Randomised, Double-blind, Placebo-controlled, Phase IIb/Phase III Study to Evaluate the Efficacy and Safety of Spesolimab in Patients With Moderate to Severe Hidradenitis Suppurativa. Lunsayil 1.
Phase: PHASE2
Conditions: Hidradenitis Suppurativa
Sponsor: Boehringer Ingelheim

BI-VQD-12177_40-106_AD-03 (21.0)
Clinical Trial Protocol
TITLE PAGE
Document Number:
c40061625-02
EudraCT No.
EU Clinical Trial No.
2022-501074-19-00
BI Trial No.
1368-0098
BI Investigational
Medicinal Product
Spevigo®, spesolimab
Title
Randomised, double-blind, placebo-controlled, 
Phase IIb/Phase III study to evaluate the efficacy and safety of 
spesolimab in patients with moderate to severe hidradenitis 
suppurativa. Lunsayil 1.
Lay Title
A study to test whether spesolimab helps people with a skin 
disease called hidradenitis suppurativa
Clinical Phase
IIb/III
Clinical Trial Leader
Coordinating 
Investigator
Current Version and 
Date
Final Version 2.0 02 Nov 2023
Original Protocol 
Date
02 Dec 2022
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 2023 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission.

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CLINICAL TRIAL PROTOCOL SYNOPSIS
Company name
Boehringer Ingelheim
Original Protocol 
date
Latest revision date
Final protocol Version 1, 02 Dec 2022
BI trial number
EU CT number
1368-0098
2022-501074-19-00
Title of trial
Randomised, double-blind, placebo-controlled, 
Phase IIb/Phase III study to evaluate the efficacy and safety of 
spesolimab in patients with moderate to severe hidradenitis 
suppurativa. Lunsayil 1.
Coordinating 
Investigator
Trial sites
Multi-centre trial conducted in approximately 40 countries
Clinical phase
IIb/III
Trial rationale
Hidradenitis suppurativa (HS) is an inflammatory skin disease 
characterised by recurrent inflammatory nodules, painful 
abscesses and fistulous tracts also called tunnels that may be 
draining a malodourous exudate. Patients with HS have one of 
the lowest quality of life measures of any dermatologic disease.
Spesolimab is a humanised, selective antibody that blocks the 
activation of the interleukin-36 receptor (IL-36R). It is 
hypothesised that by interfering with this mechanism, 
spesolimab may decrease neutrophilic and other immune cells
influx in lesions, thereby directly impact abscesses and draining 
fistulas, a high unmet medical need in HS. No other IL-36 
receptor antagonist is currently approved, that would provide 
information on identified risks in molecules of this class.
Study 1368-0098 consists of 2 parts: a dose finding Phase IIb
(Part 1), designed to primarily support the decision on optimal 
spesolimab dosing in patients with moderate to severe HS with 
existing draining tunnels (dT); a confirmatory Phase III (Part 2), 
designed to confirm positive benefit/risk ratio of spesolimab in 
HS.

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Benefit-risk 
assessment and 
ethical 
considerations
Spesolimab has shown acceptable tolerability so far in clinical trials 
of multiple indications. Considering the medical need for 
development of a more effective and well tolerated drug for the 
therapy of HS, the benefit of this trial is considered to outweigh the 
potential risks.
The placebo control until
is required to control for 
investigator bias and/or beneficial effects of being in a clinical trial.
By switching placebo recipients to active treatment from 
this protocol ensures an opportunity for all trial participants to 
receive active investigational medicinal product (IMP) treatment
during the study.
Trial objectives
Part 1 (Phase IIb)
The primary objectives of the dose finding phase are as follows:
(1) to demonstrate a non-flat dose response curve, evaluate the 
quantitative treatment effect size, and evaluate the dose-response 
relationship based on the primary endpoint of percent change 
from baseline in dT count at 
(2) to determine an optimal dose for Part 2 by incorporating 
information of available safety and of efficacy based on the 
primary endpoint of percent change from baseline in dT count at 
The secondary objectives are as follows:
(1) to demonstrate non-flat dose response curve based on selected 
secondary and further efficacy endpoints at 
(2) to evaluate the quantitative treatment effect size of percent 
change from baseline in dT count at
and absolute change 
from baseline in International Hidradenitis Suppurativa Severity 
Score System (IHS4) value at 
(3) to evaluate the sustainability of spesolimab efficacy up to 
 and up to 
(4) to assess safety of spesolimab.
The secondary objectives will be served by selected secondary and 
further efficacy endpoints, as well as safety endpoints.
Part 2 (Phase III)
The primary objective of the confirmatory phase is to demonstrate 
superiority of
 of 
spesolimab (identified on the basis of Phase IIb data analysis) 
against placebo in the mean percent change from baseline in dT 
count at 
The secondary objectives are as follows:
(1) to demonstrate superiority of spesolimab against placebo for 
the key secondary endpoints.
(2) to assess safety of spesolimab.

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Trial endpoints
Part 1 (Phase IIb)
Efficacy
Primary endpoint
Percent change from baseline in dT count at
Secondary endpoint

Percent change from baseline in dT count at 

Absolute change from baseline in IHS4 value at 

Absolute change from baseline in IHS4 value at 
Safety
Occurrence of treatment emergent adverse events (TEAEs).
Part 2 (Phase III)
Final endpoints for Part 2 will be supported by study results 
available at the time of Part 1 primary analysis.
Efficacy
Primary endpoint
Percent change from baseline in dT count at 
Key secondary endpoints
The followings are considered as potential key secondary endpoints. 
These may be amended according to Part 1 results.

Absolute change from baseline in IHS4 value at 

Absolute change from baseline in Hidradenitis Suppurativa Area 
Severity Index (HASI) score at 

Achievement of Hidradenitis Suppurativa Clinical Response 
(HiSCR50) at
HiSCR50 is defined as at least a 50% reduction in the total 
abscess and inflammatory nodule (AN) count with no increase in 
abscess count and no increase in dT count relative to baseline.

Percent change from baseline in abscess count at

Achievement of at least a 50% reduction in dT count at 
 
relative to baseline.

Achievement of at least a 50% reduction in abscess and dT 
(AdT) count at 
 relative to baseline.

Achievement of at least a 50% reduction in ANdT count at 
 relative to baseline.

Achievement of at least 30% reduction from baseline in 
Numerical rating Scale (NRS30) in Patient’s Global Assessment 
of HS pain at 
Safety
Occurrence of TEAEs.

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Trial design
Part 1 (Phase IIb) and Part 2 (Phase III)
International, multi-center, placebo-controlled, double blind, 
randomised trial assessing the efficacy and safety of spesolimab 
versus placebo in patients with moderate to severe HS over 
.
Total number of 
trial participants 
randomised
Part 1 (Phase IIb)
Part 2 (Phase III)
Number of trial 
participants per
treatment group
Part 1 (Phase IIb)
Part 2 (Phase III)

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Diagnosis,
main inclusion 
and exclusion 
criteria
Part 1 (Phase IIb) and Part 2 (Phase III)
Diagnosis:
Moderate to severe HS based on IHS4 criteria.
Part 1 (Phase IIb)
Main inclusion criteria (additional criteria clarifications may be 
found in the body of protocol):

Of full age of consent at screening.

Moderate to severe HS, based on IHS4 criteria, for at least 
6 months prior to and including Baseline visit.

HS lesions in
distinct anatomic area.

Biologic naive or TNFi-exposed for HS.

For biologic naïve, inadequate response to an adequate course of 
appropriate oral antibiotics for treatment of HS in the last 1 year
prior to the Baseline visit, as per investigator discretion

Total AN count 

Total dT count
Main exclusion criteria:

Use of restricted medications that interferes with the assessment 
of HS.

Prior exposure to any immunosuppressive biologic other than 
TNFi for HS.

Prior exposure to IL-36R inhibitors including spesolimab.
Part 2 (Phase III)
For inclusion and exclusion criteria, except for potential criteria
which will be confirmed after analysis of Phase IIb results, the same 
criteria as Part 1 (Phase IIb) will need to be met.
Trial intervention 
and test product
Spesolimab

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Dose and mode of 
administration
Part 1 (Phase IIb)
By group up to Visit 14 

High dose group

Medium dose group 

Low dose group 
By group from Visit 14 

From Visit 14
 trial participants in high and medium 
dose groups will receive 

From Visit 14 
 trial participants in low dose group 
will receive

Based on inadequate clinical response as per protocol, up-
titration
will be possible 
when applicable (low dose group).
From Visit 23 
on, trial participants will continue to 
receive the previously assigned dosing regimen until the results of 
primary analysis 
 are available. Upon availability of the 
Phase IIb primary analysis efficacy and safety results, the dosing 
regimen might be adapted from Visit 23 
through 
amendment.
Part 2 (Phase III)
The dosing regimen will be selected based on Phase IIb primary 
analysis.
Comparator 
product
Placebo.

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Dose and mode of 
administration
Part 1 (Phase IIb)

Up to Visit 14 
but not including this visit, matching.

From Visit 14
trial participants in the placebo group 
will be switched to
Visit 23 
 

From Visit 23 
on, trial participants will continue to 
receive the previously assigned dosing regimen until the results 
of primary analysis 
are available. Upon availability of 
the Phase IIb primary analysis efficacy and safety results, the 
dosing regimen might be adapted from Visit 23 
through amendment.
Part 2 (Phase III)

Up to
 matching.From 
 trial participants in the 
placebo group will be switched to a dose regimen selected on the 
basis of Phase IIb.
Duration of 
treatment
Part 1 (Phase IIb)
Administration of treatment will be up to
 The final 
assessment of treatment effect will be on
(EoT visit).
Part 2 (Phase III)
Administration of treatment will be up to
 The final 
assessment of treatment effect will be on 
(EoT visit).

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Statistical 
methods
Part 1 (Phase IIb)
To account for the repeated nature of the data and the covariates in 
the model,
Percent change from baseline in dT count will be used as the 
response variable 
 The
 include fixed 
categorical effects of treatment at each visit,
at each visit. Visit will be treated 
as the repeated measure with an unstructured covariance structure 
used to model the within-patient measurements.
Part 2 (Phase III)
The primary endpoint is percent change from baseline in dT count at 
 Restricted maximum likelihood estimation based on a 
mixed-effect model for repeated measures analysis will be used to 
obtain adjusted means for the treatment effects. This model will 
include categorical fixed effects for treatment at each visit, 
at baseline, and categorical baseline dT count at each visit. 
The primary treatment comparisons will be the contrast between 
treatment at 
Significance tests will be based on adjusted treatment differences 
using a one-sided α of 0.025.

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FLOWCHART
Part 1 (Phase IIb): Flowchart will be consolidated for Part 2 (Phase III) based on the primary analyses and/or interim analyses of Part 1.
Trial Periods
Screening
Treatment Period - up to 
Visit
1
2
Baseline
3
4
5
6
7*
8
9*
10
11
12
13
14
15*
16
17
18
19
20*
21
22*
23
Day 
Time window for visits (days)
n.a.
none
±1
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3

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FLOWCHART
Part 1 (Phase IIb): Flowchart will be consolidated for Part 2 (Phase III) based on the primary analyses and/or interim analyses of Part 1. 
(cont.)
Trial Periods
Screening
Treatment Period - up to 
Visit
1
2
Baseline
3
4
5
6
7*
8
9*
10
11
12
13
14
15*
16
17
18
19
20*
21
22*
23
Day 
Time window for visits (days)
n.a.
none
±1
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3

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FLOWCHART
Part 1 (Phase IIb): Flowchart will be consolidated for Part 2 (Phase III) based on the primary analyses and/or interim analyses of Part 1. 
(cont.)
Trial Periods
Screening
Treatment Period - up to 
Visit
1
2
Baseline
3
4
5
6
7*
8
9*
10
11
12
13
14
15*
16
17
18
19
20*
21
22*
23
Day 
Time window for visits (days)
n.a.
none
±1
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Trial Periods
Treatment Period – after
up to
EoT
Safety 
Follow-Up
Visit
24*
25
26*
27
28*
29
30*
31
EoT2
EoS
Day 
admin or 98 days 
from EoT.
Time window for visits (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
+7

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FLOWCHART
Part 1 (Phase IIb): Flowchart will be consolidated for Part 2 (Phase III) based on the primary analyses and/or interim analyses of Part 1. 
(cont.)
Trial Periods
Treatment Period – after 
up to
EoT
Safety 
Follow-Up
Visit
24*
25
26*
27
28*
29
30*
31
EoT2
EoS
Day 
98 days 
from EoT.
Time window for visits (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
+7

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FLOWCHART
Part 1 (Phase IIb): Flowchart will be consolidated for Part 2 (Phase III) based on the primary analyses and/or interim analyses of Part 1. 
(cont.)
Trial Periods
Treatment Period – after 
 up to
EoT
Safety 
Follow-Up
Visit
24*
25
26*
27
28*
29
30*
31
EoT2
EoS
Day 
or 98 days 
from EoT.
Time window for visits (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
+7
All adverse events19
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
Completion of patient participation 
X
HiSCR: Hidradenitis Suppurativa Clinical Response, IHS4: International Hidradenitis Suppurativa Severity Score System, HASI: Hidradenitis Suppurativa Area Severity Index, HS-
PGA: Hidradentis Suppurativa Physician's Global Assessment, DLQI: Dermatology Life Quality Index, HiS-QoL: Hidradenitis Suppurativa Quality of Life, PGI-C: Patient Global 
Assessment of Change, PGI-S: Patient Global Assessment of Severity, HODS: Hidradenitis odour and drainage scale, HADS: Hospital Anxiety and Depression Scale, C-SSRS: 
Columbia-Suicide Severity rating Scale, IHS4: International Hidradenitis Suppurativa Severity Score System
*
Visits should happen at site. However, for Visits 7, 9, 15, 20, 22, 24, 26, 28, and 30, trial participants will be offered the possibility to have home nursing visits if 
locally allowed. In exceptional circumstances (i.e. pandemic, conflict, other), visits might take place by phone just to collect safety information.
1
Day of randomisation/day of first intake of randomized medication. If needed, some Visit 2 assessments may be conducted within 2 days before or after the actual 
visit date after consultation with the sponsor.

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2
Trial participants who discontinue trial treatment prematurely should undergo the End of Treatment (EoT) visit as soon as possible. All trial participants
are expected to complete EoT visit, and EoS visit 
after their last trial drug intake or 
from EoT. 
For trial participants entering the 
 the EoT visit will be their EoS visit in trial 1368-0098 (see also footnotes #10 and #20).
3
Xc is a complete physical examination. Xt is a targeted physical examination. See Section 5.2.1. If home visits take place for Visits 7, 9, 15, 20, 22, 24, 26, 28, and 
30, instead of visits at site, a targeted physical examination may be done by a home-nurse. 
4
Measurements of vital signs should precede blood sampling to avoid the impact of blood sampling on the vital measurements at all dosing visits. Additional 
assessments of vital signs should be performed approximately at 10 minutes post-dose for
and approximately 5 minutes and 1 hour post dose 
for
See Section 5.2.2.
5
Women of childbearing potential only. A serum pregnancy test will be performed at screening. Urine pregnancy tests will be performed at all other visits indicated 
in the Flowchart. In case of a positive urine pregnancy test, a serum pregnancy test will be done. Urine pregnancy testing should be done prior to administration 
of study drug. Study drug should only be administered in case of a negative test result. More frequent testing should be done if required by the local regulation or 
per investigator judgment.
6
It is preferred, but trial participants do not have to be fasted for the blood sampling for the safety laboratory. At visits with study drug administration, this should 
be done prior to the study drug administration. See Table 5.2.3: 1 for detailed information of the tests. If needed, safety lab samples for Visit 2 can be drawn within 
48 hours before the actual visit date. If screening visit is done less than 7 days earlier of Visit 2 (baseline), safety laboratory test can be omitted at Visit 2.
7
Infection testing: at screening and at EoT visit. See Section of safety laboratory parameters for complete list of testing required (see Table 5.2.3: 2). For Japan 
only, if there is no chest X-ray test or CT taken within 3 months prior to Visit 1, it should be taken at screening visit. For South Africa only, tuberculosis infection 
testing should be done approximately at 6 months intervals. For this reason, participants from South Africa QuantiFERON testing should be done at visit 19.
8
ECG measurements should always precede blood sampling and drug administration. The ECG measurements need to be conducted at timepoints indicated in the 
Flowchart. Additional ECG measurements may be performed if the investigator deems it clinically indicated.
9
10
Trial participants who terminate study drug early should do the EoT visit as soon as possible. These participants will then do EoS visits,
after last study 
drug administration. When this discontinuation happens before Visit 14 
, in addition to safety follow up assessment, trial participants ideally should also 
continue visits for assessments of efficacy until
as per Flowchart. 
11
Desoxyribonucleic Acid (DNA) banking sample is optional. This sampling is only possible if the trial participant agreed by signing a separate informed consent. 
For details, please see Section 5.5.
12
Skin biopsy is mandatory at selected sites and should be sampled under ultrasound (US) guidance. For all other sites it is optional. Sites without the US required 
capabilities cannot perform skin biopsies. See Section 5.4.4.
13
US lesion evaluation is mandatory at selected sites with US capabilities. For all other sites it is optional. See Section 5.4.3.
14
IHS4 is used to classify trial participant’s severity at baseline. IHS4 will be derived from lesions count by a trained health care professional
15
Trial participant diaries will be handed to trial participants with the objective to collect daily information about NRS Pain and Pruritus from baseline, after being 
trained, till Visit 19 
 After Visit 19, NRS pain and NRS pruritus will be collected on a daily basis during the 7 days prior to the next scheduled visit 
(prior to Visit 23, Visit 27, Visit 31, and EoT visit). Site staff will collect the diaries from trial participants at visits indicated in the Flowchart to assess pain and 
pruritus since last visit. See Section 5.1.1.
16
At Screening, the C-SSRS baseline/screening scale will be completed. At all subsequent visits the “since last visit” scale will be completed.

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17a At Visit 2, instructions for paper version of patient’s daily diary will be dispensed to trial participants. Site staff should provide adequate training. Two weekly 
diaries and one additional 
17b Once electronic diary is available instructions for electronic diary will be dispensed to trial participants. Site staff should provide adequate training. Trial participant
diary captures
until Visit 19. From Visit 23, trial participants will record data for pain and 
pruritus during the last 7 days before the applicable visits (one daily diary on the last 7 days before the next scheduled visit). Analgesic use and other interventions 
to manage pain will be collected at the same time points, but in paper format.
18
Trial participant’s diaries returned by participants must be reviewed while the trial participant is in the consultation, so that any information can be clarified in an 
interview with the trial participant, if needed. 
19
For local tolerability at the administration site of the IMP, the investigator will perform an assessment during the study drug administration visit and at the time of 
AE assessment by questioning retrospectively since the last visit. Any observed local tolerability reaction, e.g. “swelling”, “induration”, “heat”, “redness” should 
be evaluated and reported as adverse events. 
20
All trial participants completing 
of the trial may be 
21
For South Africa only, tuberculosis infection testing should be done approximately at 6 months intervals. For this reason, participants from South Africa 

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TABLE OF CONTENTS
TITLE PAGE .........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOWCHART.......................................................................................................................10
TABLE OF CONTENTS ......................................................................................................17
ABBREVIATIONS AND DEFINITIONS...........................................................................21
1.
INTRODUCTION...............................................................................................26
1.1
MEDICAL BACKGROUND.............................................................................26
1.2
DRUG PROFILE................................................................................................26
1.3
RATIONALE FOR PERFORMING THE TRIAL.........................................30
1.4
BENEFIT - RISK ASSESSMENT.....................................................................30
1.4.1
Benefits.................................................................................................................30
1.4.2
Risks .....................................................................................................................31
1.4.2.1
Coronavirus disease 2019 .....................................................................................39
1.4.3
Discussion.............................................................................................................39
2.
TRIAL OBJECTIVES AND ENDPOINTS......................................................40
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS........40
2.1.1
Main objectives....................................................................................................40
2.1.2
Primary endpoints...............................................................................................41
2.1.3
Secondary endpoints...........................................................................................41
2.2
FURTHER OBJECTIVES AND FURTHER ENDPOINTS ..........................42
2.2.1
Further objectives ...............................................................................................42
2.2.2
Further endpoints ...............................................................................................42
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.........................46
3.1
OVERALL TRIAL DESIGN.............................................................................46
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)......................................................................................50
3.3
SELECTION OF TRIAL POPULATION .......................................................52
3.3.1
Main diagnosis for trial entry ............................................................................52
3.3.2
Inclusion criteria .................................................................................................53
3.3.3
Exclusion criteria ................................................................................................53
3.3.4
Discontinuation of trial participants from treatment or assessments............55
3.3.4.1
Discontinuation of trial treatment .........................................................................56
3.3.4.2
Withdrawal of consent to trial participation .........................................................57
3.3.4.3
Discontinuation of the trial by the sponsor...........................................................58
4.
TREATMENTS...................................................................................................59
4.1
INVESTIGATIONAL TREATMENTS ...........................................................59
4.1.1
Identity of the investigational medicinal products...........................................59
4.1.2
Selection of doses in the trial and dose modifications......................................60
4.1.3
Method of assigning trial participants to treatment groups ...........................62
4.1.4
Blinding and procedures for unblinding...........................................................62

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4.1.4.1
Blinding.................................................................................................................62
4.1.4.2
Emergency unblinding and breaking the code......................................................63
4.1.5
Drug assignment and administration of doses for each trial participant......63
4.1.6
Packaging, labelling, and re-supply...................................................................66
4.1.7
Storage conditions...............................................................................................67
4.1.8
Drug accountability.............................................................................................67
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS ................................................................................................68
4.2.1
Other treatments and emergency procedures..................................................68
4.2.2
Restrictions ..........................................................................................................69
4.2.2.1
Restrictions regarding concomitant treatment ......................................................69
4.2.2.2
Restrictions on diet and lifestyle...........................................................................71
4.2.2.3
Contraception requirements..................................................................................71
4.2.3
Concomitant medications/interventions ...........................................................71
4.2.3.1
Antibiotic use during the trial ...............................................................................72
4.2.3.2
Analgesics use during the trial..............................................................................72
4.2.3.3
Lesion intervention ...............................................................................................72
4.3
TREATMENT COMPLIANCE........................................................................73
5.
ASSESSMENTS..................................................................................................74
5.1
ASSESSMENT OF EFFICACY........................................................................74
5.2
ASSESSMENT OF SAFETY.............................................................................78
5.2.1
Physical examination ..........................................................................................78
5.2.2
Vital signs.............................................................................................................78
5.2.3
Safety laboratory parameters ............................................................................79
5.2.4
Electrocardiogram ..............................................................................................83
5.2.5
Other safety parameters.....................................................................................83
5.2.5.1
Local tolerability...................................................................................................83
5.2.6
Assessment of adverse events.............................................................................84
5.2.6.1
Definitions of AEs ................................................................................................84
5.2.6.1.1
Adverse event........................................................................................................84
5.2.6.1.2
Serious adverse event............................................................................................85
5.2.6.1.3
AEs considered “Always Serious”........................................................................85
5.2.6.1.4
Adverse events of special interest.........................................................................86
5.2.6.1.5
Intensity (severity) of AEs....................................................................................87
5.2.6.1.6
Causal relationship of AEs....................................................................................87
5.2.6.2
Adverse event collection and reporting ................................................................88
5.2.6.2.1
AE collection.........................................................................................................88
5.2.6.2.2
AE reporting to the sponsor and timelines............................................................89
5.2.6.2.3
Pregnancy..............................................................................................................89
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS...................................................................................90
5.3.1
Assessment of pharmacokinetics .......................................................................90
5.3.2
Methods of sample collection .............................................................................90
5.3.2.1
Plasma sampling for pharmacokinetic analysis ....................................................90
5.3.2.2
Sampling for ADA/NAb assessment ....................................................................90

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5.3.3
Analytical determinations ..................................................................................91
5.3.4
Pharmacokinetic - pharmacodynamic relationship.........................................91
5.4
ASSESSMENT OF BIOMARKERS.................................................................91
5.4.1
Biochemical and cellular biomarkers................................................................92
5.4.3
Imaging biomarkers............................................................................................92
5.4.4
Methods of sample collection .............................................................................92
5.4.5
Analytical determinations ..................................................................................93
5.5
BIOBANKING ....................................................................................................94
5.6
OTHER ASSESSMENTS...................................................................................94
5.7
APPROPRIATENESS OF MEASUREMENTS..............................................95
6.
INVESTIGATIONAL PLAN.............................................................................96
6.1
VISIT SCHEDULE.............................................................................................97
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS .................98
6.2.1
Screening period..................................................................................................99
6.2.2
Treatment period ..............................................................................................101
6.2.3
Follow-up period and trial completion............................................................102
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE....................................................................................................................103
7.1
NULL AND ALTERNATIVE HYPOTHESES .............................................103
7.2
PLANNED ANALYSES...................................................................................105
7.2.1
General considerations .....................................................................................105
7.2.2
Handling of intercurrent events.......................................................................105
7.2.3
Primary objective analyses...............................................................................107
7.2.3.1
Sensitivity analyses.............................................................................................110
7.2.3.2
Subgroup analyses...............................................................................................110
7.2.3.3
Supplementary analyses......................................................................................111
7.2.4
Secondary objective analyses...........................................................................111
7.2.5
Further objective analyses................................................................................112
7.2.6
Safety analyses...................................................................................................112
7.2.7
Other analyses ...................................................................................................113
7.2.8
Interim analyses ................................................................................................113
7.3
HANDLING OF MISSING DATA .................................................................114
7.4
RANDOMISATION .........................................................................................115
7.5
DETERMINATION OF SAMPLE SIZE .......................................................116
8.
INFORMED CONSENT, TRIAL RECORDS, DATA PROTECTION, 
PUBLICATION POLICY, AND ADMINISTRATIVE STRUCTURE ......118
8.1
TRIAL APPROVAL, PATIENT INFORMATION, INFORMED 
CONSENT .........................................................................................................118
8.2
DATA QUALITY ASSURANCE ....................................................................119
8.3
RECORDS.........................................................................................................119
8.3.1
Source documents .............................................................................................119
8.3.2
Direct access to source data and documents...................................................120
8.3.3
Storage period of records .................................................................................121
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS ................................121

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8.5
STATEMENT OF CONFIDENTIALITY AND TRIAL PARTICIPANT 
PRIVACY ..........................................................................................................121
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ...........................................................................................122
8.6
TRIAL MILESTONES.....................................................................................122
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL .................................123
9.
REFERENCES..................................................................................................125
9.1
PUBLISHED REFERENCES..........................................................................125
10.
APPENDICES...................................................................................................128
10.1
............128
10.2
TRIAL 
..........................................................................129
10.3
HIDRADENITIS SUPPURATIVA CLINICAL RESPONSE (HISCR)......130
10.4
INTERNATIONAL HIDRADENITIS SUPPURATIVA SEVERITY 
SCORE SYSTEM (IHS4).................................................................................131
10.5
HIDRADENITIS SUPPURATIVA AREA AND SEVERITY INDEX 
(HASI) ................................................................................................................132
10.6
HIDRADENITIS SUPPURATIVA PHYSICIAN GLOBAL 
ASSESSMENT (HS-PGA) ...............................................................................133
10.7
PAIN NUMERICAL RATING SCALE (NRS PAIN)...................................134
10.8
PRURITUS NUMERICAL RATING SCALE (NRS PRURITUS)..............135
10.9
DERMATOLOGY LIFE QUALITY INDEX (DLQI) ..................................136
10.10
HIDRADENITIS SUPPURATIVA QUALITY OF LIFE (HIS-QOL)........138
10.11
FACIT-FATIGUE.............................................................................................140
10.12
PATIENT GLOBAL IMPRESSION OF CHANGE (PGI-C) ......................141
10.13
PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S)....................142
10.14
HIDRADENITIS SUPPURATIVA ODOUR AND DRAINAGE SCALE 
(HODS)...............................................................................................................143
10.15
HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS) ...................144
10.16
WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT 
QUESTIONNAIRE FOR HS (WPAI-HS)......................................................145
10.17
EUROQOL 5 DIMENSIONS 5-LEVEL (EQ-5D-5L)...................................147
10.19
TRIAL PARTICIPANT FEEDBACK............................................................162
10.20
DIAGNOSIS OF ANAPHYLAXIS .................................................................163
10.21
COVID-19 RISK ASSESSMENT....................................................................164
10.22
FITZPATRICK SKIN TYPE SCALE............................................................166
11.
CONFIDENTIALITY STATEMENT DESCRIPTION OF GLOBAL 
AMENDMENT(S).............................................................................................167

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ABBREVIATIONS AND DEFINITIONS
AD
Atopic Dermatitis
ADA
Anti-drug antibody
ADCC
Antibody-dependent cellular cytotoxicity
AdT
Abscess and draining fistula/tunnel count
AE
Adverse event
AESI
Adverse event of special interest
ALCOA
Attributable, legible, contemporaneous, original, accurate 
ALT
Alanine aminotransferase
AN
Abscess and inflammatory nodule
AN count
Abscess and inflammatory nodule count
ANdT count
Abscess, inflammatory nodule, and draining fistula/tunnel count
AST
Aspartate aminotransferase
AUC
Area under the curve
BI
Boehringer Ingelheim
BSA
Body Surface Area
CA
Competent authority
CDC
Complement-dependent cytotoxicity
CKD-EPI
Chronic kidney disease Epidemiology Collaboration
Cmax
Maximum concentration
COVID-19
Coronavirus disease 2019
CQM
Clinical quality monitoring
CRA
Clinical research associate
CRF
Case report form, paper or electronic (sometimes referred to as “eCRF”)
CRO 
Contract research organisation
C-SSRS
Columbia-Suicide Severity rating Scale
CT
Clinical trial
CTCAE
Common Terminology Criteria for Adverse Events
CTP
Clinical trial protocol
CTR
Clinical trial report
DILI
Drug induced liver injury
DLQI
Dermatology life quality index
DMC 
Data monitoring committee

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DNA
Desoxyribonucleic Acid
dT
Draining fistula/tunnel
EC
Ethics committee
ECG
Electrocardiogram
eCRF
Electronic case report form
eDC
Electronic data capture
EoS
End of study
EoT
End of treatment
EQ-5D-5L
EuroQol 5 dimensions 5-level
EU
European Union
EudraCT
European Union drug regulating authorities clinical trials
FACIT
Functional assessment of chronic illness therapy 
FAS
Full Analysis Set
FDA
Food and Drug Administration
FUP
Follow-up
GBS
Guillain-Barré syndrome
GCP
Good clinical practice
GMP
Good manufacturing practice
GPP
Generalized pustular psoriasis
HAs
Health authorities
HADS
Hospital anxiety and depression scale
HASI
Hidradenitis suppurativa area and severity index
HiSCR
Hidradenitis suppurativa clinical response
HiS-QoL
Hidradenitis suppurativa quality of life
HIV
Human immunodeficiency virus
HODS
Hidradenitis suppurativa odour and drainage scale
HS
Hidradenitis suppurativa
hs-CRP
High-sensitivity c-reactive protein 
HT29
Hypertriptoid-29
HV
Healthy Volunteers
I&D
Incision and Drainage
i.v.
Intravenous
IB
Investigator’s brochure

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IC90
90% of maximal inhibitory concentration
ICF
Informed consent form
ICH
International Council on Harmonisation
IEC
Independent ethics committee
IFNγ
Interferon gamma
Ig
Immunoglobulin
IGRA
Interferon gamma release assay
IHS4
International hidradenitis suppurativa severity score system 
IL(-)36
Interleukin 36
IL(-)36R
Interleukin 36 receptor
IL(-)36RN
Interleukin 36 receptor antagonist
IMP
Investigational medicinal product
ISPOR
International Society for Pharmacoeconomics & Outcomes Research
IPDs
Important protocol deviations
IQRMP
Integrated Quality and Risk Management Plan
IRB
Institutional review board
IRT
Interactive response technology
ISF
Investigator site file
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
K2EDTA
Dipotassium ethylendiaminetetraacetic acid
KO mutation
Knockout mutation
LPLT
Last patient last treatment
LTE
Long Term Extension
MCID
Minimal Clinical Important Difference
MedDRA
Medical Dictionary for drug regulatory activities
MRD
Multiple rising dose
mRNA
Messenger RNA
NAb
Neutralizing antibody
N count
Inflammatory nodule count
NETosis
Neutrophil extracellular trap-osis

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NF-κB
Nuclear factor-kappa B
NOAEL
No-observed-adverse-effect level
NRI
Non response imputation
NRS
Numerical rating scale
NRS30
Reduction of 30% in numerical rating scale
OPU
Operative unit
PBMC
Peripheral blood mononuclear cell
PCR
Polymerase chain reaction
PD
Pharmacodynamics
PFS
Pre-filled syringes
PGA
Physician global assessment
PGI-C
Patient Global Impression of Change
PGI-S
Patient Global Impression of Severity
PK
Pharmacokinetic(s)
POAB
Patient organisation advisory board
PoCC
Proof of Clinical Concept
PPD
Purified protein derivative
PPS
Per-protocol set
PPP
Palmoplantar pustulosis
PROs
Patient reported outcomes
PSPV
Patient Safety Pharmacovigilance
PT
Preferred term
PTM
Planned Time
q2w
Once every 2 weeks
qw
Every week
RAs
Regulatory authorities
RCTC
Rheumatology common toxicity criteria
REP
Residual effect period
RNA
Ribonucleic acid
ROW
Rest of the world
RS
Randomised set
s.c.
Subcutaneous
SAE
Serious adverse event

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SAF
Safety Analysis Set 
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SDTM
Standard Data Tabulation Model
SFQ
Site Feasibility Questionnaire
SoC
Standard of care
SOP
Standard operating procedure
SPI
Stability and Packaging Information
SRD
Single rising dose
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
TBA
Trial Bio Analyst
TBIL
Total bilirubin 
TEAE
Treatment-emergent adverse events
TMF
Trial master file
TNF
Tumor necrosis factor
TNFi
Tumor Necrosis Factor inhibitor
TS
Treated set
TSAP
Trial statistical analysis plan
TST
Tuberculin-skin testing
UC
Ulcerative colitis
ULN
Upper limit of normal
US
Ultrasound
vs.
Versus
WHO
World Health Organisation
WOCBP
Woman of childbearing potential
WPAI-HS
Work Productivity and Activity Impairment Questionnaire for HS

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1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
Hidradenitis suppurativa (HS) is an inflammatory skin disease characterised by recurrent 
inflammatory nodules, painful abscesses and fistulous tracts also called tunnels that may be 
draining a malodourous exudate. Patients with HS have one of the lowest quality of life 
measures of any dermatologic disease. Lesions characteristically occur in the axillary, groin, 
infra-mammary, and/or anogenital regions of the body. Significant pain is a major symptom 
and lesion sequalae include scarring, and psychological distress. The average age of onset is 
during the early 20s [R20-3184]. The prevalence of HS is estimated to be 0.3% globally, 
ranging from 0.2% to 0.6%, with variability across geographic settings [R22-3282].
Treatment often begins with topical or oral antibiotics, such as topical clindamycin and oral 
tetracycline, followed by the use of other antibiotics if there is no improvement. When topical 
medications and oral antibiotics fail, or the disease has progressed, biologics are 
recommended [R20-3177]. Adalimumab is the only approved biologic, with a Hidradenitis 
Suppurativa Clinical Response (HiSCR50: at least a 50% reduction in the total abscess and 
inflammatory nodule [AN] count with no increase in abscess count and no increase in 
draining fistulas/tunnels [dT] count relative to baseline) rate of 42% to 59% versus placebo 
response rate of 26% to 28%, with a schedule of weekly subcutaneous dosing. When drug 
treatment management is insufficient or ineffective, surgery is the only option, leading to 
burdensome healing periods.
Some of the most burdensome HS symptoms from patient perspective are pain, drainage and 
explosive openings, itch, skin tightness (scarring), odour, fatigue, and flu-like symptoms. 
Patients report to be unsatisfied with the level of control offered by currently available 
treatment options. Unmet needs from the patient perspective include the need for new 
medical treatments with favourable efficacy and tolerability profiles. In qualitative evidence, 
the most important treatment goals from the patient perspective were relief from or 
improvement in pain, drainage (including explosive openings) and fatigue.
Clearly, current therapeutic options have their limitations, and there is a high need for safe 
and effective treatment that provides rapid control and fast resolution of skin signs and 
symptoms. In particular, reduction of draining tunnels (dTs) represents a high unmet medical 
need.
1.2
DRUG PROFILE
Mode of action
Spesolimab is a humanised, selective antibody that blocks the activation of the human 
interleukin-36 receptor (IL-36R). IL-36 is a potent activator of neutrophil infiltration. In 
patients with generalised pustular psoriasis (GPP), spesolimab treatment rapidly stopped the 
flare and cleared pustules, the primary lesions in GPP. 
HS and GPP have similarity in neutrophil infiltration. IL-36 alpha, beta, and gamma mRNA 
expression are upregulated in lesioned skin in HS patients, with a decrease in IL36RN 
expression [R20-3047]. In the context of HS, neutrophils are shown to undergo neurophil 

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extracellular trap-osis (NETosis) leading to secretion of type I interferons [R20-3155].
Navrazhina et al. showed that in HS lesional skin, a IL-36/IL-17 mediated feed forward 
mechanism may play a role in the pathogenesis of dTs [R22-2400]. It is hypothesised that by 
interfering with this mechanism, spesolimab may decrease neutrophilic and other immune 
cell infiltrations, thereby directly impact abscesses and dTs, a high unmet medical need in 
HS.
Key pharmacokinetic and immunogenicity characteristics
Spesolimab has been characterised by typical IgG1 monoclonal antibody pharmacokinetics
(PK). PK data showed that exposure increased with increasing dose in a dose proportional 
manner from 0.3 mg/kg to 20 mg/kg following intravenous (i.v.) administration of 
spesolimab to healthy volunteers. In healthy volunteers, the geometric mean spesolimab 
clearance (gCV%) was 0.146 (23.3%) L/day. The corresponding terminal half-life was 28.8 
(25.1%) days. The clearance in GPP patients was approximately 25% higher. 
Comparing the exposures between the 300 mg subcutaneous (s.c.) dose and 300 mg i.v. dose, 
a s.c. bioavailability of ~70% was determined. No differences in PK were observed between 
Caucasians and Japanese subjects.
Immunogenicity
In healthy volunteers, ADA to spesolimab was developed with a median onset time ranging 
4-17 weeks across trials. Overall, the ADA incidence was comparable between i.v. and s.c. 
administration. The ADA incidence appeared to be higher in females, though the maximum 
titer was comparable between males and females. Following single dose administrations of 
s.c. or i.v. spesolimab, the ADA incidence rate was 39%-52% in females, compared with 
19~24% in males. The impact of ADA on spesolimab PK was overall mild in healthy 
volunteers. Following i.v. administration, lowered spesolimab concentration was only 
observed in 1 subject in trial 1368-0001, and possibly in 2-3 subjects in trial 1368-0043 (all 
with maximum titer greater than 11 400). Following s.c. administration, ADA formation may 
have contributed to the lowered spesolimab concentrations in some volunteers with 
maximum titer higher than 11 400 in trial 1368-0029.
Details of immunogenicity results in other indications can be found in the current 
Investigator’s Brochure (IB) [c03320877-11].
Residual Effect Period (REP)
The REP of spesolimab is 16 weeks. This is the period after the last dose with measurable 
drug levels and/or pharmacodynamic effects still likely to be present.

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Data from non-clinical studies
Non-clinical pharmacology
Spesolimab binds to human IL-36R with a binding avidity of less than 1 pM. Spesolimab 
inhibits IL36 ligand-stimulated NF-κB activation in HT29 cells and transformed epithelial 
cells and in primary human dermal fibroblasts or intestinal myofibroblasts with IC90 values in 
a consistent range of 0.7 to 3.7 nM. Spesolimab also inhibits IL8 release in IL36-stimulated
human dermal fibroblasts and IFNγ secretion in human peripheral blood mononuclear cell
(PBMC) stimulated with IL36α, IL36β, or IL36γ combined with IL12.
Mutations of two key residues (L234 and L235) to alanine were made to spesolimab to 
abrogate FcR binding activity and function. Direct assessment of the impact of the mutations 
in the IgG1 FcR binding sites on both antibody-dependent cellular cytotoxicity (ADCC) and 
complement-dependent cytotoxicity (CDC) effector functions revealed that the mutations 
abrogate both ADCC and CDC effector functions and indicate that spesolimab will be a non-
depleting therapy in vivo.
Toxicology
Spesolimab does not bind to IL-36R from common toxicology species. Therefore, 
meaningful toxicity studies of the molecule cannot be performed in any animal species with 
spesolimab. However, hazard identification studies of the mode-of-action of IL-36R 
inhibition were performed in mice using a mouse specific anti-IL-36R monoclonal antibody 
(BI 674304). Details of results concluding to a no-observed-adverse-effect level (NOAEL) of 
50 mg/kg/day can be found in the current IB [c03320877-11].
Data from clinical studies
This section presents the high-level summary of results from clinical studies. For a more 
detailed description of the spesolimab profile, please refer to the current IB [c03320877-11].
First in human single rising dose trial 1368-0001 [c09985235-01]
Spesolimab has been administered as a single i.v. dose to healthy volunteers. A total of 
78 subjects were randomised within 11 sequential dose groups to active drug (dose range: 
0.001 to 10 mg/kg body weight) or placebo. In total, 58 subjects received spesolimab and 
20 subjects received placebo. All subjects completed the trial according to the protocol.
In total, 49 out of 78 subjects (62.8%) were reported with at least 1 AE while on-treatment 
(spesolimab: 36 out of 58 subjects [62.1%]; placebo: 13 out of 20 subjects [65.0%]). All AEs 
were of mild or moderate intensity. There were no serious AEs, no AEs that led to 
discontinuation of trial drug, no protocol-specified AEs of special interest and no other 
significant AEs according to project definition. All AEs were resolved by the end of the trial. 
No relevant changes were observed in safety laboratory tests, vital signs, and ECGs. 
Importantly, there were no relevant differences in frequencies of subjects with treatment 
emergent AEs between the treatment groups, and no dose-dependency was observed.
Multiple rising dose trial 1368-0002 [c18789185-01]
In a multiple rising dose trial, spesolimab or placebo have been administered to 40 healthy 
volunteers at multiple ascending intravenous (i.v.) doses of 3, 6, 10 and 20 mg/kg given qw 
for 4 weeks (i.e. 4 administrations) or a single dose of 20 mg/kg (8 subjects each, 3:1 on 
active or placebo). Overall, spesolimab was well tolerated. There were no dose dependent 
AEs and no SAEs. In all cases the AEs were of mild or moderate intensity. Furthermore, 

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there were no clinically relevant abnormalities on treatment with spesolimab with respect to 
safety laboratory, vital signs, or ECGs as assessed by a central reader.
Phase IIa trial 1368-0052
The efficacy and safety of spesolimab in patients with moderate to severe HS was 
Open label extension (OLE) trial 1368-0067
Summary

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1.3
RATIONALE FOR PERFORMING THE TRIAL
Study 1368-0098 consists of 2 parts: a dose finding phase (Phase IIb), designed to primarily 
support the decision on optimal spesolimab dosing in patients with moderate to severe HS, 
but also collect data on 
 and accrue long term 
safety/efficacy experience on optimal spesolimab dosing once available; a confirmatory 
phase (Phase III), designed to confirm the efficacy and safety of optimal spesolimab dosing 
in patients with moderate to severe HS.
Based on the medical background (see Section 1.1) and drug profile (see Section 1.2), there is 
an unmet medical need in HS, and spesolimab may directly have a positive impact on this 
high unmet medical need. In addition, no other IL-36 receptor antagonist is currently 
approved, to provide information on identified risks in molecules of this class. Therefore, the 
knowledge of the safety and risk profile of compounds in this class is limited. To perform this 
trial will provide further efficacy and safety profile of spesolimab for further development, 
which may help to provide alternative treatment option for patients with moderate to severe 
HS.
The study of
will mostly be hypothesis-generating or supportive to 
endpoints. These findings will be used to expand our understanding of the disease HS and the 
investigational compound, e.g. by learning more about the drug mechanism or the biology of 
the disease, to correlate patient subgroups with differential responses to treatment and/or to 
prognosis, 
In order to be able to address future scientific questions, trial participants will be asked to 
voluntarily
(please see Section 5.5. If the trial participant 
agrees, banked samples may be used for 
 and drug 
1.4
BENEFIT - RISK ASSESSMENT
Spesolimab potential benefit in HS and associated risk is still at an early stage of definition. 
Participation in this trial may help providing future benefit to patients with HS if spesolimab 
development in this indication proves to be successful. Of note, spesolimab is currently 
approved in the USA for the treatment of GPP flare at the dose of 900 mg i.v, followed by an 
additional 900 mg i.v. dose if symptoms persist. HS is a different skin disease and required a
separate clinical development to establish spesolimab benefit/risk ratio in this indication.
1.4.1
Benefits
Before initiation of this trial, approximately
have been exposed to 
of spesolimab regardless of dose. Spesolimab was safe and well 
tolerated in three healthy volunteers' trials at all dose groups up to the highest tested dose of 
20 mg/kg body weight given once a week for up to 4 weeks (for details see the latest version 
of spesolimab IB [c03320877-11]). Subsequently, several clinical studies exploring efficacy 
and safety of spesolimab in different indications have been conducted or are ongoing. 

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Spesolimab has been tested in single dose (10 mg/kg i.v.) in GPP and in multiple doses up to 
900 mg i.v. in PPP which were all safe and well tolerated.
1.4.2
Risks
No other IL-36 receptor antagonist is currently approved, that would provide further 
information on identified risks in molecules of this class. The knowledge of the safety and 
risk profile of compounds in this class is still considered limited. However, the safety profile 
of spesolimab is considered acceptable based on available data from completed trials.
In order to protect the trial participant’s safety during conduct of this trial, an independent 
Data Monitoring Committee (DMC) will periodically review clinical trial safety data. For 
details, please see Section 8.7. In addition to the AE tracking, planned interim analysis at 
of Part 1 of the trial will also contribute to the monitoring of any safety signal (see 
Section 7.2.8).
For potential risks, Table 1.4.2: 1 lists the possible risks for spesolimab as well as theoretical 
risks derived from general safety considerations of immunomodulatory drugs and from this 
trial specific procedures. For details on treatment-related risks, refer to Section 1.2 and IB
[c03320877-11].

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Table 1.4.2: 1
Overview of trial-related and potential risks
Possible or known risks 
of clinical relevance for 
this trial
Summary of data, rationale for the risk
Mitigation strategy
Systemic hypersensitivity 
reaction
After administration of any biologic agent or protein, 
there is a possibility of occurrence of immediate 
(such as anaphylaxis) or delayed (such as drug 
reaction with eosinophilia and systemic symptoms) 
adverse immune reactions. 
Patients with a history of allergy/hypersensitivity to 
the systemically administered trial medication agent 
or its excipients are excluded from the trial.
In case of systemic hypersensitivity reactions 
including anaphylactic reaction emerging during or 
after administration of trial medication, the 
investigator should consider in accordance with 
severity of the reaction and local standard of care to 
interrupt and treat the condition.
Systemic hypersensitivity reaction is defined as an 
adverse event of special interest (AESI); see 
Section 5.2.6.1.4. It is subject to close monitoring 
and investigators are requested to assess these 
conditions using the criteria discussed in the 
statement paper from Sampson HA [R11-4890].

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Infections 
(serious, 
severe, opportunistic)
Inhibition of the immune response with an immune-
modulating biologic may increase the risk of 
infections.
A recent characterisation
of individuals with 
homozygous IL-36R KO mutations revealed that 
normal immune function was broadly preserved 
suggesting that IL-36 signaling pathway inhibition 
may not substantially compromise host defenses 
[R17-3632].
In clinical trials with spesolimab, a higher proportion 
of patients with mild to moderate infections was seen 
in the spesolimab treatment group than in the 
placebo treatment group.
Nevertheless, there was no indication of an increased 
frequency of patients with severe, serious, and 
opportunistic 
infections 
in 
association 
with 
spesolimab treatment.
Screening procedures for infections are defined for 
this trial. Patients with any relevant chronic or acute 
infections including human immunodeficiency virus 
(HIV), viral hepatitis or tuberculosis are excluded 
from the trial. Treatment of infections should be 
initiated promptly according to standards of care.
Severe infections and opportunistic infections are 
considered AESIs for this trial; see Section 5.2.6.1.4. 
These conditions and serious infections are subject 
to close monitoring.

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Malignancies
Inhibition of the immune response with an 
immunomodulatory drug may potentially impair 
immune defences and thus theoretically decrease 
immune defence against malignancies.
A recent characterisation
of individuals with 
homozygous IL-36R KO mutations revealed that 
normal immune function was broadly preserved 
suggesting that IL-36 signaling pathway inhibition 
does not compromise host defenses [R17-3632]
Patients with a recent history of malignancy will be 
excluded from participation in this trial. In case of 
occurrence of malignant neoplasm other than 
appropriately treated basal cell carcinoma or 
squamous cell carcinoma of the skin or in situ 
carcinoma of uterine cervix, the investigator should 
discontinue treatment with spesolimab. Diagnostics 
and treatment have to be initiated according to local 
standard of care.
Malignancies represent always serious adverse 
events and are subject to close monitoring; see 
Section 5.2.6.1.3.

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Peripheral neuropathy
Three cases reported by the investigator as Guillain-
Barré syndrome (GBS) were received in ongoing 
clinical trials with spesolimab. 
Case #1 was from the Phase II open label extension 
trial 1368-0017/ indication UC. Case #2 was from 
the Phase II open label extension trial 1368-0024/ 
indication PPP. Case #3 was from the Phase II open 
label extension trial 1368-0067/indication HS. 
A panel of independent neurologists and experts in 
the study of neuropathies assessed the 3 cases. Only 
1 met level 4 diagnostic certainty for the diagnosis of 
GBS (lowest level on Brighton scale of 1 to 4). In 
that case, there was a coincident infection with 
SARS-CoV-2. The other 2 cases were assessed as 
not GBS. Observed cases showed a heterogenous 
pattern.
As per assessment by the panel of external 
neurologists the nonspecific symptoms and findings 
in all three cases may best be referred to as peripheral 
neuropathy.
A causal association with spesolimab for any of the 
reported cases was assessed to be unlikely as per 
independent external expert adjudication.
Timely detection, evaluation, and follow-up of 
suspected peripheral neuropathies to ensure patients´ 
safety. 
Use of dedicated questions to elicit neurologic 
history during screening and exclusion criteria to 
avoid selection of patients with acute demyelinating 
neuropathy.
Targeted follow-up questions to gather detailed 
information in case of any event during trial to 
ensure proper decision making. 

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Trial procedures
Blood sampling
Inflammation of the wall of 
the vein. Injuring of a nerve 
while inserting the venous 
catheter, 
potentially 
resulting in paraesthesia, 
reduced sensibility, and/or 
pain 
for 
an 
indefinite 
period.
General risk, acceptable in framework of trial 
participation. 
As with all blood sampling, there is a risk of mild 
pain, local irritation, or bruising (a black or blue 
mark) at the puncture site. Furthermore, there is a 
small risk of lightheadedness and/or fainting. In rare 
cases, the puncture site can also become infected, or 
nerves may be damaged, inducing long-lasting 
abnormal 
sensations 
(paresthesia), 
impaired 
sensation of touch and persistent pain.
Evaluation of the medical expertise of the trial sites 
is a part of site feasibility assessment. To ensure 
participant safety, all events or symptoms reported 
will be managed according to the judgment of the 
investigator.
These risks will be addressed by careful safety 
monitoring and risk mitigation measures such as
(a) pressure on the puncture site for approximately 5 
minutes 
after 
the 
needle 
extraction, 
is 
recommended.
(b) close clinical monitoring for AEs.
(c) selection of experienced sites and site staff.
(d) safety recommendations provided in laboratory 
manual.
Skin biopsy
Can cause local bruising, inflammation, nerve 
damage and pain.
These risks will be addressed by careful safety 
monitoring and risk mitigation measures such as
(a) close clinical monitoring for AEs.
(b) selection of experienced sites and site-staff.
(c) staff training.

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Other risks
Administration of placebo
If the trial participant is randomised to 
receive a placebo, the participant’s condition 
could get worse during the trial.
The placebo control is required to control for investigator 
bias and/or beneficial effects of being in a clinical trial. 
The rationale for switching placebo trial participants to 
active treatment at Visit 14 
is to give these trial 
participants
the 
opportunity 
to 
receive 
active 
investigational medicinal product (IMP) treatment from 
that visit.
The use of rescue medication is foreseen in this trial for 
participants experiencing a worsening of their HS 
condition; see Section 4.2.3.
Suicidal ideation and 
behaviour*
Increased risk of suicidal ideation and 
behaviour is present in the population of 
patients with HS
‘Baseline/ screening’ version of C-SSRS will be 
administered with the aim to exclude patients with active 
moderate to severe symptomatology present within a 
specified time prior to the screening or screening visit. 
‘Since last visit’ version of C-SSRS will be administered 
with the aim to monitor trial participant’s safety during the 
trial and to initiate actions for the participant’s safety if 
such actions are deemed necessary.
All C-SSRS reports of suicidal ideation type 4 or 5 and all 
reports of suicidal behavior represent SAEs and are subject 
to close monitoring; see Section 5.2.5.2. Participants with 
C-SSRS score of 4 or 5 have the trial treatment 
discontinuation criteria (see Section 3.3.4.1)

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Table 1.4.2: 1 Overview of trial-related and potential risks (cont.)
Drug-induced liver injury 
(DILI)
Although rare, a potential for DILI is under constant 
surveillance by sponsors and regulators. Therefore, 
DILI is considered as a standard risk in all BI 
development programs.
Timely detection, evaluation, and follow-up of 
laboratory alterations in selected liver laboratory 
parameters to ensure trial participant’ safety (see also 
Section 5.2.6.1.4). Trial treatment discontinuation 
criteria as well as criteria for trial treatment restart 
are implemented for relevant cases.
*
This is due to a higher risk in the population of patients with HS and not specifically due to the mechanism itself

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Regarding reactions to injections/infusions, specific safety measures will be taken during the 
trial. Following the injection/infusion the trial participants will be monitored for reactions at 
the site according to the Instructions for Preparation and Handling of Spesolimab/Placebo 
which can be found in the Investigator Site File (ISF). Local tolerability will be carefully 
monitored in this study (see Section 5.2.5.1).
Based on the findings in the non-clinical studies conducted to date and in accordance with 
international regulatory guidelines, the inclusion of Women of Child Bearing Potential 
(WOCBP) in this study is justified. To minimise the risk of unintentional exposure of an 
embryo or fetus to the investigational drug, WOCBP must agree to the requirements for the 
pregnancy testing (see Flowchart) and contraceptive methods; see Section 4.2.2.3.
1.4.2.1
Coronavirus disease 2019
At the time of this original protocol, the COVID-19 pandemic is active in many countries.
Given the unique circumstances created by the pandemic, specific consideration has been 
given to the benefits and risks of the trial as they relate to the pandemic and potential 
SARS-CoV-2 infection; see Appendix 10.21.
1.4.3
Discussion
Based on the drug profile (see Section 1.2), there is no mechanism- or compound-related 
safety concerns of spesolimab. It is expected that trial participants with moderate to severe 
HS will not be exposed to unacceptable, undue risks, and AEs.
In the context of the unmet medical need and anticipated benefit of spesolimab, based upon 
the available non-clinical and clinical information (see Section 1.2), the benefit risk 
evaluation of the compound is favourable.
Considering the medical need for the development of a better tolerated and more effective 
treatment for patients with moderate to severe HS, the expected benefit outweighs the 
potential risks.

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2.
TRIAL OBJECTIVES AND ENDPOINTS
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS
Final endpoints for Part 2 will be supported by study results available at the time of Part 1 
primary analysis
2.1.1
Main objectives
Study 1368-0098 consists of 2 parts: dose finding Phase IIb (Part 1), designed to find the 
optimal dose in patients with moderate to severe HS for Phase III development; confirmatory 
Phase III (Part 2), designed to assess the efficacy and safety of spesolimab in patients with 
moderate to severe HS. Patients recruited in Part 1 cannot participate in Part 2.
Part 1 (Phase IIb)
The dose finding phase (Part 1) will characterise the dose-response curve and exposure-
response relationship and will support identifying the dose of spesolimab providing the most 
adequate benefit/risk to patients with moderate to severe HS by assessing 3 dosing regimens 
(for detailed dosing regimens, please see Section 3.1 and Section 4.1.4) and placebo. 
The primary objective of dose finding phase are as follows (for summary measure of 
treatment effect, please see Section 2.1.2):
(1) to demonstrate a non-flat dose response curve, evaluate the quantitative treatment effect 
size, and evaluate the dose-response relationship based on the primary endpoint of percent 
change from baseline in dT count at 
(2) to determine an optimal dose candidate for Part 2 by incorporating information of 
available safety and of efficacy based on the primary endpoint of percent change from
baseline in dT count at 
The secondary objectives are as follows:
(1) to demonstrate non-flat dose response curve based on selected secondary and further 
efficacy endpoints at 
(2) to evaluate the quantitative treatment effect size of percent change from baseline in dT
count at
and absolute change from baseline in International Hidradenitis 
Suppurativa Severity Score System (IHS4) value at 
(3) to evaluate the sustainability of spesolimab efficacy up to 
.
(4) to assess safety of spesolimab.
The secondary objectives will be served by selected secondary and further efficacy endpoints, 
as well as safety endpoints (for list of secondary and further endpoints, please see 
Section 2.1.3 and Section 2.2.2).
The primary and secondary analyses will be based on Full analysis set (FAS), defined as trial 
participants randomised in Part 1 and having received at least 1 dose of study drug. Treatment 
comparisons will be performed regardless of treatment adherence.

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Part 2 (Phase III)
Because of the use of modelling,
in Part1.
The confirmatory phase aims to provide substantial evidence of the efficacy, safety, and 
tolerability of spesolimab in comparison to placebo in trial participants with moderate to 
severe HS.
Part 2 will not be conducted if the analysis of Part 1 (Phase IIb) at
data cut-off does 
not conclude to potential of spesolimab for demonstrated clinical benefit versus placebo in 
terms of effect size and sustainability. The dose
for 
Part 2 (Phase III) will be based on all available data at the time of primary analysis when last 
trial participant complete Visit 10 
The primary objective of the confirmatory phase (Part 2) is to demonstrate superiority of one 
dosing regimen 
of spesolimab (identified on the 
basis of Phase IIb data analysis) against placebo in the 
from baseline in 
The secondary objectives are as follows:
(1) to demonstrate superiority of spesolimab against placebo for the key secondary 
endpoints (please see Section 2.1.3). 
(2) to assess safety of spesolimab. 
The primary and secondary analyses will be based on the TS, defined as trial participants
randomised in Part 2 and having received at least 1 dose of study drug. Treatment 
comparisons will be performed regardless of treatment adherence.
2.1.2
Primary endpoints
Part 1 (Phase IIb)
Percent change from baseline in dT count at
Part 2 (Phase III)
Percent change from baseline in dT count at 
2.1.3
Secondary endpoints
Part 1 (Phase IIb)
Efficacy
Secondary endpoint

Percent change from baseline in dT count at 

Absolute change from baseline in IHS4 value at 

Absolute change from baseline in IHS4 value at 

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Safety
Occurrence of treatment emergent adverse events (TEAEs)
Part 2 (Phase III)
Efficacy
Key secondary endpoints
The following key secondary endpoints will be considered. These may be amended according 
to Part 1 results:

Absolute change from baseline in IHS4 value at 

Absolute change from baseline in Hidradenitis Suppurativa Area Severity Index (HASI) 
score at 

Achievement of Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 16:
HiSCR50 is defined as at least a 50% reduction in the total abscess and inflammatory 
nodule (AN) count with no increase in abscess count and no increase in dT count relative 
to baseline.

Percent change from baseline in abscess count at 

Achievement of at least a 50% reduction in dT count at 
relative to baseline.

Achievement of at least a 50% reduction in abscess and dT (AdT) count at 
relative to baseline

Achievement of at least a 50% reduction in ANdT count at
 relative to baseline.

Achievement of at least 30% reduction from baseline in Numerical rating Scale (NRS30) 
in Patient’s Global Assessment of HS pain at 
Safety
Occurrence of TEAEs.
2.2
FURTHER OBJECTIVES AND FURTHER ENDPOINTS
2.2.1
Further objectives
Further objectives are to evaluate further measures of efficacy including effect size up to 
 the pharmacokinetics (PK), the immunogenicity (anti-drug antibody [ADA] and 
neutralizing antibody [NAb]) of spesolimab, and to explore biomarkers related to changes in 
HS and IL36 pathway after treatment (assessment of gene expression levels in skin biopsies 
and whole blood, evaluation of serum proteomics and imaging markers acquired by 
ultrasound [US]).
2.2.2
Further endpoints
For further endpoints, time-point defined as “at each scheduled assessment” refers to 
scheduled assessment for the related outcome as per Flowchart. More details and additional 
further endpoints may be defined in the TSAP.

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Part 1 (Phase IIb)
Efficacy
Lesion counts clinical endpoints

Percent change from baseline in dT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in dT count at each scheduled 
assessment.

Occurrence of complete elimination of dT at each scheduled assessment.

Time to first occurrence of complete elimination of dT during the treatment period.

Percent change from baseline in abscess count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in abscess count at each scheduled 
assessment.

Occurrence of complete elimination of abscess at each scheduled assessment.

Percent change from baseline in total AdT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in AdT count at each scheduled 
assessment.

Percent change from baseline in inflammatory nodule (N) count at each scheduled 
assessment.

Percent change from baseline in total ANdT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in ANdT count at each scheduled 
assessment.
Response-, score-, and flare-related clinical endpoints

Achievement of HiSCR50 at each scheduled assessment.

Absolute change from baseline in IHS4 value at each scheduled assessment.

Achievement of IHS4-55 response (defined as at least 55% reduction from baseline) at 
each scheduled assessment.

Absolute change from baseline in HASI score at each scheduled assessment.

Achievement of Physician's Global Assessment (PGA) score of 0 or 1 at each scheduled 
assessment.

Occurrence of at least one HS flare at each scheduled assessment: defined as at least 25 % 
increase in AN count with a minimum increase of 2 relative to baseline.

Time to first occurrence of HS flare during the treatment period.
Patient reported outcomes (PROs)

Achievement of at least 30% reduction from baseline in Numerical rating scale (NRS30) 
in Patient’s Global Assessment of HS pain at each scheduled assessment.

Absolute change from baseline in Hidradenitis Suppurativa Quality of Life (HiS-QoL) 
total score at each scheduled assessment.

Absolute change from baseline in FACIT-Fatigue scale score at each scheduled 
assessment.

Absolute change from baseline in Dermatology Life Quality Index (DLQI) score at each 
scheduled assessment.

Absolute change from baseline in Patient Global Impression of Change (PGI-C) score 
over time.

Absolute change from baseline in Patient Global Impression of Severity (PGI-S) score 
over time.

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
Change from baseline in Hidradenitis Suppurativa odour and drainage scale (HODS) at 
each scheduled assessment.

Change from baseline in NRS Pruritus at each scheduled assessment.

Change from baseline in Hospital Anxiety and Depression Scale (HADS) at each 
scheduled assessment.
Part 2 (Phase III)
Efficacy

Achievement of HiSCR50 at each scheduled assessment.

Percent change from baseline in dT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in dT count at each scheduled 
assessment.

Occurrence of complete elimination of dT at each scheduled assessment.

Time to first occurrence of complete elimination of dT during the treatment period.

Percent change from baseline in abscess count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in abscess count at each scheduled 
assessment.

Occurrence of complete elimination of abscess at each scheduled assessment.

Percent change from baseline in total AdT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in AdT count at each scheduled 
assessment.

Percent change from baseline in N count at each scheduled assessment.

Absolute change from baseline in IHS4 value at each scheduled assessment.

Achievement of IHS4-55 response (defined as at least 55% reduction from baseline) at 
each scheduled assessment.

Absolute change from baseline in HASI score at each scheduled assessment.

Achievement of at least 30% reduction from baseline in Numerical rating scale (NRS30) 
in Patient’s Global Assessment of HS pain at each scheduled assessment.

Percent change from baseline in total ANdT count at each scheduled assessment.

Achievement of at least 50% reduction from baseline in ANdT count at each scheduled 
assessment.

Achievement of PGA score of 0 or 1 at each scheduled assessment.

Absolute change from baseline in HiS-QoL total score at each scheduled assessment.

Absolute change from baseline in FACIT-Fatigue scale score at each scheduled 
assessment.

Absolute change from baseline in DLQI score at each scheduled assessment.

Absolute change from baseline in PGI-C score over time.

Absolute change from baseline in PGI-S score over time.

Change from baseline in HODS at each scheduled assessment.

Change from baseline in NRS Pruritus at each scheduled assessment.

Change from baseline in HADS at each scheduled assessment.

Occurrence of at least one HS flare at each scheduled assessment: defined as at least 25 % 
increase in AN count with a minimum increase of 2 relative to baseline.

Time to first occurrence of HS flare during the treatment period.

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
Work Productivity and Activity Impairment Questionnaire for HS (WPAI-HS) - change 
from baseline in WPAI-HS at each scheduled assessment.

EQ-5D-5L- change from baseline in EQ-5D at each scheduled assessment.

Number of surgeries 

Days of hospitalisation

Days out of work/unemployment

Number of emergency room visits

Steroid free time/remission

Hormonal therapy free time (in women)

Antibiotics free time/remission

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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN 
This is an international, Phase IIb/III multi-center, double-blind, placebo-controlled, 
randomised trial assessing the efficacy and safety of spesolimab versus placebo in patients 
with moderate to severe HS. Approximately
participants in Part 1 (Phase IIb) and 
participants in Part 2 (Phase III) will be randomised. A sufficient number of trial 
participants will be screened to meet this randomisation target. Trial participants recruited in 
Part 1 cannot participate in Part 2. An overview of trial design is presented in Figure 3.1: 1.
Part 1 (Phase IIb)
Trial participants will be enrolled (screened) into the trial at Visit 1, and treatment will be 
initiated at Visit 2.
Screening and randomisation
After signing the informed consent, trial participants will enter the screening period for up to 
28 days, and if all eligibility criteria are met, trial participants will be randomised in a
 
ratio to either active group, including high dose, medium dose, and low dose group, or 
placebo group
 The randomisation will be stratified for 
and 
at 
baseline
 For stratification, the details are described in Section 7.4.
At least approximately 
participants from 
population (meaning a 
corresponding
and a maximum of approximately 
participants from 
population (meaning a corresponding
 are planned to be randomised, respectively. These participants who were 
previously 
might have had a primary or a secondary failure of 
Primary failure of 
is defined as lack of efficacy after at least 
3 months of treatment with an agent
(patients who never responded), and 
secondary failure is defined as loss of clinical efficacy in a trial participant after initial 
response to an agent 
(patients who initially responded but then relapsed). 
Additionally,
might have 
due to AE or stopped for 
other reason. 
Approximately 
participants with baseline 
 and 
participants 
with baseline
are planned to be randomised, respectively.
No stratification beyond those prior described
will 
be applied for the trial participants.
Study 
in the Flowchart represents the 
 
is used for Day 1.

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Treatment phase
Once randomised, trial participants will start a treatment period of 
 Administration 
of treatment will be up to 
 The final assessment of treatment effect will be on 
(EoT visit).
For the first 
 according to the assigned dose group, trial participants will be 
administered an initial
dose of spesolimab 
high dose group], 
[medium dose group], or 
[low dose group]
at Visit 2 
Visit 3
 Visit 4 
, and Visit 5 
 or matching placebo.
From Visit 6 
to Visit 9 
(both inclusive), trial participants will be 
administered a 
 of spesolimab (either 
[high dose 
group],
[medium dose group], or 
[low dose group] according to the assigned 
dose group), or matching placebo. For trial participants initially randomised to spesolimab 
group, from Visit 10 
to Visit 31 
(both inclusive), the participants will be 
administered a 
dose of spesolimab: either 
(high and medium dose 
group) or
low dose group)
according to the assigned dose group). 
From Visit 14
, there is an option of increasing the dose to the maximum 
subcutaneous dose of 
(applied to low dose treatment group 
participants only, via IRT in a blinded manner) if they have
 compared to baseline and the investigator agrees 
with the dose increase. 
For trial participants initially randomised to placebo group, from Visit 10
to 
Visit 13
(both inclusive), the participants will be administered a matching placebo 
Visit 14 
to Visit 31 
(both inclusive), the 
participants will be
dose of spesolimab 
From Visit 23 
on, trial participants will continue to receive the assigned dosing 
regimen, at least until the results of
are available. Upon 
availability of the Phase IIb (Part 1) primary analysis efficacy and safety results, the dosing 
regimen may be adapted from Visit 23 
. For more detailed drug assignment and 
administration of doses for each trial participant, please see Section 4.1.5.
Follow-up phase and end of study
Trial participants completing EoT visit
of the study may roll over to an
if they agree and meet the eligibility criteria 
 These trial participants are not 
required to complete a safety follow-up period, and their EoT visit will be considered also 
their end of study (EoS) visit, which is the
Trial participants, who permanently discontinue trial drug earlier than Visit 31 
 or 
do not qualify to enter the LTE trial for any other reason, will be invited to do the EoT visit 
instead of the next planned visit and will then enter a safety follow-up period
 

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Part 2 (Phase III)
Part 2 (Phase III) will start after completion of primary analysis of Part 1 (Phase IIb), 
assessment of further development benefit, interaction with HAs, and approval by IRB/EC in 
participating countries.
Screening and randomisation
After signing the informed consent, trial participants will enter the screening period for up to 
28 days, and if all eligibility criteria are met, trial participants will be randomised in a 1:1 
ratio to either active group or placebo group. The randomisation will be stratified for
and 
 
 Recruitment ratios guidance for 
trial participants 
will be reviewed and revised, if needed, after the primary analysis of Part 1 is available and in 
light of the consolidated entry criteria for Part 2. Approximately 
participants with 
baseline 
are planned to be 
randomised, respectively.
Treatment phase
Once randomised, trial participants will start a treatment period of 
(treatment 
administered period is from Visit 2 
to 
, both inclusive, and an assessment 
done at 
). From Visit 2 
prior to 
is not inclusive), trial 
participants will be administered
of spesolimab with selected dosing 
regimen based on primary analysis of Part 1 (Phase IIb) or matching placebo. From 
to 
(both inclusive), all participants (both initially randomised to spesolimab group 
and placebo group) will be administered a 
of spesolimab with selected 
dosing regimen based on primary analysis of Part 1 (Phase IIb).
Follow-up phase and end of study
Same rule is applied as Part 1. Please see “Follow-up phase and end of study” in Part 1.

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IC = Informed Consent, V = Study Visit, W = Week (study weeks), FUP = Follow Up, EoT = End-of-Treatment, 
EoS = End-of-Study, REP = Residual Effect Period
a
b
Upon availability of the efficacy and safety results of 
(Part 1)
 
c
If trial participants meet criteria for inadequate clinical response and the investigator agrees with 
participants in low dose spesolimab group can be 
from
 to
on; see 
Section 3.1.
d
e
after last dose or 
from EoT
f
Part 2 
will start after 
of Part 1 
 assessment of further development benefit, 
interaction with HAs, and approval by IRB/EC
Figure 3.1: 1 Trial design
An overview of all relevant trial activities is provided in the Flowchart. For visit schedules 
and details of trial procedures at selected visits, refer to Section 6.1 and Section 6.2, 
respectively.

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3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)
Overall, an operationally seamless Phase IIb (Part 1)/Phase III (Part 2) design is selected to 
streamline spesolimab development in HS while ensuring trial participant safety and 
flexibility to inform Phase III design with Phase IIb-generated evidence.
Primary and secondary endpoints selection for Phase IIb (Part 1)
 Draining tunnels are lesions with high impact for the trial 
participants, and drainage represents one of the highest unmet needs based on two BI Patients 
Organisation Advisory Boards (see below in this section). The pathophysiology of dT 
suggests a potential key role for the blockade of IL36 receptor activation by spesolimab.
Therefore, it is 
planned to use 
as the primary endpoint which would not be 
possible to evaluate in patients without any 
 at baseline.
Overall feasibility of the trial
BI considers selection and development of clinically meaningful outcomes assessments that 
remain a high unmet need such as %
to be an appropriate tool being used for 
what it is intended for, evaluating novel therapies targeting moderate to severe HS patients 
suffering from
 Prior to implementing
endpoint 
for Part 2 of trial 1368-0098, BI is planning to work with external experts in the HS field and 
create and define validation plans (i.e. establishment of content validity and other 
measurement properties) for this endpoint in parallel to Part 1 (Phase IIb), 
Placebo controlled treatment for both Part 1 (Phase IIb) and Part 2 (Phase III)
The placebo control is required to control for investigator bias and/or beneficial effects of 
being in a clinical trial. The rationale for switching placebo trial participants to active 
treatment at
is to give these participants the opportunity to receive active 
investigational medicinal product (IMP) treatment 
 For the benefit-risk 
assessment of using placebo, please see Section 1.4.
Dose ranging for Part 1 (Phase IIb)
Data from prior studies of spesolimab in HS are indicative of a need for dose ranging work 
and for further investigations over the efficacy profile of this molecule in HS. The primary 
analysis will be conducted after all trial participants complete 
 In addition, a 

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will be conducted after all trial participants complete 
visit.
 Additionally, the exposure-response relationship 
for the key efficacy endpoints will be characterised using population PKPD modelling 
approaches that will be defined and reported separately. 
dose up to 
for Part 1 (Phase IIb)
The potential benefit of the
dosing regimen will be determined with up to
data, limiting unnecessary over exposure until 
if no benefit is shown.
dose group for Part 1 (Phase IIb)
A
group is needed for a robust modelling approach. From 
 trial 
participants in this group may be 
the dose of
based on clinical 
response, as per protocol.
For more information regarding selection of doses in the trial, please see Section 4.1.2.
DMC
An independent DMC is involved in monitoring of overall safety and efficacy. For details, 
please see Section 8.7.
Feedback on trial design from patient or patient organisation
On
a Patient Organisation Advisory Board (POAB) meeting was held with 
the objective to seek patient and patient organisation input and advice to inform the HS
programme concerning the following topics: dosing and administration, clinical trial 
endpoints, Patient Reported Outcomes (PROs) and long-term trial participation.
On 
the second POAB meeting was held with the following objectives: 

Gain feedback on the design of the trial

Confirm what supporting materials should be used in the trial

Understand what psychological support is needed
On
 the third POAB meeting was held with the following objectives: 

Get additional feedback to improve management of visit procedures and patient 
facing materials targeted for trial participants.

Get feedback about the ICF content, design and administration.
The input received from these meetings has been considered whenever possible to add 
flexibility and to have a more patient centric protocol.

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Feedback on clinical trial experience
This trial will include an option for participants to complete anonymised questionnaires to 
provide feedback on their clinical trial experience. Providing this feedback is not required for 
trial participation, and information collected from these questionnaires will not be analysed as 
part of the clinical data for the trial (see Appendix 10.19).
3.3
SELECTION OF TRIAL POPULATION
A total of approximately 
 in Part 1 (Phase IIb) and 
in Part 2 
(Phase III) will be randomised in this trial. A sufficient number of participants will be screened 
to meet this randomised goal. Trial participants will be recruited across multiple sites in 
multiple countries. The minimum planned number of participants per site 
Screening of participants for this trial is competitive, i.e. screening for the trial will stop at all 
sites at the same time once a sufficient number of participants has been screened. 
Investigators will be notified about screening completion and will then not be allowed to 
screen additional participants for this trial. Participants already in screening at this time will 
be allowed to continue to randomisation if eligible.
A trial screening log collecting information on patients considered for participation and 
reason not enrolled (=signed informed consent) if applicable will be maintained. This 
screening log will be maintained in the Investigator Site File (ISF). Also, a log of all 
participants enrolled into the trial (i.e. who have signed informed consent) will be maintained 
in the ISF irrespective of whether they have been treated with investigational drug or not.
Even for screen failure participants, a minimum of information will be collected: participant
number, inform consent version and date, demographics, eligibility and reason for screen 
failure. In case of a SAE during the screening period, information on SAE, relevant other 
AEs, and concomitant treatment will be collected.
If retrospectively it is found that a trial participant has been randomised in error (=did not 
meet all inclusion criteria or met one or more exclusion criteria), the sponsor or delegate 
should be contacted immediately. Based on an individual benefit-risk assessment, a decision 
will be made whether continued trial participation is possible or not.
Trial participants can be re-screened (see also Section 6.2.1). The previous participant 
number will be provided by 
and the information will be collected in the eCRF. 
3.3.1
Main diagnosis for trial entry
Patients aged 18 years or older, with moderate to severe HS will be included in the trial if those 
patients fulfil all the inclusion criteria and do not meet any of the exclusion criteria.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the in- and exclusion criteria.

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3.3.2
Inclusion criteria
Part 1 (Phase IIb)
1. Of full age of consent (according to local legislation, at least ≥ 18 years) at screening.
2. Signed and dated written informed consent in accordance with ICH-GCP and local 
legislation prior to admission to the trial.
3. Moderate to severe HS, based on IHS4 criteria, at least 6 months prior to and including 
Baseline visit, as determined by the investigator through participant interview and/or 
review of the medical history (if IHS4 scoring is not available for the period before 
screening, equivalent scoring based on scoring systems as HS-PGA or Hurley are 
acceptable on the basis of documented investigator assessment)
4. HS lesions
anatomic areas
5. Biologic naive or 
for HS.
6. For biologic naïve, inadequate response to an adequate course of appropriate oral 
antibiotics for treatment of HS in the last 1 year prior to the Baseline visit, as per 
investigator discretion. All participants must have previous exposure to antibiotics for 
HS.
7. Total AN count of 
at Baseline visit.
8. Total dT count 
Baseline visit
9. Women of childbearing potential (WOCBP) must be ready and able to use highly 
effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less 
than 1% per year when used consistently and correctly, for the duration of the trial and 
 
after last administration. A list of contraception methods meeting these criteria and 
instructions on the duration of their use is provided in the participant information and in 
Section 4.2.2.3
Part 2 (Phase III)
Except for potential criteria, which will be confirmed after primary analysis of Phase IIb 
results, the same inclusion criteria as Part 1 (Phase IIb) will need to be met.
3.3.3
Exclusion criteria
Part 1 (Phase IIb)
1. Participants who must or wish to continue the intake of restricted medications (see 
Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the 
trial.
2. Prior exposure to any immunosuppressive/immunomodulatory biologic other than TNFi 
for HS.
3. Prior exposure to IL-36R inhibitors including spesolimab.
4. Treated with any investigational device or investigational drug of chemical or biologic 
nature within a minimum of 30 days or 5 half-lives of the drug, whichever is longer, prior 
to Visit 2 (Baseline visit)
5. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. 
Women who stop nursing before the study drug administration do not need to be excluded 
from participating.

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6. Participants with history of allergy/hypersensitivity to the systemically administered trial 
medication agent or its excipients.
7. Participants with a transplanted organ (with exception of a corneal transplant >12 weeks 
prior to screening) or who has ever received stem cell therapy (e.g., Remestemcel-L)
8. Participants with any documented active or suspected malignancy or history of 
malignancy within 5 years prior to the screening visit, except appropriately treated basal 
cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of 
uterine cervix.
9. Participants with active or latent tuberculosis (TB) (trial participants are required to be 
tested during the screening visit):

participants with active TB should be excluded.

participants will be screened with Interferon Gamma Release Assay (IGRA) such as 
QuantiFERON or T-spot. Participants with positive IGRA are excluded, unless they 
have completed treatment for active or latent TB per investigator discretion, at the 
time of screening. Participants with untreated latent tuberculosis may be included if 
treatment of latent tuberculosis as per local guidelines is initiated prior to 
randomization and completed during the course of the trial.

participants with indeterminate QuantiFERON or invalid/borderline T-spot may be
retested with IGRA (once), and if inconclusive, should have a PPD skin test. Under 
certain conditions (e.g. unavailability of additional IGRA testing tubes, inability to 
process the IGRA [availability of freezer, centrifuge, etc.]), Tuberculin-Skin testing 
(TST) may be considered for retesting, but this should be discussed with the sponsor 
on a case-by-case basis.

Under exceptional circumstances and only after discussion with sponsor, PPD skin 
test, also called TST, can be performed if IGRA is not available or inconclusive. A 
tuberculin skin test reaction ≥10 mm (≥5 mm if receiving ≥15 mg/d prednisone or 
other immunosuppressant) is considered positive. Patients with a positive TST are
excluded, unless they have completed treatment as above.

(Only for Japan: If there is no chest X-ray test or CT taken within 3 months prior to 
Visit 1, it should be taken as tuberculosis screening test.)
10. Participants with active systemic infection within 2 weeks of Visit 2 (Baseline visit). 
These participants can be re-screened after completed treatment of the acute infection, as 
per investigator discretion.
11. Participants with relevant chronic infections as determined by the investigator, including 
human immunodeficiency virus (HIV) or viral hepatitis. The corresponding laboratory 
tests will be performed during screening. In case of a positive hepatitis C antibody test, a 
positive reflex testing for Hepatitis C RNA PCR is considered positive. For hepatitis B, 
exclusion criterion is met with positive Hepatitis B surface antigen; positive HBV DNA 
PCR (HBV DNA PCR is done in case of positive Hepatitis B core antibody and negative 
Hepatitis B surface antigen). A patient can be re-screened if the patient was treated and is 
cured from the acute infection.
12. Major surgery (major according to the investigator’s assessment) performed within 
12 weeks prior to first study drug administration (Visit 2-Baseline visit) or planned during 
the study (e.g. hip replacement, aneurysm removal, stomach ligation)
13. Participants with severe, progressive, or uncontrolled hepatic disease, defined as >3-fold 
Upper Limit of Normal (ULN) elevation in AST, ALT, or alkaline phosphatase, or >2-
fold ULN elevation in total bilirubin at screening visit. Trial participants with Gilbert´s 

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syndrome can be included unless total bilirubin elevation was >5-fold ULN at screening 
visit and unless proportions of bilirubin fractions are inconsistent with diagnosis of 
Gilbert´s syndrome.
14. Participants at screening with a severe, progressive, or uncontrolled condition as renal, 
hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, psychiatric 
disease (including history or suspicion of chronic alcohol or drug abuse) other than HS, or 
signs and symptoms thereof, in the opinion of the investigator would compromise the 
safety of the participant or the quality of the data, and would make the study participant 
unreliable to adhere to the protocol, to comply with all study visits/procedures, or to 
complete the trial.
15. Planned use of laser or other hair removal procedures over HS-affected areas during the 
trial period.
16. Participants with any suicidal ideation of type 4 or 5 on the C-SSRS in the past 12 months
prior to screening visit (i.e. active suicidal thoughts with method and intent but without 
specific plan, or active suicidal thoughts with method, intent and plan)
17. Participants with any suicidal behavior in the past 2 years prior to screening visit (i.e. 
actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior)
18. Previous enrolment in this trial (exception: trial participants re-screened)
19. Presence of acute demyelinating polyneuropathy.
20. Confirmed or suspected acute SARS-CoV-2 infection. Participants who recovered from a 
SARS-CoV-2 infection may be eligible: 14 days or more from first symptoms or from 
first PCR test confirmation to randomisation, whichever is shorter AND at least 14 days 
without SARS-CoV-2 symptoms. If local criteria are stricter, they will apply.
21. Trial participants who weigh <40 kg.
Part 2 (Phase III)
Except for potential criteria, which will be confirmed after analysis of Phase IIb results, the
same criteria as Part 1 (Phase IIb) will need to be met.
3.3.4
Discontinuation of trial participants from treatment or assessments
Trial participants may discontinue trial treatment or withdraw consent to trial participation as 
a whole (“withdrawal of consent”) with very different implications; please see Section 3.3.4.1
and Section 3.3.4.2. 
In case of premature permanent discontinuation of trial treatment, the EOT visit procedures 
will be done at the earliest, followed by a safety follow up visit 
after the last drug 
administration. For those trial participants with premature discontinuation happening before 
visit 14 
, in addition to safety follow up assessment, trial participants ideally should 
also continue visits for assessment of efficacy up to Visit 14
as per Flowchart. For 
these cases only the IMP administration will be skip.
The decision to discontinue trial treatment or withdraw consent to trial participation and the 
reason must be documented in the source documents and in the CRF.
Measures to control the withdrawal rate include careful trial participant selection, appropriate 
explanation of the trial requirements and procedures prior to trial enrolment, as well as the
explanation of the consequences of withdrawal.

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If the reason for discontinuation is an AE, please follow the requirements for AE collection 
reporting (see Section 5.2.6.2). If the reason for discontinuation is death, this should be 
reported on the SAE form as well, regardless of causal relationship.
3.3.4.1
Discontinuation of trial treatment
An individual trial participant will discontinue trial treatment if:

The trial participant wants to discontinue trial treatment. The trial participant will be 
asked to explain the reasons but has the right to refuse to answer.

The trial participant has repeatedly shown to be non-compliant with important trial 
procedures and, in the opinion of the investigator, the safety of the trial participant
cannot be guaranteed as participant is not willing or able to adhere to the trial 
requirements in the future.

The trial participant uses/requires certain restricted medications, such as 
immunosuppressive / immunomodulatory biologics, investigational products/devices, 
IL-36 receptor inhibitors (as mentioned in Section 4.2.2), for any indication. 

The trial participant can no longer receive trial treatment as per physician’s discretion 
(such as surgery, adverse events, other diseases)

The trial participant should not receive subsequent doses of trial treatment if a hepatic 
injury alert (see Section 5.2.6.1.4) is confirmed without identification of an alternative 
cause in the work-up according to the “DILI checklist”.

The trial participant develops suicidal ideation of type 4 or 5 in the Columbia-Suicide 
Severity rating Scale (C-SSRS) or any suicidal behaviour (see Section 4.2.1 on 
Individual stopping rules related to specific AEs) 

The trial participant is unable to receive trial treatment consecutively for 
or 
more for any reason

If the participant experiences an infection with SARS CoV 2 (as confirmed by local 
standards) or any significant systemic infection based on the investigator’s judgement, 
interruption of study medication should be considered. The participant may resume 
trial treatment following recovery of the infection if the participant is expected to 
derive clinical benefit, at the discretion of the investigator.

In case a trial participant becomes pregnant during the study the IMP should be 
discontinued. The pregnancy will be followed as described in Section 5.2.6.2.3

If peripheral neuropathy is suspected, treatment with spesolimab must be temporarily 
discontinued until a full neurological investigation has been conducted. After 
completion of the neurological investigation, treatment can be restarted based on 
medical judgement of the investigator
In case the infusion of study drug is permanently discontinued before the whole amount of 
the prepared solution has been administered to the trial participant, every effort should be 
made to complete all remaining study assessments of the visit.
Trial participants who discontinue treatment permanently and prematurely prior to the 
planned EoT visit 
should be registered as discontinued from treatment in IRT. 
These participants should follow the scheduled visits as much as possible as defined in the 
Flowchart: the EoT visit procedures should be conducted either immediately or as soon as 

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possible, followed by the Follow-up visit (EoS) 
after the last trial drug 
administration date. All efforts should be made to keep the trial participant in observation for 
at least 
 after the last dose of the study drug for safety reasons. All trial participants 
should have an EoS visit and assessments as per Flowchart must be done during the EoS
visit.
For all trial participants, the reason for permanent discontinuation from trial treatment (e.g. 
AEs) must be recorded according the options available in the CRF. This data will be included 
in the trial database and reported.
In the event of force majeure or other disrupting circumstances (e.g. pandemic, war; please 
see Section 6), physical participant visits to the sites may not be feasible or may need to be 
restricted to ensure participant safety. Based on a thorough assessment of the benefits and 
risks, the investigator may still decide to continue trial treatment. Where permitted by local 
law and regulations, trial medication may be shipped directly to the participants’ home in 
agreement with the sponsor. In that case, a home visit service would assist the participant 
with medication administration. In case these options cannot be locally implemented, the IMP 
will be temporarily discontinued.
When new efficacy or safety information becomes available, Boehringer Ingelheim will 
review the benefit-risk-assessment and, if needed, pause or discontinue the trial treatment for 
all trial participants or take any other appropriate action to guarantee the safety of the trial 
participants. 
3.3.4.2
Withdrawal of consent to trial participation
Trial participants may withdraw their consent to trial participation at any time without the 
need to justify the decision.
If a trial participant wants to withdraw consent, the investigator should be involved in the 
discussion with the trial participant and explain the difference between trial treatment 
discontinuation and withdrawal of consent to trial participation, as well as explain the options 
for continued follow-up after trial treatment discontinuation; please see Section 3.3.4.1.
Withdraw of consent is when the trial participant declines any further participation in the 
clinical trial and is confirmed when the patient meets all of the below:
•
Does not want to take trial medication any longer and
•
Does not want to continue to come to the site/clinic for protocol scheduled trial visits 
after treatment discontinuation and 
•
Does not want to be contacted periodically and
•
Does not want to be contacted at the end of the trial and 
•
Does not provide access to the own health records
If any of these is not met, then it is not a withdrawn of consent.

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3.3.4.3
Discontinuation of the trial by the sponsor
Boehringer Ingelheim reserves the right to discontinue the trial overall or at a particular trial
site at any time for the following reasons:
1. Failure to meet expected enrolment goals overall or at a particular trial site.
2. New efficacy or safety information invalidating the earlier positive benefit-risk
assessment; please see Section 3.3.4.1.
3. Deviations from GCPs, the trial protocol, or the contract impairing the appropriate 
conduct of the trial.
Further treatment and follow up of trial participants affected will occur as described in 
Section 3.3.4.1.
The investigator/the trial site will be reimbursed for reasonable expenses incurred in case of 
trial termination (except in case of the third reason).

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4.
TREATMENTS
4.1
INVESTIGATIONAL TREATMENTS
4.1.1
Identity of the investigational medicinal products
Table 4.1.1: 1
Test product spesolimab solution 
Substance:
Spesolimab (Spevigo®)
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Unit strengths:
Spesolimab
Posology:
See Section 3.1.
Table 4.1.1: 2
Test product BI matching placebo solution
Substance:
Placebo matching to spesolimab
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Unit strengths:
Mode of administration:
Posology:
See Section 3.1.
Table 4.1.1: 3
Test product spesolimab solution
Substance:
Spesolimab (Spevigo®)
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Unit strengths:
Spesolimab
Mode of administration:
Posology:
See Section 3.1.

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Table 4.1.1: 4
Test product BI matching placebo solution 
Substance:
Placebo matching to spesolimab
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Unit strengths:
Mode of administration:
Posology:
See Section 3.1.
4.1.2
Selection of doses in the trial and dose modifications
Part 1 (Phase IIb)
The main trial objectives of Part 1 in this trial is provided in Section 2.1.1.
dosing regimens are defined (for details, see Section 3.1) in this trial: one middle 
dosing regimen (middle dose group)
one higher dosing regimen (high dose group); and one lower dosing regimen (low dose 
group). 
 Taken together, trial participants randomised to active treatment in 
1368-0052 received 
 then 
 starting 
 Those randomised to placebo in 1368-0052 received placebo until Week 10. 
Starting 
and after final evaluation of Study 1368-0052 (EoT visit), the former 
placebo trial participants
 Thereafter all trial participants were continued 
Safety for the lower and medium dosing regimen is supported by the safety profile observed 
in Study 

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In the healthy volunteer (HV) study (1368-0002), 6 healthy volunteers were exposed to the 
highest 20 mg/kg dose. In those 6 trial participants, no serious adverse event (SAE) or 
adverse event of special interest (AESI) were reported. At PT level, the most frequently 
reported treatment-emergent AEs (more than 20% of the trial participants who received 
spesolimab in the MRD part) were nasopharyngitis, headache, and injection site erythema. 
All AEs resolved by the end of the trial or were followed up sufficiently. No relevant changes 
were observed in safety laboratory tests, vital signs, and ECGs. Based on these safety 
findings from the 1368-0002 study, the highest dose planned for the 1368-0098 study can be 
considered as acceptable.
Table 4.1.2: 1
1.
Observed exposures in HV study (gMean, n=4)
2.
 AUC from 
 for comparison purpose
After the last dose is administered at 
 final efficacy, PK, and ADA/NAb
assessments will be made at the end of the dosing interval, 
 after the last dose at
(EOT visit). The last safety assessment will be done 
 after the last 
administration. Prolonging Part 1 participants treatment with spesolimab beyond 
allows to: 1) switch prior placebo recipients to active treatment, 2) explore further how
spesolimab efficacy and safety profile is maintained, and 3) explore further potential
immunogenicity of spesolimab in HS patients, up to approximately 1 year.

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Part 2 (Phase III)
Dose regimens to serve trial objectives of Part 2 (Phase III), defined in Section 2.1.1, will be 
selected according to Part 1 (Phase IIb) results. Justification of selecting the dose regimens 
will be clarified in an amended CTP.
4.1.3
Method of assigning trial participants to treatment groups
For both Part 1 and Part 2, after the assessment of all in- and exclusion criteria, each eligible 
trial participant will be randomised to a treatment group at Visit 2 according to a 
randomisation plan, please see Section 7.4.Randomisation codes will be generated through a 
validated software and kept blinded to the trial team, sites and trial participants. Access to the 
codes will be controlled and documented.
An
 The investigator will receive all necessary 
instructions to access the 
 from the sponsor. Detailed 
functions and procedures will 
be documented in the user requirement specifications mutually agreed to by the sponsor and 
the
4.1.4
Blinding and procedures for unblinding
4.1.4.1
Blinding
Part 1 (Phase IIb)
Trial participants, investigators, central reviewers, and everyone (except for specified project 
members [e.g. PK]) involved in trial conduct or with any other interest in this double-blind 
trial will remain blinded regarding the randomised treatment assignments until the database is 
declared ready for final analysis according to the sponsor’s SOPs. 
Further details, regarding the timepoint of unblinding the database for analyses including 
primary, interim, and final analysis, are documented in the TSAP or logistics plan.
The randomisation codes will be provided to bioanalytics before the last trial participant 
completed the
 visit of Phase IIb (Part 1) of the trial to exclude placebo samples from 
the PK and ADA analysis. Bioanalytics will not disclose the randomisation code or the 
results of their measurements until the database lock.
For the primary analysis at
 and interim analysis at 
 a respective team 
(“shadow team”) independent of the main trial team will be formed to conduct the necessary 
analysis and reporting steps and ensure to maintain the blind and restrict access to the 
randomisation codes from the main trial team. Details of data transfer, timelines, and 
involved trial functions during this process will be described in a separate logistics plan 
which will also specify details on data access.

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Part 2 (Phase III)
Trial participants, investigators, central reviewers, and everyone involved in trial conduct, 
trial analysis, or with any other interest in this double-blind trial will remain blinded 
regarding the randomised treatment assignments until the database is declared ready for 
analysis according to the sponsor’s SOPs. Further details, regarding the timepoint of 
unblinding the database for analysis, will be documented in the TSAP.
The responsible bioanalyst of the external bioanalytical laboratory will receive the 
randomisation codes prior to last trial participant completed to allow for the exclusion from 
the analyses of PK and ADA samples taken from placebo trial participants.
The TBA may receive unblinding data from the external bioanalytical laboratory after the last 
trial participant completed the last visit but prior to official unblinding of the analysis 
database at the end of the trial for preparation of data transfer e.g. check file structure prior to 
data upload and SDTM transformation and bioanalytical report writing. Bioanalytics will not 
disclose the randomisation code or the results of their measurements until the database lock.
Part 1 (Phase IIb) and Part 2 (Phase III)
The access to the randomisation code will be kept restricted until its documented release per 
sponsor SOP.
A fully external DMC will perform an un-blinded safety and efficacy assessment at specified 
intervals in order to ensure that trial participants are protected from potential harm, please refer 
to Section 8.7 for further details.
4.1.4.2
Emergency unblinding and breaking the code
Emergency unblinding will be available to the investigator via IXRS and emergency service. 
It must only be used in an emergency when the identity of the trial drug must be known to the 
investigator in order to provide appropriate medical treatment or otherwise assure safety of 
trial participants. The treatment allocation should not be disclosed to the sponsor unless this 
is explicitly requested. The reason for unblinding must be documented in the source 
documents and/or appropriate CRF page.
Due to the requirements to report Suspected Unexpected Serious Adverse Reactions 
(SUSARs), it may be necessary for a representative from BI’s Pharmacovigilance group to 
access the randomisation code for individual trial participants during trial conduct. The 
access to the code will only be given to authorised PSPV representatives for processing in the 
Pharmacovigilance database and not be shared further.
4.1.5
Drug assignment and administration of doses for each trial participant
Trial participants for Part 1 will be treated with spesolimab or matching placebo as indicated 
in the Flowchart and Section 3.1. Trial participants for Part 2 treatment schedule will be 
simplified, based on the results from Part 1 data available when the primary analysis will be 
conducted. Therefore, the rest of this section applies to study participants in Part 1. This 
section will be duly amended to include any change applied to drug administration for study 
participants in Part 2 after the Part 1 primary analysis has been conducted.

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As briefly described in Section 4.1.3, the medication will be assigned 
 
There are no special requirements on drug administration in relation to meals. Administration 
of study medication should occur after ECG and after blood sampling.
If available, a pharmacist should prepare the study medication. The so-called four eye 
principle (two-person rule) should be applied for preparation (e.g. choosing the correct vials 
with the correct medication number) and administration of trial medication.
(Visits 2, 3, 4, and 5
Trial participants will receive
 spesolimab or matching placebo. The administration of the 
trial medication will be done by a trained health care professional. Detailed instructions for 
the preparation of the 
 the 
and the 
are provided in the ISF. The administration of 
doses will be done at site. 
(Visit 6 to 31
Trial participants will receive
of spesolimab or matching placebo. 
 
provided in the ISF.
is allowed.
Monitoring after administration
Trial participants should be closely monitored for AEs, including signs and symptoms of 
 hypersensitivity reactions, for 2 hours after the first dose of trial 
drug administered at Day 1 (Visit 2) and 1 hour following all other doses of trial drug. Study 
personnel should observe the
They 
should also ask trial participants about itching, dizziness or shortness of breath. Trial 
participants should be advised to notify site personnel in case they experience redness, 
swelling or other changes at the
 They should further be advised that if they 
experience itching all over or a feeling of being swollen, dizzy or short of breath, they should 
seek emergency medical attention immediately and notify site personnel, see Section 5.2.6
about AE reporting.
In case of safety concerns, e.g. due to
 it is in the discretion of the 
investigator or his/her designee to adapt the 
and - provided no further safety 
concern exist -
 Further, based on
medical judgment he/she will 
provide medications such as steroids, etc, as needed (see Section 4.2.1 for handling of 
. Detailed instructions for handling of 
are also provided 
in the “Instructions for Pharmacist” document placed in the ISF. Pre-medications for further 
 might be considered and will be agreed on between investigator and BI clinical
monitor.

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Dose modifications or dose adjustments are not permitted except as per protocol (see 
Section 3.1 possible 
 from 
of Part 1 (implemented by IRT if applicable
as per allocated blind treatment group). In exceptional cases of missed or delayed visits, if 
any of these visits have to be rescheduled, the date of subsequent visit should be calculated 
from baseline (Visit 2). After Visit 5 
, in case of delayed visits, IMP can be 
administered with a minimum interval of 7 days from the next dose, only after discussion and 
approval from the sponsor.
Table 4.1.5: 1
Placebo controlled period of Part 1 (Up to Visit 14
Administration of trial drug
Table 4.1.5: 2
Overview of treatment course from Visit 15 
up to Visit 31
Administration of trial drug
From Visit 23
on, trial participants will continue to receive the previously 
assigned dosing regimen until the results of primary analysis 
are available. Upon 
availability of the Phase IIb (Part 1) primary analysis efficacy and safety results, the dosing 
regimen may be adapted from Visit 23 

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Table 4.1.5: 3
Dosage and treatment schedule for the
Visit 2 (baseline)
Visit 3
Visit 4
Visit 5
Table 4.1.5: 4
Dosage and treatment schedule for the 
4.1.6
Packaging, labelling, and re-supply
The investigational medicinal products will be provided by BI or a designated CRO. They 
will be packaged and labelled in accordance with the principles of Good Manufacturing 
Practice (GMP). Re-supply to the sites will be managed via an
 which will also 
monitor expiry dates of supplies available at the sites.
The label will be prepared according to EU Regulation No. 536/2014, Annex 6, Section D. 
Omitting certain particulars with the following justifications: 

“Investigator” was omitted from the label because patient cards are used.

Additionally, each kit assigned to a patient will be registered as such in the IXRS. 
“Visit number” is omitted from the label as each kit assigned to a participant has a kit 
number and it be registered in the
Should local regulations outside the EU require these particulars, they will be added to the 
country-specific label text.
For the description of the label, refer to the ISF.

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4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area according to the recommended storage conditions on the medication label. The shipping, 
labelled storage conditions and the available stability data used for assessment in the event of 
a temperature excursion described in the Stability and Packaging Information (SPI) is 
reflected in the Mini-tag® profile. The Mini-tag® is validated and is the leading temperature 
monitoring system used for IMP in this trial. Site staff will be trained on its usage by the time 
the medication is received at site. For details of storage conditions, please refer to the ISF. A 
Mini-tag® status site log must be maintained for documentation.
If the storage conditions are found to be outside the specified range, the Clinical Research 
Associate CRA (as provided in the list of contacts) must be contacted immediately.
For more details, please see the relevant instructions in the ISF.
4.1.8
Drug accountability
The investigator or designee will receive the investigational drugs delivered by the sponsor or 
delegate when the following requirements are fulfilled:

Availability of a signed and dated clinical trial protocol.

Approval of the clinical trial protocol by the IRB/ethics committee.

Availability of a signed and dated clinical trial contract between the sponsor or 
delegate and the investigational site.

Approval/notification of the regulatory authority, e.g., competent authority.

Availability of the curriculum vitae of the Principal Investigator.

Availability of the proof of a medical license for the Principal Investigator (if 
applicable)

Availability of FDA Form 1572 (if applicable)
Investigational drugs are not allowed to be used outside the context of this protocol. They 
must not be forwarded to other investigators or clinics.
The investigator or designee must maintain records of the product’s delivery to the trial site, 
the inventory at the site, the use by each trial participant, and the return to the sponsor or
warehouse/drug distribution centre or alternative disposal of unused products. If applicable,
the sponsor or warehouse/drug distribution centre will maintain records of the disposal. 
These records will include dates, quantities, batch/serial numbers, expiry (‘use by’) dates, and 
the unique code numbers assigned to the investigational medicinal product and trial 
participants. The investigator or designee will maintain records that document adequately that 
the trial participants were provided the doses specified by the CTP and reconcile all 
investigational medicinal products received from the sponsor. At the time of return to the 
sponsor and/or appointed CRO, the investigator or designee must verify that no remaining 
supplies are in the investigator’s possession.

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4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS
4.2.1
Other treatments and emergency procedures
Systemic hypersensitivity including
and anaphylactic reaction
In case of systemic hypersensitivity including 
and anaphylactic reaction 
emerging during or after
of trial medication, the investigator should 
consider in accordance with severity of the reaction and local standard of care to
-
Immediately interrupt the
-
Treat with systemic antihistamines, i.v. steroids, and in case of a severe allergic 
reaction (eg, anaphylactic reaction) epinephrine
Also draw a plasma sample for IgE and ADA as detailed in the Laboratory Manual (ISF). 
Please initiate the evaluation of histamine, serum tryptase, and complement components.
In case of 
 based on trial participant’s clinical 
course and medical judgment, the
be re-initiated/the
be 
continued in case of mild or moderate 
(according 
to Common Terminology Criteria for Adverse Events (CTCAE) grading in section of the 
ISF) at lower speed with gradual increase to complete the 
as detailed in 
the Instructions for Preparation and Handling of spesolimab/placebo in the ISF. In any case, 
the total duration of 
 should not exceed 
. Information about the 
maximum time between the start of 
trial participant is detailed in the Instructions for Pharmacist filed on the ISF.
In case of anaphylactic reaction based on the criteria discussed in the statement paper from 
Sampson HA (Appendix 10.20 [R11-4890]) suspected to be caused by the trial medication, 
the investigator should permanently discontinue treatment with spesolimab.
When a delayed hypersensitivity reaction is suspected, please draw a blood sample for 
laboratory assessment and evaluate for signs of extra-cutaneous organ involvement. The 
decision to discontinue treatment and/or restart treatment after resolution of the reaction 
should be based on reaction type and severity. See Section 3.3.4 for reference.
Severe infections (according to CTCAE grading in Section 15 of the ISF), serious infections, 
opportunistic or mycobacterium tuberculosis infections
Treatment of the infection should be initiated promptly according to local standard of care. 
No further trial medication should be administered until the active infection has been 
resolved. Treatment with spesolimab may be restarted when the trial participant has 
recovered according to investigator’s assessment. See Section 3.3.4 for reference.
Malignancies
In case of occurrence of malignant neoplasm other than appropriately treated basal cell 
carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix, the 
investigator should discontinue treatment with spesolimab. See Section 3.3.4 for reference.
Diagnostics and treatment must be initiated according to local standard of care (SoC).

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Suicidality
In case a trial participant develops suicidal ideation of type 4 or 5 in the Columbia-Suicide 
Severity rating Scale (C-SSRS) (i.e. active suicidal thoughts with method and intent but 
without specific plan, or active suicidal thoughts with method, intent and plan) or any suicidal 
behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or 
behaviour), the trial participant should immediately be referred to a mental health 
professional for further work-up and permanently discontinue trial treatment. See 
Section 3.3.4 for reference.
Overall, the choice of SoC treatment will be left at the discretion of the investigator. The 
sponsor will not provide/supply SoC treatments to the sites.
Any of the above treatments (including an estimate on dispensed medication), defined in this 
section, must be documented in the source data and documented in CRF (concomitant 
medications and AEs) and the corresponding AE report, if applicable.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
Trial participants must not participate in another investigational drug or device trial or receive 
other investigational treatment(s) while enrolled in this trial.
The following medications/medication classes are restricted during trial treatment and prior 
to Visit 2 for durations as specified in Table 4.2.2.1: 1. Please see Section 3.3.4 for 
withdrawal information regarding the use of restricted medications.

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Table 4.2.2.1: 1
Restricted medications in Part 1 (Phase IIb)*
Medications/ 
medication classes
Washout period prior to 
V2 (baseline) 
V2 to V14
From V14 to EoT
Systemic antibiotics1
4 weeks 
Restricted for HS
except for HS-disease 
worsening after V6
(definition in 
Section 4.2.3) 
Restricted for HS except 
for HS-disease worsening 
after V14
Systemic 
corticosteroids2
2 weeks 
Restricted for HS. 
For non-HS indications,
only short courses are 
allowed2
Restricted for HS2
Immunosuppressive/ 
immunomodulatory 
biologics
12 weeks or 5 half-lives 
whichever is longer
Restricted for HS and 
non-HS indications
Restricted for HS and 
non-HS indications
Other systemic non-
biologic 
immunomodulatory and 
immunosuppressive 
agents
4 weeks or 5 half-lives 
whichever is longer
Restricted for HS and 
non-HS indications
Restricted for HS and 
non-HS indications
Live vaccines3
6 weeks 
Restricted 
Restricted
Opioid analgesics
2 weeks 
Restricted for HS and 
non-HS indications
Restricted for HS4
Spironolactone5
1 week
Restricted for HS and 
non-HS indications
Restricted for HS
Metformin5
1 week
Restricted for HS and 
non-HS indications
Restricted for HS
Topical cannabis oil
1 week6
Restricted for HS
Permitted
Systemic medicinal 
cannabis
3 weeks 
Restricted for HS and 
non-HS indications
Restricted for HS
Topical corticosteroids 
for HS7
2 weeks
Restricted for HS
Restricted for HS up to 
Visit 23. 
Topical JAK inhibitors
12 weeks
Restricted for HS
Restricted for HS up to 
Visit 23
* Restricted medications are expected to be revised and adapted if needed for Part 2 (Phase III)
1 Some conditions apply on the use of systemic antibiotics, please see Section 4.2.3.1.
2 Systemic corticosteroids as short courses, i.e. approximately 1- 2 weeks at the discretion of the investigator, can be used 
for indications other than HS
3 Live vaccines are restricted for 16 weeks after the last dose of spesolimab.
4 After Visit 14
 opioid analgesics other than tramadol are restricted for HS.
5 Restricted if used for HS. If used for non-HS indication, dose should be stable for at least 12 weeks prior to V2.
Metformin and spironolactone can be initiated for non-HS indications after Visit 14
6 Restricted if used over HS-affected areas. Other alternative therapies for HS are restricted, unless permitted after 
discussion with the investigator and trial team.
7 Prior to Visit 23 
, topical corticosteroids are allowed for non HS indications for areas not concurrently involved 
by HS.
8 Use of immunomodulatory/immunosuppressive biologics other than
for HS meets exclusion criterion #2.

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4.2.2.2
Restrictions on diet and lifestyle
No specific restrictions on diet or lifestyle of the trial participants are required.
4.2.2.3
Contraception requirements
Throughout the trial, and for a period of at least
after last trial drug administration,
WOCBP must use highly effective methods of birth control per ICH M3 (R2) that result in a 
low failure rate of less than 1% per year when used consistently and correctly. A list of 
contraception methods meeting these criteria is provided in the participant information.
Female trial participants
Examples of acceptable methods of birth control for this trial:

Combined (oestrogen and progestogen containing) hormonal birth control that prevents 
ovulation (oral, intravaginal, transdermal)

Progestogen-only hormonal birth control that prevents ovulation (oral, injectable, 
implantable)

Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

Vasectomised sexual partner with documented absence of sperm
OrTrial participants must abstain from male-female sex. This is defined as being in line 
with the preferred and usual lifestyle of the trial participant. Periodic abstinence (e.g.,
calendar, ovulation, symptomthermal, post-ovulation methods), declaration of abstinence 
for the duration of exposure to study drug, and withdrawal are not acceptable.
Male trial participants
Because of the negative outcome of the completed BI teratogenicity study, a double barrier 
method of contraception is not required. Contraception of male trial participants and female 
partners of male trial participants are not required. Systematic collection of pregnancy data in 
female partners of clinical trial participant is not required [c03320877-11].
4.2.3
Concomitant medications/interventions
The following sections provide definition of certain terms used in this trial and additional 
information on certain concomitant medications and lesion interventions. The sponsor will 
not provide/supply these treatments to the sites. 
Any medication received by trial participant from Visit 1 should be recorded in the 
appropriate concomitant medications page in the eCRF.
Rescue medication is defined as the treatment for HS disease worsening and includes 
systemic antibiotics and/or immunosuppressive biologics such as TNF-inhibitors. 
HS Disease worsening is defined as total AN count is 150% of baseline AN count. For 
example, for a baseline AN count of 10, disease worsening should be interpreted as an AN 
count of 15 and above.

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4.2.3.1
Antibiotic use during the trial
Non-HS use
From randomisation up to Visit 14 
 systemic antibiotics can be used for 
indications other than HS for a duration of less than or equal to 4 weeks. The same restriction 
applies to the period from Visit 14 
to Visit 23 
, with a maximum of 4 
consecutive weeks of systemic antibiotics allowed for non-HS indications.
HS use (as defined above in Section 4.2.3):

At or after Visit 6 
, if the trial participant requires systemic antibiotics for 
HS disease worsening (as defined above in Section 4.2.3) , monotherapy with
doxycycline 100 mg orally twice daily may be used for a maximum period of 2 
weeks, and not more than a total of 4 weeks up to Visit 23 
. After V23 
, systemic antibiotics can be used for HS disease worsening (duration as per 
investigator discretion).

Please refer to the ISF for alternative oral antibiotics allowed in this trial. 

Parenteral antibiotics are restricted for HS until
based on roll over 
status.
Concomitant use of systemic antibiotic therapy for treatment of HS other than the above is 
not allowed.
4.2.3.2
Analgesics use during the trial
Opioid analgesics are restricted for HS and non-HS indications up to Visit 14 
After Visit 14 
 opioid analgesics other than tramadol are restricted for HS. After 
Visit 14, opioid analgesics can be allowed for non-HS indications as per investigator 
discretion.
If a trial participant is on a non-opioid analgesic for HS and non-HS indication (e.g. 
osteoarthritis), the patient may continue the analgesic, provided the dose is stable for 14 days 
prior to Baseline and it is anticipated to remain stable throughout the study.
If a trial participant's pain (HS-related or non-HS-related) worsens after Baseline, they may 
initiate or increase the non-opioid analgesic therapy.
Use of analgesics will be documented in the Patient Diary and the CRF.
4.2.3.3
Lesion intervention
In the event that an acutely painful lesion occurs that requires immediate intervention, 
physicians will have the option to perform protocol-allowed interventions.
Only two types of interventions are allowed in this trial: intra-lesional steroid and Incision 
and Drainage (I&D). 

If I&D is performed, only over the counter antiseptic wash can be used. Concomitant 
medications associated with the lesion intervention must be captured in the medical 
records.

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
Intralesional steroid injections of triamcinolone up to 
 can be used for a single 
lesion at one time. 
Up to Visit 14 
 a total of two protocol-allowed interventions are permissible. After 
Visit 14 
up to Visit 23 
, a total of two protocol-allowed interventions 
are permissible. For each period, an intervention can maximally occur on two different 
lesions at the same time or on the same lesion at two different study visits. From Visit 23 
to EoT, there are no restriction in the number of lesion interventions.
Lesions that have been subjected to intervention should not be counted in future assessments.
4.3
TREATMENT COMPLIANCE
Compliance will be verified by the CRA authorized by the sponsor.
Treatment compliance is defined as good if between 80-120% of scheduled 
 as per 
protocol are received. If the treatment compliance is not between 80-120%, site staff will be 
reminded about the importance of treatment compliance. However, randomised participants 
will not be discontinued for poor compliance without prior discussion with the monitor or 
designee.

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5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
The primary, secondary and further endpoints of the study are specified in Section 2.1.2, 
Section 2.1.3 and Section 2.2.2, respectively.
Efficacy assessments are primarily based on the reduction of HS lesions count evaluated by 
the investigator (or appropriately qualified delegate). Adequate identification and counting of 
draining tunnels, abscesses, and inflammatory nodules are key and require careful training.
As much as possible, the same or a reduced number of well-trained evaluators should be 
assessing lesions at one investigative site to reduce unspecific variability as much as possible.
Efficacy will also be assessed in this study according to patient’s reporting outcomes
including the assessment of skin pain, pruritus, but also drainage and odour, Dermatology
Life Quality Index, HiS-QoL.
The description of specific scores, index, or PROs used as efficacy outcome is provided 
below.
Part 1 (Phase IIb) and Part 2 (Phase III)
1. International Hidradenitis Suppurativa Severity Score System (IHS4)
The IHS4 is a validated, clinical scoring system for dynamic assessment of HS severity. 
Determining IHS4 requires counting nodules, abscesses and dT/sinus tracts making it 
straightforward to apply in clinical trials [R20-3045]. IHS4 will be evaluated at the time-
points mentioned in the Flowchart, and the detail is provided in Appendix 10.4.
2. Hidradenitis Suppurativa Clinical Response (HiSCR50)
The HiSCR50 is one of the most well-known and widely used outcome assessment in HS 
clinical trials. The HiSCR50 is defined as at least a 50% reduction from baseline in the 
total AN count, 
[R20-2976]. HiSCR50 will be 
evaluated at the time-points mentioned in the Flowchart. Appendix 10.3.
3. Hidradenitis Suppurativa Area and Severity Index (HASI)
The HASI is modelled after the Psoriasis Activity and Severity Index (PASI). Four classic 
signs of HS-related inflammation (erythema, induration, open ulcer, and dTs) are 
included. Each variable in HASI is scored on a Likert scale (0-3) for each predetermined 
body region.
 
This is converted 

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HASI will be evaluated at the time-points mentioned in the Flowchart, and the 
detail is provided in Appendix 10.5.
4. Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA)
This documents the physician’s assessment of the patient’s HS at a given time-point. It 
scores patient disease severity (as either clear, minimal, mild, moderate to severe, or very 
severe) based on abscesses, dT, inflammatory nodule, and non-inflammatory nodule 
[R20-3046]. HS-PGA will be evaluated at the time-points mentioned in the Flowchart,
and the detail is provided in Appendix 10.6.
5. Pain Numerical Rating Scale (NRS Pain)
The HS Pain NRS is an endpoint for the assessment of HS-related pain severity for 
clinical trials with patients with HS. The Patient Global Assessment of HS Pain will be 
used to assess the worst HS pain. Ratings will range from 0 (no HS pain) to 10 (HS pain 
as bad as you can imagine). It is a unidimensional measure of pain intensity and can be 
administered daily with minimal trial participant burden. Recall period is 24 h and 
response is given by an 11-point scale ranging from 0 to 10; see Appendix 10.7.
6. Pruritus Numerical Rating Scale (NRS Pruritus)
The HS Pruritus NRS is an endpoint for the assessment of HS-related pruritus severity for 
clinical trials with patients with HS. The Patient Global Assessment of HS Pruritus will 
be used to assess the worst HS pruritus. Ratings will range from 0 (no itch) to 10 (HS 
worst imaginable itch). It is a unidimensional measure of pruritus intensity and can be 
administered daily with minimal trial participant burden. Recall period is 24 h and 
response is given by an 11-point scale ranging from 0 (“no itch”) to 10 (“worst 
imaginable itch”). Trial participants are asked to rate the intensity of their itch using this 
scale; see Appendix 10.8.
7. Dermatology Life Quality Index (DLQI)
The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers 
six domains including symptoms and feelings, daily activities, leisure, work and school, 
personal relationships and treatment [R05-2548]. The DLQI has a one-week recall period. 
Response categories include “not relevant” (score of 0), “not at all” (score of 0), “a little” 
(score of 1), “a lot” (score of 2) and “very much” (score of 3). Question 7 is a “yes”/“no” 
question where “yes” is scored as 3, see Appendix 10.9.
The DLQI will be analysed under six headings as shown in Table 5.1: 1 [R05-2548].

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Table 5.1: 1
DLQI
Domain
Question Number
Score
Symptoms and feelings
Questions 1 and 2
Score maximum 6
Daily activities
Questions 3 and 4
Score maximum 6
Leisure
Questions 5 and 6
Score maximum 6
Work and school
Question 7
Score maximum 3
Personal Relationships
Questions 8 and 9
Score maximum 6
Treatment
Question 10
Score maximum 3
8. Hidradenitis Suppurativa Quality of Life (HiS-QoL)
The HiS-QoL is a patient-administered, 17-item instrument to measure HS-specific 
quality of life in clinical trials with a 7-day recall period [R20-3156]. The 17-item HiS-
QoL included four symptom items, eight activity-adaptation items, and five psychosocial 
items.
9. Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue)
The FACIT-Fatigue is a 13-item questionnaire [R10-6433], [R07-4311], [R16-0029] that 
assesses self-reported fatigue and its impact upon daily activities and function. Answers 
are based on a 5-point Likert scale. Responses of “not at all”, “a little”, “somewhat”, 
“quite a bit”, and “very much” are available for each question and correspond to scores of 
0, 1, 2, 3, and 4, respectively (total score range: 0-52).
10. Patient Global Impression of Change (PGI-C)
The PGI-C is a 1-item tool assessing the change of HS by start of taking the study 
medication by 5-point Likert-type scale. The first assessment of PGI-C is performed at 
Visit 6 
 and after that, as indicated in the Flowchart. The tool is required for 
anchoring of other instruments and endpoints, see Appendix 10.12.

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11. Patient Global Impression of Severity (PGI-S)
The PGI-S is a 1-item tool assessing the severity of HS over the last week by 4-point 
Likert-type Scale. The first assessment of PGI-S is performed at Visit 2 
. The 
tool is required for anchoring of other instruments and endpoints; see Appendix 10.13.
12. Hidradenitis Suppurativa odour and drainage scale (HODS)
The HODS is an 8-item scale developed to assess the HS-related drainage and odour in 
patients. It covers two domains: drainage (5 items) and odour (3 items). The response 
options range from 1-5. Higher scores depict worse outcome of the concept being 
assessed; see Appendix 10.14.
13. Hospital Anxiety and Depression Scale (HADS)
The HADS is an instrument for screening anxiety and depression in non-psychiatric 
populations. The HADS consists of 14 items, 7 each for anxiety and depression 
symptoms; possible scores range from 0 to 21 for each subscale; see Appendix 10.15.
Part 2 (Phase III) only
14. Work Productivity and Activity Impairment Questionnaire for HS (WPAI-HS)
WPAI-HS is 6-item instrument to assess the effect of hidradenitis suppurativa on ability 
to work and perform normal daily activities; see Appendix 10.16.
15. EuroQol 5 dimensions 5-level (EQ-5D-5L)
Assessment of changes in quality of life using the EuroQol-5D-5L. The descriptive 
system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort,
and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, 
moderate problems, severe problems, and extreme problems. The EQ VAS records the 
patient’s self-rated health on a vertical visual analogue scale, where the endpoints are 
labelled ‘The best health you can imagine’ and ‘The worst health you can imagine’; see 
Appendix 10.17.
The Patient Global Assessment of HS Pain and HS Pruritus will be completed on a diary (one
scale for pain and another for pruritus), on a daily basis by trial participants from Visit 2 
through Visit 19 
After Visit 19, NRS pain and NRS pruritus will be 
collected on a daily basis during the 7 days prior to the next scheduled visit as per Flowchart.
For details, refer to the Flowchart.
For the daily assessments, trial participants should be instructed that, before they go to bed, 
they complete the assessment based on a recall period of the "last 24 hours" and respond to 
the items. This training should be documented in trial participant clinical records.
Further instructions on diary completion can be found in the ISF.

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5.2
ASSESSMENT OF SAFETY
Safety will be assessed descriptively based on the following observations and 
examinations:

Physical examination

Vital signs

Clinical laboratory values (haematology, clinical chemistry, coagulation, infection 
testing and urinalysis)

12-lead ECG

AEs

Serious AEs (SAEs)

Intensity of AEs assessed by CTCAE grading version 5.0 (refer to ISF for details)

Suicidality
The detailed corresponding observations and examinations are described in the following 
respective subsection.
5.2.1
Physical examination
Physical examinations will be performed at the time points specified in the Flowchart.
A complete physical examination will be performed at screening. It includes at a minimum 
general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin.
For subsequent visits, targeted physical examinations will be done. Targeted physical 
examination should include examination of the skin (involved areas) and examination 
pertinent to adverse events or abnormal results from lab test, ECG and/or vital signs.
Measurement of height and body weight will be performed at the time-points specified in the 
Flowchart. BMI will be automatically calculated.
The results must be included in the source documents available at the site. 
5.2.2
Vital signs
Vital signs will be evaluated at the time-points specified in the Flowchart. This includes 
temperature, respiratory rate, systolic and diastolic blood pressure, and pulse rate 
(electronically or by palpation count for 1 minute). The results must be included in the trial 
participant’s source documents. Measurement of vital signs should precede blood sampling at 
all visits.
At dosing visits, vital sign evaluations will be performed pre-dose and additional evaluations 
will be taken post-dose, approximately 5 and 60 minutes after 
The 
investigator should evaluate the clinical significance of the results. Clinically abnormal 
findings will be reported as baseline condition or AEs.

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At dosing visits for 
administration, vital signs evaluations will be 
performed pre-dose and, again, approximately 10 minutes after the end of drug 
administration. At Visit 6
 and Visit 7 
 additional 
measurements will be performed approximately 60 minutes post-dose 
5.2.3
Safety laboratory parameters
Safety laboratory parameters to be assessed are listed in Table 5.2.3: 1. For the sampling 
time-points, please see the Flowchart. More frequent blood sampling than the defined in the 
Flowchart may be done whenever the investigator deems necessary. Unscheduled safety 
laboratory examinations will be reported in the CRF along with the results.
It is preferred, but trial participants do not have to be fasted for the blood sampling for the 
safety laboratory. Instructions regarding sample collection, sample handling/processing, and 
sample shipping are provided in the Laboratory Manual in the ISF.
All analyses will be performed by a central laboratory, and the respective reference ranges 
will be provided in the ISF.
The central laboratory will send reports to the investigator. It is the responsibility of the 
investigator to evaluate the laboratory reports. Clinically relevant abnormal findings as 
judged by the investigator will be reported as baseline conditions or AEs (please refer to 
Section 5.2.6). A clinically relevant value may be either in- or outside the reference range. 
Clinically relevant abnormal laboratory test results must be confirmed and should be repeated 
until normalisation or stabilisation or until an alternative explanation has been found. 
Abnormal laboratory values will be graded for intensity by using CTCAE Version 5.0 
criteria.
In case the criteria for hepatic injury are fulfilled, a number of additional measures will be 
performed (please see Section 5.2.6.1 and the DILI Checklist provided in the ISF. The 
amount of blood taken from the trial participant concerned will be increased due to this 
additional sampling.

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Table 5.2.3: 1
Safety laboratory tests
Functional lab group
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hbc (HbA1c) (Only at baseline)
Red Blood Cell Count/Erythrocytes
Reticulocyte Count
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes
Diff. Automatic
Neutrophils (relative and absolute count)
Eosinophils (relative and absolute count)
Basophils (relative and absolute count)
Monocytes (relative and absolute count)
Lymphocytes (relative and absolute count)
Diff. Manual (if Diff Automatic is 
abnormal)
Neutrophils, bands (Stabs)
Neutrophils, polymorphonuclear (PMN)
Eosinophils
Basophils
Monocytes
Lymphocytes
Coagulation
Activated Partial Thromboplastin Time (aPTT)
Prothrombin time (INR)
Fibrinogen
Enzymes
AST (GOT)
ALT (GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
CK-MB, only if CK is elevated
Gamma-Glutamyl Transferase (GGT/γ-GT)
Lactic Dehydrogenase (LDH)
Amylase
Lipase
Electrolytes
Calcium
Sodium
Potassium
Chloride

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Table 5.2.3:1
Safety laboratory tests (cont.)
Functional lab group
Test name
Substrates
Glucose
BUN (blood urea nitrogen)
Uric acid
Creatinine2
eGFR (estimated by CKD-EPI formula) (only at screening)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Troponin (Reflex, in case of elevated CK)
Protein, Total
Albumin
C-Reactive Protein (CRP and hs-CRP [high sensitivity –
CRP])
Cholesterol, total
Triglycerides
LDL-Cholesterol
HDL-Cholesterol
Specific gamma-globulin quantification
Hypersensitivity
IgE1
Complement C3
Complement C4
Complement total
Histamine
Tryptase
Urine Pregnancy test (only for female 
patients of childbearing potential)
Human Chorionic Gonadotropin in urine
Serum Pregnancy test (only for female 
patients of childbearing potential at 
screening. At later visits only if urine 
pregnancy test is positive)
Human Serum Chorionic Gonadotropin
Hormones (only at screening)
TSH (free T3 and free T4 in case of abnormal TSH result)
Urinalysis (dipstick)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocytes
Urine WBC/Leukocytes
Urine pH

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Table 5.2.3:1
Safety laboratory tests (cont.)
Functional lab group
Test name
Urine-Sediment (microscopic examination, 
only if urine analysis abnormal)
Urine Sediment Bacteria
Urine Cast in Sediment
Urine Squamous Epithelial Cells
Urine Sed. Crys., Unspecified
Urine Sediment RBC/Erythrocytes
Urine Sediment WBC/Leucocytes
Urine (only at screening)
Albumin (quantitative)
Infection Testing
See Table 5.2.3: 2
1
Only in case of allergic reaction
2
Creatinine can be measured by any of the three serum creatinine assays listed in the table below:
Short name
Name of serum creatinine assay
Substrate
Other information
CREE
Creatinine, enzymatic
creatinine
Enzymatic
CREJIDMS
Creatinine, Jaffe, IDMS
creatinine
Jaffe reaction, IDMS standardised
CREJ
Creatinine, Jaffe, Not IDMS
creatinine
Jaffe reaction, Not IDMS standardised
Table 5.2.3: 2
Exclusionary laboratory tests (including infection and pregnancy testing)
Functional lab group
Test name 
Infection Testing
Hepatitis B Surface Antigen (qualitative)
Hepatitis B Surface Antibody (qualitative) (Only 
for Japan)
Hepatitis B core Antibody (qualitative)
HBV-DNA PCR (quantitative) at screening (Visit 
1) and EOT Visit1
Hepatitis C Antibody (qualitative)6
HIV-1, and HIV-2 Antibody (qualitative)
QuantiFERON®-TB-Gold Plus, 2,3, 4,5
T-spot TB test
Serum pregnancy test (only for female trial 
participants of childbearing potential)
Human Serum Chorionic Gonadotropin
1
A HBV-DNA PCR should be done if Hepatitis B core Antibody is positive and Hepatitis B Surface Antigen is negative. 
These evaluations should be conducted at screening and at the EOT visit. (Only for Japan: a HBV-DNA PCR should be 
done if Hepatitis B core Antibody and/or Hepatitis B Surface Antibody is positive and Hepatitis B Surface Antigen is 

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negative. These evaluations should be conducted at screening and at the EOT visit. If HBV DNA level is undetectable at 
screening, the patient can participate in this trial. But HBV DNA level will be monitored at least every 6 months.)
2
There is the trial site option to perform a PPD skin test. (Only for Japan: Chest X-ray test or CT chest should be done if 
not done within 3 months prior to Visit 1.)
3
Trial participants with indeterminate QuantiFERON or invalid/borderline T-spot may be retested with IGRA (once) and 
if inconclusive should have a PPD skin test.
4
In trial participants with a negative IGRA or PPD skin test, the test should be repeated at the EoT visit. Results of the 
PPD test should be collected in the CRF.
5
Only for South Africa: Additionally, the tuberculosis infection testing will be repeated approximately 6 months from 
baseline 
 On clinical suspicion of Tuberculosis, infection testing can be performed as per the 
investigator’s discretion at any time during the study.
6
Positive Hepatitis C antibody should be confirmed with Hepatitis C RNA PCR.
The investigator will use the exclusionary lab test results for the assessment of the 
participants’ eligibility for the trial. The infection testing will be repeated at EoT visit as per 
defined criteria.
5.2.4
Electrocardiogram
The 12-lead ECGs must be administered by a qualified technologist and results will be 
recorded as scheduled in the Flowchart. The investigator or a designee will evaluate whether 
the ECG is normal or abnormal and assess clinical relevance. ECGs may be repeated for 
quality reasons. Additional ECGs may be recorded for safety reasons. Dated and signed 
printouts of ECG with findings should be documented in participant’s medical record.
Clinically relevant abnormal findings will be reported either as baseline condition (if 
identified at the screening visit) or otherwise as AEs and will be followed up and/or treated as 
medically appropriate.
5.2.5
Other safety parameters
Trial participants with a history of malignancy (except for specific cancers) will be excluded 
from this trial per the exclusion criteria (Section 3.3.3). All cases of malignancies that are 
detected during the trial will be reported as SAEs, see Section 5.2.6.
5.2.5.1
Local tolerability
Local tolerability at the administration site of trial medication will be assessed by the 
investigator during the study drug administration visit and at the time of AE assessment by 
questioning retrospectively since the last visit. Any observed local tolerability reaction, e.g. 
“swelling”, “induration”, “heat”, “redness”, “pain”, and other findings should be reported as 
an adverse event, see Section 5.2.6.
Suicidal thoughts and behaviour will be assessed by the Columbia-Suicide Severity Rating 
Scale (C-SSRS) [R08-1147]. The C-SSRS is a semi-structured, investigator-rated interview, 
developed by clinical experts in cooperation with the FDA, assessing both suicidal behaviour
and suicidal ideation. It does not give a global score but provides some categorical and some 
severity information specifically for behaviour and ideation.

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The baseline/screening scale of the C-SSRS will be administered for eligibility confirmation 
and the follow-up scale at all visits for assessment of suicidality. 
The C-SSRS interview may be administered by any type of physician, psychologist, clinical 
social worker, mental health counsellor, nurse, or coordinator with C-SSRS training. It has a 
typical duration of five minutes and causes only a low burden on trial participants. At a 
minimum, the interview consists of 2 screening questions related to suicidal ideation and 4 
related to suicidal behaviour and may be expanded to up to 17 items in case of positive 
responses. Free text entries are allowed for; the investigator has to directly evaluate the scale 
and write a report. In this trial, paper forms will be used for the assessment of the C-SSRS, 
and results will be transcribed into the e-CRF.
The C-SSRS has been widely used in large multinational clinical trials. The C-SSRS will be 
administered at the Screening Visit/Visit 1 (using the ‘baseline/screening’ version) with the 
aim to exclude patients with active moderate to severe symptomatology within a specified 
time prior to the screening or screening visit. The lifetime and the past year history of suicidal 
ideation and behaviour will also be recorded. After the screening visit, the assessment ‘since 
last visit’ version will be performed at each visit. The investigator is to review positive and 
negative reports for plausibility and clinical relevance. Doubtful reports may be repeated, or 
reports may be validated by a consulting psychiatrist or other mental health professional 
expert. If there is a confirmed positive report of suicidal behaviour or suicidal ideation type 4 
or 5 after start of trial (see Section 3.3.4.1 for reference about discontinuation), the 
investigator is to immediately interview the trial participant and/or is to consult a mental 
health professional. If the positive report is confirmed, appropriate actions for the trial 
participant’s safety have to be initiated.
All C-SSRS reports of suicidal ideation type 4 or 5 and all reports of suicidal behaviour must 
be reported as separate SAEs by the investigator. For ‘Self-injurious behaviour, without 
suicidal intent’, standard AE/SAE reporting rules are to be applied. For each negative report 
(suicidal ideation type 1, 2, or 3) after the start of the trial, the investigator is to decide on the 
basis of clinical judgment whether it represents an AE as defined in the protocol, and if it is 
considered an AE, then it must be reported accordingly.
5.2.6
Assessment of adverse events
Data and information necessary for the thorough assessment of AEs, SAEs, and AESIs will 
be reported to the sponsor via eCRF. This may include specific data and information not 
prospectively specified in this protocol.
5.2.6.1
Definitions of AEs
5.2.6.1.1
Adverse event
An AE is defined as any untoward medical occurrence in a trial participant or clinical 
investigation subject administered a medicinal product and which does not necessarily have 
to have a causal relationship with this treatment.

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An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether considered drug-related or not.
The following should also be recorded on the appropriate eCRFs, BI SAE form (if 
applicable):

Worsening of the underlying disease (for definition, see Section 4.2.3) or of other 
pre-existing conditions.

Changes in vital signs, ECG, physical examination, and laboratory test results, if they 
are judged clinically relevant by the investigator.
If such abnormalities already exist prior to trial inclusion, they will be considered as baseline 
conditions and should be collected in the eCRF only.
5.2.6.1.2
Serious adverse event
A SAE is defined as any AE, which fulfils at least one of the following criteria:

Results in death.

Is life-threatening, which 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 that hypothetically might 
have caused death if more severe.

Requires inpatient hospitalisation or prolongation of existing hospitalisation.

Results in persistent or significant disability or incapacity.

Is a congenital anomaly/birth defect.

Is deemed serious for any other reason if it is an important medical event when based 
on appropriate medical judgement which may jeopardise the participant and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalisation or development of dependency or 
abuse.
For Japan only: an event that possibly leads to disability will be handled as “deemed serious 
for any other reason” and, therefore, reported as an SAE.
5.2.6.1.3
AEs considered “Always Serious”
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of AEs, which by their nature, can always be 
considered to be “serious” even though they may not have met the criteria of an SAE as 
defined in Section 5.2.6.1.2. The latest list of “Always Serious AEs” can be found in the eDC 
system. A copy of the latest list of “Always Serious AEs” will be provided upon request. 
These events should always be reported as SAEs as described in Section 5.2.6.2.
Cancers of new histology and exacerbations of existing cancer must be classified as a serious 
event regardless of the time since discontinuation of the drug and must be reported as 
described in Section 5.2.6.2, subsections “AE Collection” (Section 5.2.6.2.1) and “AE 
reporting to sponsor and timelines” (Section 5.2.6.2.2).

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5.2.6.1.4
Adverse events of special interest
The term “adverse event of special interest” (AESI) relates to any specific AE that has been 
identified at the project level as being of particular concern for prospective safety monitoring 
and safety assessment within this trial, e.g. the potential for AEs based on knowledge from 
other compounds in the same class. AESIs need to be reported to the sponsor’s 
Pharmacovigilance Department within the same timeframe that applies to SAEs; please see 
Section 5.2.6.2.2.
The following are considered as AESIs:
Systemic hypersensitivity including infusion reaction and anaphylactic reaction
Any suspicion of severe infusion reaction systemic/hypersensitivity reaction and of any 
potential cases of anaphylaxis should be defined and assessed using the criteria discussed in 
the statement paper from Sampson HA (Appendix 10.20 [R11-4890]), see Section 4.2.1 for 
“Other treatments and emergency procedures”.
Severe infections (according to CTCAE grading in Section 15 of the ISF)
(See Section 4.2.1 for “Other treatments and emergency procedures”)
Opportunistic and mycobacterium tuberculosis infections
These include pneumocystis jirovecii, BK virus disease including PVAN, CMV, post-
transplant lymphoproliferative disorder (EBV), progressive multifocal leucoencephalopathy, 
bartonellosis (disseminated only), blastomycosis, toxoplasmosis, coccidioidomycosis,
histoplasmosis, aspergillosis (invasive only), candidiasis (invasive or pharyngeal), 
cryptococcosis, other invasive fungi (mucormycosis [zygomycosis, rhizopus, mucor, 
lichtheimia], scedosporium/pseudallescheria boydii, fusarium), legionellosis, listeria 
monocytogenes (invasive only), tuberculosis, nocardiosis, non-tuberculous mycobacterium, 
salmonellosis (invasive only), HBV reactivation, herpes simplex (invasive only), herpes 
zoster, strongyloides (hyperinfection syndrome and disseminated forms only), 
paracoccidioides, penicillium marneffei, sporothrix schenckii, cryptosporidium species 
(chronic only), microsporidiosis, leishmaniasis (visceral only), trypanosoma cruzi infection 
(Chagas’ disease) (disseminated only), campylobacteriosis (invasive only),  shigellosis 
(invasive only), vibriosis (invasive due to vibrio vulnificus), HCV progression [R17-2617].
Potential Severe DILI
A potential severe Drug Induced Liver Injury (DILI) that requires follow-up is defined by any 
of the following alerts (alterations) of hepatic laboratory parameters: 
1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation ≥3x ULN 
and total bilirubin (TBIL) ≥2x ULN measured at the same visit, or in samples drawn 
within 30 days of each other, OR
2. AST or ALT elevation ≥3x ULN and INR ≥1.5x ULN measured at the same visit, or in 
samples drawn within 30 days of each other, OR
3. AST or ALT elevation ≥3x ULN with new onset, or worsening of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%), 
OR
4. AST or ALT elevation ≥5x ULN

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These laboratory findings constitute a hepatic injury alert, and participants showing any of
these lab abnormalities need to be followed up according to the “DILI checklist” provided in 
the eDC system.
In case of clinical signs or symptoms of hepatic injury (icterus, unexplained encephalopathy, 
unexplained coagulopathy, right upper quadrant abdominal pain, etc.) without lab results 
(ALT, AST, TBIL) available, the investigator should make sure these parameters are 
analysed, if necessary, in an unscheduled blood test. Should the results meet the criteria of 
hepatic injury alert, the procedures described in the DILI checklist should be followed.
Additionally, with participants having a normal AST and ALT at baseline, the emergence of 
an isolated AST or ALT elevation between ≥3-fold and <5x ULN requires repeat testing 
within 72 hours. DILI Checklist is not required unless repeat testing triggers alerts 1, 2, 3, or 
4, mentioned above.
The following events should lead to immediate discontinuation of trial treatment (active or 
comparator):

Hepatic injury alert numbers 1, 2, or 3

Hepatic injury alert number 4, if persists >2 weeks

AST or ALT elevation >8x ULN
Following completion of the DILI Checklist, if the BI investigational drug cannot be 
excluded as a possible cause of DILI event, then discontinuation should be made permanent 
without rechallenge. If an alternate causality, e.g. acute viral hepatitis, is confirmed by the 
DILI Checklist evaluation, then BI investigational drug may be re-started, if warranted.
Peripheral neuropathy
Any event suspected or diagnosed as peripheral neuropathy would be considered as an AESI.
For the treatment interruption rules, please see Section 3.3.4.1.
5.2.6.1.5
Intensity (severity) of AEs
The intensity (severity) of AEs should be classified and recorded in the CRF according to the 
CTCAE version 5.0.
5.2.6.1.6
Causal relationship of AEs
Medical judgement should be used to determine the relationship between the AE and the BI 
investigational compound, considering all relevant factors, including pattern of reaction, 
temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant 
medication, concomitant diseases, and relevant history. 
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be as follows:

The event is consistent with the known pharmacology of the trial drug.

The event is known to be caused by or attributed to the drug class.

A plausible time to onset of the event relative to the time of drug exposure.

Evidence that the event is reproducible when the drug is re-introduced.

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
No medically sound alternative aetiologies that could explain the event (e.g. 
pre-existing or concomitant diseases, or co-medications)

The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome)

An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is reduced)
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be as follows:

No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days/weeks of 
drug administration; an allergic reaction weeks after discontinuation of the trial drug 
concerned)

Continuation of the event despite the withdrawal of the medication, considering the 
pharmacological properties of the compound (e.g. after 5 half-lives); of note, this 
criterion may not be applicable to events whose time course is prolonged despite 
removing the original trigger

There is an alternative explanation, e.g. situations where other drugs or underlying 
diseases appear to provide a more likely explanation for the observed event than the 
drug concerned

Disappearance of the event even though the trial drug treatment continues or remains 
unchanged
5.2.6.2
Adverse event collection and reporting
5.2.6.2.1
AE collection
The investigator shall maintain and keep detailed records of all AEs in the participant files.
Per default SAEs/AESIs should be reported via the eCRF in the EDC system. If the EDC 
system is not or no longer available (e.g. after database lock), the BI paper SAE form should 
be used; please see Section 5.2.6.2.2.
For trial participants not rolling over to LTE trial, the following must be collected and 
documented on the appropriate CRF(s) by the investigator:

From signing the informed consent onwards until the individual participant’s end of trial
(usually the EoS visit, please see Section 6.2.3): 
all AEs (serious and non-serious) and all AESIs

After the individual participant’s end of trial: 
the investigator does not need to actively monitor the participant for new AEs but should
only report any occurrence of cancer of new histology and trial drug-related SAEs and 
trial drug-related AESIs of which the investigator may become aware of by any means of 
communication, e.g. phone call; those AEs should be reported on the BI SAE form (see 
Section 5.2.6.2.2), but not on the CRF
For trial participants rolling over to LTE trial the following must be collected and 
documented on the appropriate CRF(s) by the investigator or delegated:

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From signing the informed consent of the parent trial onwards until the first dose of trial 
medication in the LTE trial: all AEs (serious and non-serious) and all AESIs.
5.2.6.2.2
AE reporting to the sponsor and timelines 
The investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the AE or SAE eCRF pages to the sponsor’s unique entry point
immediately (within 24 hours of becoming aware of the event), the country specific process
will be described in the ISF. The same timeline applies if follow-up information becomes 
available. In specific occasions, the investigator could inform the sponsor upfront via 
telephone in addition.
With receipt of any further information on these events, follow-up reports have to be 
provided. For follow-up information, the same rules and timeline apply as for initial 
information. All (S)AEs, including those persisting after individual participant’s end of trial
must be followed up until they have resolved, have been assessed as “chronic” or “stable”, or 
no further information can be obtained. Should the EDC system not be available for more 
than 24 hours, reporting must occur via the BI paper SAE forms.
For Japan:
The investigator must report medical device (prefilled syringes) failure of the trial medication 
that leads to AEs, SAE and/or AESI or is judged as a potential cause for leading SAEs by the 
investigator on the Product/Device Complaints Form to the sponsor. Please refer the 
instruction in ISF for further reporting requirements of medical device (prefilled syringes) 
failure accompanied with AEs, SAE and/or AESI or judged as a potential cause for leading 
SAEs.
5.2.6.2.3
Pregnancy
In rare cases, pregnancy might occur in a clinical trial. Once a trial participant has been 
enrolled in the clinical trial and has taken trial medication, the investigator must report any 
drug exposure during pregnancy in a trial participant immediately (within 24 hours) by means 
of Part A of the Pregnancy Monitoring Form to the sponsor’s unique entry point.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up and reported to the sponsor’s unique entry point on the Pregnancy Monitoring 
Form for Studies (Part B).
The ISF will contain the Pregnancy Monitoring Form for Studies (Part A and B).
As pregnancy itself is not to be reported as an AE, in the absence of an accompanying SAE 
and/or AESI, only the Pregnancy Monitoring Form for Studies is to be completed. However, 
if there is an SAE and/or AESI associated with the pregnancy, it must be reported in 
accordance with the rules and timeline as described in Section 5.2.6.2.2.

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5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
5.3.1
Assessment of pharmacokinetics
Spesolimab concentrations will be reported descriptively.
Trial participants do not have to be fasted for the PK and ADA/NAb blood sampling. Refer 
to the Flowchart for the time points of PK and ADA/NAb sample collection. Date and exact 
time of drug administration and PK and ADA/NAb sampling will be recorded on CRFs. See 
for reference Appendix 10.1. At study visits with study drug administration, pre-dose 
PK/ADA/NAb samples will be obtained approximately within 2 hours prior to start of 
 
 At 
Day 1, post-dose PK samples will also be obtained 
approximately 5 minutes after end of 
5.3.2
Methods of sample collection
Handling procedures can be found in the laboratory manual in the ISF. Samples will be stored 
in a freezer set at the analytical laboratory until the finalisation of the clinical trial report 
(CTR). The study samples will be discarded after completion of the additional investigations 
but not later than 5 years upon the final study report has been signed.
5.3.2.1
Plasma sampling for pharmacokinetic analysis
For quantification of spesolimab plasma concentrations, approximately 3.0 mL of blood will 
be taken from a forearm vein into a K2EDTA (ethylendiaminetetraacetic acid) anticoagulant 
blood-drawing tube at the time points listed in the Flowchart under PK sampling. The plasma 
samples may be used for further methodological investigations, (e.g. stability testing) 
however, only data related to the analyte will be generated by these additional investigations. 
5.3.2.2
Sampling for ADA/NAb assessment
For ADA assessment, approximately 3.0 mL of blood will be taken from a forearm vein into 
a K2EDTA anticoagulant blood-drawing tube at the time-points listed in the Flowchart under 
plasma ADA/NAb sampling. For NAb assessment, approximately 3.0 mL of blood will be 
taken from a forearm vein into a serum blood drawing tube at the time-points listed in the 
Flowchart under ADA/NAb sampling. 

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The plasma/serum samples may be used for further methodological investigations, e.g.for 
further investigations to characterise ADA response or to address Health Authority questions 
regarding the results/methodology, however only data related to the anti-drug antibodies will 
be generated by these additional investigations. 
5.3.3
Analytical determinations
Spesolimab plasma concentrations will be determined by a validated assay. 
The presence of ADA to spesolimab will be assessed via a tiered approach using a validated 
assay (screening, confirmatory, and titration analysis, as appropriate). Time-points that are 
confirmed positive may be further characterised using a validated NAb assay.
5.3.4
Pharmacokinetic - pharmacodynamic relationship
No formal analysis of pharmacokinetic/pharmacodynamic relationships is planned.
If the data suggest a pharmacokinetic/pharmacodynamic relationship of special parameters,
e.g., an exploratory analysis may be performed.
Correlation between drug concentration and response may be made if adequate data are
available. In addition, exploratory correlations may also be made between drug concentration
and AEs.
Data may also be used to develop pharmacokinetic/pharmacodynamic models using nonlinear
mixed effect modelling techniques, if feasible. For this purpose, data may also be combined
with data from other trials. Modelling activities will be planned and documented separately
according to internal and external guidelines and Standard Operating Procedures (SOP).
5.4
ASSESSMENT OF BIOMARKERS
This section refers to exploratory biomarkers. Established biomarkers of efficacy and safety 
are described and discussed in Section 5.1 and Section 5.2.
The further objectives, related to 
exploratory biomarkers, are specified in Section 2.2.1.

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5.4.1
Biochemical and cellular biomarkers
5.4.3
Imaging biomarkers
5.4.4
Methods of sample collection
Detailed instructions on sampling, preparation, processing, shipment, and storage of samples 
are provided in the laboratory manual in ISF. For sampling time-points, refer to the 
Flowchart.
Whole blood for gene expression analysis
For the assessment of RNA expression, whole blood will be collected from a forearm vein 
and stored according to standard procedure provided in ISF.
Skin biopsy and US lesion evaluation
For the skin biopsies, one punch biopsy from lesional skin will be collected at Visit 2 
and Visit 10 
. An additional paired non-lesional skin biopsy will also be 
collected at baseline.

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Selected trial sites with US capability
At selected trial sites with US capability, skin biopsies (lesional and non-lesional) will be
obtained as mandatory. Skin biopsies will be done under US guidance to ensure optimal skin 
biopsy selection and increase the quality of sampling.
All other trial sites (i.e. other than selected trial sites)
Skin biopsies (lesional and non-lesional) and US lesion evaluation with US imaging will be 
optional.
Study samples
The study samples will be discarded after completion of any investigations, but not later than 
2 years after the biomarker report has been signed. Any leftover samples or derived material 
from pre-specified analyses (e.g. RNA, DNA, and blood) may be used for method 
development/validation but will be destroyed no later than 2 years after the biomarker report 
has been signed. Exceptions are remainders of study samples for which a participant has 
voluntarily accepted a biobanking option and has provided a signed ICF (see Section 5.5).
5.4.5
Analytical determinations
Serum, whole blood and skin biomarkers will be analysed using established parameters for 
each analyte and the corresponding matrix.
Characteristics of the analytical methods for the analysis of the biomarkers will be given in 
detail in an accompanying technical/biomarker report. 
The biomarker assay analysis of all biomarker samples will be performed in a staged 
approach. The initial analysis will focus on selected time-points, and depending on these 
results, a decision will be made about further analysis of all samples. This is due to the 

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exploratory nature of the mechanism being tested and the timing of effect on candidate 
biomarkers in the study. And this approach may also imply that not all collected samples will 
be analysed, especially in case of termination of the project/trial.
5.5
BIOBANKING
Participation in biobanking is voluntary and not a prerequisite for participation in the trial. 
Biobanking will only occur after a separate biobanking informed consent has been given in 
accordance with local ethical and regulatory requirements.
Unspecified DNA banking:
An additional blood sample for DNA banking will be collected in 
at Visit 2 (see Flowchart). 
5.6
OTHER ASSESSMENTS
Assessments PROs
Administration of paper or electronic PRO (PRO/ePRO) assessments will be in accordance 
with the guidance from regulatory authorities and international societies (e.g. ISPOR). Trial 
participants are required to fill PRO/ePRO assessments on their own in a quiet area/room at 
the frequency as specified in the CTP, without being influenced by the investigator or other 
members of the trial team. The PRO/ePRO assessments are to be completed by the 
participant without any help from or interpretation/translation by other people. If this is not 
possible, the PRO/ePRO assessments are not to be done.
The completion of PRO/ePRO assessment by the participant and the mode of administration 
will be documented.
Photo images
Photographs of trial participant’s skin affected areas are collected to document clinical 
condition during the clinical trial, i.e. before and during the treatment. Photo images will be 
mandatory at selected sites who will also be collecting skin biopsies and US images for lesion 
evaluation. All trial participants in the selected sites must accept photoimaging. For all other 
sites, photoimaging will be optional. An informed consent on photoimaging and related 
signature must be obtained from the concerned trial participants. Trial participants accepting 
the photoimaging to be taken must sign an informed consent.
Trial participants who consent will have photographs taken at the designated study visits 
listed in the Flowchart.
The skin photo images will be obtained using a standardised software and supplied to the trial 
site by a digital imaging vendor. The photographs taken using this software are automatically 

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uploaded to the vendor’s central secured server using an encrypted data transfer and 
anonymous subject allocation. Training and detailed instructions will be provided by the 
imaging vendor.
5.7
APPROPRIATENESS OF MEASUREMENTS
All methods used in this trial are standard methods.

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6.
INVESTIGATIONAL PLAN
The trial will be conducted worldwide as multinational trial at multiple sites experienced in 
the management of dermatologic diseases, including dermatological conditions such as HS.
The regions and clinical sites will be selected based on the availability of patients with HS 
and their experience in conduct of clinical trials and use of the clinical assessments.
Part 2 investigational plan will be detailed in an amendment based on Part 1 safety and 
efficacy available data at the time of Part 1 primary analysis. The following text of this 
section applies to Part 1 of the study described in this protocol.
All trial participants are to adhere to the visit schedule as specified in the Flowchart. Each 
visit date (With its window) up to EoT is to be counted from Visit 2 
 at Day 1 (first 
trial drug administration day). If any of these visits have to be rescheduled, the date of 
subsequent visit should be calculated from Day 1.
For trial participants not rolling over to LTE trial, FUP refers to Follow-up visit which will be
scheduled 
after last study drug administration. EoT refers to the End of Treatment 
visit at 
(or earlier if a trial participant terminates study drug before 
EoS refers to End of Study visit which will be scheduled 
after last study drug 
administration (after REP period). It is considered to be the safety follow-up and it should 
happen 112 days after the last drug administration or 98 days after the EoT visit.
For trial participants rolling over to LTE trial, EoT and EoS dates will be the same. These 
patients will not undergo the safety follow-up period because they will be followed in the 
LTE trial. For these trial participants EoT visit of this trial and first visit of the LTE trial 
should occur the same day. 
Additional visits for the purpose of re-testing of laboratory parameters or AE monitoring may 
be included as deemed necessary by the investigator.
In the event of force majeure or other disruptive circumstances (e.g., pandemic, war) the
execution of the investigational plan as per this clinical trial protocol may not be feasible.
With the consent of the participant, the sponsor and investigator may agree on alternative,
back-up or rescue methodology which may include virtual trial participant visits and
assessments, home healthcare nurse visits, or bio-sample pick up from the participant’s home.
The implementation of these measures will depend on participant’s consent, operational
feasibility, local law and regulations. If alternative methodology is implemented, the
deviations from the original plan will be precisely documented.
Reported Outcomes (PROs) assessments:
Patient Reported outcomes should be completed by the trial participants on their own at site, 
or on their own at home (only applicable when paper versions are used). During the 
completion of the PROs, the participants should be in a quiet area/room and, as much as 
possible, with limited interaction (only checking comfort of participants) with the investigator 

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or other members of the study team. Questionnaires could be filled within 24 hours prior to 
scheduled visit for the PRO assessment. There is no specific order for the PROs completion.
PROs are listed in Section 2.2. as secondary/further endpoints. Electronic or paper version of 
PROs and diaries will be implemented based on availability, feasibility, translations, etc.
6.1
VISIT SCHEDULE
Study procedures to be performed at each visit are listed in the Flowchart and the respective 
protocol sections. Please, refer to Section 5 and Appendix 10 for explanations of procedures.
Visits may take place as site visits. However, Visits 7, 9, 15, 20, 22, 24, 26, 28, and 30 could 
be performed as home visits if acceptable according to local laws and regulations, see 
Flowchart as reference for procedures to be held during home visits. The type of visit, on-site 
visit or trial participant’s home visit, will be documented in the clinical history and it will be 
reflected in the eCRFs. The trial procedures conducted/collected during an on-site visit are 
equivalent to trial procedures conducted at trial participant’s home visit. Oversight on the 
type of visits will be ensured during CQM. 
Site staff will agree with the trial participant how they would like to be reminded in advanced 
about their visits, i.e. phone call prior the scheduled visit or through another procedure agreed 
with the trial participant.
In those visits requiring safety labs and urine pregnancy test procedures, they should take 
place prior to the study drug administration. Pre-dose PK/ADA samples will be obtained
approximately within 2 hours prior to
administration.
Measurements of vital signs should be assessed pre-dose at all dosing visits, and it should 
precede blood sampling to avoid the impact of it on the vital measurements.
The following sequence of procedures at each visit (where applicable) is recommended: and 
can be done within each visit window (See Flowchart):
1. C-SSRS
2. PROs
3. Patient diaries (all diaries to be handled/completed by 1st day of the visit)
4. AE and concomitant therapy collection; smoking/tobacco/nicotine status
5. Physical examinations (including pre-dose vital signs)
6. ECG
7. Draining fistula count
8. Abscess and inflammatory nodule count
9. HiSCR, IHS4, HS-PGA, and HASI assessment
10. Photographs of skin lesions
11. US lesion evaluation (if applicable. See Section 5.4.3)
12. Skin biopsies (done guided by US)
13. Blood and urine sampling, urine pregnancy testing (if applicable), PK, ADA/NAb, and 
biomarkers.
14. Assign (IRT)/Administer study drug
15. Local tolerability
16. Post-dose vital signs

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In exceptional cases, if standard visits at the trial site are impossible, because of COVID-19 
related safety risks, the investigator must assess the risk-benefit for each individual patient 
and may decide to perform a visit remotely if this is in the best interests of the trial 
participants and if agreed with the sponsor.
All COVID-19 related deviations from the original schedule of visits and procedures will be 
documented and the implications considered for the analysis of the trial data.
All deviations from the original schedule of visits and procedures will be documented and the 
implications considered for the analysis of the trial data. 
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
In the event of force majeure or other disrupting circumstances remote visits may have to be 
performed as follows: by video call or phone, whatever is available and feasible for each trial 
participant. Video call is the preferred option as C-SSRS interview benefits from body 
language and eye contact information that can be missed by phone.
If a participant is not able or willing to come to the site for a trial visit, remote visits (by 
video call or phone) should be performed instead. The following assessment can be done 
remotely:

Collection of adverse events from last visit

Any change in concomitant therapies from last visit

C-SSRS
NRS for pain and pruritus, DLQI, HiS-QoL, FACIT-Fatigue scale, Patient Global Impression 
of Change (PGI-C), Patient Global Impression of Severity (PGI-S), HADS, HODS. – Those 
questionnaires will be available in paper or electronic format. These questionnaires should be 
answered by the participant. Participants will be supplied with the questionnaires to be filled 
out at home. The questionnaires should be answered on the day of the remote visit or within 
the visit window range and sent back to the site thereafter.
Home Healthcare Nurse
Only for visits where a Home Healthcare Nurse is an option, the following assessments can 
be done at the participant’s home, when applicable according to the Flowchart:

C-SSRS

Physical examination

Vital signs

Administration of study medication

NRS Pain and NRS pruritus: Review completed Patient’s Diary in case paper version is 
used. Or oral check completed when electronic version is used

Review paper HS pain medication diary

AEs collection

Concomitant therapy review

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And remind the trial participant about the date for the next study visit. 
The study medication will be sent from site to the patient’s home by courier. The nurse 
performing the home visit should check that the medication is fit for use. After the visit is 
completed, the nurse should send to site the documentation from the visit. The used and 
unused medication will be returned to site by the courier vendor (within 72 hours after the 
visit) for accountability purposes and destruction. 
Safety lab, as per Flowchart
If blood sampling for central lab at the trial site is not possible, in exceptional cases (e.g., due 
to COVID-19 pandemic, travel restrictions, central lab kit stock out issues, etc.), the safety 
lab analyses can be performed at a local lab until central lab testing becomes available. The 
results of the local lab tests must be transferred to the investigator to ensure medical review 
and proper documentation of the lab results with clinical relevance for safety on the clinical 
records and in the eCRFs as AEs. 
Under these exceptional circumstances, standard collection of lab values, must be included in 
eCRFs by site staff as accreditation/reference ranges are required.
6.2.1
Screening period
Screening Period
Study requirements, including the procedure for the follow-up of prematurely withdrawn 
patients must be fully explained to the trial participant and written informed consent obtained 
prior to initiating any study-related evaluation. The importance of staying in the trial until 
completion of all study requirements will be emphasized. No trial procedures should be done 
unless the patient has consented to taking part in the trial.
Once consented, the patient is considered to be enrolled in the trial and has started screening. 
The trial participant should be recorded on the enrolment log and be registered in 
 as a 
screened patient. Trial participants will be assigned a patient number generated via the
system.
Screening (Visit 1) should normally take place no more than 28 days before Visit 2. Visit 1 
procedures may be completed over multiple physical visits, if needed. The time window for 
Visit 1 may be extended at the discretion of the CT Manager in conjunction with the CT 
Leader on a case by case basis.
For the comprehensive list of the trial procedures required at the Screening Visit (Visit 1) 
please refer to Flowchart. Trial participants who have a laboratory test value that makes their 
participation uncertain may have the test repeated to determine eligibility; however, the result 
must be available prior to Visit 2 (Day 1). Baseline conditions and medical history will be 
assessed during screening.
During the screening visit, the following demographics information will be collected:

Age on the day of informed consent (in years) 

Sex (male, female in order to describe the trial participant`s sex at birth)

Gender identity (male, female, non-binary, not answered, or other in order to describe 
how the trial participant self-identifies, regardless of their genotypic or phenotypic 

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sex) if 1) locally accepted (i.e. based on HA/EC/IRB acceptance, independent of 
acceptance by investigators or participants), 2) investigators are willing to ask, and 
3) participants are willing to reply

For women of childbearing potential, yes/no in order to characterise the patient 
population and as a basis for contraception requirements

Ethnicity and race in order to sufficiently characterise the patient population, to 
support possible subgroup analyses
Baseline Conditions
Chronic diseases, current observable conditions, any new clinically relevant findings 
discovered from the physical examination, ECG, safety labs, and any condition requiring 
therapy will be reported on the Baseline Condition eCRF page. The smoking status and 
history based on the calculation of pack-years will be collected as well.
Infection screening
Infection testing will include tuberculosis, hepatitis B, hepatitis C, and HIV assessments (see 
Section 3.3.3 and Table 5.2.3: 2).
Medical History
Medical history of HS, including the previous treatment, will be collected and reported in the 
eCRF.
Information on clinically significant previous and concomitant illnesses, other than HS, or 
any clinically significant signs or symptoms that are present before informed consent, or pre-
existing conditions identified through findings from assessments and examinations done 
during the screening visits will be recorded as medical and surgical history at screening on 
the Baseline Condition page in the eCRF.
Fitzpatrick skin type
Assessment on the type of skin should be done using the Fitzpatrick skin type scale, see 
Appendix 10.22 for reference.
Patients who fail screening (i.e. does not meet the eligibility criteria) following Visit 1
assessments should be registered as a screen failure in 
Re-Screening
Re-screening of a previously screen failed patient will be permitted only once in a case by 
case basis in agreement with the Sponsor. Details of 
procedures can be found in the 
manual located in the Investigator Site File (ISF).
For the comprehensive list of the trial procedures required at the Screening Visit (Visit 1) 
please refer to the Flowchart.
Re-screened patients will need to sign a new informed consent before any re-screening 
procedures and will be given a new unique trial participant number. Trial participant numbers 
from screen-failed participants cannot be re-used. If a patient is re-screened and there are 
valid screening determinations from his/her previous participation in the trial, like for 

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example safety labs, performed within 28 days prior to baseline (visit 2), these do not need to 
be repeated.
6.2.2
Treatment period
When eligibility of the patient to participate in the trial is confirmed, randomisation via
will be performed at Visit 2. The administration of treatment is from Visit 2
to Visit 
31 
. The final assessment of treatment effect will be on 
(EoT visit).
Procedures described in the Flowchart for each visit should be performed.
Baseline (Visit 2) and following site visits can be done in two consecutive days, or within the 
corresponding time window for visits (±1 or ±3 day) range, if needed. If this is the case, then 
it is important to keep certain procedures together. This is the proposal the site should follow 
in relation to the procedures listed in Section 6.1:
Day 1: 
1. C-SSRS
2. PROs
3. Patient Diaries (to review from last visit and hand out new diaries to be completed)
4. AE and concomitant therapy collection; smoking/tobacco/nicotine status
5. Abscess and inflammatory nodule count
6. Draining fistula count
7. HiSCR, IHS4, HS-PGA, and HASI assessment
8. Photographs of skin lesions
9. US lesion evaluation (if applicable. See Section 5.4.3)
10. Skin biopsies (done guided by US)
Day 2:
3. AE 
4. Physical examinations (including pre-dose vital signs)
5. ECG
12. Blood and urine sampling, urine pregnancy testing (if applicable), PK, ADA/NAb, and 
biomarkers.
13. Assign 
/Administer study drug
14. Local tolerability
15. Post-dose vital signs
For the CRFs, the visit date should be the first date of that visit procedures.
During the 
of the treatment period, the 
are administered at
visits (Visit 2 to Visit 5) with 
of 
spesolimab or matching placebo. Please see the Flowchart, Section 3.1 and Section 4.1.4 for 
further details.

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Period
From Visit 6 to Visit 31, 
are administered 
will be used at each visit. Please see the Flowchart, 
Section 3.1 and Section 4.1.4 for further details.
At visits during the treatment period, venipuncture (i.e. safety laboratories, PK, ADA,
biomarkers) and skin biopsies should be the last procedures performed prior to study drug
administration. Only after all blood specimens are collected, and urine pregnancy testing (if
applicable) is done, each eligible patient will receive a dose of the assigned trial medication.
6.2.3
Follow-up period and trial completion
Treatment completion
Treatment completion is defined as a trial participant having completed treatments till 
planned EoT visit 
. A trial participant is considered to have completed the trial in 
case any of the following applies:

Completion of planned follow-up period (= End-of-trial Visit completed)

Lost to follow-up

Refusal to be followed-up

Death
For all randomized patients, termination of trial medication (EoT) and trial completion (EoS) 
must be recorded on the corresponding CRFs. For trial participants completing the 
randomized trial treatment regularly at 
(EoT) and not rolling-over to the LTE trial, 
safety follow-up visits will be performed at Follow-up visit (EoS visit).
All trial participants not entering the LTE trial are expected to complete EoT visit, and EoS 
visit 
after their last trial drug intake (Visit 31) or 
after EoT visit.
Trial participants who roll over to the LTE trial will complete their participation in the trial at 
(EoT visit). However, if for whatever reason these patients rolling over to the LTE 
trial have not been randomized after 
 from the EoT, safety follow-up visit will be 
performed 
after their last trial drug intake. During this period AEs and AESI should 
be collected, see Section 5.2.6.2.1.
If needed, in the opinion of the investigator, after the EoS visit, additional visits may be 
scheduled for continued safety monitoring.
Abnormal assessments or lab values judged clinically relevant by the investigator will be 
monitored until they returned to a medically acceptable level.
Trial completion:
Trial completion is defined as a trial participant having reached the EoS visit per protocol (or 
rolled over to LTE trial and therefore have completed an EoT/EoS visit).

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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
The trial consists of two parts, Part 1 (Phase IIb) and Part 2 (Phase III) which, for the purpose 
of statistical analyses, are considered independent.
7.1
NULL AND ALTERNATIVE HYPOTHESES
Part 1 (Phase IIb)
Statistical hypotheses to be tested for the primary endpoint are:
The null hypothesis is that there is a flat dose response curve comparing the placebo and the 
spesolimab dose groups on the primary endpoint of percent change from baseline in dT count 
at 
 The alternative hypothesis is that there is a non-flat dose response curve indicating 
a benefit of spesolimab over placebo. These hypotheses testing are non-confirmatory.
All secondary endpoints of Phase IIb (Part 1) will be evaluated in an exploratory manner; no 
adjustment for multiple testing is needed.
Part 2 (Phase III)

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7.2
PLANNED ANALYSES
7.2.1
General considerations
All statistical analysis sets are defined by study part (Part 1 (Phase IIb), Part 2 (Phase III)). 
Analysis sets of two study parts will always be independent.
For each study part the following analysis sets will be defined for statistical analyses:
Entered Set (ES): This trial participant set includes all trial participants who signed 
informed consent. The ES will be used for the analyses of trial participant disposition.
Randomised Set (RS): This trial participant set includes all randomized trial participants.
Full analysis set (FAS): This trial participant set includes all trial participants who are 
randomised and received at least one dose of study drug. The FAS is the main analysis set for 
Part 1/2 (Phase IIb/III) safety and efficacy analyses. Patients will be analyzed according to 
their planned treatment group.
Safety Analysis Set (SAF): This subject set includes all subjects who were randomized and 
received at least one dose of study drug. This is the main analysis set for safety. Subjects will 
be analyzed according to the actual treatment received.
Further analysis sets will be defined in the TSAP, if needed.
Data from trial participants who are screened but not randomized will be listed but not 
included in any summary statistics or inferential statistics.
Important deviations of the protocol will include deviations of the key inclusion and 
exclusion criteria, incorrect medication taken, concomitant use of restricted medications and 
any other deviations of the protocol deemed important by the study team. All decisions 
concerning important protocol deviations will be made prior to un-blinding of the database 
for the final trial analysis.
7.2.2
Handling of intercurrent events
Part 1 (Phase IIb)
The expected intercurrent events of interest in this trial are:

Use of rescue therapy

Treatment discontinuation without restricted medication

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
Treatment discontinuation with restricted medication
The strategies for handling intercurrent events in this trial are as follows:
Primary strategies for primary and secondary endpoints:
All intercurrent events will be handled using the treatment policy approach as defined in ICH 
E9(R1). Use of “treatment policy” approach disregards the intercurrent event and uses the 
value of the variable regardless of the occurrence of the intercurrent event.
No deaths are expected in this trial. In the unlikely event of death occurring, it will be 
handled using a hypothetical approach as defined in ICH E9(R1). Use of the “hypothetical 
approach” considers the effect of what would have happened if the intercurrent event did not 
occur.
Table 7.2.2: 1
Primary strategies for handling of intercurrent events as per ICH 
E9(R1): Part 1
Intercurrent event
Primary strategy for 
primary endpoint
Primary strategy for 
secondary endpoints
Use of rescue therapy
Treatment policy
Treatment policy
Treatment discontinuation 
without restricted medication
Treatment policy
Treatment policy
Treatment discontinuation with 
restricted medication
Treatment policy
Treatment policy
Death
Hypothetical
Hypothetical
Each analysis will reference the strategy for handling intercurrent events that it will be 
estimating. The estimand for each main analysis in this protocol is the combination of the 
relevant detailed clinical objective from Section 2.1 and this strategy.
Any intercurrent events that are not listed will be decided by blinded review based on the 
general principle outlined, and corresponding strategies will be documented in the TSAP.
Part 2 (Phase III)
The expected intercurrent events of interest in this trial are:

Use of rescue therapy

Treatment discontinuation without restricted medication

Treatment discontinuation with restricted medication
The strategies for handling intercurrent events in this trial are as follows:
Primary strategies for primary and key secondary endpoints:
All intercurrent events will be handled using the treatment policy approach as defined in ICH 
E9(R1). Use of “treatment policy” approach disregards the intercurrent event and uses the 
value of the variable regardless of the occurrence of the intercurrent event.

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No deaths are expected in this trial. In the unlikely event of death occurring, it will be 
handled using a hypothetical approach as defined in ICH E9(R1) for continuous endpoints, 
and a mixture of hypothetical and composite strategy as defined in ICH E9(R1) for binary 
endpoints. Use of the “hypothetical approach” considers the effect of what would have 
happened if the intercurrent event did not occur. Use of the ‘composite approach’ considers 
that a poor outcome will be expected.
Table 7.2.2: 2
Primary strategies for handling of intercurrent events as per ICH 
E9(R1): Part 2
Intercurrent event
Primary strategy for 
primary endpoint
Primary strategy for key 
secondary endpoints
Continuous
Binary
Use of rescue therapy
Treatment policy
Treatment 
policy
Treatment policy
Treatment discontinuation 
without restricted 
medication
Treatment policy
Treatment 
policy
Treatment policy
Treatment discontinuation 
with restricted medication
Treatment policy
Treatment 
policy
Treatment policy
Death
Hypothetical
Hypothetical
Hypothetical/ 
Composite
Each analysis will reference the strategy for handling intercurrent events that it will be 
estimating. The estimand for each main analysis in this protocol is the combination of the 
relevant detailed clinical objective from Section 2.1 and this strategy.
Any intercurrent events that are not listed will be decided by blinded review based on the 
general principle outlined, and corresponding strategies will be documented in the TSAP.
7.2.3
Primary objective analyses
Part 1 (Phase IIb)
The primary endpoint for Phase IIb is percent change from baseline in dT count at
The primary analysis consists of a
of quantitative treatment benefit.
is used to evaluate 
several possible dose response models (patterns), and to identify the best-fitting model or 
subset of models.
To account for the repeated nature of the data and the covariates in the model,
will be carried out in SAS and covariate adjusted fixed effect estimates of average 

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response for each dose group and the covariance matrix will be extracted from the fit and 
used for 
Percent change from baseline in dT count will be used as the response variable in the 
 The 
 will include fixed categorical effects of treatment at each visit,
status at baseline, and categorical baseline dT count at each visit. Visit will be treated as the 
repeated measure with an unstructured covariance structure used to model the within-trial 
participant measurements.
The placebo effect in percent change from baseline in dT count at
is assumed to be -
10%, and the maximum effect in percent change from baseline in dT count at 
within 
the investigated dose range relative to placebo is assumed to be -30%. The following model 
assumptions and resulting graphs (Figure 7.2.3: 1) have been selected for
to cover 
both plausible and a diverse range of dose response patterns. Planned total dose before
will be used to evaluate dose response curve.

Linear

Exponential:

Emax:

SigEmax: 

BetaMod:

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The optimal contrasts corresponding to the candidate models will be shown in the TSAP. For 
the final evaluation these contrasts will be updated using the estimated means for each dose 
group and the estimated variance-covariance matrix extracted from the primary analysis 
model.
A non-flat dose response is established if at least one dose response pattern is statistically 
significant, rejecting the null hypothesis of a flat dose response relationship over percent 
change from baseline in dT count at
 jointly for each of the candidate dose response 
models with a contrast test controlled for the family-wise type I error rate at 1-sided α of 
0.05.
If non-flat dose-response is established, the statistically significant (best fitting) model(s) 
from the above candidate set are refitted to the data to generate new estimates for all model 
parameters. If more than one model is significant, the weighted average model will be 
evaluated to identify the
 for Part 2 
. The target dose(s) can be 
estimated from each significant model by accounting for safety. Doses within the dose range 
investigated will be considered.
In addition to the results from 
, a beneficial treatment effect relative to placebo will 
be evaluated. 
Baseline is defined as the last available data collected at Visit 2 prior to administration of first 
dose of study medication, or last available screening data if Visit 2 data are missing.

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The primary analysis will be performed using the TS, as defined in Section 7.2.1. All 
available data from the TS in each active treatment arm and the placebo arm up to Week 8 
will be used. Trial participants will be analysed according to the stratum to which they belong 
(regardless of any mis-assignment to treatment based on identification of the wrong stratum), 
as such an error occurs before randomisation and is therefore consistent with regulatory 
guidance.
In the primary analysis intercurrent events are handled with treatment policy approach, 
except for death (unexpected), see Section 7.2.2.
Part 2 (Phase III)
The primary endpoint for Phase III part is percent change from baseline in dT count at 
Restricted maximum likelihood estimation based on a mixed-effect model for repeated 
measures analysis will be used to obtain adjusted means for the treatment effects. This model 
will include categorical fixed effects for treatment at each visit, 
status at baseline, and 
categorical baseline dT count at each visit. The primary treatment comparisons will be the 
contrast between treatment at 
Significance tests will be based on adjusted treatment differences using a one-sided α of 
0.025. The primary treatment comparison will be the contrast of percent change from 
baseline in dT count at
between treatments.
Full details will be specified in the TSAP.
Baseline is defined as the last available data collected prior to administration of first dose of 
study medication.
The primary analysis will be performed using the TS, as defined in Section 7.2.1. All 
available data from the TS in the active treatment arm and the placebo arm up to 
will be used. Trial participants will be analysed according to the stratum to which they belong 
(regardless of any mis-assignment to treatment based on identification of the wrong stratum), 
as such an error occurs before randomisation and is therefore consistent with regulatory 
guidance.
In the primary analysis intercurrent events are handled with treatment policy approach, 
except for death (unexpected), see Section 7.2.2.
7.2.3.1
Sensitivity analyses
For each study part
Sensitivity analyses based on different missing data imputation scheme will be specified in 
the TSAP.
Further details will be specified in the TSAP.
7.2.3.2
Subgroup analyses
 A complete list of subgroup analyses will be specified in the TSAP.

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7.2.3.3
Supplementary analyses
A complete list of supplementary analyses will be specified in the TSAP.
7.2.4
Secondary objective analyses
All secondary endpoints are specified in Section 2.1.3.
Part 1 (Phase IIb)
Secondary endpoints
Continuous endpoints will be analysed using a
effect of baseline of outcome measures at each visit. Visit will be 
treated as repeated measure with an unstructured covariance matrix for the within trial 
participant variability and all visits with planned measurements of the outcome variable as 
well as all dose groups (placebo, low dose, medium dose and high dose) will be included in 
the model. The TSAP will specify approaches to be taken to resolve possible non-
convergence issues, including if necessary the selection of a simpler covariance structure.
will also be used for selected secondary endpoints to evaluate the 
treatment effect of multiple dose regimens of spesolimab vs. placebo, if needed.
Any p-values presented for secondary endpoints will be considered nominal in nature and no 
adjustment for multiplicity will be made.
All secondary endpoints will be summarized descriptively.
Same as for the primary endpoint, the primary analysis of secondary endpoints will be 
performed on the TS using a treatment policy approach for handling the intercurrent events 
except for death (unexpected), see Section 7.2.2.
Part 2 (Phase III)

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7.2.5
Further objective analyses
All further endpoints are specified in Section 2.2.2 and will be considered exploratory in 
nature.
Part 1 (Phase IIb)
Continuous further endpoints will be analysed using 
. Time to event further 
endpoints will be analysed using Kaplan-Meier plot or by Cox regression model if needed. 
Binary further endpoints will be summarized descriptively via frequency tables or by logistic 
regression model if needed. Count further endpoints will be summarized descriptively or by 
negative binomial model if needed.
Further details will be specified in the TSAP if needed.
The PK concentration or parameters will be summarized descriptively.
Part 2 (Phase III)
Further details will be specified in the TSAP if needed.
The PK concentration or parameters will be summarized descriptively.
7.2.6
Safety analyses
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA). Standard BI summary tables and listings will be produced. All adverse events 
with an onset between start of treatment and end of the REP, a period of 16 weeks after the 
last dose of trial medication, will be assigned to the on-treatment period for evaluation.
The safety analysis will be performed by treatment at onset.
Safety analyses will be based on the TS. In general, safety analyses will be descriptive in 
nature and will be based on BI standards. No hypothesis testing is planned.
Statistical analysis and reporting of adverse events will concentrate on treatment-emergent 
adverse events, i.e. all adverse events occurring between start of treatment and end of the 
REP. Adverse events that start before first drug intake and deteriorate under treatment will 
also be considered as ‘treatment-emergent’. Adverse events will be summarized by treatment 
at onset, and the treatment at onset of AE for the drug-related AE.

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Frequency, severity, and causal relationship of adverse events will be tabulated by system 
organ class and preferred term after coding according to the current version of the Medical 
Dictionary for Drug Regulatory Activities (MedDRA) at database lock.
Laboratory data will be analysed both quantitatively as well as qualitatively. The latter will 
be done via comparison of laboratory data to their reference ranges. Values outside the 
reference range as well as values defined as clinically relevant will be summarised. Treatment 
groups will be compared descriptively with regard to distribution parameters as well as with 
regard to frequency and percentage of trial participants with abnormal values or clinically 
relevant abnormal values.
Vital signs, physical examinations, or other safety-relevant data observed at screening, 
baseline, during the course of the trial and at the end-of-trial evaluation will be assessed with 
regard to possible changes compared with findings before start of treatment.
Further details will be specified in the TSAP.
7.2.7
Other analyses
Immunogenicity
Details on immunogenicity data analyses will be specified in the TSAP.
Biomarker analyses
Biomarker results may or may not be reported in the CTR. In case they are reported outside 
the CTR, the biomarker analysis plan will be defined in a separate document (otherwise the 
biomarker analysis plan will be described in the TSAP).
7.2.8
Interim analyses
The primary analysis for Part 1 will be conducted after the last trial participant completes the 
visit. A respective team (“shadow team”) independent of the main trial team will be 
formed to conduct the necessary analyses and ensure to maintain the blind and restrict access 
to the randomisation codes from the main trial team. Details of this process will be described 
in a separate logistics plan which will also specify details on data access. The trial team 
members, trial participants, and investigators will remain blinded until the end of Part 1. The 
sponsor will make a decision for proceeding into Part 2 (Phase III). This recommendation 
will include the selection of appropriate dose(s) for Part 2 and may also include modification 
to inclusion/exclusion criteria, sample size and endpoints. The sponsor intends to seek health 
authority feedback on the cumulative data available after Part 1 
 and the resulting proposed final design for Phase III to 
assess the benefit/risk of spesolimab in HS.
The 
for Part 1 will be conducted after the last trial participant
completes the 
visit and the efficacy effect size will be evaluated. Trial participants 
and investigators will remain blinded until the end of this study part. 
No adjustment of the family-wise Type I error for Part 2 is needed after Part 1 (Phase IIb), as 
the analysis sets of Part 1 (Phase IIb) and Part 2 (Phase III) are independent.

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7.3
HANDLING OF MISSING DATA
Part 1 (Phase IIb)
Efficacy endpoints
In the primary analysis of primary and secondary endpoints, missing data will not be imputed 
except for death (unexpected), where a poor outcome will be assigned. The mixed effect 
model will handle missing data based on a likelihood method under the ‘missing at random 
assumption’. Sensitivity analyses for handling missing primary and secondary endpoints data 
will be specified in the TSAP.
Full details on the handling of missing data will be specified in the TSAP prior to unblinding.
Safety endpoints
Missing or incomplete AE dates will be imputed according to BI standards. Other missing 
safety data will not be imputed.
PK endpoints
Handling of missing PK data will be performed according to the relevant Corporate 
Procedure (001-MCS-30-476). PK parameters that cannot be reasonably calculated based on 
the available drug concentration-time data will not be imputed.
Part 2 (Phase III)
Efficacy endpoints
In the primary analysis of primary and continuous key secondary endpoints, missing data will 
not be imputed except for death (unexpected), where a poor outcome will be assigned. The 
mixed effect model will handle missing data based on a likelihood method under the ‘missing 
at random assumption’.
Sensitivity analyses for handling missing primary and continuous key secondary endpoints 
data will be specified in the TSAP.
In the primary analysis of binary key secondary endpoints, a No Response Imputation (NRI) 
approach will be applied to the missing visits up to 
 that is, imputing as a failure to 
achieve a response in the visits with missing endpoint score, however:
-
If there are available data at the visits both before and after the visit with a missing 
outcome, then impute as a success only if both the preceding and the following 
measurement indicate success.
-
Otherwise, impute as a failure to achieve a response (i.e. no response imputation)
NRI is a conservative imputation scheme because it assumes that missing data due to any 
reason is related to treatment failure.
Sensitivity analyses for handling missing binary key secondary endpoints data will be 
specified in the TSAP.
Full details on the handling of missing data will be specified in the TSAP prior to unblinding.

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Safety endpoints
Missing or incomplete AE dates will be imputed according to BI standards. Other missing 
safety data will not be imputed.
PK endpoints
Handling of missing PK data will be performed according to the relevant Corporate 
Procedure (001-MCS-30-476). PK parameters that cannot be reasonably calculated based on 
the available drug concentration-time data will not be imputed.
7.4
RANDOMISATION
Part 1 (Phase IIb)
Stratification for Japan versus rest of the world (ROW) will be performed in order to assure 
that sufficient trial participants per treatment group are recruited specifically to support 
individual country submission to HAs in Japan; these strata will be treated as operational 
strata and will not be included into the analyses of efficacy endpoints.
Separate randomisation lists will be prepared for Japan and ROW. In ROW randomisation
list, the randomisation will be stratified by 
 at baseline 
 and baseline
Stratification will be done by the 
IRT system. Eligible trial participants from ROW will be parallel randomized in blocks to 
double-blind treatment, and will be randomized to spesolimab high dose, spesolimab medium 
dose, spesolimab low dose or placebo in a 1:1:1:1 ratio. In Japan randomisation list, the 
randomisation will not be stratified within the 
system. Eligible trial participants from 
Japan will be parallel randomized in blocks to double-blind treatment, and will be 
randomized to spesolimab high dose, spesolimab medium dose, spesolimab low dose and 
placebo in a 1:1:1:1 ratio.
BI will arrange for the randomisation and the packaging and labelling of trial medication. The 
randomisation list will be generated using a validated system, which involves a pseudo-
random number generator so that the resulting treatment will be both reproducible and non-
predictable. The block size for each randomisation list (ROW/Japan) will be documented in 
the Clinical Trial Report. Access to the codes will be controlled and documented.
Part 2 (Phase III)
The randomisation will be stratified by 
at baseline 
and baseline 
Stratification will be done by the
system. Eligible trial participants will be parallel randomized in blocks to double-blind 
treatment and will be randomized to spesolimab at selected dose regimen or placebo in a 1:1 
ratio.
BI will arrange for the randomisation and the packaging and labelling of trial medication. The 
randomisation list will be generated using a validated system, which involves a pseudo-
random number generator so that the resulting treatment will be both reproducible and non-
predictable. The block size will be documented in the Clinical Trial Report. Access to the 
codes will be controlled and documented.

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7.5
DETERMINATION OF SAMPLE SIZE
Part 1 (Phase IIb)
The probability of success of this trial is defined as the probability to obtain a significant test 
for non-flat dose-response curve for primary endpoint.
The sample size calculation in this part is based on an assumed standard deviation of 50% for 
the primary endpoint, as well as on the pre-specified models listed in Section 7.2.3. The 
maximum effect in percent change from baseline in dT count at 
within dose range 
relative to placebo is assumed to be
. The mean percent change from baseline in dT 
count at 
is assumed to be 
for placebo. These estimates are derived from
The following power has been evaluated for the candidate set of possible dose response 
patterns based on current expectation (Table 7.5: 1).
Calculations were performed using R version 4.0.5.
Part 2 (Phase III)
Results from the 
 No data on the treatment effect of spesolimab 
beyond 
is available. Assuming the treatment effect of spesolimab on HS could be 
maintained at least up to 
the mean percent change from baseline 
for spesolimab at selected dose regimen.
For sample size calculation for the primary endpoint in Part 2, a common standard deviation 
(SD) of 50% for percent change from baseline in
is assumed for both 
spesolimab at selected dose regimen and placebo groups. The 
 

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considering one-sided alpha of 2.5%.
Sample size may be reassessed based on efficacy effect size from
Calculations were performed using R version 4.0.5.

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8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND 
ADMINISTRATIVE STRUCTURE
The trial will be carried out in compliance with the protocol, the ethical principles laid down 
in the Declaration of Helsinki, in accordance with the ICH Harmonised Guideline for Good 
Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs), the EU directive 
2001/20/EC, the EU regulation 536/2014, the Japanese GCP regulations (Ministry of Health 
and Welfare Ordinance No. 28, March 27, 1997), and other relevant regulations. Investigators 
and site staff must adhere to these principles. Deviation from the protocol, the principles of 
ICH GCP or applicable regulations will be treated as “protocol deviation”.
Standard medical care (prophylactic, diagnostic, and therapeutic procedures) remains the 
responsibility of the treating physician of the trial participant.
The investigator will inform the sponsor or delegate immediately of any urgent safety 
measures taken to protect the trial participants against any immediate hazard, as well as of 
any serious breaches of the protocol or of ICH GCP.
The Boehringer Ingelheim transparency and publication policy can be found on the following 
web page: trials.boehringer-ingelheim.com. The rights of the investigator and of the sponsor
with regard to publication of the results of this trial are described in the investigator contract. 
As a rule, no trial results should be published prior to finalisation of the Clinical Trial Report.
The certificate of insurance cover is made available to the investigator and it is stored in the 
ISF.
8.1
TRIAL APPROVAL, PATIENT INFORMATION, INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to participation in the trial, written informed consent must be obtained from each 
participant (or the participant’s legally accepted representative) according to ICH-GCP and to 
the regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent form, and any additional 
participant-information form retained by the investigator as part of the trial records. A signed 
copy of the informed consent (main, specific for optional procedures, biogenetics) and any 
additional participant information must be given to each participant or the participant’s 
legally accepted representative.
The investigator or delegate must give a full explanation to trial participants based on the
participant information form. A language understandable to the trial participant should be 
chosen, technical terms and expressions avoided, if possible. 
The trial participant must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the trial participant’s own free will with 

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the informed consent form after confirming that the trial participant understands the contents. 
The investigator or
 delegate must sign (or place a seal on) and date the informed consent 
form. If a trial collaborator has given a supplementary explanation, the trial collaborator also 
signs (or places a seal on) and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.
The consent and re-consenting process should be properly documented in the source 
documentation.
8.2
DATA QUALITY ASSURANCE
A risk-based approach is used for trial quality management. It is initiated by the assessment 
of critical data and processes for trial participant protection and reliability of the results as 
well as identification and assessment of associated risks. An Integrated Quality and Risk 
Management Plan or alternative plan, in line with the guidance provided by ICH Q9 and 
ICH-GCP E6, documents the rationale and strategies for risk management during trial 
conduct including monitoring approaches, vendor management and other processes focusing 
on areas of greatest risk.
Continuous risk review and assessment may lead to adjustments in trial conduct, trial design 
or monitoring approaches. 
A quality assurance audit/inspection of this trial may be conducted by the sponsor, sponsor’s 
designees, or by IRB/IEC or by regulatory authorities. The quality assurance auditor will 
have access to all medical records, the investigator’s trial-related files and correspondence, 
and the informed consent documentation of this clinical trial.
8.3
RECORDS
CRFs for individual trial participants will be provided by the sponsor. See Section 4.1.4.2 for 
rules about emergency code breaks. For drug accountability, refer to Section 4.1.8.
8.3.1
Source documents
In accordance with regulatory requirements, the investigator should prepare and maintain 
adequate and accurate source documents and trial records that include all observations and 
other data pertinent to the investigation on each trial participant. Source data as well as 
reported data should follow the “ALCOA principles” and be attributable, legible, 
contemporaneous, original and accurate. Changes to the data should be traceable (audit trail).
Data reported on the CRF must be consistent with the source data or the discrepancies must 
be explained.
The current medical history of the participant may not be sufficient to confirm eligibility for
the trial and the investigator may need to request previous medical histories and evidence of 
any diagnostic tests. In this case, the investigator must make at least one documented attempt 
to retrieve previous medical records. If this fails, a verbal history from the trial participant, 
documented in their medical records, would be acceptable.
Copies of source data necessary for imaging biomarkers (i.e. US) will be sent to an external 
supplier for a centralised reading. For further details, please refer to the ISF and/or imaging 
manual. Before sending or uploading those copies, the investigator must ensure that all 
participant identifiers (e.g. participant’s name, initials, address, phone number, social security 

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number) have properly been removed or redacted from any copy of the participants’ source 
documents.
If the trial participant is not compliant with the protocol, any corrective action e.g. re-training 
must be documented in the participant file.
For the CRF, data must be derived from source documents, for example:

Participant signed informed consent

Participant identification: sex, year of birth (in accordance with local laws and 
regulations)

Participant participation in the trial (substance, trial number, participant number, date 
participant was informed)

Dates of participant’s visits, including dispensing and administration of trial
medication

Medical history (including trial indication and concomitant diseases, if applicable)

Medication history

Adverse events and outcome events (onset date [mandatory], and end date [if 
available])

Serious adverse events (onset date [mandatory], and end date [if available])

Concomitant therapy (start date, changes)

Originals or copies of laboratory results and other imaging or testing results, with 
proper documented medical evaluation (in validated electronic format, if available)

Patient reported outcome forms (including diary) and corresponding investigator 
assessment form completed on paper

ECG results (original or copies of printouts) trace and assessment of normal or 
abnormal

Completion of participant’s participation in the trial” (end date; in case of premature 
discontinuation document the reason for it).

Prior to allocation of a trial participant to a treatment into a clinical trial, there must be 
documented evidence in the source data (e.g. medical records) that the trial participant 
meets all inclusion criteria and does not meet any exclusion criteria. The absence of 
records (either medical records, verbal documented feedback of the participant or 
testing conducted specific for a protocol) to support inclusion/exclusion criteria does 
not make the participant eligible for the clinical trial
In addition to paper forms, Patient Reported Outcome forms and dairy can be completed on 
an e-device provided by an external vendor. During conduct of the trial, access to the data 
will be possible via the vendor portal. Data from e-PRO and Central lab will be directly 
uploaded into CDR system for downstream data analysis. After completion of the trial a copy 
of the collected data will be sent to the applicable sites for archiving.
8.3.2
Direct access to source data and documents
The investigator/institution will allow site trial-related monitoring, audits, IRB/IEC review 
and regulatory inspections. Direct access must be provided to the CRF and all source 
documents/data, including progress notes, copies of laboratory and medical test results, which 
must always be available for review by the CRA, auditor and regulatory inspector (e.g. FDA). 

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They may review all CRFs and informed consents. The accuracy of the data will be verified 
by direct comparison with the source documents described in Section 8.3.1. The sponsor or 
delegate will also monitor compliance with the protocol and GCP.
In the event of force majeure or other disrupting circumstances (e.g. pandemic, war; please 
see Section 6), site access may be restricted, thus limiting the ability to perform standard site 
monitoring activities on site such as on-site source data review and source data verification. 
Therefore, some of these activities may be performed remotely or replaced by centralised 
monitoring to the extent possible, based on a documented risk assessment and in alignment 
with local regulations.
8.3.3
Storage period of records
Trial sites:
The trial sites must retain the source and essential documents (including ISF) according to 
contract or the local requirements valid at the time of the end of the trial (whatever is longer).
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with
regulatory requirements. 
AE/AESI are processed in the global Safety Database and assessed for the company causal 
relationship as well as the expectedness of the event according to the reference safety 
information. Individual Case Safety Reports (ICSR) are subsequently reported according to 
local Regulations. Reporting to the EMA will be done via E2B transmission of ICSRs to the 
Eudravigilance CT Module.
8.5
STATEMENT OF CONFIDENTIALITY AND TRIAL PARTICIPANT
PRIVACY
Data protection and data security measures are implemented for the collection, storage and 
processing of trial participant data in accordance with the principles 7 and 12 of the WHO 
GCP handbook. 
To ensure confidentiality of records and personal data, only pseudonymised data will be
transferred to the sponsor by using a participant identification number instead of the trial 
participant’s name. The code is only available at the site and must not be forwarded to the 
sponsor. In case participant’s records will be forwarded e.g. for SAE processing or 
adjudication committees, personal data that can identify the trial participant will be redacted 
by the site prior to forwarding. Access to the participant files and clinical data is strictly 
limited: personalised treatment data may be given to the trial participant’s personal physician 
or to other appropriate medical personnel responsible for the trial participant’s welfare. Data 
generated at the site as a result of the trial need to be available for inspection on request by 
the participating physicians, the sponsor’s representatives, by the IRB/IEC and the regulatory 
authorities.
A potential data security breach will be assessed regarding the implications for rights and 
privacy of the affected persons. Immediate actions as well as corrective and preventive 

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actions will be implemented. Respective regulatory authorities, IRBs/IECs and trial 
participants will be informed as appropriate.
8.5.1
Collection, storage and future use of biological samples and corresponding 
data 
Measures are in place to comply with the applicable rules for the collection, biobanking and 
future use of biological samples and clinical data, in particular:

Sample and data usage have to be in accordance with the separate biobanking 
informed consent

The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external banking facility are qualified for the storage of biological samples 
collected in clinical trials

An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to ICF is in place

A fit for the purpose documentation (biomarker proposal, analysis plan and report) 
ensures compliant usage

A fit for purpose approach will be used for assay/equipment validation depending on 
the intended use of the biomarker data

Samples and/or data may be transferred to third parties and other countries as 
specified in the biobanking ICF
8.6
TRIAL MILESTONES
The first act of recruitment represents the start of the trial and is defined as the date when 
the first trial participant in the whole trial signs informed consent.
The end of the trial is defined as the date of the last visit of the last trial participant in the 
whole trial (“Last Participant Completed”).
The “Last Participant Last Treatment” (LPLT) date is defined as the date on which the last 
trial participant in the whole trial is administered the last dose of trial treatment (as scheduled 
per protocol or prematurely). Individual investigators will be notified of SUSARs occurring 
with the trial medication until 30 days after LPLT at their site.
Early termination of the trial is defined as the premature termination of the trial due to any 
reason before the end of the trial as specified in this protocol.
Temporary halt of the trial is defined as any unplanned interruption of the trial by the 
sponsor with the intention to resume it.
Suspension of the trial is defined as an interruption of the trial based on a Health Authority 
request.
The initiation of the Phase III will be driven by the results of the Primary analysis at
and the interim analysis at 
of the Phase IIb.
The IEC/competent authority in each participating EU member state will be notified about 
the trial milestones according to the respective laws.

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A final report of the clinical trial data will be written only after all trial participants have 
completed the trial in all countries (EU or non-EU) to incorporate and consider all data in the 
report.
The sponsor will submit to the EU database a summary of the final trial results within one 
year from the end of a clinical trial as a whole, regardless of the country of the last trial 
participant (EU or non-EU).
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL
The trial is sponsored by Boehringer Ingelheim (BI).
A Coordinating Investigator is responsible to coordinate investigators at the different sites 
participating in this trial. Tasks and responsibilities are defined in a contract.
A DMC will be established. Members of the DMC are independent of BI, they are physicians 
experienced in the treatment of the disease under investigation and a statistician.
The DMC will evaluate safety data, efficacy data as detailed in the DMC charter. While 
DMC members may be unblinded, measures are in place to ensure the blinding for everyone
else involved in the trial. Regular DMC meetings will be held at specified intervals. The 
DMC will recommend continuation, modification or termination of the trial as detailed in the 
DMC charter. DMC recommendations as well as the final BI decision will be reported to the 
appropriate Regulatory Authorities (RAs)/Health Authorities (HAs), IRBs/ECs, and to 
investigators as requested by local law. The tasks and responsibilities of the DMC are 
specified in a charter. The relevant documents (minutes of DMC meetings, contracts etc.) will 
be stored in the TMF.
Relevant documentation on the participating (Principal) Investigators (e.g. their curricula 
vitae) will be filed in the ISF.
The investigators will have access to the BI web portal Clinergize to access documents 
provided by the sponsor.

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BI has appointed a Clinical Trial Leader responsible for coordinating all required activities, in 
order to:

Manage the trial in accordance with applicable regulations and internal SOPs.

Direct the clinical trial team in the preparation, conduct, and reporting of the trial.

Ensure appropriate training and information of Clinical Trial Managers (CT 
Managers), Clinical Research Associates (CRAs), and investigators of participating 
countries.
In the participating countries, the trial will be performed by the respective local or regional 
BI-organisation (Operative Unit, OPU) in accordance with applicable regulations and BI 
SOPs, or by a Contract Research Organisation (CRO) based on a contract. The CRO will 
perform project management, clinical field monitoring, medical monitoring, and reporting.
Data Management and Statistical Evaluation will be done by BI according to BI SOPs.
Tasks and functions assigned in order to organise, manage, and evaluate the trial are defined 
according to BI SOPs. A list of responsible persons and relevant local information can be 
found in the ISF.
A central laboratory service, a central images service, and an IRT vendor will be used in this 
trial. Details will be provided in the 
Manual and Central Laboratory Manual, available in 
the ISF.

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9.
REFERENCES
9.1
PUBLISHED REFERENCES
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Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a 
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216.
R07-4311
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring 
fatigue and other anemia-related symptoms with the Functional 
Assessment of Cancer Therapy (FACT) measurement system. J Pain 
Symptom Manage. 1997;13(2):63-74.
R08-1147
Posner K. State of the science: measurement of suicidal adverse events 
and the Columbia Suicide Severity Rating Scale. 47th NCDEU Ann 
Mtg, Boca Raton, 11 - 14 Jun 2007. 2007;15.
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Greenland S, Robins JM. Estimation of a common effect parameter 
from sparse follow-up data. Biometrics; 1985; 41; 55-68.
R10-1424
Pinheiro J, Bornkamp B, Bretz F. Design and analysis of dose-finding 
studies combining multiple comparisons and modeling procedures. J 
Biopharm Stat. 2006;16(5):639-656.
R10-6433
Webster K, Cella D, Yost K. The Functional Assessment of Chronic 
Illness Therapy (FACIT) Measurement System: properties, 
applications, and interpretation. Health Qual Life Outcomes. 
2003;1:79.
R11-4890
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF, Bock 
SA, Branum A, et al. Second symposium on the definition and 
management of anaphylaxis: summary report - second National 
Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium. 2nd Symp of the National Institute 
of Allergy and Infectious Disease (NIAID)/Food Allergy and 
Anaphylaxis (FAA) Network on the Definition and Management of 
Anaphylaxis, Jul 2005. J Allergy Clin Immunol. 2006;117(2):391-397.
R16-0029
Cella D, Yount S, Sorensen M, Chartash E, Sengupta N, Grober J. 
Validation of the Functional Assessment of Chronic Illness Therapy 
Fatigue Scale relative to other instrumentation in patients with 
rheumatoid arthritis. J Rheumatol. 2005;32(5):811-819.
R17-2617
Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, 
Polgreen P, et al. Opportunistic infections and biologic therapies in 
immune-mediated inflammatory diseases: consensus 
recommendations for infection reporting during clinical trials and 
postmarketing surveillance. Ann Rheum Dis. 2015;74:2107-2116.
R17-3632
Mahil SK, Catapano M, Meglio P di, Dand N, Ahlfors H, Carr IM, et 
al. An analysis of IL-36 signature genes and individuals with IL1RL2 

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knockout mutations validates IL-36 as a psoriasis therapeutic target. 
Sci Transl Med. 2017; 9; eaan2514.
R20-2976
Kimball AB, Sobell JM, Zouboulis CC, Gu Y, Williams DA, 
Sundaram M, et al. HiSCR (Hidradenitis Suppurativa Clinical 
Response): a novel clinical endpoint to evaluate therapeutic outcomes 
in patients with hidradenitis suppurativa from the placebo-controlled 
portion of a phase 2 adalimumab study. J Eur Acad Dermatol 
Venereol. 2016;30:989–994.
R20-3045
Zouboulis CC, Tzellos T, Kyrgidis A, Jemec GBE, Bechara FG, 
Giamarellos-Bourboulis EJ, et al. European Hidradenitis Suppurativa 
Foundation Investigator Group. Development and validation of the 
International Hidradenitis Suppurativa Severity Score System (IHS4), 
a novel dynamic scoring system to assess HS severity. Br J Dermatol. 
2017;177:1401-1409.
R20-3046
Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, 
Gniadecki R, et al. Adalimumab for the treatment of moderate to 
severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern 
Med. 2012;157:846–855.
R20-3047
Hessam S, Sand M, Gambichler T, Skrygan M, Rueddel I, Bechara 
FG. Interleukin-36 in hidradenitis suppurativa: evidence for a 
distinctive proinflammatory role and a key factor in the development 
of an inflammatory loop. British Journal of Dermatology. 
2018;178:761–767.
R20-3155
Byrd AS, Carmona-Rivera C, O'Neil LJ, Carlucci PM, Cisar C, 
Rosenberg AZ, et al. Neutrophil extracellular traps, B cells, and type I 
interferons contribute to immune dysregulation in hidradenitis 
suppurativa. Sci Transl Med. 2019;11;eaav5908. 
R20-3156
Kirby JS, Thorlacius L, Villumsen B, Ingram JR, Garg A, Christensen 
KB, et al. The Hidradenitis Suppurativa Quality of Life (HiS-QoL) 
score: development and validation of a measure for clinicaltrials. 
British Journal of Dermatology. 2020;183:340–348.
R20-3177
Zouboulis CC, Desai N, Emtestam L, Hunger RE, Ioannides D, Juhasz 
I, et al. EDF Guideline for Hidradenitis Suppurativa/Acne Inversa 
(HS) – S1 Guideline. European Dermatology Forum. J Eur Acad 
Dermatol Venereol. 2015;29:619-644.
R20-3184
Zouboulis CC, Marmol V del, Mrowietz U, Prens EP, Tzellos T, 
Jemec GBE. Hidradenitis Suppurativa/Acne Inversa: criteria for 
diagnosis, severity assessment, classification and disease evaluation. 
2015;231(2):184-90.
R22-3282
Phan K, Charlton O, Smith SD. Global prevalence of hidradenitis 
suppurativa and geographical variation - systematic review and meta-
analysis. Biomedical Dermatology. 2020;4(2):1-6.

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R22-2400
Navrazhina K, Frew JW, Gilleaudeau P, Sullivan-Whalen M, Garcet 
S, Krueger JG. Epithelialized tunnels are a source of inflammation in 
hidradenitis suppurativa. J Allergy Clin Immunol. 2021;147(6):2213-
2224.

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10.
APPENDICES
10.1

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10.2
TRIAL 
Trial period
Treatment period

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10.3
HIDRADENITIS SUPPURATIVA CLINICAL RESPONSE (HISCR)
Defined as at least a 50% reduction from baseline in the total abscess and inflammatory 
nodule count, with no increase in the abscess or draining fistula count. 
Fig. Source: HUMIRA Hidradenitis Suppurativa Clinical Response (HiSCR) Data 
(humiradermpro.com)

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10.4
INTERNATIONAL HIDRADENITIS SUPPURATIVA SEVERITY SCORE 
SYSTEM (IHS4)
International Hidradenitis Suppurativa Severity Score System (IHS4). A nodule 
(inflammatory nodule) is a raised, three-dimensional, round, infiltrated lesion with a diameter 
of >10 mm. An abscess is a tender but fluctuating mass with a diameter of >10 mm, 
surrounded by an erythematous area; the middle of an abscess contains pus. A draining tunnel 
is a raised, tender but fluctuating longitudinal mass of variable length and depth, ending at the 
skin surface, and sometimes oozing a fluid. Fistulae and sinuses are examples of tunnels. 
Fig. source: [R20-3045].

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10.5
HIDRADENITIS SUPPURATIVA AREA AND SEVERITY INDEX (HASI)

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10.6
HIDRADENITIS SUPPURATIVA PHYSICIAN GLOBAL ASSESSMENT 
(HS-PGA)

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10.7
PAIN NUMERICAL RATING SCALE (NRS PAIN)

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10.8
PRURITUS NUMERICAL RATING SCALE (NRS PRURITUS)
The NRS is comprised of one item and represents the numbers 0 (“no itch”) to 10 (“worst
imaginable itch”). Trial participants are asked to rate the intensity of their itch using this 
scale. It features high reliability and concurrent validity and is a popular choice for all 
patients due to its simple format.
Time needed for completion: 1 minute
It can be interpreted as follows:
NRS= 0 - no pruritus
NRS <3 - mild pruritus
NRS  >  3< 7 - moderate pruritus
NRS > 7< 9 - severe pruritus
NRS > 9 - very severe pruritus

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10.9
DERMATOLOGY LIFE QUALITY INDEX (DLQI)

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10.10
HIDRADENITIS SUPPURATIVA QUALITY OF LIFE (HIS-QOL)

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10.11
FACIT-FATIGUE 
FACIT Fatigue Scale (Version 4)
Below is a list of statements that other people with your illness have said are
important. Please circle or mark one number per line to indicate your response
as it applies to the past 7 days.

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10.12
PATIENT GLOBAL IMPRESSION OF CHANGE (PGI-C) 

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10.13
PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) 

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10.14
HIDRADENITIS SUPPURATIVA ODOUR AND DRAINAGE SCALE 
(HODS) 

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10.15
HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS)

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10.16
WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT 
QUESTIONNAIRE FOR HS (WPAI-HS)
Work Productivity and Activity Impairment Questionnaire:
Hidradenitis Suppurativa, V2.0 (WPAI: Hidradenitis Suppurativa)
The following questions ask about the effect of your hidradenitis suppurativa on your 
ability to work and perform regular activities. Please fill in the blanks or circle a 
number, as indicated.
1.
Are you currently employed (working for pay)? 
_____ NO ___ YES
If NO, check “NO” and skip to question 6.
The next questions are about the past seven days, not including today.
2. During the past seven days, how many hours did you miss from work because of
problems associated with your hidradenitis suppurativa? Include hours you 
missed on sick days, times you went in late, left early, etc., because of 
hidradenitis suppurativa. Do not include time you missed to participate in this 
study.
_____ HOURS
3. During the past seven days, how many hours did you miss from work because of 
any other reason, such as vacation, holidays, time off to participate in this study?
_____HOURS
4. During the past seven days, how many hours did you actually work?
_____HOURS (If “0”, skip to question 6.)

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5. During the past seven days, how much did your hidradenitis suppurativa affect 
your productivity while you were working? 
Think about days you were limited in the amount or kind of work you could do, 
days you accomplished less than you would like, or days you could not do your 
work as carefully as usual. If hidradenitis suppurativa affected your work only a
little, choose a low number. Choose a high number if hidradenitis suppurativa 
affected your work a great deal. 
Consider only how much hidradenitis suppurativa affected 
productivity while you were working.
Hidradenitis 
suppurativa 
had no effect 
on work
Hidradenitis 
suppurativa 
completely 
prevented me 
from working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6. During the past seven days, how much did your hidradenitis suppurativa affect 
your ability to do your regular daily activities, other than work at a job? 
By regular activities, we mean the usual activities you do, such as work around 
the house, shopping, childcare, exercising, studying, etc. Think about times you 
were limited in the amount or kind of activities you could do and times you 
accomplished less than you would like. If hidradenitis suppurativa affected your 
activities only a little, choose a low number. Choose a high number if hidradenitis 
suppurativa affected your activities a great deal. 
Consider only how much hidradenitis suppurativa affected your ability 
to do your regular daily activities, other than work at a job.
Hidradenitis 
suppurativa 
had no effect 
on my daily 
activities
Hidradenitis 
suppurativa 
completely 
prevented me 
from doing my 
daily activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
WPAI: Hidradenitis Suppurativa V2.0 (US English) 

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10.17
EUROQOL 5 DIMENSIONS 5-LEVEL (EQ-5D-5L)

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COLUMBiA-SUICIDE SEVERITY 
RATING SCALE 
(C-SSRS)
Baseline/Screening Version
Version 1/14/09
Posner, K.; Brent, D.; Lucas, C.; Gould, M.; Stanley, B.; Brown, G.; 
Fisher, P.; Zelazny, J.; Burke, A.; Oquendo, M.; Mann, J.
Disclaimer:
This scale is intended to be used by individuals who have received training in its administration. 
The questions contained in the Columbia-Suicide Severity Rating Scale are suggested probes. 
Ultimately, the determination of the presence of suicidal ideation or behavior depends on the 
judgment of the individual administering the scale.
Definitions of behavioral suicidal events in this scale are based on those used in The 
Columbia Suicide History Form, developed by John Mann, MD and Maria Oquendo, MD, 
Conte Center for the Neuroscience of Mental Disorders (CCNMD), New York State Psychiatric 
Institute, 1051 Riverside Drive, New York, NY, 10032. (Oquendo M. A., Halberstam B. & 
Mann J. J., Risk factors for suicidal behavior: utility and limitations of research instruments. In 
M.B. First [Ed.] Standardized Evaluation in Clinical Practice, pp. 103 -130, 2003.)
For reprints of the C-SSRS contact Kelly Posner, Ph.D., New York State Psychiatric Institute, 
1051 Riverside Drive, New York, New York, 10032; inquiries and training requirements 
contact posnerk@nyspi.columbia.edu
© 2008 The Research Foundation for Mental Hygiene, Inc. 

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SUICIDAL IDEATION
Ask questions 1 and 2. If both are negative, proceed to “Suicidal 
Behavior” section. If the answer to question 2 is “yes”, ask questions 3, 
4 and 5. If the answer to question 1 and/or 2 is “yes”, complete 
“Intensity of Ideation” section below.
Lifetime: 
Time 
He/She Felt 
Most 
Suicidal
Past 
Months
1.  Wish to be Dead
Subject endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep and 
not wake up.
Have you wished you were dead or wished you could go to 
sleep and not wake up?
If yes, describe:
Yes No
Yes No
2.  Non-Specific Active Suicidal Thoughts
General non-specific thoughts of wanting to end one’s 
life/commit suicide (e.g., “I’ve thought about killing myself”) 
without thoughts of ways to kill oneself/associated methods, 
intent, or plan during the assessment period.
Have you actually had any thoughts of killing yourself?
If yes, describe:
Yes No
Yes No
3.  Active Suicidal Ideation with Any Methods (Not Plan) without Intent to 
Act
Subject endorses thoughts of suicide and has thought of at least 
one method during the assessment period. This is different than a 
specific plan with time, place or method details worked out (e.g., 
thought of method to kill self but not a specific plan). Includes 
person who would say, “I thought about taking an overdose but I 
never made a specific plan as to when, where or how I would 
actually do it… and I would never go through with it.”
Have you been thinking about how you might do this?
If yes, describe:
Yes No
Yes No
4.  Active Suicidal Ideation with Some Intent to Act, without Specific Plan
Active suicidal thoughts of killing oneself and subject reports 
having some intent to act on such thoughts, as opposed to “I 
have the thoughts but I definitely will not do anything about 
them.”
Have you had these thoughts and had some intention of acting 
on them?
If yes, describe:
Yes No
Yes No

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5.  Active Suicidal Ideation with Specific Plan and Intent
Thoughts of killing oneself with details of plan fully or partially worked out and subject has some 
intent to carry it out.
Have you started to work out or worked out the details of how 
to kill yourself? Do you intend to carry out this plan?
If yes, describe:
Yes No
Yes No
INTENSITY OF IDEATION
The following features should be rated with respect to the most severe type of 
ideation (i.e.,1-5 from above, with 1 being the least severe and 5 being the most 
severe). Ask about time he/she was feeling the most suicidal.
Most Severe
Most Severe
Lifetime -Most Severe Ideation:   
___________
Type # (1-5)
Description of Ideation
Past 12 Months -
Most Severe Ideation:   
___________
Type # (1-5)
Description of Ideation
Frequency
How many times have you had these thoughts?
____
____
(1) Less than 
once a week
(2) Once a 
week
(3) 2-5 times 
in week
(4) Daily or 
almost daily
(5) Many 
times each 
day
Duration
When you have the thoughts how long do they last?
(1) Fleeting - few seconds or 
minutes
(2) Less than 1 hour/some of the 
time
(3) 1-4 hours/a lot of time
(4) 4-8 hours/most of 
day
(5) More than 8 
hours/persistent or 
continuous
____
____
Controllability
Could/can you stop thinking about killing yourself or wanting to die if you want 
to?
(1) Easily able to control 
thoughts
(2) Can control thoughts with 
little difficulty
(3) Can control thoughts with 
some difficulty
(4) Can control thoughts 
with a lot of difficulty
(5) Unable to control 
thoughts
(0) Does not attempt to 
control thoughts
____
____
Deterrents
Are there things - anyone or anything (e.g., family, religion, pain of death) -
that stopped you from wanting to die or acting on thoughts of committing 
suicide?
(1) Deterrents definitely 
stopped you from attempting 
suicide
(2) Deterrents probably stopped 
you
(3) Uncertain that deterrents 
stopped you
(4) Deterrents most 
likely did not stop you
(5) Deterrents definitely 
did not stop you
(0) Does not apply
____
____

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Reasons for Ideation
What sort of reasons did you have for thinking about wanting to die or killing 
yourself? Was it to end the pain or stop the way you were feeling (in other words 
you couldn’t go on living with this pain or how you were feeling) or was it to get 
attention, revenge or a reaction from others? Or both?
(1) Completely to get attention, 
revenge or a reaction from 
others
(2) Mostly to get attention, 
revenge or a reaction from 
others
(3) Equally to get attention, 
revenge or a reaction from 
others and to end/stop the 
pain
(4) Mostly to end or stop 
the pain (you couldn’t 
go on living with the 
pain or how you were 
feeling)
(5) Completely to end or 
stop the pain (you 
couldn’t go on living 
with the pain or how 
you were feeling)
(0) Does not 
apply
____
____

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SUICIDAL BEHAVIOR
(Check all that apply, so long as these are separate events; must ask 
about all types)
Lifetime
Past __ Years
Actual Attempt:
A potentially self-injurious act committed with at least some wish to die, as a result of act. 
Behavior was in part thought of as method to kill oneself. Intent does not have to be 100%. 
If there is any intent/desire to die associated with the act, then it can be considered an actual 
suicide attempt. There does not have to be any injury or harm, just the potential 
for injury or harm. If person pulls trigger while gun is in mouth but gun is broken so no 
injury results, this is considered an attempt.
Inferring Intent: Even if an individual denies intent/wish to die, it may be inferred clinically 
from the behavior or circumstances. For example, a highly lethal act that is clearly not an 
accident so no other intent but suicide can be inferred (e.g., gunshot to head, jumping from 
window of a high floor/story). Also, if someone denies intent to die, but they thought that 
what they did could be lethal, intent may be inferred.
Have you made a suicide attempt?
Have you done anything to harm yourself?
Have you done anything dangerous where you could have died?
What did you do?
Did you______as a way to end your life?
Did you want to die (even a little) when you_____?
Were you trying to end your life when you_____?
Or did you think it was possible you could have died from_____?
Or did you do it purely for other reasons/without ANY intention of killing 
yourself (like to relieve stress, feel better, get sympathy, or get something 
else to happen)? (Self-Injurious Behavior without suicidal 
intent)
If yes, describe:
Has subject engaged in Non-Suicidal Self-Injurious Behavior?
Yes No
Yes No
Total # of 
Attempts
______
Total # of 
Attempts
______
Yes No
Yes No
Interrupted Attempt:
When the person is interrupted (by an outside circumstance) 
from starting the potentially self-injurious act (if not for that, 
actual attempt would have occurred).
Overdose: Person has pills in hand but is stopped from ingesting. Once they ingest any pills, 
this becomes an attempt rather than an interrupted attempt. Shooting: Person has gun 
pointed toward self, gun is taken away by someone else, or is somehow prevented from 
pulling trigger. Once they pull the trigger, even if the gun fails to fire, it is an attempt. 
Jumping: Person is poised to jump, is grabbed and taken down from ledge. Hanging: Person 
has noose around neck but has not yet started to hang - is stopped from doing so.
Has there been a time when you started to do something to end your life but 
someone or something stopped you before you actually did anything?
If yes, describe:
Yes No
Yes No
Total # of 
interrupted
______
Total # of 
interrupted
______
Aborted Attempt:
When person begins to take steps toward making a suicide attempt, but stops themselves 
before they actually have engaged in any self-destructive behavior. Examples are similar to 
interrupted attempts, except that the individual stops him/herself, instead of being stopped 
by something else.
Has there been a time when you started to do something to try to end your 
life but you stopped yourself before you actually did anything?
If yes, describe:
Yes No
Yes No
Total # of 
aborted
______
Total # of 
aborted
______
Preparatory Acts or Behavior:
Acts or preparation towards imminently making a suicide attempt. This can include 
anything beyond a verbalization or thought, such as assembling a specific method (e.g., 
buying pills, purchasing a gun) or preparing for one’s death by suicide (e.g., giving things 
away, writing a suicide note).
Yes No
Yes No

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Have you taken any steps towards making a suicide attempt or preparing to 
kill yourself (such as collecting pills, getting a gun, giving valuables away 
or writing a suicide note)?
If yes, describe:
Suicidal Behavior:
Suicidal behavior was present during the assessment period?
Yes No
Yes No
Answer for Actual Attempts Only
Most 
Recent 
Attempt 
Date:
Most Lethal 
Attempt 
Date:
Initial/First 
Attempt 
Date:
Actual Lethality/Medical Damage:
0.  No physical damage or very minor 
physical damage (e.g., surface scratches).
1.  Minor physical damage (e.g., lethargic 
speech; first-degree burns; mild bleeding; 
sprains).
2.  Moderate physical damage; medical 
attention needed (e.g., conscious but 
sleepy, somewhat responsive; second-
degree burns; bleeding of major vessel).
3.  Moderately severe physical damage; 
medical hospitalization and likely 
intensive care required (e.g., comatose 
with reflexes intact; third-degree burns 
less than 20% of body; extensive blood 
loss but can recover; major fractures).
4.  Severe physical damage; medical
hospitalization with intensive care 
required (e.g., comatose without reflexes; 
third-degree burns over 20% of body; 
extensive blood loss with unstable vital 
signs; major damage to a vital area).
5.  Death
Enter 
Code
______
Enter Code
______
Enter Code
______
Potential Lethality: Only Answer if 
Actual Lethality=0
Likely lethality of actual attempt if no 
medical damage (the following examples, 
while having no actual medical damage, 
had potential for very serious lethality: put 
gun in mouth and pulled the trigger but gun 
fails to fire so no medical damage; laying 
on train tracks with oncoming train but 
pulled away before run over).
0 = Behavior not likely to result in injury
1 = Behavior likely to result in injury but 
not likely to cause death
Enter 
Code
______
Enter Code
______
Enter Code
______

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2 = Behavior likely to result in death 
despite available medical care

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COLUMBIA-SUICIDE SEVERITY
RATING SCALE
(C-SSRS)
Since Last Visit
Version 1/14/09
Posner, K.; Brent, D.; Lucas, C.; Gould, M.; Stanley, B.; 
Brown, G.; Fisher, P.; Zelazny, J.; Burke, A.; Oquendo, 
M.; Mann, J.
Disclaimer:
This scale is intended to be used by individuals who have received training in 
its administration. The questions contained in the Columbia-Suicide Severity 
Rating Scale are suggested probes. Ultimately, the determination of the 
presence of suicidal ideation or behavior depends on the judgment of the 
individual administering the scale.
Definitions of behavioral suicidal events in this scale are based on those 
used in The Columbia Suicide History Form, developed by John Mann, 
MD and Maria Oquendo, MD, Conte Center for the Neuroscience of 
Mental Disorders (CCNMD), New York State Psychiatric Institute, 1051 
Riverside Drive, New York, NY, 10032. (Oquendo M. A., Halberstam B. & 
Mann J. J., Risk factors for suicidal behavior: utility and limitations of 
research instruments. In M.B. First [Ed.] Standardized Evaluation in 
Clinical Practice, pp. 103 -130, 2003.)
For reprints of the C-SSRS contact Kelly Posner, Ph.D., New York State 
Psychiatric Institute, 1051 Riverside Drive, New York, New York, 10032; 
inquiries and training requirements contact posnerk@nyspi.columbia.edu
© 2008 The Research Foundation for Mental Hygiene, Inc.

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SUICIDAL IDEATION
Ask questions 1 and 2. If both are negative, proceed to “Suicidal Behavior” section. If 
the answer to question 2 is “yes”, ask questions 3, 4 and 5. If the answer to question 1 
and/or 2 is “yes”, complete “Intensity of Ideation” section below.
Since Last Visit
1.  Wish to be Dead
Subject endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep and not wake 
up.
Have you wished you were dead or wished you could go to sleep and not wake up?
If yes, describe:
Yes
No
2.  Non-Specific Active Suicidal Thoughts
General non-specific thoughts of wanting to end one’s life/commit suicide (e.g., “I’ve thought about killing 
myself”) without thoughts of ways to kill oneself/associated methods, intent, or plan during the assessment 
period.
Have you actually had any thoughts of killing yourself?
If yes, describe:
Yes
No
3.  Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
Subject endorses thoughts of suicide and has thought of at least one method during the assessment period. 
This is different than a specific plan with time, place or method details worked out (e.g., thought of method 
to kill self but not a specific plan). Includes person who would say, “I thought about taking an overdose but I 
never made a specific plan as to when, where or how I would actually do it…..and I would never go through 
with it”.
Have you been thinking about how you might do this?
If yes, describe:
Yes
No
4.  Active Suicidal Ideation with Some Intent to Act, without Specific Plan
Active suicidal thoughts of killing oneself and subject reports having some intent to act on such thoughts, as 
opposed to “I have the thoughts but I definitely will not do anything about them”.
Have you had these thoughts and had some intention of acting on them?
If yes, describe:
Yes
No
5.  Active Suicidal Ideation with Specific Plan and Intent
Thoughts of killing oneself with details of plan fully or partially worked out and subject has some intent to 
carry it out.
Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out 
this plan?
If yes, describe:
Yes
No
INTENSITY OF IDEATION
The following features should be rated with respect to the most severe type of ideation (i.e.,1-5 
from above, with 1 being the least severe and 5 being the most severe).
Most Severe
Most Severe 
Ideation:
________
Type # (1-5)
Description of Ideation
Frequency
How many times have you had these thoughts?
____
(1) Less than 
once a 
week
(2) Once a week
(3) 2-5 times in week
(4) Daily or almost 
daily
(5) Many times 
each day
Duration
When you have the thoughts how long do they last?
(1) Fleeting - few seconds or minutes
(2) Less than 1 hour/some of the time
(3) 1-4 hours/a lot of time
(4) 4-8 hours/most of day
(5) More than 8 hours/persistent or 
continuous
____

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Controllability
Could/can you stop thinking about killing yourself or wanting to die if you want to?
(1) Easily able to control thoughts
(2) Can control thoughts with little difficulty
(3) Can control thoughts with some difficulty
(4) Can control thoughts with a lot of 
difficulty
(5) Unable to control thoughts
(0) Does not attempt to control thoughts
____
Deterrents
Are there things - anyone or anything (e.g., family, religion, pain of death) - that stopped 
you from wanting to die or acting on thoughts of committing suicide?
(1) Deterrents definitely stopped you from attempting 
suicide
(2) Deterrents probably stopped you
(3) Uncertain that deterrents stopped you
(4) Deterrents most likely did not stop 
you
(5) Deterrents definitely did not stop 
you
(0) Does not apply
____
Reasons for Ideation
What sort of reasons did you have for thinking about wanting to die or killing yourself? 
Was it to end the pain or stop the way you were feeling (in other words you couldn’t go 
on living with this pain or how you were feeling) or was it to get attention, revenge or a 
reaction from others? Or both?
(1) Completely to get attention, revenge or a reaction from 
others
(2) Mostly to get attention, revenge or a reaction from 
others
(3) Equally to get attention, revenge or a reaction from 
others and to end/stop the pain
(4) Mostly to end or stop the pain (you 
couldn’t go on living with the pain 
or how you were feeling)
(5) Completely to end or stop the pain 
(you couldn’t go on living with the 
pain or how you were feeling)
(0) Does not apply
____

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SUICIDAL BEHAVIOR
(Check all that apply, so long as these are separate events; must ask about all types)
Since Last 
Visit
Actual Attempt:
A potentially self-injurious act committed with at least some wish to die, as a result of act. Behavior was in part 
thought of as method to kill oneself. Intent does not have to be 100%. If there is any intent/desire to die associated 
with the act, then it can be considered an actual suicide attempt. There does not have to be any injury or 
harm, just the potential for injury or harm. If person pulls trigger while gun is in mouth but gun is broken so no 
injury results, this is considered an attempt.
Inferring Intent: Even if an individual denies intent/wish to die, it may be inferred clinically from the behavior or 
circumstances. For example, a highly lethal act that is clearly not an accident so no other intent but suicide can be 
inferred (e.g., gunshot to head, jumping from window of a high floor/story). Also, if someone denies intent to die, 
but they thought that what they did could be lethal, intent may be inferred.
Have you made a suicide attempt?
Have you done anything to harm yourself?
Have you done anything dangerous where you could have died?
What did you do?
Did you______as a way to end your life?
Did you want to die (even a little) when you_____?
Were you trying to end your life when you_____?
Or Did you think it was possible you could have died from_____?
Or did you do it purely for other reasons/without ANY intention of killing yourself (like to 
relieve stress, feel better, get sympathy, or get something else to happen)? (Self-Injurious Behavior 
without suicidal intent)
If yes, describe:
Has subject engaged in Non-Suicidal Self-Injurious Behavior?
Yes
No
Total # of 
Attempts
______
Yes
No
Interrupted Attempt:
When the person is interrupted (by an outside circumstance) from starting the potentially self-injurious act (if not 
for that, actual attempt would have occurred).
Overdose: Person has pills in hand but is stopped from ingesting. Once they ingest any pills, this becomes an 
attempt rather than an interrupted attempt. Shooting: Person has gun pointed toward self, gun is taken away by 
someone else, or is somehow prevented from pulling trigger. Once they pull the trigger, even if the gun fails to 
fire, it is an attempt. Jumping: Person is poised to jump, is grabbed and taken down from ledge. Hanging: Person 
has noose around neck but has not yet started to hang - is stopped from doing so.
Has there been a time when you started to do something to end your life but someone or 
something stopped you before you actually did anything?
If yes, describe:
Yes
No
Total # of 
interrupted
______
Aborted Attempt:
When person begins to take steps toward making a suicide attempt, but stops themselves before they actually have 
engaged in any self-destructive behavior. Examples are similar to interrupted attempts, except that the individual 
stops him/herself, instead of being stopped by something else.
Has there been a time when you started to do something to try to end your life but you stopped 
yourself before you actually did anything?
If yes, describe:
Yes
No
Total # of aborted
______
Preparatory Acts or Behavior:
Acts or preparation towards imminently making a suicide attempt. This can include anything beyond a 
verbalization or thought, such as assembling a specific method (e.g., buying pills, purchasing a gun) or preparing 
for one’s death by suicide (e.g., giving things away, writing a suicide note).
Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such 
as collecting pills, getting a gun, giving valuables away or writing a suicide note)?
If yes, describe:
Yes
No
Suicidal Behavior:
Suicidal behavior was present during the assessment period?
Yes
No
Suicide:
Yes
No
Answer for Actual Attempts Only
Most Lethal 
Attempt 
Date:

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Actual Lethality/Medical Damage:
0.  No physical damage or very minor physical damage (e.g., surface scratches).
1.  Minor physical damage (e.g., lethargic speech; first-degree burns; mild bleeding; sprains).
2.  Moderate physical damage; medical attention needed (e.g., conscious but sleepy, somewhat responsive; 
second-degree burns; bleeding of major vessel).
3.  Moderately severe physical damage; medical hospitalization and likely intensive care required (e.g., comatose 
with reflexes intact; third-degree burns less than 20% of body; extensive blood loss but can recover; major 
fractures).
4.  Severe physical damage; medical hospitalization with intensive care required (e.g., comatose without reflexes; 
third-degree burns over 20% of body; extensive blood loss with unstable vital signs; major damage to a vital 
area).
5.  Death
Enter Code
______
Potential Lethality: Only Answer if Actual Lethality=0
Likely lethality of actual attempt if no medical damage (the following examples, while having no actual medical 
damage, had potential for very serious lethality: put gun in mouth and pulled the trigger but gun fails to fire so no 
medical damage; laying on train tracks with oncoming train but pulled away before run over).
0 = Behavior not likely to result in injury
1 = Behavior likely to result in injury but not likely to cause death
2 = Behavior likely to result in death despite available medical care
Enter Code
______

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10.19
TRIAL PARTICIPANT FEEDBACK
Optional Trial Participant Feedback Questionnaires:
This trial will include an option for participants to complete anonymised questionnaires, 
‘Trial Participant Feedback Questionnaire’, to provide feedback on their clinical trial 
experience. Individual participant level responses will not be reviewed by investigators. 
Responses will be used by the sponsor to understand where improvements can be made in the 
clinical trial process. These questionnaires will not collect data about the participant’s 
disease, symptoms, treatment effect, or AEs and therefore will not be part of the trial data or 
clinical trial report. The questionnaires will be implemented after local regulatory approval, 
when applicable, and after consent of the trial participant. Providing feedback is optional and 
not required for participation in the trial.

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10.20
DIAGNOSIS OF ANAPHYLAXIS
Clinical Criteria for diagnosing anaphylaxis [R11-4890]
PEF, Peak expiratory flow; BP, blood pressure
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 
month to 1 year, less than (70 mm Hg +[2 x age] from 1 to 10 years, and less than 90 
mm Hg from 11 to 17 years.
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, 
or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], 
syncope, incontinence)
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-
tongue- uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP*
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s 
baseline

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10.21
COVID-19 RISK ASSESSMENT
Table 10.21: 1
Overview of trial-related risks due to COVID-19
Possible or known risks of 
clinical relevance for this 
trial
Summary of data, 
rationale for the risk
Mitigation strategy
Investigational Medicinal Product: BI 655130
SARS-CoV-2 infection
Similar to other immune 
modulating biological 
treatments, spesolimab may 
potentially increase the risk 
of infections. However, the 
available pharmacological, 
non-clinical and clinical 
data do not indicate an 
increased risk of contracting 
SARS-CoV-2 or severe 
clinical courses due to the 
treatment with BI 655130.
Furthermore, according to 
the Centers for Disease 
Control and Prevention 
there is limited information 
regarding risk factors for 
severe COVID-19 disease. 
However, based on 
currently available 
information and clinical 
expertise, older adults and 
people of any age who have 
serious not well controlled 
underlying medical 
conditions might be at 
higher risk for severe illness 
from COVID-19. So , 
participants with moderate 
to severe Hidradenitis 
suppurativa may be at risk 
of a severe clinical course of 
COVID-19.
Even though the risks 
associated with BI 655130
treatment are considered 
low, risk mitigation 
measures, such as exclusion 
of patients with increased 
risk of infections, close 
monitoring of AEs, as well 
as guidance on handling of 
acute infections occurring 
during the trial have been 
included in the spesolimab 
clinical trial protocol (CTP), 
please refer to 
Section 1.4.2.1. Also, 
potential participants with 
active or recent 
SARS-CoV-2 infection will 
only be included upon full 
recovery (see Section 3.3.3). 
A suspected SARS-CoV-2
infection while in the trial 
will be confirmed with an 
immediate PCR or antigen 
test. If positive, the 
participant will follow the 
local quarantine rules and 
should be treated, as any 
other acute infection, with 
standard of care. Trial 
treatment may be continued 
based on the discretion of 
the investigator (see 
Section 3.3.4.1). Then, 
treatment may be resumed 
following recovery from 
SARS-CoV-2 infection if 
clinical benefit is expected.

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Table 10.21: 1          Overview of trial-related risks due to COVID-19 (cont.)
Possible or known risks of 
clinical relevance for this 
trial
Summary of data, 
rationale for the risk
Mitigation strategy
Trial procedures
Trial conduct and protocol-
defined procedures are not 
expected to increase the risk 
of contracting SARS-CoV-2 
or to aggravate the course of 
an infection.
Other risks
Risk of contracting 
SARS-CoV-2
Travelling to the site or 
being at the site for trial 
visits may potentially 
increase the risk of 
contracting SARS-CoV-2.
The number of site visits is 
limited to the minimum 
required for the successful 
conduct of the trial. Further 
protective measures (e.g. 
social distancing, wearing 
masks) are recommended to 
be taken. Measures are in 
place to ensure continued 
participant treatment, 
monitoring, and safety even 
if site visits are not possible 
(see Section 4.1 and 
Section 6.2).

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10.22
FITZPATRICK SKIN TYPE SCALE
The Fitzpatrick skin type (or phototype) depends on the amount of melanin pigment in the 
skin. This is determined by constitutional colour (white, brown, or black skin) and the effect 
of exposure to ultraviolet radiation (tanning).

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11.
CONFIDENTIALITY STATEMENT DESCRIPTION OF
GLOBAL AMENDMENT(S)
Date of amendment
02 Nov 2023
EudraCT number
EU CT number
2022-501074-19-00
BI Trial number
1368-0098
BI Investigational 
Medicinal Product(s)
Spevigo®, spesolimab
Title of protocol
Randomised, double-blind, placebo-controlled, 
Phase IIb/Phase III study to evaluate the efficacy and 
safety of spesolimab in patients with moderate to 
severe hidradenitis suppurativa. Lunsayil 1.
Global Amendment due to urgent safety reasons
Add “x” 
ifapplicable
Global Amendment
X
Section to be changed

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APPROVAL / SIGNATURE PAGE 
 
Document Number: 
 
Technical Version Number:
 
Document Name: 
 
 
 
                                                                                                                 
 
Title: 
 
 
 
 
                                                                                                                   
 
Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c40061625
2.0
clinical-trial-protocol-version-02
Randomised, double-blind, placebo-controlled, Phase IIb/Phase III study to evaluate
the efficacy and safety of spesolimab in patients with moderate to severe hidradenitis
suppurativa. Lunsayil 1.
Author-Clinical Trial Leader
03 Nov 2023 13:20 CET
Approval-Biostatistics
03 Nov 2023 14:42 CET
Approval-Clinical Program
03 Nov 2023 16:22 CET
Verification-Paper Signature
Completion
04 Nov 2023 14:58 CET

Boehringer Ingelheim 
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c40061625
2.0