the Sponsor or designee electronically (eg, laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of study participants are being 
protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH-GCP, and all applicable regulatory requirements. 
Some study-specific assessments may be conducted remotely according to the study protocol 
during a pandemic or other exceptional circumstance (eg, hurricanes) due to the need to 
implement safety measures and guidance from regulatory authorities (refer to Section 8). Remote 
monitoring visits may be conducted during the COVID-19 pandemic or under other exceptional 
circumstances as deemed appropriate to ensure study participants’ safety where local regulations 
permit. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he or she relocate 
or move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
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study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report. 
10.1.6.1 
Case report form completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
electronic CRFs and in all required reports. 
Any change or correction to the CRF after saving must be accompanied by a reason for the 
change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF. 
Detailed instructions will be provided in the CRF Completion Guidelines. 
10.1.7 
Source documents 
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 CRFs are not considered 
acceptable source documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Electronic Patient-Reported Outcome (ePRO) measures (eg, DLQI, EQ-5D-3L, WPAI-SHP, 
TSQM-9, HiSQOL, Daily HS Symptom Diary, HS Symptom Questionnaire, PGI-S-HS, 
PGI-C-HS, PGI-S-SP, and PGI-C-SP) will be completed by each participant 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). 
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 study participant’s source documents. 
The Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
Electronic data records must be saved and stored as instructed by UCB (or designee). 
10.1.8 
Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
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completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further bimekizumab development 
10.1.9 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
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10.2 
Appendix 2: Clinical laboratory tests 
• The tests detailed in the table below will be performed by the central laboratory. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
Mean corpuscular 
hemoglobin 
Mean corpuscular 
hemoglobin 
concentration 
Mean corpuscular 
volume 
White Blood Cell Count 
with Differential: 
Neutrophils 
Lymphocytes 
Atypical lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry 
Blood urea 
nitrogen 
Potassium 
Alanine aminotransferasea 
Total and direct 
bilirubina,b 
Creatinine 
Sodium 
Aspartate aminotransferasea 
Glucose (record 
fasting or 
nonfasting in CRF) 
Bicarbonate 
Calcium 
Alkaline phosphatase 
Gamma 
glutamyltransferase 
Uric acid 
Chloride 
Magnesium 
hs-CRPc 
Lactate 
dehydrogenase 
Total 
cholesterol 
 
 
Routine 
Urinalysis 
Specific gravity 
pH, glucose, protein, ketones, nitrite, blood by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Other 
Screening Tests 
Pregnancy testingd 
Follicle stimulating hormonee 
Urine drug screen (amphetamines, barbiturates, cocaine, opiates, cannabinoids, and 
benzodiazepines) 
Serology (human immunodeficiency virus, Hepatitis B, Hepatitis C) 
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Protocol-Required Safety Laboratory Assessments 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CRF=case report form; 
hs-CRP=high-sensitivity C-reactive protein; RBC=red blood cell; ULN=upper limit of normal 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.2 and Appendix 6 (Section 10.6). All events of ≥3×ULN ALT or 
AST with coexisting ≥2×ULN total bilirubin in the absence of ≥2×ULN alkaline phosphatase, with no 
alternative explanation for the biochemical abnormality may indicate severe liver injury (possible Hy’s Law) 
and must be reported as an SAE (excluding studies of hepatic impairment or cirrhosis). 
b If total bilirubin is >ULN, a direct bilirubin estimation (%) will be performed. 
c hs-CRP will be tested at specified visits (Table 1‒1). 
d A serum pregnancy test will be performed at Screening for all women of childbearing potential. A urine 
pregnancy test (urine dipstick analyzed locally) is also required at the Baseline Visit and all other visits in the 
Schedule of Activities (Table 1‒1). Pregnancy test results must be negative prior to administering IMP. 
e A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, 
in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient. 
Investigators must document his or her review of each laboratory safety report. 
Laboratory and/or analyte results (eg, hs-CRP, immunogenicity, PK) that could unblind the study 
will not be reported to any blinded study personnel as long as the study remains blinded. 
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10.3 
Appendix 3: Adverse events – definitions and procedures for 
recording, evaluating, follow-up, and reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of IMP, whether or not considered related to the IMP. 
• 
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of IMP. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECG, radiological scans, vital signs measurements), including those 
that worsen from Baseline, considered clinically significant in the medical and scientific 
judgment of the Investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after IMP administration even though it may have been 
present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either IMP or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the 
signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfil the definition of an AE or SAE. 
 
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Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the Investigator to be more 
severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
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Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from Baseline is 
not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Important medical events: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• 
Examples of such events include, but are not limited to, potential Hy’s law, invasive or 
malignant cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
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Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) related 
to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records 
to UCB in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 
should be used as a supportive standardization instrument to evaluate AEs and SAEs but the final 
intensity grading by the Investigator must be mild, moderate, or severe. 
 
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Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between IMP and each occurrence of 
each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to IMP administration will be considered and 
investigated. 
• 
The Investigator will also consult the Investigator’s Brochure and/or Product Information, for 
marketed products, in his or her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he or she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• 
The Investigator may change his or her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the participant is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, 
the Investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information. 
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Reporting of SAEs 
SAE Reporting to UCB via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use the paper 
SAE data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to the UCB study 
physician by telephone. 
• 
Contacts for SAE reporting can be found on the page after the title page of this protocol. 
 
SAE Reporting to UCB via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the Medical Monitor or UCB study physician. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found on the page after the title page of this protocol. 
 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single follicle stimulating hormone measurement is 
insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. 
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Highly Effective Contraceptive Methodsa 
Highly Effective Contraceptive Methods That Are User Dependentb 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly Effective Methods That Are User Independent 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the IMP. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
NOTES:  
a) In case of newly started contraception pills/intrauterine devices, Investigator should consider the 
correct timing of starting/applying such methods in relation to the menstrual cycle and the 
manufacturing instruction as when these newly started methods would become effective. 
b) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants 
participating in clinical studies. 
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. 
• Additional pregnancy testing should be performed as indicated in the Schedule of Activities 
(Table 1‒1) during the treatment period and at 20 weeks after the last dose of IMP and as 
required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected 
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Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive IMP. If the study participant is later found to be on 
placebo, then pregnancy data collection can stop. 
• In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, 
the Investigator or designee is asked to contact the subject to request consent of the partner 
via the Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC 
and should be available in the Investigator site file. In case of questions about the consent 
process, the Investigator may contact the UCB/CRO contract monitor for the study. The 
Investigator will complete the 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 Patient Safety department is also the primary contact for any questions 
related to the data collection for the partner pregnancy, eventual birth, and follow up. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 1 working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the 
follow-up will be at least 12 months after the delivery date. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or indication for 
the procedure. 
Female Participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue IMP or be withdrawn from the study. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 1 working day of learning of a participant’s 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. Generally, the follow-up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy related SAE considered reasonably related to the IMP by the Investigator will be 
reported to the Sponsor as described in Section 8.3.5. While the Investigator is not obligated 
to actively seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting. 
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10.5 
Appendix 5: Genetics 
Use and Analysis of DNA 
Samples for potential future exploratory biomarker research will be collected and stored from 
consenting participants in the study. This sampling is optional for study participants and requires 
a separate informed consent. A decision not to consent does not exclude the study participant 
from the study: 
• Blood sample for DNA. 
These samples will only be used to further understanding of HS and/or how biomarkers, 
including genetic variation, may affect response or be affected by treatment with bimekizumab, 
background products, and/or concomitant medications in study participants with HS. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Participants with potential drug-induced liver injury must be assessed to determine if IMP must 
be discontinued, as outlined in Section 7.1.2. 
All PDILI events must be reported as an AE, and PDILI events meeting SAE criteria should be 
reported to the Sponsor within 24 hours of learning of the occurrence. Any PDILI event that 
meets the criterion for potential Hy’s Law must be reported within 24 hours of 
learning of the occurrence as an AE of special interest (see Section 8.3.6), and, if applicable, also 
reported as an SAE (Section 8.3). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 10‒1 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 10.6.1). 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 7.1.2.1.1). 
 
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Table 10‒1: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥3×ULN 
≥2×ULNb 
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 10.6.3); 
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 
≥3×ULN 
NA 
Yes 
≥8×ULN 
NA 
NA 
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Table 10‒1: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
≥5×ULN 
(and ≥2× 
Baseline) 
and 
<8×ULN 
<2×ULN 
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 10.6.2). 
 
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 
≥5×ULN (and 
≥2× 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 10.6.3). 
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 ≥5×ULN 
<8×ULN, IMP should be 
temporarily withheld and 
subject should undergo repeat 
test in 2 weeks. 
Continue IMP if ALT or AST 
values <5×ULN; continue to 
monitor at least twice per week 
until values normalize, 
stabilize, or return to within 
baseline values. 
If ALT or AST remains 
≥5×ULN after second retest, 
immediate IMP discontinuation 
required. 
Continue to monitor until values 
normalize, stabilize, or return to 
within baseline values.d 
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Table 10‒1: Required investigations and follow-up for PDILI 
Laboratory value 
 
Immediate 
Follow up 
ALT or 
AST 
Total 
bilirubin 
Symptomsa of 
hepatitis or 
hypersensitivity 
Consultation 
requirements 
Actions 
Testing 
Evaluation 
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 ≥2×ULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor. 
c Details provided in Section 10.6.1 . 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 10.6.2. 
e Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of 
the Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed. 
 
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The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor. 
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result. 
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages. 
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative. 
When IMP is stopped due to PDILI (as described in Section 7.1.2.1), 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 10.6.2 are met, rechallenge with IMP may be appropriate. 
The approach to investigate PDILI is summarized in Table 10‒1. 
10.6.1 
Consultation with Medical Monitor and local hepatologist 
Potential drug-induced liver injury events require notification of the Medical Monitor or UCB 
study physician within 24 hours (eg, by laboratory alert), and the study participant must be 
discussed with the Medical Monitor or UCB study physician as soon as possible. If required, the 
study participant 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 10.6.3) and SAE report (if applicable). 
10.6.2 
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 7.1.2 and Table 10‒1 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. 
10.6.2.1 
IMP restart/rechallenge 
Study participants who are immediately discontinued from IMP due to having met certain 
criteria for PDILI (as described in Section 7.1.2 and Table 10‒1), but for whom an alternative 
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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: 
• The results of additional testing and monitoring described in Section 10.6.3 and 
Section 7.1.2.1.1 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 study participant. 
• The study participant has shown clear therapeutic benefit from the IMP. 
• Study participant’s ALT or AST elevations do not exceed ≥3×ULN. 
• Study participant’s total bilirubin is <1.5×ULN. 
• Study participant has no signs or symptoms of hypersensitivity. 
• The rechallenge is approved by the UCB study 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 study participant. 
• Study participant agrees to the Investigator-recommended monitoring plan and understands 
his or her individual benefit risk for restarting IMP and this is adequately documented. 
10.6.3 
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 10‒2 (laboratory measurements) and Table 10‒3 (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 study participant 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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Table 10‒2: 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 
Urine drug screena 
Chemistry 
Amylase 
Sodium, potassium, chloride, glucose, blood urea nitrogen, creatinine 
Total bilirubin, ALP, AST, ALT, gamma-glutamyltransferase, total 
cholesterol, albumin 
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct 
bilirubin 
Serum creatine phosphokinase and lactate dehydrogenase to evaluate possible 
muscle injury causing transaminase elevation 
Additional 
Prothrombin time/INRb 
Serum pregnancy testc 
PK sample 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
HBcAb-IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; 
INR=international normalized ratio; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; 
RNA=ribonucleic acid; ULN=upper limit of normal 
a Tests in addition to the specified analytes may be performed based on the Investigator’s 
medical judgment and study participant history. 
b Measured only for study participants with ALT >8×ULN, 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). 
c For women of childbearing potential. 
Additional information to be collected is presented in Table 10‒3. 
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Table 10‒3: 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 
 
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10.7 
Appendix 7: Medical device AEs, Adverse device effects, SAEs, 
and device deficiencies: definition and procedures for 
recording, evaluating, follow-up, and reporting 
Not applicable to this study. 
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10.8 
Appendix 8: Rapid alert procedures 
Not applicable to this study. 
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10.9 
Appendix 9: Country-specific requirements 
Country-specific requirements will be provided separately, as applicable. 
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10.10 
Appendix 10: Abbreviations and trademarks 
ADAb 
anti-drug antibody 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AN 
abscess and inflammatory nodule 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
CAT 
computed axial tomography 
COVID-19 
coronavirus disease 2019 
CPK 
creatine phosphokinase 
CRF 
case report form 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXR 
chest x-ray 
DLQI 
Dermatology Life Quality Index 
DMC 
Data Monitoring Committee 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic Case Report form 
eC-SSRS 
electronic Columbia-Suicide Severity Rating Scale 
EQ-5D-3L 
European Quality-of-Life 5 dimensions-3 level questionnaire 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
HCV 
hepatitis C virus 
HiSCR 
Hidradenitis Suppurativa Clinical Response 
HiSCR25 
a 25% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count 
HiSCR50 
a 50% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count 
HiSCR75 
a 75% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count 
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HiSCR90 
a 90% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count 
HiSCR100 
a 100% reduction in the total AN count with no increase from Baseline 
in abscess or draining tunnel count 
HiSQOL 
Hidradenitis Suppurativa Quality of Life 
HRT 
hormonal replacement therapy 
HS 
hidradenitis suppurativa 
hs-CRP 
high-sensitivity C-reactive protein 
HSSDD 
Hidradenitis Suppurativa Symptom Daily Diary 
HSSQ 
Hidradenitis Suppurativa Symptom Questionnaire 
IBD 
inflammatory bowel disease 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IGRA 
interferon gamma release assay 
IHS4 
International Hidradenitis Suppurativa Severity score system 
IL 
interleukin 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
LTBI 
latent tuberculosis infection 
M. 
Mycobacterium 
mAb 
monoclonal antibody 
NTM 
nontuberculous mycobacterial 
NRS 
numeric rating scale 
NSAID 
nonsteroidal anti-inflammatory drug 
PDILI 
potential drug-induced liver injury 
PEOT 
Premature End of Treatment Visit 
PGI-C-HS 
Patient Global Impression of Change in Hidradenitis Suppurativa 
Severity 
PGI-C-SP 
Patient Global Impression of Change in Severity of Skin Pain 
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PGI-S-HS 
Patient Global Impression of Hidradenitis Suppurativa Severity 
PGI-S-SP 
Patient Global Impression of Severity of Skin Pain 
PHQ-9 
Patient Health Questionnaire Depression Module-9 
PK 
pharmacokinetic(s) 
PRN 
as needed 
PRO 
patient-reported outcome 
PSO 
psoriasis 
 
 
 
 
QOL 
quality of life 
RS 
Randomized Set 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sc 
subcutaneous 
SFU 
Safety Follow-up 
TEAE 
treatment-emergent adverse event 
TB 
tuberculosis 
TSQM-9 
Treatment Satisfaction Questionnaire – Medication 9 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
WPAI-SHP 
Workers Productivity and Activity Impairment Questionnaire: Specific 
Health Problem 
 
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10.11 
Appendix 11: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment 
(Amendment 4) is located directly before the Table of Contents. 
Amendment 3 (09 Feb 2021) 
Overall Rationale for the Amendment 
The main reason for this protocol amendment is due to Regulatory Agency feedback and to 
provide procedural clarifications. 
Section # and Name 
Description of Change 
Brief Rationale 
Title page  
• National Clinical Trial (NCT) 
number has been added  
NCT number was received on 
24 Jan 2020 
Serious adverse event 
reporting  
• Fax and email for Japan have been 
removed  
To align with safety reporting 
guidelines 
1.1 Synopsis 
2.1 Study rationale 
2.2 Background 
• Updated description of 
bimekizumab and other minor 
edits 
• Order of secondary efficacy 
endpoints aligned with closed 
testing procedure (Figure 9-1) 
Rationale is the same as the 
description 
1.1 Synopsis (Treatment 
Groups and Duration) 
 
• Updated Baseline antibiotic 
therapy strata to remove the 30% 
cap on enrollment 
• Sentences updated as unblinded 
efficacy data analysis is planned to 
be provided when approximately 
66% of study participants have 
reached the primary efficacy 
endpoint at Week 16 rather than 
50% and 100%. 
Removed the Baseline 
antibiotic strata cap per US 
FDA advice (Baseline 
antibiotic use should coincide 
with the prevalence of 
antibiotic use for the disease) 
To align with the final Data 
Monitoring Committee Charter 
(DMC) Charter and DMC 
Statistical Analysis Plan (SAP)  
1.3 Schedule of activities 
• Extended the line for concomitant 
medications and adverse events to 
show they are collected through 
the Safety Follow-Up Visit 
• Added an additional footnote that 
past medical history includes 
tobacco and alcohol use  
• Added Note in footnotes that study 
assessments could be completed 
remotely in exceptional 
circumstances 
• Footnote “n” (formally footnote 
“m”) has been updated regarding 
collection of Hurley Stage 
To align collection of adverse 
events and concomitant 
medications with the protocol 
body text 
 
To include/clarify that tobacco 
and alcohol use is part of the 
medical history 
Provided operational flexibility 
to allow assessments to be 
collected remotely due to 
COVID-19 or other exceptional 
circumstance (eg, hurricanes) 
 
Clarification to make footnote 
“n” consistent with the table 
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Section # and Name 
Description of Change 
Brief Rationale 
regarding collection of Hurley 
Stage 
3 Objectives and endpoints 
Other 
• Order of secondary efficacy 
endpoints aligned with closed 
testing procedure (Figure 9-1) 
• Other safety topics of interest 
endpoints were updated 
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 Patient Health 
Questionnaire 9 (PHQ-9) and 
will be captured via routine 
adverse event (AE) reporting 
during the study. This update is 
considered a procedural change. 
 
Rational for reordering the 
secondary efficacy endpoints is 
the same as the description. 
4.1 Overall design 
4.2 Scientific rationale for 
study design 
• Updated Baseline antibiotic strata 
to remove the 30% cap on 
enrollment 
Removed the Baseline 
antibiotic strata cap per US 
FDA advice (Baseline 
antibiotic use should coincide 
with the prevalence of 
antibiotic use for the disease) 
5.1 Inclusion criteria 
• Criteria #2 added text that 
diagnosis must be verifiable 
through medical notes and 
documentation 
Criteria #5 was edited for clarity, 
and added text that 
diagnosis/inadequate response 
must be verifiable through medical 
notes and documentation 
Clarification of criteria 
5.2 Exclusion criteria 
• Criterion #16 text was updated to 
clarify use of the Screening 
Version of the electronic 
Columbia-Suicidality Severity 
Rating Scale (eC-SSRS) 
• Criterion #19 was updated to 
exclude participants with prior use 
of an IL-17 biologic response 
modifier or participation in an 
IL-17 biologic response modifier 
study unless an appropriate 
washout period (within 6 months 
Clarification of criterion #16 as 
it is actually collected and 
assessed 
Criterion #19 was modified to 
allow enrollment of a moderate 
to severe HS population with 
real-world prior use of other 
medications with appropriate 
washout periods 
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Section # and Name 
Description of Change 
Brief Rationale 
prior to the Baseline Visit or 
5 half-lives, whichever is greater) 
has been performed 
5.4 Screen failures 
• Added bullet explaining that study 
participants who require incision 
and drainage procedures for HS 
lesions are to be screen failed 
Updated the screen failure 
criteria 
6.5.1 Permitted 
concomitant treatments  
• Wound care updated to add that 
use of wound care dressings will 
be recorded  
• Added Lesion care 
• Updated Baseline antibiotic strata 
to remove the 30% cap on 
enrollment 
Clarifications of and additions 
to allowed concomitant 
treatments Removed the 
Baseline antibiotic strata cap 
per US FDA advice (Baseline 
antibiotic use should coincide 
with the prevalence of 
antibiotic use for the disease) 
6.5.2 Prohibited 
concomitant treatments 
• Added washout periods for 
systemic antibiotics if applicable; 
other biologics; IL-17, IL-12, and 
IL-23 inhibitors; and janus kinase 
inhibitors 
• Filgotinib and Upadacitnib added 
under janus kinase inhibitors 
• Text added to clarify topical drugs 
• Added herbal medications for HS 
and a washout period 
• Updated vaccine criteria 
• Text added to clarify that 
medications listed are currently 
available medications, but the 
protocol will account for medicine 
approvals in a given class during 
the course of the study 
Clarification of prohibited 
medications/therapies and the 
criteria for their exclusion and 
to allow enrollment of a 
moderate to severe HS 
population with real-world 
prior use of other medications 
(current and future) with 
appropriate washout periods 
7.1 Discontinuation of 
study medication 
• Added a paragraph to clarify 
procedures if a study participant 
tested positive for COVID-19 or a 
suspected COVID-19 infection 
Updated for the COVID-19 
pandemic 
7.1.2.1 PDILI 
discontinuation criteria  
• Removed ‘and permanent’ from 
the first sentence and a 
crossreference to Section 10.6.2.1 
has been included 
To be consistent with the PDILI 
criteria throughout the protocol 
and Appendix 10.6 
7.1.3 Treatment 
interruptions 
• Text was updated to clarify that 
doses of IMP that were missed due 
to a reasonable interfering AE that 
does not allow administration of 
IMP due to safety reasons, will not 
be considered for the evaluation of 
study participant discontinuation. 
Clarification of study 
procedures. 
 
In line with the exclusion 
criterion regarding infections, a 
specific infection-related IMP 
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Section # and Name 
Description of Change 
Brief Rationale 
It is still used to calculate 
compliance. 
• A specific infection-related IMP 
interruption criterion has been 
added 
interruption criterion was added 
to clarify that participants with 
serious or recurrent infections 
not responding to standard 
therapies are not exposed to 
immunomodulatory therapies 
until their infection has 
resolved. This is in line with 
most biologic therapies, 
including other anti-IL17s. 
7.2 Participant 
discontinuation/withdrawal 
from the study 
• Added cross-reference to 
pregnancy section  
Clarification of study 
procedures 
8 Study Assessments and 
Procedures 
• Added text about allowing study 
assessments to be performed 
remotely during a pandemic or 
other exceptional circumstance 
Updated to allow study to 
proceed during COVID-19, and 
other exceptional circumstances 
(eg, hurricanes) 
8.1.1 Lesion count 
• Removed “hypertrophic” from 
description of scars and added “HS 
lesions” 
Clarification of lesion 
definition 
8.1.4.6 Euro-Quality of 
Life 5-Dimensions, 3 
levels 
• Removed sentences #2 and #3 
regarding summary index scores 
• Added a clarification to the last 
sentence 
Sentence removed in line with 
SAP update as index scores are 
not required for the clinical 
study report 
8.2.2 Vital signs 
• Noncontact forehead added to 
body temperature measurement 
Updated for the COVID-19 
pandemic and to align with the 
electronic Case Report Form 
(eCRF) 
8.2.6.1 Assessments at 
Screening 
• Specified that the TB questionnaire 
is administered by the Investigator 
or their designee 
Clarification of study procedure 
8.2.6.3.3 Tuberculosis 
questionnaire 
• Specified that the questionnaire is 
administered by the Investigator or 
their designee 
Clarification of study procedure 
8.3 Adverse events and 
serious adverse events 
• Added statement that cases of 
COVID-19 infection will be 
recorded as AEs (or SAEs , as 
required) 
Updated for the COVID-19 
pandemic 
8.3.5 Pregnancy  
• Bulletpoint #2 “or be down-titrated 
as instructed at the early 
discontinuation visit” was deleted  
Down titration of bimekizumab 
is not required if IMP needs to 
be discontinued 
8.3.7 Other safety topics of 
interest 
• Deleted depression from list of 
AEs considered safety topics of 
interest 
• Updated “liver function test 
changes/enzyme elevations” to 
With progressive development 
of bimekizumab and based on 
the ongoing review of emerging 
safety data, depression has been 
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Section # and Name 
Description of Change 
Brief Rationale 
“hepatic events and potential drug-
inducted liver injury (PDILI)” 
• Clarified major “adverse” 
cardiovascular events 
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 
 
To align with UCB internal 
documents regarding 
assessment of hepatic events 
and PDILI 
 
Typographical error corrected 
for major adverse 
cardiovascular events 
9.1.7 COVID-19 Free Set 
• Addition of subsection for a 
COVID-19 Free analysis set  
Updated for the COVID-19 
pandemic 
9.3.1 Analysis of the 
primary efficacy endpoint 
• Cross reference added to Section 
9.3.4 for additional sensitivity 
analyses related to the assessment 
of COVID-19 pandemic on the 
primary efficacy endpoint analysis 
Updated for the COVID-19 
pandemic 
9.3.2 Analysis of 
secondary efficacy 
endpoints  
• Points #3 and #4 have been 
reordered to be consistent with 
Figure 9-1 (Closed Testing 
Procedure).  
• Missing figure caption was added  
Rational is the same as the 
description 
9.3.4 COVID-19 impact 
analysis 
• Addition of subsection for 
COVID-19 impact analysis  
Updated for the COVID-19 
pandemic 
9.4.1 Safety analysis  
• Addition of sentence that 
Summaries of Confirmed and 
Suspected COVID-19 TEAEs, 
respectively, will be presented and 
their definitions will be provided in 
the SAP 
Updated for the COVID-19 
pandemic 
9.5 Handling of protocol 
deviations 
• Added statement that COVID-
related protocol deviations would 
be listed and summarized 
separately 
Updated for the COVID-19 
pandemic 
9.7.1 Data Monitoring 
Committee  
• Sentences updated as unblinded 
efficacy data analysis is planned to 
be provided when 66% of study 
participants have reached the 
To align with the final DMC 
Charter and DMC SAP 
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Section # and Name 
Description of Change 
Brief Rationale 
primary efficacy endpoint at Week 
16 rather than at 50% and 100%.  
10.1.6 Data quality 
assurance 
• Added statement about performing 
some study-specific assessments 
remotely under certain exceptional 
circumstances 
Updated for the COVID-19 
pandemic and other exceptional 
circumstances (eg, hurricanes) 
10.4 Appendix 4: 
Contraceptive guidance 
and collection of 
pregnancy information 
• Deleted footnote “c” regarding 
hormonal contraception. 
“Hormonal contraception may be 
susceptible to interaction with the 
IMP, which may reduce the 
efficacy of the contraceptive 
method. In this case, 2 highly 
effective methods of contraception 
should be utilized during the 
treatment period and for at least 20 
weeks after the last dose of IMP” 
To be consistent with other 
studies in the bimekizumab 
program 
10.6 Appendix 6: Liver 
safety – suggested actions 
and follow-up assessments 
• Paragraph #2 has been updated to 
add that PDILI events meeting 
SAE criteria should be reported to 
the Sponsor within 24 hours of 
learning of the occurrence. The 
requirement to report to the study 
site has been removed.  
Correction of typographical 
error and clarification of 
reporting procedures 
10.11 Appendix 11: 
Protocol amendment 
history 
• Updated with changes from 
previous global amendment  
Self-evident 
Throughout 
• Minor editorial and formatting 
revisions 
Minor edits and formatting 
revisions that do not impact 
content were made for 
readability and/or clarity 
 
Amendment 2 (16 Dec 2019) 
Overall Rationale for the Amendment 
The main reason for global protocol amendment 2 was to update the study 
discontinuation/withdrawal criteria for study participants with IBD.  
Section # and Name 
Description of Change 
Brief Rationale 
7.2 Participant 
discontinuation/withdrawal 
from the study 
• Added text to IBD 
discontinuation/withdrawal criteria 
Previously approved text 
relating to 
discontinuation/withdrawal 
criteria for IBD was 
inadvertently removed 
from the original version 
of the protocol dated 
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Section # and Name 
Description of Change 
Brief Rationale 
29 Oct 2019. It is now 
being replaced 
7.2 Participant 
discontinuation/withdrawal 
from the study 
• Fixed numbering in list of criteria  
Corrected typographical 
error in list numbering 
10.11 Appendix 11: Protocol 
amendment history 
• Updated with changes from previous 
global protocol amendment 1  
Updated 
 
Amendment 1 (06 Dec 2019) 
Overall Rationale for the Amendment 
The main reason for global protocol amendment 1 was to update the company name in line with 
the new Code of Companies and Associations recently adopted by Belgium.  
Section # and Name 
Description of Change 
Brief Rationale 
Title page 
• Updated company name from UCB 
Biopharma SPRL to UCB Biopharma 
SRL 
Change in company 
name on 02 Dec 2019 
3 Objectives and Endpoints 
• Clarified wording of exploratory 
biomarker objective 
Clarification of objective 
with current genetics and 
biomarkers sections 
(Section 8.7 and 
Section 8.9, respectively) 
8.2.6.3.7 Tuberculosis 
management of LTBI, active 
TB, or other NTB infection 
identified during study 
• Figure 8-1 was updated to reflect 
Screening terminology as follows: 
− 
Green ovals that said “subject 
eligible for study continuation” or 
“subject eligible to continue the 
study” in original protocol were 
changed to say “subject eligible for 
study” 
− 
Red ovals that said “withdraw 
from the study” were changed to 
say “subject NOT eligible for 
study” 
Figure 8-1 was corrected 
to reflect Screening 
terminology 
10.11 Appendix 11: Protocol 
amendment history 
• Stated location of summary of changes 
table for the current amendment  
Updated 
 
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11 
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3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016a;375(5):422-34. 
Kimball AB, Sobell JM, Zouboulis CC, Gu Y, Williams DA, Sundaram M, et al. HiSCR 
(Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic 
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outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 
2 adalimumab study. J Eur Acad Dermatol Venereol. 2016b;30(6):989-94. 
McMillan, K. Hidradenitis suppuratica: number of diagnosed patients, demographic 
characteristics, and treatment patterns in the United States. Am J Epidemiol. 
2014;179(12):1477-83. 
Martorell A, García-Martínez FJ, Jiménez-Gallo D, Pascual JC, Pereyra-Rodriguez J, Salgado L, 
Vilarrasa E. An update on hidradenitis suppurativa (part I): epidemiology, clinical aspects, and 
definition of disease severity. Actas Dermo-Sifiliográficas (English Edition). 2015 Nov 
1;106(9):703-15. 
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. 
Naldi L. Epidemiology. In: Hidradenitis Suppurativa. Chapter 8. Jemec GB, Revuz J, Leyden J, 
editors. Springer-Verlag. 2006:58-64. 
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. 
Prens E, Deckers I. Pathophysiology of hidradenitis suppurativa: an update. J Am Acad 
Dermatol. 2015;73(5):S8-11. 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. PharmacoEconomics. 1993:4(5):353-65. 
Revuz JE, Canoui-Poitrine F, Wolkenstein P, Vialette C, Gabison G, Pouget F, et al. Prevalence 
and factors associated with hidradenitis suppurativa: results from two case-control studies. J Am 
Acad Dermatol. 2008;59(4):596-601. 
Riis PT, Søeby K, Saunte DM, Jemec GB. Patients with hidradenitis suppurativa carry a higher 
systemic inflammatory load than other dermatological patients. Archives of dermatological 
research. 2015 Dec 1;307(10):885-9. 
Riis PT, Vinding GR, Ring HC, Jemec GB. Disutility in patients with hidradenitis suppurativa: a 
cross-sectional study using EuroQoL-5D. Acta Derm Venereol. 2016;96(2):222-6. 
Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring of hidradenitis suppurativa 
reflecting the role of tobacco smoking and obesity. Br J Dermatol. 2009;161(4):831-9. 
Schlapbach C, Hänni T, Yawalkar N, Hunger RE. Expression of the IL-23/TH17 pathway in 
lesions of hidradenitis supprativa. J Am Acad Dermatol. 2011;65(4):790-8. 
Sun H, Snyder E, Koch GG. Statistical planning in confirmatory clinical trials with multiple 
treatment groups, multiple visits, and multiple endpoints. J Biopharmaceut Stat. 
2018;28(1):189-211. 
Thorlacius L, Ingram JR, Villumsen B, et al. A core domain set for hidradenitis suppurativa trial 
outcomes: an international Delphi process. Br J Dermatol. 2018. 
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Van der Zee HH, de Ruiter L, Van Den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated 
levels of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐10 in hidradenitis 
suppurativa skin: a rationale for targeting TNF‐α and IL‐1β. British Journal of Dermatology. 
2011 Jun;164(6):1292-8. 
Vender R, Lynde C, Ho V, Chau D, Poulin-Costello M. Work productivity and healthcare 
resource utilization outcomes for patients on etanercept for moderate to severe plaque psoriasis: 
Results from a 1-year, multicentre, open-label, single-arm study in a clinical setting. Appl Health 
Econ Health Policy. 2012:10(5):343-53. 
von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J 
Dermatol. 2001;144:809-13. 
Wolkenstein P, Loundou A, Barrau K, Auquier P, Revuz J; Quality of Life Group of the French 
Society of Dermatology. Quality of life impairment in hidradenitis suppurativa: a study of 61 
cases. J Am Acad Dermatol. 2007;56:621–3. 
Zouboulis CC, Desai N, Emtestam L, Hunger RE, Loannides D, Juhász I, et al. European S1 
guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol 
Venereol. 2015;29(4):619-44. 
Zouboulis CC, Tzellos T, Kyrgidis A. Development and validation of IHS4, a novel dynamic 
scoring system to assess hidradenitis suppurativa/acne inversa severity. Br J Dermatol. 
2017;177:1401-9. 
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SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice. 
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Approval Signatures
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Document Number:
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Title:
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Approved Date:
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Document Approvals
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Statistical Analysis Plan 
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STATISTICAL ANALYSIS PLAN  
Study: HS0004 
Product: Bimekizumab 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER STUDY EVALUATING THE 
EFFICACY AND SAFETY OF BIMEKIZUMAB IN STUDY 
PARTICIPANTS WITH MODERATE TO SEVERE HIDRADENITIS SUPPURATIVA 
 
 
 
 
 
 
SAP/Amendment Number Date 
Final SAP 
29 May 2020 
SAP Amendment 1 
15 Oct 2021  
SAP Amendment 2 
06 Jul 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. 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 9 
1 
INTRODUCTION ........................................................................................................... 13 
2 
PROTOCOL SUMMARY ............................................................................................... 13 
2.1 
Study objectives ........................................................................................................... 13 
2.1.1 
Primary objective ................................................................................................. 13 
2.1.2 
Secondary objectives ........................................................................................... 13 
2.1.3 
Other objectives ................................................................................................... 13 
2.1.4 
Exploratory objective ........................................................................................... 13 
2.2 
Study endpoints ............................................................................................................ 14 
2.2.1 
Efficacy endpoints ............................................................................................... 14 
2.2.1.1 
Primary efficacy endpoint ......................................................................... 14 
2.2.1.2 
Secondary efficacy endpoints .................................................................... 14 
2.2.1.3 
Other efficacy endpoints ........................................................................... 14 
2.2.2 
Pharmacokinetic and pharmacogenomic endpoints ............................................. 16 
2.2.2.1 
Pharmacokinetic endpoints ........................................................................ 16 
2.2.2.2 
Exploratory pharmacogenomic endpoints ................................................. 16 
2.2.3 
Safety endpoints ................................................................................................... 16 
2.2.3.1 
Secondary safety endpoints ....................................................................... 16 
2.2.3.2 
Other safety endpoints ............................................................................... 16 
2.2.4 
Immunological endpoints .................................................................................... 17 
2.3 
Study design and conduct ............................................................................................ 17 
2.3.1 
Study description ................................................................................................. 17 
2.3.2 
Study periods ....................................................................................................... 18 
2.3.2.1 
Screening Period ........................................................................................ 18 
2.3.2.2 
Initial Treatment Period (Weeks 0-16) and Maintenance Treatment Period 
(Weeks 16-48) ........................................................................................... 18 
2.3.2.3 
Safety Follow-up Visit .............................................................................. 18 
2.3.3 
Study duration per participant ............................................................................. 18 
2.3.4 
Planned number of participants and sites ............................................................ 19 
2.3.5 
Anticipated regions and countries ....................................................................... 19 
2.4 
Determination of sample size ....................................................................................... 19 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 21 
3.1 
General presentation of summaries and analyses ........................................................ 21 
3.2 
General study level definitions .................................................................................... 22 
3.2.1 
Relative day ......................................................................................................... 22 
3.2.2 
Mapping of data from Premature End of Treatment visits .................................. 23 
3.3 
Definition of Baseline values ....................................................................................... 23 
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3.4 
Protocol deviations....................................................................................................... 24 
3.5 
Analysis sets................................................................................................................. 24 
3.5.1 
Enrolled Set ......................................................................................................... 24 
3.5.2 
Randomized Set ................................................................................................... 24 
3.5.3 
Safety Set ............................................................................................................. 24 
3.5.4 
Full Analysis Set .................................................................................................. 24 
3.5.5 
Active Medication Set ......................................................................................... 25 
3.5.6 
Maintenance Set ................................................................................................... 25 
3.5.7 
Per-Protocol Set ................................................................................................... 25 
3.5.8 
Pharmacokinetics Per-Protocol Set ...................................................................... 25 
3.5.9 
COVID-19 Free Set ............................................................................................. 25 
3.6 
Treatment assignment and treatment groups ............................................................... 25 
3.7 
Center pooling strategy ................................................................................................ 25 
3.8 
Coding dictionaries ...................................................................................................... 26 
3.9 
Definition of an intercurrent event ............................................................................... 26 
3.10 
Changes to protocol-defined analyses ......................................................................... 27 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 28 
4.1 
Adjustments for covariates .......................................................................................... 28 
4.2 
Handling of dropouts or missing data .......................................................................... 28 
4.2.1 
Efficacy data ........................................................................................................ 28 
4.2.1.1 
Handling missing data for the primary efficacy endpoint ......................... 28 
4.2.1.2 
Handling missing data for the secondary efficacy endpoints .................... 29 
4.2.1.3 
Handling missing data for the other efficacy endpoints ............................ 29 
4.2.1.4 
Missing Data Overview and Summary...................................................... 29 
4.2.2 
Missing data algorithms for efficacy analyses ..................................................... 31 
4.2.2.1 
MI – MCMC / Monotone Regression ....................................................... 31 
4.2.2.2 
MI – MCMC / Reference-based imputation .............................................. 36 
4.2.2.3 
Tipping Point Analysis .............................................................................. 37 
4.2.3 
Rationale for estimand ......................................................................................... 39 
4.2.3.1 
Composite estimand .................................................................................. 39 
4.2.3.2 
Hypothetical estimand ............................................................................... 40 
4.2.4 
Dates and times .................................................................................................... 40 
4.3 
Interim analyses and data monitoring .......................................................................... 42 
4.3.1 
Data monitoring committee ................................................................................. 42 
4.3.2 
Interim analysis .................................................................................................... 42 
4.4 
Multicenter studies ....................................................................................................... 42 
4.5 
Multiple comparisons/multiplicity ............................................................................... 42 
4.6 
Use of an efficacy subset of participants ..................................................................... 44 
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4.7 
Active-control studies intended to show equivalence .................................................. 44 
4.8 
Examination of subgroups ........................................................................................... 44 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 46 
5.1 
Study participant disposition........................................................................................ 46 
5.2 
Impact of COVID-19 ................................................................................................... 46 
5.3 
Protocol deviations....................................................................................................... 47 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 47 
6.1 
Demographics .............................................................................................................. 47 
6.2 
Other Baseline characteristics ...................................................................................... 48 
6.3 
Medical history and concomitant diseases ................................................................... 49 
6.4 
Prior and concomitant medications .............................................................................. 49 
6.4.1 
Assignment of medications to study period ......................................................... 50 
6.4.2 
Classification of participants as analgesic, antihistamine users .......................... 50 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 51 
8 
EFFICACY ANALYSES ................................................................................................ 51 
8.1 
Lesion count assessment .............................................................................................. 52 
8.2 
Primary efficacy endpoint ............................................................................................ 53 
8.2.1 
Derivation of HiSCR50 at Week 16 ..................................................................... 57 
8.2.2 
Primary analysis of the primary efficacy endpoint .............................................. 58 
8.2.3 
Sensitivity analyses of the primary efficacy endpoint ......................................... 59 
8.2.3.1 
Nonresponse imputation ............................................................................ 59 
8.2.3.2 
MI-MCMC / Reference-based imputation ................................................ 59 
8.2.3.3 
Tipping point analysis ............................................................................... 59 
8.2.3.4 
Treatment policy ........................................................................................ 60 
8.2.3.5 
Analysis on observed cases ....................................................................... 60 
8.2.3.6 
Analysis on FAS ........................................................................................ 60 
8.2.3.7 
Analysis on PPS ........................................................................................ 60 
8.2.3.8 
Analysis on CFS ........................................................................................ 60 
8.2.3.9 
Analysis including COVID-19 impact as intercurrent event .................... 60 
8.2.3.10 
Cochran-Mantel-Haenszel test .................................................................. 61 
8.2.3.11 
Center-by-Treatment Interaction ............................................................... 61 
8.3 
Secondary efficacy endpoints ...................................................................................... 62 
8.3.1 
HiSCR75 at Week 16 ............................................................................................ 67 
8.3.2 
Flare by Week 16 ................................................................................................. 67 
8.3.3 
Change from Baseline in DLQI Total Score at Week 16 .................................... 67 
8.3.3.1 
Primary analysis of change from Baseline in DLQI Total score at Week 
16 69 
8.3.3.2 
Sensitivity analysis of change from Baseline in DLQI Total score at Week 
16 69 
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8.3.4 
Change from Baseline in Skin Pain score at Week 16, as assessed by the “worst 
skin pain” item in the HSSDD ............................................................................. 69 
8.3.4.1 
Primary analysis of change from Baseline in skin pain score at Week 16 70 
8.3.4.2 
Sensitivity analysis of change from Baseline in skin pain score at Week 
16 70 
8.3.5 
HSSDD skin pain response at Week 16 .............................................................. 70 
8.3.5.1 
Primary analysis of skin pain response at Week 16 .................................. 70 
8.3.5.2 
Sensitivity analyses of Skin Pain Response at Week 16 ........................... 71 
8.4 
Other efficacy endpoints .............................................................................................. 71 
8.4.1 
HiSCR endpoints ................................................................................................. 71 
8.4.1.1 
HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 ............................ 71 
8.4.1.2 
Time to response of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and 
HiSCR100 ................................................................................................... 72 
8.4.1.3 
HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response at both 
Weeks 16 and 48 ....................................................................................... 73 
8.4.1.4 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100 among Week 16 Responders73 
8.4.1.5 
Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 in 
Week 16 responders .................................................................................. 73 
8.4.1.6 
Partial response .......................................................................................... 74 
8.4.2 
Lesion count ......................................................................................................... 74 
8.4.2.1 
Change from Baseline in lesion count ....................................................... 74 
8.4.2.2 
AN count of 0, 1, or 2 ................................................................................ 75 
8.4.2.3 
AN25, AN50, AN75, AN90, AN100................................................................ 75 
8.4.3 
Flare relative to Baseline ..................................................................................... 75 
8.4.4 
Time to flare by Week 16 .................................................................................... 76 
8.4.5 
Time to flare by Week 48 .................................................................................... 76 
8.4.6 
International Hidradenitis Suppurativa Severity Score System (IHS4)............... 77 
8.4.7 
HS-Physician’s Global Assessment 6-point scale ............................................... 77 
8.4.8 
High Sensitivity C-Reactive Protein (hs-CRP) .................................................... 80 
8.4.9 
Initiation of systemic antibiotic rescue therapy ................................................... 81 
8.4.10 
Time to initiation of systemic rescue therapy in the Initial Treatment Period .... 81 
8.4.11 
Time to an intercurrent event in the Initial Treatment Period ............................. 81 
8.4.12 
Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) ................................ 82 
8.4.13 
Hidradenitis Suppurativa Symptom Questionnaire (HSSQ) ............................... 83 
8.4.14 
DLQI .................................................................................................................... 84 
8.4.15 
Hidradenitis Suppurativa Quality of Life (HiSQOL) .......................................... 84 
8.4.16 
Patient Global Impression of HS Severity (PGI-S-HS) ....................................... 86 
8.4.17 
Patient Global Impression of Change in HS Severity (PGI-C-HS) ..................... 86 
8.4.18 
Patient Global Impression of Severity of Skin Pain (PGI-S-SP) ......................... 86 
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8.4.19 
Patient Global Impression of Change in Severity of Skin Pain (PGI-C-SP) ....... 86 
8.4.20 
Euro-Quality of Life 5-Dimensions, 3 levels (EQ-5D-3L) ................................. 87 
8.4.21 
Work Productivity and Activity Impairment Questionnaire–Specific Health 
Problem (WPAI-SHP) v2.0 adapted to HS scores ............................................... 87 
8.4.22 
Treatment Satisfaction Questionnaire – Medication-9 ........................................ 88 
8.4.23 
Lesion intervention .............................................................................................. 89 
8.5 
Additional statistical analyses of other efficacy endpoints .......................................... 89 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 90 
9.1 
Pharmacokinetics ......................................................................................................... 90 
9.2 
Pharmacodynamics ...................................................................................................... 91 
9.3 
Immunogenicity ........................................................................................................... 91 
9.3.1 
Autoantibodies ..................................................................................................... 91 
9.3.2 
Anti-bimekizumab antibodies .............................................................................. 91 
10 SAFETY ANALYSES ..................................................................................................... 95 
10.1 
Extent of exposure ....................................................................................................... 95 
10.1.1 
Exposure during the Initial Treatment Period ..................................................... 96 
10.1.1.1 
Study medication duration (days) .............................................................. 96 
10.1.1.2 
Time at risk (days) ..................................................................................... 96 
10.1.2 
Exposure during the Maintenance Treatment Period .......................................... 97 
10.1.2.1 
Study medication duration (days) .............................................................. 97 
10.1.2.2 
Time at risk (days) ..................................................................................... 97 
10.1.3 
Exposure during the Initial and Maintenance Treatment Period ......................... 98 
10.1.3.1 
Study medication duration (days) .............................................................. 98 
10.1.3.2 
Time at risk (days) ..................................................................................... 98 
10.2 
Adverse events ............................................................................................................. 99 
10.2.1 
Data considerations .............................................................................................. 99 
10.2.1.1 
COVID-19 related considerations ........................................................... 101 
10.2.2 
AE summaries .................................................................................................... 101 
10.2.3 
Other Safety topics of interest ........................................................................... 103 
10.2.3.1 
Infections (serious, opportunistic, fungal and TB) .................................. 103 
10.2.3.2 
Malignancies ........................................................................................... 106 
10.2.3.3 
Major adverse cardiac event .................................................................... 106 
10.2.3.4 
Neutropenia ............................................................................................. 108 
10.2.3.5 
Suicidal Ideation and Behavior ............................................................... 108 
10.2.3.6 
Inflammatory bowel disease .................................................................... 109 
10.2.3.7 
Hypersensitivity (including anaphylaxis) ................................................ 110 
10.2.3.8 
Hepatic events and PDILI ....................................................................... 111 
10.3 
Clinical laboratory evaluations .................................................................................. 111 
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10.4 
Vital signs, physical findings, and other observations related to safety .................... 114 
10.4.1 
Vital signs .......................................................................................................... 114 
10.4.2 
Electrocardiograms ............................................................................................ 115 
10.4.3 
Other safety endpoints ....................................................................................... 115 
10.4.3.1 
Physical examination ............................................................................... 116 
10.4.3.2 
Columbia-Suicide Severity Rating Scale (C-SSRS) ............................... 116 
10.4.3.3 
Assessment and management of TB and TB risk factors ........................ 116 
10.4.3.4 
Pregnancy testing .................................................................................... 117 
10.4.3.5 
Patient Health Questionnaire (PHQ)-9 scores ......................................... 117 
11 REFERENCES .............................................................................................................. 118 
12 APPENDICES ............................................................................................................... 120 
12.1 
Appendix A: MedDRA algorithmic approach to anaphylaxis ................................... 120 
12.2 
Appendix B: Definition of CTCAE grades ................................................................ 122 
13 AMENDMENT TO THE STATISTICAL ANALYSIS PLAN .................................... 124 
13.1 
Amendment 1 ............................................................................................................. 124 
13.2 
Amendment 2 ............................................................................................................. 177 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................... 206 
 
LIST OF TABLES 
Table 2‒1: 
Power calculation assumptions and methods ................................................... 20 
Table 3‒1: 
Geographic regions and corresponding countries ............................................ 25 
Table 4‒1: 
Missing data handling approach by endpoint priority and type ....................... 30 
Table 4‒2: 
Imputation allowable ranges by variable ......................................................... 33 
Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint ................................... 53 
Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses ............................... 62 
Table 8‒3: 
Dermatology Life Quality Index ...................................................................... 68 
Table 8‒4: 
HS-Physician's Global Assessment 6-point scale ............................................ 77 
Table 8‒5: 
Hidradenitis Suppurative Quality of Life ........................................................ 85 
Table 10‒1: 
Cardiovascular event classifications .............................................................. 107 
Table 10‒2: 
Neuropsychiatric event classifications ........................................................... 109 
Table 10‒3: 
IBD event classifications ............................................................................... 110 
Table 10‒4: 
Definitions of Markedly Abnormal Liver Function Values .......................... 112 
Table 10‒5: 
Definitions of Markedly Abnormal Biochemistry Values ............................. 113 
Table 10‒6: 
Definitions of Markedly Abnormal Hematology Values ............................... 113 
Table 10‒7: 
Definitions of Markedly Abnormal Blood Pressure Values .......................... 115 
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Table 12‒1: 
Definition of CTCAE grades by biochemistry parameters ............................ 122 
Table 12‒2: 
Definitions of CTCAE grades by hematology parameter .............................. 122 
Table 2‒1: 
Power calculation assumptions and methods ................................................. 180 
Table 13‒2: 
Imputation allowable ranges by variable ....................................................... 182 
Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint ................................. 187 
Table 813‒2: Estimand Details and Attributes for Secondary Analyses ............................. 189 
Table 13‒1: 
Cardiovascular event classifications .............................................................. 201 
Table 13‒2: 
Neuropsychiatric event classifications ........................................................... 203 
Table 13‒3: 
IBD event classifications ............................................................................... 204 
 
LIST OF FIGURES 
Figure 2-1: 
Study Schematic............................................................................................... 17 
Figure 4-1: 
Sequence of testing .......................................................................................... 44 
Figure 13-1: 
Sequence of testing ........................................................................................ 185 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
List of Abbreviations 
%ΔAN 
percentage change from Baseline in abscess and inflammatory 
nodule count 
ADAb 
anti-bimekizumab antibodies 
AE(s) 
adverse event(s) 
ALP 
alkaline phosphatase 
ALQ 
above the limit of quantification 
ALT 
alanine aminotransferase 
AMS 
Active Medication Set 
AN 
abscess and inflammatory nodule 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
BKZ 
bimekizumab 
BLQ 
below the limit of quantification 
CFB 
change from Baseline 
CFS 
COVID-19 Free Set 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
CV-CAC 
Cardiovascular Event Adjudication Committee 
DLQI 
Dermatology Life Quality Index 
DMC 
data monitoring committee 
eCDF 
empirical cumulative distribution function 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eC-SSRS 
electronic Columbia-Suicide Severity Rating Scale 
EAER 
exposure adjusted event rate 
EAIR 
exposure adjusted incident rate 
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List of Abbreviations 
EQ-5D-3L 
European Quality of Life-5 Dimensions-3 Level questionnaire 
ES 
Enrolled Set 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
geoCV 
geometric coefficient of variation 
GGT 
gamma-glutamyltransferase 
HiSCR 
Hidradenitis Suppurativa Clinical Response 
HiSQOL 
Hidradenitis Suppurativa Quality of Life 
HLT 
high level term 
HS 
hidradenitis suppurativa 
hs-CRP 
high sensitivity C-reactive protein 
HSSDD 
Hidradenitis Suppurativa Symptom Daily Diary 
HSSQ 
Hidradenitis Suppurativa Symptom Questionnaire 
IBD 
Inflammatory bowel disease 
IBD-CAC 
Inflammatory Bowel Disease Adjudication Committee 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IDC 
Infectious Disease Committee 
IGRA 
interferon gamma release assay 
IHS4 
International Hidradenitis Suppurativa Severity Scoring System 
IMP 
investigational medicinal product 
LFT 
liver function tests 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
LSM 
least square mean 
MACE 
major cardiovascular events 
MAR 
missing at random 
MCID 
minimal clinically important difference 
MCMC 
Markov-Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
MI-MCMC 
multiple imputation Markov-Chain Monte Carlo 
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List of Abbreviations 
MS 
Maintenance Set 
MSR 
minimum significant ratio 
n 
number of study participants 
NAb 
neutralizing antibody 
NI 
Negative Immunodepletion 
nR 
New Ratio 
NRI 
nonresponder imputation 
NRS 
numeric rating scale  
NS 
Negative Screen 
OC 
observed case 
PD 
pharmacodynamic(s) 
pDILI 
potential drug induced liver injury 
PEOT 
premature end of treatment 
PGI-C-HS 
Patient Global Impression of Change in Hidradenitis Suppurativa 
Severity 
PGI-C-SP 
Patient Global Impression of Change in Severity of Skin Pain 
PGI-S-HS 
Patient Global Impression of Hidradenitis Suppurativa Severity 
PGI-S-SP 
Patient Global Impression of Severity of Skin Pain 
PHQ-9 
Patient Health Questionnaire 9 
PI 
Positive Immunodepletion 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
PPS 
Per-Protocol Set 
PS 
Positive Screen 
PT 
preferred term 
 
 
 
 
QTcF 
QT corrected for heart rate using Fridericia’s formula 
RS 
Randomized Set 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
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List of Abbreviations 
SFU 
Safety Follow-up 
SIB 
suicidal ideation and behavior 
SMQ 
standardized MedDRA query 
SOC 
system organ class 
SS 
Safety Set 
SSD 
Safety Signal Detection 
TEAE 
treatment-emergent adverse event 
TEMA 
treatment-emergent markedly abnormal 
TSQM-9 
Treatment Satisfaction Questionnaire – Medication 9 
ULN 
upper limit of normal 
VAS 
visual analogue scale  
WHODD 
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) defines the scope of statistical analyses and provides a 
detailed description of statistical methodology to support the final clinical study report (CSR).  
The SAP is based on the Protocol Amendment 4, 6 May 2022 and the Japan-specific amendment 
4.1, 16 June 2022. If a future protocol amendment necessitates a substantial change to the 
statistical analysis of the study data, this SAP may be amended accordingly. The content of this 
SAP is compatible with the International Council for Harmonisation (ICH)/Food and Drug 
Administration (FDA) E9 Guidance documents. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective of this study is to evaluate the efficacy of bimekizumab in study 
participants with moderate to severe hidradenitis suppurativa (HS). 
2.1.2 
Secondary objectives 
The secondary objectives of this study are to:  
• Evaluate the efficacy of bimekizumab on other measures of disease activity in study 
participants with moderate to severe HS 
• Evaluate the safety of bimekizumab in study participants with moderate to severe HS 
2.1.3 
Other objectives 
The other objectives of this study are to:  
• Evaluate the efficacy of bimekizumab on Hidradenitis Suppurativa Clinical Response 
(HiSCR), other HS Scores, and other clinical measures of disease activity at various 
timepoints in study participants with moderate to severe HS 
• Evaluate the efficacy of bimekizumab on abscesses, nodules, and draining tunnels at various 
timepoints in study participants with moderate to severe HS 
• Evaluate the efficacy of bimekizumab on patient-reported outcome measures at various 
timepoints in study participants with moderate to severe HS 
• Evaluate the effect of bimekizumab on other safety measures at various timepoints in study 
participants with moderate to severe HS 
• Evaluate the pharmacokinetics (PK) of bimekizumab in study participants with moderate to 
severe HS 
• Evaluate the immunogenicity of bimekizumab (antidrug antibodies) in study participants 
with moderate to severe HS 
2.1.4 
Exploratory objective 
The exploratory objective of the study is to evaluate biomarkers in study participants with 
moderate to severe HS.  
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2.2 
Study endpoints 
2.2.1 
Efficacy endpoints 
2.2.1.1 
Primary efficacy endpoint 
The primary efficacy endpoint is the HiSCR50 (defined as at least a 50% reduction from Baseline 
in the total abscess and inflammatory nodule [AN] count with no increase from Baseline in 
abscess or draining tunnel count) at Week 16. 
2.2.1.2 
Secondary efficacy endpoints 
The secondary efficacy endpoints are defined as: 
• HiSCR75 response (defined as at least a 75% reduction from Baseline in the total AN count 
with no increase from Baseline in abscess or draining tunnel count) at Week 16 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Baseline) by Week 16 
• Absolute change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at 
Week 16 
• Absolute change from Baseline (CFB) in Skin Pain score at Week 16, as assessed by the 
“worst skin pain” item (11-point numeric rating scale) in the HS Symptom Daily Diary 
(HSSDD) 
• Skin pain response based on the threshold for clinically meaningful change (defined as at 
least a 3 point decrease from Baseline in HSSDD weekly worst skin pain score) at Week 16 
among study participants with a score of ≥3 at Baseline  
2.2.1.3 
Other efficacy endpoints 
The other efficacy endpoints are defined as: 
• Time to response of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100  
• HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100  
• Absolute change from Baseline in International Hidradenitis Suppurativa Severity Score 
System (IHS4) 
• Change from Baseline in the HS-Physician’s Global Assessment 6-point scale 
• Absolute and percentage change from Baseline in high-sensitivity C-reactive protein 
(hs-CRP) 
• Initiation of systemic antibiotic rescue therapy 
• HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 at both Weeks 16 and 48 
• Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 in Week 16 
responders 
• Partial responders (defined as a ≥25% reduction in AN count from Baseline [Week 0]) at 
Week 16 who progress to HiSCR50 during the Maintenance Treatment Period 
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• Partial responders (defined as a ≥25% reduction in AN count from Baseline [Week 0]) at 
Week 16 who progress to HiSCR75, HiSCR90, and HiSCR100 response during the 
Maintenance Treatment Period 
• Change and percentage change from Baseline in lesion counts (abscess count, inflammatory 
nodule count, AN count, and draining tunnel count)  
• AN count of 0, 1, or 2 
• AN25, AN50, AN75, AN90, AN100  (defined as a 25%, 50%, 75%, 90%, 100% reduction in the 
total AN count relative to Baseline) 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Week 16) by Week 48 
• Time to flare from Weeks 0 to 16 
• Time to flare from Week 16 to 48 
• Absolute and percentage change (worst and average skin pain) from Baseline in HS Skin 
Pain score (11-point numeric rating scale) 
• Skin pain response based on the threshold for clinically meaningful change (defined as at 
least a 3 point decrease from Baseline in HSSDD weekly worst skin pain score) among study 
participants with a score of ≥3 at Baseline 
• Skin pain response (at least a 30% reduction and at least a 1-point reduction from Baseline in 
HSSDD weekly worst skin pain score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline 
• Skin pain response (at least a 30% reduction and at least a 1-point reduction from Baseline in 
HSSDD weekly average skin pain score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline 
• Skin pain response (at least a 30% reduction and at least a 1-point reduction from Baseline in 
HS Skin Pain score [11-point numeric rating scale]) assessed by the HSSQ among study 
participants with a score of ≥3 at Baseline 
• Absolute change from Baseline in DLQI Total Score 
• DLQI Total Score of 0 or 1 
• Minimum clinically important difference (MCID) (improvement from Baseline of 4 or more) 
in the DLQI Total Score among study participants with a Baseline score of at least 4 
• Absolute change from Baseline in Hidradenitis Suppurativa Quality of Life (HiSQOL) 
domain scores (symptoms, psychosocial, activities and adaptations) and Total score 
• Patient Global Impression of HS Severity (PGI-S-HS) 
• Patient Global Impression of Change of HS Severity (PGI-C-HS) 
• Patient Global Impression of Severity of Skin Pain (PGI-S-SP) 
• Patient Global Impression of Change of Skin Pain (PGI-C-SP) 
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• Absolute change from Baseline in each of the other HS Symptoms - itch, drainage or oozing 
of HS lesions, and smell or odor 
• Response on other HS Symptoms (11-point numeric rating scale) - itch, drainage or oozing 
of HS lesions, and smell or odor 
• Responses to the European Quality of Life-5 Dimensions-3 Level questionnaire (EQ-5D-3L), 
absolute and changes from Baseline in EQ-5D-3L visual analog scale (VAS) scores 
• Absolute change from Baseline in Work Productivity and Activity Impairment 
Questionnaire-Specific Health Problem (WPAI-SHP) v2.0 adapted to HS scores 
• Domain Scores (effectiveness, convenience and global satisfaction) on the Treatment 
Satisfaction Questionnaire – Medication-9 (TSQM-9) 
2.2.2 
Pharmacokinetic and pharmacogenomic endpoints 
2.2.2.1 
Pharmacokinetic endpoints 
The PK endpoint is the plasma bimekizumab concentrations over the study duration. 
2.2.2.2 
Exploratory pharmacogenomic endpoints  
Genomic, genetic, epigenetic, proteins, and metabolite biomarkers may be measured to evaluate 
the relationship with response to treatment with bimekizumab, HS disease biology, and 
inflammatory and immune response processes. The candidate exploratory biomarkers are the 
blood or blood derivative (eg, plasma) concentrations of cytokines and chemokines of relevance 
to the IL-17A/F signaling pathway and HS biology.  
Additional biomarkers may include, but will not be limited to, plasma complement 
concentrations. 
A specific SAP will be written to describe the analysis methods for those endpoints, as the 
results will not be summarized in the CSR. The nature and format of these analyses will be 
detailed in this SAP.  
2.2.3 
Safety endpoints 
2.2.3.1 
Secondary safety endpoints 
The secondary safety endpoints are 
• Treatment-emergent Adverse Events (TEAEs) 
• Serious TEAEs 
• TEAEs leading to withdrawal from study 
2.2.3.2 
Other safety endpoints 
The other safety endpoints are 
• Adverse events of special interest (Hy’s Law) 
• Other safety topics of interest: infections (serious, opportunistic, fungal, and TB), 
neutropenia, hypersensitivity (including anaphylaxis), suicidal ideation and behavior, major 
adverse cardiovascular events, hepatic events and potential drug-induced liver injury 
(PDILI), malignancies, and inflammatory bowel disease. 
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• Absolute change from Baseline in the Patient Health Questionnaire (PHQ-9) score 
• Absolute change from Baseline in vital signs 
• Absolute change from Baseline in clinical laboratory values (chemistry and hematology) 
• Electrocardiogram (ECG) results 
2.2.4 
Immunological endpoints 
The immunological endpoints are 
• Bimekizumab antidrug antibodies 
• Bimekizumab neutralizing antibodies  
The results of the bimekizumab neutralizing antibody analysis will not be summarized in the 
CSR for this study. All neutralizing antibody analyses will be detailed in the integrated 
immunogenicity SAP. 
2.3 
Study design and conduct 
2.3.1 
Study description 
HS0004 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, pivotal study 
evaluating the efficacy and safety of bimekizumab in study participants with moderate to severe 
HS. Study participants meeting the inclusion criteria who do not meet any exclusion criteria will 
complete a Screening Period of 14 days to up to 5 weeks; a double-blind, 48-week Treatment 
Period comprising a 16-week Initial Treatment Period and 32-week Maintenance Treatment 
Period; and a 20-week Safety Follow-up (SFU) Period following the final injection of 
investigational medicinal product (IMP) if study participants do not enter a subsequent extension 
study (HS0005) or withdraw prematurely from treatment.  
Study participants will be randomized in a 2:2:2:1 ratio (stratified by Hurley Stage and current 
antibiotic use) to 1 of 3 dose regimens of bimekizumab or placebo as shown in the schematic 
(Figure 2-1).  
Figure 2-1: Study Schematic 
 
HiSCR50=a 50% reduction in the total abscess and inflammatory nodule count with no increase from Baseline in 
abscess or draining tunnel count; 
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IMP=investigational medicinal product; 
 
*Week 16 = primary endpoint (HiSCR50 bimekizumab versus placebo) 
a Study participant should discontinue from the study from Week 32 on if no partial response is achieved (partial 
response is defined as ≥25% improvement in abscess and inflammatory nodule count relative to Baseline [Week 0] 
lesion values,) 
b Study participants achieving an improvement of at least 25 % in abscess and inflammatory nodule count continue 
in HS0005 (Extension Study). 
c 20-week Safety Follow-up (from last IMP injection) for any study participant who discontinues from study prior to 
Week 48, or who does not continue in HS0005. 
2.3.2 
Study periods 
2.3.2.1 
Screening Period 
The Screening Period will last a minimum of 14 days up to a maximum of 5 weeks prior to 
randomization. 
2.3.2.2 
Initial Treatment Period (Weeks 0-16) and Maintenance Treatment 
Period (Weeks 16-48) 
Eligible study participants will be randomized in a 2:2:2:1 ratio as noted in the Study Schema to: 
• Bimekizumab
 from Weeks 0 to 48 
• Bimekizumab
 from Weeks 0 to 48 
• Bimekizumab
 to Week 16, continuing on 
 from Weeks 16 to 48 
• Placebo to Week 16, continuing on bimekizumab 
 from Weeks 16 to 48 
2.3.2.3 
Safety Follow-up Visit 
All study participants not continuing in the extension study, including those withdrawn from 
IMP as well as those completing all study visits, will have an SFU Visit 20 weeks after their final 
dose of IMP. 
2.3.3 
Study duration per participant 
The total duration of study participation in HS0004 will be 68 to 71 weeks for those who 
complete HS0004 and do not participate in the extension study HS0005 and 50 to 53 weeks for 
those who participate in HS0005 and, thus, do not participate in the 20‑week SFU Period. The 
study is comprised of the following: periods: 
• Screening Period: 14 days up to a maximum of 5 weeks prior to randomization 
• Initial Treatment Period: 16 weeks 
• Maintenance Treatment Period: 32 weeks 
• Safety Follow-Up Period: 20 weeks after the last dose of IMP  
A study participant will be considered to have completed the study if he or she completed the 
Week 48 visit.  
The end of the study is defined as the date of the last scheduled procedure for the last study 
participant in the study globally, including the SFU, as applicable. 
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2.3.4 
Planned number of participants and sites 
A total of approximately 490 study participants will be randomized into the study. The planned 
number of study sites is approximately 100. 
2.3.5 
Anticipated regions and countries 
The regions planned for study conduct are Western Europe, Central/Eastern Europe, North 
America and Asia/Australia, with possible extension to other regions and countries. 
A subset of tables, listings, and figures will be repeated for the subgroup of participants 
randomized in Japan. A list of these outputs will be added to the tables, figures, and listings 
shells. 
2.4 
Determination of sample size 
A total of 490 study participants will be randomly assigned in a 2:2:2:1 ratio (stratified by Hurley 
Stage and current antibiotic use) to the following treatment arms: 
• Bimekizumab 
 during Initial Treatment Period (Weeks 0-16) and Maintenance 
Treatment (Weeks 16-48) Period, N=140 
• Bimekizumab 
 during Initial Treatment Period (Weeks 0-16), and Bimekizumab 
 during Maintenance Treatment Period (Weeks 16-48), N=140 
• Bimekizumab 
 during Initial Treatment (Weeks 0-16) and Maintenance 
Treatment Periods (Weeks 16-48), N=140 
• Placebo during Initial Treatment Period (Weeks 0-16), and Bimekizumab 
 
during Maintenance Treatment Period (Weeks 16-48), N=70 
The analysis of the primary efficacy endpoint and secondary efficacy endpoints are based on a 
comparison of bimekizumab versus placebo at Week 16, with alpha adjustment strategy as 
indicated in Section 4.5. 
The power to detect a statistically significant difference for each of the endpoints are shown in 
Table 2‒1. Notably, with a 2-sided significance level of 0.025, the sample size of 140:70 
provides 73% power for detecting at least a difference of 1.5 (bimekizumab 
 vs placebo) for 
the Worst Skin Pain change from Baseline (CFB) endpoint. 
Given the high level of power for each of the primary and key secondary endpoints at the 
0.025 significance level for the 
 comparison (power≥0.89), and per the alpha spending 
strategy, there is a high likelihood that the 
 comparison of Worst Skin Pain CFB vs placebo 
will be allowed to be tested against the 0.05 level of significance. The power for this latter test is 
81%. The sample size is thus ultimately driven by the Worst Skin Pain CFB endpoint. 
Furthermore, the randomization ratio of 2:2:2:1 has been chosen to provide study participants 
with a high probability (6/7 ~ 86%) of being randomized to active study drug. 
After randomization for this study was complete, an additional endpoint to assess Worst Skin 
Pain response was included in the sequential testing procedure. This additional endpoint is based 
on the threshold for clinically meaningful change and is defined as at least a 3 point decrease 
from Baseline in HSSDD weekly worst skin pain score at Week 16 among study participants 
with a score of ≥3 at Baseline. Note that the power calculations reported in Table 2‒1for this 
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endpoint are based on the sample size that was initially driven by the Worst Pain CFB endpoint 
as described above. With a 2-sided significance level of 0.025, the sample size of 104:52 in the 
subset of participants reporting Baseline HSSDD worst skin pain score at or beyond the 
threshold for clinically meaningful change (ie, Baseline HSSDD ≥3) provides 53% power for 
detecting a statistically significant difference between bimekizumab 
 and placebo in the 
proportion of Worst Pain responders.  
Note that the power at the 0.025 level of significance associated with this endpoint for the 
comparison between bimekizumab 
and placebo is 95%. The 
 comparison of Worst 
Skin Pain response vs placebo against the 0.05 level of significance is therefore likely, and the 
power at this significance level is 65%. Given the strength of the power for the bimekizumab 
arm vs placebo across endpoints, it is considered acceptable to have a relatively low  
power for this final endpoint in the testing sequence for the bimekizumab 
 treatment arm vs 
placebo. 
Table 2‒1: 
Power calculation assumptions and methods 
Endpoint 
Power 
α = 0.025,  
2-sided 
Assumptions 
 
 
Week 16 Bimekizumab 
 
N=280a 
Week 16 Bimekizumab 
 
N=140 
Week 16 Placebo 
N=70 
HiSCR50 
0.99 
0.90 
Proportion 
responders=0.60 
Proportion 
responders=0.50 
Proportion 
responders=0.25 
HiSCR75 
0.99 
0.98 
Proportion 
responders=0.45 
Proportion 
responders=0.35 
Proportion 
responders=0.10 
Flare 
0.99 
0.99 
Proportion of participants 
with flare by 
Week 16=0.09 
Proportion of participants 
with flare by 
Week 16=0.19 
Proportion of participants 
with flare by 
Week 16=0.52 
DLQI 
0.99 
0.96 
Mean CFB=-5.4; 
SD=6.8 
Mean CFB=-4.8; 
SD=6.8 
Mean CFB=-0.8; 
SD=6.6 
Worst Skin 
Pain CFBb 
0.89 
0.73 
Mean CFB=-2.2; 
SD=3.2 
Mean CFB=-2.0; 
SD=3.2 
Mean CFB=-0.5; 
SD=3.7 
Worst 
Skin Pain 
Responsec 
0.95 
0.53 
Proportion 
responders=0.53 
Proportion 
responders=0.43 
Proportion 
responders=0.23 
CFB=change from Baseline; 
 SD=standard deviation 
Note: Estimates for HS0004 are based on Week 12 data from the HS0001 study. 
a Pooled
 at Week 16 from 
 and 
 arms 
b Within-participant average of Worst Skin Pain according to 24-hour recall. 
c Assumes N=208, 104, 52 in 
 and placebo, respectively, to account for Worst Skin Pain score at or 
above 3 (ie, the threshold for clinically meaningful change from Baseline) 
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3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, study participants data listings, and 
statistical output will be performed using SAS Version 9.4 or higher. All tables and listings will 
use Courier New font size 9.  
Descriptive statistics will be displayed to provide an overview of the study results. For 
continuous variables, descriptive statistics will include number of study participants with 
available measurements (n), mean, standard deviation (SD), median, minimum, and maximum.  
For PRO continuous variables, descriptive statistics will also include variable score, absolute and 
percentage changes from baseline, Q1 and Q3, 10th, and 90th percentiles. 
If no participants have data at a given time point, then only n=0 will be presented. The other 
descriptive statistics will be left blank. If n < 3 then the n, minimum, and maximum only will be 
presented. The other descriptive statistics will be left blank. If n = 3 n, mean, median, minimum 
and maximum will be presented only. The other descriptive statistics will be left blank. 
For categorical variables, the number and percentage of study participants in each category will 
be presented. Unless otherwise noted, the denominator for percentages will be based on the 
number of study participants included in the respective analysis set. Study participants with 
missing data will be accounted for using the following approaches: 
• For summaries of demographics and Baseline characteristics: percentages will be based on 
all study participants in the analysis set and a “Missing” category (corresponding to study 
participants with missing data for the variable being summarized) will be included as the last 
row in the list of categories being summarized. 
• For summaries of efficacy and safety endpoints, unless otherwise specified: percentages will 
be based only on those study participants with observed data for the variable being 
summarized. As the denominator may be different from the number of study participants in 
the analysis set being considered, the denominator will be displayed in the table. The general 
format for displaying this will be “n/Nsub (%).” 
Percentages will be presented to 1 decimal place. If the percentage is 100%, a decimal will not 
be presented. If the count is 0, the percentage will not be presented. Typically, the % sign will be 
presented in the column header, but not with each individual value. 
For the purpose of the tabulations the lower and upper confidence limits for the percentages will 
be truncated at 0 and 100% respectively. Confidence intervals (CIs) for the response rates in 
efficacy summaries based on nonresponder imputation (NRI) will be computed using the Wilson 
approximation. 
For bimekizumab PK concentrations, summary statistics will include geometric mean, geometric 
coefficient of variation (CV), 95% CIs for geometric mean, arithmetic mean, SD, median, 
minimum, and maximum. All summaries of PK variables will be based on the observed values. 
No imputation will be used. 
Decimal places for descriptive statistics will be subject to the following rules: 
• “n” will be an integer 
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• Mean, SD, and median will use 1 additional decimal place compared to the original data 
• CV [%] will be presented with 1 decimal place 
• Minimum and maximum will have the same number of decimal places as the original value. 
Derived variables in general will display the mean, SD, and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics. 
When reporting individual values and descriptive statistics for PK concentration data, the 
following rules will apply with regard to rounding and precision: 
• Individual values will be reported to the same level of precision as received from the 
bioanalytical laboratory 
• Descriptive statistics will be reported to the same level of precision as the individual data for 
the minimum and maximum, and to 1 additional significant figure for the mean (arithmetic 
and geometric), median, SD, and 95% CI for the geometric mean  
• The geometric coefficient of variances (geoCV) will be reported as a percentage to 1 decimal 
place 
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 2-sided and will be performed at 
the 0.05 level of significance unless specified otherwise. The significance levels used as part of 
the multiple testing procedure are detailed in Section 4.5.  
Per protocol, visit windows are ±3 days from the date of first dose. The 20-week SFU Visit 
window is ±7 days from the date of the final dose. All by-visit summaries will contain nominal 
(ie, scheduled) visits only. Unscheduled visits will not be mapped to scheduled visits except for 
assessments that occur within a 3-day time 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. 
This will only occur for selected vendor data. The only exception to this rule is for unscheduled 
assessments that occur up to 3 days after the Baseline visit. These unscheduled visits will remain 
as unscheduled as the Baseline assessment cannot be after the first dose of study drug 
administration. See Section 3.3 for more details on the definition of Baseline values. 
A complete set of data listings containing all documented data as well as calculated data (eg, 
change from Baseline) will be generated. 
3.2 
General study level definitions 
3.2.1 
Relative day 
The relative day will be included in different listings and will be calculated as follows: 
• If the start (stop) date occurred on or after the first dose, but prior to the double-blind drug 
stop date, relative day is calculated as start (stop) date minus first dose date + 1 
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• If the start (stop) date occurred after the last dose of double-blind drug, the relative day to the 
most recent dose is calculated as start (stop) date minus most recent dose date. The relative 
day in this situation will be preceded by a ‘+’ 
• If the start (stop) date occurred before the first dose, the relative day is calculated as start 
(stop) date minus first dose date. The relative day in this situation will be preceded by a ‘-‘. 
For AEs, relative days for start and stop dates will be calculated as the number of days since the 
first injection of the medication. For non-treatment emergent AEs, relative day of onset will be 
negative if the event started and stopped before the first dose. Relative day will only be 
computed for fully completed dates and will be missing for partial dates. 
Relative day will be calculated from first dose of IMP for all treatment groups, and additionally 
from first dose of bimekizumab for the Placebo/BKZ 
 arm. 
3.2.2 
Mapping of data from Premature End of Treatment visits 
If the Premature end of treatment (PEOT) visit occurs at a scheduled visit as outlined in the 
schedule of assessments, then no mapping is necessary, and any early withdrawal assessments 
will correspond to that scheduled visit. The PEOT assessments that occur on a date after a 
scheduled visit will be assigned to the next scheduled site visit per the protocol following the last 
visit where assessments were available. This approach means that there is a chance that data will 
be mapped to a visit where a given assessment was not actually collected per the protocol 
schedule of assessments. Such data will not be summarized in by-visit tables (though it will be 
available in the listings).  
The only exception to the above rule is for anti-bimekizumab antibody assessments, in which all 
PEOT assessments will be assigned to the next scheduled visit at which anti-bimekizumab 
antibodies are assessed. All by-visit summaries will contain nominal visits only. Unscheduled 
visits will not be mapped to scheduled visits. Note that based on the early withdrawal mapping 
conventions described above, a mapped PEOT visit is considered as observed at that visit and 
will be summarized as such in the tables.  
3.3 
Definition of Baseline values 
Section 8.3.4 details the derivation of the Baseline value for the HSSDD assessment. For all 
other assessments, the below applies. 
A Baseline value for a participant is defined as the latest non-missing measurement for that 
participant up to and including the day of administration of first study medication, unless 
otherwise stated. If a Baseline assessment is taken on the same day as first administration of 
study medication, 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 study medication administration. 
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 study medication 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 study medication. One exception to this rule is plasma concentration of 
bimekizumab. If Baseline plasma concentration is measured at a time after the first 
administration of study medication, then it will not be eligible to be considered as a Baseline 
plasma concentration. Such cases will be discussed with the quantitative clinical pharmacologist.  
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For randomized participants for whom no start date of treatment is available, the Baseline value 
will be considered as the last available value on or before the randomization date.  
If a Baseline measurement is missing or not collected, and a Screening value is available, the 
Screening value will be utilized as Baseline instead.  
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 of the components, but the Baseline visit is missing 1 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 will be based on the first injection of study treatment, 
regardless of whether or not it is an active treatment. 
3.4 
Protocol deviations 
Important protocol deviations are deviations from the protocol that could potentially have a 
meaningful impact on study conduct or on the primary and key secondary efficacy, key safety, or 
PK outcomes for an individual participant. The criteria for identifying important protocol 
deviations will be defined within the appropriate protocol-specific document at study start. 
Important protocol deviations will be reviewed as part of the ongoing data cleaning process. 
Important protocol deviations including those that lead to exclusion from the analysis sets will be 
identified and documented prior to unblinding.  
Deviations related to the Coronavirus Disease 2019 (COVID-19) global pandemic are 
unavoidable deviations from the protocol due to confirmed COVID-19 infection, suspected 
COVID-19 infection, general circumstances around COVID-19 without infection or any other 
deviation from the protocol due to COVID-19. COVID-19 protocol deviations will also be 
reviewed separately as part of the ongoing data cleaning process. 
3.5 
Analysis sets 
3.5.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all participants who have given informed consent. 
3.5.2 
Randomized Set 
The Randomized Set (RS) will consist of all participants randomized into the study. 
3.5.3 
Safety Set 
The Safety Set (SS) will consist of all participants who received at least 1 dose (full or partial) of 
IMP. The SS will be used for the demographic, safety, and immunogenicity analyses.  
3.5.4 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all study participants who received at least 1 dose 
(full or partial) of IMP and had a valid Baseline measurement and a post-Baseline measurement 
for abscess, inflammatory nodules, and draining tunnel counts.  
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3.5.5 
Active Medication Set 
The Active Medication Set (AMS) will consist of all participants who have received at least 1 
dose (full or partial) of bimekizumab. The AMS will be used for summaries of safety that 
include all data from the Initial Treatment Period and/or Maintenance Treatment Period. 
3.5.6 
Maintenance Set 
The Maintenance Set (MS) will consist of all participants who have received at least 1 dose (full 
or partial) of bimekizumab in the Maintenance Treatment Period. 
3.5.7 
Per-Protocol Set 
The Per-Protocol Set (PPS) will consist of all study participants in the FAS who had no 
important protocol deviations affecting the primary efficacy variable. Important protocol 
deviations will be predefined and study participants with important protocol deviations will be 
evaluated during ongoing data cleaning meetings prior to unblinding of the data. 
3.5.8 
Pharmacokinetics Per-Protocol Set 
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of study participants who received 
at least 1 full dose of bimekizumab and provided at least 1 quantifiable plasma concentration 
post-dose without important protocol deviations that would affect the PK.  
3.5.9 
COVID-19 Free Set 
The COVID-19 Free Set (CFS) will consist of all study participants randomized into the study 
and who have no COVID-19 impact through Week 16. This analysis set will be used for 
sensitivity analysis of the primary efficacy endpoint. 
3.6 
Treatment assignment and treatment groups 
It is expected that participants receive treatment as randomized and hence safety analyses will be 
based on the SS, as randomized. However, if after unblinding it is determined that participants 
randomized to placebo in the Initial Treatment Period received bimekizumab at any time within 
the first 16 weeks, then for safety analyses these participants will be reallocated to the 
appropriate bimekizumab treatment group, unless otherwise specified. Participants randomized 
to bimekizumab will only be reallocated to the placebo treatment group if they never received 
bimekizumab. Efficacy analyses will be according to randomized treatment and not actual 
treatment received. 
For the purposes of Initial Treatment Period analyses for the 
 dosing regimen, the 
bimekizumab treatment arms of 
 and bimekizumab 
 
treatment groups will be pooled. 
3.7 
Center pooling strategy 
Geographic regions have been categorized as North America, Western Europe, Central/Eastern 
Europe, and Asia/Australia. Below is a table of geographic regions with corresponding countries.   
Table 3‒1: 
Geographic regions and corresponding countries 
Region 
Countries 
North America 
Canada, United States 
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Table 3‒1: 
Geographic regions and corresponding countries 
Region 
Countries 
Western Europe 
France, Germany, Ireland, Italy, Spain, United 
Kingdom 
Central/Eastern Europe 
Bulgaria, Czech Republic, Hungary, Poland 
Asia/Australia 
Australia, Israel, Japan 
  
The following center pooling algorithm will be used for each geographic region: 
• If a center has 21 or more participants, then no pooling will be done for that center. 
• Centers with fewer than 21 participants will be ordered from largest to smallest with pooling 
proceeding in the following manner: 
− Two or more centers will be combined until the cumulative participant total is at least 21. 
− Once a pooled center has at least 21 participants, the process will continue in an iterative 
fashion for the subsequent centers in the ordered list, where a new pooled center begins 
each time at least 21 participants has been reached in the previous pool. 
− If this iterative process reaches the end of the ordered list of centers where the final 
pooled center has fewer than 21 participants, then the participants from the centers in that 
pool will be combined with the pooled center formed in the previous iteration. 
This procedure is only to be performed within a geographic region – there will be no pooling of 
centers across regions. 
In the event that the percentage of randomized participants is less than 10% in either of the 
Asia/Australia or Central/Eastern Europe regions, the two regions will be combined as a 
geographic region stratum for efficacy modeling, so that there are no modeling convergence 
issues across efficacy variables.  
3.8 
Coding dictionaries 
Adverse events and medical history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA®) version 19.0. 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD) version MAR2021 B3 or later. Medical procedures will not be coded. 
3.9 
Definition of an intercurrent event 
Handling of intercurrent events is one of the key elements for the analysis of efficacy endpoints. 
An intercurrent event is defined as receipt of systemic antibiotic rescue medication or 
discontinuation of study treatment due to an AE or lack of efficacy (See Section 8.2.2). 
Receipt of systemic antibiotic rescue medication is defined as initiating any systemic antibiotic 
on or after Baseline for any reason (including in response to an AE). The only exception to this 
rule is if a participant randomized to the antibiotic stratum on a tetracycline antibiotic interrupts 
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their stable dose of tetracycline antibiotic during the study and subsequently restarts the same 
tetracycline antibiotic as confirmed using the coded preferred term. The restarted dose and 
frequency of the antibiotic must be the same or lower than the regimen prior to the interruption. 
The dates of an intercurrent event are as follows: 
• For receipt of systemic antibiotic rescue medication: start date of the antibiotic 
• For discontinuation of study treatment due to an AE or lack of efficacy: Last study treatment 
date + 17 days. Note: study treatment discontinuation includes study discontinuation. 
The choice of 17 days is intended to capture the interval between dosing and lesion assessments 
(14 days), as well as the visit window (3 days). 
An additional sensitivity analysis will be conducted where missing data due to COVID-19 will 
be considered an intercurrent event and will be imputed as a nonresponse at that particular visit. 
This will be identified when there are missing data at a visit that has been impacted by COVID-
19 according the COVID-19 impact CRF page. The date of this intercurrent event will be the 
date of the impacted visit. 
3.10 
Changes to protocol-defined analyses 
The MS and AMS were added as analysis sets. 
The endpoints for PGI-S-HS, PGI-S-SP, PGI-C-HS, and PGI-C-SP were clarified in 
Section 2.2.1.3 to indicate that absolute change from Baseline will not be calculated, as these are 
categorical endpoints. 
The HiSQOL endpoint was clarified to show that there are only 3 domains: symptoms, 
psychosocial, activities and adaptations and to add total score. 
 
In Protocol Amendment 4, the secondary efficacy endpoint for skin pain response based on the 
worst skin pain HSSDD score is defined as a decrease from Baseline in HSSDD weekly worst 
skin pain score at or beyond the threshold for clinically meaningful change at Week 16. In this 
SAP, this endpoint is defined to include the exact value of the clinically meaningful threshold of 
3, so that the skin pain response based on the HSSDD worst skin pain score is defined as at least 
a 3 point decrease from Baseline in HSSDD weekly worst skin pain score at Week 16 among 
study participants with a score of ≥3 at Baseline. 
The following other efficacy endpoints are included in the protocol but will not be included as 
part of the analysis: 
• Skin pain response based on the threshold for clinically meaningful change (defined as at 
least a 3 point decrease from Baseline in HS Symptom Questionnaire (HSSQ) weekly worst 
skin pain score) among study participants with a score of ≥3 at Baseline 
• Response on other HS Symptoms (11-point numeric rating scale) - itch, drainage or oozing 
of HS lesions, and smell or odor 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Week 16) by Week 48 
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The calculation of nominal p-values has been added for selected efficacy endpoints. These 
nominal p-values are not controlled for multiplicity and should not be used to declare statistical 
significance. 
The protocol defines the PK-PPS separately by period, but there will only be one PK-PPS for the 
overall study. 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
The primary efficacy analyses and selected secondary analyses will be adjusted for the 2 
randomization stratification variables: 
• Hurley Stage at Baseline (II or III) 
• Baseline antibiotic use (Yes or No) 
If a participant is stratified in the incorrect stratum (ie, the stratum recorded in the Interactive 
voice or web Response System differs from the actual stratum the participant belongs to), the 
actual stratum will be used for the analysis.  
The continuous secondary endpoints will also include the Baseline value as a covariate.  
The Worst Skin Pain secondary endpoints (change from Baseline continuous endpoint and pain 
response binary endpoint) will also include analgesic use as a covariate. 
4.2 
Handling of dropouts or missing data 
4.2.1 
Efficacy data 
Different approaches will be used to handle missing data including how intercurrent events 
(defined as receipt of systemic antibiotic rescue medication or discontinuation of study treatment 
due to an AE or lack of efficacy prior to the given visit) will be considered. A composite strategy 
will be implemented in which a positive clinical outcome is defined as the study participant 
achieving HiSCR50 at the given visit and not receiving systemic antibiotic rescue medication, and 
not discontinuing study treatment due to an AE or lack of efficacy through that visit.  
4.2.1.1 
Handling missing data for the primary efficacy endpoint 
If study participants have an intercurrent event as defined in Section 3.9, then the primary 
efficacy variable at that timepoint and all subsequent timepoints (whether the data were observed 
or not) will be set to “nonresponse” as the study participant has not met the criteria for response 
based on the composite estimand defined in Section 8.2. All remaining missing data for the 
endpoint will be imputed using multiple imputation Markov-Chain Monte Carlo method (MI-
MCMC)/monotone regression for the primary analysis. 
In addition, sensitivity analyses using NRI, MI-MCMC/reference-based methods, tipping point 
analysis, and observed case (OC) methods will be performed, which will assess the impact of 
different methods of handling missing data. 
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4.2.1.2 
Handling missing data for the secondary efficacy endpoints 
For secondary binary efficacy endpoints, intercurrent events will be handled, and missing data 
will be imputed, using the same methods as for the primary efficacy endpoint. NRI and OC 
methods will be performed as sensitivity analyses.  
For secondary continuous efficacy endpoints, MI-MCMC/monotone regression is the primary 
method for imputing missing data, regardless of whether the missing data are preceded by an 
intercurrent event. That is, if an intercurrent event occurs on or before a visit,  the result for that 
visit will be treated as missing and then imputed. If the imputation model cannot converge, last 
observation carried forward (LOCF) will be used. The OC method will be performed as a 
sensitivity analysis. 
4.2.1.3 
Handling missing data for the other efficacy endpoints 
For other binary efficacy endpoints, missing data will be imputed using the same method as the 
primary efficacy endpoint. NRI and OC methods will be performed as sensitivity analyses of 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100. 
For other continuous efficacy endpoints, the MI-MCMC/monotone regression method will be 
used to impute missing data as the primary method, regardless of whether the missing data are 
preceded by an intercurrent event. That is, if an intercurrent event occurs on or before a visit,  the 
result for that visit will be treated as missing and imputed with the missing data. If the imputation 
model cannot converge, LOCF will be used.  
For other ordinal endpoints (EQ-5D-3L, PGI-S-HS, PGI-C-HS, PGI-S-SP, PGI-C-SP), the OC 
method will be applied as the primary analysis method. No imputation is applied. 
4.2.1.4 
Missing Data Overview and Summary 
In summary, the approaches listed below will be used in this study for handling missing data for 
efficacy endpoints as appropriate: 
• NRI: Participants who have missing data at the timepoint of interest are treated as though 
they did not respond to the treatment. This approach is also referred to as Composite 
Estimand (NRI). 
• Multiple Imputation (MI) – MCMC / Monotone Regression: Using multiple imputation 
methodology, intermittent missing data are imputed based on the MCMC method, and 
monotone missing data are imputed using monotone regression. 
• MI–MCMC / Reference-based imputation: Using multiple imputation methodology, 
intermittent missing data are imputed based on the MCMC method, and monotone missing 
data are imputed using an imputation model based on placebo (reference) data. 
• LOCF: Post-Baseline missing data are imputed by carrying forward the last available 
observation (including Baseline). 
• Tipping point analyses: Assumptions will be made about average outcomes among the 
subsets of participants who prematurely discontinued study treatment. Various “delta 
adjustments” will be made to the assumed responses among missing data in each treatment 
arm with varying degrees of plausibility in order to identify assumptions about the missing 
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data under which the conclusions change (O’Kelly, 2014). Then, the plausibility of such 
assumptions is discussed. 
• Observed case (OC): Missing data are not imputed. Only participants with available data 
who have not discontinued study treatment at the given timepoint are considered. Study 
participants with missing data or who have prematurely discontinued study treatment will be 
treated as missing.  
• Treatment policy strategy: All available data observed at the time point of interest will be 
considered, regardless of the occurrence of intercurrent events. This means the analysis 
includes on- and off-treatment values collected after study participants prematurely 
discontinued study treatment but agreed to remain on the study and continued to attend visits 
and provide assessments at those visits as well as values from study participants who 
received rescue antibiotic medication. Those observed values will be analyzed according to 
the study participant’s randomized treatment. Study participants 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. 
The following table depicts which missing data handling approaches will be used based on 
endpoint priority (primary, secondary, other) and endpoint type (responder, continuous, ordinal).  
 
Table 4‒1: 
Missing data handling approach by endpoint priority and type 
End-point 
Priority 
Endpoint 
Type 
Com-
posite 
Esti-
mand 
(NRI) 
Modified 
Composite 
Estimand 
(MI) 
 
MI  
(MCMC/ 
Reference
-based) 
Tipping 
Point 
Treat-
ment 
Policy 
Hypo-
thetical 
Esti-
mand 
OC 
Primary 
Responder 
Sa 
P 
Sa 
S 
Sa 
 
S 
Secondary 
included 
in the 
statistical 
testing 
procedure 
Responder 
Sa 
P 
 
 
 
 
S 
Continuous 
 
 
 
 
 
P 
S 
Secondary 
not 
included 
in 
statistical 
testing 
procedure 
Binary 
X 
X 
 
 
 
 
X 
Continuous 
 
 
 
 
 
X 
X 
Other 
Responder 
Xd 
X 
 
 
 
 
Xd 
Continuous  
 
 
 
 
 
X 
Xb 
Ordinal 
 
 
 
 
 
Xc 
Xc 
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MI=multiple imputation, NRI=Nonresponder imputation, OC=Observed case, P=Primary method, S=Sensitivity 
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 due to AE or lack of efficacy or receipt of rescue antibiotic medication are imputed as 
nonresponse, and other missing data are also imputed as nonresponse. 
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 or receipt of rescue antibiotic medication are imputed 
as nonresponse, and other missing data are imputed via a multiple imputation model.  
Note: Hypothetical Estimand (MI) refers to the approach where outcomes for study participants without an 
intercurrent event of study treatment discontinuation are as observed, and outcomes for study participants with the 
intercurrent event are imputed via a multiple imputation model. 
a Imputation method is applied on continuous data, and responder endpoint is derived from the continuous endpoint 
based on complete data set where applicable. 
b Required only for by-visit summaries of variables whose value at Week 16 is part of the hierarchical testing 
procedure. 
c For variables with multiple categories, data will be summarized as observed with an additional missing row to 
capture missing data at a given visit. 
d NRI/OC sensitivity analysis will be performed only for HiSCR50, HiSCR75, HiSCR90, HiSCR100 summaries.  
4.2.2 
Missing data algorithms for efficacy analyses 
These descriptions focus on the missing data procedures themselves and do not specifically 
account for dealing with intercurrent events, which is addressed in their respective sections. 
4.2.2.1 
MI – MCMC / Monotone Regression 
In many cases, missing efficacy data due to study treatment discontinuation should be dependent 
on the observed efficacy scores, but independent of unobserved data. This would be consistent 
with a missing at random (MAR) pattern of missingness. To investigate the efficacy results 
under the assumption of data being MAR, a multiple imputation method will be applied. 
Binary endpoint 
For a binary endpoint (eg, HiSCR50), the procedure is as follows: 
1. Create a data set, one for each treatment group of participants with observed values and those 
needing estimation by multiple imputation. For the imputation step, a distinction is made 
between non-monotone missing values (ie, intermittent missing values between completed 
assessments) and monotone missing values (ie, where all participants data are missing after a 
given time point). 
a. For the intermittent missing values, the missing values in each data set will be filled in using 
the MCMC method with multiple chain, monotone missing data imputing pattern, and non-
informative prior 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 762 and all other multiple imputation procedures 
described in this SAP will use this same seed as well. The resulting 100 imputed data sets 
will have a monotone missing pattern and will be imputed using a method for monotone 
missingness. Note that a separate imputation procedure must be invoked in SAS for each 
treatment group as the seed cannot be set for by groups beyond the first when using a by 
statement in PROC MI. 
b. For monotone missing data, monotone regression will be used to impute missing data. A 
separate regression model is estimated for each variable with missing values (ie, 
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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 data set has a 
monotone missing data pattern, the process is repeated sequentially for variables with 
missing values. This procedure will be based on the100 imputed datasets generated from the 
MCMC procedure and will be performed by imputation. The SAS® PROC MI procedure 
will be used for the imputation. 
In both cases, Hurley Stage at Baseline, Baseline antibiotic use, and value of the variable of 
interest at Baseline and at each post-Baseline visit (prior to the time point of interest) will be 
included in the imputation model. The post- Baseline values will need to be specified in 
chronological order in the imputation model so that SAS® PROC MI imputes variables from 
left to right (eg, the Week 2 value will be first imputed using regression based on the 
Baseline value, and then Week 4 value will be imputed using regression based on Baseline 
and Week 2 values, etc). The resulting data sets for each treatment arm will be combined into 
one complete data set based on each of the 100 imputations. 
Note: The imputation model based on the MCMC method will only allow joint multivariate 
normal variables. Therefore, Hurley Stage at Baseline and Baseline antibiotic use will be re-
coded as indicator variables. For Baseline antibiotic use, this will simply be 0 for Baseline 
antibiotic non-users and 1 for Baseline antibiotic users. For Hurley Stage at Baseline, this 
will be 0 for Hurley Stage II participants and 1 for Hurley Stage III participants. In order to 
achieve model convergence, Baseline antibiotic use may be dropped from the model. If 
convergence is still not obtained, then Hurley Stage at Baseline may also be dropped from 
the model. Additionally, if a variable is dropped in order to allow convergence for one model 
in a study, that variable does not have to be dropped from other models in the study if the 
model converges without dropping the variable. In other words, model convergence should 
be evaluated for each efficacy variable independently. 
Note: The imputation of each lesion type (inflammatory nodule, abscess, draining tunnel, etc) 
will be performed separately. The 100 data sets obtained for each type will be merged by 
imputation number and subject number.  
2. For each complete imputed data set, the dichotomous responder variable (eg, HiSCR 0 or 1) 
will be computed. Each complete imputed data set will then be analyzed based on the logistic 
regression model. 
Note: For derivation of HiSCR response, the AN, inflammatory nodule, abscess, and draining 
tunnel (fistula/sinus tract) counts at Week 16 in the imputed data sets will be compared 
directly to the observed Baseline counts to determine response. If values outside of the pre-
defined range of values for lesion count (<0) are imputed, they will be cut off as appropriate 
after the multiple imputation procedure but before deriving the responder variable. For 
example, an imputed draining tunnel (fistula/sinus tract) count of -1 would be changed to 0 
before deriving the HiSCR responder variable. Additional ranges for values for secondary 
and other endpoints are defined in Table 4-2.  
Note: Standard rounding rules will also be applied to the imputed values of endpoints that 
can only take integer values (eg, abscess count). For example, if a study participant has an 
abscess count imputed as 2.4, this imputed value would be rounded down to 2. This rounding 
step is performed after the multiple imputation but before deriving the responder variable.  
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Table 4‒2: 
Imputation allowable ranges by variable 
Variable 
Minimum Value 
Maximum Value 
Integer Values Only 
Lesion counta 
0 
-- 
Yes 
DLQI total score 
0 
30 
Yes 
hs-CRP 
LLOQ/2 
-- 
No 
HSSDD item score 
0 
10 
No 
HSSQ item score 
0 
10 
Yes 
HiSQOL symptom 
status score 
0 
16 
Yes 
HiSQOL psychosocial 
impact score 
0 
20 
Yes 
HiSQOL impact on 
physical activities score 
0 
32 
Yes 
EQ-5D-3L VAS 
0 
100 
Yes 
WPAI dimension 
scores 
0 
100 
No for variables: “Percent work 
time missed due to problem” and 
“Percent overall work impairment 
due to problem”. 
Yes for variables: “Percent 
impairment while working due to 
problem” and “Percent activity 
impairment due to problem”. 
These two variables can only take 
values that are multiples of 10. 
a Lesion counts will be imputed separately for each lesion type (abscesses, draining tunnels [fistulas/sinus tracts], 
inflammatory nodules, non-draining tunnels [fistulas/sinus tracts], non-inflammatory nodules, HS scars). The 
imputed lesion counts will be used to derive the endpoints that are dependent on the lesion count data (eg, HiSCR50). 
 
3. Estimates of the adjusted responder rate for each treatment group and the associated SE are 
obtained from the logistic regression of each of the 100 imputed data sets. These estimates 
will be combined for overall inference using Rubin’s rules, which account for the uncertainty 
associated with the imputed values (Rubin, 1987), and the combined estimates and SEs will 
be used to construct 95% CIs using the logit scale. This will be done using SAS PROC 
MIANALYZE. 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. 
Note: The (unadjusted) proportion of responders will be calculated at each time point by 
treatment group from the imputed datasets using SAS PROC FREQ. These results will also 
be combined into an overall inference using SAS PROC MIANALYZE. 
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Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below: 
As the estimates of the odds ratios from the logistic regression models in Step 3 follow a log-
normal distribution, a log transformation is needed to normalize these 100 odds ratio estimates. 
That 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 odds ratio estimates from the logistic regression model are used when combining into a 
single inference (Step 3). Additionally, the SE for the odds ratios are transformed as follows:  
𝑆𝐸= log(UCL) - log (LCL)
2Zα/2
 
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 (2.24 for a 97.5% CI). The estimates of the log odds ratio for 
Bimekizumab relative to placebo and the corresponding upper and lower CLs will be provided. 
The odds ratio will be then estimated by exponentiating the estimate of the log odds ratio. The 
odds ratio and the confidence limits of the odds ratio will be estimated as follows:  
 
𝑂𝑅=  exp (Log odds ratio estimate) 
 
𝐿𝐶𝐿=  𝑂𝑅∗exp (−𝑆𝐸∗𝑍𝛼2
⁄ ) 
 
𝑈𝐶𝐿=  𝑂𝑅∗exp (𝑆𝐸∗𝑍𝛼2
⁄ ) 
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 (2.24 
for a 97.5% CI). These calculations will be done such that odds ratios and corresponding CIs are 
calculated for the odds ratio of bimekizumab vs. placebo. 
Note: If one dose regimen is tested at the 0.05 significance level as determined in Section 4.5, 
then the confidence interval will be 95% instead of 97.5% for that dose with a corresponding Zα/2 
of 1.96. 
In addition to calculating the odds ratio, associated CIs, and p-values for the pairwise 
comparisons of bimekizumab and placebo, the estimated proportion of responders (ie, estimated 
responder rate) and the difference in the proportion of responders between each bimekizumab 
treatment group and placebo will be estimated, and 2-sided 95% CIs will be created for each 
difference. The creation of the estimates of the differences will be completed for each 
bimekizumab treatment group using the process detailed below: 
1. Use the logistic regression model to calculate: 
Least squares mean estimates of the log odds of bimekizumab (GB) and placebo (GP), as well 
as their corresponding standard errors (SB and SP, respectively). 
Standard error of the least squares mean estimate of the log odds ratio (SR) 
2. Compute estimates for predicted proportions using the following transformations: 
PB = exp(GB)/(1 + exp(GB)) 
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PP = exp(GP)/(1 + exp(GP)) 
The difference in proportions is then given by: 
D = PB – PP 
3. 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 MCMC method for multiple imputation, 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. 
Note that this procedure indicates that the imputation model will be applied for each treatment 
group separately in PROC MI, which will be the default method. However, in the event there are 
computational challenges with the imputation model (eg, due to a standard deviation of 0 for 
responses of a given imputation), it is acceptable to modify the imputation model to include 
treatment as a variable in the model rather than running a separate model for each treatment 
group. It should be noted that doing so assumes that treatment does not interact with any of the 
other variables in the imputation model. 
Continuous endpoint  
For continuous endpoints (eg, Change from Baseline in DLQI total score at Week 16), the MI 
method will be applied as follows: 
1. 
The MCMC/monotone regression method described above in Step 1 for binary endpoints 
will be performed. 
2. 
Based on the multiply imputed data sets obtained for the given variable, the change from 
Baseline will be derived for each of the 100 complete imputed data sets based on the 
observed Baseline value and the observed/imputed post-Baseline values. Note that if the 
value itself is being summarized, no additional derivation is needed. 
3. 
If a statistical model is being used for the analysis of the variable, then that will be 
performed for each imputation in this step. If no statistical model is being used, then 
simple descriptive statistics will be calculated.  
4. 
For data excluding hs-CRP, the following rules apply. The results of the 100 imputed 
data sets (based on the statistical model or descriptive statistics) are combined with 
means and standard errors calculated using Rubin’s rules (via PROC MIANALYZE). 
Note that for the 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. Thus, for median, 
Q1, Q3, minimum and maximum, the following approach will apply: 
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− 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, then the mean of the means will also be 
presented to 1 decimal place). 
For hs-CRP only, the following rules apply. The hs-CRP data will be presented using the 
geometric mean, 95% CI for the geometric mean, median, Q1, Q3, minimum and maximum. The 
change from Baseline will be expressed as the ratio to Baseline in the summaries. The following 
approach will be applied: 
• Following the MI procedure, the ratio to Baseline will be calculated for any of the imputed 
values  
• The natural logarithm of the absolute values and of the ratios to Baseline will be calculated 
• The logged values will be summarized (using PROC MEANS) by treatment, visit and 
imputation  
• The datasets will be combined using PROC MIANALYZE in order to get the mean and 95% 
CI estimates from the absolute values and ratios to Baseline (based on logged data) across 
imputations 
• The estimates of the mean and 95% CI will be back-transformed to obtain the geometric 
mean and 95% CI on the original scale 
• For the median, Q1, Q3, minimum and maximum the procedure outlined above for the other 
endpoints will be followed 
If the imputation model cannot converge, LOCF will be used. 
4.2.2.2 
MI – MCMC / Reference-based imputation 
MI-MCMC / Reference-based imputation will be implemented as a supportive analysis for the 
primary efficacy endpoint (through Week 16). 
In this case, placebo will be described as the reference arm.  
This procedure will use an imputation model based on data from the placebo group only 
(Mallinckrodt, 2013). Reference-based MI assumes that the statistical behavior of the 
bimekizumab and placebo-treated participants after discontinuing study medication becomes that 
of the placebo-treated participants. All timepoints after discontinuation of the double-blind study 
treatment for both the bimekizumab and placebo groups will be considered missing. Multiple 
imputations are used to replace missing outcomes for bimekizumab- and placebo-treated 
participants who discontinued using multiple draws from the posterior predictive distribution 
estimated from the placebo arm. For binary efficacy endpoints (eg, HiSCR50 at Week 16), 
imputation will be done on the lesion counts before assessing the imputed results for HiSCR50 
response. 
The steps for the procedure are as follows: 
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1. For non-monotone (intermittent) missing data, MCMC will be used to impute lesion count 
data, with Baseline antibiotic use, Hurley Stage at Baseline, and lesion count at Baseline and 
at each post-Baseline visit (in chronological order) being included in the imputation model. 
This will be done only once for each participant in order to provide a dataset with monotone 
missing data. 
2. Data will be processed sequentially by repeatedly calling SAS® PROC MI to impute missing 
outcome data at visits t=1, … T, where T is Week 16 for HiSCR50. 
a. Initialization. Set t=1 (Baseline visit) 
b. Iteration. Set t=t+1. Create a data set combining records from bimekizumab- and placebo-
treated participants with columns for covariates (Hurley Stage at Baseline and Baseline 
antibiotic use) and outcomes at visits 1 to t. Outcomes for all bimekizumab-treated 
participants 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 participants 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, 
Baseline antibiotic use, and Hurley Stage at Baseline. Note that only placebo data will be 
used to estimate the imputation model since no outcome is available for bimekizumab-treated 
participants at visit t. Consequently, the input dataset should include all study participants 
from placebo but only study participants from the bimekizumab arm that have values at 
timepoint t missing. 
d. Repeat steps 2a-2c, 100 times with different seed values (seeds ranging from 853 to 952) to 
create 100 imputed complete data sets. Study participants whose missing values were 
imputed in the last PROC MI call will be included in the input dataset for the next 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 inflammatory nodules will be updated to 0 in the case of an imputed 
value less than 0. 
e. Analysis. For each completed data set, the outcome (response or change from Baseline) will 
be calculated using the complete datasets (with no missing data). 
3. Each complete imputed data set will then be analyzed based on the statistical model specified 
in this study (logistic regression). The Week 16 results from logistic regression of each of the 
100 imputed data sets will be combined 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. 
4.2.2.3 
Tipping Point Analysis 
Tipping point analyses will also be implemented as a supportive analysis for the primary efficacy 
endpoint. 
The objective of the tipping point analyses is to evaluate the sensitivity of results to departures 
from the missing at random assumption and to identify the point at which departures cause 
results to "tip" from statistically significant to statistically non-significant. As such, these tipping 
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point analyses will only be performed if the primary efficacy analysis results in a statistically 
significant treatment effect. 
For tipping point analyses, data for participants after the intercurrent event date (See Section 3.9) 
will be changed to missing prior to imputation but will not be changed to non-response after 
imputation.  
The worst-case scenario will be evaluated first. All missing primary endpoint values for study 
participants randomized to bimekizumab (where missing values include observations after the 
intercurrent event date and any other missing values) will be imputed as non-responders, while 
all missing values for placebo-randomized study participants will be imputed as responders. 
While there is little justification for such an approach, it makes the most putative assumption 
possible against a bimekizumab 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 odds ratio of bimekizumab versus placebo remains significant, then 
no further tipping point analyses are needed. 
If this analysis based on the worst-case scenario results in a p-value that is not significant (eg, 
greater than 0.025), then additional tipping point analyses will be performed to identify the point 
at which results switch or “tip” from significant to non-significant. Note that each bimekizumab 
dose of 
 and 
 will be compared to placebo independently for these 
analyses. If one dose regimen is tested at the 0.05 significance level as determined in Section 4.5, 
then the p-value in this analysis method will be 0.05 instead of 0.025 throughout for that dose. In 
the tipping point analysis, a shift parameter or delta adjustment is applied to missing, and 
subsequently imported primary endpoint values (where missing values include observations after 
the intercurrent event and any other missing values). These delta implemented on the primary 
endpoint as follows: 
1. Data after intercurrent event date (See Section 3.9) will be set to missing. 
2. The same MCMC method described in Section 4.2.2.1 (Step 1a) will be implemented for 
non-monotone (intermittent) missing pattern values, using the same imputation model. This 
will be based on 100 sets of imputations. 
3. Based on the 100 datasets obtained in Step 2, a monotone regression model will be applied 
(using the same imputation model as in Step 2) as described in Section 4.2.2.1 (Step 1b). This 
will be based on 1 imputation.  
4. Delta adjustments will be made to imputed lesion count values at Week 16, independently in 
each treatment group as described below. 
5. Delta adjusted imputed values will be truncated so that they are within the range of allowable 
values for each component. 
6. Following the delta adjustments for the lesion counts, HiSCR50 will then be derived based on 
the delta-adjusted multiply imputed data sets obtained for each component.  
7. Each of the 100 imputed datasets will then be analyzed using a logistic regression model with 
factors of treatment group, Baseline Hurley Stage, and Baseline antibiotic use. 
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8. The results obtained from the 100 logistic regression analyses in Step 7 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.  
9. Steps 4 to 8 will be repeated so that, at each iteration, missing values are adjusted with a 
larger delta than at the previous iteration. The process will go on until the p-value for the 
odds ratio between bimekizumab and placebo is no longer statistically significant (eg, ≥ 
0.025). The odds ratio, 97.5% CI (or 95% depending on the significance level being used for 
testing), and p-values obtained for each value of delta will be combined in one single table.  
The delta adjustments result in study participants randomized to bimekizumab with missing data 
having a lower probability of response compared to study participants randomized to placebo 
with missing data. Since HiSCR50 response is an endpoint for which high lesion counts are 
associated with a less favorable outcome:  
• A positive adjustment is applied to the imputed value for study participants randomized to 
bimekizumab in order to increase the imputed value and decrease the likelihood of response. 
• A negative adjustment is applied to the imputed value for study participants randomized to 
placebo in order to decrease the imputed value and increase the likelihood of response. 
To start, imputed values within each lesion type, will be adjusted by the same value in each 
treatment arm. This adjustment will be 5% of the observed range within that lesion type. 
Depending on the results obtained, this adjustment will be multiplied for step 9 above (2 times, 3 
times the initial adjustment) until the p-value is no longer statistically significant.  
Additionally, study participants randomized to bimekizumab with an intercurrent event should be 
set to non-response, after applying the delta adjustment outlined in Step 6 above. This ensures 
study participants randomized to bimekizumab do not have a higher probability of response in 
the tipping point analyses compared to the primary analysis (ie, a study participant randomized 
to bimekizumab who is non-responder in the primary analysis cannot become a responder in the 
tipping point analyses). 
4.2.3 
Rationale for estimand 
Intercurrent events have been identified within the estimands for this study because of their 
potential to impact efficacy assessments linked with the primary and secondary study objectives. 
In order to account for the effect of any observed post-randomization intercurrent events on the 
efficacy analyses, the following estimand strategies will be implemented when evaluating the 
primary and secondary efficacy endpoints: 
• A composite estimand strategy will be used for the primary analysis of the primary and  
binary secondary endpoints (HiSCR50, HiSCR75, flare, HS worst skin pain response); 
• A hypothetical estimand will be used for the primary analysis of the continuous secondary 
endpoints (CFB in DLQI total score and in “worst skin pain” item for the HSSDD). 
4.2.3.1 
Composite estimand 
A composite estimand strategy as defined in Section 8.2.2 allows incorporation of the two 
intercurrent events (eg, receipt of systemic antibiotic rescue medication or discontinuation of 
study treatment due to an AE or lack of efficacy) within the definition of the endpoint. These 
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intercurrent events are considered meaningful to the efficacy outcome following receipt of study 
medication. For example, within the proposed composite estimand framework, a randomized 
study participant who discontinues from study treatment due to lack of efficacy prior to Week 16 
will be considered a treatment failure at Week 16 regardless of the lesion count assessment 
performed at that visit. 
The assumptions and robustness of the primary analysis (modified composite estimand as 
defined in Section 8.2.2) will be assessed through the sensitivity analyses defined in 
Section 8.2.3. The impact of intercurrent event handling and data imputation methods on 
endpoint derivation will also be assessed via the analyses of lesion counts and derived HiSCR 
variables as specified in Section 8.4.2.1 and Section 8.4.1.1, respectively. 
4.2.3.2 
Hypothetical estimand 
The hypothetical estimand is defined in Section 8.3 and involves a data-driven approach to 
account for the potential impact of intercurrent events (eg, receipt of systemic antibiotic rescue 
medication or discontinuation of study treatment due to an AE or lack of efficacy) on the 
analysis of continuous efficacy endpoints. Under this framework, outcomes for study participants 
without an intercurrent event are analyzed as observed. Conversely, outcomes for study 
participants with an intercurrent event are imputed via a multiple imputation model, ie any 
recorded data on or after the intercurrent event will be set to missing and imputed via multiple 
imputation following the strategy established in Section 4.2.2.1.  
4.2.4 
Dates and times 
For analyses of AEs and concomitant medication usage, a complete date is required in order to 
correctly identify the AE or medication as occurring during treatment or not, and for correctly 
assigning an AE or concomitant medication to the Initial Treatment Period or Maintenance 
Treatment Period. 
For purposes of imputing missing components of partially-reported start and stop dates for AEs 
and for medication use, the algorithms listed below will be followed. Start and stop dates of AEs 
or concomitant medication will be displayed as reported in the participant data listings (ie, no 
imputed values will be displayed in data listings). 
Partial AE and concomitant medication start dates will be imputed as follows: 
• Imputation of Partial Start Dates 
− If only the month and year are specified: 
◦ 
If the month and year of first dose of study medication is the same as the month and 
year of the partial start date, then use the date of first dose of study medication, 
◦ 
Else, if the month and year of the partial start date are the same as the month and year 
of a study medication switch date, then use the date of study medication switch, 
◦ 
Otherwise, use the 1st of the month of the partial start date; 
− If only the year is specified: 
◦ 
If the year of first dose of study medication is the same as the year of the partial start 
date, then use the date of first dose of study medication, 
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◦ 
Else, if the year of the partial date is the same as the year of a study medication 
switch date, then use the date of study medication switch, 
◦ 
Otherwise, use the 1st of January of the year of the partial start date; 
− If the start date is completely unknown: 
◦ 
If the stop date is unknown or not prior to the date of first dose of study medication, 
then use the date of first dose of study medication, 
◦ 
If the stop date is prior to the date of first dose of study medication, then use the 1st of 
January of the year of the stop date. 
• Imputation of Partial Stop Dates 
− If only the month and year are specified, : 
◦ 
Use the last day of the month of the partial stop date; 
− If only the year is specified  
◦ 
use December 31st of the year of the partial stop date; 
− If the stop date is completely unknown,  
◦ 
Do not impute the stop date. 
Note that if the stop date or the imputed stop date is prior to the imputed start date, then follow 
the procedure outlined below: 
• If only the year of the start date is specified: 
− If the year of start date is the same as the year of first dose of study medication and the 
imputed stop date is after the date of first dose of study medication, then set the start date 
to the date of first dose of study medication, 
− Otherwise, set the 1st January of the year of the start date; 
• If only the month and year of start date are specified: 
− If the month and year of the start date is the same as the month and year of first dose of 
study medication and the imputed stop date is on or after the date of first dose of study 
medication then set the start date to the date of first dose of study medication, 
− If the month and year of the start date is the same as the month and year of first dose of 
study medication and the imputed stop date is before the date of first dose of study 
medication then set the start date to the 1st of the month of partial start date. 
Missing start times for medications will be imputed as 00:00h or with the time of dosing for 
events occurring on the date of IMP administration in case of missing hour and minute. 
Otherwise start times with only missing minutes will be imputed with :00 or with the minutes of 
dosing for events occurring on the date and hour of IMP administration. 
In the event of ambiguity or incomplete data that makes it impossible to determine whether a 
medication was concomitant or an AE was treatment emergent, the medication will be 
considered as concomitant or the AE will be considered treatment emergent. Similarly, in the 
event of ambiguity or incomplete data which makes it impossible to determine whether a 
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medication or AE is to be assigned to the Initial Treatment Period or to the Maintenance 
Treatment Period (or both, for medications), then the medication will be assigned to both 
Treatment Periods, and the AE will be assigned to the Initial Treatment Period. 
4.3 
Interim analyses and data monitoring 
4.3.1 
Data monitoring committee 
An independent data monitoring committee (DMC) will periodically review unblinded efficacy 
and safety data to assess the benefit/risk of bimekizumab in study participants with moderate to 
severe HS. Efficacy data summaries and individual study participant-level data listings may be 
provided to the DMC to put the safety review in the context of risk/benefit. Any data to be 
provided is specified per the DMC charter. In addition, unblinded efficacy data analysis is 
planned to be provided to the DMC when approximately 66% of study participants have reached 
the primary efficacy endpoint at Week 16. At this analysis, formal primary endpoint comparisons 
between each bimekizumab dose and placebo will be provided so the DMC can make an 
assessment regarding the futility of each dose group. However, no early stopping of a treatment 
group or study will be made on the basis of superior efficacy. Therefore, no alpha adjustment is 
planned since the efficacy analyses will only be for futility. 
Measures to ensure that unblinded interim results are not disseminated beyond the DMC will be 
implemented. Details of futility stopping boundaries and decision rules are detailed in the DMC 
Charter. The details regarding the outputs to be produced and the analyses to be performed will 
be provided in a separate DMC SAP. 
4.3.2 
Interim analysis 
In addition to the futility analysis described in the previous section, an unblinded interim analysis 
will be performed and a corresponding interim CSR may be written after the last study 
participant has completed the Week 48 visit, or after the last study participant has prematurely 
discontinued prior to reaching Week 48. The purpose of this interim analysis is to perform a 
comprehensive evaluation of all available double-blind data to prepare regulatory submissions 
for approval of the HS indication. A final analysis and updated final CSR will be prepared once 
all data (through to the SFU visit) have been collected.  
4.4 
Multicenter studies 
The center-by-treatment interaction will be tested by adding center and a center-by-treatment 
interaction term (Section 8.2.3.11). In the model, center will be based on the original centers 
prior to pooling (Section 3.7). However, if the model is unable to converge due to a low number 
of participants at a given center, a pooling by center will be applied in order to allow the model 
to converge. If convergence is still not achieved, a pooling by region will be applied. If 
convergence still cannot be achieved, this analysis will not be performed. Detailed strategy in 
Section 3.7 will be applied. 
4.5 
Multiple comparisons/multiplicity 
To control the overall type I error rate at 0.05 for the multiple comparisons in the primary and 
secondary efficacy endpoints, a closed testing procedure under a parallel gatekeeping framework 
will be applied (Sun, 2018). 
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Under this framework, each bimekizumab dose of 
 and 
 will be 
compared to placebo in the first instance at a familywise error rate of 0.025 (α/2). 
Simultaneously within each dose, closed testing for the primary and secondary efficacy 
endpoints will be performed as follows: 
1. Step 1: Test HiSCR50 at significance level 0.025. 
2. Steps 2 to 6 – If Step 1 is significant at 0.025 then test each secondary endpoint sequentially 
in the order shown in Figure 4-1, moving to the next step only if significance achieved at 
0.025. 
3. In the event that Step 6 is significant at 0.025 for a given dose, then Steps 1 to 6 will be 
repeated for the other dose using a significance level of 0.05. 
The secondary efficacy variables supporting the primary efficacy variable are listed below, and 
will be included in the multiplicity adjustment using the analysis methods specified in 
Section 8.3: 
1. Proportion of study participants who achieve HiSCR75 at Week 16.  
a. bimekizumab
 vs placebo 
b. bimekizumab 
 vs placebo 
2. Proportion of study participants who experience at least 1 flare by Week 16, with flare 
defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 relative 
to Baseline.  
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
3. Absolute CFB in DLQI Total Score at Week 16. 
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
4. Absolute CFB in Skin Pain Score at Week 16, as assessed by the “worst skin pain” item 
(11-point numeric rating scale) in the HSSDD. 
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
5. Skin pain response at Week 16, based on the threshold for clinically meaningful change 
(defined as at least a 3 point decrease from Baseline in HSSDD weekly worst skin pain 
score) at Week 16 among study participants with a score of ≥3 at Baseline.  
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
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Figure 4-1: Sequence of testing 
 
AN=abscess and inflammatory nodule; DLQI=Dermatology Life Quality Index; HiSCR50=a 50% reduction in the 
total AN count with no increase from Baseline in abscess or draining tunnel count; HiSCR75=a 75% reduction in 
the total AN count with no increase from Baseline in abscess or draining tunnel count; HS=hidradenitis 
Suppurativa; 
 
HS skin pain response is tested among study participants with a score of ≥3 at Baseline. 
4.6 
Use of an efficacy subset of participants 
A sensitivity analysis of the primary endpoint will be performed based on the FAS, the PPS, and 
the CFS. 
4.7 
Active-control studies intended to show equivalence 
Not applicable. 
4.8 
Examination of subgroups 
Subgroup analyses will be performed on the HiSCR50, HiSCR75, flare, and worst skin pain 
response endpoints by visit for the Initial Treatment Period and Maintenance Treatment Period. 
Additional subgroup analyses will be performed on the CFB in the worst skin pain score as 
measured by HSSDD and in the DLQI total score through Week 16 as described below. 
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Along with the tables described, there will be tables for HiSCR50, HiSCR75, flare, and skin pain 
response endpoints which display the response difference and 95% CIs between each 
bimekizumab dose regimen versus placebo for each of the subgroups at Week 16. Corresponding 
forest plots will be prepared.  
The following subgroup variables will be determined using Baseline data, except for analgesic 
use, lesion intervention, and antibody positivity:  
• Age (<40 years, 40 to <65 years, ≥65 years) 
• Gender (male, female) 
• Disease duration (<median, ≥median) 
The median disease duration will be calculated based on all participants in the analysis set used 
for analysis. 
• Region (North America [Canada, USA], Western Europe [France, Germany, Ireland, Italy, 
Spain, United Kingdom], Central/Eastern Europe [Bulgaria, Czech Republic, Hungary, 
Poland], Asia/Australia [Australia, Israel, Japan]) 
• Weight (≤100 kg, >100 kg) 
• BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2) 
• Race (Black or African American, White, All Other Races [American Indian or Alaska 
Native, Asian, Native Hawaiian or Other Pacific Islander, Other/Mixed]) 
• Systemic antibiotic therapy at randomization (yes, no) 
• Prior biologic therapy for any indication (yes, no) 
• Prior biologic therapy for HS (yes, no) 
• Hurley Stage at Baseline (II or III) 
• Analgesic users (yes, no), separately for the Initial Treatment Period and the Maintenance 
Treatment Period (Section 6.4.2 specifies how participants are classified as analgesic users) 
• Lesion intervention (yes, no), separately for the Initial Treatment Period and the Maintenance 
Treatment Period  
• Antibody positivity (confirmatory assay: negative or positive; see Section 9.3.2) 
• Antihistamine users during the Initial Treatment Period (yes, no) (Section 6.4.2 specifies how 
participants are classified as antihistamine users) (applicable only to the skin pain response 
endpoint) 
The following subgroups for analysis on the CFB in the worst skin pain score as measured by 
HSSDD and in the DLQI total score will be determined based on medication use during the 
Initial Treatment Period:  
• Antihistamines users during the Initial Treatment Period (yes, no) (Section 6.4.2 specifies 
how participants are classified as antihistamine users) 
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• Analgesics users during the Initial Treatment Period (yes, no) (Section 6.4.2 specifies how 
participants are classified as analgesic users) 
• Systemic antibiotic therapy start/increase after randomization during the Initial Treatment 
Period (yes, no) 
All summaries will be based on imputed data as appropriate and will include descriptive statistics 
only.  
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Study participant disposition 
Summaries of reasons for screen failures (for ES), disposition of participants (for ES), 
disposition of analysis sets (for RS), disposition and discontinuation reasons in the Initial 
Treatment Period (for RS) and the Maintenance Treatment Period (for MS), as well as the 
participants who discontinued due to AEs in the Initial Treatment Period (for RS) and 
Maintenance Treatment Period (for MS) will be produced. The disposition of participants for all 
participants screened will include the number of participants included in each analysis set (ES, 
RS, SS, FAS, AMS, MS, PPS, and PK-PPS) overall and by site. 
Participants are defined as completing the Initial Treatment Period if they have a Week 16 visit, 
or if they fail to attend the Week 16 visit but attend at least one visit in the Maintenance 
Treatment Period. 
The following listings for participant disposition will be provided: participants who did not meet 
study eligibility criteria (for ES), participant disposition (for ES), participant discontinuation 
(RS), visit dates (for RS), participant analysis sets (for ES), participants excluded from efficacy 
analysis (for RS).  
To assess participant disposition (entry and periods in the study) during the COVID-19 
pandemic, study participant disposition will also be assessed by period of the COVID-19 
pandemic (pre – during – post), by comparing the dates of visits (or events) to the dates of the 
COVID-19 pandemic period. The dates to categorize the periods of the COVID-19 pandemic 
(pre/during/post) are 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 
5.2 
Impact of COVID-19 
A listing of visits affected by COVID-19 will be presented based on the ES including the visit, 
date of visit, relationship to COVID-19, impact category and a narrative (short description) of the 
event. These data will be summarized for non-randomized participants and by treatment group 
and overall, for enrolled participants. 
A summary of study visits by COVID-19 pandemic period (pre – during – post) will be 
presented for participants enrolled prior to and during the pandemic.  
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In addition, in order to assess the potential impact of COVID-19 on the collection and reporting 
of efficacy data, a separate summary on the RS will be presented to display missing data as well 
as data collected via an alternative modality (e.g.: phone, video call) for efficacy endpoints 
included in the hierarchy (Section 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. Note that the remote contingencies for COVID-
19 or other exceptional circumstances are not applicable to efficacy assessments and 
documentation (eg, lesion-based assessments, photography) that require direct face-to-face 
physician/participant interaction. 
5.3 
Protocol deviations 
Summaries, based on the RS and the MS, displaying the number and percentage of participants 
with an important protocol deviation (including a summary of participants excluded from the 
PPS or PK-PPS due to important protocol deviations) by treatment group in the Initial Treatment 
Period and in the Maintenance Treatment Period, respectively, will be provided. A separate 
summary of participants with protocol deviations related to COVID-19 will be provided. 
A by-participant listing of protocol deviations will be provided. Protocol deviations (eg, missing 
assessments or visits) related to COVID-19 will be listed separately. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
All summaries detailed in this section will be performed on the RS by treatment group. 
Summaries for demographics and other baseline characteristics will also be repeated on SS and 
MS. If the RS and SS are identical, the SS summaries will not be created. 
6.1 
Demographics 
Demographic variables will be summarized by treatment group and overall. 
The following continuous variables will be summarized using descriptive statistics (number of 
study participants, mean, SD, minimum, median, and maximum). 
• Age (years) 
• Height (cm) 
• Weight (kg) 
• BMI (kg/m2)  
BMI (kg/m2) will be calculated as: 
BMI = Weight (kg)
(Height (m))2. 
The following categorical variables will be summarized generally using frequency counts and 
percentages. 
• Age group (≤18, 19-<65, ≥65 years)  
• Age group (18-<65, 65-<85, ≥85 years) 
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• Age group (<40, 40-<65, ≥65 years) 
• Body weight (≤100 kg, >100 kg) 
• Gender 
• Race 
• Ethnicity  
• Ethnic subgroup 
• BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2) 
• Region 
• Smoking history 
• Country 
By-participant listing of demographics for all study participants screened will be provided. 
Childbearing potential and lifestyle will be collected at Screening.  
6.2 
Other Baseline characteristics 
The following Baseline disease characteristics will be summarized by treatment group: 
• Lesion counts by anatomical region and lesion type, total lesion counts across anatomical 
regions by lesion type, Hurley Stage by anatomical region and worst overall Hurley Stage 
across anatomical regions 
• IHS4 score, individual items of the HSSDD, HS-Physician’s Global Assessment, DLQI total 
score and HiSQOL domain and total scores 
• hs-CRP 
• Duration of disease (years) 
Duration of disease (years) will be calculated as: 
Disease Duration =
(Date of randomization−Date of HS Diagnosis1)
365.25
. 
1If the date of HS diagnosis is partial, it will 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). 
Note that if the date of randomization is missing then the duration of disease will be derived 
using the date of screening. If the imputed date results in a participant having a disease duration 
of less than 6 months and the inclusion criterion related to having HS for at least 6 months is 
confirmed to not have been violated, then the participant’s duration of disease will be set to 6 
months. If that criterion has been violated, then the participant’s duration of disease will be the 
imputed value of less than 6 months.  
• Duration of disease (<median, ≥median) 
The median disease duration will be calculated based on all participants in the analysis set used 
for the summary. 
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• Baseline antibiotic use (yes, no) (According to the randomization strata) 
• Baseline antibiotic use (yes, no) (Derived) 
• Hurley Stage at Baseline (According to the randomization strata) 
• Hurley Stage at Baseline (Derived) 
In addition, the following Baseline disease characteristics will be summarized by the derived 
Baseline Hurley Stage and by the derived Baseline antibiotic use and treatment group for the RS: 
• IHS4 score 
• “worst skin pain score” and "average skin pain score" in the HSSDD 
• HS-Physician’s Global Assessment 
• DLQI total score 
•  hs-CRP 
• Duration of disease (years) 
• Total lesion counts 
6.3 
Medical history and concomitant diseases 
Previous and ongoing medical history will be summarized by treatment groups, system organ 
class (SOC), and preferred term (PT) using MedDRA®. Medical procedures are not coded.  
The following listings for medical history and concomitant diseases will be provided: medical 
history, HS history, concomitant medical procedures, previous and ongoing medical history 
glossary, previous and ongoing medical history conditions, and procedure history.  
6.4 
Prior and concomitant medications 
Prior medications include any medications that started before the start date of study medication. 
Concomitant medications are any medication that has a start date on or after the start date of 
study medication, or any medication that has a start date on or before the last dose of study 
medication + 28 days (whether placebo or bimekizumab).  
Any medication that started before the first dose of IMP and continued after will be classified as 
both prior and concomitant. Such medications will therefore be counted in the tabulations for 
both prior and concomitant medication. 
Details of imputation methods for missing or partial dates are described in Section 4.2.4. 
The number and percentage of participants taking prior medications will be summarized by 
treatment group, overall and by ATC class, presenting Anatomical Main Group (ATC Level 1), 
Pharmacological Subgroup (ATC level 3), and PT. Prior antibiotic medications will be 
summarized similarly. 
The number and percentage of participants taking concomitant medications will be summarized 
similarly for the Initial Treatment Period and Maintenance Treatment separately. The number 
and percentage of participants taking concomitant antibiotic medications, antihistamines, and 
analgesics  will be summarized separately by treatment group, overall, and by ATC class, 
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presenting Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC level 3), 
and PT for the Initial Treatment Period and Maintenance Treatment Period separately. 
Separate summaries will be presented for participants taking rescue medication for the Initial 
Treatment Period and Maintenance Treatment Period separately, identified by a ‘yes’ response to 
the ‘Is this a rescue medication’ question on the electronic case report form (eCRF). This 
summary will be performed separately for analgesic use and antibiotic use. 
Additional summaries for the Initial Treatment Period and Maintenance Treatment Period will be 
presented for participants taking systemic antibiotic medications that qualify as intercurrent 
events as described in Section 3.9.  
The number and percentage of study participants with concomitant vaccines for COVID-19 will 
be summarized by treatment group, overall and by World Health Organization Drug Dictionary 
Standardized Drug Grouping (SDG), presenting SDG subgroup, and preferred term. The SDG 
subgroup Vaccines for COVID-19 will be used to identify vaccines for COVID-19 using the 
narrow scope; this subgroup is divided further into separate subgroups which is the level that will 
be presented. The number of individual occurrences of the vaccine for COVID-19 will also be 
summarized.  
A listing of concomitant vaccines for COVID-19 will be provided. 
6.4.1 
 Assignment of medications to study period 
The following rules will be used to assign a concomitant medication to a study period: 
• Initial Treatment Period: a medication will be assigned to the Initial Treatment Period if it 
has been taken at least once between the first administration of IMP on Day 1 up to Week 16. 
This includes medications that started prior to the Initial Treatment Period and those that 
continued into the Maintenance Treatment Period. 
• Maintenance Treatment Period: a medication will be assigned to the Maintenance 
Treatment Period if it has been taken at least once between Week 16 and the final visit. This 
includes medications that started prior to the Maintenance Treatment Period. 
Thus, a medication taken from the time of the first drug administration in the Initial Treatment 
Period to any timepoint after Week 16 will be assigned to both the Initial Treatment Period and 
the Maintenance Treatment Period. 
Methods for dealing with partial dates are specified in Section 4.2.4. 
6.4.2 
Classification of participants as analgesic, antihistamine users 
If a participant has taken a new analgesic/increased regimen of analgesic, or taken an 
antihistamine, on 1 or more days (need not be consecutive) in a study period (Initial Treatment 
Period or Maintenance Treatment Period), then for that period the participant will be classified as 
an analgesic or antihistamine user, respectively. The period under consideration is to match the 
period as defined for the HSSDD for the Initial Treatment Period or HSSQ for the Maintenance 
Treatment Period, based on dates/times of the medications taken.  
New analgesic/increased regimen of analgesic use, regardless of indication, is defined as an 
analgesic medication with start date on or after the first dose of study medication. Stable 
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analgesics (ie, analgesics which were taken already before randomization) will not be included in 
this category of analgesic user. This classification will be used for selected subgroup analyses. 
Antihistamine use is identified by considering the ATC classification. This classification is used 
for analyzing the Worst Itch endpoint and for selected subgroup analyses, by visit, for the Initial 
Treatment Period and Maintenance Period as applicable. 
Additionally, if a participant has taken a new analgesic/increased regimen of analgesic on 1 or 
more days (need not be consecutive) prior to the Week 16 visit, then for that week the participant 
will be classified as an analgesic user. This classification will be used to adjust the formal 
analysis of the Worst Skin Pain secondary endpoints. If there is a visit date but no HSSDD 
available at the visit, then the analgesic/antihistamine user status for that week will be derived 
based on the visit date.  If there is no visit available, then the weekly analgesic/antihistamine user 
status will default to the analgesic/antihistamine status for the overall study period. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Due to the method of administration of the treatments, compliance will be examined in terms of 
completed injections.  
Treatment compliance will be calculated as: 
𝑁𝑎𝑐𝑡𝑢𝑎𝑙
𝑁𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑
 ×  100% 
where 𝑁𝑎𝑐𝑡𝑢𝑎𝑙 is the total number of actual (completed) injections, and 𝑁𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 is the total 
number of expected injections. In this study, dosing occurs 
 from Week 0 to Week 
46, where 2 injections are administered at each given visit either with active dosing or placebo 
injection. It is expected that a participant should complete a total of 48 injections by the end of 
study. If a participant discontinues early, then the number of expected injections is based on the 
time of early discontinuation relative to the dosing visits. For example, if a participant 
discontinues after Week 8 visit and prior to Week 10 visit, the total number of expected 
injections will be 10. 
A summary of percent treatment compliance categorized as <75% and ≥75% will be provided by 
treatment group for each study period (Initial Treatment Period for the RS, Maintenance 
Treatment Period for the MS, and the combined Initial and Maintenance Treatment Period for 
the AMS). 
A by-participant listing of treatment compliance will be provided. 
8 
EFFICACY ANALYSES 
All efficacy analyses of primary, secondary, and other variables will be performed on the RS 
unless otherwise specified. All efficacy summary tables will be displayed by treatment sequence 
unless otherwise specified. The primary and secondary endpoints, and their components, will 
also be summarized by the derived Hurley Stage at Baseline (grouping each stage and overall) 
and treatment sequence and by the derived Baseline antibiotic use (yes/no and overall)  and 
treatment group. 
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8.1 
Lesion count assessment 
The primary efficacy endpoint and some of the secondary and other efficacy endpoints discussed 
in Section 8.3 and Section 8.4 are based on the assessment and/or counts of different types of 
lesions in the following main anatomical regions at each visit.  
• Inguinal (groin)  
• Axillary (armpit) 
• Chest/breast 
• Gluteal 
• Abdomen including supra pubic 
• Back 
• Head 
• Neck 
• Leg 
• Other 
These anatomical regions are further classified into the following locations, for the left and right 
sides of the body, as applicable: 
• Inguinal excluding genital and pubic area 
• Inguinal including genital and pubic area  
• Submammary  
• Intermammary 
• Chest 
• Breast  
• Gluteal – Buttocks  
• Gluteal – Perianal/Perineal  
• Scalp 
• Face 
All “Other” anatomical regions with lesions present will be specified in free text on the eCRF.  
The number of each of the following types of lesions will be recorded in each anatomical region, 
and then summed across all anatomical regions: 
• Abscesses 
• Inflammatory nodules  
• Non-inflammatory nodules  
• Draining tunnels (fistulas/sinus tracts) 
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• Non-draining tunnels (fistulas/sinus tracts)  
• HS scars 
If participants undergo lesion interventions as specified in the study protocol, the affected lesions 
will be counted by the Investigator as permanently present, thus accounting for potential bias due 
to the intervention. Section 8.4.23 specifies how the intervention data will be presented. 
8.2 
Primary efficacy endpoint 
The primary and sensitivity analyses of HiSCR50 response at Week 16 are summarized in 
Table 8‒1. 
Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Primary Objective: To evaluate the efficacy of bimekizumab in study participants with moderate to 
severe HS 
HiSCR50 
Primary 
(Section 8.2.2) 
HiSCR50 
response at 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. A 
composite strategy will 
be used, ie, the 
occurrence of an 
intercurrent event will 
be handled by 
evaluating the 
corresponding 
participants as treatment 
failures 
(nonresponders). 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values will 
be imputed using MI 
– MCMC/Monotone 
Regression under a 
missing at random 
assumption. 
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Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.1) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis 
where the occurrence of 
an intercurrent event 
will be handled by 
evaluating the 
corresponding 
participants as 
nonresponders. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values for 
any other reason will 
also be imputed as 
nonresponders. 
HiSCR50 
Sensitivity 
(Section 8.2.3.2) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values will 
be imputed using MI 
– Reference-Based 
Regression under a 
missing not at 
random assumption. 
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Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.3)   
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategya, as 
for the primary analysis. 
A tipping point 
analysis will be used 
where 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. The 
odds ratio versus 
placebo is based on a 
logistic regression 
for each value of 
delta.  
HiSCR50 
Sensitivity 
(Section 8.2.3.4) 
HiSCR50 
response at 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
treatment policy 
strategy, whereby the 
data from the Initial 
Treatment Period are 
used regardless of 
whether the intercurrent 
event occurred. 
The odds ratio versus 
placebo is based on a 
logistic regression, as 
for the primary 
analysis.  
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Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.5) 
HiSCR50 
response at 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
lesion count assessment 
at Week 16 who have 
not had an intercurrent 
event on or before Week 
16 are included. 
The odds ratio versus 
placebo is based on a 
logistic regression. 
Missing values will 
not be imputed. 
HiSCR50 
Sensitivity 
(Section 8.2.3.6 ) 
HiSCR50 
response at 
Week 16 
 
FAS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo is based on a 
logistic regression, as 
for the primary 
analysis. 
HiSCR50 
Sensitivity 
(Section 8.2.3.7) 
HiSCR50 
response at 
Week 16 
 
PPS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo is based on a 
logistic regression, as 
for the primary 
analysis.  
HiSCR50 
Sensitivity 
(Section 8.2.3.8) 
HiSCR50 
response at 
Week 16 
 
CFS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo is based on a 
logistic regression, as 
for the primary 
analysis.  
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Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.9) 
HiSCR50 
response at 
Week 16 
 
RS 
The same two 
intercurrent events used 
for the primary analysis 
will be used. Any 
missing data due to 
COVID-19 will also be 
considered an 
intercurrent event. A 
composite strategy will 
be used, ie, the 
occurrence of an 
intercurrent event will 
be handled by 
evaluating the 
corresponding 
participants as treatment 
failures 
(nonresponders). 
The odds ratio versus 
placebo is based on a 
logistic regression, as 
for the primary 
analysis.  
HiSCR50 
Sensitivity 
(Section 8.2.3.10
) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
stratified Cochran-
Mantel-Haenszel 
(CMH) test. Missing 
values not preceded 
by an intercurrent 
event will be 
imputed using MI – 
MCMC/Monotone 
Regression under a 
missing at random 
assumption. 
CFS=Covid-19 Free Set; CMH=Cochran-Mantel-Haenszel; COVID-19=coronavirus disease 2019; FAS=Full 
Analysis Set; HiSCR=Hidradenitis Suppurativa Clinical Response; IES=intercurrent event(s) strategy; 
MCMC=Markov Chain Monte Carlo; MI= multiple imputation; PLS=Population-level summary; Pop=Population; 
PPS=Per-Protocol Set; RS=Randomized Set 
a The composite estimand strategy will be modified in the tipping point analysis such that participants with 
intercurrent events will be treated as nonresponders only in the bimekizumab treatment groups. 
8.2.1 
Derivation of HiSCR50 at Week 16 
The following algorithm will be applied to derive HiSCR50 at each visit, based on total lesion 
counts across anatomical regions for the 3 relevant lesion types recorded as specified above in 
Section 8.1: 
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1. Calculate the AN count at each visit as the total number of abscesses plus the total number of 
inflammatory nodules, across all anatomical regions 
2. Calculate the percentage change from Baseline in AN count (%ΔAN) at each visit as  
 
100 × (𝐴𝑁 𝑐𝑜𝑢𝑛𝑡 𝑎𝑡 𝑝𝑜𝑠𝑡-𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑖𝑠𝑖𝑡 𝑚𝑖𝑛𝑢𝑠 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝐴𝑁 𝑐𝑜𝑢𝑛𝑡) 
/ (𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝐴𝑁 𝑐𝑜𝑢𝑛𝑡) 
3. Calculate the change from Baseline in the abscess count by subtracting the Baseline abscess 
count from the abscess count at each post-Baseline visit  
4. Calculate the change from Baseline in the draining tunnel (fistula/sinus tract) count by 
subtracting the Baseline draining tunnel (fistula/sinus tract) count from the draining tunnel 
(fistula/sinus tract) count at each post-Baseline visit 
5. If the %ΔAN is less than or equal to -50%, and the change from Baseline in the abscess count 
is zero or negative (ie, non-positive) together with a non-positive change from Baseline in the 
draining tunnel (fistula/sinus tract) count, then the HiSCR50 will be assigned a value of 1 (ie, 
HiSCR50 is achieved); otherwise, the HiSCR50 will be assigned a value of 0 (ie, HiSCR50 is 
not achieved). 
In cases where the inflammatory nodule, abscess or draining tunnel (fistula/sinus tract) count is 
missing and will not allow for the HiSCR50 calculation, the rules for handling missing values in 
the analysis will be applied (Section 4.2.1 and Section 8.2.3). 
The primary efficacy endpoint is attained if the participant has a HiSCR50 of 1 at Week 16.  
8.2.2 
Primary analysis of the primary efficacy endpoint 
The primary endpoint is the HiSCR50 response at Week 16 and corresponding analyses are based 
on the RS. The primary efficacy analysis will evaluate the composite estimand in the RS as 
described in Table 8‒1. The composite estimand combines the clinically meaningful 
improvement from Baseline based on the HiSCR50 response and completion of study treatment 
through Week 16 without receiving systemic antibiotic rescue medication or discontinuing IMP 
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=Study participants meeting the protocol-specified inclusion/exclusion criteria.  
2. Study participant-level outcome=HiSCR50 at Week 16. 
3. Intercurrent event handling=An intercurrent event is defined as receipt of systemic antibiotic 
rescue medication or discontinuation of study treatment due to an AE or lack of efficacy 
prior to Week 16. More information is provided in Section 3.9. A composite strategy will be 
implemented in which a positive clinical outcome is defined as achieving HiSCR50 at Week 
16 and not receiving systemic antibiotic rescue medication, and not discontinuing study 
treatment due to an AE or lack of efficacy through Week 16. Any missing data at Week 16 
that are not preceded by an intercurrent event will be imputed using multiple imputation as 
defined in Section 4.2.1. The rationale for this composite estimand is provided in 
Section 4.2.3.1.  
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4. Population-level summary measure=conditional odds ratio comparing bimekizumab to 
placebo adjusted for stratification factors used in the randomization. 
The statistical hypothesis for the HiSCR50 response at Week 16 is that the conditional odds ratio 
for the HiSCR50 response in the bimekizumab treatment group relative to the placebo group is 
equal to 1.  
The primary analysis will be based on a logistic regression model including a fixed effect for 
treatment, Hurley stage at Baseline, and Baseline antibiotic use. The odds ratio versus placebo, 
p-value (from Wald test), and 97.5% CI will be calculated. If one dose regimen is tested at the 
0.05 significance level as determined in Section 4.5, then the confidence interval will be 95% 
instead of 97.5% for that dose with a corresponding Zα/2 of 1.96. 
The number and percentage of participants who are HiSCR50 responders at Week 16 will be 
summarized.  
By-participant listings of HiSCR responder endpoints will be provided. 
8.2.3 
Sensitivity analyses of the primary efficacy endpoint  
The following sensitivity analyses for the primary efficacy endpoint will be performed to 
evaluate the assumptions related to the handling of missing data. Details of the estimands for 
each analysis are described in Table 8‒1. 
8.2.3.1 
Nonresponse imputation 
As a sensitivity analysis, any missing data at Week 16 that are not preceded by an intercurrent 
event (ie, receipt of systemic antibiotic rescue medication or discontinuation of study treatment 
due to an AE or lack of efficacy) will be imputed as nonresponse. That is, participants who 
experience an intercurrent event will be imputed as nonresponder at the timepoint of the event 
and all subsequent timepoints (including any recorded data after the event), and all missing data 
will also be imputed as nonresponse. 
The same analysis model as in the primary efficacy analyses will then be used on the imputed 
data set. 
8.2.3.2 
MI-MCMC / Reference-based imputation 
Deviations from the missing at random pattern will be evaluated using a reference-based MI 
approach (see Section 4.2.2.2 ). Intermittent missing data will be imputed using the MCMC 
method. The remaining monotone missing data will be assumed to follow a missing not at 
random pattern. These data will be imputed using a reference-based approach in which the MI 
model is based on data from the placebo group, thereby assuming that monotone missing data 
follow a trajectory similar to the placebo group.  
The same analysis model as in the primary efficacy analyses will then be used on the imputed 
data set. 
8.2.3.3 
Tipping point analysis  
Tipping point analyses will be performed to evaluate missingness assumptions. 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 study participants who have missing data and are randomized to bimekizumab have a 
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lower probability of response compared to study participants who have missing data and were 
randomized to placebo. This includes the worst-case scenario where study participants who have 
missing data and are randomized to bimekizumab are considered nonresponders, while study 
participants 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. 
Refer to Section 4.2.2 for more details on the methodology.  
8.2.3.4 
Treatment policy 
The treatment policy strategy for addressing intercurrent events will be considered. This will be 
based on an analysis of all available data at Week 16 regardless of the occurrence of intercurrent 
events. This analysis will use the same models specified for the primary analysis, where study 
participants are analyzed according to their randomized treatment, even if they discontinued 
study treatment for any reason prior to Week 16. Even though efforts will be made to collect the 
primary outcome data for all study participants at Week 16, there may still be some study 
participants for whom Week 16 efficacy data cannot be obtained. In this case, missing data will 
be imputed using multiple imputation under the assumption of MAR (see Section 4.2.2). The 
same analysis model as in the primary efficacy analyses will then be used on the imputed data set 
and the resulting inferential statistics will then be combined into a single inference using Rubin's 
rule. 
8.2.3.5 
Analysis on observed cases 
An additional supportive analysis will be based on observed data only for study participants with 
a lesion count assessment at Week 16 who have not had an intercurrent event on or before Week 
16. Study participants with missing data at Week 16 will be treated as missing (see 
Section 4.2.2). 
The same analysis model as in the primary efficacy analyses will then be used on the imputed 
data set. 
8.2.3.6 
Analysis on FAS 
The primary efficacy analyses from Section 8.2.2 will be repeated based on the FAS.  
8.2.3.7 
Analysis on PPS 
The primary efficacy analyses from Section 8.2.2 will be repeated based on the PPS.  
8.2.3.8 
Analysis on CFS 
The primary efficacy analyses from Section 8.2.2 will be repeated based on the CFS.  
8.2.3.9 
Analysis including COVID-19 impact as intercurrent event 
An additional sensitivity analysis will include an additional intercurrent event. The composite 
estimand combines the clinically meaningful improvement from Baseline based on the HiSCR50 
response and completion of study treatment through Week 16 without receiving systemic 
antibiotic rescue medication or discontinuing IMP due to an AE or lack of efficacy. 
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The following 4 attributes describe the estimand that will be used to define the treatment effect 
of interest for this sensitivity efficacy analysis:  
1. Population=Study participants meeting the protocol-specified inclusion/exclusion criteria.  
2. Study participant-level outcome=HiSCR50 at Week 16. 
3. Intercurrent event handling=An intercurrent event is defined as receipt of systemic antibiotic 
rescue medication, discontinuation of study treatment due to an AE or lack of efficacy prior 
to Week 16, or missing data due to COVID-19. More information is provided in Section 3.9. 
A composite strategy will be implemented in which a positive clinical outcome is defined as 
achieving HiSCR50 at Week 16 and not receiving systemic antibiotic rescue medication, not 
discontinuing study treatment due to an AE or lack of efficacy through Week 16, and not 
having missing data due to COVID-19. Any missing data at Week 16 that are not preceded 
by an intercurrent event will be imputed using multiple imputation as defined in 
Section 4.2.1. 
4. Population-level summary measure=conditional odds ratio comparing bimekizumab to 
placebo adjusted for stratification factors used in the randomization. 
The same imputation techniques and analysis model as in the primary efficacy analyses will then 
be used. 
8.2.3.10 
Cochran-Mantel-Haenszel test 
The primary efficacy analyses from Section 8.2.2 will be repeated where the CMH test with 
fixed effects for treatment, Hurley stage at Baseline, and Baseline antibiotic use will be used as 
stratification variables. Pairwise treatment comparisons will be made based on the CMH test 
using the p-value for the general association. The odds ratio and associated confidence interval 
(CI) based on the Wald test will be provided. 
8.2.3.11 
Center-by-Treatment Interaction 
The center-by-treatment interaction will be tested by adding center and a center-by-treatment 
interaction term in the logistic regression model described in Section 8.2.2. In the model, center 
will be based on the original centers prior to pooling. However, if the model is unable to 
converge due to a low number of participants at a given center, a pooling (see Section 3.7) will 
be described in order to allow the model to converge. In order to obtain reasonable estimates of 
variability for a treatment arm at a given center, a minimum of 21 participants will be considered 
acceptable for a center to be included in the model without pooling. Given the 2:2:2:1 
randomization allocation scheme, this should provide a minimum of about 12 participants in the 
bimekizumab 
 treatment group, 6 participants in the bimekizumab 
 
treatment group, and 3 participants in the placebo treatment group. Centers with fewer than 21 
participants will be eligible for pooling. The pooling algorithm used is described in Section 3.7. 
In order to achieve model convergence, other explanatory variables eg, Baseline Hurley Stage 
and Baseline antibiotic use may be dropped from the model. If model convergence is still not 
achieved, region and a region-by-treatment interaction term will be added to the model instead. 
Regions are defined in Section 3.7. 
If the center-by-treatment interaction is not found to be significant (α=0.05), then no further 
analyses will be performed. On the other hand, if the interaction is significant, further analyses 
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will be conducted to determine which center or centers may be the source of interaction. This 
will be done by running the logistic regression model (including the interaction term) where each 
center will be systematically removed from the model. This impact of a given center will be 
based on the change in the interaction p-value when that center is removed. The center or centers 
that appear to be driving the significant interaction effect will then be removed from the model to 
verify that conclusions remain the same with or without the influential center(s). This sensitivity 
analysis will be based on RS with MI/MCMC Monotone Regression for missing data.  
8.3 
Secondary efficacy endpoints 
The secondary efficacy analyses will be performed based on the RS. Sensitivity analyses of the 
secondary endpoints will be performed on the CFS. 
Missing data handling and sensitivity analyses of the secondary efficacy endpoints are described 
in Section 4.2.1.2. 
The analyses of the secondary endpoints are summarized in Table 8‒2 . 
Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Secondary Objective: Evaluate the efficacy of bimekizumab on other measures of disease activity in 
study participants with moderate to severe HS 
HiSCR75 
Secondary 
(Section 8.3.1) 
HiSCR75 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
logistic regression, as 
for the primary 
analysis.  
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Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Flare 
Secondary 
(Section 8.3.2) 
Flare by 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. A 
composite strategy will 
be used, ie, the 
occurrence of an 
intercurrent event will 
be handled by 
evaluating the 
corresponding 
participants as treatment 
failures (flare). 
The odds ratio versus 
placebo based on a 
logistic regression, as 
for the primary 
analysis. 
DLQI 
Secondary 
(Section 8.3.3.
1)  
Change 
from 
Baseline in 
DLQI total 
score to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
hypothetical strategy, 
whereby all data at and 
after the intercurrent 
event will be treated as 
missing.  
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the 
DLQI total score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will be 
imputed using MI – 
MCMC/Monotone 
Regression under a 
missing at random 
assumption. 
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Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
DLQI 
Secondary - 
Sensitivity 
(Section 8.3.3.
2 )  
Change 
from 
Baseline in 
DLQI total 
score to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
DLQI total score at 
Week 16 who have not 
had an intercurrent event 
on or before Week 16 
are included. 
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the 
DLQI total score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will not be 
imputed. 
HSSDD 
Secondary  
(Section 8.3.4.
1) 
Change 
from 
Baseline in 
worst skin 
pain score, 
as assessed 
by “worst 
skin pain” 
item in 
HSSDD to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
hypothetical strategy, 
whereby all data at and 
after the intercurrent 
event will be treated as 
missing. 
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the worst 
skin pain score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will be 
imputed using MI – 
MCMC/Monotone 
Regression under a 
missing at random 
assumption. 
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Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HSSDD 
Secondary  
(Section 8.3.4.
2) 
Change 
from 
Baseline in 
worst skin 
pain score, 
as assessed 
by “worst 
skin pain” 
item in 
HSSDD to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
HSSDD worst skin pain 
score at Week 16 who 
have not had an 
intercurrent event on or 
before Week 16 are 
included. 
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the worst 
skin pain score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will not be 
imputed. 
HSSDD 
Secondary  
(Section 8.3.5.
1) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
logistic regression, as 
for the primary 
analysis.  
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Table 8‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HSSDD 
Secondary 
Sensitivity 
(Section 8.3.5.
2.1) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
Composite strategy, as 
for the primary analysis 
where the occurrence of 
an intercurrent event 
will be handled by 
evaluating the 
corresponding 
participants as 
nonresponders. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values for 
any other reason will 
also be imputed as 
nonresponders. 
HSSDD 
Secondary 
Sensitivity 
(Section 8.3.5.
2.2) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
HSSDD worst skin pain 
score at Week 16 who 
have not had an 
intercurrent event on or 
before Week 16 are 
included. 
The odds ratio versus 
placebo is based on a 
logistic regression. 
Missing values will 
not be imputed. 
AE=adverse event; ANCOVA=analysis of covariance; DLQI=Dermatology Life Quality Index; 
HiSCR=Hidradenitis Suppurativa Clinical Response; HSSDD=Hidradenitis Suppurativa Symptom Daily Diary; 
IES=intercurrent event(s) strategy; LSMD=Least Squares Mean Difference; MCMC=Markov Chain Monte 
Carlo; MI=multiple imputation; PLS=Population-level summary; Pop=Population; RS=Randomized Set 
a Analysis includes all study participants in the RS with a Baseline HSSDD Worst Skin Pain score of 3 or higher. 
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8.3.1 
HiSCR75 at Week 16 
A categorical response variable, HiSCR75 at Week 16 is defined to be equal to 1 if %ΔAN is less 
than or equal to -75%, and the change from Baseline in the abscess count is zero or negative (ie, 
non-positive) together with a non-positive change from Baseline in the draining tunnel 
(fistula/sinus tract) count, and 0 otherwise. This definition is introduced for identifying 
participants who respond to the treatment (1 = responder, 0 = nonresponder). The definition of 
percentage improvement from Baseline is given in Section 8.2.1. 
For HiSCR75 at Week 16, logistic regression as specified for the primary analysis will be 
implemented to test for superiority. The same analysis approach as outlined for the primary 
efficacy endpoint will be applied. 
8.3.2 
Flare by Week 16 
See Section 8.2.1 for the derivation of AN count. 
Disease flare by Week 16 is defined as at least a 25% increase in AN count with an absolute 
increase of ≥2 AN relative to Baseline is observed by Week 16. A participant’s disease flare 
status (yes/no) will be determined at each visit. 
The number of participants who experience at least 1 disease flare by Week 16 will be analyzed 
using a logistic regression model including a fixed effect for treatment, Hurley stage at Baseline, 
and Baseline antibiotic use. The odds ratio versus placebo, p-value (from Wald test), and CI will 
be calculated. Missing data will be handled as described in Section 4.2.1.2. 
8.3.3 
Change from Baseline in DLQI Total Score at Week 16 
The DLQI is a questionnaire designed for use in adult participants with skin diseases and has 
been used in patients with HS. This is a validated, quality-of-life questionnaire that covers 6 
domains including symptoms and feelings, daily activities, leisure, work and school, personal 
relationships, and treatment, as assessed over the past week.  
The scoring of each answer for the DLQI is as follows: 
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Table 8‒3: 
Dermatology Life Quality Index 
DLQI Scoring 
Response 
Score 
Very much 
3 
A lot 
2 
A little 
1 
Not at all 
0 
Not relevant 
0 
Question unanswered 
0 
Q7: ‘prevented work or studying’ = yes 
3 
The DLQI total score is calculated by adding the score of each question. The maximum score is 
30, and the minimum score is 0. The higher the score, the more quality of life is impaired. 
Meaning of DLQI Total Score 
0-1 = no effect at all on patient’s life 
2-5 = small effect on patient’s life 
6-10 = moderate effect on patient’s life 
11-20 = very large effect on patient’s life 
21-30 = extremely large effect on patient’s life 
This categorization will not be utilized in the analysis. 
Because Q7 has a sub-question (referred to as Q7a here) after the leading yes/no question, some 
clarifying rules for scoring are provided: 
• If Q7 is marked as “yes”, a score of 3 is given regardless of the responses to Q7a. 
• If Q7 is marked as “no”, “not relevant”, or is missing and Q7a is “A lot”, a score of 2 is 
given. 
• If Q7 is marked as “no”, “not relevant”, or is missing and Q7a is “A little”, a score of 1 is 
given. 
• If Q7 is marked as “no”, “not relevant”, or is missing and Q7a is “Not at all”, a score of 0 is 
given. 
• If Q7 is marked as “no” or “not relevant” and Q7a is missing, a score of 0 is given. 
• If Q7 is missing and Q7a is missing, Q7 is considered unanswered (see below for details on 
how this impacts the DLQI total score). 
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If 1 question is left unanswered, this is scored 0 and the scores are summed and expressed as 
usual out of a maximum of 30. If 2 or more questions are left unanswered, the questionnaire is 
not scored. 
Change from Baseline in DLQI total score is defined as Week 16 DLQI total score minus 
Baseline DLQI total score.  
8.3.3.1 
Primary analysis of change from Baseline in DLQI Total score at 
Week 16 
Missing data imputation described in Section 4.2.1.2 will be applied. 
Change from Baseline in DLQI total score will be presented by treatment group. The analysis 
model will be based on an ANCOVA with fixed effects of treatment, Hurley Stage at Baseline, 
Baseline antibiotic use and Baseline value as a covariate. The least square mean (LSM), standard 
error (SE), and 95% CI for the LSM will be presented by treatment group. For the comparison 
between placebo and bimekizumab: the difference between the LSM, the associated 97.5% CI 
for the contrasts, and the corresponding p-value will be presented. If one dose regimen is tested 
at the 0.05 significance level as determined in Section 4.5, then the confidence interval will be 
95% instead of 97.5% for that dose with a corresponding Zα/2 of 1.96. Estimand and intercurrent 
event details are specified in Table 8‒2.  
8.3.3.2 
Sensitivity analysis of change from Baseline in DLQI Total score at 
Week 16 
A sensitivity analysis using the same analysis model as in Section 8.3.3.1 will be used, based on 
observed data. Estimand and intercurrent event details are specified in Table 8‒2. 
8.3.4 
Change from Baseline in Skin Pain score at Week 16, as assessed by 
the “worst skin pain” item in the HSSDD 
The items on the HSSDD assess patients’ perception of the core symptoms of HS experienced in 
the past 24 hours: pain, smell or odor, drainage or oozing from HS lesions, and itch on an 
11-point numeric rating scale (NRS). Two items assess skin pain: worst skin pain and average 
skin pain.  
Weekly averages will be derived for each of the items of the HSSDD for weeks matching the 
post-Baseline dosing weeks up to Week 16. A weekly average is the sum of the scored item over 
the course of the study week divided by the number of days on which the item was completed. 
The weekly averages will be relative to the respective visit date except for Baseline, which will 
be anchored to the first dose of study drug. A weekly average will only be calculated if at least 4 
non-missing values (not necessarily consecutive) are available. Otherwise, the HSSDD weekly 
average for the given question will be set to missing.  
Baseline will be computed as the average from the first 7 consecutive day period in which there 
are at least 4 non-missing entries. That is, first consider the first 7 consecutive days prior to the 
Baseline visit, but not including the Baseline visit day itself. If there are at least 4 non-missing 
values (not necessarily consecutive), then the Baseline average will be calculated. If there are 
less than 4 values, the 7 consecutive day period will move one day earlier. If there are at least 4 
non-missing values (not necessarily consecutive) in that period, then the Baseline average will be 
calculated. This will continue until there are at least 4 non-missing values in a 7 consecutive day 
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period in the 14 days prior to Baseline. If there is no period in which there are at least 4 non-
missing entries, then the Baseline value will be set to missing.  
Change from Baseline in worst skin pain score is defined as the average Week 16 worst skin pain 
score minus the Baseline worst skin pain score. Missing data imputation described in 
Section 4.2.1.2 will be applied to the weekly averages and not to the individual daily PRO data. 
8.3.4.1 
Primary analysis of change from Baseline in skin pain score at Week 
16 
Change from Baseline in worst skin pain score will be presented by treatment group. The 
analysis model will be based on an ANCOVA with fixed effects of treatment, Hurley Stage at 
Baseline, Baseline antibiotic use, analgesic use (Section 6.4.2) and Baseline value as a covariate.  
The LSM, SE, and 95% CI for the LSM will be presented by treatment group. For the 
comparison between placebo and bimekizumab, the difference between the LSM, the associated 
97.5% CI for the contrasts, and the corresponding p-value will be presented. If one dose regimen 
is tested at the 0.05 significance level as determined in Section 4.5, then the confidence interval 
will be 95% instead of 97.5% for that dose with a corresponding Zα/2 of 1.96. 
8.3.4.2 
Sensitivity analysis of change from Baseline in skin pain score at 
Week 16 
A sensitivity analysis using the same analysis model as in Section 8.3.4.1 will be used, based on 
observed data. Estimand and intercurrent event details are specified in Table 8‒2. 
8.3.5 
HSSDD skin pain response at Week 16 
The analysis set for the analyses of the skin pain response will be restricted to those study 
participants in the RS with a Baseline worst skin pain score of 3 or higher. The weekly scores 
and Baseline score are derived as specified in Section 8.3.4. 
8.3.5.1 
Primary analysis of skin pain response at Week 16 
Skin pain response at Week 16, as assessed by the “worst skin pain” item in the HSSDD, is 
defined as an improvement in the weekly worst skin pain score of at least 3 points versus 
Baseline.  
The primary analysis will be based on a logistic regression model including a fixed effect for 
treatment, Hurley stage at Baseline, Baseline antibiotic use, and analgesic use (Section 6.4.2). 
The odds ratio versus placebo, p-value (from Wald test), and 97.5% CI will be calculated. If one 
dose regimen is tested at the 0.05 significance level as determined in Section 4.5, then the 
confidence interval will be 95% instead of 97.5% for that dose. Missing data will be handled as 
specified in Section 4.2.1.2. Estimand and intercurrent event details are specified in Table 8‒2. 
The number and percentage of participants who are pain responders at Week 16 will be 
summarized by treatment group.  
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By-participant listings of pain response status will be provided.  
8.3.5.2 
Sensitivity analyses of Skin Pain Response at Week 16 
8.3.5.2.1 
Nonresponse imputation 
As a sensitivity analysis, any missing data at Week 16 that are not preceded by an intercurrent 
event (Table 8‒2) will be imputed as nonresponse. That is, participants who experience an 
intercurrent event will be imputed as nonresponder at the timepoint of the event and all 
subsequent timepoints (including any recorded data after the event), and all missing data will 
also be imputed as nonresponse. 
The same analysis model as Section 8.3.5.1 will then be used on the imputed data set. 
8.3.5.2.2 
Analysis on observed cases 
An additional supportive analysis will be based on observed data only for study participants with 
a worst skin pain score at Week 16 who have not had an intercurrent even on or before 
Week 16. Study participants with missing data or who have prematurely discontinued study 
treatment will be treated as missing (see Section 4.2.2). 
The same analysis model as in Section 8.3.5.1 will then be used on the imputed data set. 
8.4 
Other efficacy endpoints 
The other efficacy endpoints are listed below and will be evaluated according to the planned 
assessments in the protocol. This excludes the timepoints for the primary and secondary 
endpoints specified above in Section 8.2.1 and Section 8.3.  
Missing data handling for these endpoints is described in Section 4.2.1.3. 
8.4.1 
HiSCR endpoints 
8.4.1.1 
HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100  
Categorical response variables  HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 are 
defined to be equal to 1 if %ΔAN is less than or equal to -25%, -50%, -75%, -90%, and -100%, 
respectively, and the change from Baseline in the abscess count is zero or negative (ie, 
non-positive) together with a non-positive change from Baseline in the draining tunnel 
(fistula/sinus tract) count, and  0 otherwise. This definition is introduced for identifying study 
participants who respond to the treatment (1 = responder, 0 = nonresponder). The definition of 
percentage improvement from Baseline is given in Section 8.2.1. 
HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response will be summarized using 
frequency tables by treatment group and visit.  
A line plot of the HiSCR responder (HiSCR50, HiSCR75, HiSCR90, and HiSCR100) rate over time, 
by treatment group, will be produced. 
In order to investigate the effect of intercurrent event handling and missing data handling on the 
binary response variables, the following iterations of each of the aforementioned plots (HiSCR50, 
HiSCR75, HiSCR90, and HiSCR100, respectively) will be presented, with corresponding summary 
statistics tables: 
• Observed data only (non-imputation for either intercurrent events or missing data) 
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• Non-response imputation to reflect intercurrent events, non-imputation for missing data 
• Full imputation: non-response imputation to reflect intercurrent events, imputation for 
missing data per Section 4.2.1.3   
Bar charts of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 will be produced by visit and Hurley 
Stage at Baseline for the Initial Treatment Period and the combined Initial and Maintenance 
Treatment Period. These bar charts will be repeated for HiSCR by visit and Baseline antibiotic 
use. 
Another bar chart of HiSCR rate at Week 16 will be produced by Hurley Stage at Baseline and 
Baseline antibiotic use. 
In addition to the above bar charts, a stacked bar chart displaying whether the criteria are met 
(yes/no) for each of the component data used in the calculation of HiSCR (%ΔAN, abscess count 
and draining tunnel [fistula/sinus tract] count) will be generated by treatment group and visit. 
This graph will summarize the proportion of participants in each of the 8 different yes/no binary 
responses at each visit (2 x 2 x 2 response combination) at each visit. 
8.4.1.2 
Time to response of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and 
HiSCR100 
See Section 8.4.1.1 for the derivation of HiSCR. 
Initial Treatment Period 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) during the Initial 
Treatment Period will each be calculated as: 
Min (Date of first HiSCRxx response, Date of Week 16 visit) – Date of first dose of study 
medication + 1, here xx represents 25, 50, 75, 90, 100 respectively. All visits including 
unscheduled visits are considered. 
Participants who discontinue study treatment without achieving a given HiSCR response prior to 
Week 16 visit will be censored at the date of last lesion count assessment. Participants who reach 
the Week 16 Visit without achieving the given response will be censored at the date of the 
Week 16 Visit. Participants who experience an intercurrent event prior to achieving a HiSCR 
response will be censored at the date of the intercurrent event. Participants will be censored at 
Baseline if there is no Baseline lesion count assessment or no Post-Baseline lesion count 
assessment. 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response during Initial Treatment 
Period will each be estimated and presented using the Kaplan-Meier product-limit method for 
each treatment group.  
Kaplan-Meier plots of time to HiSCR responses will be presented by treatment group. In these 
Kaplan-Meier plots, the line will start at 0 (since there are no responders at Week 0) and will 
increase over time, representing time to achieving the response. 
The median time to response, including the 2-sided 95% confidence interval, will be calculated 
for each treatment. Comparisons of bimekizumab vs placebo will be analyzed using a log-rank 
test stratified by Hurley Stage at Baseline and Baseline antibiotic use. 
Combined Initial and Maintenance Treatment Period 
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An additional time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) during the 
combined Initial and Maintenance Treatment Period will be calculated as above, where the Week 
48 visit is considered instead of Week 16. 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response during the combined 
Initial and Maintenance Treatment Period will each be estimated and presented using the 
Kaplan-Meier product-limit method for each treatment group.  
Kaplan-Meier plots of time to HiSCR responses will be presented by treatment group. In these 
Kaplan-Meier plots, the line will start at 0 (since there are no responders at Week 0) and will 
increase over time, representing time to achieving the response. 
The median time to response, including the 2-sided 95% confidence interval, will be calculated 
for each treatment. 
8.4.1.3 
HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response at both 
Weeks 16 and 48 
See Section 8.4.1.1 for the derivation of HiSCR response. 
The number and percentage of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders 
at both Weeks 16 and 48 will be summarized based on the RS and MS. 
Missing data for the above summaries will be handled using NRI. That is, participants are 
counted as responders only if they have an observed HiSCR at both Weeks 16 and 48 and have 
no intercurrent events through Week 48. Otherwise, they are treated as not responding.  
8.4.1.4 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100 among Week 16 
Responders 
See Section 8.4.1.1 for the derivation of HiSCR response. 
Summaries of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders at each visit from Week 
16 through Week 48 will be summarized based on a subset of participants in the MS who 
achieve response at Week 16. The summaries will be as follows: 
• HiSCR50 responder rate based on participants who achieved HiSCR50 response at Week 16 
• HiSCR75 responder rate based on participants who achieved HiSCR75 response at Week 16 
• HiSCR90 responder rate based on participants who achieved HiSCR90 response at Week 16 
• HiSCR100 responder rate based on participants who achieved HiSCR100 response at Week 16 
Line plots of the above HiSCR responder rate categories over time (from Week 16 to Week 48), 
by treatment group, will be produced. 
8.4.1.5 
Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 
in Week 16 responders 
See Section 8.4.1.1 for the derivation of HiSCR response. 
Time to loss of response will be based on the MS and include only participants who had the 
corresponding HiSCR response at Week 16 (considering intercurrent event handling from the 
composite estimand described in Section 8.2.2). 
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Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) is defined as: 
Date of loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 - Date of Week 16 
treatment administration + 1.  
Time to loss of response will be estimated and presented using the Kaplan-Meier product-limit 
method for each treatment. Participants who experience an intercurrent event prior to loss of 
response will be considered as having lost response on the date of intercurrent event. Participants 
who reach the Week 48 Visit without loss of response will be censored at the date of the Week 
48 Visit. Participants who discontinue treatment or study, for reasons other than those already 
defined for an intercurrent event, and who have not yet displayed loss of response by the time of 
withdrawal, will be censored at the date of the last lesion count assessment. 
8.4.1.6 
Partial response 
See Section 8.2.1 for the derivation of AN count. 
A partial response is defined as a ≥25% reduction in AN count from Baseline (Week 0) at a 
particular timepoint. 
The number and percentage of participants who are partial responders at Week 16 and become 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders in the Maintenance Treatment Period 
will be summarized by treatment group and visit. These analyses will be based on the subset of 
participants in the MS that are partial responders but not HiSCR50, HiSCR75, HiSCR90, and 
HiSCR100 responders, respectively, at Week 16. These summaries will be based on observed case 
data and will not consider the occurrence of intercurrent events. 
8.4.2 
Lesion count 
8.4.2.1 
Change from Baseline in lesion count 
At each visit, lesion counts will be summarized by treatment group, anatomical region, and 
lesion type. The following lesion types will be summarized: 
• Abscesses 
• Inflammatory nodules 
• ANs 
• Non-inflammatory nodules  
• Draining tunnels (fistulas/sinus tracts) 
• Non-draining tunnels (fistulas/sinus tracts)  
• HS scars 
Total lesion counts (ie, the total across all anatomical regions) will be summarized by visit and 
lesion type, treatment group, overall and by Baseline Hurley Stage. Summaries will also be 
presented for the change and percentage change from Baseline in lesion counts by anatomical 
region and total lesion counts by lesion type.  
A line plot of the percentage change from Baseline in AN count over time by treatment group 
will be produced. Separate plots will also be produced for the percentage change from Baseline 
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in the abscess count, inflammatory nodules count, and draining tunnel count, respectively, over 
time. 
In order to investigate the effect of intercurrent events and missing data handling on lesion count 
data, the following additional iterations of each of the aforementioned plots (percentage change 
in AN count, abscess count, inflammatory nodule count and draining tunnel count, respectively) 
will be presented, with corresponding summary statistics tables: 
• Intercurrent events:  
− Participants who have experienced intercurrent events 
− Participants who have not experienced intercurrent events 
• Missing data handling:  
− Observed lesion counts (i.e., non-imputation) 
− Imputed lesion counts 
Lesion count data will be listed by treatment group and anatomical region and will show 
region-specific Hurley Stage and worst overall Hurley Stage for each participant and visit. The 
total count for each type of lesion, across all anatomical regions at each visit will be listed 
separately. For the total abscess count and total draining tunnel (fistula/sinus tract) count, the 
change from Baseline will be listed; for the AN count, the percentage change from Baseline will 
be listed. 
8.4.2.2 
AN count of 0, 1, or 2 
The number and percentage of participants with an AN count of 0, 1, or 2 will be presented by 
treatment group and visit. The denominator for the percentage calculations will be the number of 
participants in each treatment group in the RS with non-missing data at each visit. 
8.4.2.3 
AN25, AN50, AN75, AN90, AN100 
Categorical response variables AN25, AN50, AN75, AN90, and AN100 are defined to be equal to 1 if 
%ΔAN is less than or equal to -25%, -50%, -75%, -90%, and -100%, respectively, and 0 
otherwise. This definition is introduced for identifying participants who respond to the treatment 
(1 = responder, 0 = nonresponder). The definition of percentage change from Baseline is given in 
Section 8.2.1. 
AN25, AN50, AN75, AN90, and AN100 response will be summarized using frequency tables by 
treatment group for each visit. 
8.4.3 
Flare relative to Baseline 
See Section 8.3.2 for the derivation of flare. 
Disease flare status will be summarized by treatment group and visit using frequencies and 
percentages. The denominator for the percentage calculations will be the number of participants 
with non-missing data in each treatment group. This summary will also include the number of 
participants with any flare in the Initial Period, Maintenance Period, and the combined Initial and 
Maintenance Period. A bar chart of percentage of participants with flare, by visit and treatment, 
will be presented. 
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In addition, for each participant, the number of flares during the Initial Treatment Period will be 
calculated and summarized by treatment group. A corresponding histogram summarizing the 
number of flares during the Initial Treatment Period will be presented. 
8.4.4 
Time to flare by Week 16 
See Section 8.3.2 for the derivation of flare. 
Time to flare (in days) during the Initial Treatment Period will each be calculated as: 
Min (Date of first flare, Date of Week 16 visit) – Date of first dose of study medication + 1. 
All visits in the Initial Treatment Period including unscheduled visits are considered. 
Participants who discontinue study treatment without experiencing a flare prior to Week 16 Visit 
will be censored at the date of last lesion count assessment. Participants who reach the Week 16 
Visit without experiencing a flare will be censored at the date of the Week 16 Visit. Participants 
who experience an intercurrent event prior to experiencing a flare will be treated as experiencing 
a flare at the date of the intercurrent event. Participants will be censored at Baseline if there is no 
Baseline lesion count assessment or no Post-Baseline lesion count assessment. 
Time to flare will be estimated and presented using the Kaplan-Meier product-limit method for 
each treatment group.  
Kaplan-Meier plots of time to flare will be presented by treatment group. In these Kaplan-Meier 
plots, the line will start at 0 and will increase over time, representing time to achieving the 
response. 
The median time to flare, including the 2-sided 95% confidence interval, will be calculated for 
each treatment. Comparisons of bimekizumab vs placebo will be analyzed using a log-rank test 
stratified by Hurley Stage at Baseline and Baseline antibiotic use. 
8.4.5 
Time to flare by Week 48 
See Section 8.3.2 for the derivation of flare relative to Baseline. 
Time to flare (in days) during the combined Initial and Maintenance Treatment Period will be 
calculated as: 
Min (Date of first flare, Date of Week 48 visit) – Date of first dose of study medication + 1. 
All visits in the up to Week 48 including unscheduled visits are considered. 
Flare will be defined relative to the Baseline visit. Participants who discontinue study treatment 
without experiencing a flare prior to Week 48 visit will be censored at the date of last lesion 
count assessment. Participants who reach the Week 48 Visit without experiencing a flare will be 
censored at the date of the Week 48 Visit. Participants who experience an intercurrent event prior 
to experiencing a flare will be treated as experiencing a flare at the date of the intercurrent event. 
Participants will be censored at Baseline if there is no Baseline lesion count assessment or no 
Post-Baseline lesion count assessment. 
Time to flare will each be estimated and presented using the Kaplan-Meier product-limit method 
for each treatment group.  
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Kaplan-Meier plots of time to flare will be presented by treatment group. In these Kaplan-Meier 
plots, the line will start at 0 and will increase over time, representing time to achieving the 
response. 
The median time to flare, including the 2-sided 95% confidence interval, will be calculated for 
each treatment.  
8.4.6 
International Hidradenitis Suppurativa Severity Score System (IHS4) 
The IHS4 is a validated scoring tool to dynamically assess HS severity to be used both in 
real-life and clinical trials settings (Zouboulis et al, 2017). The determination of the IHS4 score 
requires counting the inflammatory nodules, abscesses and draining tunnels (fistulas/sinus 
tracts), making it straightforward to apply in both research and clinical practice and easy to use 
in conjunction with the HiSCR. 
𝐼𝐻𝑆4 = (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑖𝑛𝑓𝑙𝑎𝑚𝑚𝑎𝑡𝑜𝑟𝑦 𝑛𝑜𝑑𝑢𝑙𝑒𝑠× 1) + (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑎𝑏𝑠𝑐𝑒𝑠𝑠𝑒𝑠× 2) 
+ (𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑟𝑎𝑖𝑛𝑖𝑛𝑔 𝑡𝑢𝑛𝑛𝑒𝑙𝑠 (𝑓𝑖𝑠𝑡𝑢𝑙𝑎𝑠/𝑠𝑖𝑛𝑢𝑠 𝑡𝑟𝑎𝑐𝑡𝑠 ) × 4) 
The IHS4 score will be derived based on observed component total lesion count data; in the case 
of missing component data, the IHS4 score will be missing.  
The observed IHS4 score, change and percentage change from Baseline will be summarized by 
treatment group and visit. Missing IHS4 scores will be imputed using the multiple imputation 
procedure specified in Section 4.2.2.1, where IHS4 scores will be derived based on the imputed 
lesion counts.  
The IHS4 scores will be categorized into 3 HS categories (mild HS: ≤3, moderate HS: 4-10, 
severe HS: ≥11). 
The number and percentage of participants in each category (mild, moderate, severe) will be 
presented by treatment group and visit. The denominator for the percentages will be based on the 
number of participants in the given treatment group and visit for which there are no missing data 
(OC).  
Shift tables for the changes from Baseline in this scale will be presented for each post-Baseline 
visit by treatment group. The denominator for the percentages will be based on the number of 
participants in the given treatment group and visit for which there is no missing data for the 
change (OC). 
8.4.7 
HS-Physician’s Global Assessment 6-point scale 
The HS-Physician’s Global Assessment is a validated 6-point scale that is used to measure 
improvement in inflammatory nodules, abscesses, and draining tunnels. The HS-Physician’s 
Global Assessment scale is defined in Table 8‒4. 
Table 8‒4: 
HS-Physician's Global Assessment 6-point scale 
Score 
Rating 
Description 
0 
Clear 
No abscesses, no draining tunnels (fistulas/sinus tracts), no nodules 
1 
Minimal 
No abscesses, no draining tunnels (fistulas/sinus tracts), no inflammatory 
nodules, presence of non-inflammatory nodules 
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Table 8‒4: 
HS-Physician's Global Assessment 6-point scale 
Score 
Rating 
Description 
2 
Mild 
No abscesses or draining tunnels (fistulas/sinus tracts), and less than 5 
inflammatory nodules, or 
Single abscess or draining tunnel (fistula/sinus tract), and no 
inflammatory nodules 
3 
Moderate 
No abscesses or draining tunnels (fistulas/sinus tracts), and at least 5 
inflammatory nodules, or 
Single abscess or draining tunnel (fistula/sinus tract) in the presence of 
inflammatory nodules, or 
Between 2 and 5 abscesses or draining tunnels (fistulas/sinus tracts) with 
or without inflammatory nodules, up to 10 
4 
Severe 
Between 2 and 5 abscesses and draining tunnels (fistulas/sinus tracts), 
with inflammatory nodules that are greater than 10 
5 
Very severe 
More than 5 abscesses or draining tunnels (fistulas/sinus tracts) 
The gradings will be derived on a participant-level basis (ie, across all anatomical regions) based 
on the following rules: 
• Clear:  
− number of abscesses = 0; 
− number of draining tunnels (fistulas/sinus tracts) = 0; 
− number of inflammatory nodules = 0; 
− number of non-inflammatory nodules = 0; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
• Minimal:  
− number of abscesses = 0; 
− number of draining tunnels (fistulas/sinus tracts) = 0; 
− number of inflammatory nodules = 0; 
− number of non-inflammatory nodules ≥ 1; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
• Mild:  
− number of abscesses = 0; 
− number of draining tunnels (fistulas/sinus tracts) = 0; 
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− number of inflammatory nodules ≥ 1 and ≤ 4; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
OR 
− sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) = 1; 
− number of inflammatory nodules = 0; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
• Moderate:  
− number of abscesses = 0; 
− number of draining tunnels (fistulas/sinus tracts) = 0; 
− number of inflammatory nodules ≥ 5; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
OR 
− sum number of abscesses and number of draining tunnels (fistulas/sinus tracts) = 1; 
− number of inflammatory nodules ≥1; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
OR 
− sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) ≥ 2 and 
≤ 5; 
− number of inflammatory nodules ≤ 10; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
• Severe:  
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− sum of number of abscesses and number of draining tunnels (fistulas/sinus tracts) ≥ 2 and 
≤ 5; 
− number of inflammatory nodules > 10; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit; 
• Very Severe:  
− sum of number of and number of draining tunnels (fistulas/sinus tracts) > 5; 
− number of inflammatory nodule – no limit; 
− number of non-inflammatory nodules – no limit; 
− number of non-draining tunnels (fistulas/sinus tracts) – no limit; 
− number of HS scars – no limit 
The number and percentage of participants at each level of the assessment scale (Clear, Minimal, 
Mild, Moderate, Severe and Very severe) will be presented by treatment group and visit. The 
denominator for the percentages will be based on the number of participants in the given 
treatment group and visit for which there are no missing data for the HS-Physician’s Global 
Assessment.  
Shift tables for the changes from Baseline in this scale will be presented for each post-Baseline 
visit by treatment group. The denominator for the percentages will be based on the number of 
participants in the given treatment group and visit for which there is no missing data for the 
change from Baseline in HS-Physician’s Global Assessment. 
The HS-Physician’s Global Assessment will be listed by treatment group and participant at each 
visit. 
8.4.8 
High Sensitivity C-Reactive Protein (hs-CRP) 
Concentrations of hs-CRP, changes from Baseline, and percent change from Baseline will be 
summarized by treatment group and visit, where percent change is calculated as 
Percent change from Baseline = 100 × Post Baseline hs-CRP −Baseline hs-CRP
Baseline hs-CRP
 
Summary statistics will include n, arithmetic mean, SD, median, Q1, Q3, minimum and 
maximum. For the ratio to Baseline, summary statistics will include n, geometric mean, geoCV, 
median, Q1, Q3, minimum and maximum. 
The ratio to Baseline will be calculated as follows:  
Ratio to Baseline = hs-CRP at post-Baseline / hs-CRP at Baseline visit 
The ratio to Baseline will also be summarized by treatment group and visit.  
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For the hs-CRP data, measurements that are below the limit of quantification (BLQ) will be 
imputed with half of the lower limit of quantification (LLOQ) for the purpose of calculating 
summary statistics, changes from Baseline, and ratio to Baseline. 
Concentrations of hs-CRP, changes from Baseline, and ratio to Baseline will be listed. 
8.4.9 
Initiation of systemic antibiotic rescue therapy 
See Section 3.9 for the definition of a systemic antibiotic rescue therapy. 
The number of participants that use rescue antibiotic therapy will be summarized by treatment 
group for each period. 
8.4.10 
Time to initiation of systemic rescue therapy in the Initial Treatment 
Period 
See Section 3.9 for the definition of a systemic antibiotic rescue therapy. 
Time to initiation of systemic rescue therapy (in days) during the Initial Treatment Period will be 
calculated as: 
Min (Date of initiation of rescue therapy, Date of change in the dose/type of current 
antibiotic, Date of Week 16 visit) – Date of first dose of study medication + 1.  
Participants who discontinue the study without initiating systemic rescue therapy prior to Week 
16 visit will be censored at the date of discontinuation. Participants who reach the Week 16 Visit 
without initiating systemic rescue therapy will be censored at the date of the Week 16 Visit. 
Participants will be censored at Baseline if there is no Post-Baseline visit. 
Time to initiation of systemic rescue therapy will be estimated and presented using the 
Kaplan-Meier product-limit method for each treatment group.  
Kaplan-Meier plots of time to initiation of systemic rescue therapy will be presented by 
treatment group. In these Kaplan-Meier plots, the line will start at 0 and will increase over time, 
representing time to requiring rescue therapy. 
The median time to initiation of systemic rescue therapy, including the 2-sided 95% confidence 
interval, will be calculated for each treatment. Comparisons of bimekizumab vs placebo will be 
analyzed using a log-rank test stratified by Hurley Stage at Baseline and Baseline antibiotic use. 
8.4.11 
Time to an intercurrent event in the Initial Treatment Period 
See Section 3.9 for the definition of an intercurrent event. 
Time to an intercurrent event (in days) during the Initial Treatment Period will be calculated as: 
Min (Date of intercurrent event, Date of Week 16 visit) – Date of first dose of study 
medication + 1.  
Participants who discontinue the study without experiencing an intercurrent event prior to Week 
16 visit will be censored at the date of discontinuation. That includes participants who 
discontinue from the study for reasons other than Adverse Event and Lack of Efficacy. 
Participants who reach the Week 16 Visit without experiencing an intercurrent event will be 
censored at the date of the Week 16 Visit. Participants will be censored at Baseline if there is no 
Post-Baseline visit. 
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Time to an intercurrent event will be estimated and presented using the Kaplan-Meier 
product-limit method for each treatment group.  
Kaplan-Meier plots of time to initiation of systemic rescue therapy will be presented by 
treatment group. In these Kaplan-Meier plots, the line will start at 0 and will increase over time, 
representing time to intercurrent event. 
The median time to an intercurrent event, including the 2-sided 95% confidence interval, will be 
calculated for each treatment. Comparisons of bimekizumab vs placebo will be analyzed using a 
log-rank test stratified by Hurley Stage at Baseline and Baseline antibiotic use. 
8.4.12 
Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) 
See Section 8.3.4 for details on HSSDD Baseline and weekly average definitions and 
derivations.  
Percent change from Baseline in HSSDD responses for worst and average skin pain score is 
defined as  
Percent change from Baseline = 100 × Post Baseline HSSDD score −Baseline HSSDD score
Baseline HSSDD score
 
Change from Baseline in each HSSDD item (worst skin pain, average skin pain, smell or odor, 
itch at its worst, and amount of drainage or oozing) score will be summarized using descriptive 
statistics by treatment group and visit, based on weekly averages. The table will display 
descriptive statistics for the Baseline, followed by descriptive statistics for the change from 
Baseline for all visits. Percentage change will be summarized for the worst and average skin pain 
items.  
Additionally, change from Baseline in each HSSDD item will be evaluated by treatment group at 
Week 16 via continuous empirical cumulative distribution function (eCDF) plots showing the 
absolute change from Baseline on the horizontal axis and the cumulative percent of participants 
experiencing that change on the vertical axis. 
Change from Baseline in Worst Skin Pain score and Worst Itch score will additionally be 
summarized by visit and by analgesic and antihistamine use status (Section 6.4.2), respectively. 
HSSDD response based on clinically meaningful change for the worst skin pain item is defined 
as at least a 3-point reduction from Baseline in HSSDD among study participants with a score of 
≥3 at Baseline, based on weekly averages. 
The number and percentage of responders based on clinically meaningful change for the worst 
skin pain item will be summarized by treatment group and visit. 
The number and percentage of participants who were responders based on clinically meaningful 
change at any timepoint in the Initial Treatment Period will be summarized by treatment group 
for the worst skin pain item. 
HSSDD response for the worst skin pain and average skin pain items is defined as at least a 30% 
reduction and at least a 1-point reduction from Baseline among study participants with a score of 
≥3 at Baseline. The number and percentage of responders for each item will be summarized by 
treatment group and visit. 
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The number and percentage of participants who were responders (based on the 30% 
improvement and 1 point improvement definition) at any timepoint in the Initial Treatment 
Period will be summarized by treatment group for the worst skin pain and average skin pain 
items. 
The number and percentage of participants that complete the HSSDD will be calculated for each 
visit by treatment group. A participant will be counted as completing the HSSDD at a visit if the 
minimum number of daily entries is present to calculate the weekly average (see Section 8.3.4). 
The percentage will be based on the number of participants in the RS. A participant will be 
considered a completer at a visit if the weekly average can be calculated for that visit. 
8.4.13 
Hidradenitis Suppurativa Symptom Questionnaire (HSSQ) 
The 4 items on the HS Symptom Questionnaire (HSSQ) assesses participants’ perception of the 
core symptoms of HS experienced in the past 7 days - skin pain, smell or odor, drainage or 
oozing from HS lesions, and itch on an 11-point NRS. 
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 participant. 
Summary statistics of the actual values and change and percentage change from Baseline values 
will be used to summarize each HSSQ item for each visit by treatment group. The table will 
display descriptive statistics for the Baseline, followed by descriptive statistics for the change 
from Baseline for all visits. 
Additionally, change from Baseline in each HSSQ item will be evaluated by treatment group at 
Week 16 and at Week 48 via continuous eCDF plots showing the absolute change from Baseline 
on the horizontal axis and the cumulative percent of participants experiencing that change on the 
vertical axis. 
Missing data for the continuous change from Baseline will be handled by using MI via the 
MCMC and monotone regression method specified in Section 4.2.1.3. 
HSSQ response for skin pain item is defined as at least a 30% reduction and at least a 1-point 
reduction from Baseline in HS Skin Pain score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline. 
The number and percentage of responders for skin pain item will be summarized by treatment 
group and visit based on the MS. 
The number and percentage of participants who were responders at any timepoint in the 
Maintenance Treatment Period will be summarized by treatment group for the skin pain score 
based on the MS. 
Change from Baseline in skin pain score and itch score will additionally be summarized by visit 
and by analgesic and antihistamine use status (Section 6.4.2), respectively. 
The number and percentage of participants that complete the HSSQ will be calculated for each 
visit by treatment group. The percentage will be based on the number of participants in the MS.  
The summary will be repeated where the percentage is based on the subset of participants who 
complete each particular visit. A participant will be considered a completer at a visit if each of 
the items are completed at that visit. 
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8.4.14 
DLQI 
See Section 8.3.3 for the derivation of DLQI total score. 
A DLQI total score of 0 or 1 indicates no impact of the skin disease on health-related quality of 
life and will be summarized. 
A participant is considered to have achieved the minimally clinical important difference (MCID) 
if their individual improvement (ie, decrease) from Baseline in total score is >=4. A 4-point 
improvement in the DLQI total score (DLQI response) has been reported to be meaningful for 
the participant (within-participant MCID). The summary of MCID will be restricted to 
participants with a DLQI total score of at least 4 at Baseline to ensure that it is possible for the 
participant to achieve the MCID. 
The DLQI related efficacy variables are defined as follows: 
• Change from Baseline in DLQI total score is defined as Post-Baseline DLQI total score 
minus Baseline DLQI total score. 
• Percent of study participants achieving a DLQI total score of 0 or 1 is defined as the number 
of study participants with DLQI total score of 0 or 1 divided by the number of study 
participants in RS. 
• Percent of study participants achieving a MCID in DLQI total score is defined as the number 
of study participants with improvement from Baseline in total score of 4 or more divided by 
the number of study participants in RS that have a Baseline DLQI total score of at least 4. 
Missing data for the DLQI total score will be handled by using MI via the MCMC and monotone 
regression method specified in Section 4.2.1.3. 
Change from Baseline in DLQI total score will be summarized using descriptive statistics by 
treatment group and visit. The table will display descriptive statistics for the Baseline, followed 
by descriptive statistics for the change from Baseline for all visits. 
Frequency tables will be produced to show the number and percentage of DLQI responders for 
MCID for each visit by treatment groups.  
The number and percentage of participants achieving a DLQI total score of 0 or 1 at each visit 
will be summarized descriptively using counts and percentages by treatment group and visit.  
The number and percentage of participants that complete the DLQI total score will be calculated 
for each visit by treatment group. The percentage will be based on the number of participants in 
the RS. The summary will be repeated where the percentage is based on the subset of 
participants who complete each particular visit. A participant will be considered a completer at a 
visit if the total score is calculated at that visit. 
A by-participant listing of the DLQI questionnaire, DLQI total score, change from Baseline and 
DLQI response for MCID and 0 or 1 data will be provided by treatment group. 
8.4.15 
Hidradenitis Suppurativa Quality of Life (HiSQOL) 
The HiSQOL includes 17 items assessed using a 7-day recall period, grouped in 3 subscales: 
symptoms, psychosocial, activities and adaptation. 
The assessment of each item of the HiSQOL is as follows: 
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Table 8‒5: 
Hidradenitis Suppurative Quality of Life 
HiSQOL Scoring 
Response 
Score 
Unable to do, due to my HS 
4 
Extremely 
4 
Very Much 
3 
Moderately 
2 
Slightly 
1 
Not at all 
0 
I normally do not do this, HS did not influence 
0 
I am not sexually active 
0 
I do not work or study 
0 
Unanswered 
0 
The HiSQOL total score is calculated by adding the score of each question. The maximum score 
is 68, and the minimum score is 0.  
Subscale scores will be summarized for each of the 3 subscales. The maximum scores for the 
subscales are 16 (symptoms), 20 (psychosocial), and 32 (activities and adaptations), and the 
minimum score is 0 for all subscales. 
For all scores, the higher the score, the more quality of life is impaired. 
Summary statistics of the actual values and change from Baseline values will be used to 
summarize HiSQOL domain and total scores for each visit by treatment group. The table will 
display descriptive statistics for the Baseline, followed by descriptive statistics for the change 
from Baseline for all visits. 
Additionally, change from Baseline in each HiSQOL subscale will be evaluated by treatment 
group at Week 16 and at Week 48 via continuous eCDF plots showing the absolute change from 
Baseline on the horizontal axis and the cumulative percent of participants experiencing that 
change on the vertical axis. 
Missing data for the continuous change from Baseline will be handled by using MI via the 
MCMC and monotone regression method specified in Section 4.2.1.3. The imputed HiSQOL 
total score will be derived based on the imputed subscales. 
The number and percentage of participants that complete the HiSQOL will be calculated for each 
visit by treatment group. The percentage will be based on the number of participants in the RS 
(or MS, as appropriate). The summary will be repeated where the percentage is based on the 
subset of participants who complete each particular visit. A participant will be considered a 
completer at a visit if the total score is calculated at that visit. 
A by-participant listing of the HiSQOL questionnaire, HiSQOL responses, domain and total 
scores and change from Baseline will be provided. 
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8.4.16 
Patient Global Impression of HS Severity (PGI-S-HS) 
The PGI-S-HS is a single item to assess study participants perceptions of the overall severity of 
HS over the past 7 days (none, mild, moderate, severe, very severe).  
The number and percentage of participants with each response will be summarized for each visit 
by treatment group based on OC data. 
The number and percentage of participants that complete the PGI-S-HS will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS. The summary will be repeated where the percentage is based on the subset of participants 
who complete each particular visit. A participant will be considered a completer at a visit if the 
response is nonmissing at that visit. 
8.4.17 
Patient Global Impression of Change in HS Severity (PGI-C-HS) 
The PGI-C-HS is a single item to assess study participants perception of the change in HS since 
they started taking the study medication (much better, a little better, no change, a little worse, 
much worse). 
The number and percentage of participants with each response will be summarized for each visit 
by treatment group based on OC data. 
The number and percentage of participants that complete the PGI-C-HS will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS (or MS, as appropriate). The summary will be repeated where the percentage is based on the 
subset of participants who complete each particular visit. A participant will be considered a 
completer at a visit if the response is nonmissing at that visit. 
8.4.18 
Patient Global Impression of Severity of Skin Pain (PGI-S-SP) 
The PGI-S-SP is a single item to assess study participants’ perceptions of the severity of their 
skin pain from their HS lesions, over the past 7 days (none, mild, moderate, severe, very severe). 
The number and percentage of participants with each response will be summarized for each visit 
by treatment group based on OC data. 
The number and percentage of participants that complete the PGI-S-SP will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS (or MS, as appropriate). The summary will be repeated where the percentage is based on the 
subset of participants who complete each particular visit. A participant will be considered a 
completer at a visit if the response is nonmissing at that visit. 
8.4.19 
Patient Global Impression of Change in Severity of Skin Pain (PGI-C-
SP) 
The PGI-C-SP is a single item to assess study participants’ perceptions of change in their skin 
pain from their HS lesions, since they started taking the study medication (much better, a little 
better, no change, a little worse, much worse). 
The number and percentage of participants with each response will be summarized for each visit 
by treatment group based on OC data. 
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The number and percentage of participants that complete the PGI-C-SP will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS. The summary will be repeated where the percentage is based on the subset of participants 
who complete each particular visit. A participant will be considered a completer at a visit if the 
response is nonmissing at that visit. 
8.4.20 
Euro-Quality of Life 5-Dimensions, 3 levels (EQ-5D-3L) 
The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and 
psychological status with 3 possible answers for each item (1=no problem, 2=moderate problem, 
3=severe problem). In addition, there is a VAS to indicate the general health status with 100 
indicating the best health status. 
Change from Baseline in EQ-5D-3L VAS scores is defined as Post-Baseline EQ-5D-3L VAS 
score minus Baseline EQ-5D-3L VAS score. 
Responses to EQ-5D-3L will be summarized based on OC only as primary analysis. No 
imputation is applied to responses to EQ-5D-3L but is applied to EQ-5D-3L VAS scores. 
Changes from Baseline in EQ-5D-3L VAS will be summarized using descriptive statistics by 
treatment group and visit. The table will display descriptive statistics for the Baseline, followed 
by descriptive statistics for the change from Baseline for all visits. 
The number and percentage of participants with each response in the EQ-5D-3L will be 
summarized for each visit by treatment group based on OC data. 
The number and percentage of participants that complete the EQ-5D-3L will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS. The summary will be repeated where the percentage is based on the subset of participants 
who complete each particular visit. A participant will be considered a completer at a visit if each 
of the domains and VAS are completed at that visit. 
8.4.21 
Work Productivity and Activity Impairment Questionnaire–Specific 
Health Problem (WPAI-SHP) v2.0 adapted to HS scores 
The WPAI-SHP V2.0 is a patient-reported questionnaire that assesses study participant’s 
employment status, work absenteeism, work impairment while working (presenteeism), overall 
work, and daily activity impairment attributable to a specific health problem. It has been used in 
several clinical studies of biologic therapy in participants with plaque PSO. 
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. 
The scoring rules for the WPAI-SHP are as follows: 
Questions: 
• 1 = currently employed 
• 2 = hours missed due to specified problem 
• 3 = hours missed other reasons 
• 4 = hours actually worked 
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• 5 = degree problem affected productivity while working 
• 6 = degree problem affected regular activities 
Scores:  
• Percent work time missed due to problem: [Q2 hours/(Q2 hours +Q4 hours)]*100 
• Percent impairment while working due to problem: [Q5 score/10]*100 
• Percent overall work impairment due to problem: [Q2 hours/(Q2 hours +Q4 hours)+[(1-(Q2 
hours/(Q2 hours +Q4 hours))x(Q5 score/10)] ]*100 
• Percent activity impairment due to problem: [Q6 score/10]*100 
A negative number will indicate a reduction in the score/improvement for participants. 
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 participant. 
Summary statistics of the actual values and change from Baseline values will be used to 
summarize WPAI-SHP for each visit by treatment group. The table will display descriptive 
statistics for the Baseline, followed by descriptive statistics for the change from Baseline for all 
visits. 
Missing data for the continuous change from Baseline will be handled by using MI via the 
MCMC and monotone regression method specified in Section 4.2.1.3. 
The number and percentage of participants that complete the WPAI-SHP will be calculated for 
each visit by treatment group. The percentage will be based on the number of participants in the 
RS. The summary will be repeated where the percentage is based on the subset of participants 
who complete each particular visit. A participant will be considered a completer at a visit if the 
percentages in each dimension are calculated at that visit. 
A by-participant listing of the WPAI-SHP questionnaire, WPAI-SHP domains and change from 
Baseline will be provided. 
8.4.22 
Treatment Satisfaction Questionnaire – Medication-9 
The TSQM-9 is an abbreviated 9-item version of the TSQM, excluding the side effects of 
medication domain. The domains included in the TSQM-9 include effectiveness (3 items), 
convenience (3 items) and global satisfaction (3 items). The TSQM-9 domain scores range from 
0 to 100 with higher scores representing higher satisfaction. 
The scores for each measure are as follows: 
• Global Satisfaction:  
− If no items are missing: ([Sum(Item 7 to Item 9) – 3]/14)*100 
− If either Item 7 or 8 is missing: ([Sum(the two completed items)) – 2]/10)*100 
− If Item 9 is missing: ([Sum(Item 7 and Item 8))-2]/8)*100 
• Effectiveness 
− If no items are missing: ([Item 1 + Item 2 + Item 3) – 3]/18)*100 
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− If one item is missing: ([(Sum(the two completed items) – 2]/12)*100 
• Convenience 
− If no items are missing: ([Sum(Item 4 to Item 6) – 3]/18)*100 
− If one item is missing: ([Sum(the two completed items) – 2]/12*100 
Frequency tables will be produced to summarize answers provided to each of the 9 items of the 
TSQM-9 at Weeks 16 and 48 by treatment group. Responses to TSQM-9 will be summarized 
based on OC. No imputation will be applied. 
The number and percentage of participants that complete the TSQM-9 will be calculated for each 
visit by treatment group. The percentage will be based on the number of participants in the RS.  
The summary will be repeated where the percentage is based on the subset of participants who 
complete each particular visit. A participant will be considered a completer at a visit if each of 
the domains are completed at that visit. 
A by-participant listing of TSQM-9 will be provided. 
8.4.23 
Lesion intervention 
Investigators will have the option to perform interventions in the event an acutely painful lesion 
occurs that requires immediate intervention. 
The following rules will be used to assign a lesion intervention to a study period: 
• Initial Treatment Period: a lesion intervention will be assigned to the Initial Treatment 
Period if it has been performed between the first administration of IMP on Day 1 up to and 
including Week 16.  
• Maintenance Treatment Period: a lesion intervention will be assigned to the Maintenance 
Treatment Period if it has been performed between Week 16 through the Week 48 visit.  
Methods for dealing with partial dates are specified in Section 4.2.4. 
A listing of participants who receive any lesion intervention will be provided. 
The number and percentage of participants who receive at least 1 lesion intervention will be 
summarized by treatment group for the Initial Treatment Period, Maintenance Treatment Period, 
and the combined Initial and Maintenance Treatment Period. 
The number and percentage of participants with 2, 3, and 4 or more lesion interventions will also 
be summarized by treatment group for the Initial Treatment Period, Maintenance Treatment 
Period, and the combined Initial and Maintenance Treatment Period. 
The number and percentage of participants with 2 or more lesion interventions performed on the 
same lesion will be summarized by treatment group for the Initial Treatment Period, 
Maintenance Treatment Period, and the combined Initial and Maintenance Treatment Period.  
8.5 
Additional statistical analyses of other efficacy endpoints 
For selected other efficacy variables, it is of interest to perform statistical tests and to calculate 
inferential statistics. As these tests are not part of the multiplicity-controlled procedure, the 
associated p-values are considered nominal and are not controlled for multiplicity.  
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For binary variables, the analysis will follow what was specified for the primary analysis of the 
primary endpoint and the corresponding p-value reported. Missing values will be imputed as for 
the primary analysis. For continuous variables, the MI – MCMC / Monotone Regression 
approach used for the secondary continuous endpoint will be applied for the imputation model. 
The analysis model will be as for the corresponding secondary continuous endpoint analysis, 
unless otherwise indicated.  
Below is a list of variables for which these nominal p-values will be calculated. The results of 
these inferential tests will be presented in a single table summarizing the testing performed 
outside of the multiplicity-controlled testing procedure. 
All tests will be for both 
 vs Placebo and 
 vs Placebo (tested separately) 
and will be performed for the Week 12 and Week 16 visits only. If the Week 16 visit test is 
already part of the controlled testing procedure in the primary or secondary analyses, only Week 
12 is indicated here. 
• HiSCR50 at Week 12 
• HiSCR75 at Week 12 
• HiSCR90 
• HiSCR100 
• Flare by Week 12 
• Time to flare by Week 12 (based on time-to-event analysis per Section 8.4.4 and adjusted 
appropriately) 
• IHS4 change from Baseline 
• IHS4 percentage change from Baseline 
• HS Physician’s Global Assessment: rate of participants who are Clear or Mild 
• DLQI total score change from Baseline at Week 12 
• Worst Skin Pain per HSSDD change from Baseline at Week 12 
• Skin Pain response per HSSDD at Week 12 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
Pharmacokinetic variables will be analyzed for all participants in the PK-PPS. Bimekizumab 
plasma concentrations will be summarized for each treatment at each scheduled visit. 
PK summaries will be based on observed values. No imputation will be used. However, if 
plasma concentration measurements are below the level of quantification (BLQ), then for 
calculation of the derived statistics the result will be set to ½ of the lower level of quantification 
(LLOQ). Descriptive statistics including geometric mean, geometric coefficient of variation, and 
geometric mean 95% CI if applicable will be calculated if at least 2/3 of the values of interest are 
above the LLOQ. If this is not the case, only median, minimum, and maximum will be presented.  
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Geometric mean plasma concentration will be plotted by treatment group, and by cumulative 
antibody status for participants randomized to bimekizumab on linear and log linear scale. In 
addition, HiSCR50 response (0=not achieved, 1=achieved) assessed at each PK visit (excluding 
Week 1) will be plotted against the visit's bimekizumab plasma concentration, separated by 
treatment group. Spaghetti plots of bimekizumab plasma concentrations by week from 
bimekizumab first dosing separated by treatment group and antibody status will be presented for 
participants with and without HiSCR50 response at Week 16. 
If the dosing for a visit is +/- 7 days out of window, then the plasma concentration from that visit 
and all subsequent visits will be excluded from the PK summary. In addition, if the PK sampling 
date is >1 day after the dosing date, then the plasma concentration from that visit will be 
excluded from the PK summary. 
All PK concentrations collected will be listed irrespective of the dosing or sampling occurring 
out of window.  
9.2 
Pharmacodynamics 
Not applicable. 
9.3 
Immunogenicity 
9.3.1 
Autoantibodies 
Not applicable. 
9.3.2 
Anti-bimekizumab antibodies 
Anti-bimekizumab antibodies (ADAb) will be measured using a 3-tiered assay approach: 
screening assay, confirmatory assay, and titration assay. Samples confirmed as positive within 
the confirmatory assay will be further evaluated for the presence of neutralizing anti-
bimekizumab antibodies specific to IL-17AA, IL-17FF or both. Samples will be taken at 
Baseline, then at study Weeks 4, 8, 12, 16, 20, 24, 36 and 48, and at PEOT and SFU timepoints.  
ADAb samples are not analyzed when study participants are on a treatment other than 
bimekizumab. For study participants who switch from placebo to bimekizumab, samples are 
analyzed starting at the visit when the switch to bimekizumab occurs (Week 16). The sample at 
Week 16 will act as the Baseline for that treatment group.  
The screening cut point will be used to determine the status of anti-bimekizumab antibodies in 
the test sample as Positive Screen (PS) or Negative Screen (NS). For samples presenting anti-
bimekizumab antibody levels that are PS, a further confirmatory assay will be performed, and the 
result of which will be reported as either Positive Immunodepletion (PI) or Negative 
Immunodepletion (NI).  
ADAb status for each sample will be derived as follows: 
• Sample values that are either NS, or PS and NI and where the bimekizumab concentration is 
less than the validated ADAb assay drug tolerance limit will be defined as anti-bimekizumab 
antibody negative. 
• Sample values that are either NS, or PS and NI and where the bimekizumab concentration 
exceeds the validated ADAb assay drug tolerance limit will be defined as inconclusive.  
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• Sample values that are PS and PI will be defined as ADAb positive (regardless of availability 
of a titer value) 
• Missing or non-evaluable samples will be defined as missing 
Positive immunodepletion samples will be titrated, and the ADAb titer (reciprocal dilution factor 
including minimum required dilution) will be reported. Subsequently, PI samples will also be 
subject to a neutralizing assay to evaluate the potential of ADAb to neutralize the target binding 
of bimekizumab (IL-17AA or IL-17FF or both) in vitro. 
Cumulative ADAb status will be derived as follows: 
The ADAb status (positive, negative or missing) will be considered in a cumulative manner at 
each time point.  
A study participant will be counted positive from the first visit at which the study participant 
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 study participant has only negative ADAb samples or only one missing/inconclusive sample 
with all other ADAb samples being negative, the study participant will be classified as negative. 
An exception remains for the Baseline Visit where only one sample could be available. If the 
sample is missing/inconclusive, then the sample will be classified as being negative for the 
cumulative ADAb status. 
Otherwise, the study participant will be classified in the missing ADAb category. 
Overall ADAb status will be derived as follows: 
A study participant will be classified as: 
• Positive if the study participant has at least one positive sample up to the time point of 
interest (regardless of having missing/inconclusive data). 
• Negative if the study participant has all the samples negative or only one 
missing/inconclusive sample with negative ADAb samples up to the timepoint of interest. 
• Missing if the study participant has more than one missing ADAb result (or have more than 
one inconclusive sample) and all other available ADAb samples are negative up to the time 
point of interest.  
ADAb categories will be derived as follows: 
• Pre ADAb negative – treatment-emergent ADAb negative (Category 1): Includes study 
participants who are anti-bimekizumab antibody negative at Baseline and anti-bimekizumab 
antibody negative at all sampling points during the period of interest (one post-Baseline 
missing/inconclusive sample is allowed for subjects with pre- anti-bimekizumab antibody 
negative sample). This group also includes study participants who have a missing or 
inconclusive sample (either missing or inconclusive or insufficient volume) at Baseline (ie, 
pre-treatment) with all post-Baseline samples as ADAb negative. 
• Pre ADAb negative – treatment-emergent ADAb positive (Category 2): Includes study 
participants who are ADAb negative at Baseline and ADAb positive at any sampling points 
post-Baseline during the period of interest. This group also includes study participants who 
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have a missing sample (either missing or insufficient volume) at Baseline (ie, pre-treatment) 
with 1 or more post-Baseline samples as ADAb positive. 
• Pre ADAb positive – treatment-emergent reduced ADAb (Category 3): Includes study 
participants who are ADAb positive at Baseline, and ADAb negative at all sampling points 
post-Baseline during the period of interest. 
• Pre ADAb positive – treatment-emergent unaffected ADAb positive (Category 4): 
Includes study participants who are ADAb positive at Baseline and are ADAb positive at any 
sampling point post-Baseline during the period of interest with titer values of the same 
magnitude as Baseline (ie, less than a predefined fold difference from the Baseline titer). 
− For this analysis, this is set at an increase of less than the validated Minimum Significant 
Ratio (MSR) of 2.07-fold from Baseline.  
• Pre ADAb positive – treatment-emergent ADAb boosted positive (Category 5): Includes 
study participants who ADAb positive at Baseline and are ADAb positive at any sampling 
point post-Baseline during the period of interest with increased titer values compared to 
Baseline (equal to or greater than a predefined fold difference increase from Baseline titer 
which will be defined within the validation of the assay). 
− For this analysis, this is set at an increase equal to or greater than the validated MSR of 
2.07-fold from Baseline.  
− Note: for any study participant who is ADAb positive at Baseline and ADAb positive at a 
post-Baseline time point during the period of interest, but for whom titers are not 
available to determine treatment unaffected or treatment boosted status, the study 
participant will be considered as treatment boosted, assuming no other samples are 
available. 
• ADAb Inconclusive (Category 6): Includes study participants who have an ADAb positive 
Baseline (pre-treatment) sample and some post-Baseline samples during the period of interest 
are missing or inconclusive, while other post-Baseline samples are ADAb negative. 
• Total treatment-emergent ADAb positivity (Category 7 [Categories 2 and 5 combined]): 
Includes study participants who are pre ADAb negative – treatment-emergent ADAb positive 
(Category 2) and pre ADAb positive – treatment boosted ADAb positive (Category 5).  
• Total prevalence of pre- ADAb positivity (Category 8 [Categories 3, 4, 5 and 6 
combined]): Study participants that are tested ADAb positive at Baseline. 
• Missing: Includes study participants who are ADAb negative, missing, or inconclusive at 
Baseline with some post-Baseline samples as missing or inconclusive, and other samples as 
ADAb negative. 
For purposes of efficacy subgroup analyses based on anti-bimekizumab antibody status, the 
following categories can also be used: 
• ADAb positive – This is defined as study participants who are anti-bimekizumab antibody 
positive on at least 2 time points while on treatment (ie, excluding Baseline, excluding SFU). 
• ADAb negative – Study participants for who either:  
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− All samples (including Baseline) are ADAb negative and there are no missing or 
inconclusive samples 
− Only 1 sample is ADAb positive and all other samples (including Baseline) are ADAb 
negative or missing or inconclusive 
− Only 1 sample is missing or inconclusive and the remaining ADAb samples are negative.  
• ADAb missing - Defined as study participants who do not fulfil the criteria for one of the 2 
groups listed above. 
The rationale for requiring at least 2 time points in which ADAb levels are above the specified 
cut point is to exclude those study participants who have only one occurrence of ADAb levels 
during the course of treatment. Including such study participants would increase the number of 
ADAb positive study participants with potentially no impact on efficacy. 
In the case that a sample is collected 1 or more days following the scheduled visit date in which 
the drug was administered, the ADAb results for that sample will be associated with the 
scheduled visit and summarized accordingly. Such samples will also be considered when ADAb 
results are summarized over a given study period. 
Analysis 
Immunogenicity will be assessed through summary tables and figures, and listing of individual 
results by participants. All analyses will be run on the AMS, unless specified otherwise. 
• Summary of ADAb status overall and by each visit separated by treatment group 
• Summary of the time-point of the first occurrence of ADAb positivity during the treatment 
period by treatment group. A plot of the titer by time to first ADAb positivity will be 
prepared. 
• All individual participant-level ADAb results will be listed. 
• The number and percentage of participants in each of the 8 ADAb categories during the 
treatment period by treatment group. 
• The prevalence of immunogenicity, separated by treatment group, and defined subcategory, 
will be reported by visit, defined as (cumulative) proportion of participants having confirmed 
positive ADAb samples at any visit up to and including that visit. Missing samples will not 
be included in the denominator. 
• The time to achieving treatment-emergent ADAb positivity, separated by treatment group 
and defined subcategory, will be analyzed based on Kaplan-Meier methods. This will be 
shown only for Categories 2 and 8 above. Participants will be considered to have an event at 
the time point at which treatment emergent ADAb positive is first achieved (taking the MSR 
into consideration for sub-category 5). Participants classified as treatment-emergent ADAb 
negative will be censored at the time of the last available ADAb result. 
• A summary of HiSCR50 responders at Week 16, separated by treatment group, as a function 
of ADAb titer will be presented graphically. 
• Individual plots of plasma bimekizumab concentrations/ ADAb titer both plotted on the Y-
axes by visit (x-axis) for the full treatment period (excluding SFU for interim analyses and 
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including SFU for final analyses) will be presented for participants with and without 
HiSCR50 response at Week 16. 
• Spaghetti plots of ADAb titer (y-axis) by visit (x-axis), separated by treatment group for all 
ADAb positive participants, including Baseline positive participants. 
• Box plots of ADAb titer (logscale) by time to first ADAb positivity by treatment group. 
The groups for defining ADAb status for safety subgroup analyses are as follows:  
• AEs starting before first ADAb positive result 
• AEs starting on or after first ADAb positive result 
• AEs for participants who were always ADAb negative  
This is further explained in Section 10.2.2  
10 
SAFETY ANALYSES 
All analysis of safety variables will be performed using the SS, MS, and AMS. 
The AMS will be used for summaries of safety that include data from the Initial Treatment 
Period and Maintenance Treatment Period. 
Summaries of safety will be presented for the Initial Treatment Period, Maintenance Treatment 
Period, and combined Initial and Maintenance Treatment Period unless specified otherwise. 
10.1 
Extent of exposure 
Summaries for exposure will be provided. This consists of a descriptive summary of study 
medication duration in days. In addition, total study medication duration and time at risk will be 
summarized in years by treatment group and treatment period (ie, the Initial Treatment Period, 
the Maintenance Treatment Period, and the Initial and Maintenance Treatment Period). Summary 
of exposure in Maintenance Treatment Period will be on MS. The cumulative study medication 
duration will be summarized for study participants exposed for given durations of time. For the 
cumulative duration through Week 48 the following categories for duration will be used: 
• >0 weeks 
•  ≥4 weeks 
•  ≥8 weeks 
• ≥12 weeks 
• ≥16 weeks 
• ≥20 weeks 
• ≥24 weeks 
• ≥28 weeks 
• ≥32 weeks 
• ≥40 weeks 
• ≥48 weeks 
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Definitions for study medication duration and time at risk in days are provided below for each 
period. Time at risk will be summarized in years. Time at risk in years is calculated by dividing 
the time at risk in days by 365.25.  
Throughout this section, date of last clinical contact for each participant is defined as the 
maximum of (last visit date including SFU visit, last imputed AE start date, date of study 
termination or completion, last date of study drug administration). 
10.1.1 
Exposure during the Initial Treatment Period 
Definitions for study medication duration (days) and time at risk (days) during the Initial 
Treatment Period are provided as follows: 
10.1.1.1 
Study medication duration (days) 
Definitions for study medication duration (days) are provided as follows: 
• Date of last dose in the Initial Treatment Period – Date of first dose in the Initial Period + 
 
 
Note: The use of 
 assumes a
 dosing interval (bimekizumab 
 and 
placebo). For participants randomized to bimekizumab 
, this will be adjusted based 
on the dosing interval (eg, use Date of last bimekizumab dose in the Initial Treatment Period – 
Date of first dose in the Initial Period + 
 
Note: If date of last dose in the Initial Treatment Period + 
 (or + 
 in the case of 
 dosing) extends to a date beyond the date of first dose in the Maintenance Treatment 
Period, then this calculation reverts to:  
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Treatment Period + 1.  
• For participants who die during the Initial Period, if date of last dose in the Initial Period + 
 
(or date of last bimekizumab dose in the Initial Treatment Period + 
 in the case 
of 
dosing) extends to a date beyond the date of death, then this calculation reverts to:  
− Date of death – Date of first dose in the Initial Period + 1. 
10.1.1.2 
Time at risk (days) 
Definitions for time at risk (days) are provided as follows: 
• For participants who complete the Week 16 visit and continue to the Maintenance Treatment 
Period:  
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Period + 1. 
• For participants who discontinue on or prior to the final visit of the Initial Period, use the 
minimum of the following:  
− Date of last dose in the Initial Treatment Period – Date of first dose in the Initial 
Treatment Period + 141 
− The total number of days in the Initial Treatment Period (112 days). For AEs that 
emerged after 112 days but still within the 140 days window, those AEs would be 
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classified as TEAE, but will be excluded from the output based on the Initial Treatment 
Period. However, these AEs will be included in the AE summaries for Maintenance 
Treatment Period. 
− Date of last clinical contact – Date of first dose in the Initial Treatment Period + 1.  
• For participants who die prior to the final visit of the Initial Treatment Period: Date of death 
– date of first dose in the Initial Period +1. 
10.1.2 
Exposure during the Maintenance Treatment Period 
Definitions for study medication duration (days) and time at risk (days) during the Maintenance 
Treatment Period are provided as follows: 
10.1.2.1 
Study medication duration (days) 
Definitions for study medication duration (days) are provided as follows: 
• Date of last dose in the Maintenance Treatment Period – date of first dose in the Maintenance 
Treatment Period + 
  
The use of 
 assumes a
 dosing interval. For participants randomized to bimekizumab 
 in the Maintenance Treatment Period, this will be adjusted based on the dosing 
interval (eg, use Date of last bimekizumab dose in the Maintenance Treatment Period – date of 
first dose in the Maintenance Treatment Period + 
). 
Note: If date of last dose in the Maintenance Treatment Period + 
 (or 
 in the 
case of
 dosing) extends to a date beyond the final visit date of the Maintenance Treatment 
Period (not including SFU), then this calculation reverts to:  
− Final visit date of the Maintenance Treatment Period (not including SFU) – date of first 
dose in the Maintenance Treatment Period + 1.  
• For participants who die during the Maintenance Treatment Period, then this calculation 
reverts to:  
− Date of death – Date of first dose in the Maintenance Treatment Period + 1. 
10.1.2.2 
Time at risk (days) 
Definitions for time at risk (days) are provided as follows: 
• For participants who complete the Maintenance Treatment Period as planned and continue 
into an extension study (and, therefore, do not have the SFU visit in the feeder study):  
− Date of last visit of the Maintenance Treatment Period – Date of first dose in the 
Maintenance Treatment Period + 1. 
• For participants who die prior to the final visit of the Maintenance Treatment Period:  
− Date of death – Date of first dose in the Maintenance Period + 1. 
• For all other participants, use the minimum of the following:  
o Date of last dose in the Maintenance Treatment Period – Date of first dose in the 
Maintenance Treatment Period + 141 days. 
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o Date of last clinical contact – Date of first dose in the Maintenance Treatment Period 
+ 1.  
Note: This group could include participants who discontinue the Maintenance Treatment 
Period early, participants who complete the Maintenance Treatment Period as scheduled 
but choose not to continue into an extension study, or participants who are ongoing in the 
SFU period at the time of the data snapshot. 
10.1.3 
Exposure during the Initial and Maintenance Treatment Period 
Definitions for study medication duration (days) and time at risk (days) during the Initial and the 
Maintenance Treatment Period are provided as follows: 
10.1.3.1 
Study medication duration (days) 
Definitions for study medication duration (days) are provided as follows: 
• Sum of study medication durations from the individual Initial and Maintenance Treatment 
Period. 
Note: The algorithms for calculating these durations are specified in Section 10.1.1.1 and 
Section 10.1.2.1. 
Note: If date of last dose in the Initial Treatment Period + 
 (or 
 in the case of 
 dosing) extends to a date beyond the date of first dose in the Maintenance Treatment 
Period, then this calculation reverts to:  
− Sum of study medication durations from the individual Initial and Maintenance 
Treatment Periods - 1.  
10.1.3.2 
Time at risk (days) 
 Definitions for time at risk (days) are provided as follows: 
• For participants who complete the Maintenance Treatment Period as planned and continue 
into an extension study (and, therefore, do not have the SFU visit in the feeder study):  
− Final visit date – Date of first dose + 1. 
• For participants who die prior to the final visit:  
− Date of death – Date of first dose in the + 1. 
• For all other participants, use the minimum of the following:  
− Date of last dose – Date of first dose + 141 days. 
− Date of last clinical contact – Date of first dose + 1.  
Note: This group could include participants who discontinue early, participants who 
complete the Maintenance Treatment Period as scheduled but choose not to continue into an 
extension study, or participants who are ongoing in the SFU period at the time of the data 
snapshot (in the case of the interim analysis). 
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10.2 
Adverse events 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of IMP, whether or not considered related to the IMP. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of IMP. 
10.2.1 
Data considerations 
Treatment-emergent AEs are defined as those AEs that have a start date on or following the first 
dose of study treatment through the final dose of study treatment + 140 days (covering the 20-
week SFU period). If it is not possible (due to partial dates) to determine whether or not an AE is 
treatment-emergent then it will be assumed to be a TEAE.  
An AE will be assigned to the Initial Treatment Period if it started between the first 
administration of IMP on Day 1 up to Week 16. An AE will be assigned to the Maintenance 
Treatment Period if it started between the Week 16 study drug administration and Week 48. 
If an AE occurs on the date of a treatment switch, the event is attributed to the original treatment. 
The only exception to this is if the AE fulfills any of the criteria specified below: 
• Events that fulfill the anaphylaxis criteria for acute events (refer to Appendix A in 
Section 12.1) 
• Hypersensitivity events identified by the SMQ “Hypersensitivity (SMQ)” (see Section 12.1  
Appendix A) 
• Events with an high level term (HLT) of “Administration site reactions NEC” 
• Events with an HLT of “Injection site reactions” 
The rules for imputing partial start or stop dates are outlined in Section 4.2.4.  
Any TEAEs that occur during the SFU Period will be attributed to the period in which the 
participant was before initiating the SFU Period. 
Duration of AEs will not be calculated if there is missing stop date information. 
If the intensity of an AE is unknown, it is considered as severe. If the relationship to study drug 
is missing, it is considered as related. Note that if the seriousness of an adverse event is 
unknown, every attempt should be made to resolve this prior to a snapshot for an interim analysis 
or database lock; in the exceptional case that the seriousness of an adverse event is still missing 
then no imputation should be applied for this characteristic. 
Adverse events will be presented as “number of participants (percentage of participants) [number 
of events]”. In this style of output, “[number of events]” will include all cases of an AE including 
repeat occurrences in individual participants, while “number of participants” will count each 
participant only once. 
Subject time at risk represents the time a participant is at risk for having an AE. The definitions 
for subject time at risk (in days) are outlined in Section 10.1. These definitions will be used for 
exposure-adjusted AE summaries. 
Selected AE summaries will include the exposure-adjusted incident rate (EAIR) with associated 
95% CI and the exposure adjusted event rate (EAER). 
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The EAIR is defined as the number of participants (n) with a specific AE adjusted for the 
exposure and will be scaled to 100 subject-years: 
 
𝐸𝐴𝐼𝑅= 100 × 𝑛/ ∑(𝑇𝐸𝑥𝑝(𝑖))
𝑁
𝑖=1
 
 
Where TExp(i) is the exposure time and N is the number of participants at risk. 
If a participant has multiple events, the time of exposure is calculated to the first occurrence of 
the AE being considered. If a participant has no events, the total time at risk is used. 
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990; Fay and Feuer, 1997): 
 
 
 
 
 
 
where n is the number of participants 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. 
The EAER will be the number of AEs including repeat occurrences in individual participants 
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 total number of AEs, TRisk is the time at risk for each participant, and N is the 
total number of participants at risk. 
No confidence interval will be computed for EAER. 
Selected summaries, as specified in Section 10.2.2, will include the risk difference between 
bimekizumab and placebo. The risk difference is calculated as: 
𝑅𝐷= 𝐼𝑃𝐵𝐾𝑍−𝐼𝑃𝑃𝐵𝑂 
where 𝐼𝑃𝐵𝐾𝑍 is the incidence proportion for the bimekizumab-treated group and 𝐼𝑃𝑃𝐵𝑂 is the 
incidence proportion for the placebo group. Note that incidence proportion simply refers to the 
percentage of participants within the specified treatment group that experienced a given adverse 
event. 
The standard error for the risk difference is calculated as follows: 
𝑆𝐸𝑅𝐷= √(𝐼𝑃𝐵𝐾𝑍× (1 −𝐼𝑃𝐵𝐾𝑍
𝑛𝐵𝐾𝑍
)) + (𝐼𝑃𝑃𝐵𝑂× (1 −𝐼𝑃𝑃𝐵𝑂
𝑛𝑃𝐵𝑂
)) 
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where 𝑛𝐵𝐾𝑍 is the number of participants in the bimekizumab-treated group and 𝑛𝑃𝐵𝑂 is the 
number of participants in the placebo group.  
The corresponding confidence interval for the risk difference is as follows: 
𝐶𝐼𝑅𝐷= 𝑅𝐷 ± 𝑍1−𝛼2
⁄ × (𝑆𝐸𝑅𝐷)  
where 𝑍1−𝛼2
⁄  is the 𝑍 statistic for the corresponding level of alpha. For the risk difference 
confidence intervals calculated in this SAP, 1.96 will be used (corresponding to a two-sided 
alpha of 0.05 and 95% confidence interval). The risk difference and corresponding CI will be 
displayed as percentage. 
10.2.1.1 
COVID-19 related considerations 
To assess the impact of COVID-19 mass vaccination on TEAEs, a sensitivity analysis will 
present all TEAEs excluding TEAEs assessed as exclusively related to COVID-19 vaccine by 
the investigator. TEAEs recorded as related to both study medication and COVID-19 vaccination 
should not be excluded. A complementary table and listing of TEAEs related to COVID-19 
vaccine will be presented. 
Another sensitivity analysis will present all TEAEs excluding TEAEs with start date on or up to 
5 days after date of COVID-19 vaccine. Note that study participants may receive more than one 
administration of COVID-19 vaccine. A complementary table and listing of TEAEs with start 
date on or up to 5 days after date of COVID-19 vaccine will also be presented. 
10.2.2 
AE summaries 
The following summaries will be provided by treatment group for the Initial Treatment Period,  
and the Initial and Maintenance Treatment Period combined based on the SS, and AMS 
respectively. In addition, all summaries of TEAEs based on “100 subject years” will include 
EAIR (with 95% confidence interval) and EAER. For AEs that emerged after 112 days but still 
within the 140 days window, those AEs would be classified as TEAE. These AEs will be 
excluded from the outputs based on the Initial Period but included in the AE summaries for 
Initial and Maintenance Treatment Period.  
• Incidence of TEAEs – Overview 
• Incidence of TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of Serious TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of TEAEs Leading to Study Participant Discontinuation per 100 subject years by 
SOC, HLT, and PT  
• Incidence of TEAEs Leading to Death by SOC, HLT, and PT  
• Incidence of TEAEs by Maximum Relationship by SOC, HLT, and PT  
• Incidence of Serious TEAEs by Relationship SOC, HLT, and PT – Note: For EudraCT 
reporting purposes 
• Incidence of Related Serious TEAE by SOC, HLT, and PT 
• Incidence of Severe TEAE per 100 subject years by SOC, HLT, and PT 
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• Incidence of TEAEs Leading to Death by Relationship by SOC, HLT, and PT – Note: For 
EudraCT reporting purposes  
• Incidence of TEAEs by Maximum Severity, SOC, HLT, and PT 
• Incidence of TEAEs by decreasing frequency of PT 
• Incidence of TEAEs Above Reporting Threshold of 5% by SOC and PT 
• Incidence of Non-Serious TEAEs by SOC, HLT, and PT 
• Incidence of Non-Serious TEAEs by Maximum Relationship SOC, HLT, and PT 
• Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% by SOC and PT 
• Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% by Relationship SOC 
and PT 
• Incidence of Related TEAEs per 100 subject years by SOC, HLT, and PT 
• Incidence of Related TEAEs Above Reporting Threshold of 5% by SOC and PT 
• Incidence of TEAEs – Suspected and Confirmed COVID-19 cases by SOC, HLT and PT 
• Incidence of TEAEs Excluding TEAEs Exclusively Related to COVID-19 Vaccine by SOC, 
HLT, and PT 
• Incidence of TEAEs Exclusively Related to COVID-19 Vaccine by SOC, HLT, and PT 
• Incidence of COVID-19 Vaccine Interval Censored TEAEs by SOC, HLT, and PT 
• Incidence of COVID-19 Vaccine Interval TEAEs by SOC, HLT, and PT 
Suspected and confirmed COVID-19 cases will be identified with the preferred terms “Corona 
virus infection” or “Corona virus test positive”. 
The following subset of tables will also be presented for the Maintenance Treatment Period using 
the MS: 
• Incidence of TEAEs – Overview 
• Incidence of TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of Serious TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of TEAEs Leading to Discontinuation per 100 subject years by SOC, HLT, and PT  
• Incidence of TEAEs Leading to Death by SOC, HLT, and PT  
The following tables will be presented for the Initial Treatment Period: 
• Incidence of TEAEs Above Reporting Threshold of 5% with Risk Differences by SOC and 
PT 
• Incidence of Serious TEAEs and Risk Differences by SOC and PT  
The following table will be presented for the combined Initial and Maintenance Treatment 
Period. This summary will include only AEs that occur while a participant is on bimekizumab. 
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Any AEs in the Initial Treatment Period that begin while a participant is on placebo will be 
excluded. 
• Incidence of TEAEs per 100 subject years by SOC, HLT, and PT and by Time of Onset 
Relative to Anti-bimekizumab Antibody Status. 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) 
The tables with risk differences will also be accompanied by figures (dot plots) which show the 
incidence of the adverse events and corresponding 95% risk difference confidence intervals. 
These will be ordered by descending order of risk difference (bimekizumab vs placebo). 
10.2.3 
Other Safety topics of interest 
The following are AEs considered to be other safety topics of interest that require special 
statistical analyses. Along with the tables described, there will be a table which displays the risk 
difference and 95% confidence intervals for each of the topics of interest in the Initial Treatment 
Period. A corresponding figure (with dot plots) will be prepared. 
A by-participant listing of all AEs of safety topics of interest will be presented by type of safety 
topics of interest. 
10.2.3.1 
Infections (serious, opportunistic, fungal and TB) 
• Incidence of Serious Infection TEAEs per 100 subject years by SOC, HLT and PT  
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. 
• Incidence of Fungal Infection TEAEs per 100 subject years by SOC, HLT and PT 
Fungal infections will be summarized in a stand-alone table. The table will include all 
TEAEs (serious and non-serious) that code into the High Level Group Term (HLGT) 
“Fungal infectious disorders” 
• Incidence of Opportunistic Infection TEAEs per 100 subject years by SOC, HLT and 
PT  
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Opportunistic infections (including tuberculosis) will be summarized in a stand-alone table. 
The table will include all TEAEs identified using UCB-defined search criteria . 
The following steps will be followed for identifying and reviewing opportunistic infections: 
Identification Process 
The steps below outline 2 ways in which opportunistic infections (or potential opportunistic 
infections) can be identified: 
Step 1: Refer to column B of the spreadsheet, which identifies the PTs to be classified as 
opportunistic infections using either a single ‘x’ or a double ‘xx’. 
• All TEAEs that code to a PT flagged with a single ‘x’ need to also be serious to be 
considered an opportunistic infection. 
• All TEAEs that 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 will be flagged for 
case-by-case review by the study physician.  
Review Process 
Opportunistic infections for a given study will be reviewed on the following occasions: 
• At quarterly Infectious Disease Committee (IDC) Meetings, listings will be produced for 
each study (see details below) and reviewed by the corresponding study physician ahead of 
the IDC Meeting. These listings will be posted as part of the broader Safety Signal Detection 
(SSD) deliverable to a folder named for the given quarter (eg, 2018Q4) on the SharePoint. 
They will be based on the same data cut as the one used for SSD and will be delivered at the 
same time as the SSD outputs. The IDC will then agree on the final adjudication for each 
potential opportunistic infection. 
• For each study, a final listing for opportunistic infections (in the format described below) will 
be produced and agreed upon between the study physician and the IDC prior to finalizing the 
database. 
In each of the circumstances described above, the study programming team will produce an 
Excel listing that will be provided to the project lead statistician, project lead programmer, and to 
the study physician (who will subsequently provide it to the IDC). The Excel listing will contain 
the following columns (using the descriptions below as the column headings in the Excel listing): 
• Study ID 
• Unique Participant ID 
• AE Term (Verbatim) 
• AE Preferred Term 
• AE System Organ Class 
• AE High Level Term 
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• AE Low Level Term 
• Date of Onset 
• Outcome of Adverse Event 
• Date of Outcome 
• TEAE Flag 
• Serious Adverse Event? 
• Relationship to Study Medication  
• Intensity 
• Action Taken with IMP 
• Opportunistic Infection – Automatic 
• Opportunistic Infection – Manual Review 
• Flag 
• Data Cut Date 
• Opportunistic Infection – Final Adjudication 
Note the following about the final 5 variables in this listing: 
• Opportunistic Infection – Automatic: This is flagged as “Y” if the criteria for automatic 
selection as described in “Step 1” of the identification process are met. 
• Opportunistic Infection – Manual Review: This is flagged as “Y” if the criteria for case-by-
case selection as described in “Step 2” of the identification process are met. 
• Flag – This has a value of either “NEW” or “OLD”. It is marked as “NEW” if the event is 
appearing for the first time in that run of the listing. Otherwise, if it has appeared previously, 
it is marked as “OLD”. Unique records are determined by USUBJID AESPID for purposes 
of identifying whether an event has been modified from a previous run. 
• Date – Only for cases where Flag is “NEW”, this field will be populated with the data cut 
date for that particular run of the listing. 
• Opportunistic Infection – Final Adjudication – For new events, this is always left blank by 
the programmers. It will be completed by the study physician/IDC for every event that 
appears in the listing. For events adjudicated as opportunistic, the field will be populated with 
a “Y”.  
Following each review by the study physician and IDC, the Opportunistic Infection – Final 
Adjudication column will be completed (as described above), and the spreadsheets for each study 
will be returned to the study programming team via e-mail (coordinated by the IDC secretary). 
Then, for subsequent runs of the listing, the study programming teams will incorporate 
adjudications from previous runs. 
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10.2.3.2 
Malignancies 
• Incidence of Malignant or Unspecified Tumours TEAEs per 100 subject years by SOC, 
HLT and PT 
These events will be presented in the following tables: 
− One table will be based on the criteria Standardized MedDRA Query (SMQ) = 
“Malignant or unspecified tumours (SMQ)”  
− One table will be based on the criteria SMQ = “Malignant tumours (SMQ)”. 
SMQ search will include all TEAEs which code to a PT included in the Scope=Narrow group 
within each SMQ. 
Note that the events included in the “Malignancies” table will be a subset of the events included 
in the “Malignancies (including unspecified)” table. While the “Malignant tumours (SMQ)” is 
most relevant, “Malignant or unspecified tumours (SMQ)” must be reviewed for potential 
malignancies. 
The output tables will include 2 different overall incidence rows: 
• The first overall incidence row will summarize “Any Malignancy” and this row will 
summarize the incidence of all AEs flagged for inclusion in the table (using the appropriate 
SMQ depending on the table), regardless of the HLT it codes to.  
• The second overall incidence row will summarize “Any Malignancy excluding non 
melanomic skin cancers HLT” and this row will summarize the incidence of AEs flagged for 
inclusion in the table (using the appropriate SMQ depending on the table), excluding those 
which code to an HLT of “skin neoplasms malignant and unspecified (excl melanoma)”. 
10.2.3.3 
Major adverse cardiac event  
• Incidence of Adjudicated Major Cardiac Event (MACE) TEAEs per 100 subject years 
by SOC, HLT and PT 
Potential cardiovascular events are adjudicated by the independent Cardiovascular Event 
Adjudication Committee (CV-CAC) according to the CV-CAC Charter (version 6.0).  
Adjudicated events are classified by the CV-CAC to one of the event types as defined in 
Table 10‒1. The classification of an event as a Major Adverse Cardiac Event (MACE) is also 
determined by the CV-CAC. Events which are classified by the CV-CAC as any of the event 
types identified in the third column of Table 10‒1 will be considered an extended MACE. Note 
that extended MACE is determined programmatically and includes a broader scope definition of 
MACE.  
MACE as determined by the CV-CAC will be presented in a table and listing. Extended MACE 
will be presented separately in a table and listing. 
Another table and listing will present the adjudicated cardiovascular events by type. For each 
cardiovascular event type, the individual PTs which fall within each event type will be 
summarized. This listing will indicate whether each event was determined to be a MACE and/or 
an extended MACE. 
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Additionally, a listing of all events identified for potential review by the CV-CAC will be 
produced. This listing will indicate whether each event was identified by the CV-CAC Chair for 
full committee review.  
Table 10‒1: Cardiovascular event classifications 
Event 
Type 
Code 
Event Type 
Extended MACE 
1 
Non-Fatal Myocardial Infarction (MI) 
Yes 
2 
Non-Fatal Stroke: hemorrhagic 
Yes 
3 
Non-Fatal Stroke: ischemic 
Yes 
4 
Non-Fatal Stroke: embolic 
Yes 
5 
Non-Fatal Stroke: undeterminable 
Yes 
6 
Hospitalization or ER for Unstable Angina 
with urgent revascularization 
Yes 
7 
Hospitalization or ER for Unstable Angina 
without urgent revascularization 
No 
8 
Hospitalization for Heart Failure 
Yes 
9 
Transient Ischemic Attack (TIA) 
No 
10 
Coronary Revascularization Procedures (e.g. 
percutaneous coronary intervention, 
coronary artery bypass grafting) 
Yes 
11 
Urgent Revascularization Procedures (i.e. 
due to symptoms of brain ischemia or 
pending infarction) 
Yes 
12 
Arrhythmia (not associated with ischemia) 
No 
13 
Peripheral Arterial Event 
No 
14 
Venous Thromboembolic Event: pulmonary 
embolism (PE) 
No 
15 
Venous Thromboembolic Event: deep vein 
thrombosis (DVT) 
No 
16 
Venous Thromboembolic Event: PE and 
DVT 
No 
17 
Other CV Event 
No 
18 
Death due to Myocardial Infarction (MI) 
Yes 
19 
Death due to Stroke 
Yes 
20 
Sudden Cardiac Death 
Yes 
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Table 10‒1: Cardiovascular event classifications 
Event 
Type 
Code 
Event Type 
Extended MACE 
21 
Other CV Death (e.g. heart failure, 
pulmonary embolism, cardiovascular 
procedure-related) 
Yes 
22 
Cardiovascular: Undetermined Cause of 
Death (i.e. cause of death unknown) 
Yes 
23 
Non-Cardiovascular Death 
No 
24 
Non-Cardiovascular Event 
No 
99 
Inadequate information to adjudicate 
No 
CV=Cardiovascular; DVT=Deep Vein Thrombosis; ER=Emergency Room; MACE= Major Adverse Cardiac Event; 
MI=Myocardial Infarction; PE=Pulmonary Embolism; TIA=Transient Ischemic Attack. 
MACE is determined by the adjudication committee and is not identified programmatically based on event type.  
10.2.3.4 
Neutropenia  
• Incidence of Neutropenia TEAEs per 100 subject years by SOC, HLT and PT 
This table will be 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 
10.2.3.5 
Suicidal Ideation and Behavior  
• Incidence of Suicidal Ideation or Behavior TEAEs per 100 subject years by SOC, HLT 
and PT 
Potential neuropsychiatric events are adjudicated by the independent Neuropsychiatric 
Adjudication Committee according to the Neuropsychiatric Adjudication Committee (version 
8.0). Adjudicated events are classified by the Committee as Suicidal or Non-suicidal. 
Adjudicated events are also further classified by the Committee to one of the event types as 
defined in Table 10‒2. Suicidal Ideation and Behavior (SIB) is defined as events classified by the 
Committee as Suicidal. 
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A table and listing will present SIB events. 
Another table and listing will present the adjudicated neuropsychiatric events by type. For each 
neuropsychiatric event type, the individual PTs which fall within each event type will be 
summarized. This listing will indicate whether each event was determined to be Suicidal or Non-
Suicidal. For event type suicidal ideation, the listing will also indicate if intent was present and if 
the suicidal ideation was clinically significant. 
Additionally, a listing of all events identified for potential review by the Committee will be 
produced. This listing will indicate whether each event was identified by the Neuropsychiatric 
Event Adjudication Committee Chair for full committee review.  
Table 10‒2: Neuropsychiatric event classifications 
Event Type Code 
Event Classification 
Event Type 
1 
Suicidal 
Suicidal events/completed 
suicide 
2 
Suicidal 
Suicide attempt 
3 
Suicidal 
Preparatory acts toward 
imminent suicidal behavior 
4 
Suicidal/Non-suicidala 
Suicidal ideation 
7 
Non-suicidal 
Nonsuicidal Self-injurious 
behavior 
8 
Non-suicidal 
Nonsuicidal Other 
99 
Not applicable 
Inadequate information to 
adjudicate 
a Suicidal ideation event types can be classified by the Neuropsychiatric Adjudication Committee as Suicidal or 
Non-suicidal  depending on whether intent to die was present. 
10.2.3.6 
Inflammatory bowel disease 
• Incidence of Inflammatory Bowel Disease TEAEs per 100 subject years by SOC, HLT 
and PT 
Selected gastrointestinal events are adjudicated by the independent Inflammatory Bowel Disease 
(IBD) Adjudication Committee (IBD-CAC) according to the IBD-CAC Charter (version 3.0).  
Adjudicated events are classified by the IBD-CAC into one of the diagnostic types as defined in 
Table 10‒3. The events will further be classified as definite, probable or possible IBD. 
An overview of adjudicated IBD events 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 History of IBD CRF page ("Does subject have a history of IBD?”). 
This overview table will present events adjudicated by the IBD-CAC as either possible, probable 
or definite IBD. Definite and probable IBD will also be aggregated and summarized in this table. 
In addition, this table will summarize each IBD event classification (possible, probable or 
definite) separately. 
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Another table and listing will present the adjudicated IBD events by type. For each IBD event 
type, the individual PTs which fall within each event type will be summarized.  
Additionally, a listing of all events identified for potential review by the IBD-CAC will be 
produced. This listing will indicate whether each event was identified by the IBD-CAC Chair for 
full committee review. 
A further supportive listing will present the individual diagnostic criteria met for each 
adjudicated IBD event.  
Table 10‒3: IBD event classifications 
Event Type 
Code 
Event Type (Classification and diagnosis) 
Classification 
1 
Possible Inflammatory Bowel Disease – Crohn’s Disease 
Possible 
2 
Probable Inflammatory Bowel Disease – Crohn’s Disease 
Probable 
3 
Definite Inflammatory Bowel Disease – Crohn’s Disease 
Definite 
4 
Possible Inflammatory Bowel Disease – Ulcerative Colitis 
Possible 
5 
Probable Inflammatory Bowel Disease – Ulcerative Colitis 
Probable 
6 
Definite Inflammatory Bowel Disease – Ulcerative Colitis 
Definite 
7 
Possible Inflammatory Bowel Disease – type unclassified 
Possible 
8 
Probable Inflammatory Bowel Disease – type unclassified 
Probable 
9 
Definite Inflammatory Bowel Disease – type unclassified 
Definite 
10 
Symptoms not consistent with Inflammatory Bowel Disease 
Not 
applicable 
11 
Possible Inflammatory Bowel Disease – Microscopic Colitis 
Possible 
12 
Probable Inflammatory Bowel Disease – Microscopic Colitis 
Probable 
13 
Definite Inflammatory Bowel Disease – Microscopic Colitis 
Definite 
14 
Possible Inflammatory Bowel Disease – no further differentiation 
possible 
Possible 
15 
Probable Inflammatory Bowel Disease – no further differentiation 
possible 
Probable 
16 
Definite Inflammatory Bowel Disease – no further differentiation 
possible 
Definite 
99 
Not enough information to adjudicate 
Not 
applicable 
IBD=inflammatory bowel disease. 
Note: IBD diagnoses of “microscopic colitis” and “no further differentiation possible” were added in an adjudication 
charter amendment, accounting for the event type numbering. 
10.2.3.7 
Hypersensitivity (including anaphylaxis) 
• Incidence of Anaphylactic Reaction TEAEs per 100 subject years by SOC, HLT and PT 
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A separate 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 1 day after). An AE glossary table will also be produced to summarize the 
MedDRA coding for these events. The glossary table will include the following fields: reported 
term, PT, LLT, HLT, and SOC. 
A separate table will be prepared to summarize hypersensitivity events, identified using the SMQ 
“Hypersensitivity (SMQ)”. All TEAEs which code to a PT included in the Scope=Narrow search 
will be included in this table. 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 separate table will be prepared to summarized injection site reactions, identified 
using the HLTs: “Administration site reactions NEC” and “Injection site reactions”. 
10.2.3.8 
Hepatic events and PDILI 
• Incidence of hepatic events TEAEs per 100 subject years by SOC, HLT and PT 
A table for hepatic events will be created based on the SMQ of “Drug related hepatic disorders - 
comprehensive search (SMQ)”. However, these 2 sub-SMQs are to be excluded: “Liver 
neoplasms, benign (incl cysts and polyps) (SMQ)” and “Liver neoplasms, malignant and 
unspecified (SMQ)“. For each of the above SMQs, 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 will not be limited to events 
that the investigator determined to be related to study drug. 
Cases of potential Hy’s Law will be reported separately in a liver function test table. 
10.3 
Clinical laboratory evaluations 
Laboratory values, including markedly abnormal laboratory values will be presented 
descriptively by treatment group for the SS, MS, and AMS. 
The markedly abnormal tables and those based on common terminology criteria for AEs 
(CTCAE) grade will be produced only for selected laboratory variables. 
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. For tables where multiple measurements 
over a period of time are considered (as in shift tables), unscheduled and repeat visits will be 
considered as long as they were collected in the period being summarized (values observed more 
than 140 days after the last administration of study medication are not considered). All 
summaries will be presented in SI units and will be based on observed case values. In the case 
where laboratory values are below the LLQ, then these will be set to the midpoint between 0 and 
the lower limit of quantification for the purpose of summarizing the data. The following 
summaries are required: 
• A summary of the absolute and change from Baseline values in each laboratory variable by 
treatment group and visit 
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• A summary of the number and percentage of participants experiencing markedly abnormal 
values at any time while on treatment (assessment on or following the first dose of study 
treatment through the minimum of period of interest (Week 16) or date of last dose + 140 
days) by laboratory variable and treatment group. Two separate tables will show results for 
the Initial Treatment Period (for the SS) and the Initial and Maintenance Treatment Period 
(for the AMS). 
• A summary of the number and percentage of participants with a given CTCAE grade 
(0,1,2,3, or 4) based on minimum/maximum post-baseline value by laboratory variable and 
treatment group. Two separate tables will show results for the Initial Treatment Period (for 
the SS) and the Initial and Maintenance Treatment Period (for the AMS). 
• A shift table of the number and percentage of participants experiencing CTCAE grade 
0,1,2,3, or 4 values (as applicable) at Baseline to maximum post-Baseline CTCAE grade, by 
laboratory variable and treatment group. Two separate tables will show results for the Initial 
Treatment Period (for the SS) and the Initial and Maintenance Treatment Period (for the 
AMS). 
• A by-participant listing of all laboratory data (including urinalysis) will be provided. This 
listing will be presented by treatment group and will include: center, participant identifier, 
age, sex, race, weight, visit, laboratory variable, result (with abnormal values flagged as “L” 
or “H” accordingly) and unit.  
Markedly abnormal values are defined as those with a severity of Grade 3 and above based on 
the CTCAE criteria Version 4.03. Definitions of markedly abnormal values using the Grade 3 cut 
points are given in the tables below for age ranges of ≥17 years Table 10‒4 for markedly 
abnormal liver function test values, Table 10‒5 for markedly abnormal biochemistry values and 
Table 10‒6 for markedly abnormal hematology values). Tables summarizing markedly abnormal 
values will include a summary (counts and percentages) of markedly abnormal labs observed at 
any time while on treatment (ie, treatment-emergent markedly abnormal [TEMA]). For this 
summary, Baseline values and values observed more than 140 days after the last administration 
of study medication are not considered. The laboratory results classified as Grade 3 or Grade 4 
will be summarized and listed separately. 
Table 10‒4: Definitions of Markedly Abnormal Liver Function Values 
 
Parameter name 
Conventional 
Standard 
Abnormal 
Designation 
Unit 
Criteria 
Unit 
Criteria 
ALP 
U/L 
>5.0 x ULN 
U/L 
>5.0 x ULN 
AH 
ALT 
U/L 
>5.0 x ULN 
U/L 
>5.0 x ULN 
AH 
AST 
U/L 
>5.0 x ULN 
U/L 
>5.0 x ULN 
AH 
Total Bilirubin 
mg/dL 
>3.0 x ULN 
umol/L 
>3.0 x ULN 
AH 
GGT 
U/L 
>5.0 x ULN 
U/L 
>5.0 x ULN 
AH 
 
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Table 10‒5: Definitions of Markedly Abnormal Biochemistry Values 
 
Parameter name 
Conventional 
Standard 
Abnormal 
Designation 
Unit 
Criteria 
Unit 
Criteria 
Creatinine1 
mg/dL 
> 3.0 x 
Baseline or 
>3.0 x ULN 
umol/L 
> 3.0 x 
Baseline or 
>3.0 x ULN 
AH 
Glucose 
mg/dL 
<40 
>250 
mmol/L 
<1.7 
>13.9 
AL 
AH 
Calcium 
mg/dL 
>12.5 
<7.0 
mmol/L 
>3.1 
<1.75 
AH 
AL 
Magnesium 
mg/dL 
>3.0 
<0.9 
mmol/L 
>1.23 
<0.4 
AH 
AL 
Potassium 
mmol/L 
>6.0 
<3.0 
mmol/L 
>6.0 
<3.0 
AH 
AL 
Sodium 
mmol/L 
>155 
<130 
mmol/L 
>155 
<130 
AH 
AL 
Cholesterol 
mg/dL 
>400 
mmol/L 
>10.34 
AH 
1 The markedly abnormal definitions for creatinine are based on the logical or, if either criterion is met the 
creatinine value will be designated as abnormal high. 
 
Table 10‒6: Definitions of Markedly Abnormal Hematology Values 
 
Parameter name 
Conventional 
Standard 
Abnormal 
Designation 
Unit 
Criteria 
Unit 
Criteria 
Hemoglobin 
g/dL 
<8.0 
>4.0 above ULN  
g/L 
<80 
>40 above ULN  
AL 
AH 
Lymphocytes Absolute 
109/L 
<0.5 
>20.0 
109/L 
<0.5 
>20.0 
AL 
AH 
Neutrophils Absolute 
109/L 
<1.0 
109/L 
<1.0 
AL 
Platelets 
109/L 
<50 
109/L 
<50 
AL 
WBC/Leukocytes 
109/L 
<2.0 
>100 
109/L 
<2.0 
>100 
AL 
AH 
Abbreviations: AH=abnormal high; AL=abnormal low; ALP = alkaline phosphatase; ALT= alanine 
aminotransferase; AST = aspartate aminotransferase; dL = deciliter; GGT: gamma-glutamyltransferase; L = liter; 
mg = milligram; mmol = millimoles; μg = microgram; ULN = upper limit of normal, WBC=white blood cells. 
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The table for markedly abnormal liver function tests (LFTs) will contain data beyond the 
CTCAE Grade 3 thresholds outlined in Table 10-1 above in order to allow for a more thorough 
review of elevated LFTs. There will be 1 table, which will list the count and percentage of 
participants meeting the below criteria at any time during the study: 
• AST: >3xULN, >5xULN, >8xULN, >10xULN, >20xULN 
• ALT:   >3xULN, >5xULN, >8xULN, >10xULN, >20xULN 
• AST or ALT: >3xULN, >5xULN, >8xULN, >10xULN, >20xULN 
• Total Bilirubin: >1.5xULN, >2xULN  
• ALP: >1.5xULN 
For any participant with at least one markedly abnormal LFT (AST >3xULN, ALT >3xULN, 
bilirubin >3xULN, or ALP >1.5xULN) the New Ratio (nR) will be calculated as the ratio of 
either ALT or AST (whichever is higher) to ALP, all expressed as multiples of their ULN as 
follows: 
• nR = [maximum(AST/ULN or ALT/ULN)]/(ALP/ULN) 
Any pDILI will be summarized (all criteria must be met at the same assessment): 
• (AST or ALT > 3xULN) and Total Bilirubin > 1.5xULN 
• (AST or ALT > 3xULN) and Total Bilirubin > 2xULN   
In addition, a table will be produced to summarize potential Hy’s Law cases. The following 
definition will be used in that table: 
•  [AST ≥3xULN or ALT ≥3xULN] and Total Bilirubin ≥2xULN in the absence of ALP 
≥2xULN  
In order to meet the above potential Hy’s Law criteria, a participant must experience the 
elevation in bilirubin and ALT or AST (and the absence of ALP elevation, if applicable) at the 
same assessment. For example, a participant who experiences a ≥2 x ULN elevation of bilirubin 
at one visit and a ≥3xULN elevation in ALT (or AST) at a subsequent visit has not fulfilled the 
Hy’s Law criteria. 
Potential hepatotoxicity (meeting one of the PDILI or Hy’s Law laboratory criteria at least once) 
will be considered with and without symptoms potentially associated with hepatitis or 
hypersensitivity according to the investigator (reported on the Symptoms of Hepatitis and 
Hypersensitivity CRF page). 
10.4 
Vital signs, physical findings, and other observations related to 
safety 
10.4.1 
Vital signs 
The following vital signs variables will be summarized: systolic blood pressure (mmHg), 
diastolic blood pressure (mmHg), body temperature (°C) and heart rate (beats/min). The 
following summaries will be provided for the SS: 
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• A summary of the absolute and change from Baseline value for each vital sign variable by 
treatment group and visit. 
• A summary of the number and percentage of participants experiencing at least 1 markedly 
abnormal value for a vital sign variable as defined in Table 10‒7, by treatment group and 
period (Initial Treatment Period [SS], and Initial and Maintenance Treatment Period [AMS]). 
Unscheduled and repeat visits will be considered as long as they were collected in the period 
being summarized (values observed more than 140 days after the last administration of study 
medication are not considered). 
Table 10‒7: 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 
Diastolic blood pressure (mmHg) 
<50 and a decrease from 
Baseline of ≥15 
>105 and an increase from 
Baseline of ≥15 
A by-participant listing of all vital signs data will be provided. This listing will be presented by 
treatment group and will include: center, participant identifier, age, sex, race, weight, visit, vital 
sign variable and result (with abnormal values flagged as “L” or “H” accordingly). 
10.4.2 
Electrocardiograms 
Electrocardiogram data will be analyzed by treatment group and visit for the SS.  
A summary of the number and percentage of participants with normal, abnormal ECG results, as 
determined by the central reader, will be presented for all applicable visits. 
The following ECG variables will be summarized (absolute values and change from Baseline) by 
visit: QT corrected for heart rate using Friderica’s formula (QTcF), RR, PR, QRS and QT. 
QTc outliers are defined as QTcF values following dosing that are greater than 450 ms or are 
increases from Baseline greater than 30 ms. QTcF outliers will be highlighted in the data listing 
and summarized using the following categories: 
• Values >450 ms, >480 ms, >500 ms 
• Increase from Baseline of >30 ms, increase from Baseline of >60 ms, increase from Baseline 
of >90 ms 
• Values >450 ms and increases of >30 ms. Values >500 ms and increases of >60 ms 
The number and percentage of participant who meet the ECG outlier criteria at any assessment 
post first dose will be summarized for each period. 
Two separate by-participant listing of all 12-lead ECG data will be provided based on 
interpretation from central reader and from site, respectively. 
10.4.3 
Other safety endpoints 
For by-visit summaries, unscheduled and repeat visits will not be summarized, but these data will 
be included in listings. By-visit tables should include the SFU visit. Summaries over a period of 
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time (as in shift tables), unscheduled and repeat visits will be considered as long as they were 
collected in the period being summarized (values observed more than 140 days after the last 
administration of study medication are not considered). 
10.4.3.1 
Physical examination 
Abnormal results of the physical examination together with details of abnormalities: abnormality 
clinically significant or not, will be listed by participant and visit for SS. 
10.4.3.2 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
The eC-SSRS questionnaire will be self-administered by the study participant and assessed by 
trained study personnel. This scale will be used to assess SIB that may occur during the study. 
Results of the eC-SSRS will be summarized using the number of participants and percentage 
with (i) suicidal ideation, (iii) suicidal behavior, (iii) suicidal ideation or behavior, and (iv) self-
injurious behavior without suicidal intent. 
Self-injurious behavior without suicidal intent is defined as an event in the category non-suicidal 
self-injurious injuries. 
The incidence of participants with suicidal ideation, suicidal behavior, suicidal ideation or 
behavior, and self-injurious behavior will be summarized for the Initial Treatment Period and the 
combined Initial and Maintenance Treatment Period by treatment group. 
A by-participant listing of the eC-SSRS questionnaire data will be provided by treatment group. 
10.4.3.3 
Assessment and management of TB and TB risk factors 
A summary of the number and percentage of participants with negative, positive, and 
indeterminate   IGRA (Interferon-Gamma Release Assay) results at Screening and Week 44 will 
be presented. 
A by-participant listing of the “Evaluation of signs and symptoms of tuberculosis” questionnaire 
data and IGRA results will be provided by treatment group. 
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By-participant listing of the result of chest x-ray for tuberculosis will be provided by treatment 
group. 
10.4.3.4 
Pregnancy testing 
Pregnancy testing will consist of serum testing at the Screening. The pregnancy test will be urine 
at all other visits. 
A by-participant listing of the pregnancy test data will be provided by treatment group. 
10.4.3.5 
Patient Health Questionnaire (PHQ)-9 scores 
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 
scores indicating worse state. A score of 5 to 9 is considered to be minimal symptoms of 
depression. If any of the 9 questions are missing, then the score is treated as missing. 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.  
Change from Baseline in PHQ-9 is derived as post-Baseline score minus Baseline score.  
A summary of the absolute and change from Baseline value will be presented by treatment group 
and visit. 
The percentage of study participants with scores below 5, between 5 and 9, between 10 and 14, 
between 15 and 19, and greater than or equal to 20 in PHQ-9 will be summarized as a shift from 
Baseline by visit and treatment group based on observed values. 
The percentage of study participants with scores ≥ 15 at any post-Baseline visit and the number 
and percentage of study participants with scores ≥ 20 at any post-Baseline visit will be 
summarized by treatment group based on observed values. This summary will also include the 
percentage of study participants with increase from baseline ≥ 5 at any post-Baseline visit. 
The number and percentage of participants that complete the PHQ-9 will be calculated for each 
visit by treatment group. The percentage will be based on the number of participants in the RS. 
The summary will be repeated where the percentage is based on the subset of participants who 
complete each particular visit. 
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11 
REFERENCES 
Common Terminology Criteria for Adverse Events (CTCAE); Version 4.0 June 2010.U.S. 
Department of Health and Human Services 
Dauden E, Griffiths CE, Ortonne JP, Kragballe K, Molta CT, Robertson D, et al. Improvements 
in patient reported outcomes in moderate to severe psoriasis patients receiving continuous or 
paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol 
Venereol. 2009;23(12):1374 82. 
Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35(11):1095-108. 
Esmann S, Dufour DN, Jemec GB. Questionnaire based diagnosis of hidradenitis suppurativa: 
specificity, sensitivity and positive predictive value of specific diagnostic questions. Br J 
Dermatol. 2010;163(1):102 6. 
Guidance for Industry: E9 Statistical Principles for Clinical Trials. US Department of Health and 
Human Services, Food and Drug Administration. ICH 1998. 
Hurley H. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial 
benign pemphigus: surgical approach. In: Dermatologic surgery. Roenigh R, Roenigh H, editors. 
Marcel Dekker. 1989:729 39. 
Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, Gniadecki R. Adalimumab for the 
treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern 
Med. 2012;157(12):846 55. 
Kimball AB, Jemec GB, Yang M, Kageliery A, Signorovitch JE, Okun MM, et al. Assessing the 
validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response 
(HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 
2014;171(6):1434 42. 
Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, et al. Two Phase 
3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016a;375(5):422 34. 
Kimball AB, Sobell JM, Zouboulis CC, Gu Y, Williams DA, Sundaram M, et al. HiSCR 
(Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic 
outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 
2 adalimumab study. J Eur Acad Dermatol Venereol. 2016b;30(6):989 94. 
Mallinckrodt CH, Lin Q, Lipkovich I, and Molenberghs G. A structured approach to choosing 
estimands and estimators in longitudinal clinical trials. Pharmaceutical Statistics 2012; 11:456-
61. 
O'Kelly, Michael, and Bohdana Ratitch. Clinical trials with missing data: A guide for 
practitioners. John Wiley & Sons, 2014 
Ratitch, B., Lipkovich, I., O’Kelly, M. Combining Analysis Results from Mutiply Imputed 
Categorical Data, PharmaSUG, 2013, SP03 
Rubin D.B. 1987. Multiple Imputation for Nonresponse in Surveys. New York: John Wiley and 
Sons. 
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Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring of hidradenitis suppurativa 
reflecting the role of tobacco smoking and obesity. Br J Dermatol. 2009;161(4):831 9. 
Sun H, Snyder E, Koch GG. Statistical planning in confirmatory clinical trials with multiple 
treatment groups, multiple visits, and multiple endpoints. J Biopharmaceut Stat. 
2018;28(1):189-211. 
UpToDate. 2011. Modified Hidradenitis Suppurativa Score (HSS). [ONLINE] Available at: 
http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?36/33/37400. [Accessed 27 
November 2017]. 
Zouboulis CC, Kyrgidis A, Jemec GBE, Bechara FG, Giamarellos Bourboulis EJ, Ingram JR, et 
al. Development and validation of IHS4, a novel dynamic scoring system to assess hidradenitis 
suppurativa/acne inversa severity. British Journal of Dermatology. 2017 June 21.  
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12 
APPENDICES 
12.1 
Appendix A: MedDRA algorithmic approach to anaphylaxis 
The SMQ Anaphylactic reaction consists of three parts:  
• A narrow search containing PTs that represent core anaphylactic reaction terms (Category 
A – core anaphylactic reaction 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 
Nasal obstruction 
Asthma 
Oedema mouth 
Bronchial oedema 
Oropharyngeal spasm 
Bronchospasm 
Oropharyngeal swelling 
Cardio-respiratory distress 
Respiratory arrest 
Chest discomfort 
Respiratory distress 
Choking 
Respiratory failure 
Choking sensation 
Reversible airways obstruction 
Circumoral oedema 
Sensation of foreign body 
Cough 
Sneezing 
Cyanosis 
Stridor 
Dyspnoea 
Swollen tongue 
Hyperventilation 
Tachypnoea 
Irregular breathing 
Throat tightness 
Laryngeal dyspnoea 
Tongue oedema 
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Laryngeal oedema 
Tracheal obstruction 
Laryngospasm 
Tracheal oedema 
Laryngotracheal oedema 
Upper airway obstruction 
Mouth swelling 
Wheezing 
 
▪ Category C (Angioedema/Urticaria/Pruritus/Flush terms) 
Allergic oedema 
Oedema 
Angioedema 
Periorbital oedema 
Erythema 
Pruritus 
Eye oedema 
Pruritus allergic 
Eye pruritus 
Pruritus generalised 
Eye swelling 
Rash 
Eyelid oedema 
Rash erythematous 
Face oedema 
Rash generalised 
Flushing 
Rash pruritic 
Generalised erythema 
Skin swelling 
Injection site urticaria 
Swelling 
Lip oedema 
Swelling face 
Lip swelling 
Urticaria 
Nodular rash 
Urticaria papular 
Ocular hyperaemia 
 
 
▪ 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 (as anaphylaxis is an acute event, imputed dates should not be used in the 
algorithmic approach):  
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o A narrow term or a term from Category A;  
o A term from Category B - (Upper Airway/Respiratory) AND a term from Category C - 
(Angioedema/Urticaria/Pruritus/Flush);  
o 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 B: Definition of CTCAE grades 
Table 12‒1: Definition of CTCAE grades by biochemistry parameters 
Parameter  
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Creatinine1 
High 
umol/L 
>1-1.5x 
Baseline or 
>ULN-1.5 x 
ULN 
>1.5-3.0x 
Baseline or 
>1.5 – 3.0 x 
ULN 
>3.0x 
Baseline or 
>3.0 – 6.0 x 
ULN 
>6.0 x ULN 
Sodium 
Low 
mmol/L 
130-<LLN 
N/A 
120-<130 
<120 
Sodium 
High 
mmol/L 
>ULN-150 
>150-155 
>155-160 
>160 
Potassium2 
Low 
mmol/L 
3.0-<LLN 
3.0-<LLN 
2.5-<3.0 
<2.5 
Potassium 
High 
mmol/L 
>ULN-5.5 
>5.5-6.0 
>6.0-7.0 
>7.0 
Calcium 
Low 
mmol/L 
2.0-<LLN 
1.75-<2.0 
1.5-<1.75 
<1.5 
Calcium 
High 
mmol/L 
>ULN-2.9 
>2.9-3.1 
>3.1-3.4 
>3.4 
Magnesium 
Low 
mmol/L 
0.5-<LLN 
0.4-<0.5 
0.3-<0.4 
<0.3 
Magnesium 
High 
mmol/L 
>ULN-1.23 
N/A 
>1.23-3.30 
>3.30 
Cholesterol 
High 
mmol/L 
>ULN-7.75 
>7.75-10.34 
>10.34-
12.82 
>12.82 
1 The CTCAE Grade definitions for creatinine are based on the logical or the highest applicable CTCAE grade 
should be assigned to a creatine value. 
2 The decreased potassium criterion of 3.0-<LLN is specified for both CTCAE Grade 1 and Grade 2; values meeting 
this criterion will be counted as Grade 2. 
Table 12‒2: Definitions of CTCAE grades by hematology parameter 
Parameter 
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Low 
g/L 
100-<LLN 
80-<100 
<80 
N/A 
Hemoglobin1 
High 
g/L 
>0-20 
above ULN 
or >0-20 
above 
Baseline if 
Baseline is 
above ULN 
>20-40 
above ULN 
or >20-40 
above 
Baseline if 
Baseline is 
above ULN 
>40 above 
ULN or 
>40 above 
Baseline if 
Baseline is 
above ULN 
N/A 
Platelets 
Low 
109/L 
75-<LLN 
50-<75 
25-<50 
<25 
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Table 12‒2: Definitions of CTCAE grades by hematology parameter 
Parameter 
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
WBC 
Low 
109/L 
3-<LLN 
2-<3 
1-<2 
<1 
WBC 
High 
109/L 
N/A 
N/A 
>100 
N/A 
Lymphocytes 
Low 
109/L 
0.8-<LLN 
0.5-<0.8 
0.2-<0.5 
<0.2 
Lymphocytes 
High 
109/L 
N/A 
>4-20 
>20 
N/A 
Neutrophils 
Low 
109/L 
1.5-<LLN 
1.0-<1.5 
0.5-<1.0 
<0.5 
LLN=lower limit of normal; N/A=not applicable; ULN=upper limit of normal, WBC=white blood cells  
1 The CTCAE Grade definitions to be applied are dependent on the Baseline hemoglobin value. If the baseline value 
is > ULN then the criteria relative to Baseline is applicable, otherwise the criteria relative to ULN is applicable.  
 
 
Note that participants 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. 
 
 
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13 
AMENDMENT TO THE STATISTICAL ANALYSIS PLAN  
13.1 
Amendment 1 
Rationale for the amendment 
The main purposes of this amendment were:  
• General update to analyses to align with protocol amendment 3. 
• Procedural clarifications from discussions and feedback provided at meetings  
• Update to align with the bimekizumab program standards and safety topics of interest 
Modifications and changes 
Global Changes 
Typos and formatting were updated throughout the document. 
Global changes: 
The following changes were made throughout the SAP: 
• References to Section 3.9 were added through the efficacy sections to clarify definition and 
handling of intercurrent events 
• PRO endpoint terminology was updated to match protocol (eg, Worst Pain score in HSSDD 
instead of Worst Pain in HSSDD) 
Specific changes 
In addition to the global changes, the following specific changes have been made (formats as 
missing spaces or redundant spaces are not listed, typos): 
Change #1 
The following abbreviations have been added: 
CFS 
COVID-19 Free Set 
COVID-19 
coronavirus disease 2019 
NI 
Negative Immunodepletion 
nR 
New Ratio 
NS 
Negative Screen 
pDILI 
potential drug induced liver 
injury 
PI 
Positive Immunodepletion 
PS 
Positive Screen 
Change #2 
Section 1 Introduction 
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The protocols were updated: 
The SAP is based on the Protocol Amendment 3 2, 9 February 2021 16 December 2019 and the 
Japan-specific amendment 3.1 2.1, 11 February 2021 19 December 2019.  
Change #3 
Section 2.2 Study endpoints 
The following text was added: 
The endpoints based on HS Symptom Daily Diary (HSSDD) and Hidradenitis Suppurativa 
Symptom Questionnaire (HSSQ) pain responses are based on the current definitions, which are 
continuous. It is anticipated that a responder (binary) endpoint will be defined for the HSSDD 
and HSSQ pain items as well as other symptom items prior to database lock and unblinding, 
based on separate ongoing, blinded, psychometric analyses aiming to determine threshold for 
within-patient clinically meaningful improvement.  
The below HSSDD and HSSQ pain response endpoints and analyses will be adjusted 
accordingly in a future SAP amendment. 
Change #4 
Section 2.2.1.2 Secondary Efficacy endpoints 
The secondary endpoints were updated: 
The secondary efficacy endpoints are defined as: 
• HiSCR75 response (defined as at least a 75% reduction from Baseline in the total AN count 
with no increase from Baseline in abscess or draining tunnel count) at Week 16 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Baseline) by Week 16 
• Absolute change from Baseline in Dermatology Life Quality Index (DLQI) Total Score 
at Week 16 
• Absolute change from Baseline in Skin Pain score at Week 16, as assessed by the “worst 
pain” item (11-point numeric rating scale) in the HS Symptom Daily Diary (HSSDD) 
• Absolute change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at 
Week 16 
Change #5 
Section 2.2.1.3 Other efficacy endpoints 
The following text was added: 
• Absolute change from Baseline in Hidradenitis Suppurativa Quality of Life (HiSQOL) 
domain scores (symptoms, psychosocial, activities and adaptations) and Total score 
Change #6 
Section 2.2.3.2 Other safety endpoints 
The other safety topics of interest were updated: 
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• Other safety topics of interest: infections (serious, opportunistic, fungal, and TB), 
neutropenia, hypersensitivity (including anaphylaxis), suicidal ideation and behavior, 
depression, major adverse cardiovascular events, hepatic events and potential drug-
induced liver injury (PDILI),function test changes/enzyme elevations, malignancies, and 
inflammatory bowel disease. 
Change #7 
Section 2.3.1 Study description 
The following sentence was deleted: 
Enrollment of study participants currently using antibiotics will be capped at 30% of overall 
enrollment. 
Change #8 
Section 3.1 General presentation of summaries and analyses 
The following text was added: 
For PRO continuous variables, descriptive statistics will also include variable score, 
absolute and percentage changes from baseline, Q1 and Q3, 10th, and 90th percentiles. 
If no participants have data at a given time point, then only n=0 will be presented. The 
other descriptive statistics will be left blank. If n < 3 then the n, minimum, and maximum 
only will be presented. The other descriptive statistics will be left blank. If n = 3 n, mean, 
median, minimum and maximum will be presented only. The other descriptive statistics 
will be left blank. 
For categorical variables, the number and percentage of study participants in each category will 
be presented. Unless otherwise noted, the denominator for percentages will be based on the 
number of study participants included in the respective analysis set. Study participants with 
missing data will be accounted for using the following approaches: 
• For summaries of demographics and Baseline characteristics: percentages will be based on 
all study participants in the analysis set and a “Missing” category (corresponding to study 
participants with missing data for the variable being summarized) will be included as the last 
row in the list of categories being summarized. 
• For summaries of efficacy and safety endpoints, unless otherwise specified: percentages will 
be based only on those study participants with observed data for the variable being 
summarized. As the denominator may be different from the number of study participants in 
the analysis set being considered, the denominator will be displayed in the table. The general 
format for displaying this will be “n/Nsub (%).” 
Percentages will be presented to 1 decimal place. If the percentage is 100%, a decimal will not 
be presented. If the count is 0, the percentage will not be presented. Typically, the % sign will be 
presented in the column header, but not with each individual value. 
For the purpose of the tabulations the lower and upper confidence limits for the percentages will 
be truncated at 0 and 100% respectively. Confidence intervals (CIs) for the response rates in 
efficacy summaries based on nonresponder imputation (NRI) will be computed using the 
Wilson approximation. 
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Change #9 
Section 3.3 Definition of Baseline 
The following text was added: 
For randomized participants for whom no start date of treatment is available, the Baseline value 
will be considered as the last available value on or before the randomization date.   
Change #10 
Section 3.4 Protocol deviations 
The following text was added: 
Deviations related to the Coronavirus Disease 2019 (COVID-19) global pandemic are 
unavoidable deviations from the protocol due to confirmed COVID-19 infection, suspected 
COVID-19 infection, general circumstances around COVID-19 without infection or any other 
deviation from the protocol due to COVID-19. COVID-19 protocol deviations will also be 
reviewed separately as part of the ongoing data cleaning process. 
Change #11 
The following section was added: 
COVID-19 Free Set (Section 3.5.9) 
The COVID-19 Free Set (CFS) will consist of all study participants randomized into the study 
and who have no COVID-19 impact through Week 16. This analysis set will be used for 
sensitivity analysis of the primary efficacy endpoint. 
Change #12 
Section 3.8 Coding dictionaries 
The following sentence was updated: 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD) version MAR2021 B3 or later.SEP2015. Medical procedures will not be coded. 
Change #13 
The following section was added: 
Definition of an intercurrent event (Section 3.9) 
Handling of intercurrent events is one of the key elements for the analysis of efficacy endpoints. 
An intercurrent event is defined as receipt of systemic antibiotic rescue medication or 
discontinuation of study treatment due to an AE or lack of efficacy (See Section 8.2.2). 
Receipt of systemic antibiotic rescue medication is defined as initiating any systemic antibiotic 
on or after Baseline for any reason (including in response to an AE). The only exception to this 
rule is if a participant randomized to the antibiotic stratum on a tetracycline antibiotic interrupts 
their stable dose of tetracycline antibiotic during the study and subsequently restarts the same 
tetracycline antibiotic as confirmed using the coded preferred term. The restarted dose and 
frequency of the antibiotic must be the same or lower than the regimen prior to the interruption. 
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The dates of an intercurrent event are as follows: 
• For receipt of systemic antibiotic rescue medication: start date of the antibiotic 
• For discontinuation of study treatment due to an AE or lack of efficacy: Last study treatment 
date + 17 days. Note: study treatment discontinuation includes study discontinuation. 
The choice of 17 days is intended to capture the interval between dosing and lesion assessments 
(14 days), as well as the visit window (3 days). 
An additional sensitivity analysis will be conducted where missing data due to COVID-19 will 
be considered an intercurrent event and will be imputed as a nonresponse at that particular visit. 
This will be identified when there are missing data at a visit that has been impacted by COVID-
19 according the COVID-19 impact CRF page. The date of this intercurrent event will be the 
date of the impacted visit. 
Change #14 
Section 3.10 Changes to protocol-defined analyses 
The following text was added: 
The HiSQOL endpoint was clarified to show that there are only 3 domains: symptoms, 
psychosocial, activities and adaptations and to add total score. 
Also, the following endpoint was added to the list of protocol endpoints not included in the 
analysis: 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Week 16) by Week 48 
Change #15 
Section 4.1 Adjustments for covariates 
The following text was added: 
If a participant is stratified in the incorrect stratum (ie, the stratum recorded in the Interactive 
voice or web Response System differs from the actual stratum the participant belongs to), the 
actual stratum will be used for the analysis.  
Change #16 
Section 4.2.1.4 Missing Data Overview and Summary 
The following text was added: 
In summary, the approaches listed below will be used in this study for handling missing data for 
efficacy endpoints as appropriate: 
• NRI: Participants who have missing data at the timepoint of interest are treated as though 
they did not respond to the treatment. This approach is also referred to as Composite 
Estimand (NRI). 
• Multiple Imputation (MI) – MCMC / Monotone Regression: Using multiple imputation 
methodology, intermittent missing data are imputed based on the MCMC method, and 
monotone missing data are imputed using monotone regression. 
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• MI–MCMC / Reference-based imputation: Using multiple imputation methodology, 
intermittent missing data are imputed based on the MCMC method, and monotone missing 
data are imputed using an imputation model based on placebo (reference) data. 
• LOCF: Post-Baseline missing data are imputed by carrying forward the last available 
observation (including Baseline). 
• Tipping point analyses: Assumptions will be made about average outcomes among the 
subsets of participants who prematurely discontinued study treatment. Various “delta 
adjustments” will be made to the assumed responses among missing data in each treatment 
arm with varying degrees of plausibility in order to identify assumptions about the missing 
data under which the conclusions change (O’Kelly, 2014). Then, the plausibility of such 
assumptions is discussed. 
• Observed case (OC): Missing data are not imputed. Only participants with available data 
who have not discontinued study treatment at the given timepoint are considered. Study 
participants with missing data or who have prematurely discontinued study treatment will be 
treated as missing. For OC summaries, intercurrent events are not handled differently than 
other missing data. 
• Treatment policy strategy: All available data observed at the time point of interest will 
be considered, regardless of the occurrence of intercurrent events. This means the 
analysis includes on- and off-treatment values collected after study participants 
prematurely discontinued study treatment but agreed to remain on the study and 
continued to attend visits and provide assessments at those visits as well as values from 
study participants who received rescue antibiotic medication. Those observed values 
will be analyzed according to the study participant’s randomized treatment. Study 
participants 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. 
Table 4-1 was updated: 
Table 4‒1: 
Missing data handling approach by endpoint priority and type 
Endpoint 
Priority 
Endpoint 
Type 
Com
posite 
Estmi
nad 
(NRI) 
Modified 
Composite 
Estimand 
(MI) 
 
MI  
(MCMC/ 
Referenc
e-based) 
Tipping 
Point 
Treat-
ment 
Policy 
Hypo-
thetical 
Estimand 
OC 
Primary 
Responder 
Sa 
P 
Sa 
S 
Sa 
 
S 
Secondary 
included 
in the 
statistical 
testing 
procedure 
Responder 
Sa 
P 
 
 
 
 
S 
Continuou
s 
 
 
 
 
 
P 
S 
Binary 
X 
X 
 
 
 
 
X 
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Secondar
y not 
included 
in 
statistical 
testing 
procedur
e 
Continuo
us 
 
 
 
 
 
X 
X 
Other 
Responde
r 
Xd 
X 
 
 
 
 
Xd 
Continuo
us  
 
 
 
 
 
X 
Xb 
Ordinal 
 
 
 
 
 
Xc 
Xc 
B=Backup method,  LOCF=Last observation carried forward, MCMC=Markov Chain Monte Carlo, MI=multiple 
imputation, NRI=Nonresponder imputation, OC=Observed case, P=Primary method, S=Sensitivity method, 
X=Method to be used (no priority designated). 
Note: Composite estimand (NRI) refers Backup method is only applicable when the primary method is unable to 
the approach in which data preceded by the intercurrent event of study treatment discontinuationconverge 
due to AE or lack of efficacy or receipt of rescue antibiotic medication are imputed as nonresponse, and other 
missing data are also imputed as nonresponse. 
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 or receipt of rescue antibiotic 
medication are imputed as nonresponse, and other missing data are imputed via a multiple imputation model.  
Note: Hypothetical Estimand (MI) refers to the approach where outcomes for study participants without an 
intercurrent event of study treatment discontinuation are as observed, and outcomes for study 
participantschallenges with the intercurrent event are imputed via a multiple imputation model. 
a Imputation method is applied on continuous data, and responder endpoint is derived from the continuous endpoint 
based on complete data set where applicable. 
b Required only for by-visit summaries of variables whose value at Week 16 is part of the hierarchical testing 
procedure. 
c For variables with multiple categories, data will be summarized as observed with an additional missing row 
to capture missing data at a given visit. 
c Participants with intercurrent events are imputed as nonresponders for all subsequent timepoints before the 
imputation method is applied for all other missing data.   
d NRI/OC sensitivity analysis will be performed only for HiSCR50, HiSCR75, HiSCR90, HiSCR100 summaries.   
e The treatment policy estimand will use the same MI-MCMC/Monotone Regression defined for the primary 
analysis, with the exception that participants with intercurrent events will not be treated as nonresponders for all 
subsequent timepoints before the imputation method is applied for missing data. 
Change #17 
Section 4.2.2 Missing data algorithms for efficacy analyses 
The section has been moved from Section 4.2.1.5 and split into Section 4.2.2.1, Section 4.2.2.2, 
and Section 4.2.2.3. 
Change #18 
Section 4.2.2.1 MI – MCMC/Monotone Regression 
This section was updated to the following text: 
In many cases, missing efficacy data due to study treatment discontinuation should be dependent 
on the observed efficacy scores, but independent of unobserved data. This would be consistent 
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with a missing at random (MAR) pattern of missingness. To investigate the efficacy results 
under the assumption of data being MAR, a multiple imputation method will be applied. as 
follows: 
Binary endpoint 
For a binary endpoint (eg, HiSCR50), the procedure is as follows: 
6. Create a data set, one for each treatment group of participants with observed values 
and those needing estimation by multiple imputation. For the imputation step, a 
distinction is made between non-monotone missing values (ie, intermittent missing 
values between completed assessments) and monotone missing values (ie, where all 
participants data are missing after a given time point). 
c. For the intermittent missing values, the missing values in each data set will be filled in 
using the MCMC method with multiple chain, monotone missing data imputing 
pattern, and non-informative prior 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 762 and all 
other multiple imputation procedures described in this SAP will use this same seed as 
well. The resulting 100 imputed data sets will have a monotone missing pattern and will 
be imputed using a method for monotone missingness. Note Create a data set, one for 
each treatment group (note that a separate imputation procedure must be invoked in SAS for 
each treatment group as the seed cannot be set for by groups beyond the first when using a by 
statement), of participants with observed values and those needing estimation by multiple 
imputation. The intermittent missing lesion counts in PROC MI. 
d. each data set (ie, missing values for a given subject that has available data before and after 
the missing timepoint) will be filled in using the MCMC method, with a total of 100 sets of 
imputations being performed. The seed used for these imputations will be 762 (note that all 
other multiple imputation procedures described in this SAP related to MCMC/Monotone 
regression analyses will use this same seed as well). For monotone missing data (ie, where all 
participant data is missing after a given timepoint), monotone regression will then 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 data set has a monotone missing data pattern, the process is repeated 
sequentially for variables with missing values. This procedure will be based on the100 
imputed datasets generated from sets of imputations already created using the MCMC 
procedure and method such that there will be performed by imputation. The SAS® PROC 
MI procedure will be used for the imputation. 
1.  data sets in total. In both cases, Hurley Stage at Baseline, Baseline antibiotic use, and 
value of the variable of interest lesion count at Baseline and at each post-Baseline visit 
(prior to the time point of interest in chronological order, see notes below about visits 
to include for different analysis sets) will be included in the imputation model. The post- 
Baseline values will need to be specified in chronological order in the imputation 
model so that SAS® PROC MI imputes variables from left to right (eg, the Week 2 
value will be first imputed using regression based on the Baseline value, and then 
Week 4 value will be imputed using regression based on Baseline and Week 2 
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values, etc).Note that lesion count at earlier visits will also be used as predictors for the 
model of lesion count at later visits. The resulting data sets for each treatment arm will be 
combined into one complete data set based on each of the 100 imputations. 
Note: The imputation model based on the MCMC method will only allow joint 
multivariate normal numeric variables. Therefore, Hurley Stage at Baseline and Baseline 
antibiotic use will be re-coded as indicator variables. For Baseline antibiotic use, this will 
simply be 0 for Baseline antibiotic non-users and 1 for Baseline antibiotic users. For Hurley 
Stage at Baseline, this will be 0 for Hurley Stage II participants and 1 for Hurley Stage III 
participants. In order to achieve model convergence, Baseline antibiotic use may be dropped 
from the model. If convergence is still not obtained, then Hurley Stage at Baseline may also 
be dropped from the model. Additionally, if a variable is dropped in order to allow 
convergence for one model in a study, that variable does not have to be dropped from 
other models in the study if the model converges without dropping the variable. In 
other words, model convergence should be evaluated for each efficacy variable 
independently. 
Note: The imputation of each lesion type (inflammatory nodule, abscess, draining 
tunnel, etc) will be performed separately. The 100 data sets obtained for each type will 
be merged by imputation number and subject number.  
2. For each complete imputed data set, the dichotomous responder variable (eg, HiSCR 0 or 
1) based on the imputed %ΔAN and draining tunnel (fistula/sinus tract) count will be 
computed. Each complete imputed data set will then be analyzed based on the logistic 
regression model. 
Note: For derivation of HiSCR response, the AN, inflammatory nodule, abscess, and draining 
tunnel (fistula/sinus tract) counts at Week 16 in the imputed data sets will be compared 
directly to the observed Baseline counts to determine response. If values outside of the pre-
defined range of values for lesion count (<0) are imputed, they will be cut off as appropriate 
after the multiple imputation procedure but before deriving the responder variable. For 
example, an imputed draining tunnel (fistula/sinus tract) count of -1 would be changed to 0 
before deriving the HiSCR responder variable. Additional ranges for values for secondary 
and other endpoints are defined in Table 4-2.   
Note: Standard rounding rules will also be applied to the imputed values of endpoints 
that can only take integer values (eg, abscess count). For example, if a study participant 
has an abscess count imputed as 2.4, this imputed value would be rounded down to 2. 
This rounding step is performed after the multiple imputation but before deriving the 
responder variable.  
Table 4‒2: 
Imputation allowable ranges by variable 
Variable 
Minimum Value 
Maximum Value 
Integer Values Only 
Lesion counta 
0 
-- 
Yes 
DLQI total score 
0 
30 
Yes 
hs-CRP 
LLOQ/2 
-- 
No 
HSSDD item score 
0 
10 
Yes 
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Table 4‒2: 
Imputation allowable ranges by variable 
Variable 
Minimum Value 
Maximum Value 
Integer Values Only 
HSSQ item score 
0 
10 
Yes 
IHS4 
0 
-- 
No 
HiSQOL total score 
0 
68 
Yes 
HiSQOL symptom 
status score 
0 
16 
Yes 
HiSQOL psychosocial 
impact score 
0 
20 
Yes 
HiSQOL impact on 
physical activities score 
0 
32 
Yes 
EQ-5D-3L VAS 
0 
100 
Yes 
WPAI dimension 
scores 
0 
100 
No for variables: “Percent work 
time missed due to problem” and 
“Percent overall work impairment 
due to problem”. 
Yes for variables: “Percent 
impairment while working due to 
problem” and “Percent activity 
impairment due to problem”. 
These two variables can only take 
values that are multiples of 10. 
PHQ-9 
0 
27 
Yes 
a Lesion counts will be imputed separately for each lesion type (abscesses, draining tunnels [fistulas/sinus tracts], 
inflammatory nodules, non-draining tunnels [fistulas/sinus tracts], non-inflammatory nodules, HS scars). The 
imputed lesion counts will be used to derive the endpoints that are dependent on the lesion count data (eg, 
HiSCR50). 
 
7. Estimates of the adjusted responder rate for each treatment group and the associated 
SE are obtained The Week 16 results from the specified statistical analysis (logistic 
regression model per Section 8.2.2) of each of the 100 imputed data sets. These estimates 
will be combined for overall inference using Rubin’s rules, which account for the uncertainty 
associated with the imputed values (Rubin, 1987), and the combined estimates and SEs 
will be used to construct 95% CIs using the logit scale. This will be done using SAS 
PROC MIANALYZE. 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). This will be done using SAS PROC MIANALYZE. 
Note: The (unadjusted) proportion of responders will be calculated at each time point 
by treatment group from the imputed datasets using SAS PROC FREQ. These results 
will also be combined into an overall inference using SAS PROC MIANALYZE. 
Note that this procedure indicates that the imputation model will be applied for each treatment 
group separately in PROC MI, which will be the default method. However, in the event that 
there are computational challenges with the imputation model (eg, due to a standard deviation of 
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0 for responses of a given imputation), it is acceptable to modify the imputation model to include 
treatment as a variable in the model rather than running a separate model for each treatment 
group. It should be noted that doing so assumes that treatment does not interact with any of the 
other variables in the imputation model. 
Some key points to consider relative to the calculation of the odds ratios and corresponding 
confidence intervals are noted below: 
As the estimates of the odds ratios from the logistic regression models in Step 3 follow a log-
normal distribution, a log transformation is needed to normalize these 100 odds ratio estimates. 
That 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 odds ratio estimates from the logistic regression model are used when combining into a 
single inference (Step 3). Additionally, the SE for the odds ratios are transformed as 
follows:the use of PROC MIANALYZE in step 3). Appropriate transformations to the standard 
errors and p-values will also be made in order to get the correct confidence intervals. For the 
logistic regression using the p-value for the general association the Wilson-Hilferty 
transformation will be used (Ratitch, 2013).  
𝑺𝑬= log(UCL) - log (LCL)
2Zα/2
 
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 (2.24 for a 97.5% CI). The estimates of the log odds ratio 
for Bimekizumab relative to placebo and the corresponding upper and lower CLs will be 
provided. The odds ratio will be then estimated by exponentiating the estimate of the log 
odds ratio. The odds ratio and the confidence limits of the odds ratio will be estimated as 
follows:  
 
𝑶𝑹=  exp (Log odds ratio estimate) 
 
𝑳𝑪𝑳=  𝑶𝑹∗𝐞𝐱𝐩 (−𝑺𝑬∗𝒁𝜶𝟐
⁄ ) 
 
𝑼𝑪𝑳=  𝑶𝑹∗𝐞𝐱𝐩 (𝑺𝑬∗𝒁𝜶𝟐
⁄ ) 
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 (2.24 for a 97.5% CI). These calculations will be done such that odds ratios 
and corresponding CIs are calculated for the odds ratio of bimekizumab vs. placebo. 
Note: . If one dose regimen is tested at the 0.05 significance level as determined in 
Section 4.5, then the confidence interval will be 95% instead of 97.5% for that dose, with a 
corresponding Zα/2 of1.96. 
In addition to calculating the odds ratio, associated CIs, and p-values for the pairwise 
comparisons of bimekizumab and placebo, the estimated proportion of responders (ie, 
estimated responder rate) and the difference in the proportion of responders between each 
bimekizumab treatment group and placebo will be estimated, and 2-sided 95% CIs will be 
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created for each difference. The creation of the estimates of the differences will be 
completed for each bimekizumab treatment group using the process detailed below: 
8. Use the logistic regression model to calculate: 
Least squares mean estimates of the log odds of bimekizumab (GB) and placebo (GP), as 
well as their corresponding standard errors (SB and SP, respectively). 
Standard error of the least squares mean estimate of the log odds ratio (SR) 
9. 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 
10. 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 MCMC method for multiple imputation, as previously outlined, Missing data for 
continuous components of the primary endpoint and binary secondary efficacy endpoints will be 
imputed using MI as appropriate.  
The above describes the procedure for binary endpoints. For continuous endpoints,  the MI 
procedure will be similar to that described above with the following differences:  
11. The absolute value of the given variable will be imputed. Once imputation has been 
performed across the 100 iterations specified, any values outside of the range of the given 
variable will be truncated accordingly. 
12. The change from Baseline values will be computed based on the complete data sets. 
13. The analysis model will be based on ANCOVA (Section 8.3.3 and Section 8.3.4) as opposed 
to logistic regression. 
For other efficacy variables, MI will be used to account for missing values. The calculation 
steps impute missing data when possible and where specified. If the imputation model cannot 
converge, LOCF will be used. The MI procedure will also be similar to that 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. 
Note that this procedure indicates that the imputation model will be applied for each 
treatment group separately in PROC MI, which will be the default method. , for continuous 
and binary endpoints respectively. However, in the event there are computational challenges 
with the imputation model (eg, due to a standard deviation of 0 for responses of a given 
imputation), it is acceptable to modify the imputation model to include treatment as a 
variable in the model rather than running a separate model for each treatment group. It 
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should be noted that doing so assumes that treatment does not interact with any of the 
other variables in the imputation model. 
Continuous endpoint  
For continuous endpoints (eg, Change from Baseline in DLQI total score at Week 16), the 
MI method will be applied as follows: 
5. 
The MCMC/monotone regression method described above in Step 1 for binary 
endpoints will be performed. 
6. 
Based on the multiply imputed data sets obtained for the given variable, the change 
from Baseline will be derived for each of the 100 complete no inferential statistics will 
be calculated for the imputed data sets based on the observed Baseline value and the 
observed/imputed post-Baseline values. Note that if the value itself is being 
summarized, no additional derivation is needed. 
7. 
If a statistical model is being used for the analysis of the variable, then that will be 
performed for each imputation in this step. If no statistical model is being used, then 
simple descriptive statistics will be calculated.  
8. 
For data excluding hs-CRP, the following rules apply. The results of the 100 
imputed data sets (based on the statistical model or descriptive statistics) are 
combined with means and standard errors Means and standard errors will be 
calculated using Rubin’s rules (via PROC MIANALYZE). Note that for the 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. Thus, for median, Q1, Q3, minimum 
and maximum, the following approach will apply:that will be used when summarizing 
continuous secondary efficacy variables by subgroup. 
− 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, then the mean of the 
means will also be presented to 1 decimal place). 
For hs-CRP only, the following rules apply. The hs-CRP data will be presented using the 
geometric mean, 95% CI for the geometric mean, median, Q1, Q3, minimum and 
maximum. The change from Baseline will be expressed as the ratio to Baseline in the 
summaries. The following approach will be applied: 
• Following the MI procedure, the ratio to Baseline will be calculated for any of the 
imputed values  
• The natural logarithm of the absolute values and of the ratios to Baseline will be 
calculated 
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• The logged values will be summarized (using PROC MEANS) by treatment, visit and 
imputation  
• The datasets will be combined using PROC MIANALYZE in order to get the mean and 
95% CI estimates from the absolute values and ratios to Baseline (based on logged data) 
across imputations 
• The estimates of the mean and 95% CI will be back-transformed to obtain the 
geometric mean and 95% CI on the original scale 
• For the median, Q1, Q3, minimum and maximum the procedure outlined above for the 
other endpoints will be followed 
If the imputation model cannot converge, LOCF will be used. 
Change #19 
Section 4.2.2.2 MI – MCMC/ Referenced-based imputation 
The steps of the procedure were updated to:  
The steps for the procedure are as follows: 
1. For non-monotone (intermittent) missing data, MCMC will be used to impute lesion 
count data, with Baseline antibiotic use, Hurley Stage at Baseline, and lesion count at 
Baseline and at each post-Baseline visit (in chronological order) being included in the 
imputation model. This will be done only once for each participant in order to provide a 
dataset with monotone missing data. 
2. Data will be processed sequentially by repeatedly calling SAS® PROC MI to impute 
missing outcome data at visits t=1, … T, where T is Week 16 for HiSCR50. 
a. Initialization. Set t=1 (Baseline visit) 
b. Iteration. Set t=t+1. Create a data set combining records from bimekizumab- and 
placebo-treated participants with columns for covariates (Hurley Stage at Baseline 
and Baseline antibiotic use) and outcomes at visits 1 to t. Outcomes for all 
bimekizumab-treated participants 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 
participants 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. Run MCMC to impute Impute missing values for visit t using 
previous outcomes for visits 1 to t-1, Baseline antibiotic use, and Hurley Stage at 
Baseline. Note that only placebo data will be used to estimate the imputation 
model since no outcome is available for bimekizumab-treated participants at 
visit t. Consequently, the input dataset should include all study participants 
from placebo but only study participants from the bimekizumab arm that 
have values at timepoint t missing. 
d. Repeat steps 2a-2c, 100 times with different seed values (seeds ranging from 853 
to 952) to create 100 imputed complete data sets. Study participants whose 
missing values were imputed in the last PROC MI call will be included in the 
input dataset for the next PROC MI call. Standard rounding rules will be 
applied to the imputed values. If the MI procedure yields a value outside of 
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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 inflammatory nodules will be updated to 0 in 
the case of an imputed value less than 0. 
e. Analysis. For each completed data set, the outcome (response or change from 
Baseline) will be calculated using the complete datasets (with no missing data). 
3. Each complete imputed data set will then be analyzed based on the statistical model 
specified in this study (logistic regression). The Week 16 results from logistic regression 
of each of the 100 imputed data sets will be combined 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. 
Change #20 
Section 4.2.2.3 Tipping Point Analysis 
The steps for performing the tipping point analysis were updated: 
Tipping point analyses will also be implemented as a supportive analysis for the primary efficacy 
endpoint. 
The objective of the tipping point analyses is to evaluate the sensitivity of results to 
departures from the missing at random assumption and to identify the point at which 
departures cause results to "tip" from statistically significant to statistically non-
significant. As such, these identify assumptions about the missing data under which the 
conclusions from the main analysis change, ie, under which there is no longer 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<0.025). Note that each 
bimekizumab dose of 
 and 
 will be compared to placebo independently 
for these analyses. If one dose regimen is tested at the 0.05 significance level as determined in 
Section 4.5, then the p-value in this analysis method will be 0.05 instead of 0.025 throughout for 
that dose. 
For tipping point analyses, data for participants after As a first step, the intercurrent event 
date (See Section 3.9) will be changed to missing prior to imputation but will not be 
changed to non-response after imputation.  
The worst-case scenario will be evaluated first. All missing primary endpoint values for 
(HiSCR50 at Week 16). Specifically, all study participants with a missing HiSCR50 at Week 16 
who have been randomized to bimekizumab (where missing values include observations after 
the intercurrent event date and any other missing values) will be imputed as non-
responders, while all missing values for placebo-randomized study participants with a 
missing HiSCR50 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 
bimekizumab 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 odds ratio of bimekizumab versus placebo remains significant is less 
than 0.025 for the particular bimekizumab dose regimen, then no further tipping point 
analyses are needed. 
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If this analysis based on the worst-case scenario results in a p-value that is not significant (eg, 
greater than 0.025), then additional tipping point analyses will be performed to identify. Several 
assumptions will be made about average outcomes among the point at which results switch or 
“tip” from significant to non-significant. Note that subsets of study participants who 
prematurely discontinued study treatment and hence have a monotone missing data pattern 
(O’Kelly, 2014). In practice, it implies different delta adjustments will be made to the assumed 
responses on the monotone missing data in each bimekizumab dose of 
 and 
 will be compared to placebo independently for these analyses. If one dose 
regimen is tested at the 0.05 significance level as determined in Section 4.5, then the with 
various degrees of plausibility with the goal to find for each treatment group the “tipping point” 
that will significantly reverse the primary result that yielded a p-value in this analysis method 
will be 0.05 instead of 0.025 throughout for that dose. In the tipping point analysis, a shift 
parameter or delta adjustment is applied to missing, and subsequently imported primary 
endpoint values (where missing values include observations after the intercurrent event 
and any other missing values). These delta adjustments will be done on the lesion count and 
will be implemented on the primary endpoint as follows: 
10. Data after intercurrent event date (See Section 3.9) will be set to missing. 
11. The same MCMC method described in Section 4.2.2.1 (Step 1a) will be implemented for 
non-monotone (intermittent) missing pattern values, using the same imputation model. 
This will be based on 100 sets of imputations. This will be done only once for each study 
participant to provide a dataset with monotone missing data.  
12. Based on the 100 datasets obtained in Step 2, a monotone regression model will be 
applied (using the same imputation model as in Step 2) as described in Section 4.2.2.1 
(Step 1b).1) while adjusting the imputed values by various delta adjustments. This will be 
based on 1 imputation.  
13. Delta adjustments will be made to imputed lesion count values at Week 16, 
independently in each treatment group as described below. 
14. Delta adjusted imputed values will be truncated so that they are within the range of 
allowable values for each component. 
15. Following the delta adjustments for the individual components lesion counts,of the 
composite endpoint HiSCR50 will then be derived based on the delta-adjusted multiply 
imputed data sets obtained for each component endpoint of interest.  
Several scenarios will be considered to define these shift parameters. Once defined, the same 
shift parameter value will be applied on the imputed endpoint value for all visits. Scenario 1 
will assume that study participants randomized to bimekizumab and who have missing data 
have a lower probability of response compared to study participants randomized to placebo 
with missing data.  
− For endpoints for which high scores are associated with a more favorable outcome, it will 
mean that:  
▪ A negative shift is applied to the imputed value for study participants randomized 
to bimekizumab to decrease the imputed value. 
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▪ A positive shift is applied to the imputed value for study participants randomized 
to placebo to increase the imputed value. 
− For endpoints 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 study participants randomized 
to bimekizumab to decrease the imputed value. 
▪ A negative shift is applied to the imputed value for study participants randomized 
to placebo to increase the imputed value. 
For each continuous variable, a set of possible values will be first pre-defined for the shift 
parameter (example: 0, 1, 2, 3).  
16. Each of the 100 imputed datasets will then be analyzed using a logistic regression model 
with factors of treatment group, , Baseline Hurley Stage, and Baseline antibiotic use. 
17. The results obtained from the 100 logistic regression analyses in Step 7 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.  
18. Steps 4 to 8 will be repeated so that, at each iteration, missing values are adjusted with 
a larger delta than at the previous iteration. Depending on the results obtained, shift 
parameters with more granularity (eg, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9) may also be 
investigated. The process will go on until the p-value for the odds ratio between 
bimekizumab and placebo is no longer statistically significant (eg, ≥ 0.025). The odds ratio, 
97.5% CI (or 95% depending on the significance level being used for testing), and p-
values obtained for each value of delta will be combined in one single table.   
The delta adjustments result in study participants randomized to bimekizumab with 
missing data having a lower probability of response compared to study participants 
randomized to placebo with missing data. Since HiSCR50 response is an endpoint for which 
high lesion counts are associated with a less favorable outcome:  
• A positive adjustment is applied to the imputed value for study participants 
randomized to bimekizumab in order to increase the imputed value and decrease the 
likelihood of response. 
• A negative adjustment is applied to the imputed value for study participants 
randomized to placebo in order to decrease the imputed value and increase the 
likelihood of response. 
To start, imputed values within each values within each lesion type, will be adjusted by the 
same value in each treatment arm. This adjustment will be 5% of the observed range 
within that lesion type. Depending on the results obtained, this adjustment will be 
multiplied for step 9 above (2 times, 3 times the initial adjustment) until the p-value is no 
longer statistically significant. This can be an adjustment of preselected integer values (eg, 1, 2, 
and 3) or adjustments at intervals equal to a percentage of the allowable range of the component 
(eg, 5% of range of 10 to give 0.5, 1, 1.5 etc.). Depending on the results obtained, more granular 
adjustments (eg, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9) may also be implemented to better 
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identify the point at which results "tip". More robust primary analysis results will require larger 
adjustments to tip the results from significant to insignificant. 
Additionally, study participants randomized to bimekizumab with an intercurrent event 
should be set to non-response, after applying the delta adjustment outlined in Step 6 above. 
This ensures study participants randomized to bimekizumab do not have a higher 
probability of response in the tipping point analyses compared to the primary analysis (ie, 
a study participant randomized to bimekizumab who is non-responder in the primary 
analysis cannot become a responder in the tipping point analyses). 
Change #21 
New section was added. 
Rationale for estimand (Section 4.2.3): 
Intercurrent events have been identified within the estimands for this study because their 
potential to impact efficacy assessments linked with the primary and secondary study objectives. 
In order to account for the effect of any observed post-randomization intercurrent events on the 
efficacy analyses, the following estimand strategies will be implemented when evaluating the 
primary and secondary efficacy endpoints: 
• A composite estimand strategy will be used for the primary analysis of the binary secondary 
endpoints (HiSCR50, HiSCR75, flare), 
• A hypothetical estimand will be used for the primary analysis of the continuous secondary 
endpoints (change from Baseline in DLQI total score and in “worst pain” item for the 
HSSDD). 
Change #22 
New section was added. 
Composite estimand (Section 4.2.3.1): 
A composite estimand strategy as defined in Section 8.2.2 allows incorporation of the two 
intercurrent events (eg, receipt of systemic antibiotic rescue medication or discontinuation of 
study treatment due to an AE or lack of efficacy) within the definition of the endpoint. These 
intercurrent events are considered meaningful to the efficacy outcome following receipt of study 
medication. For example, within the proposed composite estimand framework, a randomized 
study participant who discontinues from study treatment due to lack of efficacy prior to Week 16 
will be considered a treatment failure at Week 16 regardless of the lesion count assessment 
performed at that visit. 
The assumptions and robustness of the primary analysis (modified composite estimand as 
defined in Section 8.2.2) will be assessed through the sensitivity analyses defined in 
Section 8.2.3. The impact of intercurrent event handling and data imputation methods on 
endpoint derivation will also be assessed via the analyses of lesion counts and derived HiSCR 
variables as specified in Section 8.4.2.1 and Section 8.4.1.1, respectively. 
Change #23 
New section was added. 
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Hypothetical estimand (Section 4.2.3.2): 
The hypothetical estimand is defined in Section 8.3 and involves a data-driven approach to 
account for the potential impact of intercurrent events (eg, receipt of systemic antibiotic rescue 
medication or discontinuation of study treatment due to an AE or lack of efficacy) on the 
analysis of continuous efficacy endpoints. Under this framework, outcomes for study participants 
without an intercurrent event are analyzed as observed. Conversely, outcomes for study 
participants with an intercurrent event are imputed via a multiple imputation model, ie any 
recorded data on or after the intercurrent event will be set to missing and imputed via multiple 
imputation following the strategy established in Section 4.2.2.1.   
Change #24 
Section 4.2.4 Dates and times 
Partial stop and end date imputation rules were updated: 
• Imputation of Partial Start Dates 
− If only the month and year are specified: 
◦ 
If the month and year of first dose of study medication is the same as the month and 
year of the partial start date, then use the date of first dose of study medication, 
◦ 
Else, if the month and year of the partial start date are the same as the month 
and year of a study medication switch date, then use the date of study 
medication switch, 
◦ 
Otherwise, use the 1st of the month of the partial start date; 
− If only the year is specified: 
◦ 
If the year of first dose of study medication is the same as the year of the partial 
start date, then use the date of first dose of study medication, 
◦ 
Else, if the year of the partial date is the same as the year of a study medication 
switch date, then use the date of study medication switch, 
◦ 
Otherwise, use the 1st of January of the year of the partial start date; 
− If the start date is completely unknown: 
◦ 
If the stop date is unknown or not prior to the date of first dose of study medication, 
then use the date of first dose of study medication, 
◦ 
If the stop date is prior to the date of first dose of study medication, then use the 1st 
of January of the year of the stop date. 
• Imputation of Partial Stop Dates 
− If only the month and year are specified, : 
◦ 
Use the last day of the month of the partial stop date; 
− If only the year is specified  
◦ 
use December 31st of the year of the partial stop date; 
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− If the stop date is completely unknown,  
◦ 
Do not impute the stop date. 
Note that if the stop date or the imputed stop date is prior to the imputed start date, then 
follow the procedure outlined below: 
• If only the year of the start date is specified: 
− If the year of start date is the same as the year of first dose of study medication and 
the imputed stop date is after the date of first dose of study medication, then set the 
start date to the date of first dose of study medication, 
− Otherwise, set the 1st January of the year of the start date; 
• If only the month and year of start date are specified: 
− If the month and year of the start date is the same as the month and year of first 
dose of study medication and the imputed stop date is on or after the date of first 
dose of study medication then set the start date to the date of first dose of study 
medication, 
− If the month and year of the start date is the same as the month and year of first 
dose of study medication and the imputed stop date is before the date of first dose of 
study medication then set the start date to the 1st of the month of partial start date. 
Change #25 
Section 4.6 Use of an efficacy subset of participants 
The section was updated to: 
A sensitivity analysis of the primary endpoint will be performed based on the FAS, the PPS, and 
the CFS. 
Change #26 
Section 4.8 Examination of subgroups 
This section was updated to: 
Subgroup analyses will be performed on the HiSCR50, HiSCR75, and flare endpoints by visit for 
the Initial Treatment Period and Maintenance Treatment Period separately. Additional 
subgroup analyses will be performed on the change from Baseline in the worst pain score 
as measured by HSSDD and in the DLQI total score through Week 16 as described below. 
Along with the tables described, there will be tables for HiSCR50, HiSCR75, and flare which 
display the response difference and 95% CIs between each bimekizumab dose regimen versus 
placebo for each of the subgroups at Week 16. Corresponding forest plots will be prepared.  
The following subgroup variables will be determined using Baseline data, except for analgesic 
use, lesion intervention, and antibody positivity:  
• Age (<40 years, 40 to <65 years, ≥65 years) 
• Gender (male, female) 
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• Disease duration (<median, ≥median) 
The median disease duration will be calculated based on all participants in the analysis set 
used for analysis. 
• Region (North America [Canada, USA], Western Europe [France, Germany, Ireland, Italy, 
Spain, United Kingdom], Central/Eastern Europe [Bulgaria, Czech Republic, Hungary, 
Poland], Asia/Australia [Australia, Israel, Japan]) 
• Weight (≤100 kg, >100 kg) 
• BMI (<25 kg/m2, 25 to <30 kg/m2, ≥30 kg/m2) 
• Race (Black or African American, White, All Other Races [American Indian or Alaska 
Native, Asian, Native Hawaiian or Other Pacific Islander, Other/Mixed]) 
• Systemic antibiotic therapy at randomization (yes, no) 
• Prior biologic therapy for any indication (yes, no) 
• Prior biologic therapy for HS (yes, no) 
• Hurley Stage at Baseline (II or III) 
• Analgesic users (yes, no), separately for the Initial Treatment Period and the Maintenance 
Treatment Period (Section 6.4.2 specifies how participants are classified as analgesic users) 
• Lesion intervention (yes, no), separately for the Initial Treatment Period and the Maintenance 
Treatment Period 
• Antibody positivity (confirmatory assay: negative or positive) 
Any analgesic rescue medication taken during the study, lesion, intervention (including new 
post-Baseline antibiotic use or dose adjustments) and antibody positivity are the only subgroups 
that are not determined by Baseline data. They will be presented in a separate table. 
Subgroup analyses will also be performed by visit The following subgroups for analysison the 
change from Baseline in the worst pain score as measured byHSSDD and in the DLQI total 
score through Week 16. The following subgroups for analysis will be determined based on 
medication use during the Initial Treatment Period:  
• Antihistamines users during the Initial Treatment Period (yes, no) (Section 6.4.2 specifies 
how participants are classified as antihistamine users) 
• Analgesics users during the Initial Treatment Period (yes, no) (Section 6.4.2 specifies how 
participants are classified as analgesic users) 
• Systemic antibiotic therapy start/increase after randomization during the Initial Treatment 
Period (yes, no) 
All summaries will be based on imputed data as appropriate and will include descriptive statistics 
only.  
Change #27 
Section 5. 1 Study participant disposition 
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The following sentence was added: 
Participants are defined as completing the Initial Treatment Period if they have a Week 16 visit, 
or if they fail to attend the Week 16 visit but attend at least one visit in the Maintenance 
Treatment Period. 
The following summaries were also added: 
To assess participant disposition (entry and periods in the study) during the COVID-19 
pandemic, study participant disposition will also be assessed by period of the COVID-19 
pandemic (pre – during – post), by comparing the dates of visits (or events) to the dates of the 
COVID-19 pandemic period. The dates to categorize the periods of the COVID-19 pandemic 
(pre/during/post) are 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 
Change #28 
The following new section was added: 
Impact of COVID-19 (Section 5.2) 
A listing of visits affected by COVID-19 will be presented based on the ES including the visit, 
date of visit, relationship to COVID-19, impact category and a narrative (short description) of the 
event. These data will be summarized for non-randomized participants and by treatment group 
and overall, for enrolled participants. 
A summary of study visits by COVID-19 pandemic period (pre – during – post) will be 
presented for participants enrolled prior to and 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 on the RS will be presented to display missing data as well 
as data collected via an alternative modality (e.g.: phone, video call) for efficacy endpoints 
included in the hierarchy (Section 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. Note that the remote contingencies for COVID-
19 or other exceptional circumstances are not applicable to efficacy assessments and 
documentation (eg, lesion-based assessments, photography) that require direct face-to-face 
physician/participant interaction. 
Change #29 
Section 5.3 Protocol deviations 
The following text has been added:  
A separate summary of participants with protocol deviations related to COVID-19 will be 
provided. 
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A by-participant listing of protocol deviations will be provided. Protocol deviations (eg, missing 
assessments or visits) related to COVID-19 will be listed separately. 
Change #30 
Section 6.2 Other Baseline characteristics 
The last 5 bullets were updated: 
• Duration of disease (<median, ≥median) 
The median disease duration will be calculated based on all participants in the analysis set 
used for the summary. 
• Baseline antibiotic use (yes, no) (According to the randomization strata) 
• Baseline antibiotic use (yes, no) (Derived) 
• Hurley Stage at Baseline (According to the randomization strata) 
• Hurley Stage at Baseline (Derived) 
The following text was added or the additional summaries: 
In addition, the following Baseline disease characteristics will be summarized by the derived 
Baseline Hurley Stage and by the derived Baseline antibiotic use and treatment group for the RS 
Change #31 
Section 6.4 Prior and concomitant medications 
The following sentence was updated: 
Prior medications include any medications that started before prior to the start date of study 
medication. Concomitant medications are any medication that has a start date on or after the 
start date of study medication, or any medication that has a start date on or before the last 
dose of study medication + 28 days (whether placebo or bimekizumab). medications taken at 
least 1 day in common with dosing period.  
 
The following sentence was added: 
Additional summaries for the Initial Treatment Period and Maintenance Treatment Period will be 
presented for participants taking systemic antibiotic medications that qualify as intercurrent 
events as described in Section 3.9.  
Change #32 
Section 8 Efficacy Analyses 
This section was updated: 
All efficacy analyses of primary, and secondary, and other variables will be performed on the 
RS unless otherwise specified.  All efficacy analyses of other efficacy variables will be 
performed on the RS and MS unless otherwise specified.  All efficacy summary tables will be 
displayed by treatment sequence unless otherwise specified.  The primary and secondary 
endpoints, and their components, will also be summarized by the derived Hurley Stage at 
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Baseline (grouping each stage and overall) and treatment sequence and by the derived Baseline 
antibiotic use (yes/no and overall)  and treatment group. 
Change #33 
Section 8.2 Primary efficacy endpoint 
The following rows in Table 8-2 were added or amended: 
Table 8-1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Primary Objective: To evaluate the efficacy of bimekizumab in study participants with moderate to 
severe HS 
HiSCR50 
Sensitivity 
(Section 8.2.3.1) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis 
where the occurrence 
of an intercurrent 
event will be handles 
by evaluating the 
corresponding 
participants as 
nonresponders. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values for 
any other reason will 
also be imputed as 
nonresponders. 
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Table 8-1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.2) 
HiSCR50 
response at 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of 
study treatment due to 
an AE or lack of 
efficacy prior to Week 
16. The intercurrent 
events will be handled 
using a hypothetical 
strategy, whereby all 
data at and after the 
intercurrent event will 
be treated as 
missing.Composite 
strategy, as for the 
primary 
analysis.Composite 
strategy, as for the 
primary analysis. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values will 
be imputed using MI 
– Reference-Based 
Regression under a 
missing not at 
random assumption. 
HiSCR50 
Sensitivity 
(Section 8.2.3.3)   
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategya, as 
for the primary analysis. 
A tipping point 
analysis will be used 
where 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. The 
odds ratio versus 
placebo is based on a 
logistic regression 
for each value of 
delta.  
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Table 8-1: 
Estimand Details and Attributes for Primary Endpoint 
 
 
Estimands for Primary Endpoint 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HiSCR50 
Sensitivity 
(Section 8.2.3.8) 
HiSCR50 
response at 
Week 16 
 
CFS 
Composite strategy, as 
for the primary 
analysis. 
The odds ratio 
versus placebo is 
based on a logistic 
regression, as for 
the primary 
analysis.  
HiSCR50 
Sensitivity 
(Section 8.2.3.9) 
HiSCR50 
response at 
Week 16 
 
RS 
The same two 
intercurrent events 
used for the primary 
analysis will be used. 
Any missing data due 
to COVID-19 will also 
be considered an 
intercurrent event. A 
composite strategy will 
be used, ie, the 
occurrence of an 
intercurrent event will 
be handled by 
evaluating the 
corresponding 
participants as 
treatment failures 
(nonresponders). 
The odds ratio 
versus placebo is 
based on a logistic 
regression, as for 
the primary 
analysis.  
HiSCR50 
Sensitivity 
(Section 8.2.3.10
) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
stratified Cochran-
Mantel-Haenszel 
(CMH) test. Missing 
values not preceded 
by an intercurrent 
event will be 
imputed using MI – 
MCMC/Monotone 
Regression under a 
missing at random 
assumption. 
CFS=Covid-19 Free Set; CMH=Cochran-Mantel-Haenszel; COVID-19=coronavirus disease 2019; FAS=Full 
Analysis Set; HiSCR=Hidradenitis Suppurativa Clinical Response; IES=intercurrent event(s) strategy; 
MCMC=Markov Chain Monte Carlo; MI= multiple imputation; PLS=Population-level summary; Pop=Population; 
PPS=Per-Protocol Set; RS=Randomized Set 
a The composite estimand strategy will be modified in the tipping point analysis such that participants with 
intercurrent events will be treated as nonresponders only in the bimekizumab treatment groups. 
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Change #34 
Section 8.2.2 Primary analysis o the primary efficacy endpoint 
The following text was updated: 
The primary analysis will be based on a logistic regression model including a fixed effect for 
treatment, Hurley stage at Baseline, and Baseline antibiotic use. The odds ratio versus placebo, 
p-value (from Wald test), and 97.5% CI will be calculated. If one dose regimen is tested at 
the 0.05 significance level as determined in Section 4.5, then the confidence interval will be 
95% instead of 97.5% for that dose with a corresponding Zα/2 of1.96 . 
Change #35 
New section was added: 
Analysis on CFS (Section 8.2.3.8) 
The primary efficacy analyses from Section 8.2.2 will be repeated based on the CFS.  
Change #36 
New section was added: 
Analysis including COVID-19 as intercurrent event (Section 8.2.3.9) 
An additional sensitivity analysis will include an additional intercurrent event. The composite 
estimand combines the clinically meaningful improvement from Baseline based on the HiSCR50 
response and completion of study treatment through Week 16 without receiving systemic 
antibiotic rescue medication or discontinuing IMP 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 this sensitivity efficacy analysis:  
5. Population=Study participants meeting the protocol-specified inclusion/exclusion criteria.  
6. Study participant-level outcome=HiSCR50 at Week 16. 
7. Intercurrent event handling=An intercurrent event is defined as receipt of systemic antibiotic 
rescue medication, discontinuation of study treatment due to an AE or lack of efficacy prior 
to Week 16, or missing data due to COVID-19. More information is provided in Section 3.9. 
A composite strategy will be implemented in which a positive clinical outcome is defined as 
achieving HiSCR50 at Week 16 and not receiving systemic antibiotic rescue medication, not 
discontinuing study treatment due to an AE or lack of efficacy through Week 16, and not 
having missing data due to COVID-19. Any missing data at Week 16 that are not preceded 
by an intercurrent event will be imputed using multiple imputation as defined in 
Section 4.2.1. 
8. Population-level summary measure=conditional odds ratio comparing bimekizumab to 
placebo adjusted for stratification factors used in the randomization. 
The same imputation techniques and analysis model as in the primary efficacy analyses will then 
be used. 
Change #37 
Section 8.3 Secondary efficacy endpoints 
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The following text has been added: 
Sensitivity analyses of the secondary endpoints will be performed on the CFS. 
Change #38 
Section 8.3.2 Flare by Week 16 
The following text was deleted: 
Disease flare status will be summarized by treatment group and visit using frequencies and 
percentages. The denominator for the percentage calculations will be the number of participants 
with non-missing data in each treatment group. A bar chart of percentage of subjects with flare, 
by visit and treatment, will be presented. 
In addition, for each participant, the number of flares during the Initial Treatment Period will be 
calculated and summarized by treatment group.  A corresponding histogram summarizing the 
number of flares during the Initial Treatment Period will be presented. 
Change #39 
Section 8.3.3 DLQI Total Score at Week 16 
The following paragraph was updated to: 
Change from Baseline in DLQI total score will be presented by treatment group.  The analysis 
model will be based on an ANCOVA with fixed effects of treatment, Hurley Stage at Baseline, 
Baseline antibiotic use and Baseline value as a covariate. The least square mean (LSM), standard 
error (SE), and 95% CI for the LSM will be presented by treatment group.  For the comparison 
between placebo and bimekizumab: the difference between the LSM, the associated 97.595% CI 
for the contrasts, and the corresponding p-value will be presented. If one dose regimen is 
tested at the 0.05 significance level as determined in Section 4.5, then the confidence 
interval will be 95% instead of 97.5% for that dose with a corresponding Zα/2 of1.96. 
Change #40 
Section 8.3.4 Skin Pain score at Week 16, as assessed by the “worst pain” item in the 
HSSDD 
This section was updated: 
The items on the HSSDD assess patients’ perception of the core symptoms of HS experienced in 
the past 24 hours: pain, smell or odor, drainage or oozing from HS lesions, and itch on an 
11-point numeric rating scale (NRS). Two items assess skin pain: worst skin pain and average 
skin pain.  
Weekly averages will be derived for each of the items of the HSSDD for weeks matching the 
post-Baseline dosing weeks up to Week 16. A weekly average is the sum of the scored item 
over the course of the study week divided by the number of days on which the item was 
completed. The weekly averages will be relative to the respective visit date except for Baseline, 
which will be anchored to the first dose of study drug. A weekly average will only be calculated 
if at least 4 non-missing values (not necessarily consecutive) are available. Otherwise, the 
HSSDD weekly average for the given question will be set to missing.  
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Baseline will be computed as the average from the first 7 consecutive day period in which 
there are at least 4 non-missing entries. That is, first consider the first 7 consecutive days 
prior to the Baseline visit, but not including the Baseline visit day itself. If there are at least 
4 non-missing values (not necessarily consecutive), then the Baseline average will be 
calculated. If there are less than 4 values, the 7 consecutive day period will move one day 
earlier. If there are at least 4 non-missing values (not necessarily consecutive) in that 
period, then the Baseline average will be calculated. This will continue until there are at 
least 4 non-missing values in a 7 consecutive day period in the 14 days prior to Baseline. If 
there is no period in which there are at least 4 non-missing entries, then the Baseline value 
will be set to missing. Baseline will be computed as the average from the 2 weeks prior to 
Baseline, up to and including the data from the Baseline visit. If less than 7 non-missing values 
are available for a given question, the Baseline for the given question will be set to missing. 
Change from Baseline in worst skin pain score is defined as the average Week 16 worst skin pain 
score minus the Baseline worst skin pain score. Missing data imputation described in 
Section 4.2.1.2 will be applied to the weekly averages and not to the individual daily PRO data. 
Change from Baseline in worst skin pain score will be presented by treatment group. The 
analysis model will be based on an ANCOVA with fixed effects of treatment, Hurley Stage at 
Baseline, Baseline antibiotic use, analgesic use (Section 6.4.2) and Baseline value as a covariate. 
A treatment-by-analgesic-use interaction term will also be added to the model and removed if not 
significant.  
The LSM, SE, and 95% CI for the LSM will be presented by treatment group.  For the 
comparison between placebo and bimekizumab, the difference between the LSM, the associated 
97.5 95% CI for the contrasts, and the corresponding p-value will be presented. If one dose 
regimen is tested at the 0.05 significance level as determined in Section 4.5, then the 
confidence interval will be 95% instead of 97.5% for that dose with a corresponding Zα/2 
of1.96. 
Change #41 
Section 8.4.1.2 Time to response of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 
The following text was updated: 
Initial Treatment Period 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) during the Initial 
Treatment Period will each be calculated as: 
Min (Date of first HiSCRxx response, Date of Week 16 visit) – Date of first dose of study 
medication Baseline visit + 1, here xx represents 25, 50, 75, 90, 100 respectively. All visits 
including unscheduled visits are considered. 
Participants who discontinue study treatment without achieving a given HiSCR response prior to 
Week 16 visit will be censored at the date of last lesion count assessment.discontinuation. 
Participants who reach the Week 16 Visit without achieving the given response will be censored 
at the date of the Week 16 Visit. Participants who experience an intercurrent event prior to 
achieving a HiSCR response will be censored at the date of the intercurrent event. Participants 
will be censored at Baseline if there is no Baseline lesion count assessment or no Post-Baseline 
lesion count assessment. 
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The following text was deleted: 
Combined Initial and Maintenance Treatment Period 
An additional time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) during the 
combined Initial and Maintenance Treatment Period will be calculated as above, where the Week 
48 visit is considered instead of Week 16. 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response during the combined 
Initial and Maintenance Treatment Period will each be estimated and presented using the 
Kaplan-Meier product-limit method for each treatment group. These summaries will be limited 
to participants randomized to bimekizumab. 
Kaplan-Meier plots of time to HiSCR responses will be presented by treatment group. In these 
Kaplan-Meier plots, the line will start at 0 (since there are no responders at Week 0) and will 
increase over time, representing time to achieving the response. 
The median time to response, including the 2-sided 95% confidence interval, will be calculated 
for each treatment. 
Maintenance Treatment Period 
For participants randomized to placebo, an additional time to HiSCR25, HiSCR50, HiSCR75, 
HiSCR90, and HiSCR100 (in days) during the Maintenance Treatment Period will be calculated 
as: 
Min (Date of first HiSCRxx response, Date of Week 48 visit) – Date of Week 16 visit + 1, 
here xx represents 25, 50, 75, 90, 100 respectively. All visits including unscheduled visits are 
considered. 
Participants who discontinue study treatment without achieving a given HiSCR response prior to 
Week 48 visit will be censored at the date of discontinuation. Participants who reach the Week 
48 Visit without achieving the given response will be censored at the date of the Week 48 Visit. 
Participants who experience an intercurrent event will be censored at the date of the intercurrent 
event. Participants will be censored at Week 16 if there is no Post-Week 16 lesion count 
assessment. 
Time to HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response during the Maintenance 
Treatment Period will each be estimated and presented using the Kaplan-Meier product-limit 
method for the placebo/bimekizumab
 treatment group.  
The median time to response, including the 2-sided 95% confidence interval, will be calculated 
for each treatment. 
Change #42 
New section was added: 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100 among Week 16 Responders (Section 8.4.1.4) 
See Section 8.4.1.1 for the derivation of HiSCR response. 
Summaries of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders at each visit from Week 
16 through Week 48 will be summarized based on a subset of participants in the MS who 
achieve response at Week 16. The summaries will be as follows: 
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• HiSCR50 responder rate based on participants who achieved HiSCR50 response at Week 16 
• HiSCR75 responder rate based on participants who achieved HiSCR75 response at Week 16 
• HiSCR90 responder rate based on participants who achieved HiSCR90 response at Week 16 
• HiSCR100 responder rate based on participants who achieved HiSCR100 response at Week 16 
Line plots of the above HiSCR responder rate categories over time (from Week 16 to Week 48), 
by treatment group, will be produced. 
Change #43 
Section 8.4.1.5 Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 in 
Week 16 responders 
The following text has been updated: 
See Section 8.4.1.1 for the derivation of HiSCR response. 
Time to loss of response will be based on the MS and include only participants who had the 
corresponding HiSCR response at Week 16 (considering intercurrent event handling from 
the composite estimand described in Section 8.2.2). 
Time to loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 (in days) is defined as: 
Date of loss of response of HiSCR50, HiSCR75, HiSCR90, and HiSCR100 - Date of Week 16 
treatment administration + 1.  
Time to loss of response will be estimated and presented using the Kaplan-Meier product-limit 
method for each treatment. Participants who experience an intercurrent event prior to loss of 
response will be considered as having lost response on the date of intercurrent event. 
Participants who reach the Week 48 Visit without loss of response will be censored at the date of 
the Week 48 Visit. Participants who discontinue treatment or study, for reasons other than those 
already defined for an intercurrent event, and who have not yet displayed loss of response by the 
time of withdrawal, will be censored at the date of the last lesion count assessment withdrawal. 
The summary for each HiSCR response will include only participants who had the corresponding 
HiSCR response at Week 16. 
Change #44 
Section 8.4.1.6 Partial Response 
The following paragraph was updated: 
The number and percentage of participants who are partial responders at Week 16 and become 
HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders in the Maintenance Treatment Period 
will be summarized by treatment group and visit. These analyses will be based on the subset of 
participants in the MS RS that are partial responders but not HiSCR50, HiSCR75, HiSCR90, and 
HiSCR100 responders, respectively, at Week 16. These summaries will be based on observed 
case data and will not consider the occurrence of intercurrent events. 
Change #45 
New section was added: 
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Flare relative to Baseline (Section 8.4.3) 
See Section 8.3.2 for the derivation of flare. 
Disease flare status will be summarized by treatment group and visit using frequencies and 
percentages. The denominator for the percentage calculations will be the number of participants 
with non-missing data in each treatment group. This summary will also include the number of 
participants with any flare in the Initial Period, Maintenance Period, and the combined Initial and 
Maintenance Period. A bar chart of percentage of participants with flare, by visit and treatment, 
will be presented. 
In addition, for each participant, the number of flares during the Initial Treatment Period will be 
calculated and summarized by treatment group. A corresponding histogram summarizing the 
number of flares during the Initial Treatment Period will be presented. 
Change #46 
The following section was deleted: 
Flare by Week 48 (Section 8.4.3) 
See Section 8.2.1 for the derivation of AN count. 
Disease flare by Week 48 is defined when at least a 25% increase in AN count with an absolute 
increase of ≥2 AN relative to Week 16 is observed by Week 48.  A participant’s disease flare 
status (yes/no) will be determined at each visit in the Maintenance Treatment Period using these 
criteria and will be listed with the other lesion count assessment data in the data listings. 
The number of participants who experience at least 1 disease flare by Week 48 will be 
summarized by treatment group. 
Disease flare status during the Maintenance Period will also be summarized by treatment group 
and visit using frequencies and percentages. The denominator for the percentage calculations 
will be the number of participants with non-missing data in the Maintenance Treatment Period in 
each treatment group. A bar chart of percentage of subjects with flare, by visit and treatment, 
will be presented. 
In addition, for each participant, the number of flares during the Maintenance Treatment Period 
will be calculated and summarized by treatment group.  A corresponding histogram summarizing 
the number of flares during the Maintenance Treatment Period will be presented. 
Change #47 
Section 8.4.4 Time to flare by Week 16 
This section was updated as follows: 
See Section 8.3.2 for the derivation of flare by Week. 
Time to flare (in days) during the Initial Treatment Period will each be calculated as: 
Min (Date of first flare, Date of Week 16 visit) – Date of first dose of study medication 
Baseline visit + 1. All visits in the Initial Treatment Period including unscheduled visits are 
considered. 
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Participants who discontinue study treatment without experiencing a flare prior to Week 16 Visit 
will be censored at the date of last lesion count assessment. discontinuation. Participants who 
reach the Week 16 Visit without experiencing a flare will be censored at the date of the the 
Week 16 Visit. Participants who experience an intercurrent event prior to experiencing a flare 
will be treated as experiencing a flare at the date of the intercurrent event. Participants will be 
censored at Baseline if there is no Baseline lesion count assessment or no Post-Baseline lesion 
count assessment. 
Time to flare will be estimated and presented using the Kaplan-Meier product-limit method for 
each treatment group.  
Kaplan-Meier plots of time to flare will be presented by treatment group. In these Kaplan-Meier 
plots, the line will start at 0 and will increase over time, representing time to achieving the 
response. 
The median time to flare response, including the 2-sided 95% confidence interval, will be 
calculated for each treatment. Comparisons of bimekizumab vs placebo will be analyzed using a 
log-rank test stratified by Hurley Stage at Baseline and Baseline antibiotic use. 
Change #48 
Section 8.4.5 Time to flare by Week 48 
This section was updated as follows: 
See Section 8.3.2 for the derivation of flare relative to Baseline by Week 48. 
Maintenance Treatment Period 
Time to flare (in days) during the Maintenance Treatment Period will each be calculated as: 
Min (Date of first flare, Date of Week 48 visit) – Date of Week 16 visit + 1. All visits in the 
Maintenance Treatment Period including unscheduled visits are considered. 
Participants who discontinue study treatment without experiencing a flare prior to Week 48 visit 
will be censored at the date of discontinuation. Participants who reach the Week 48 Visit without 
experiencing a flare will be censored at the date of the Week 48 Visit. Participants who 
experience an intercurrent event will be treated as experiencing a flare at the date of the 
intercurrent event. Participants will be censored at Week 16 if there is no Baseline lesion count 
assessment or no Post-Week 16 lesion count assessment. 
Time to flare will each be estimated and presented using the Kaplan-Meier product-limit method 
for each treatment group.  
Kaplan-Meier plots of time to flare will be presented by treatment group. In these Kaplan-Meier 
plots, the line will start at 0 and will increase over time, representing time to achieving the 
response. 
The median time to response, including the 2-sided 95% confidence interval, will be calculated 
for each treatment.  
Combined Initial and Maintenance Treatment Period 
Time to flare (in days) during the combined Initial and Maintenance Treatment Period will be 
calculated as: 
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Min (Date of first flare, Date of Week 48 visit) – Date of first dose of study medication 
Baseline visit + 1. All visits in the up to Week 48 including unscheduled visits are 
considered. 
Flare will be defined relative to the Baseline visit. Participants who discontinue study treatment 
without experiencing a flare prior to Week 48 visit will be censored at the date of last lesion 
count assessment. discontinuation. Participants who reach the Week 48 Visit without 
experiencing a flare will be censored at the date of the Week 48 Visit. Participants who 
experience an intercurrent event prior to experiencing a flare will be treated as experiencing a 
flare at the date of the intercurrent event. Participants will be censored at Baseline if there is no 
Baseline lesion count assessment or no Post-Baseline lesion count assessment. 
Time to flare will each be estimated and presented using the Kaplan-Meier product-limit method 
for each treatment group. This summary will be limited to participants randomized to 
bimekizumab. 
Kaplan-Meier plots of time to flare will be presented by treatment group. In these Kaplan-Meier 
plots, the line will start at 0 and will increase over time, representing time to achieving the 
response. 
The median time to flare response, including the 2-sided 95% confidence interval, will be 
calculated for each treatment.  
Change #49 
Section 8.4.6 International Hidradenitis Suppurativa Severity Score System (IHS4) 
The following sentence was added: 
The observed IHS4 score, change and percentage change from Baseline will be summarized by 
treatment group and visit. Missing IHS4 scores will be imputed using the multiple imputation 
procedure specified in Section 4.2.2.1, where IHS4 scores will be derived based on the 
imputed lesion counts.  
Change #50 
Section 8.4.10 Time to initiation of systemic rescue therapy in the Initial Treatment Period 
The following text was updated: 
See Section 3.9 for the definition of a systemic antibiotic rescue therapy. 
Time to initiation of systemic rescue therapy (in days) during the Initial Treatment Period will be 
calculated as: 
Min (Date of initiation of rescue therapy, Date of change in the dose/type of current 
antibiotic, Date of Week 16 visit) – Date of first dose of study medication Baseline visit + 
1.  
Participants who discontinue the study treatment without initiating systemic rescue therapy prior 
to Week 16 visit will be censored at the date of discontinuation. Participants who reach the Week 
16 Visit without initiating systemic rescue therapy will be censored at the date of the Week 16 
Visit. Participants will be censored at Baseline if there is no Baseline lesion count assessment or 
no Post-Baseline visit lesion count assessment. 
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Change #51 
Section 8.4.11 Time to an intercurrent event in the Initial Treatment Period 
The following text was updated: 
See Section 3.9 for the definition of an intercurrent event. 
Time to an intercurrent event (in days) during the Initial Treatment Period will be calculated as: 
Min (Date of intercurrent event initiation of rescue therapy, Date of change in the dose/type 
of current antibiotic, Date of withdrawal due to AE or lack of efficacy, Date of Week 16 
visit) – Date of first dose of study medication Baseline visit + 1.  
Participants who discontinue the study treatment without experiencing an intercurrent event 
prior to Week 16 visit will be censored at the date of discontinuation. That includes 
participants who discontinue from the study for reasons other than Adverse Event and 
Lack of Efficacy. Participants who reach the Week 16 Visit without experiencing an intercurrent 
event will be censored at the date of the Week 16 Visit. Participants will be censored at Baseline 
if there is no Baseline lesion count assessment or no Post-Baseline visit lesion count assessment. 
Change #51 
Section 8.4.12 Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) 
The following sentence was updated: 
Change from Baseline in Worst Pain score and Worst Itch score at Week 16 will additionally 
be summarized by visit and by analgesic and antihistamine use status (Section 6.4.2), 
respectively. 
Change #53 
Section 8.4.13 Hidradenitis Suppurativa Symptom Questionnaire (HSSQ) 
The following text was updated: 
HSSQ response for pain item score is defined as at least a 30% reduction and at least a 1-unit 
reduction from Baseline in HSSQ among study participants with a score of ≥3 at Baseline. 
The number and percentage of responders for pain item score will be summarized by treatment 
group and visit based on the MS. 
The number and percentage of participants who were responders at any timepoint in the 
Maintenance Treatment Period will be summarized by treatment group for the skin pain score 
based on the MS. 
Change from Baseline in pain score and itch score will additionally be summarized by visit 
and by analgesic and antihistamine use status (Section 6.4.2), respectively. 
Change #54 
Section 8.4.15 Hidradenitis Suppurativa Quality of Life (HiSQOL) 
The following text was updated: 
Summary statistics of the actual values and change from Baseline values will be used to 
summarize HiSQOL domain and total scores for each visit by treatment group. The table will 
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display descriptive statistics for the Baseline, followed by descriptive statistics for the change 
from Baseline for all visits. 
Missing data for the continuous change from Baseline will be handled by using MI via the 
MCMC and monotone regression method specified in Section 4.2.1.3. The imputed HiSQOL 
total score will be derived based on the imputed subscales. 
The number and percentage of participants that complete the HiSQOL will be calculated for each 
visit by treatment group.  The percentage will be based on the number of participants in the RS 
(or MS, as appropriate).  The summary will be repeated where the percentage is based on the 
subset of participants who complete each particular visit. 
A by-participant listing of the HiSQOL questionnaire, HiSQOL responses, domain and total 
scores and change from Baseline will be provided. 
Change #55 
Section 9.1 Pharmacokinetics 
The following sentence was updated: 
All However, all PK concentrations collected will be listed irrespective of the dosing or 
sampling occurring out of window.  
Change #56 
Section 8.2.3.1 Derivation of palmoplantar IGA response 
Anti-bimekizumab antibodies (ADAb) will be measured using a 3-tiered assay approach: 
screening assay, confirmatory assay, and titration assay. Samples confirmed as positive within 
the confirmatory assay will be further evaluated for the presence of in a neutralizing anti-assay 
to evaluate the potential of the ADAb to neutralize the activity of bimekizumab antibodies 
specific to IL-17AA, IL-17FF(IL17A or IL17F, or both) in-vitro. Samples will be taken at 
Baseline, then at study Weeks 4, 8, 12, 16, 20, 24, 36 and 48, and at PEOT and SFU timepoints.  
The screening Screening, confirmatory, and titer cut point will be used to determine points of 
the status of anti-bimekizumab antibodies in respective assays will be determined by the test 
sample as Positive Screen (PS) or Negative Screen (NS). For bioanalytical laboratory based 
either on commercially available drug-naïve samples presenting anti-bimekizumab antibody 
levels that are PS, a further confirmatory assay will be performed, and the result of which 
will be reported as either Positive Immunodepletion (PI) or Negative Immunodepletion 
(NI).  
ADAb status for each sample will be derived as follows: 
• Sample values that are either NS, or PS and NI and where the bimekizumab 
concentration is less than the validated ADAb assay drug tolerance limit will be defined 
as anti-bimekizumab antibody negative. 
• Sample values that are either NS, or PS and NI and where the bimekizumab 
concentration exceeds the validated ADAb assay drug tolerance limit will be defined as 
inconclusive.  
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• Sample values that are PS and PI will be defined as ADAb positive (regardless of 
availability of a titer value) 
• Missing or non-evaluable samples will be defined as missing 
Positive immunodepletion samples will be titrated, and the ADAb titer (reciprocal dilution 
factor including minimum required dilution) will be reported. Subsequently, PI samples 
will also be subject to a neutralizing assay to evaluate the potential of ADAb to neutralize 
the target binding of bimekizumab (IL-17AA or IL-17FFIL17F or both) in vitro. 
The following definitions will be applied regarding ADAb status of each test samples: 
• An ADAb status will be confirmed as positive for any sample with an ADAb level that is 
positive screen and positive immunodepletion. 
• An ADAb status of negative will be concluded for any sample with an ADAb level that is 
either negative screen or (positive screen and negative immunodepletion). 
If the titer for an ADAb level that is positive screen and positive immunodepletion is missing, 
then a conservative approach will be used and ADAb status will be consider as positive. No 
imputation rules apply for the missing titer. If the ADAb level is positive screen but no 
confirmatory result could be determined, then a conservative approach will be used and ADAb 
status will be consider as positive. 
Anomalous values will be not included in summaries/analysis and will be reviewed and flagged.  
by the Clinical Pharmacologist. 
There are different levels of classification for ADAb status, the definitions are as follows: 
For each participant an overall ADAb status will be derived:  
• Overall Positive is defined as having at least one value that is confirmed positive during the 
treatment period.  
• Overall Negative is defined as having no values that are confirmed positive at any time in the 
treatment period.  
The treatment period does not include Baseline/pre-treatment samples or SFU. 
Furthermore, the following subcategories for each subject will be derived: 
• Pre ADAb negative – treatment-emergent ADAb negative (Category 1): Includes study 
participants who are anti-bimekizumab antibody negative at Baseline and anti-
bimekizumab antibody negative at all sampling points during the period of interest (one 
post-Baseline missing/inconclusive sample is allowed for subjects with pre- anti-
bimekizumab antibody negative sample). This group also includes study participants 
who have a missing or inconclusive sample (either missing or inconclusive or 
insufficient volume) at Baseline (ie, pre-treatment) with all post-Baseline samples as 
ADAb negative. 
• Pre ADAb negative – treatment-emergent ADAb positive (Category 2): Includes study 
participants who are ADAb negative at Baseline and ADAb positive at any sampling 
points post-Baseline during the period of interest. This group also includes study 
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participants who have a missing sample (either missing or insufficient volume) at 
Baseline (ie, pre-treatment) with 1 or more post-Baseline samples as ADAb positive. 
• Pre ADAb positive – treatment-emergent reduced ADAb (Category 3): Includes study 
participants who are ADAb positive at Baseline, and ADAb negative at all sampling 
points post-Baseline during the period of interest. 
• Pre ADAb positive – treatment-emergent unaffected ADAb positive (Category 4): 
Includes study participants who are ADAb positive at Baseline and are ADAb positive 
at any sampling point post-Baseline during the period of interest with titer values of the 
same magnitude as Baseline (ie, less than a predefined fold difference from the Baseline 
titer). 
• For this analysis, this is set at an increase of less than the validated Minimum 
Significant Ratio (MSR) of 2.07-fold from Baseline.  
• Pre ADAb positive – treatment-emergent ADAb boosted positive (Category 5): Includes 
study participants who ADAb positive at Baseline and are ADAb positive at any 
sampling point post-Baseline during the period of interest with increased titer values 
compared to Baseline (equal to or greater than a predefined fold difference increase 
from Baseline titer which will be defined within the validation of the assay). 
− For this analysis, this is set at an increase equal to or greater than the validated 
MSR of 2.07-fold from Baseline.  
− Note: for any study participant who is ADAb positive at Baseline and ADAb positive 
at a post-Baseline time point during the period of interest, but for whom titers are 
not available to determine treatment unaffected or treatment boosted status, the 
study participant will be considered as treatment boosted, assuming no other 
samples are available. 
• ADAb Inconclusive (Category 6): Includes study participants who have an ADAb 
positive Baseline (pre-treatment) sample and some post-Baseline samples during the 
period of interest are missing or inconclusive, while other post-Baseline samples are 
ADAb negative. 
• Total treatment-emergent ADAb positivity (Category 7 [Categories 2 and 5 combined]): 
Includes study participants who are pre ADAb negative – treatment-emergent ADAb 
positive (Category 2) and pre ADAb positive – treatment boosted ADAb positive 
(Category 5).  
• Total prevalence of pre- ADAb positivity (Category 8 [Categories 3, 4, 5 and 6 
combined]): Study participants that are tested ADAb positive at Baseline. 
• Missing: Includes study participants who are ADAb negative, missing, or inconclusive 
at Baseline with some post-Baseline samples as missing or inconclusive, and other 
samples as ADAb negative. 
Derivation for above classification will be different for the interim analysis and the final 
analysis. SFU data will be considered only for the final data analysis. That is, each instance of 
“excluding SFU” in the categories above, should be changed to “including SFU.”  
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In the case that a sample is collected 1 or more days following the scheduled visit date in which 
the drug was administered, the ADAb anti-bimekizumab antibody results for that sample will be 
associated with the scheduled visit and summarized accordingly. Such samples will also be 
considered when ADAb anti-bimekizumab antibody results are summarized over a given study 
period.   
Analysis 
Immunogenicity will be assessed through summary tables and figures, and listing of individual 
results by participants. All analyses will be run on the AMS Active Medication Set, unless 
specified otherwise. 
• Summary of ADAb anti-bimekizumab antibody status overall and by each visit separated by 
treatment group 
• Summary of the time-point of the first occurrence of ADAb anti-bimekizumab antibody 
positivity during the treatment period by treatment group. A plot of the titer by time to first 
ADAb anti-bimekizumab antibody positivity will be prepared. 
• All individual participant-level ADAb anti-bimekizumab antibody results will be listed. 
• The number and percentage of participants in each of the 8 ADAb anti-bimekizumab 
antibody categories during the treatment period by treatment group., with an additional 
category combining participants in categories 2 and 5, summarized as total treatment 
emergent. In addition, the count and percentage of participants who are pre anti-
bimekizumab positive will be calculated (this is the sum of categories 3, 4, and 5). 
• The prevalence of immunogenicity, separated by treatment group, and defined subcategory, 
will be reported by visit, defined as (cumulative) proportion of participants having confirmed 
positive ADAb anti-bimekizumab antibody samples at any visit up to and including that visit. 
Missing samples will not be included in the denominator. 
• The time to achieving treatment-emergent ADAb anti-bimekizumab antibody positivity, 
separated by treatment group and defined subcategory sub-categories 2 & 5 above, will be 
analyzed based on Kaplan-Meier methods. Participants will be considered to have an event at 
the time point at which treatment emergent ADAb anti-bimekizumab antibody positive is 
first achieved (taking the MSR into consideration for sub-category 5). Participants classified 
as treatment-emergent ADAb anti-bimekizumab antibody negative will be censored at the 
time of the last available ADAb anti-bimekizumab antibody result. 
• A summary of HiSCR50 responders at Week 16, separated by treatment group, as a function 
of ADAb titer will be presented graphically. This will be repeated for HiSCR75 responders. 
• Individual plots of plasma bimekizumab concentrations/ ADAb anti-bimekizumab antibody 
titer both plotted on the Y-axes by visit (x-axis) for the full treatment period (excluding SFU 
for interim analyses and including SFU for final analyses) will be presented for participants 
with and without HiSCR50 response at Week 16. 
• Spaghetti plots of ADAb titer (y-axis) by visit (x-axis), separated by treatment group for all 
ADAb anti-bimekizumab antibody positive participants, including Baseline positive 
participants. 
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• Box plots of ADAb titer (logscale) by time to first ADAb positivity by treatment group. 
For purposes of efficacy subgroup analyses based on anti-bimekizumab antibody status, 2 
categories will be used:  
• ADAb Anti-bimekizumab antibody positive – This is defined as participants who have 
ADAb anti-bimekizumab antibody levels above the specified cut point on at least 2 time 
points while on treatment (ie, excluding Baseline, excluding SFU).  
• ADAb Anti-bimekizumab antibody negative – Participants who are not defined as anti-
bimekizumab positive (as described above) will be defined as ADAb anti-bimekizumab 
antibody negative.  
The groups for defining ADAb anti-bimekizumab antibody status for safety subgroup analyses 
are as follows:  
• AEs starting before first ADAb anti-bimekizumab antibody positive result 
• AEs starting on or after first ADAb anti-bimekizumab antibody positive result 
• AEs for participants who were always ADAb anti-bimekizumab antibody negative  
Change #57 
Section 10.1.1 Exposure during the Initial Treatment Period 
This section was split into 2 subsection 10.1.1.1 and 10.1.1.2 for exposure duration (days) and 
time at risk (days), respectively. 
Change #58 
Section 10.1.1.1 Study medication duration (days) 
The following text was updated: 
Definitions for study medication duration (days) are provided as follows: 
• Date of last dose in the Initial Treatment Period – Date of first dose in the Initial Period + 
 
. 
Note: The use of 
 assumes a 
 dosing interval (bimekizumab 
 and 
placebo). For participants randomized to bimekizumab 
, this will be adjusted based 
on the dosing interval (eg, use Date of last bimekizumab dose in the Initial Treatment Period – 
Date of first dose in the Initial Period + 
). 
Note: If date of last dose in the Initial Treatment Period + 
 (or date of last bimekizumab 
dose in the Initial Treatment Period + 
 in the case of 
 dosing) extends to a date 
beyond the date of first dose in the Maintenance Treatment Period, then this calculation reverts 
to:  
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Treatment Period + 1.  
Change #59 
Section 10.1.1.2 Time at risk (days) 
The section was updated: 
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Definitions for time at risk (days) are provided as follows: 
For participants s who permanently discontinue study treatment: 
• Date of last dose– date of first dose + 
  
The use of 
 assumes a 
 dosing interval. For participants randomized to bimekizumab 
 this will be adjusted based on the dosing interval (eg, use Date of last 
bimekizumab dose in the Initial Treatment Period – date of first dose in the Initial Period +
 
 
Note: If date of last dose 
 (or date of last dose of bimekizumab + 
 for 
 
dosing) extends to a date beyond the final visit date (including PEOT, but not including SFU), 
then this calculation reverts to:  
− Final visit date (including PEOT, but not including SFU) – date of first dose + 1.  
Time at risk (days) 
• For participants who complete the Week 16 visit and continue to the Maintenance Treatment 
Period:  
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Period + 1. 
• For participants who discontinue on or prior to the final visit of the Initial Period, use the 
minimum of the following:  
− Date of last dose in the Initial Treatment Period – Date of first dose in the Initial 
Treatment Period + 141 
− The total number of days in the Initial Treatment Period (112 days). For AEs that 
emerged after 112 days but still within the 140 days window, those AEs would be 
classified as TEAE, but will be excluded from the output based on the Initial Treatment 
Period. However, these AEs will be included in the AE summaries for Maintenance 
Treatment Period. 
− Date of last clinical contact – Date of first dose in the Initial Treatment Period + 1.  
• For participants who die prior to the final visit of the Initial Treatment Period: Date of death 
– date of first dose in the Initial Period +1. 
Change #60 
Section 10.1.2 Exposure during the Maintenance Treatment Period 
This section was split into 2 subsection 10.1.2.1 and 10.1.2.2 for exposure duration (days) and 
time at risk (days), respectively. 
Change #61 
Section 10.1.2.1 Study medication duration (days) 
The section was updated: 
Definitions for study medication duration (days) are provided as follows: 
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• Date of last dose in the Maintenance Treatment Period – date of first dose in the Maintenance 
Treatment Period + 
  
The use of 
 assumes a 
 dosing interval. For participants randomized to bimekizumab 
 in the Maintenance Treatment Period, this will be adjusted based on the dosing 
interval (eg, use Date of last bimekizumab dose in the Maintenance Treatment Period – date of 
first dose in the Maintenance Treatment Period + 
 
Note: If date of last dose in the Maintenance Treatment Period + 
 (or date of last 
bimekizumab dose in the Maintenance Treatment Period + 
 in the case of 
 dosing) 
extends to a date beyond the final visit date of the Maintenance Treatment Period (not including 
SFU), then this calculation reverts to:  
− Final visit date of the Maintenance Treatment Period (not including SFU) – date of first 
dose in the Maintenance Treatment Period + 1.  
• Note: For participants who die during the Maintenance Treatment Period, then this 
calculation reverts to:  
− Date of death – Date of first dose in the Maintenance Treatment Period + 1. 
For participants who permanently discontinue study treatment: 
• Date of last dose– date of first dose + 
  
The use of 
 assumes a 
 dosing interval. For participants randomized to bimekizumab 
 in the Maintenance Treatment Period, this will be adjusted based on the dosing 
interval (eg, use Date of last bimekizumab dose in the Maintenance Treatment Period – date of 
first dose in the Maintenance Treatment Period + 
). 
Note: If date of last dose + 
 (or date of last dose of bimekizumab + 
 for 
 
dosing) days extends to a date beyond the final visit date (including PEOT, but not including 
SFU), then this calculation reverts to:  
− Final visit date (including PEOT, but not including SFU) – date of first dose + 1. 
Change #62 
Section 10.1.2.2 Time at risk (days) 
The text was updated: 
Definitions for time at risk (days) are provided as follows: 
• For participants who complete the Maintenance Treatment Period as planned and continue 
into an extension study (and, therefore, do not have the SFU visit in the feeder study): Final 
visit date of the Maintenance Treatment Period – date of first dose in the Maintenance 
Treatment Period + 1. 
− Date of last visit of the Maintenance Treatment Period – Date of first dose in the 
Maintenance Treatment Period + 1. 
• For participants who die prior to the final visit of the Maintenance Treatment Period: Date of 
death – date of first dose in the Maintenance Period + 1. 
− Date of death – Date of first dose in the Maintenance Period + 1. 
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• For all other participants, use the minimum of the following:  
o Date of last dose in the Maintenance Treatment Period – Date of first dose in the 
Maintenance Treatment Period + 141140 days. 
Change #63 
Section 10.1.3 Exposure during the Initial and Maintenance Treatment Period 
This section was split into 2 subsection 10.1.3.1 and 10.1.3.2 for exposure duration (days) and 
time at risk (days), respectively. 
Change #64 
Section 10.1.3.1 Study medication duration (days) 
The section was updated: 
Definitions for study medication duration (days) are provided as follows: 
• Sum of study medication durations from the individual Initial and Maintenance 
Treatment Period. 
Note: The algorithms for calculating these durations are specified in Section 10.1.1.1 and 
Section 10.1.2.1. 
Note: If date of last dose in the Initial Treatment Period + 
 (or + 
 in the case 
of 
 dosing) extends to a date beyond the date of first dose in the Maintenance 
Treatment Period, then this calculation reverts to:  
− Sum of study medication durations from the individual Initial and Maintenance 
Treatment Periods - 1.  
For participants who do not switch study treatments: 
• Date of last dose – Date of first dose + 
  
The use of 
 assumes a 
dosing interval. For participants randomized to bimekizumab 
 this will be adjusted based on the dosing interval (eg, use Date of last 
bimekizumab dose – date of first dose + 
). 
Note: If date of last dose + 
 (or date of last bimekizumab dose in the Maintenance 
Treatment Period + 
 in the case of 
dosing) extends to a date beyond the final visit 
date (including PEOT, not including SFU), then this calculation reverts to:  
− Final visit date (including PEOT, not including SFU) – Date of first dose + 1.  
• For participants who die, if date of last dose + 
 (or + 
 in the case of 
 
dosing) extends to a date beyond the date of death, then this calculation reverts to:  
− Date of death – Date of first dose + 1. 
For participants who switch study treatments (between Initial and Maintenance Treatment 
Periods): 
• Initial Treatment Period (attributed to initially randomized treatment): 
− Date of last dose in the Initial Period – Date of first dose in the Initial Period + 
  
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Note: Participants who switch study treatments are on a
 dosing schedule for the Initial 
Treatment Period. 
Note: If date of last dose in the Initial Treatment Period + 
 extends to a date beyond the 
date of first dose in the Maintenance Treatment Period, then this calculation reverts to:  
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Period + 1.  
• Maintenance Treatment Period (attributed to the treatment initiated in the Maintenance 
Treatment Period): 
− Use the study medication duration algorithm specified for the Maintenance Treatment 
Period in Section 10.1.2.1. 
Change #65 
Section 10.1.3.2 Time at risk (days) 
This section was updated: 
For participants who do not switch study treatments: Definitions for time at risk (days) are 
provided as follows: 
• For participants who complete the Maintenance Treatment Period as planned and continue 
into an extension study (and, therefore, do not have the SFU visit in the feeder study):  
− Final visit date – Date of first dose + 1. 
• For participants who die prior to the final visit:  
− Date of death – Date of first dose in the + 1. 
• For all other participants, use the minimum of the following:  
− Date of last dose – Date of first dose + 141 days. 
− Date of last clinical contact – Date of first dose + 1.  
Note: This group could include participants who discontinue early, participants who 
complete the Maintenance Treatment Period as scheduled but choose not to continue into an 
extension study, or participants who are ongoing in the SFU period at the time of the data 
snapshot (in the case of the interim analysis). 
For participants who switch study treatments (between Initial and Maintenance Treatment 
Periods): 
• Initial Treatment Period (attributed to initially randomized treatment): 
− Date of first dose in the Maintenance Treatment Period – Date of first dose in the Initial 
Period + 1.  
(Note: This assumes that anyone in this category has completed the Initial Treatment 
Period and doses [with a new study treatment] in the Maintenance Treatment Period.) 
• Maintenance Treatment Period (attributed to the treatment initiated in the Maintenance 
Treatment Period): 
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− Use the time at risk algorithm specified for the Maintenance Treatment Period in 
Section 10.1.2.2. 
Change #66 
Section 10.2.1 Data considerations 
The following sentence was added: 
If the intensity of an AE is unknown, it is considered as severe. If the relationship to study drug 
is missing, it is considered as related. Note that if the seriousness of an adverse event is 
unknown, every attempt should be made to resolve this prior to a snapshot for an interim 
analysis or database lock; in the exceptional case that the seriousness of an adverse event is 
still missing then no imputation should be applied for this characteristic. 
Change #67 
Section 10.2.2 AE summaries 
The following text was deleted: 
The following summaries will be provided by treatment group for the Initial Treatment Period, 
Maintenance Treatment Period, and the Initial and Maintenance Treatment Period combined 
based on the SS, MS, and AMS respectively. 
The following summaries were added: 
• Incidence of TEAEs – Suspected and Confirmed COVID-19 cases by SOC, HLT and PT 
Suspected and confirmed COVID-19 cases will be identified with the preferred terms “Corona 
virus infection” or “Corona virus test positive”. 
The following subset of tables will also be presented for the Maintenance Treatment Period using 
the MS: 
• Incidence of TEAEs – Overview 
• Incidence of TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of Serious TEAEs per 100 subject years by SOC, HLT, and PT  
• Incidence of TEAEs Leading to Discontinuation per 100 subject years by SOC, HLT, and PT  
• Incidence of TEAEs Leading to Death by SOC, HLT, and PT  
Change #68 
Section 10.2.3.1 Infections (serious, opportunistic, fungal and TB) 
The following text was updated: 
• Incidence of Fungal Infection TEAEs per 100 subject years by SOC, HLT and PT 
Fungal infections will be summarized in a stand-alone table. The table will include all 
TEAEs (serious and non-serious) that code into the High Level Group Term (HLGT) HLT 
“Fungal infectious disorders” 
• Incidence of Opportunistic Infection TEAEs per 100 subject years by SOC, HLT and 
PT  
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Opportunistic infections (including tuberculosis) will be summarized in a stand-alone table. 
The table will include all TEAEs identified using UCB-defined search criteria.(refer to Excel 
spreadsheet on “OI - MedDRA v19.0.xlsx” in “Bimekizumab-Safety-Topics-of-
Interest.docx”). 
Change #69 
Section 10.2.3.3 Major adverse cardiac event 
The following sentence was added: 
A separate table and listing will present the adjudicated cardiovascular events by type. For each 
cardiovascular event type (24 total), the individual PTs that fall within each event type will be 
summarized. The other 10 MACE events not listed in the table are described in the 
adjudication committee charter.   
Change #70 
Section 10.2.3.5 Suicidal ideation and behaviors 
The following paragraph was added: 
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. 
Change #71 
Section 10.2.3.6 Inflammatory bowel disease 
This section was updated: 
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 
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• 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 
• Event Type Code 99: Not enough information to adjudicate 
A table for adjudicated definite IBD events (event type codes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 
14, 15 and 169) 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 produced overall, as well as 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 History of IBD Extra-Articular Assessment 
at Screening CRF page ("Does subject have a history of IBD?”). 
A separate table will present the for adjudicated gastrointestinal probable IBD 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 codes 2, 5, and 8) as determined by the 
adjudication committee as definite IBD probable IBD and will be produced. This table will 
be produced overall, as well as stratified by participants with or without a previous medical 
history of IBD. 
A table for adjudicated possible IBD. It events (event type codes 1, 4, and 7) as determined by 
the adjudication committee will be produced. This table will also include events determined as 
Symptoms not consistent with be produced overall, as well as stratified by participants with or 
without a previous medical history of 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 separate table and listing will present the adjudicated IBD events by type. For each IBD event 
type (event type codes 1 through 1610 and 99; 1711 total), the individual PTs which fall within 
each event type will be listedsummarized.  
A third listing will present the individual diagnostic criteria met for each adjudicated IBD event. 
Change #72 
Section 10.2.3.7 Hypersensitivity (including anaphylaxis) 
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The following text was updated: 
A separate table will be prepared to summarize hypersensitivity events, identified using the SMQ 
“Hypersensitivity (SMQ)”. All TEAEs which code to a PT included in the Scope=Narrow search 
will be included in this table. 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 separate table will be prepared to summarized injection site reactions, 
identified using the HLTs: “Administration site reactions NEC” and “Injection site reactions”. 
Change #73 
Section 10.3 Clinical laboratory evaluations 
The following text was added: 
For tables where data are summarized by visit, unscheduled and repeat visits will not be 
summarized, but these data will be included in listings. For tables where multiple measurements 
over a period of time are considered (as in shift tables), unscheduled and repeat visits will be 
considered as long as they were collected in the period being summarized (values observed 
more than 140 days after the last administration of study medication are not considered). 
All summaries will be presented in SI units and will be based on observed case values. 
CTCAE grading was updated: 
Markedly abnormal values are defined as those with a severity of Grade 3 and above based on 
the CTCAE criteria Version 4.03.(U.S. Department of Health and Human Services 2017).  
And Table 10-2 was updated: 
Table 10‒2: Definitions of Markedly Abnormal Biochemistry Values 
 
Parameter name 
Conventional 
Standard 
Abnormal 
Designation 
Unit 
Criteria 
Unit 
Criteria 
Creatinine1Creatinine 
mg/dL 
> 3.0 x 
Baseline or 
>3.0 x ULN 
umolmmo
l/L 
> 3.0 x 
Baseline or 
>3.0 x ULN 
AH 
Glucose 
mg/dL 
<40 
>250 
mmol/L 
<1.7 
>13.9 
AL 
AH 
Calcium 
mg/dL 
>12.5 
<7.0 
mmol/L 
>3.1 
<1.75 
AH 
AL 
Magnesium 
mg/dL 
>3.0 
<0.9 
mmol/L 
>1.23 
<0.4 
AH 
AL 
Potassium 
mmol/L 
>6.0 
<3.0 
mmol/L 
>6.0 
<3.0 
AH 
AL 
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Table 10‒2: Definitions of Markedly Abnormal Biochemistry Values 
 
Parameter name 
Conventional 
Standard 
Abnormal 
Designation 
Unit 
Criteria 
Unit 
Criteria 
Sodium 
mmol/L 
>155 
<130 
mmol/L 
>155 
<130 
AH 
AL 
Cholesterol 
mg/dL 
>400 
mmol/L 
>10.34 
AH 
1 The markedly abnormal definitions for creatinine are based on the logical or, if either criterion is met the 
creatinine value will be designated as abnormal high. 
And the following text was added: 
• Total Bilirubin: >1.5xULN, >2xULN  
• ALP: >1.5xULN 
For any participant with at least one markedly abnormal LFT (AST >3xULN, ALT 
>3xULN, bilirubin >3xULN, or ALP >1.5xULN) the New Ratio (nR) will be calculated as 
the ratio of either ALT or AST (whichever is higher) to ALP, all expressed as multiples of 
their ULN as follows: 
• nR = [maximum(AST/ULN or ALT/ULN)]/(ALP/ULN) 
Any pDILI will be summarized (all criteria must be met at the same assessment): 
• (AST or ALT > 3xULN) and Total Bilirubin > 1.5xULN 
• (AST or ALT > 3xULN) and Total Bilirubin > 2xULN   
In addition, a table will be produced to summarize potential Hy’s Law cases. The following 
definition will be used in that table: 
•  [AST ≥3xULN or ALT ≥3xULN] and Total Bilirubin ≥2xULN in the absence of ALP 
≥2xULN  
In order to meet the above potential Hy’s Law criteria, a participant must experience the 
elevation in bilirubin and ALT or AST (and the absence of ALP elevation, if applicable) at the 
same assessment. For example, a participant who experiences a ≥2 x ULN elevation of bilirubin 
at one visit and a ≥3xULN elevation in ALT (or AST) at a subsequent visit has not fulfilled the 
Hy’s Law criteria. 
Potential hepatotoxicity (meeting one of the PDILI or Hy’s Law laboratory criteria at least 
once) will be considered with and without symptoms potentially associated with hepatitis or 
hypersensitivity according to the investigator (reported on the Symptoms of Hepatitis and 
Hypersensitivity CRF page). 
Change #74 
Section 10.4.1 Vital signs 
The following text was added: 
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Unscheduled and repeat visits will be considered as long as they were collected in the period 
being summarized (values observed more than 140 days after the last administration of study 
medication are not considered). 
Change #75 
Section 10.4.3 Other safety endpoints 
The following text was added: 
For by-visit summaries, unscheduled and repeat visits will not be summarized, but these data will 
be included in listings. By-visit tables should include the SFU visit. Summaries over a period of 
time (as in shift tables), unscheduled and repeat visits will be considered as long as they were 
collected in the period being summarized (values observed more than 140 days after the last 
administration of study medication are not considered). 
Change #76 
Section 10.4.3.2 Columbia-Suicide Severity Rate Scale (C-SSRS) 
The following text was updated: 
The incidence of participants with suicidal ideation, suicidal behavior, suicidal ideation or 
behavior, and self-injurious behavior will be summarized for the Initial Treatment Period and 
the combined Initial and Maintenance Treatment Period by treatment group for each 
treatment. 
Change #77 
Section 10.3.4.5 Patient Health Questionnaire (PHQ)-9 scores 
The following text was updated: 
A In addition, a categorical summary of the absolute and change from Baseline value scores 
will be presented by treatment group and visit. 
The percentage of study participants with scores below a corresponding shift table. The 
following categories will be presented: 0-4; 5, between 5 and 9, between 10 and 14, between 
15 and 19, and greater than or equal to 20 in PHQ-9 will be summarized as a shift from 
Baseline by visit and treatment group based on observed values; ≥20. 
The percentage of study participants with scores ≥ 15 at any post-Baseline visit and the 
number and percentage of study participants with scores ≥ 20 at any post-Baseline visit will 
be summarized by treatment group based on observed values. This summary will also 
include the percentage of study participants with increase from baseline ≥ 5 at any post-
Baseline visit. 
Different to other safety variables, PHQ-9 will be summarized using the MCMC/monotone 
regression approach described for continuous variables. 
The number and percentage of participants that complete the PHQ-9 will be calculated for each 
visit by treatment group.  The percentage will be based on the number of participants in the RS. 
(or MS, as appropriate).  The summary will be repeated where the percentage is based on the 
subset of participants who complete each particular visit. 
Change #78 
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Section 11 References 
The following reference was updated: 
Common Terminology Criteria for Adverse Events (CTCAE); Version 4 5.0 June 2010 
2017.U.S. Department of Health and Human Services 
Change #79 
Section 12.1 Appendix A: MedDRA algorithmic approach to anaphylaxis 
The algorithm for identifying anaphylaxis was updated: 
The SMQ Anaphylactic reaction consists of three parts:  
 
• A narrow search containing PTs that represent core anaphylactic reaction terms (Category 
A – core anaphylactic reaction 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 
Nasal obstruction 
Asthma 
Oedema mouth 
Bronchial oedema 
Oropharyngeal spasm 
Bronchospasm 
Oropharyngeal swelling 
Cardio-respiratory distress 
Respiratory arrest 
Chest discomfort 
Respiratory distress 
Choking 
Respiratory failure 
Choking sensation 
Reversible airways obstruction 
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Circumoral oedema 
Sensation of foreign body 
Cough 
Sneezing 
Cyanosis 
Stridor 
Dyspnoea 
Swollen tongue 
Hyperventilation 
Tachypnoea 
Irregular breathing 
Throat tightness 
Laryngeal dyspnoea 
Tongue oedema 
Laryngeal oedema 
Tracheal obstruction 
Laryngospasm 
Tracheal oedema 
Laryngotracheal oedema 
Upper airway obstruction 
Mouth swelling 
Wheezing 
 
▪ Category C (Angioedema/Urticaria/Pruritus/Flush terms) 
Allergic oedema 
Oedema 
Angioedema 
Periorbital oedema 
Erythema 
Pruritus 
Eye oedema 
Pruritus allergic 
Eye pruritus 
Pruritus generalised 
Eye swelling 
Rash 
Eyelid oedema 
Rash erythematous 
Face oedema 
Rash generalised 
Flushing 
Rash pruritic 
Generalised erythema 
Skin swelling 
Injection site urticaria 
Swelling 
Lip oedema 
Swelling face 
Lip swelling 
Urticaria 
Nodular rash 
Urticaria papular 
Ocular hyperaemia 
 
 
 
▪ Category D (Cardiovascular/Hypotension terms) 
Blood pressure decreased 
Blood pressure diastolic 
decreased 
Blood pressure systolic 
decreased 
Cardiac arrest 
Cardio-respiratory arrest 
Cardiovascular insufficiency 
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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:  
o A narrow term or a term from Category A;  
o A term from Category B - (Upper Airway/Respiratory) AND a term from Category C - 
(Angioedema/Urticaria/Pruritus/Flush);  
o 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)]  
Change #80 
Section 912.2 Appendix B: Definition of CTCAE grades 
Table 12-1 was updated: 
Table 12‒1:  Definitions of CTCAE grades by biochemistry parameter 
Parameter  
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Creatinine1 
High 
umol/L 
mmol/L 
>1-1.5x 
Baseline or 
>ULN-1.5 x 
ULN 
>1.5-3.0x 
Baseline or 
>1.5 – 3.0 x 
ULN 
>3.0x 
Baseline or 
>3.0 – 6.0 x 
ULN 
>6.0 x ULN 
Sodium 
Low 
mmol/L 
130-<LLN 
N/A 
120-<130 
<120 
Sodium 
High 
mmol/L 
>ULN-150 
>150-155 
>155-160 
>160 
Potassium2 
Low 
mmol/L 
3.0-<LLN 
3.0-<LLN 
2.5-<3.0 
<2.5 
Potassium 
High 
mmol/L 
>ULN-5.5 
>5.5-6.0 
>6.0-7.0 
>7.0 
Calcium 
Low 
mmol/L 
2.0-<LLN 
1.75-<2.0 
1.5-<1.75 
<1.5 
Calcium 
High 
mmol/L 
>ULN-2.9 
>2.9-3.1 
>3.1-3.4 
>3.4 
Magnesium 
Low 
mmol/L 
0.5-<LLN 
0.4-<0.5 
0.3-<0.4 
<0.3 
Magnesium 
High 
mmol/L 
>ULN-1.23 
N/A 
>1.23-3.30 
>3.30 
Cholesterol 
High 
mmol/L 
>ULN-7.75 
>7.75-10.34 
>10.34-
12.82 
>12.82 
1 The CTCAE Grade definitions for creatinine are based on the logical or and the highest applicable CTCAE 
grade should be assigned to a creatine value. 
2 The decreased potassium criterion of 3.0-<LLN is specified for both CTCAE Grade 1 and Grade 2; values 
meeting this criterion will be counted as Grade 2. 
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And Table 12-2 was updated: 
Table 12‒2:  Definitions of CTCAE grades by hematology parameter 
Parameter 
Definition 
Unit 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Low 
g/L 
100-<LLN 
80-<100 
<80 
N/A 
Hemoglobin1 
High 
g/L 
>0-20 above 
ULN or >0-
20 above 
Baseline if 
Baseline is 
above ULN 
>20-40 
above ULN 
or >20-40 
above 
Baseline if 
Baseline is 
above ULN 
>40 above 
ULN or >40 
above 
Baseline if 
Baseline is 
above ULN 
N/A 
Platelets 
Low 
109/L 
75-<LLN 
50-<75 
25-<50 
<25 
WBC 
Low 
109/L 
3-<LLN 
2-<3 
1-<2 
<1 
WBC 
High 
109/L 
N/A 
N/A 
>100 
N/A 
Lymphocytes 
Low 
109/L 
0.8-<LLN 
0.5-<0.8 
0.2-<0.5 
<0.2 
Lymphocytes 
High 
109/L 
N/A 
>4-20 
>20 
N/A 
Neutrophils 
Low 
109/L 
1.5-<LLN 
1.0-<1.5 
0.5-<1.0 
<0.5 
LLN=lower limit of normal; N/A=not applicable; ULN=upper limit of normal, WBC=white blood cells  
1 The CTCAE Grade definitions to be applied are dependent on the Baseline hemoglobin value. If the 
baseline value is > ULN then the criteria relative to Baseline is applicable, otherwise the criteria relative to 
ULN is applicable.  
13.2 
Amendment 2 
Rationale for the amendment 
The main purposes of this amendment were:  
• General update to analyses to align with protocol amendment 4. 
• Procedural clarifications from discussions and feedback provided at meetings  
• Update to align with the bimekizumab program standards and safety topics of interest 
Modifications and changes 
Global Changes 
The following changes were made throughout the SAP: 
• Typos and formatting were updated throughout the document 
• HSSDD worst pain and average pain were updated to worst skin pain and average skin pain, 
respectively 
Specific changes 
In addition to the global changes, the following specific changes have been made (typos such as 
missing spaces or redundant spaces are not listed): 
Change #1 
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List of Abbreviations 
The following abbreviations have been added: 
CFB 
change from Baseline 
CV-CAC 
Cardiovascular Event Adjudication Committee 
eCDF 
empirical cumulative distribution function 
IBD-CAC 
Inflammatory Bowel Disease Adjudication Committee 
Change #2 
Section 1 Introduction 
The protocols were updated: 
The SAP is based on the Protocol Amendment 4 3, 6 May 2022 9 February 2021 and the Japan-
specific amendment 4.1 3.1, 11 February 2021.  
Change #3 
Section 2.2 Study endpoints 
The following text was deleted: 
The endpoints based on HS Symptom Daily Diary (HSSDD) and Hidradenitis Suppurativa 
Symptom Questionnaire (HSSQ) pain responses are based on the current definitions, which are 
continuous. It is anticipated that a responder (binary) endpoint will be defined for the HSSDD 
and HSSQ pain items as well as other symptom items prior to database lock and unblinding, 
based on separate ongoing, blinded, psychometric analyses aiming to determine threshold for 
within-patient clinically meaningful improvement.  
The below HSSDD and HSSQ pain response endpoints and analyses will be adjusted 
accordingly in a future SAP amendment. 
Change #4 
Section 2.2.1.2 Secondary efficacy endpoints 
The following bullet was added: 
• Skin pain response based on the threshold for clinically meaningful change (defined as at 
least a 3 point decrease from Baseline in HSSDD weekly worst skin pain score) at Week 16 
among study participants with a score of ≥3 at Baseline 
Change #5 
Section 2.2.1.3 Other efficacy endpoints 
The following bullets were updated: 
• Skin pPain response statusain response, as assessed by the “worst pain” item in the HSSDD, 
defined as an improvement from baseline in the weekly worst skin pain score of at least 3 
units Skin pain response based on the threshold for clinically meaningful change 
(defined as at least a 3 point decrease from Baseline in HSSDD weekly worst skin pain 
score) among study participants with a score of ≥3 at Baseline 
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• Skin pain response Response in HS Skin Pain (11-point numeric rating scale) assessed by 
the HSSDD at Week 16Response (at least a 30% reduction and at least a 1-point 
reduction from Baseline in HSSDD weekly worst skin pain score [11-point numeric 
rating scale]) among study participants with a score of ≥3 at Baseline 
• Skin pain response (at least a 30% reduction and at least a 1-point reduction from 
Baseline in HSSDD weekly average skin pain score [11-point numeric rating scale]) 
among study participants with a score of ≥3 at Baseline 
• HS Symptom Questionnaire (HSSQ) response (at least a 3-unit reduction from Baseline in 
worst HS Skin Pain score [11-point numeric rating scale]) among study participants with a 
score of ≥3 at Baseline assessed HSSQ by the HSSDD in the Initial Treatment Period, and 
assessed by the HSSQ in the Maintenance Treatment PeriodSkin pain response (at least a 
30% reduction and at least a 1-point reduction from Baseline in HS Skin Pain score 
[11-point numeric rating scale]) assessed by the HSSQ among study participants with a 
score of ≥3 at Baseline 
• Absolute change from Baseline in DLQI Total Score 
• DLQI Total Score of 0 or 1 
• Minimum clinically important difference (MCID) (improvement from Baseline of 4 or more) 
in the DLQI Total Score among study participants with a Baseline score of at least 4 
• Absolute change from Baseline in Hidradenitis Suppurativa Quality of Life (HiSQOL) 
domain scores (symptoms, psychosocial, activities and adaptations) and Total score 
• Patient Global Impression of HS Severity (PGI-S-HS) 
• Patient Global Impression of Change of HS Severity (PGI-C-HS) 
• Patient Global Impression of Severity of Skin Pain (PGI-S-SP) 
• Patient Global Impression of Change of Skin Pain (PGI-C-SP) 
• Absolute change from Baseline in each of the other HS Symptoms - itch, drainage or oozing 
of HS lesions, and smell or odor. 
• Responders Response on other HS Symptoms (11-point numeric rating scale) - itch, drainage 
or oozing of HS lesions, and smell or odor 
Change #6 
Section 2.4 Determination of sample size 
The power to detect a statistically significant difference for each of the endpoints are shown in 
Table 2‒1. Notably, with a 2-sided significance level of 0.025, the sample size of 140:70 
provides 73% power for detecting at least a difference of 1.5 (bimekizumab 
 vs placebo) for 
the Worst Skin Pain change from Baseline (CFB) endpoint. 
Given the high level of power for each of the primary and key secondary endpoints at the 
0.025 significance level for the 
 comparison (power≥0.89), and per the alpha spending 
strategy, there is a high likelihood that the
 comparison of Worst Skin Pain CFB vs placebo 
for Worst Pain change from Baseline will be allowed to be tested against the 0.05 level of 
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significance. The power for this latter test is 81%. The sample size is thus ultimately driven by 
the Worst Skin Pain CFB endpoint. Furthermore, the randomization ratio of 2:2:2:1 has been 
chosen to provide study participants with a high probability (6/7 ~ 86%) of being randomized to 
active study drug. 
After randomization for this study was complete, an additional endpoint to assess Worst 
Skin Pain response was included in the sequential testing procedure. This additional 
endpoint is based on the threshold for clinically meaningful change and is defined as at 
least a 3 point decrease from Baseline in HSSDD weekly worst skin pain score) at Week 16 
among study participants with a score of ≥3 at Baseline. Note that the power calculations 
reported in Table 2‒1 for this endpoint are based on the sample size that was initially 
driven by the Worst Pain CFB endpoint as described above. With a 2-sided significance 
level of 0.025, the sample size of 104:52 in the subset of participants reporting Baseline 
HSSDD worst skin pain score at or beyond the threshold for clinically meaningful change 
(ie, Baseline HSSDD ≥3) provides 53% power for detecting a statistically significant 
difference between bimekizumab 
 and placebo in the proportion of Worst Pain 
responders.  
Note that the power at the 0.025 level of significance associated with this endpoint for the 
comparison between bimekizumab 
 and placebo is 95%. The 
comparison of 
Worst Skin Pain response vs placebo against the 0.05 level of significance is therefore 
likely, and the power at this significance level is 65%. Given the strength of the power for 
the bimekizumab 
 arm vs placebo across endpoints, it is considered acceptable to have 
a relatively low  power for this final endpoint in the testing sequence for the bimekizumab 
 treatment arm vs placebo. 
Change #7 
Section 2.4 Determination of sample size 
Table 2-1 was updated: 
Table 2‒1: 
Power calculation assumptions and methods 
Endpoint 
Power 
α = 0.025,  
2-sided 
Assumptions 
 
 
Week 16 Bimekizumab 
 
N=280a 
Week 16 Bimekizumab 
 
N=140 
Week 16 Placebo 
N=70 
HiSCR50 
0.99 
0.90 
Proportion 
responders=0.60 
Proportion 
responders=0.50 
Proportion 
responders=0.25 
HiSCR75 
0.99 
0.98 
Proportion 
responders=0.45 
Proportion 
responders=0.35 
Proportion 
responders=0.10 
Flare 
0.99 
0.99 
Proportion of participants 
with flare by 
Week 16=0.09 
Proportion of participants 
with flare by 
Week 16=0.19 
Proportion of participants 
with flare by 
Week 16=0.52 
DLQI 
0.99 
0.96 
Mean CFB=-5.4; 
SD=6.8 
Mean CFB=-4.8; 
SD=6.8 
Mean CFB=-0.8; 
SD=6.6 
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Table 2‒1: 
Power calculation assumptions and methods 
Worst 
Skin Pain 
CFBb 
0.89 
0.73 
Mean CFB=-2.2; 
SD=3.2 
Mean CFB=-2.0; 
SD=3.2 
Mean CFB=-0.5; 
SD=3.7 
Worst 
Pain 
Responsec 
0.95 
0.53 
Proportion 
responders=0.53 
Proportion 
responders=0.43 
Proportion 
responders=0.23 
CFB=change from Baseline; 
; SD=standard deviation 
Note: Estimates for HS0004 are based on Week 12 data from the HS0001 study. 
a Pooled 
 at Week 16 from 
 and 
 arms 
b Within-participant average of Worst Skin Pain according to 24-hour recall. 
c Assumes N=208, 104, 52 in 
 and placebo, respectively, to account for Worst Skin Pain score 
at or above 3 (ie, the threshold for clinically meaningful change from Baseline). 
Change #8 
Section 3.1 General presentation of summaries and analyses 
The following text was added: 
Per protocol, visit windows are ±3 days from the date of first dose. The 20-week SFU Visit 
window is ±7 days from the date of the final dose. All by-visit summaries will contain nominal 
(ie, scheduled) visits only. Unscheduled visits will not be mapped to scheduled visits except for 
assessments that occur within a 3-day time 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. 
This will only occur for selected vendor data. The only exception to this rule is for 
unscheduled assessments that occur up to 3 days after the Baseline visit. These unscheduled 
visits will remain as unscheduled as the Baseline assessment cannot be after the first dose of 
study drug administration. See Section 3.3 for more details on the definition of Baseline 
values. 
Change #9 
Section 3.5.8 Pharmacokinetics Per-Protocol Set 
The following text was deleted: 
The Pharmacokinetics Per-Protocol Set (PK-PPS) will consist of study participants who received 
at least 1 full dose of bimekizumab and provided at least 1 quantifiable plasma concentration 
post-dose without important protocol deviations that would affect the PK. The Pharmacokinetics 
Per-Protocol Set is defined separately for each of the treatment periods (ie, separately for the 
Initial Treatment Period and the Maintenance Treatment Period). 
Change #10 
Section 3.10 Changes to protocol-defined analyses 
The following text was updated: 
The following other efficacy endpoints are included in the protocol but will not be included as 
part of the analysis: 
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• Responders Response on other HS Symptoms (11-point numeric rating scale) - itch, drainage 
or oozing of HS lesions, and smell or odor 
• Flare (defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 
relative to Week 16) by Week 48 
The calculation of nominal p-values has been added for selected efficacy endpoints. These 
nominal p-values are not controlled for multiplicity and should not be used to declare 
statistical significance. 
The protocol defines the PK-PPS separately by period, but there will only be one PK-PPS 
for the overall study. 
Change #11 
Section 4.1 Adjustments for covariates 
The following sentence was updated: 
The Worst Skin Pain secondary endpoints (change from Baseline continuous 
secondaryendpoint and pain response binary endpoint) will also include analgesic use as a 
covariate. 
Change #12 
Section 4.2.1.2 Handling of missing data for the secondary efficacy endpoints 
The following paragraph was updated: 
For secondary continuous efficacy endpoints, MI-MCMC/monotone regression is the primary 
method for imputing missing data, regardless of whether the missing data are preceded by an 
intercurrent event. That is, if an intercurrent event occurs on or before a visit,  the result for that 
visit will be treated as missing and then imputedwith the missing data. If the imputation model 
cannot converge, last observation carried forward (LOCF) will be used. The OC method will be 
performed as a sensitivity analysis. 
Change #13 
Section 42.2.1 MI – MCMC/Monotone Regression 
The imputation rule for HSSDD was updated in Table 4-2. 
Table 13‒2: Imputation allowable ranges by variable 
Variable 
Minimum Value 
Maximum Value 
Integer Values Only 
Lesion counta 
0 
-- 
Yes 
DLQI total score 
0 
30 
Yes 
hs-CRP 
LLOQ/2 
-- 
No 
HSSDD item score 
0 
10 
NoYes 
HSSQ item score 
0 
10 
Yes 
HiSQOL symptom 
status score 
0 
16 
Yes 
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Table 13‒2: Imputation allowable ranges by variable 
Variable 
Minimum Value 
Maximum Value 
Integer Values Only 
HiSQOL psychosocial 
impact score 
0 
20 
Yes 
HiSQOL impact on 
physical activities score 
0 
32 
Yes 
EQ-5D-3L VAS 
0 
100 
Yes 
WPAI dimension 
scores 
0 
100 
No for variables: “Percent work 
time missed due to problem” and 
“Percent overall work impairment 
due to problem”. 
Yes for variables: “Percent 
impairment while working due to 
problem” and “Percent activity 
impairment due to problem”. 
These two variables can only take 
values that are multiples of 10. 
a Lesion counts will be imputed separately for each lesion type (abscesses, draining tunnels [fistulas/sinus tracts], 
inflammatory nodules, non-draining tunnels [fistulas/sinus tracts], non-inflammatory nodules, HS scars). The 
imputed lesion counts will be used to derive the endpoints that are dependent on the lesion count data (eg, HiSCR50). 
Change #14 
Section 4.2.3 Rationale for estimand 
The following text was added to the bullet: 
• A composite estimand strategy will be used for the primary analysis of the primary and  
binary secondary endpoints (HiSCR50, HiSCR75, flare, HS worst skin pain response), 
Change #15 
Section 4.5 Multiple comparisons/multiplicity 
Under this framework, each bimekizumab dose of 
 and 
 will be 
compared to placebo in the first instance at a familywise error rate of 0.025 (α/2). 
Simultaneously within each dose, closed testing for the primary and secondary efficacy 
endpoints will be performed as follows: 
1. Step 1: Test HiSCR50 at significance level 0.025. 
2. Steps 2 to 65 – If Step 1 is significant at 0.025 then test each secondary endpoint sequentially 
in the order shown in Figure 4-1, moving to the next step only if significance achieved at 
0.025. 
3. In the event that Step 65 is significant at 0.025 for a given dose, then Steps 1 to 6 will be 
repeated for the other dose using a significance level of 0.05. 
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The secondary efficacy variables supporting the primary efficacy variable are listed below, and 
will be included in the multiplicity adjustment using the analysis methods specified in 
Section 8.3: 
4. Proportion of study participants who achieve HiSCR75 at Week 16.  
a. bimekizumab
 vs placebo 
b. bimekizumab 
 vs placebo 
5. Proportion of study participants who experience at least 1 flare by Week 16, with flare 
defined as a ≥25% increase in AN count with an absolute increase in AN count of ≥2 relative 
to Baseline.  
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
6. CFB in DLQI Total Score at Week 16. 
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
7. Absolute change from Baseline in Skin Pain Score at Week 16, as assessed by the “worst 
skin pain” item (11-point numeric rating scale) in the HSSDD. 
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
8. Skin pain response at Week 16, based on the threshold for clinically meaningful change 
(defined as at least a 3 point decrease from Baseline in HSSDD weekly worst skin pain 
score) at Week 16 among study participants with a score of ≥3 at Baseline.  
a. bimekizumab 
 vs placebo 
b. bimekizumab 
 vs placebo 
Change #16 
Section 4.5 Multiple comparisons/multiplicity 
Figure 4-1 was updated to add the new secondary endpoint: 
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Figure 13-1: Sequence of testing 
 
AN=abscess and inflammatory nodule; DLQI=Dermatology Life Quality Index; HiSCR50=a 50% reduction in the 
total AN count with no increase from Baseline in abscess or draining tunnel count; HiSCR75=a 75% reduction in 
the total AN count with no increase from Baseline in abscess or draining tunnel count; HS=hidradenitis 
Suppurativa; 
 
HS skin pain response is tested among study participants with a score of ≥3 at Baseline. 
Change #17 
Section 4.8 Examination of subgroups 
The following text was updated: 
Subgroup analyses will be performed on the HiSCR50, HiSCR75, andflare, and worst skin pain 
response endpoints by visit for the Initial Treatment Period and Maintenance Treatment Period. 
Additional subgroup analyses will be performed on the CFB in the worst skin pain score as 
measured by HSSDD and in the DLQI total score through Week 16 as described below. 
Along with the tables described, there will be tables for HiSCR50, HiSCR75, and flare, and skin 
pain response endpoints which display the response difference and 95% CIs between each 
bimekizumab dose regimen versus placebo for each of the subgroups at Week 16. Corresponding 
forest plots will be prepared.  
Additionally, the following bullets were clarified: 
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• Antibody positivity (confirmatory assay: negative or positive. See Section 9.3.2) 
• Antihistamines users during the Initial Treatment Period (yes, no) (Section 6.4.2 
specifies how participants are classified as antihistamine users) (applicable only to the 
skin pain response endpoint) 
Change #18 
Section 6.4 Prior and concomitant medications 
The following text was added: 
The number and percentage of study participants with concomitant vaccines for COVID-19 will 
be summarized by treatment group, overall and by World Health Organization Drug Dictionary 
Standardized Drug Grouping (SDG), presenting SDG subgroup, and preferred term. The SDG 
subgroup Vaccines for COVID-19 will be used to identify vaccines for COVID-19 using the 
narrow scope; this subgroup is divided further into separate subgroups which is the level that will 
be presented. The number of individual occurrences of the vaccine for COVID-19 will also be 
summarized.  
A listing of concomitant vaccines for COVID-19 will be provided. 
Change #19 
Section 6.4.2 Classification of participants as analgesic, antihistamine users 
The section was updated as follows: 
If a participant has taken a new analgesic/increased regimen of analgesic, or taken an 
antihistamine, on 1 or more days (need not be consecutive) for a given week in a study period 
(Initial Treatment Period or Maintenance Treatment Period), then for that week period the 
participant will be classified as an analgesic or antihistamine user, respectively. The week period 
under consideration is to match the period as defined for the HSSDD week for the Initial 
Treatment Period or HSSQ week for the Maintenance Treatment Period, based on dates/times of 
the medications taken.  If there is a visit date but no HSSDD available at the visit, then the 
analgesic/antihistamine user status for that week will be derived based on the visit date.  If there 
is no visit available, then the weekly analgesic/antihistamine user status will default to the 
analgesic/antihistamine status for the overall study period. 
New analgesic/increased regimen of analgesic use, regardless of indication, is defined as an 
analgesic medication with start date on or after the first dose of study medication. Stable 
analgesics (ie, analgesics which were taken already before randomization) will not be included in 
this category of analgesic user. This classification will be used to adjust the formal analysis of 
the Worst Pain secondary endpoints and for selected subgroup analyses. 
Antihistamine use is identified by considering the ATC classification. This classification is used 
for analyzing the Worst Itch endpoint and for selected subgroup analyses, by visit, for the Initial 
Treatment Period and Maintenance Period as applicable. 
Additionally, if a participant has taken a new analgesic/increased regimen of analgesic on 1 
or more days (need not be consecutive) prior to the Week 16 visit, then for that week the 
participant will be classified as an analgesic user. This classification will be used to adjust 
the formal analysis of the Worst Skin Pain secondary endpoints. If there is a visit date but 
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no HSSDD available at the visit, then the analgesic/antihistamine user status for that week 
will be derived based on the visit date.  If there is no visit available, then the weekly 
analgesic/antihistamine user status will default to the analgesic/antihistamine status for the 
overall study period. 
Change #20 
Section 8.2 Primary efficacy endpoint 
The intercurrent event strategy for the sensitivity analysis was updated in Table 8-1: 
Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
Estimands for Primary Endpoint 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Primary Objective: To evaluate the efficacy of bimekizumab in study participants with moderate to 
severe HS 
Sensitivity 
(Section 8.2.3.2) 
HiSCR50 
response at 
Week 16 
 
RS 
Composite strategy, as 
for the primary 
analysis.The 
intercurrent events will 
be handled using a 
hypothetical strategy, 
whereby all data at and 
after the intercurrent 
event will be treated as 
missing. 
The odds ratio versus placebo 
based on a logistic regression. 
Missing values will be imputed 
using MI – Reference-Based 
Regression under a missing not at 
random assumption. 
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Table 8‒1: 
Estimand Details and Attributes for Primary Endpoint 
 
Estimands for Primary Endpoint 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Sensitivity 
(Section 8.2.3.5) 
HiSCR50 
response at 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants still on 
randomized treatment at 
Week 16 are included. 
whereby only 
participants with a 
lesion count 
assessment at Week 16 
who have not had an 
intercurrent event on 
or before Week 16 are 
included. 
The odds ratio versus placebo is 
based on a logistic regression. 
Missing values will not be 
imputed. 
Change #21 
Section 8.2.3.5 Analysis on observed cases 
The following text was updated: 
An additional supportive analysis will be based on observed data only for study participants who 
are still on the randomized treatment at Week 16.  Study participants with missing data or who 
have prematurely discontinued study treatment will be treated as missing (see Section 4.2.2). 
participants with a lesion count assessment at Week 16 who have not had an intercurrent 
event on or before Week 16. Study participants with missing data at Week 16 will be 
treated as missing (see Section 4.2.2). 
 
Change #22 
Section 8.2.3.11 Center-by-Treatment Interaction 
The following sentence was added: In order to achieve model convergence, other explanatory 
variables eg, Baseline Hurley Stage and Baseline antibiotic use may be dropped from the model. 
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If model convergence is still not achieved, region and a region-by-treatment interaction 
term will be added to the model instead. Regions are defined in Section 3.7. 
Change #23 
Section 8.3 Secondary efficacy endpoints 
The following sensitivity analyses as well as the new skin pain response secondary analysis were 
added to Table 8-2: 
Table 813‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
Secondary Objective: Evaluate the efficacy of bimekizumab on other measures of disease activity in 
study participants with moderate to severe HS 
DLQI 
Secondary - 
Sensitivity 
(Section 8.3.3.
2 )  
Change 
from 
Baseline in 
DLQI total 
score to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
DLQI total score at 
Week 16 who have not 
had an intercurrent event 
on or before Week 16 
are included. 
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the 
DLQI total score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will not be 
imputed. 
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Table 813‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HSSDD 
Secondary  
(Section 8.3.4.
2) 
Change 
from 
Baseline in 
worst skin 
pain score, 
as assessed 
by “worst 
skin pain” 
item in 
HSSDD to 
Week 16 
 
RS 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
HSSDD worst skin pain 
score at Week 16 who 
have not had an 
intercurrent event on or 
before Week 16 are 
included. 
Difference in mean 
change from 
Baseline (LSMD 
from ANCOVA) to 
Week 16 in the worst 
skin pain score for 
participants receiving 
bimekizumab versus 
placebo. Missing 
values will not be 
imputed. 
HSSDD 
Secondary  
(Section 8.3.5.
1) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
Composite strategy, as 
for the primary analysis. 
The odds ratio versus 
placebo based on a 
logistic regression, as 
for the primary 
analysis.  
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Table 813‒2: 
Estimand Details and Attributes for Secondary Analyses 
 
 
Estimands for Secondary Endpoints 
Objective 
Clinical 
Category 
Statistical 
Category 
(Section) 
Variable/ 
Endpoint 
Pop 
IES 
PLS (Analysis) 
HSSDD 
Secondary 
Sensitivity 
(Section 8.3.5.
2.1) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
Composite strategy, as 
for the primary analysis 
where the occurrence of 
an intercurrent event 
will be handled by 
evaluating the 
corresponding 
participants as 
nonresponders. 
The odds ratio versus 
placebo based on a 
logistic regression. 
Missing values for 
any other reason will 
also be imputed as 
nonresponders. 
HSSDD 
Secondary 
Sensitivity 
(Section 8.3.5.
2.2) 
Skin pain 
response at 
Week 16, 
as assessed 
by the 
“worst skin 
pain” item 
in the 
HSSDD, 
defined as 
an 
improve-
ment in the 
weekly 
worst skin 
pain score 
of at least 3 
points 
RSa 
The main intercurrent 
events are receipt of 
systemic antibiotic 
rescue medication or 
discontinuation of study 
treatment due to an AE 
or lack of efficacy prior 
to Week 16. The 
intercurrent events will 
be handled using a 
while on treatment 
strategy, whereby only 
participants with a 
HSSDD worst skin pain 
score at Week 16 who 
have not had an 
intercurrent event on or 
before Week 16 are 
included. 
The odds ratio versus 
placebo is based on a 
logistic regression. 
Missing values will 
not be imputed. 
AE=adverse event; ANCOVA=analysis of covariance; DLQI=Dermatology Life Quality Index; 
HiSCR=Hidradenitis Suppurativa Clinical Response; HSSDD=Hidradenitis Suppurativa Symptom Daily Diary; 
IES=intercurrent event(s) strategy; LSMD=Least Squares Mean Difference; MCMC=Markov Chain Monte 
Carlo; MI=multiple imputation; PLS=Population-level summary; Pop=Population; RS=Randomized Set 
a Analysis includes all study participants in the RS with a Baseline HSSDD Worst Skin Pain score of 3 or 
higher. 
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Change #24 
Section 8.3.3.1 Primary analysis of change from Baseline in DLQI Total Score 
Section 8.3.3.1 was separated from Section 8.3.3 due to the added sensitivity analysis for DLQI 
Total Score.  The following text was added: 
Change from Baseline in DLQI total score will be presented by treatment group. The analysis 
model will be based on an ANCOVA with fixed effects of treatment, Hurley Stage at Baseline, 
Baseline antibiotic use and Baseline value as a covariate. The least square mean (LSM), standard 
error (SE), and 95% CI for the LSM will be presented by treatment group. For the comparison 
between placebo and bimekizumab: the difference between the LSM, the associated 97.5% CI 
for the contrasts, and the corresponding p-value will be presented. If one dose regimen is tested 
at the 0.05 significance level as determined in Section 4.5, then the confidence interval will be 
95% instead of 97.5% for that dose with a corresponding Zα/2 of 1.96. Estimand and 
intercurrent event details are specified in Table 8‒2.  
Change #25 
The following section was added: 
Sensitivity analysis of change from Baseline in DLQI Total score at Week 16 (Section 
8.3.3.2) 
A sensitivity analysis using the same analysis model as in Section 8.3.3.1 will be used, based on 
observed data. Estimand and intercurrent event details are specified in Table 8‒2. 
Change #26 
Section 8.3.4.1 Primary analysis of change from Baseline in skin pain score at Week 16 
Section 8.3.4.1 was separated from Section 8.4.3 due to the added sensitivity analysis for 
HSSDD worst skin pain score and removed ‘A treatment by analgesic use interaction term will 
also be added to the model and removed if not significant’ from section. 
Change #27 
The following section was added: 
Sensitivity analysis of change from Baseline in skin pain score at Week 16 (Section 8.3.4.2) 
A sensitivity analysis using the same analysis model as in Section 8.3.4.1 will be used, based on 
observed data. Estimand and intercurrent event details are specified in Table 8‒2. 
Change #28 
The following sections were added: 
HSSDD skin pain response at Week 16 (Section 8.3.5) 
The analysis set for the analyses of the skin pain response will be restricted to those study 
participants in the RS with a Baseline worst skin pain score of 3 or higher. The weekly scores 
and Baseline score are derived as specified in Section 8.3.4. 
Primary analysis of skin pain response at Week 16 (Section 8.3.5.1) 
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Skin pain response at Week 16, as assessed by the “worst skin pain” item in the HSSDD, is 
defined as an improvement in the weekly worst skin pain score of at least 3 points versus 
Baseline.  
The primary analysis will be based on a logistic regression model including a fixed effect for 
treatment, Hurley stage at Baseline, Baseline antibiotic use, and analgesic use (Section 6.4.2). 
The odds ratio versus placebo, p-value (from Wald test), and 97.5% CI will be calculated. If one 
dose regimen is tested at the 0.05 significance level as determined in Section 4.5, then the 
confidence interval will be 95% instead of 97.5% for that dose. Missing data will be handled as 
specified in Section 4.2.1.2. Estimand and intercurrent event details are specified in Table 8‒2. 
The number and percentage of participants who are pain responders at Week 16 will be 
summarized by treatment group.  
By-participant listings of pain response status will be provided.  
Sensitivity analyses of Skin Pain Response at Week 16 (Section 8.3.5.2) 
Nonresponse imputation (Section 8.3.5.2.1) 
As a sensitivity analysis, any missing data at Week 16 that are not preceded by an intercurrent 
event (Table 8‒2) will be imputed as nonresponse. That is, participants who experience an 
intercurrent event will be imputed as nonresponder at the timepoint of the event and all 
subsequent timepoints (including any recorded data after the event), and all missing data will 
also be imputed as nonresponse. 
The same analysis model as Section 8.3.5.1 will then be used on the imputed data set. 
Analysis on observed case (Section 8.3.5.2.2) 
An additional supportive analysis will be based on observed data only for study participants with 
a worst skin pain score at Week 16 who have not had an intercurrent even on or before Week 16. 
Study participants with missing data or who have prematurely discontinued study treatment will 
be treated as missing (see Section 4.2.2). 
The same analysis model as in Section 8.3.5.1 will then be used on the imputed data set. 
Change #29 
Section 8.4.1.3 HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 response at both 
Weeks 16 and 48 
The following text was added: 
The number and percentage of HiSCR25, HiSCR50, HiSCR75, HiSCR90, and HiSCR100 responders 
at both Weeks 16 and 48 will be summarized based on the RS and MS. 
Change #30 
Section 8.4.12 Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) 
The following text was updated: 
See Section 8.3.4 for details on HSSDD Baseline and weekly average definitions and 
derivations.  
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Percent change from Baseline in HSSDD responses for worst and average skin pain score is 
defined as  
Percent change from Baseline = 100 × Post Baseline HSSDD score −Baseline HSSDD score
Baseline HSSDD score
 
Change from Baseline in each HSSDD item (worst skin pain, average skin pain, smell or odor, 
itch at its worst, and amount of drainage or oozing) score will be summarized using descriptive 
statistics by treatment group and visit, based on weekly averages. The table will display 
descriptive statistics for the Baseline, followed by descriptive statistics for the change from 
Baseline for all visits. Percentage change will be summarized for the worst and average skin pain 
items.  
Additionally, change from Baseline in each HSSDD item will be evaluated by treatment 
group at Week 16 via continuous empirical cumulative distribution function (eCDF) plots 
showing the absolute change from Baseline on the horizontal axis and the cumulative 
percent of participants experiencing that change on the vertical axis. 
Change from Baseline in Worst Skin Pain score and Worst Itch score will additionally be 
summarized by visit and by analgesic and antihistamine use status (Section 6.4.2), respectively. 
HSSDD response based on clinically meaningful change for the worst skin pain and average 
skin pain items is defined as at least a 3-point 30% reduction and at least a 1 point reduction 
from Baseline in HSSDD among study participants with a score of ≥3 at Baseline, based on 
weekly averages. 
The number and percentage of responders based on clinically meaningful change for each item 
the worst skin pain item will be summarized by treatment group and visit. 
The number and percentage of participants who were responders based on clinically 
meaningful change at any timepoint in the Initial Treatment Period will be summarized by 
treatment group for the worst HSskin pain score item. 
HSSDD response for the worst skin pain and average skin pain items is defined as at least a 
30% reduction and at least a 1-point reduction from Baseline among study participants 
with a score of ≥3 at Baseline. The number and percentage of responders for each item will 
be summarized by treatment group and visit. 
The number and percentage of participants who were responders based on clinically 
meaningful change at any timepoint in the Initial Treatment Period will be summarized by 
treatment group for the worst skin pain and average skin pain items. 
The number and percentage of participants that complete the HSSDD will be calculated for each 
visit by treatment group. A participant will be counted as completing the HSSDD at a visit if the 
minimum number of daily entries is present to calculate the weekly average (see Section 8.3.4). 
The percentage will be based on the number of participants in the RS. A participant will be 
considered a completer at a visit if the weekly average can be calculated for that visit. 
Change #31 
Section 8.4.13 Hidradenitis Suppurativa Symptom Questionnaire 
The following text was updated: 
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Additionally, change from Baseline in each HSSQ item will be evaluated by treatment 
group at Week 16 and at Week 48 via continuous eCDF plots showing the absolute change 
from Baseline on the horizontal axis and the cumulative percent of participants 
experiencing that change on the vertical axis. 
Missing data for the continuous change from Baseline will be handled by using MI via the 
MCMC and monotone regression method specified in Section 4.2.1.3. 
HSSQ response for skin pain item is defined as at least a 30% reduction and at least a 1-point 
reduction from Baseline in HS Skin Pain score [11-point numeric rating scale]) among study 
participants with a score of ≥3 at Baseline.  
Change #32 
Section 8.4.15 Hidradenitis Suppurativa Quality of Life 
The following text was added: 
Additionally, change from Baseline in each HiSQOL subscale will be evaluated by treatment 
group at Week 16 and at Week 48 via continuous eCDF plots showing the absolute change from 
Baseline on the horizontal axis and the cumulative percent of participants experiencing that 
change on the vertical axis. 
Change #33 
Section 8.5 Additional statistical analyses of other efficacy endpoints 
The following analysis was added 
• Skin Pain response per HSSDD at Week 12 
Change #34 
Section 9.3.2 Anti-bimekizumab antibodies 
The section was updated as follows: 
Anti-bimekizumab antibodies (ADAb) will be measured using a 3-tiered assay approach: 
screening assay, confirmatory assay, and titration assay. Samples confirmed as positive within 
the confirmatory assay will be further evaluated for the presence of neutralizing anti-
bimekizumab antibodies specific to IL-17AA, IL-17FF or both. Samples will be taken at 
Baseline, then at study Weeks 4, 8, 12, 16, 20, 24, 36 and 48, and at PEOT and SFU timepoints.  
ADAb samples are not analyzed when study participants are on a treatment other than 
bimekizumab. For study participants who switch from placebo to bimekizumab, samples 
are analyzed starting at the visit when the switch to bimekizumab occurs (Week 16). The 
sample at Week 16 will act as the Baseline for that treatment group.  
The screening cut point will be used to determine the status of anti-bimekizumab antibodies in 
the test sample as Positive Screen (PS) or Negative Screen (NS). For samples presenting anti-
bimekizumab antibody levels that are PS, a further confirmatory assay will be performed, and the 
result of which will be reported as either Positive Immunodepletion (PI) or Negative 
Immunodepletion (NI).  
ADAb status for each sample will be derived as follows: 
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• Sample values that are either NS, or PS and NI and where the bimekizumab concentration is 
less than the validated ADAb assay drug tolerance limit will be defined as anti-bimekizumab 
antibody negative. 
• Sample values that are either NS, or PS and NI and where the bimekizumab concentration 
exceeds the validated ADAb assay drug tolerance limit 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 or non-evaluable samples will be defined as missing 
Positive immunodepletion samples will be titrated, and the ADAb titer (reciprocal dilution factor 
including minimum required dilution) will be reported. Subsequently, PI samples will also be 
subject to a neutralizing assay to evaluate the potential of ADAb to neutralize the target binding 
of bimekizumab (IL-17AA or IL-17FF or both) in vitro. 
Cumulative There are different levels of classification for ADAb status will be derived as 
follows: 
The ADAb status (positive, negative or missing) will be considered in a cumulative manner 
at each time point.  
A study participant will be counted positive from the first visit at which the study 
participant 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 study participant has only negative ADAb samples or only one missing/inconclusive 
sample with all other ADAb samples being negative, the study participant will be classified 
as negative. An exception remains for the Baseline Visit where only one sample could be 
available. If the sample is missing/inconclusive, then the sample will be classified as being 
negative for the cumulative ADAb status. 
Otherwise, the study participant will be classified in the missing ADAb category. 
Overall ADAb status will be derived as follows: 
A study participant will be classified as: 
• Positive if the study participant has at least one positive sample up to the time point of 
interest (regardless of having missing/inconclusive data). 
• Negative if the study participant has all the samples negative or only one 
missing/inconclusive sample with negative ADAb samples up to the timepoint of 
interest. 
• Missing if the study participant has more than one missing ADAb result (or have more 
than one inconclusive sample) and all other available ADAb samples are negative up to 
the time point of interest.  
ADAb categories will be derived definitions are as follows: 
• Pre ADAb negative – treatment-emergent ADAb negative (Category 1): Includes study 
participants who are anti-bimekizumab antibody negative at Baseline and anti-bimekizumab 
antibody negative at all sampling points during the period of interest (one post-Baseline 
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missing/inconclusive sample is allowed for subjects with pre- anti-bimekizumab antibody 
negative sample). This group also includes study participants who have a missing or 
inconclusive sample (either missing or inconclusive or insufficient volume) at Baseline (ie, 
pre-treatment) with all post-Baseline samples as ADAb negative. 
• Pre ADAb negative – treatment-emergent ADAb positive (Category 2): Includes study 
participants who are ADAb negative at Baseline and ADAb positive at any sampling points 
post-Baseline during the period of interest. This group also includes study participants who 
have a missing sample (either missing or insufficient volume) at Baseline (ie, pre-treatment) 
with 1 or more post-Baseline samples as ADAb positive. 
• Pre ADAb positive – treatment-emergent reduced ADAb (Category 3): Includes study 
participants who are ADAb positive at Baseline, and ADAb negative at all sampling points 
post-Baseline during the period of interest. 
• Pre ADAb positive – treatment-emergent unaffected ADAb positive (Category 4): 
Includes study participants who are ADAb positive at Baseline and are ADAb positive at any 
sampling point post-Baseline during the period of interest with titer values of the same 
magnitude as Baseline (ie, less than a predefined fold difference from the Baseline titer). 
− For this analysis, this is set at an increase of less than the validated Minimum Significant 
Ratio (MSR) of 2.07-fold from Baseline.  
• Pre ADAb positive – treatment-emergent ADAb boosted positive (Category 5): Includes 
study participants who ADAb positive at Baseline and are ADAb positive at any sampling 
point post-Baseline during the period of interest with increased titer values compared to 
Baseline (equal to or greater than a predefined fold difference increase from Baseline titer 
which will be defined within the validation of the assay). 
− For this analysis, this is set at an increase equal to or greater than the validated MSR of 
2.07-fold from Baseline.  
− Note: for any study participant who is ADAb positive at Baseline and ADAb positive at a 
post-Baseline time point during the period of interest, but for whom titers are not 
available to determine treatment unaffected or treatment boosted status, the study 
participant will be considered as treatment boosted, assuming no other samples are 
available. 
• ADAb Inconclusive (Category 6): Includes study participants who have an ADAb positive 
Baseline (pre-treatment) sample and some post-Baseline samples during the period of interest 
are missing or inconclusive, while other post-Baseline samples are ADAb negative. 
• Total treatment-emergent ADAb positivity (Category 7 [Categories 2 and 5 combined]): 
Includes study participants who are pre ADAb negative – treatment-emergent ADAb positive 
(Category 2) and pre ADAb positive – treatment boosted ADAb positive (Category 5).  
• Total prevalence of pre- ADAb positivity (Category 8 [Categories 3, 4, 5 and 6 
combined]): Study participants that are tested ADAb positive at Baseline. 
• Missing: Includes study participants who are ADAb negative, missing, or inconclusive at 
Baseline with some post-Baseline samples as missing or inconclusive, and other samples as 
ADAb negative. 
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For purposes of efficacy subgroup analyses based on anti-bimekizumab antibody status, 
the following categories can also be used: 
• ADAb positive – This is defined as study participants who are anti-bimekizumab 
antibody positive on at least 2 time points while on treatment (ie, excluding Baseline, 
excluding SFU). 
• ADAb negative – Study participants for who either:  
− All samples (including Baseline) are ADAb negative and there are no missing or 
inconclusive samples 
− Only 1 sample is ADAb positive and all other samples (including Baseline) are 
ADAb negative or missing or inconclusive 
− Only 1 sample is missing or inconclusive and the remaining ADAb samples are 
negative.  
• ADAb missing - Defined as study participants who do not fulfil the criteria for one of 
the 2 groups listed above. 
The rationale for requiring at least 2 time points in which ADAb levels are above the 
specified cut point is to exclude those study participants who have only one occurrence of 
ADAb levels during the course of treatment. Including such study participants would 
increase the number of ADAb positive study participants with potentially no impact on 
efficacy. 
In the case that a sample is collected 1 or more days following the scheduled visit date in which 
the drug was administered, the ADAb results for that sample will be associated with the 
scheduled visit and summarized accordingly. Such samples will also be considered when ADAb 
results are summarized over a given study period. 
Analysis 
Immunogenicity will be assessed through summary tables and figures, and listing of individual 
results by participants. All analyses will be run on the AMS, unless specified otherwise. 
• Summary of ADAb status overall and by each visit separated by treatment group 
• Summary of the time-point of the first occurrence of ADAb positivity during the treatment 
period by treatment group. A plot of the titer by time to first ADAb positivity will be 
prepared. 
• All individual participant-level ADAb results will be listed. 
• The number and percentage of participants in each of the 8 ADAb categories during the 
treatment period by treatment group. 
• The prevalence of immunogenicity, separated by treatment group, and defined subcategory, 
will be reported by visit, defined as (cumulative) proportion of participants having confirmed 
positive ADAb samples at any visit up to and including that visit. Missing samples will not 
be included in the denominator. 
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• The time to achieving treatment-emergent ADAb positivity, separated by treatment group 
and defined subcategory, will be analyzed based on Kaplan-Meier methods. This will be 
shown only for Categories 2 and 8 above. Participants will be considered to have an event 
at the time point at which treatment emergent ADAb positive is first achieved (taking the 
MSR into consideration for sub-category 5). Participants classified as treatment-emergent 
ADAb negative will be censored at the time of the last available ADAb result. 
• A summary of HiSCR50 responders at Week 16, separated by treatment group, as a function 
of ADAb titer will be presented graphically.This will be repeated for HiSCR75 responders. 
• Individual plots of plasma bimekizumab concentrations/ ADAb titer both plotted on the Y-
axes by visit (x-axis) for the full treatment period (excluding SFU for interim analyses and 
including SFU for final analyses) will be presented for participants with and without 
HiSCR50 response at Week 16. 
• Spaghetti plots of ADAb titer (y-axis) by visit (x-axis), separated by treatment group for all 
ADAb positive participants, including Baseline positive participants. 
• Box plots of ADAb titer (logscale) by time to first ADAb positivity by treatment group. 
For purposes of efficacy subgroup analyses based on anti-bimekizumab antibody status, 2 
categories will be used:  
• ADAb positive – This is defined as participants who have ADAb levels above the specified 
cut point on at least 2 time points while on treatment (ie, excluding Baseline, excluding 
SFU).  
• ADAb negative – Participants who are not defined as anti-bimekizumab positive (as 
described above) will be defined as ADAb negative.  
The groups for defining ADAb status for safety subgroup analyses are as follows:  
• AEs starting before first ADAb positive result 
• AEs starting on or after first ADAb positive result 
• AEs for participants who were always ADAb negative  
This is further explained in Section 10.2.2.  
Change #35 
The following section was added: 
COVID-19 related considerations (Section 10.2.1.1) 
To assess the impact of COVID-19 mass vaccination on TEAEs, a sensitivity analysis will 
present all TEAEs excluding TEAEs assessed as exclusively related to COVID-19 vaccine by 
the investigator. TEAEs recorded as related to both study medication and COVID-19 vaccination 
should not be excluded. A complementary table and listing of TEAEs related to COVID-19 
vaccine will be presented. 
Another sensitivity analysis will present all TEAEs excluding TEAEs with start date on or up to 
5 days after date of COVID-19 vaccine. Note that study participants may receive more than one 
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administration of COVID-19 vaccine. A complementary table and listing of TEAEs with start 
date on or up to 5 days after date of COVID-19 vaccine will also be presented. 
Change #36 
Section 10.2.2 AE summaries 
The following AE summaries were added: 
• Incidence of TEAEs Excluding TEAEs Exclusively Related to COVID-19 Vaccine by SOC, 
HLT, and PT 
• Incidence of TEAEs Exclusively Related to COVID-19 Vaccine by SOC, HLT, and PT 
• Incidence of COVID-19 Vaccine Interval Censored TEAEs by SOC, HLT, and PT 
• Incidence of COVID-19 Vaccine Interval TEAEs by SOC, HLT, and PT 
Change #37 
Section 10.2.2 AE summaries 
The following text was added: 
The following table will be presented for the combined Initial and Maintenance Treatment 
Period. This summary will include only AEs that occur while a participant is on 
bimekizumab. Any AEs in the Initial Treatment Period that begin while a participant is on 
placebo will be excluded. 
• Incidence of TEAEs per 100 subject years by SOC, HLT, and PT and by Time of Onset 
Relative to Anti-bimekizumab Antibody Status. 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) 
The tables with risk differences will also be accompanied by figures (dot plots) which show the 
incidence of the adverse events and corresponding 95% risk difference confidence intervals. 
These will be ordered by descending order of risk difference (bimekizumab vs placebo). 
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Change #38 
Section 10.2.3.3 Major adverse cardiac event 
The entire section was updated: 
Potential cardiovascular events are adjudicated by the independent Cardiovascular Event 
Adjudication Committee (CV-CAC) according to the CV-CAC Charter (version 6.0).  
Adjudicated events are classified by the CV-CAC to one of the event types as defined in 
Table 10‒1. The classification of an event as a Major Adverse Cardiac Event (MACE) is also 
determined by the CV-CAC. Events which are classified by the CV-CAC as any of the event 
types identified in the third column of Table 10‒1 will be considered an extended MACE. Note 
that extended MACE is determined programmatically and includes a broader scope definition of 
MACE.  
MACE as determined by the CV-CAC will be presented in a table and listing. Extended MACE 
will be presented separately in a table and listing. 
Another table and listing will present the adjudicated cardiovascular events by type. For each 
cardiovascular event type, the individual PTs which fall within each event type will be 
summarized. This listing will indicate whether each event was determined to be a MACE and/or 
an extended MACE. 
Additionally, a listing of all events identified for potential review by the CV-CAC will be 
produced. This listing will indicate whether each event was identified by the CV-CAC Chair for 
full committee review.  
Table 13‒1: Cardiovascular event classifications 
Event 
Type 
Code 
Event Type 
Extended MACE 
1 
Non-Fatal Myocardial Infarction (MI) 
Yes 
2 
Non-Fatal Stroke: hemorrhagic 
Yes 
3 
Non-Fatal Stroke: ischemic 
Yes 
4 
Non-Fatal Stroke: embolic 
Yes 
5 
Non-Fatal Stroke: undeterminable 
Yes 
6 
Hospitalization or ER for Unstable Angina 
with urgent revascularization 
Yes 
7 
Hospitalization or ER for Unstable Angina 
without urgent revascularization 
No 
8 
Hospitalization for Heart Failure 
Yes 
9 
Transient Ischemic Attack (TIA) 
No 
10 
Coronary Revascularization Procedures (e.g. 
percutaneous coronary intervention, 
coronary artery bypass grafting) 
Yes 
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Table 13‒1: Cardiovascular event classifications 
Event 
Type 
Code 
Event Type 
Extended MACE 
11 
Urgent Revascularization Procedures (i.e. 
due to symptoms of brain ischemia or 
pending infarction) 
Yes 
12 
Arrhythmia (not associated with ischemia) 
No 
13 
Peripheral Arterial Event 
No 
14 
Venous Thromboembolic Event: pulmonary 
embolism (PE) 
No 
15 
Venous Thromboembolic Event: deep vein 
thrombosis (DVT) 
No 
16 
Venous Thromboembolic Event: PE and 
DVT 
No 
17 
Other CV Event 
No 
18 
Death due to Myocardial Infarction (MI) 
Yes 
19 
Death due to Stroke 
Yes 
20 
Sudden Cardiac Death 
Yes 
21 
Other CV Death (e.g. heart failure, 
pulmonary embolism, cardiovascular 
procedure-related) 
Yes 
22 
Cardiovascular: Undetermined Cause of 
Death (i.e. cause of death unknown) 
Yes 
23 
Non-Cardiovascular Death 
No 
24 
Non-Cardiovascular Event 
No 
99 
Inadequate information to adjudicate 
No 
CV=Cardiovascular; DVT=Deep Vein Thrombosis; ER=Emergency Room; MACE= Major Adverse Cardiac Event; 
MI=Myocardial Infarction; PE=Pulmonary Embolism; TIA=Transient Ischemic Attack. 
MACE is determined by the adjudication committee and is not identified programmatically based on event type.  
Change #39 
Section 10.2.3.5 Suicidal Ideation and Behavior 
The entire section was updated: 
Potential neuropsychiatric events are adjudicated by the independent Neuropsychiatric 
Adjudication Committee according to the Neuropsychiatric Adjudication Committee (version 
8.0). Adjudicated events are classified by the Committee as Suicidal or Non-suicidal. 
Adjudicated events are also further classified by the Committee to one of the event types as 
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defined in Table 10‒2. Suicidal Ideation and Behavior (SIB) is defined as events classified by the 
Committee as Suicidal. 
A table and listing will present SIB events. 
Another table and listing will present the adjudicated neuropsychiatric events by type. For each 
neuropsychiatric event type, the individual PTs which fall within each event type will be 
summarized. This listing will indicate whether each event was determined to be Suicidal or Non-
Suicidal. For event type suicidal ideation, the listing will also indicate if intent was present and if 
the suicidal ideation was clinically significant. 
Additionally, a listing of all events identified for potential review by the Committee will be 
produced. This listing will indicate whether each event was identified by the Neuropsychiatric 
Event Adjudication Committee Chair for full committee review.  
Table 13‒2: Neuropsychiatric event classifications 
Event Type Code 
Event Classification 
Event Type 
1 
Suicidal 
Suicidal events/completed 
suicide 
2 
Suicidal 
Suicide attempt 
3 
Suicidal 
Preparatory acts toward 
imminent suicidal behavior 
4 
Suicidal/Non-suicidala 
Suicidal ideation 
7 
Non-suicidal 
Nonsuicidal Self-injurious 
behavior 
8 
Non-suicidal 
Nonsuicidal Other 
99 
Not applicable 
Inadequate information to 
adjudicate 
a Suicidal ideation event types can be classified by the Neuropsychiatric Adjudication Committee as Suicidal or 
Non-suicidal  depending on whether intent to die was present. 
Change #40 
Section 10.2.3.6 Inflammatory bowel disease 
The entire section was updated: 
Selected gastrointestinal events are adjudicated by the independent Inflammatory Bowel Disease 
(IBD) Adjudication Committee (IBD-CAC) according to the IBD-CAC Charter (version 3.0).  
Adjudicated events are classified by the IBD-CAC into one of the diagnostic types as defined in 
Table 10‒3. The events will further be classified as definite, probable or possible IBD. 
An overview of adjudicated IBD events 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 History of IBD CRF page ("Does subject have a history of IBD?”). 
This overview table will present events adjudicated by the IBD-CAC as either possible, probable 
or definite IBD. Definite and probable IBD will also be aggregated and summarized in this table. 
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In addition, this table will summarize each IBD event classification (possible, probable or 
definite) separately. 
Another table and listing will present the adjudicated IBD events by type. For each IBD event 
type, the individual PTs which fall within each event type will be summarized.  
Additionally, a listing of all events identified for potential review by the IBD-CAC will be 
produced. This listing will indicate whether each event was identified by the IBD-CAC Chair for 
full committee review. 
A further supportive listing will present the individual diagnostic criteria met for each 
adjudicated IBD event.  
Table 13‒3: IBD event classifications 
Event Type 
Code 
Event Type (Classification and diagnosis) 
Classification 
1 
Possible Inflammatory Bowel Disease – Crohn’s Disease 
Possible 
2 
Probable Inflammatory Bowel Disease – Crohn’s Disease 
Probable 
3 
Definite Inflammatory Bowel Disease – Crohn’s Disease 
Definite 
4 
Possible Inflammatory Bowel Disease – Ulcerative Colitis 
Possible 
5 
Probable Inflammatory Bowel Disease – Ulcerative Colitis 
Probable 
6 
Definite Inflammatory Bowel Disease – Ulcerative Colitis 
Definite 
7 
Possible Inflammatory Bowel Disease – type unclassified 
Possible 
8 
Probable Inflammatory Bowel Disease – type unclassified 
Probable 
9 
Definite Inflammatory Bowel Disease – type unclassified 
Definite 
10 
Symptoms not consistent with Inflammatory Bowel Disease 
Not 
applicable 
11 
Possible Inflammatory Bowel Disease – Microscopic Colitis 
Possible 
12 
Probable Inflammatory Bowel Disease – Microscopic Colitis 
Probable 
13 
Definite Inflammatory Bowel Disease – Microscopic Colitis 
Definite 
14 
Possible Inflammatory Bowel Disease – no further differentiation 
possible 
Possible 
15 
Probable Inflammatory Bowel Disease – no further differentiation 
possible 
Probable 
16 
Definite Inflammatory Bowel Disease – no further differentiation 
possible 
Definite 
99 
Not enough information to adjudicate 
Not 
applicable 
IBD=inflammatory bowel disease. 
Note: IBD diagnoses of “microscopic colitis” and “no further differentiation possible” were added in an adjudication 
charter amendment, accounting for the event type numbering. 
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Change #41 
Section 10.2.3.8 Hepatic events and PDILI 
The following word was added: 
Cases of potential Hy’s Law will be reported separately in a liver function test table. 
Change #42 
Section 12.1 Appendix A: MedDRA algorithmic approach to aanphylaxis 
The following text was added: 
• 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 (as anaphylaxis is an acute event, imputed dates should not be used in the 
algorithmic approach):  
 
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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
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Version:
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Document Number:
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Title:
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Approved Date:
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Document Approvals
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Name: 
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Date of Signature: 07-Jul-2022 13:31:05 GMT+0000
Approval
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Date of Signature: 07-Jul-2022 14:42:54 GMT+0000
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