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
Phase: PHASE3
Conditions: Hidradenitis Suppurativa
Sponsor: UCB Biopharma SRL

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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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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application and any extensions or variations thereof.

Approval Signatures
Name:
HS0004-protocol-amendment-4
Version:
1. 0
Document Number:
CLIN-000188473
Title:
HS0004-Protocol Amendment 4
Approved Date:
08 May 2022
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 06-May-2022 16:01:58 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 06-May-2022 16:48:41 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Medical
Date of Signature: 08-May-2022 20:16:36 GMT+0000
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application and any extensions or variations thereof.