Clinical trial NCT05635838
Conditions: Hidradenitis Suppurativa
Keywords: Hidradenitis suppurativa skin disease ruxolitinb cream
Sponsor: Incyte Corporation
Start date: 2022-12-07; Completion date: 2024-03-14
Enrollment: 69 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of Ruxolitinib cream in participants with Hidradenitis Suppurativa. This is a randomized 16-week double-blind, vehicle-controlled (DBVC) study followed by a 16 week open label extension period (OLE) with an active treatment for participants who complete the DBVC period.

Detailed description:

Arms: arm 1: Ruxolitinib 1.5% cream BID for 16 weeks of double-blind, vehicle-controlled (DBVC) period followed by ruxolitinb 1.5% cream BID for 16 weeks in an open-label extension. arm 2: Vehicle cream BID for 16 weeks of double-blind, vehicle-controlled (DBVC) period followed by ruxolitinb 1.5% cream BID for 16 weeks in an open-label extension.
Interventions: intervention 1: Ruxolitinib cream intervention 2: Vehicle cream
Intervention descriptions: intervention 1: Ruxolitinib cream is a topical formulation applied as a thin film to affected areas. intervention 2: Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.

Protocol documents:
Prot_000.pdf: 
Official Title: A Phase 2, Double-Blind, Randomized, Vehicle-Controlled, Efficacy, 
and Safety Study of Ruxolitinib Cream in Participants With Hidradenitis Suppurativa
NCT Number: NCT05635838
Document Date: Clinical Study Protocol: 19 AUG 2022


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Protocol INCB 18424-221 
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Clinical Study Protocol 
TITLE PAGE 
INCB 18424-221
A Phase 2, Double-Blind, Randomized, Vehicle-Controlled, Efficacy, 
and Safety Study of Ruxolitinib Cream in Participants With 
Hidradenitis Suppurativa 
Product: 
Ruxolitinib Cream 
IND Number: 
77,101 
EudraCT Number: 
2022-002662-33 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 USA 
Original Protocol: 
19 AUG 2022 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
The information in this document is confidential. No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-221 Protocol (dated 19 AUG 2022) and agree to conduct the study 
as outlined. I agree to maintain the confidentiality of all information received or developed in 
connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
2. 
INTRODUCTION ......................................................................................................16 
2.1. 
Background .................................................................................................................16 
2.2. 
Study Rationale ...........................................................................................................18 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Dose ..................................................................................................18 
2.3. 
Benefit/Risk Assessment ............................................................................................19 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................20 
4. 
STUDY DESIGN .......................................................................................................22 
4.1. 
Overall Design ............................................................................................................22 
4.2. 
Overall Study Duration ...............................................................................................23 
4.3. 
Study Termination ......................................................................................................23 
5. 
STUDY POPULATION .............................................................................................23 
5.1. 
Inclusion Criteria ........................................................................................................23 
5.2. 
Exclusion Criteria .......................................................................................................24 
5.3. 
Lifestyle Considerations .............................................................................................27 
5.4. 
Screen Failures ............................................................................................................27 
5.5. 
Replacement of Participants .......................................................................................27 
6. 
STUDY TREATMENT ..............................................................................................28 
6.1. 
Study Treatment(s) Administered ...............................................................................28 
6.2. 
Preparation, Handling, and Accountability ................................................................29 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................30 
6.4. 
Study Treatment Compliance .....................................................................................31 
6.5. 
Dose Modifications .....................................................................................................31 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drugs ...........................................................................................................................31 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug to an Adverse Event ............33 
6.6. 
Concomitant Medications and Procedures .................................................................33 


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6.6.1. 
Permitted Medications and Procedures ......................................................................34 
6.6.2. 
Restricted Medications and Procedures ......................................................................34 
6.6.3. 
Prohibited Medications and Procedures .....................................................................35 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................36 
7.1. 
Discontinuation of Study Treatment ...........................................................................36 
7.1.1. 
Reasons for Discontinuation .......................................................................................36 
7.1.2. 
Discontinuation Procedures ........................................................................................37 
7.2. 
Participant Withdrawal From the Study .....................................................................37 
7.3. 
Lost to Follow-Up.......................................................................................................38 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................39 
8.1. 
Administrative and General Procedures .....................................................................39 
8.1.1. 
Informed Consent Process ..........................................................................................39 
8.1.2. 
Screening Procedures ..................................................................................................40 
8.1.3. 
Interactive Response Technology Procedure ..............................................................40 
8.1.4. 
Distribution of Reminder Cards and/or Diaries ..........................................................40 
8.1.5. 
Demography and Medical History ..............................................................................40 
8.1.5.1. 
Demographics and General Medical History .............................................................40 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................41 
8.2. 
Efficacy Assessments .................................................................................................41 
8.2.1. 
Lesion Counts .............................................................................................................41 
8.2.1.1. 
Abscess and Inflammatory Nodule Counts ................................................................42 
8.2.1.2. 
Hidradenitis Suppurativa Clinical Response ..............................................................42 
8.2.1.3. 
International Hidradenitis Suppurativa Severity Score System ..................................42 
 
43 
8.2.2. 
Hurley Stages of Hidradenitis Suppurativa ................................................................43 
8.2.3. 
Body Surface Area ......................................................................................................43 
8.2.4. 
Patient-Reported Outcomes ........................................................................................43 
8.2.4.1. 
eDiary Assessments: Skin Pain and Itch Numeric Rating Scales ...............................44 
 
44 
 
44 
 
44 
8.2.4.5. 
Patient Global Impression of Change .........................................................................45 


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45 
 
45 
 
45 
8.3. 
Safety Assessments .....................................................................................................46 
8.3.1. 
Adverse Events ...........................................................................................................46 
8.3.2. 
Physical Examinations ................................................................................................46 
8.3.3. 
Vital Signs ..................................................................................................................47 
8.3.4. 
Laboratory Assessments .............................................................................................47 
8.3.4.1. 
Pregnancy Testing ......................................................................................................48 
8.3.4.2. 
Serology ......................................................................................................................48 
 
48 
8.5. 
 Translational Assessments ....................................................49 
 
49 
8.5.2. 
Photography ................................................................................................................49 
8.6. 
Unscheduled Visits .....................................................................................................49 
8.7. 
End of Treatment and Early Termination ...................................................................49 
8.8. 
Follow-Up ...................................................................................................................50 
8.8.1. 
Safety Follow-Up ........................................................................................................50 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................51 
9.1. 
Definition of Adverse Event .......................................................................................51 
9.2. 
Definition of Serious Adverse Event ..........................................................................52 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........53 
9.4. 
Reporting of Serious Adverse Events .........................................................................55 
9.5. 
Potential Drug-Induced Liver Injury ..........................................................................56 
9.6. 
Events of Clinical Interest ..........................................................................................56 
9.7. 
Emergency Unblinding of Treatment Assignment .....................................................56 
9.8. 
Pregnancy ...................................................................................................................57 
9.9. 
Warnings and Precautions ..........................................................................................57 
9.10. 
Product Complaints ....................................................................................................57 
9.11. 
Treatment of Overdose ...............................................................................................58 
10. 
STATISTICS ..............................................................................................................59 
10.1. 
Sample Size Determination ........................................................................................59 


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10.2. 
Populations for Analysis .............................................................................................59 
10.3. 
Level of Significance ..................................................................................................59 
10.4. 
Statistical Analyses .....................................................................................................59 
10.4.1. 
Primary Analysis ........................................................................................................59 
10.4.2. 
Secondary Analysis ....................................................................................................60 
10.4.3. 
Safety Analyses ..........................................................................................................60 
10.5. 
Interim Analysis ..........................................................................................................61 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................62 
11.1. 
Investigator Responsibilities .......................................................................................62 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................63 
11.2. 
Data Management .......................................................................................................63 
11.3. 
Data Quality Assurance ..............................................................................................65 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................66 
11.5. 
Financial Disclosure ...................................................................................................66 
11.6. 
Publication Policy .......................................................................................................66 
11.7. 
Study and Site Closure................................................................................................67 
12. 
REFERENCES ...........................................................................................................68 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................70 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................72 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................75 
 


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LIST OF TABLES 
Table 1: 
Primary Objective and Endpoint ................................................................................11 
Table 2: 
Key Study Design Elements .......................................................................................11 
Table 3: 
Schedule of Activities .................................................................................................14 
Table 4: 
Objectives and Endpoints ...........................................................................................20 
Table 5: 
Study Treatment Information .....................................................................................29 
Table 6: 
Guidelines for Interruption and Restarting of Study Drug .........................................32 
Table 7: 
Definition of Hidradenitis Suppurativa Lesions .........................................................42 
Table 8: 
Hurley Stages of Hidradenitis Suppurativa ................................................................43 
Table 9: 
Required Laboratory Analytes ....................................................................................48 
Table 10: Populations for Analysis .............................................................................................59 
Table 11: Summary of Primary Analysis....................................................................................60 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................13 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
AN 
abscess and inflammatory nodule 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DBVC 
double-blind, vehicle-controlled 
 
 
DNA 
deoxyribonucleic acid 
eCOA 
electronic clinical outcome assessment 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOT 
end of treatment 
 
 
EQ VAS 
EuroQol visual analogue scale 
ET 
early termination 
FDA 
Food and Drug Administration (US) 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GFR 
glomerular filtration rate 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HiSCR 
hidradenitis suppurativa clinical response 
 
 


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Abbreviations and 
Special Terms 
Definition 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
HS 
hidradenitis suppurativa 
hsCRP 
high-sensitivity C-reactive protein 
IB 
Investigator's Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification 
IEC 
independent ethics committee 
IGA 
Investigator's Global Assessment 
IGA-TS 
Investigator's Global Assessment-Treatment Success (IGA score of 0 or 1 
with ≥ 2-grade improvement from baseline) 
IL 
interleukin 
INF 
interferon 
IRB 
institutional review board 
IRT 
interactive response technology 
IHS4 
International Hidradenitis Suppurativa Severity Score System 
ITT 
intent-to-treat 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measures 
NRS 
numeric rating scale 
OLE 
open-label extension 
 
 
 
 
 
 
PRO 
patient-reported outcome 
QD 
once daily 
QTL 
quality tolerance limits 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SoA 
schedule of activities 
SOP 
standard operating procedure 


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Abbreviations and 
Special Terms 
Definition 
STAT 
signal transducer and activator of transcription 
TEAE 
treatment-emergent adverse event 
Th1 
T-helper 1 
TNF 
tumor necrosis factor 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
 
 


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1. 
PROTOCOL SUMMARY 
A Phase 2, Double-Blind, Randomized, Vehicle-Controlled, Efficacy, and Safety Study of 
Ruxolitinib Cream in Participants With Hidradenitis Suppurativa 
Protocol Number: INCB 18424-221 
Objectives and Endpoints: 
Table 1 presents the primary objective and endpoint. 
Table 1: 
Primary Objective and Endpoint 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% 
cream BID in participants with HS. 
Change from baseline in abscess and 
inflammatory nodules (AN) count at Week 16. 
Overall Design: 
Table 2 presents the key study design elements. Further study details are presented after the 
table. 
Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of patients with hidradenitis suppurativa 
Population 
Men or women ≥ 18 years of age, who have been diagnosed with HS 
(Hurley Stage I and II) for at least 3 months; with total AN count of 3 to 
≤ 10. The AN count of 3 may affect at least 1 distinct anatomical area; 
however, an AN count of > 3 to ≤ 10 must be affecting at least 2 distinct 
anatomical areas. 
Number of Participants 
Approximately 60 participants will be randomized 1:1 to 1 of 2 treatment 
groups (ruxolitinib 1.5% cream BID or vehicle cream BID). 
Study Design 
This is a randomized, 16-week DBVC study followed by a 16 week OLE 
with an active treatment for participants who complete 16 weeks of DBVC 
period, followed by a 30-day post-treatment, safety follow-up visit. 
Estimated Duration of 
Study Participation 
Estimated total duration of participants is up to approximately 40 weeks, 
including up to 4 weeks for screening, up to 32 weeks for treatment, and 
30 days for safety follow-up. 
Data Safety Monitoring 
Board/Data Monitoring 
Committee 
No 
Coordinating Principal 
Investigator 
To be determined 


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Treatment Groups and Duration: 
This is a Phase 2, randomized, DBVC study with DBVC period of 16 weeks followed by an 
OLE period of 16 weeks. 
Participants will be screened for up to 28 days prior to the first application of ruxolitinib 1.5% 
cream or vehicle cream. Key entry criteria for participants are diagnosis of HS (Hurley Stage I or 
II) for at least 3 months before screening visit and a total AN count of 3 to ≤ 10 with no 
draining tunnels at screening and baseline. The AN count of 3 may affect at least 1 distinct 
anatomical area; however, an AN count of > 3 to ≤ 10 must be affecting at least 2 distinct 
anatomical areas. 
Approximately 60 eligible participants ≥ 18 of age will be randomized 1:1 to either ruxolitinib 
1.5% cream or vehicle cream (see Figure 1). Participants will be stratified by baseline AN count 
(≥ 3 to 4 or ≥ 5 to 10). Participants will apply either ruxolitinib 1.5% cream or vehicle cream 
(both BID) through Week 16 to the all affected areas identified at baseline. 
At Week 16, participants who meet the criteria (compliant with the Protocol and without safety 
concerns) will enter the 16-week OLE period. Participants randomized to vehicle BID in the 
DBVC period will be crossed over to ruxolitinib 1.5% cream BID and participants randomized to 
ruxolitinib 1.5% cream BID at baseline will remain on ruxolitinib 1.5% cream BID through 
Week 32 in an open-label fashion. At Week 16, the HS treatment area will be evaluated by the 
investigator to assess the disease and confirm whether treatment continuation is required 
(AN count ≥ 1 and/or Skin Pain NRS ≥ 1) during the OLE period or can otherwise (re)enter an 
observation/no treatment cycle (AN count = 0 and Skin Pain NRS = 0). During the OLE, 
participants will only treat symptomatic lesions (eg, presence of lesion, pain, and/or itch) 
including new lesions, not exceeding a total of 20% BSA. 
Treatment assignment during the DBVC period will remain blinded to investigators and 
participants until after all participants have completed study or discontinued and completed the 
safety follow-up period. 
During the DBVC and OLE periods, participants who are treated with HS lesional rescue 
medications and/or procedures (see Section 6.6.3), are considered nonresponsive to therapy, and 
will be discontinued from the study. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the implementation of potential mitigation 
strategies described in Appendix B. 
Figure 1 presents the study schema, Table 3 present the SoA. 


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Figure 1: 
Study Design Schema 
 
16 weeks
Vehicle cream BID
(N = 30 patients)
RUX 1.5% BID
(N = 30 patients)
-
Open-Label
Extension
16 weeks
• Age ≥ 18 years
• Diagnosis of HS ≥ 3 months
• 3 to ≤ 10 AN
Randomization (1:1)
Safety Follow-Up (30 days)
Investigator’s Assessment 
Recurrence 
of AN
Triggers for 
starting/ending 
cycles
Clearance of 
AN
RUX 1.5% 
BID
No 
treatment
Double-Blind, Vehicle-Controlled 
Treatment Period
Open Label Extension 
Treatment Period
Enrollment


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Table 3: 
Schedule of Activities 
Visit Day (Range) 
Screening 
Baseline 
(Day 1) 
Treatment (vehicle-controlled period) 
Treatment (open-label extension)a 
Unscheduled 
Visit 
Follow-up 
Days 
−28 to −1 
Wk 2 
(± 3 d) 
Wk 4 
(± 3 d) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 16a 
± 3 d/ 
ET1 
Wk 20 
(± 3 d) 
Wk 24 
(± 3 d) 
Wk 28 
(± 3 d) 
Wk 32 
(± 3 d/ 
ET2) 
30 days 
(+ 7) days after 
last application) 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographic, medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Contact IRT 
X 
X 
X 
X 
X 
X 
X 
X  
X 
X 
X 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Distribute ediary 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute reminder cards 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
eDiary verification 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Apply study drug in clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Weigh/dispense study drug 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Collect/weigh study drug and 
review study drug diary 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Assess study drug compliance 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
Xb 
 
 
 
 
Xc 
 
 
Xb 
Xc 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height and body weight 
X 
 
 
 
 
 
 
 
 
 
Efficacy assessments 
%BSA 
Xd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Lesion count and assessment  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Overall Hurley Stage 
X 
X 
 
 
X 
 
X 
 
 
 
X 
 
X 
Patient-reported outcome 
Skin Pain NRS 
Completed each evening through the last application of study drug. 
 
 
Itch NRS 
Completed each evening through the last application of study drug. 
 
 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening 
Baseline 
(Day 1) 
Treatment (vehicle-controlled period) 
Treatment (open-label extension)a 
Unscheduled 
Visit 
Follow-up 
Days 
−28 to −1 
Wk 2 
(± 3 d) 
Wk 4 
(± 3 d) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 16a 
± 3 d/ 
ET1 
Wk 20 
(± 3 d) 
Wk 24 
(± 3 d) 
Wk 28 
(± 3 d) 
Wk 32 
(± 3 d/ 
ET2) 
30 days 
(+ 7) days after 
last application) 
Patient-reported outcome (continued) 
Laboratory assessments 
Chemistry assessments 
X 
Xe 
 
 
 
 
X 
 
 
 
X 
Xf 
X 
Hematology assessments 
X 
Xe 
 
 
 
 
X 
 
 
 
X 
Xf 
X 
hsCRP 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
FSHg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy testh 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine Pregnancy testh 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
HIV/Hepatitis Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Translational assessments 
Photography (at selected sites) 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
a All Week 16 assessments must be completed before the participant can continue in the OLE. 
b Comprehensive physical examination at screening and Week 32/ET2 visit. The comprehensive physical examination will include assessment(s) of the following organ or body 
systems: skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief neurological 
examination. 
c A targeted physical examination may be conducted at Week 16. Targeted physical examination can be done for assessment of AE and during other visits including unscheduled 
visit as per discretion of the investigator. A targeted physical examination should only be conducted as indicated by symptoms reported by the participant, AEs, or other findings. 
d Total HS BSA (excluding the scalp) should be ≤ 20% to be eligible for study entry and continued participation. 
e Not necessary if screening assessment performed within 14 days of Day 1. 
f Laboratory assessment is optional during unscheduled visits based on investigator's discretion and clinical judgement. 
g Women of nonchildbearing potential only. Follicle-stimulating hormone is not needed in women with a documented hysterectomy, documented bilateral salpingectomy, or 
documented bilateral oophorectomy. 
h Female participants of childbearing potential will have a serum test at screening and follow-up and a urine test at other visits noted. A positive urine test must be confirmed by a 
serum test. 


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2. 
INTRODUCTION 
2.1. 
Background 
Ruxolitinib cream is a topical formulation of ruxolitinib phosphate under development for a 
variety of dermatological conditions. Ruxolitinib 1.5% cream is approved by the FDA for the 
treatment of mild to moderate AD in nonimmunocompromised patients 12 years of age and older 
whose disease is not adequately controlled with topical prescription therapies or when those 
therapies are not advisable (Opzelura™ 2021). Ruxolitinib phosphate is an inhibitor of the JAK 
family of protein TYKs. Inflammatory cytokines are strongly implicated in the pathogenesis of a 
number of inflammatory dermatoses. Because JAKs serve to translate extracellular signals from 
a number of relevant cytokines and growth factors upregulated in these inflammatory diseases, 
JAK inhibitors represent potential therapeutic agents for these disease states (Chapman et al 
2022). 
Hidradenitis suppurativa is a debilitating, chronic inflammatory skin condition that affects the 
hair follicle leading to a perifollicular lympho-histiocytic inflammation (Zouboulis et al 2015). It 
is characterized by persistent or recurrent painful inflamed nodules and abscesses, and 
purulent-discharging tunnels referred to as sinus tracts and fistulas often localized in skin folds of 
axillary, inguinal, gluteal, and perianal areas of the body (Saunte et al 2017). In more severe 
disease, irreversible scarring is identified (Sabat et al 2020). Hidradenitis suppurativa diagnosis 
is made on clinical assessment and disease severity may be measured based on clinical 
manifestations including nodule phenotype in intertriginous body areas. The course of the 
disease may vary from mild disease (recurrent appearance of solitary or multiple 
isolated abscess formation without sinus tracts or scarring) to severe disease (deep fluctuant 
abscesses, draining sinuses, and severe, interconnected sinus tracts or scars; Frew et al 2021). 
The quality of life of HS patients is significantly impacted leading to psychological impairment 
(eg, anxiety, depression, etc) and poor-body image (Kurek et al 2013, Schneider-Burrus et al 
2018). 
The estimated prevalence of HS varies depending on the different populations and methods of 
reporting. The highest prevalence (approximately 4%) has been reported in those between 20 to 
40 years of age with onset of disease usually at 20 years of age, and declining after the fifth 
decade of life (Jemec and Kimball 2015). The incidence of HS in females has been reported to be 
as high as 3 times that of men (Canoui-Poitrine et al 2013). 
The etiology of HS is multifactorial, comprised of genetic and environmental factors, lifestyle 
(eg, smoking), hormonal status, and other comorbidities (metabolic syndrome, cardiovascular 
disorders, inflammatory bowel disease, etc; Zouboulis et al 2017). 
Current treatment guidelines recommend tailoring HS treatment based on its individual 
subjective impact and objective severity of disease (Zouboulis et al 2015). The aim of initial 
management of patients with HS is to reduce lesion development and minimizing disease 
progression. Treatments may include topical antiseptics, antibiotics (clindamycin, rifampin, 
tetracyclines) as the first line of therapy, followed by intralesional steroid injections 
(triamcinolone), retinoids (acitretin), hormonal therapy (Estrace, Prefest), biologics 
(adalimumab, infliximab) and in more advanced cases, surgery. Currently, adalimumab 


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(Humira®), a TNF-α fully human monoclonal antibody administered via subcutaneous injection, 
is the only FDA-approved therapy for patients 12 years of age and older with moderate-to-severe 
HS. Adalimumab has shown modest HiSCR response rates (42% and 59% vs placebo 26% and 
28%, respectively) in each of the Phase 3 trials (Frew et al 2020). Currently, there are no 
FDA-approved therapies for patients with mild HS. Therapies to treat patients with mild HS 
remain an unmet medical need to manage disease progression into a moderate-to-severe 
condition. 
Increased expression of JAK-mediated inflammatory cytokines in HS skin suggests a potential 
therapeutic strategy for JAK-inhibitor treatment of this debilitating disease (Rumberger et al 
2020; Zouboulis et al 2021). Data suggests that the cytokines IL-1β, IL-17, IL-23, IL-10, and, to 
a lesser extent, TNF-α are involved in the pathogenesis of HS (Kelly and Prens 2016). The 
expression and/or activity of these cytokines is mediated at the intracellular level through 
JAK-STAT signaling, and primarily JAK1. Therefore, it can be reasonably expected that 
interference with the transduction of intracellular signals generated by those cytokines will 
modify/decrease the level of inflammation seen in HS and thus moderate or control disease 
activity and related signs and symptoms. JAK1 inhibitors have the potential to treat the signs and 
symptoms of HS. Studies investigating the effects of oral JAK1 inhibition (INCB054707) in HS 
showed AN count decrease, improvement in disease-specific patient-reported outcomes, and 
changes in disease-associated serum biomarkers after 8 weeks of treatment (Alavi et al 2022). 
Data taken collectively suggest that JAK inhibition may be expected to be efficacious in HS. 
Ruxolitinib is a small molecule inhibitor of the JAKs with specificity for JAK1 and JAK2, which 
play an important role in signal transduction following cytokine and growth factor binding to 
their receptors. Increased production of inflammatory cytokines and growth factors are strongly 
implicated in the pathogenesis of a number of inflammatory conditions, including, AD, vitiligo, 
and other autoimmune diseases of the skin. Because JAKs serve to translate extracellular signals 
from a number of relevant cytokines and growth factors upregulated in these inflammatory 
diseases, JAK inhibitors represent potential therapeutic agents for these diseases (Chapman et al 
2022) and worth assessing for the treatment of HS. 
The efficacy of ruxolitinib cream, a JAK 1/2 inhibitor, is well established in AD and vitiligo. 
Ruxolitinib cream has shown statistically significant and clinically meaningful efficacy in 
2 pivotal Phase 3 studies (INCB 18424-303 and -304) in participants with mild to moderate AD 
and 3% to 20% BSA (excluding the scalp; Papp et al 2021). In both AD Phase 3 studies, over 
50% (53.8% and 51.3%) of participants (≥ 12 years of age) who applied ruxolitinib 1.5% cream 
BID for 8 weeks achieved an IGA-TS (ie, IGA of 0 or 1 with ≥ 2-point improvement from 
baseline) compared with 15.1% and 7.9% of participants who applied vehicle cream. Participants 
who applied ruxolitinib cream also saw a substantial improvement in itch compared with 
participants who applied vehicle cream in both studies (50.7% and 52.2% for ruxolitinib cream 
versus 16.3% and 15.4% for vehicle, respectively). Similarly, decreases in worst skin pain scores 
were observed in the ruxolitinib 1.5% cream treatment group by Week 2 and continued to 
decrease through Week 8, with the largest decreases at each visit occurring for participants who 
applied ruxolitinib 1.5% cream. In addition, ruxolitinib 1.5% cream administered BID was safe 
and well-tolerated in adolescent and adult participants with AD. Ruxolitinib 1.5% cream is 
approved by the FDA for the treatment of mild to moderate AD in nonimmunocompromised 
patients 12 years of age and older whose disease is not adequately controlled with topical 
prescription therapies, or when those therapies are not advisable (Opzelura™ 2021). 


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Ruxolitinib 1.5% cream has demonstrated efficacy in vitiligo. Two Phase 3 studies 
(INCB 18424-306 and -307), were identically-designed, randomized, vehicle-controlled in 
adolescent and adult participants (≥ 12 years old, ≈10% of whom were adolescents) with vitiligo. 
Participants received blinded study treatment for 24 weeks and were then offered the opportunity 
to receive an additional 28 weeks of treatment with ruxolitinib 1.5% cream BID. Both met the 
primary endpoint (p < 0.0001 for both studies), demonstrating that significantly more 
participants treated with ruxolitinib 1.5% cream BID achieved a ≥ 75% improvement from 
baseline in the facial vitiligo area scoring index compared to participants treated with a vehicle 
control at Week 24. 
Based on all collective evidence, a topical JAK-inhibitor such as ruxolitinib may be an 
appropriate treatment for HS. Therefore, this study is designed to evaluate the efficacy and safety 
of ruxolitinib 1.5% cream in participants with HS and a total AN count of 3 to ≤ 10 with no 
draining tunnels. 
2.2. 
Study Rationale 
Since the pathophysiology of HS appears to involve JAK1 associated cytokines, the primary 
purpose of this study is to assess the efficacy and safety of ruxolitinib 1.5% cream BID (topical 
JAK1 and JAK2 inhibitor) in participants with HS and a total AN count of 3 to ≤ 10 with no 
draining tunnels. 
2.2.1. 
Scientific Rationale for Study Design 
JAK1 associated cytokines (IL-1β, IL-17, IL-23, IL-10, IFN-γ, and TNF-α) have been shown to 
be involved in the pathogenesis of HS (Zouboulis et al 2020). Since the expression and/or 
activity of these cytokines is mediated at the intracellular level through JAK-STAT signaling, 
ruxolitinib, a selective JAK 1/2 inhibitor, may be an appropriate treatment of HS. Moreover, 
ruxolitinib is a selective inhibitor of JAK1 and JAK2 based on its demonstrated efficacy in both 
AD and vitiligo pivotal Phase 3 trials (INCB 18424-303/-304 and INCB 18424-306/-307, 
respectively). 
This study will evaluate the efficacy and safety of ruxolitinib 1.5% cream BID in adult 
participants with 3 and ≤ 10 AN count compared to vehicle cream for 16 weeks. All participants 
completing the 16-week DBVC period and who have no safety concerns will then enter the OLE 
period to receive active treatment for an additional 16 weeks. This design will provide a 
well-controlled assessment of the efficacy and safety of ruxolitinib 1.5% cream in mild HS 
compared to vehicle. 
2.2.2. 
Justification for Dose 
The ruxolitinib cream strength and application frequency (ruxolitinib 1.5% cream BID) for this 
study was selected primarily based on data from the Phase 3 pivotal studies (INCB 18424-303 
and -304) in participants ≥ 12 years of age with AD, which evaluated the safety and efficacy of 
ruxolitinib 1.5% cream BID and ruxolitinib 0.75% cream BID. Overall, ruxolitinib 1.5% cream 
was found to be more efficacious than its ruxolitinib 0.75% cream, while the safety and 
tolerability profiles of both treatment arms were comparable and nondifferentiating. Phase 3 AD 
studies also demonstrated; 1) rapid (as early as 12 hours) and substantial decrease in itch 
following application of ruxolitinib 1.5% cream with better efficacy against itch when compared 


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to ruxolitinib 0.75% cream; and 2) Skin Pain NRS scores decreased over time, with the largest 
decreases at each visit occurring for participants who applied ruxolitinib 1.5% cream. Similarly, 
Phase 3 pivotal studies in vitiligo (INCB 18424-306 and -307) provide further support for the 
superior efficacy of ruxolitinib cream 1.5% versus vehicle cream. 
In this study, the comparison to vehicle cream is relevant to better understand the effect of 
ruxolitinib cream in the treatment of HS. The use of vehicle cream is justified considering that 
there are no available HS-specific therapies to be used as a comparator for this milder population 
(AN count 3 to ≤ 10). After the 16-week vehicle-controlled period, all participants will receive 
ruxolitinib 1.5% cream for up to 16 weeks in the OLE period. 
Given the known data and the pathogenic and clinical manifestations of HS, ruxolitinib 1.5% 
cream BID, the highest formulated strength was selected as the treatment regimen for this study. 
2.3. 
Benefit/Risk Assessment 
Ruxolitinib 1.5% cream showed statistically significant and clinically meaningful improvement 
in the signs and symptoms of AD in participants with mild to moderate AD, including IGA 
(Papp et al 2021) and symptoms such as pain. Decreases in worst skin pain scores for 
participants in the ruxolitinib cream treatment groups (0.75% and 1.5%) in both Phase 3 studies 
(INCB 18424-303 and -304) were observed by Week 2 and continued to decrease through 
Week 8 of treatment. Given that pain along with other clinical manifestations, is a very 
bothersome symptom of HS, it is anticipated that participants with HS will benefit from 
application of ruxolitinib cream. 
Safety data from the Phase 3 AD studies demonstrated that ruxolitinib 1.5% cream BID applied 
continuously for 8 weeks followed by prolonged (44 weeks) intermittent use was safe and 
well-tolerated. The TEAEs were generally Grade 1 or 2 in severity and were most often events of 
nasopharyngitis and upper respiratory tract infection. Frequencies of these events were within the 
expected range for the general AD population. 
Safety and tolerability in the Phase 2 and Phase 3 studies in vitiligo (INCB 18424-211, -306, and 
-307) showed that the rate of Grade 3 TEAEs, SAEs, and TEAEs leading to discontinuation was 
low. There were no significant TEAEs or application site events and no clinically relevant 
hematological changes suggestive of systemic toxicity. The majority of participants with vitiligo 
had good local tolerability with ruxolitinib cream use and reported application site reactions were 
all Grades 1 or 2 in severity. The most commonly reported application site reactions were 
application site pruritus in 15 participants (2.0%) and application site acne in 7 participants 
(1.0%). All other application site reactions in participants with vitiligo were reported in < 1% of 
participants overall. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ruxolitinib cream may be found in the IB. 
In summary, the cumulative efficacy and safety data of ruxolitinib 1.5% cream BID in the 
treatment of AD (≤ 20% BSA with long-term intermittent dosing) and vitiligo (≤ 10% BSA with 
long-term continuous dosing), demonstrated that it is safe and well-tolerated with no evidence of 
systemic JAK inhibition, as expected given the low systemic exposures for the topical 
formulation. 


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Based on cumulative efficacy and safety data from AD and vitiligo studies, pathogenesis of HS, 
and role of Th1 cytokines in HS, it is expected that benefit-risk ratio of ruxolitinib cream in HS 
will be positive. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 4 presents the objectives and endpoints. 
Table 4: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% 
cream BID in participants with HS. 
Change from baseline in AN count at Week 16. 
Secondary 
To further evaluate the treatment effect of 
ruxolitinib 1.5% cream BID in participants with 
HS. 
• Proportion of participants achieving AN50, 
AN75, AN90, and AN100 (at least 50%, 75%, 
90%, and 100% reduction respectively in AN 
count relative to baseline) at Week 16. 
• Change from baseline in the Skin Pain NRS 
score at Week 16. 
• Change from baseline in the Itch NRS score at 
Week 16. 
• Proportion of participants who achieve HiSCR 
at Week 16. 
Note: HiSCR is defined as at least 50% 
reduction in AN count with no increase in 
either abscess or draining fistula counts, 
relative to baseline. 
• Change from baseline in the International 
Hidradenitis Suppurativa Severity Score 
System (IHS4) score at Week 16. 
Note: IHS4 score is calculated by the number 
of inflammatory nodules (multiplied by 1) plus 
the number of abscesses (multiplied by 2) plus 
the number of draining tunnels (multiplied by 
4). 
To evaluate the safety and tolerability of 
ruxolitinib 1.5% cream BID in participants with 
HS. 
The type, frequency, and severity of AEs, and 
changes in vital signs and hematology and serum 
chemistry parameters. 


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Table 4: 
Objectives and Endpoints (Continued) 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, randomized, DBVC study in participants ≥ 18 years of age with confirmed 
diagnosis of HS. The study will consist of a 16- week DBVC period followed by a 16-week OLE 
period. 
Participants will be screened for up to 28 days prior to the first application of ruxolitinib 1.5% 
cream or vehicle cream. Key entry criteria for participants are diagnosis of HS (Hurley Stage I or 
II) for at least 3 months before screening visit and a total AN count of 3 to ≤ 10 with no 
draining tunnels at screening and baseline. The AN count of 3 may affect at least 1 distinct 
anatomical area; however, an AN count of > 3 to ≤ 10 must be affecting at least 2 distinct 
anatomical areas. 
Approximately 60 eligible participants ≥ 18 of age will be randomized 1:1 to either ruxolitinib 
1.5% cream or vehicle cream (see Figure 1). Participants will be stratified by baseline AN count 
(≥ 3 to 4 or ≥ 5 to 10). Participants will apply either ruxolitinib 1.5% cream or vehicle cream 
(both BID) through Week 16 to the all affected areas identified at baseline. 
At Week 16, participants who meet the criteria (compliant with the Protocol and without safety 
concerns) will enter the 16-week OLE period. Participants randomized to vehicle BID in the 
DBVC period will be crossed over to ruxolitinib 1.5% cream BID and participants randomized to 
ruxolitinib 1.5% cream BID at baseline will remain on ruxolitinib 1.5% cream BID through 
Week 32 in an open-label fashion. At Week 16, the HS treatment area will be evaluated by the 
investigator to assess the disease and confirm whether treatment continuation is required (AN 
count ≥ 1 and/or Skin Pain NRS ≥ 1) during the OLE period or can otherwise (re)enter an 
observation/no treatment cycle (AN count = 0 and Skin Pain NRS = 0). During the OLE, 
participants will only treat symptomatic lesions (eg, presence of AN lesion(s) and/or pain) 
including new lesions not exceeding 20% BSA. Treatment assignment during the DBVC period 
will remain blinded to investigators and participants until after all participants have completed 
the study or discontinued and completed the safety follow-up period. 
During the DBVC and OLE periods, participants who require and are treated with lesional rescue 
interventions (eg, incision and drainage or intralesional corticosteroid injection), are considered 
nonresponsive to therapy, and will be discontinued from the study. 
Figure 1 presents the study design schema, and Table 3 presents the SoA. Adherence to the study 
design requirements, including those specified in the SoA, is essential and required for study 
conduct. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the implementation of potential mitigation 
strategies described in Appendix B. 


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4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF. It is estimated that an individual 
will participate for approximately 40 weeks, including up to 28 days for screening, 16 weeks for 
treatment during the DBVC period, 16 weeks for treatment during the OLE period, and up to 
30 days for follow-up after the last application of study treatment. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if they have completed all study visits, 
including the safety follow-up visit 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract. The investigator is to notify the IRB/IEC of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively if, for example, required by regulatory decision. 
If the study is terminated prematurely, the sponsor will notify the investigators, the IRBs and 
IECs, and the regulatory bodies of the decision and reason for termination of the study. 
5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety. Therefore, 
adherence to the criteria as specified in this Protocol is essential. Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for the study. 
2. Male or female participants age 18 years or above. 
3. Diagnosis of HS based on clinical history and physical examination for at least 3 months 
before screening visit. 
4. Diagnosis of HS (Hurley I or II) with the following: 
a. A total AN count of 3 to ≤ 10, with no draining tunnels at screening and baseline 
visits. 
AND 
b. The AN count at the screening AND baseline visits: 
− AN of 3 should affect at least 1 distinct anatomical area 
− AN of > 3 to ≤ 10 should affect at least 2 distinct anatomical areas 
Note: Anatomical areas include but are not limited to left and right axilla; or left and right 
inguinocrural fold or inframammary areas. 


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5. Baseline Skin Pain or Itch NRS score ≥ 1. Baseline Skin Pain or Itch NRS is defined as 
the 7-day average of Skin Pain or Itch NRS score before Day 1 (data from a minimum of 
4 out of 7 days directly prior to Day 1 is needed). 
6. Agreement to NOT use topical and systemic antibiotics for treatment of HS during the 
study. 
7. Agreement to NOT use a diluted beach bath or topical antiseptic washes containing 
chlorhexidine gluconate or benzoyl peroxide on the areas affected by HS lesions during 
the study. 
8. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 90 days (a 
spermatogenesis cycle) after the last application of ruxolitinib cream and must refrain 
from donating sperm during this period. Permitted methods in preventing pregnancy 
(see Appendix A) should be communicated to the participants and their understanding 
confirmed. 
b. Female participants who are WOCBP must have a negative serum pregnancy test at 
screening and before the first application on Day 1 and must agree to take appropriate 
precautions to avoid pregnancy from screening through 30 days (1 menstrual cycle) 
after the last application of study ruxolitinib cream and must refrain from donating 
oocytes during this period. Permitted methods in preventing pregnancy (see 
Appendix A) should be communicated to the participants and their understanding 
confirmed. 
c. Female participants not considered to be of childbearing potential as defined in 
Appendix A are eligible. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Presence of draining tunnels at screening or at baseline visits. 
2. Total HS BSA affected (excluding scalp) is > 20%. 
3. Participants with concurrent conditions and history of other diseases: 
a. Active ongoing inflammatory diseases of the skin other than HS that might confound 
the evaluation of HS. 
b. Any other concomitant skin disorder (eg, generalized erythroderma such as 
Netherton's syndrome), pigmentation, or extensive scarring that in the opinion of the 
investigator may interfere with the evaluation of HS AN or compromise participant 
safety. 
c. Active tuberculosis; or current and/or history of latent tuberculosis unless adequately 
treated. 
d. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, or 
Wiskott-Aldrich syndrome). 
e. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline. 


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f. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chicken pox, clinically infected AD, or impetigo) within 2 weeks before 
baseline. 
g. Unstable asthma or COPD requiring systemic treatment (such as intravenous steroids) 
or hospital admission or emergency room treatment within 3 months from baseline; or 
stable asthma or COPD requiring more than 720 µg/day (2 puff BID of 180-ug dose) 
or fluticasone more than 440 μg/day (2 puffs BID of 110-ug dose) or other equivalent 
inhaled corticosteroids. 
4. Any serious illness or medical, physical, or psychiatric condition(s) that, in the 
investigator's opinion, would interfere with full participation in the study, including 
administration of study drug and attending required study visits; pose a significant risk to 
the participant; or interfere with interpretation of study data. For example: 
a. Clinically significant or uncontrolled cardiovascular disease, including unstable 
angina, acute myocardial infarction, or stroke within 6 months from Day 1 of study 
drug application, New York Heart Association Class III or IV congestive heart 
failure, and arrhythmia requiring therapy or persistent uncontrolled hypertension 
(blood pressure > 150/90 mmHg) unless approved by medical monitor/sponsor. 
b. Any malignancies or history of malignancies within 5 years before baseline with the 
exception of adequately treated or excised nonmetastatic basal cell or squamous cell 
cancer of the skin, or cervical carcinoma in situ. 
c. History of severe anemia, severe thrombocytopenia, or severe neutropenia. 
5. Any of the following clinical laboratory test results at screening: 
a. Cytopenias at screening, defined as follows: 
− Hemoglobin < 100 g/L (ie, 10 g/dL) 
− ANC < 1.5 × 109/L (ie, 1500/µL) 
− Platelet count < 1 × 1011/L (ie, 100,000/µL) 
b. Liver function tests: 
− AST or ALT ≥ 2.5 × ULN 
− Total bilirubin > 1.5 × ULN unless Gilbert's syndrome 
c. Estimated GFR < 30 mL/min/1.73 m2 (using the Chronic Kidney Disease 
Epidemiology Collaboration equation). 
d. Positive serology test results at screening for HIV antibody. 
e. History or current of acute or chronic active HBV or HCV infection. Participants who 
have recovered or have been successfully treated with no evidence of active HBVor 
HCV infection, and those who are immune due to hepatitis B vaccination can enroll. 
Participants who are positive for the hepatitis B surface antigen will be eligible if they 
are negative for HBV-DNA; participants who are positive for the anti-HCV antibody 
will be eligible if they are negative for HCV-RNA. 
f. Any other clinically significant laboratory result that, in the opinion of the 
investigator, poses a significant risk to the participant. 
6. History of treatment failure (as assessed by the investigator through study participant 
interview) for HS or any other inflammatory condition with any systemic or topical JAK 
or TYK2 inhibitor (eg, abrocitinib, baricitinib, brepocitinib, deucravacitinib, filgotinib, 
lestaurtinib, pacritinib, ruxolitinib, tofacitinib, upadacitinib). 


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7. Use of any of the following treatments within the indicated washout period before the 
baseline visit: 
a. 12 weeks or 5 half-lives (if known), whichever is longer, for systemic 
immunosuppressive or immunomodulating biologic drugs (eg, adalimumab, anakinra, 
bermekimab, bimekizumab, brodalumab, certolizumab, dupilumab, etanercept, 
golimumab, guselkumab, infliximab, iscalimab, ixekizumab, risankizumab, 
rituximab, secukinumab, vilobelimab, ustekinumab, etc). 
b. 4 weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, 
baricitinib, brepocitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, 
ruxolitinib, tofacitinib, upadacitinib, etc). 
c. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs, 
cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or 
immunomodulating agents (eg, mycophenolate or tacrolimus). 
d. 2 weeks or 5 half-lives, whichever is longer - strong systemic CYP3A4 inhibitors. 
e. 2 weeks – systemic antibiotics and immunizations with live-attenuated vaccines, 
sedating antihistamines unless on a long-term stable regimen (nonsedating 
antihistamines are permitted). 
Note: Live-attenuated vaccines are prohibited during the DBVC period. COVID-19 
vaccination is permitted. 
f. 2 weeks – topical therapy for HS (eg, topical antiseptics, topical antibiotics, topical 
corticosteroids, topical calcineurin inhibitors, other topicals). 
g. 2 weeks - any opioid treatment. 
8. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
the baseline visit with another investigational medication or current enrollment in another 
investigational drug Protocol. 
9. Participant with known allergy or reaction to any of the components of the study cream. 
10. History of alcoholism or drug addiction within 1 year before screening or current alcohol 
or drug use that, in the opinion of the investigator, will interfere with the participant's 
ability to comply with the administration schedule and study assessments. 
11. Pregnant or lactating participants, or those considering pregnancy during the period of 
their study participation. 
12. Participants with inadequate venous access in nonlesional areas or in lesional areas not 
treated by the study drug within the last 7 days. 
13. Participants who are committed to a mental health institution by virtue of an order issued 
either by the judicial or the administrative authorities. 
14. Participants who, in the opinion of the investigator, are unable or unlikely to comply with 
the administration schedule and study evaluations. 
15. Employees of the sponsor or investigator or otherwise dependents of them. 


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5.3. 
Lifestyle Considerations 
Participants should be cautioned to avoid exposure to artificial sunlight (including tanning 
booths, sun lamps, etc). If sunscreen or other cosmetics have been applied to the areas to be 
treated, participants should follow the guidance in Section 6.6 regarding concomitant 
medications. 
It is recommended that bathing, showering, excessive sweating, or swimming should not take 
place within 2 hours before and after the planned study drug application. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study treatment. 
Tests with results that fail eligibility requirements may be repeated once during screening at the 
discretion of the investigator (eg, when the investigator believes that previous borderline 
abnormal laboratory results may have resolved). Additionally, a participant who fails screening 
may repeat the screening process 1 time if the investigator believes that there has been a change 
in eligibility status. Participants who rescreen must reconsent and be assigned a new participant 
ID number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. However, as noted in the 
COVID-19–related guidance (see Appendix B), due to the evolving situation of the COVID-19 
pandemic, the sponsor may decide to recruit additional participants in the study beyond the 
expected number (eg, if a substantial number of participants withdraw early from the study). 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment(s) Administered 
Ruxolitinib 1.5% cream or matching vehicle cream will be applied as a thin film BID, with 
applications approximately 8 hours apart in the morning and in the evening at least 1 hour before 
bedtime. 
At the baseline visit, an estimate of the %BSA (≤ 20%) affected by HS (total AN count 3 to 
≤ 10) to be treated (excluding scalp) will be used by the IRT system to calculate the number of 
tubes of study drug to be dispensed. The participant will apply a thin film of study drug in front 
of site staff at the baseline/Day 1 visit by applying small amounts of study drug on each nodule 
and the surrounding area of the nodule (≈1 cm). All areas identified at baseline should continue 
to be treated through the end of the DBVC period (Week 16) unless the participant meets criteria 
for stopping study drug. If there are new AN to be treated, after consultation with the 
investigator, study drug should be applied to these AN in addition to the areas treated at baseline 
(maximum total affected areas ≤ 20% BSA), and the percentage of BSA to be treated will be 
recalculated and increased. This new estimate will be entered into the IRT system to calculate the 
number of tubes of study drug to be dispensed. Participants whose additional new areas to be 
treated in addition to the areas identified at the baseline visit exceed 20% BSA should be 
discontinued from study treatment and ET assessment should be completed. 
At Week 16 and starting the OLE period, participants will be evaluated by the investigator to 
confirm whether they: 
• require continuation of therapy due to AN count ≥ 1 and/or the presence of pain (Skin 
Pain NRS ≥ 1) or, 
• can begin an observation/no treatment cycle due to AN count = 0 and no pain [Skin Pain 
NRS of 0]).  
At Week 16, the IRT system will dispense a prespecified number of tubes according to the 
assessment of total BSA to be treated. 
Between OLE study visits, participants will treat all areas identified with HS lesions (total 
affected area not to exceed 20% BSA). If all signs and symptoms of HS resolve between study 
visits, the participant will contact the investigator to confirm that study drug applications should 
be stopped 3 days after the HS lesion (AN count = 0) have disappeared. If this 3-day window is 
during a study visit and the AN count = 0, Skin Pain NRS = 0, as assessed by the investigator, 
treatment is to be stopped at the study visit. 
Multiple cycles of treatment/no treatment may be utilized as needed and treatment start/stop 
dates should be recorded in the eDiary. If a participant has stopped treatment during the OLE 
period, treatment may be restarted after consultation with the investigator if the participant has 
an AN count ≥ 1 and/or pain (Skin Pain NRS score ≥ 1). Approval to treat additional areas may 
occur via telephone during the OLE period, although the investigator, at their discretion, may ask 
the participant to return for an unscheduled visit. 
At any time during the OLE period, if a participant's new areas to be treated in addition to the 
areas already identified at the previous visit exceed 20% BSA, then the participant should be 
discontinued from study treatment and the ET assessment should be completed. The amount of 


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study drug used per application will be determined by weighing a tube before and after the 
participant applies study drug to the affected areas. All tubes (including caps) of study cream will 
be weighed before being dispensed. All returned tubes (including caps) of study cream will also 
be weighed. 
Table 5 presents the study treatment information. 
Table 5: 
Study Treatment Information 
 
Study Treatment 1 
Study Treatment 2 
Study treatment name: 
Ruxolitinib 
Vehicle 
Mechanism of action: 
JAK 1/2 inhibitor 
Not applicable 
Dosage formulation: 
Cream 
Cream 
Treatment strength: 
1.5% 
Not applicable 
Administration instructions: 
DBVC period: Apply a thin film to affected areas identified at 
baseline in the morning and at least 1 hour before bedtime with 
applications approximately 8 hours apart for 16 weeks. 
OLE period: Apply a thin film to affected areas only in the 
morning and at least 1 hour before bedtime with applications 
approximately 8 hours apart as needed for 16 weeks. 
Packaging and labeling: 
Ruxolitinib or vehicle cream will be provided in 60 g tubes. 
Each tube will be labeled as required per country requirement. 
Storage: 
15°C-30°C (59°F-86°F) 
Status of treatment in 
participating countries: 
Investigational 
6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions (both ruxolitinib 
cream and vehicle cream are to be stored between 15°C and 30°C [59°F-86°F]) have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply study treatment. Refer to the Study Pharmacy Manual for participant 
instructions for handling of study cream. Participants should store study treatment at ambient 
temperature conditions. 
All study treatment must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff. 


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The investigator or designee is responsible for study treatment accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records). Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities. The 
investigator or designee must maintain records that document the following: 
• Delivery of study drug(s) to the study site. 
• Inventory of study drug(s) at the site. 
• Participant use of the study drug(s), including tube counts from each supply 
dispensed. 
• Return of study drug(s) to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol. The investigator 
or designee will also maintain records adequately documenting that the participants were 
provided the specified study drug. These records should include dates, quantities, and any 
available batch or serial numbers or unique code numbers assigned to the investigational product 
and study participants. 
Completed accountability records will be archived by the site. The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor). At the conclusion 
of the study, the investigator or designee will oversee the destruction of any remaining study 
drug according to institutional SOPs. If, however, local procedures do not allow on-site 
destruction, shipment of the study drug back to the sponsor is allowed. In this case, the site 
should (where local procedures allow) maintain the investigational supply until the study monitor 
inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site. At sites where the study drug is destroyed before monitor 
inspection, the monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the study materials provided to the sites. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT system. The IRT 
system will assign in a 1:1 ratio, stratified by baseline AN count (≥ 3 to 4 or ≥ 5 to 10), 
participant study number, track participant visits, randomize according to the defined parameters, 
maintain the blinding, and manage study cream inventory. Full details will be provided in the 
IRT Manual. 
Participants, investigators, and the sponsor will be blinded to each participant's treatment 
assignment during the DBVC period. During the OLE period, participants and investigators will 
remain blinded to the treatment assignment during the DBVC period. Emergency unblinding will 
occur if an AE requires the investigator to be made aware of the participant's treatment 
assignment (see emergency unblinding procedures in Section 9.7 and refer to the IRT Manual). 


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6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by site 
staff, and appropriate steps should be taken to optimize compliance during the study. 
Compliance will be assessed for frequency of application of study cream by reviewing the 
participants' diaries. Participants will also be questioned regarding study cream application 
technique, missed applications, and use of any additional topical or systemic prescriptions of 
other products or over-the-counter products. Compliance with study treatment will be evaluated 
by the participant's adherence to the BID application regimen (evaluation of actual number vs 
prescribed number of applications), documented by the site staff, and monitored by the 
sponsor/designee. 
Qualified clinical staff will review the diary entries for compliance. Participants will be 
considered compliant with the treatment regimen if they apply at least 80% but no more than 
120% of the prescribed number of applications during participation in the DBVC and OLE 
periods of the study. Participants who are noncompliant during the DBVC period and OLE 
period (if on a treatment cycle) will be reinstructed by the investigator (or designee). Participants 
who are consistently noncompliant with study drug may be withdrawn from the study. The 
decision to withdrawal a participant based on noncompliance will be made by the investigator 
after consultation with the sponsor. 
Drug accountability will be assessed by documenting the quantities of drug used between study 
visits (tube counts and weighing). At the first clinic visit and subsequent study visits, the amount 
of study cream to be applied is to be determined by weighing a tube (including the cap) before 
and after the participant applies a thin film of study cream to the affected areas. Participants will 
be instructed to bring all study cream with them to the study visits in order for site staff to assess 
study cream accountability. 
6.5. 
Dose Modifications 
There are no application adjustments/modifications allowed (decrease or increase in study drug 
frequency of application) except for drug interruption or permanent discontinuation, if needed 
(eg, for management of an AE). 
Temporary interruption could be due to an AE in the DBVC or OLE period or clearance of the 
HS in the OLE period. 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drugs 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine whether the participant should continue or discontinue study treatment. 
In some circumstances, it may be necessary to temporarily interrupt treatment with study drug 
(see Table 6). Changes to the study drug application frequency (eg, reduction to QD) are not 
allowed. 
In the event that an AE is present at a specific site of study drug application, treatment may be 
temporarily withheld only at that application site and continued elsewhere. This should be 
recorded as a dose interruption on the AE eCRF page. Except in cases of emergency, it is 
recommended that any findings of concern (eg, AE) be confirmed and that the investigator 


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consult with the medical monitor before interrupting study drug applications. Additionally, the 
investigator must obtain approval from the medical monitor before restarting study drug. 
Participants who experience a recurrence of the initial AEs upon restarting the study drug may 
need to permanently discontinue treatment with the study drug. 
Participants should be closely monitored for the development of signs and symptoms of infection 
during treatment with the study drug and up to the safety follow-up visit. Study drug should be 
interrupted if a participant develops a serious infection, an opportunistic infection, or sepsis. 
Study drug application should not be resumed until the infection is controlled. 
Instructions for application interruptions of study drug–related to laboratory abnormalities are 
outlined in Table 6. 
Table 6: 
Guidelines for Interruption and Restarting of Study Drug 
Adverse Event Related to Study Drug 
Action Taken 
Any Grade 3 laboratory abnormality 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48-72 hours whenever possible and 
immediate delivery of the laboratory results should be 
requested. 
• Interrupt study drug, based on clinical judgment in 
consultation with the medical monitor (whenever 
possible), taking into account the relatedness of the AE to 
the study drug and the participant's underlying condition. 
• Interruption may occur after the initial test result or may 
be delayed until or unless the repeat test confirms the 
laboratory abnormality; however, if the repeat test does 
confirm the laboratory abnormality, the study drug must 
be interrupted unless the medical monitor approves 
continuation. 
• At the discretion of the investigator, after consultation 
with the sponsor, study drug application may be restarted 
once the laboratory abnormality has resolved. 
Any Grade 4 laboratory abnormality 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results should be 
requested. 
• Interrupt study drug, based on clinical judgment in 
consultation with the medical monitor (whenever 
possible), taking into account the relatedness of the AE to 
the study drug and the participant's underlying condition. 
• Discontinue study drug permanently if laboratory 
abnormalities are confirmed and deemed related to study 
drug. 
Note: Adverse event grades are based on CTCAE v5. 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug to an Adverse Event 
The occurrence of unacceptable severity of an AE, such that it would interfere with study drug 
treatment or study procedures and may require that the study drug be permanently discontinued. 
Unacceptable severity is defined as follows: 
• Occurrence of an AE that is related to treatment with the study drug that, in the 
judgment of the investigator or the sponsor's medical monitor, compromised the 
participant's ability to continue study-specific procedures, or is considered to not be in 
the participant's best interest. 
• Participant presents with a worsening of HS that requires treatment with a prohibited 
concomitant medication and/or surgical intervention (see Section 6.6.3). 
• Adverse event requiring an interruption of study drug for more than 2 weeks. 
• Participants with confirmed Grade 4 laboratory abnormalities deemed related to study 
drug. 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF. 
Non-HS medications received up to 28 days before the first application of study treatment will 
be recorded in the eCRF. Any prior HS treatments received within 1 year of the first application 
of study drug will be collected, including the response to treatment and reason for stopping the 
treatment. All medications received from the first application through the follow-up period from 
the last application of study treatment will be recorded in the eCRF. Any addition, deletion, or 
change in the dose/regimen of these medications will also be recorded. 
Other relevant medications or procedures received more than 28 days before the first dose of 
study drug may be recorded in the eCRF at the discretion of the investigator or at the request of 
the sponsor based on emerging events during the study. 
Any addition, deletion, or change in the dose/regimen of these medications will also be recorded. 
Concomitant medications administered 30 days after the last application of study treatment 
should be recorded for SAEs. Concomitant treatments/procedures that are required to manage a 
participant's medical condition during the study will also be recorded in the eCRF. The medical 
monitor should be contacted if there are any questions regarding concomitant or prior therapy. 


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6.6.1. 
Permitted Medications and Procedures 
The following are permitted during the study if, in the judgement of the investigator, the intake 
of these medications and procedures will not impact the safety of the participant or efficacy of 
the treatment: 
• 
 
 Further information will be provided in the 
Study Manual. The following analgesics may be used: 
− Nonsteroidal anti-inflammatory drugs, as needed, without exceeding the 
recommended dose on the label. 
− Low dose acetyl salicylic acid (aspirin, ≤ 100 mg QD) is permitted for the 
purpose of cardiovascular prophylaxis at the discretion of the investigator. 
− Acetaminophen/paracetamol, intermittently (not to exceed 1 g/day). 
− Prescribed analgesics, at the discretion of the investigator. 
• Inhaled corticosteroids for bronchial asthma or COPD is allowed with the dose 
equivalent of budesonide (not to exceed 720 µg/day or 2 puff BID of 180-ug dose) or 
fluticasone (not to exceed 440 μg/day or 2 puffs BID of 110-ug dose) or other 
equivalent inhaled corticosteroids. 
• Use of any over-the-counter, nonprescription vitamins (excluding vitamin D and 
zinc), minerals, and phytotherapeutic, herbal, or plant-derived preparations. 
• Wound Care 
− Concomitant use of wound care dressings on HS wounds is allowed. 
6.6.2. 
Restricted Medications and Procedures 
The use of following medications and procedures is restricted to specified conditions and if 
deemed acceptable by the investigator from 14 days before the baseline visit through follow-up 
visit: 
• Use of any prescription medication to treat chronic medical conditions (such as 
hypertension) if on stable regimen in the judgement of the investigator 


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6.6.3. 
Prohibited Medications and Procedures 
No rescue therapy and/or procedural intervention is allowed for HS during the study. In addition, 
the following rescue therapies are not permitted during the study: 
• Treatment known to affect the course of HS. 
• Current opioid treatment. 
• Topical or systemic antibiotics, topical or intralesional corticosteroids, topical 
calcineurin inhibitors, systemic corticosteroids, methotrexate, dapsone, metformin, 
tretinoids/retinoids, aldactone, cyclosporine A, azathioprine and biological therapies, 
or other immunosuppressant/immunomodulators agents or any other topical or 
systemic treatment for HS. 
• Any surgery for HS including, but are not limited to, the following: 
− Incision and drainage 
− Deroofing 
− Lesion ablation (electrosurgery) 
− Local excision 
• Phototherapy (laser and pulsed light therapy) or tanning beds. 
• Topical antiseptics (eg, diluted bleach bath or washes containing chlorhexidine 
gluconate or benzoyl peroxide). 
In addition, the following therapies are not permitted during the study: 
• Strong systemic CYP3A4 inhibitors. 
• Live-attenuated vaccination during the DBVC period. 
Note: COVID-19 vaccination is permitted 
• Any investigational medication other than the study drug. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• Disease worsens during either the DBVC period or the OLE period, to the point 
where the extent of the affected area to be treated exceeds 20% BSA or there is a 
draining tunnel(s). 
• Worsening HS and treatment with a prohibited medication and/or procedure as noted 
in Section 6.6.3. 
• The participant becomes pregnant. 
• Consent is withdrawn. 
Note: Consent withdrawn means that the participant has explicitly indicated that they 
do not want to be followed any longer; in this case, no further data, except data in the 
public domain, may be collected or solicited from the participant. Participants may 
choose to discontinue study treatment and remain in the study to be followed for 
progression and survival. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
• Unacceptable toxicity occurs (see Section 6.5.2). 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, after 2 consecutive study visits and reinforcement of study drug application by site 
staff, a participant who again fails to meet compliance benchmarks at a subsequent 
visit may be considered for withdrawal from the study. The medical monitor should 
be consulted for instruction on handling the participant. 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria at the time of enrollment, the medical monitor, in collaboration with the 
investigator, will determine whether the participant should be withdrawn from study 
treatment. 
• If a participant is noncompliant with study procedures or study drug application in the 
investigator's opinion, the sponsor should be consulted for instruction on handling the 
participant. 


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7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment prior to the 
Week 32 visit, the ET visit should be conducted. Reasonable efforts should be made to have the 
participant return for a follow-up visit. The last date of the last application of study cream and 
the reason for discontinuation of study cream will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The ET visit should be performed and the date recorded. 
• The status of the participant should be updated to ET in the IRT system. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at their own request or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If a participant withdraws from the study, they may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records. If the participant 
withdraws consent for disclosure of future information, the sponsor may retain and continue to 
use any data collected before such a withdrawal of consent. 
See Table 3 for data to be collected at the time of study withdrawal and follow-up and for any 
further evaluations that need to be completed. 


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7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or their representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant. An ICF template 
will be provided by the sponsor or its designee. The sponsor or its designee must 
review and acknowledge the site-specific changes to the ICF template. The ICF 
must include a statement that the sponsor or its designee and regulatory 
authorities have direct access to participant records. 
− The ICF must contain all required elements including optional 
samples/procedures (eg, optional biopsy) and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the country(ies) in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that their personal data collected for the study will 
be used by the sponsor and/or their designee(s) in accordance with local data 
protection laws. The level of disclosure must also be explained to the participant. 
• The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
• Participants who are rescreened are required to sign a new ICF and must be assigned 
a new participant ID number. 


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (Day 1). Screening may not exceed 28 days. Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
Procedures conducted as part of the participant's routine clinical management (eg, blood counts 
or physical examinations) and obtained before signing of the ICF may be used for screening or 
baseline purposes provided that the procedure meets the Protocol-defined criteria and has been 
performed in the timeframe of the study (ie, within 28 days or less prior to Day 1). For 
participants who are enrolled in the study, information associated with eligibility requirements 
must be entered into the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
randomization and the administration of study drug. Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error. For screening assessments that are repeated, the most recent available result before 
randomization will be used to determine eligibility. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of a country's abbreviation, the site ID, and the participant ID number. Site staff 
should contact the IRT to obtain the participant ID number during screening. 
Upon determining that the participant is eligible for study entry, the IRT will be contacted to 
obtain the treatment assignment. Additionally, the IRT will be contacted at each regular study 
visit during both the DBVC period and the OLE period to update the study drug supply. 
Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and/or Diaries 
Participants will be provided with a reminder card starting on Day 1 and at all DBVC and all 
OLE visits through Week 32. The reminder card will indicate the date and time of the next visit. 
Participants will be instructed on the use of the eDiary at the screening visit. The participant will 
start using the eDiary for completion of the Skin Pain NRS and Itch NRS at screening and for 
recording study drug applications on Day 1. 
 
. Daily study drug 
administration will be recorded in the eDiary and verified by the study investigator/designee at 
study visits as shown in Table 3. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 


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history, and current illnesses. Medical history will include relevant medical and surgical 
treatments considered to be clinically significant by the investigator. 
As race and/or ethnicity data are not to be analyzed from a scientific or medical perspective, but 
rather are to be reported in a descriptive format only in the CSR, data on race and/or ethnicity 
from France must not be collected as per GDPR and local data protection law and requirements. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history will be collected at screening. Details regarding 
the participant's HS, including date of diagnosis, relevant disease characteristics, and prior 
treatments, and the reason for stopping treatments, including systemic treatments, and surgical 
procedures, will be recorded. 
8.2. 
Efficacy Assessments 
8.2.1. 
Lesion Counts 
The HS lesion counts will be assessed at each study visit (Table 3) by the investigator and used 
for calculation of efficacy parameters as follows: AN counts (Section 8.2.1.1), HiSCR 
(Section 8.2.1.2), IHS4 (Section 8.2.1.3), 
. 
 
 
 
Definitions and schematics of various HS lesions (Frew et al 2021) are provided in Table 7 to aid 
in the identification of the different morphologies. 


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Table 7: 
Definition of Hidradenitis Suppurativa Lesions 
HS Lesion 
Definition 
Schematic 
Abscess 
A tender, fluctuant (compressible), 
palpable lesion, with erythema. 
 
Inflammatory nodule 
A solid, spherical, palpable lesion >1 cm; 
tender and/or erythematous. 
Note: a noninflammatory nodule is 
defined as nontender, nonerythematous 
nodule. 
 
Tunnel (nondraining) 
Compression of surrounding structures 
does not elicit drainage of contents. 
 
Tunnel (draining)a 
A linear tract that may open onto the skin 
surface; drainage expressed at rest or with 
compression of surrounding structures.  
Note: Definitions and lesion schematics obtained from Frew et al 2021 ("tunnels may include connection to a hollow 
organ (eg, bladder, intestine) (A), blind ending (B), 2 skin-to-skin openings (C), and no opening to the surface (D). 
The original artwork was created by Bradley Winters, Penn State University"). 
a Excluded from this study. 
8.2.1.1. 
Abscess and Inflammatory Nodule Counts 
The AN counts will be recorded at all visits. The AN results will be used to calculate change in 
AN count relative to baseline, as well as AN50, AN75, AN90, and AN100, defined respectively 
as at least a 50%, 75%, 90%, and 100% decrease in AN count relative to baseline. 
8.2.1.2. 
Hidradenitis Suppurativa Clinical Response 
The HiSCR was originally developed based on the underlying Phase 2 trial of adalimumab and 
validated against meaningful changes in pain score and DLQI (Kimball et al 2016, Sabat et al 
2020). The achievement of HiSCR is defined as at least 50% reduction in AN count with no 
increase in either abscess or draining fistula counts, relative to baseline. In this study, 
participants with draining fistulas (tunnels) will be excluded from the study. Should a 
randomized participant develop a draining tunnel during the study, the participant will be 
discontinued from the study. 
8.2.1.3. 
International Hidradenitis Suppurativa Severity Score System 
The IHS4 (Zouboulis et al 2017) is a composite, dynamic score, and validated tool used to 
determine HS severity. It employs a weighted scale using the number of inflammatory nodules, 
the number of abscesses, and the number of draining tunnels (fistulas or sinuses), with respective 
weight factors of 1, 2, and 4 (Example: IHS4 score equals the number of inflammatory nodules 


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[multiplied by 1] plus the number of abscesses [multiplied by 2] plus the number of draining 
tunnels [multiplied by 4]). 
 
 
 
 
 
 
8.2.2. 
Hurley Stages of Hidradenitis Suppurativa 
The Hurley classification is a static score and was originally designed for selection of the 
appropriate treatment modality in a certain body location (Zouboulis et al 2017): medical therapy 
for Stage I, local surgery for Stage II, and wide surgical excision for Stage III (see Table 8). 
Participants who have been diagnosed with HS, Hurley Stage I or II as per inclusion criterion, 
will be enrolled into the study. The investigator (or designee) will determine the Global Hurley 
Stage in each affected anatomical region at the designated study visits listed in Table 3. 
Table 8: 
Hurley Stages of Hidradenitis Suppurativa  
Hurley Stage 
Description 
I 
Abscess formation, single or multiple, without sinus tracts and cicatrization/scarring. 
II 
One or more widely separated recurrent abscesses with tract formation and 
cicatrization/scarring. 
III 
Multiple interconnected tracts and abscesses across the entire area, with diffuse or 
near diffuse involvement. 
8.2.3. 
Body Surface Area 
Total %BSA affected by HS will be used to determine the number of tubes of study drug 
dispensed at each visit. Total %BSA affected will be estimated at each visit as outlined in the 
SoA (see Table 3). Body surface area assessment will be approximated to the nearest 0.1% using 
the Palmar Method as a guide, with the palm plus 5 digits, with fingers tucked together and 
thumb tucked to the side (handprint), considered as 1% BSA and the thumb as 0.1% BSA. 
8.2.4. 
Patient-Reported Outcomes 
Patient-reported outcomes will be assessed as outlined in the SoA (see Table 3). 
All PROs will be collected via electronic eCOA solution. Sites will be provided with training 
materials and instructions on the use of eCOA solution and will be responsible to train 
participants on eDiary use and eCOA completion. Further details on use of the eCOA devices 
will be provided in respective study documentation. 
For PROs scheduled to be completed at study visits: At Day 1, participants will complete PROs 
after eligibility is met. For subsequent visits after randomization, questionnaires will be 
completed by the participant before site personnel perform any clinic assessments to avoid 
biasing the participant's response 


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8.2.4.1. 
eDiary Assessments: Skin Pain and Itch Numeric Rating Scales 
The participant will be instructed to complete and record the Skin Pain and Itch NRS via an 
eDiary, daily, in the evening beginning on the day of screening through Week 32 or ET (see 
Table 3). 
Both the Skin Pain and Itch NRS are a daily participant-reported measure (24-hour recall) of the 
worst level of skin pain and itch intensity related to HS. 
The participants will rate the following: 
• Skin Pain NRS: Pain severity of their HS by selecting a number from 0 (no pain) to 
10 (worst imaginable pain) that best describes their worst level of pain in the past 
24 hours. 
• Itch NRS: Itch severity of their HS by selecting a number from 0 (no itch) to 10 
(worst imaginable itch) that best describes their worst level of itching in the past 
24 hours. 
The baseline Skin Pain NRS and the Itch NRS is established prior to the first dose of study drug 
as follows: 
• The average of the 7-day Itch NRS score prior to the baseline visit (minimum 4 out of 
the 7 days' data required) will be collected. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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• 
 
• 
 
• 
 
• 
 
• 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA in Table 3. 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last application of study drug. Adverse events for enrolled participants that 
begin or worsen after informed consent should be recorded on the Adverse Events Form in the 
eCRF regardless of the assumption of a causal relationship with the study drug. Conditions that 
were already present at the time of informed consent should be recorded on the Medical History 
Form in the eCRF. Adverse events (including laboratory abnormalities that constitute AEs) 
should be described using a diagnosis whenever possible rather than by individual underlying 
signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
that are considered related to the study drug/procedures, or that caused the participant to 
discontinue the study drug. Care will be taken not to introduce bias when detecting AEs and/or 
SAEs. Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences. Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments. The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.3.2. 
Physical Examinations 
At the screening visit and the Week 32/ET2 visit, a comprehensive physical examination should 
be conducted. The comprehensive physical examination will include assessment(s) of the 
following organ or body systems: skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief 
neurological examination. In addition, a participant's height and weight will be obtained during 
the screening visit. 
During the study, a targeted physical examination may be conducted by the investigator or 
medically qualified designee (per institutional policies and local standard of care) to assess AEs, 
symptoms/signs, laboratory abnormalities, or other findings. Findings from the targeted physical 
examination should be reported on the AE eCRF. 


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8.3.3. 
Vital Signs 
Vital sign measurements (to be taken at each study visit and before blood collection for 
laboratory tests) include blood pressure, pulse, respiratory rate, and body temperature. Blood 
pressure and pulse will be taken with the participant in the sitting position after 5 minutes of rest. 
Abnormal vital signs can be repeated after a rest period at the discretion of the investigator. 
Abnormal vital sign results identified after the first dose of study treatment, including those that 
worsen from baseline, considered clinically significant in the medical and scientific judgment of 
the investigator (ie, not related to progression of underlying disease) are to be reported as an AE. 
8.3.4. 
Laboratory Assessments 
See Table 9 for the list of clinical laboratory tests to be performed and Table 3 for the timing and 
frequency. A central laboratory will perform all clinical laboratory assessments for safety 
(eg, blood chemistries or hematology assessments) 
 
 Additional testing may be required by the sponsor based on emerging safety data. All 
Protocol-required laboratory assessments must be conducted in accordance with the Laboratory 
Manual. Information regarding collection, processing, and shipping of samples for laboratory 
assessment is provided in the Laboratory Manual. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 30 days after the last application of the study 
drug should be repeated until the values return to normal or baseline or are no longer considered 
clinically significantly abnormal by the investigator or medical monitor. 
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 


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Table 9: 
Required Laboratory Analytes 
Chemistry 
Hematology 
Serology 
Pregnancy Testing 
ALT 
AST 
Glucose 
Creatine kinase 
Creatinine 
Total bilirubin 
Direct bilirubin (if 
total bilirubin is 
elevated above ULN) 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• White blood cell count 
 
Differential count, 
including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Hepatitis B surface antigen 
HCV antibody 
HIV antibody 
 
HBV-DNAa 
HCV-RNAb 
Human chorionic 
gonadotropin (WOCBP only) 
 
FSH (women of 
nonchildbearing potential 
only) 
 
Female participants of 
childbearing potential only 
require a serum test at 
screening and a urine 
pregnancy test at all other 
visits. A positive urine test 
will be confirmed by a serum 
test. 
Other 
hsCRP 
Note: Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data or to rule out a 
diagnosis. 
a Reflex testing if Hepatitis B surface antigen is positive. 
b Reflex testing if HCV antibody is positive. 
8.3.4.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening. Urine pregnancy tests 
will be performed locally, as outlined in the SoA (see Table 3), and as medically indicated (eg, in 
case of loss of menstrual cycle or when pregnancy is suspected). 
If a urine pregnancy test is positive, the results must be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.8 for reporting 
requirements. 
8.3.4.2. 
Serology 
HIV and hepatitis screening assessment will be performed at the screening visit (see Table 3). 
Generally, virology and serology tests should be performed early in the screening process due to 
the length of time needed to obtain the results. Additional tests may be performed if clinically 
indicated. 
 
 
 
 
 


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, 
 
. 
 
8.5. 
 Translational Assessments 
 
 
 
 
 
 
8.5.2. 
Photography 
At select sites, photographs of the HS lesion (identified as target lesion), will be taken at visits 
indicated in Table 3. Detailed methods for capturing photographs will be provided in the Study 
Manual. 
8.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time medically warranted, including when participants 
develop new lesions of HS. Any assessments performed at those visits should be recorded in the 
eCRF. 
8.7. 
End of Treatment and Early Termination 
The EOT coincides with the Week 32 visit. A participant that completes the Week 32 visit will 
have reached the EOT with study drug. 
If a decision is made that the participant will permanently discontinue study drug prior to the 
Week 32 visit, then the ET visit should be conducted. If the ET visit coincides with a regular 
study visit, then the ET evaluations will supersede those of that scheduled visit, and the data 
should be entered in the ET page in the eCRF. If this decision does not coincide with a regular 
visit, reasonable efforts should be made to have the participant return to the site to complete the 
ET procedures. 


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8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the Week 32/ET visit and the scheduled 
follow-up visit, which should occur 30 days (+ 7 days' visit window) after the Week 32/ET visit 
(or 30 days after the last application of study drug if the Week 32/ET visit was not performed). 
Participants who have been in an observation/no treatment cycle from Week 28 or earlier until 
Week 32 do not need to complete the safety follow-up visit. 
Adverse events and SAEs must be reported up until 1) at least 30 days after the last application 
of study drug or 2) until toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. Reasonable efforts should be made to have the participant return for the 
follow-up visit and report any AEs that may occur during this period. 


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9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug-related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. 
Additional Guidance for Events Meeting the Adverse Event Definition 
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug. Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin, platelet count 
decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dose administration errors of a study drug (eg, overdose) or a 
concomitant medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the 
signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as an AE or 
SAE if they fulfill the definition of an AE or SAE. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy or appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent. If the condition is present before 
entering the study, then it should be captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs. This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency department for observation and/or treatment that would 
not have been appropriate in the physician's office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as to whether hospitalization occurred or was necessary, 
the AE should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) is not considered an SAE. 
d. Results in persistent or significant disability/incapacity 
The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle), that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
An important medical event is an event that may not result in death, be immediately life-threatening, or 
require hospitalization but may be considered serious when, based on appropriate medical judgment, 
the event may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definition. Examples of such events include new invasive or 
malignant cancers; intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization; development of 
drug dependency or drug abuse; or suspected transmission of an infectious agent via a medicinal 
product. 


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9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Events Form in the eCRF. All AEs/SAEs should be reported for enrolled participants, but 
only SAEs need to be reported for screen failure participants. For enrolled participants, conditions 
that were present at the time informed consent was given should be recorded on the Medical History 
Form in the eCRF. For detailed information, refer to the eCRF guidelines. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or designee) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Events Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested. In this 
case, all participant identifiers, with the exception of the participant ID number, will be redacted by 
the site staff on the copies of the medical records before submission. These records can be submitted 
to Incyte Pharmacovigilance by email/fax per the contact information listed as per SAE completing 
guidelines. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. When a clear diagnosis cannot be identified, each sign or symptom 
should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine the following: 
• The severity grade (CTCAE v5.0 Grade 1 to 5). See below for further instructions on the assessment 
of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug: suspected 
(yes) or not suspected (no). See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event. Note: If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on the Adverse Events Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures, and 
Non-Drug Therapy). 
Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5. If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate 
the grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 


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• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2: Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4: Life-threatening consequences; urgent treatment indicated. 
• Grade 5: Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB for study drug, in making their assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that they have reviewed the 
AE/SAE and have provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report. However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements. Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change their opinion of causality in light of follow-up information and 
submit the updated causality assessment. 
Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the Adverse Events Form in the eCRF until it has 
resolved or until it is judged to be permanent; assessment should be made at each visit (or more 
frequently if necessary) of any changes in severity, the suspected relationship to the study drug, the 
interventions required to treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology. 


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• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance (either via email/fax if paper SAE form is used or in the SAE EDC CRF) until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedure[s]), all SAEs 
occurring after the participant has signed the ICF through the last study visit or at least 30 days 
after the last application of study drug must be reported to the sponsor (or designee) 
immediately, without undue delay but not later than within 24 hours of obtaining knowledge of 
its occurrence unless otherwise specified by the Protocol. The investigator will submit any 
updated SAE data to the sponsor (or designee) immediately, without undue delay but not later 
than within 24 hours of it being available. 
Investigators are not obligated to actively seek SAE information after the safety follow-up visit 
or more than 30 days after the last dose of study drug. If the investigator learns of any SAE, 
including death, at any time during this period, and they consider the event to be reasonably 
related to the study drug or study participation, then the investigator must notify the sponsor (or 
designee) within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB (new occurrence) and is thought to be related 
to the study drug, the sponsor or its designee may urgently require further information from the 
investigator for expedited reporting to health authorities. The sponsor or its designee may need to 
issue an Investigator Notification to inform all investigators involved in any study with the same 
drug that this SAE has been reported. Suspected unexpected serious adverse reactions will be 
collected and reported to the competent authorities and relevant ethics committees in accordance 
with Directive 2001/20/EC or per national regulatory requirements in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 


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Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Events Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available). The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual or the Incyte Reference Guide for Completing the 
Serious Adverse Event Report Form. 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Report Form. Once the EDC system is functional, the 
SAE report should be retrospectively added to the EDC system and follow-up should be completed 
through the EDC. The original copy of the Serious Adverse Event Report Form and the email or 
facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference Guide for 
Completing the Serious Adverse Report Form or Study Reference Manual for details and for the 
email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system. The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation). Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs. 
9.5. 
Potential Drug-Induced Liver Injury 
Not applicable. 
9.6. 
Events of Clinical Interest 
Not applicable. 
9.7. 
Emergency Unblinding of Treatment Assignment 
In case of a medical emergency, for a participant's safety management, the procedure for 
emergency unblinding is provided to the investigator in the IRT Manual. The IRT system has an 
option to select for "Emergency Code Break" action for a given participant. After entering the 
study drug tube number and verification of the unmasking information, the 
investigator/subinvestigator will proceed to either final confirmation or cancellation of the code 
break procedure. 
If a participant's treatment assignment is unblinded, the sponsor or its designee should be notified 
immediately by telephone for awareness. 
If an investigator, the site staff performing assessments, or a participant is inadvertently 
unblinded, then the participant must discontinue study drug unless there are ethical reasons to 
have the participant remain on the study treatment. In these cases, the investigator must obtain 
specific approval from the sponsor's (or its designee's) medical monitor for the participant to 
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9.8. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method. When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluations. 
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications by following until the first 
well-baby visit. Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee. Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later. Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during the pregnancy of a study participant must be recorded and 
reported as described in Section 9.4. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4. If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.9. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB. Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications. Any 
important new safety information should be discussed with the participant during the study as 
necessary. If new significant risks are identified, they will be added to the ICF. 
9.10. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor. All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 


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The investigator or their designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information. Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, they will return a copy of the 
product complaint communication with the product. 
9.11. 
Treatment of Overdose 
There has been no clinical experience with overdose resulting from excessive use of ruxolitinib 
cream. Treatment of overdose should consist of general supportive measures. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
Approximately 60 participants will be randomized 1:1 to ruxolitinib cream 1.5% BID or vehicle 
BID. The sample size was not calculated based on statistical power calculations, but for 
demonstration of preliminary findings of clinical response. It is anticipated that a sample size of 
approximately 60 participants will permit sufficient data to be generated to assess whether 
ruxolitinib cream warrants further investigation in HS. Also, the sample size is considered 
sufficient to provide enough data for an initial evaluation of the safety profile. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 10. 
Table 10: 
Populations for Analysis 
Population 
Description 
ITT 
The ITT population includes all randomized participants. Treatment groups for this 
population will be defined according to treatment assignment at randomization. 
Safety 
The safety population includes all participants who applied study drug at least once. 
Treatment groups for this population will be determined according to the actual 
treatment the participant received on Day 1. 
10.3. 
Level of Significance 
Given that the sample size is not based on the statistical power, the significance level for primary 
efficacy analysis will be 0.1 for a two-sided test. 
10.4. 
Statistical Analyses 
10.4.1. 
Primary Analysis 
The primary analysis will be based on the ITT population. The summary of primary endpoint 
analysis is provided in Table 11. 


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Table 11: 
Summary of Primary Analysis 
Parameter 
Definition 
Treatment effect 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population 
ITT Population 
Variable 
Change from baseline in AN count at Week 16 
Population-level summary 
Mean Change from baseline in AN count at Week 16 
Note: All randomized participants, including those with missing Week 16 data, and those who discontinue study 
treatment at any time before the timepoint of interest, or discontinue from the study for any reason, will be 
included for the primary analysis. No rescue therapy or treatment switch is allowed in this study. 
The primary efficacy analysis will compare ruxolitinib 1.5% cream versus vehicle cream in the 
mean change from baseline in AN count using a MMRM. The MMRM will include the fixed 
effect of treatment group (ruxolitinib 1.5% and vehicle cream), stratification factor (AN count 
≥ 3 to 4 or AN count ≥ 5 to 10 at baseline), visit, and visit by treatment interaction. The 
variance-covariance matrix of the within-participant errors in MMRM will be modeled as 
unstructured. 
The primary alternative hypothesis (superiority of active ruxolitinib 1.5% cream BID group 
compared with vehicle) will be tested at a 2 sided α = 0.1 level using the least square mean 
estimate of the change from baseline in AN count at Week 16 from the MMRM specified above. 
Subgroup analysis by baseline characteristics will be performed. 
10.4.2. 
Secondary Analysis 
All secondary and 
 efficacy variables will be summarized using descriptive statistics 
based on the ITT population. For categorical measurements, summary statistics will include 
sample size, frequency, and percentages. For continuous measurements, summary statistics will 
include sample size, mean, median, standard deviation, standard error of the mean, minimum, 
and maximum. Summary statistics for continuous measures will be provided for baseline, the 
actual measurements at each visit, and the change and percentage change from baseline at each 
visit, if applicable. The Skin Pain NRS score for each visit will be determined by averaging the 
7 daily Skin Pain NRS scores before the corresponding visit day. If 4 or more daily scores are 
missing (out of the 7), the Skin Pain NRS score at the visit will be set to missing. The Itch NRS 
score for each visit will be determined using a similar approach. 
10.4.3. 
Safety Analyses 
Safety analyses will be conducted for the safety population. 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first application of study drug. Analysis of AEs will be limited to TEAEs, but data listings will 
include all AEs regardless of their timing to study drug administration. Adverse events will be 
tabulated by the MedDRA preferred term and system organ class. Severity of AEs will be based 
on the National Cancer Institute CTCAE v5.0 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a causal relationship to study drug will 
be considered treatment-related AEs. If the investigator does not specify the relationship of the 


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AE to study drug, then the AE will be considered treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. 
The clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned. Laboratory test values outside the normal range will be assessed for 
severity based on the normal ranges for the clinical reference laboratory. The incidence of 
abnormal laboratory values and shift tables relative to baseline will be tabulated. Descriptive 
statistics and mean change from baseline will be determined for vital signs (blood pressure, 
pulse, respiratory rate, and body temperature) at each assessment time. 
10.5. 
Interim Analysis 
There is no planned interim analysis for the study. There are 2 formal planned analyses: 
• The primary analysis will occur after the primary database lock, when all participants 
have completed the DBVC period. 
 
 
 
• The final analysis will occur when all participants have completed or withdrawn from 
the study. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol Amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC and health authorities, before the study is 
initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC. Each investigator is responsible for enrolling participants who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study during the 
retention period without receiving approval from the sponsor. The investigator 
must notify the sponsor or its designee in the event of accidental loss or 
destruction of any study records. If the investigator leaves the institution where 
the study was conducted, the sponsor or its designee must be contacted to arrange 
alternative record storage options. 


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− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations. 
The sponsor will retain the original eCRF data and audit trail. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study. As part of his or her responsibilities, the coordinating principal investigator will review 
the final CSR. Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system. The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF. The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements. Other data outside the EDC system required in the study conduct of 
the Protocol, such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and as designated by the sponsor, will have their own data flow 
management plans, study charters, 
, as applicable. 
The sponsor (or designee) will be responsible for the following: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated and/or collected, including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for the following: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
, photographs, diary data) 
or as otherwise specified in the Protocol. 


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• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail). Source data are, in general, all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data are contained in source 
documents (original records or certified copies). 
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed and 
available at the investigator's site. Examples of source documents are original 
documents, data, and records (eg, hospital records; electronic hospital records; 
clinical and office charts; laboratory notes; memoranda; participants' diaries or 
evaluation checklists; pharmacy dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiches; photographic negatives; microfilm or 
magnetic media; x-rays; participants' files; and e-records/records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in 
the clinical trial). 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, 
depending on the study. Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor. 
− As required by privacy and data protection regulations and Incyte's privacy 
policies, if any photographs of participants are to be taken, the photographs must 
be limited to the area of the face or the body that is strictly necessary and the 
photographs should be masked (ie, identifying features such as eyes, mouth, scars, 
tattoos, or unique markings or features should be either obscured with a black bar 
or digitally pixelated so as to not permit the reidentification of the participants and 
preserve their confidentiality) by a specially designated photography vendor prior 
to sending the photographs to Incyte or any other third-party vendors for analysis 
or further processing. 


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− In accordance with French regulations, sites in France must perform the masking 
before the photographs are transferred, including to any specially designated 
photography vendor, Incyte, or any other third-party vendors for analysis or 
further processing. In addition, the participant's specific consent for photographs 
shall be collected. 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring: Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan. The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing: Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct. The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection: Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product. The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents. The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Quality Assurance 
The sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations). The sponsor or designee is responsible for the data management of this 
study, including quality checking of the data. Further, monitoring details describing strategy, 
including definition of study critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical 
risk-based monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues, Protocol deviations, and monitoring techniques (eg, central, remote, or 
on-site monitoring) are provided in the Data Management Plan and the Monitoring Plan. 
Quality tolerance limits will be predefined in the Integrated Project Management Plan to identify 
systematic issues that can impact participant’s safety, efficacy results and analysis, and/or 
reliability of study results. These predefined parameters will be monitored during the study and 
can be adjusted during the study upon data review. Important deviations from the QTLs and 
remedial actions taken, including reporting to IRBs/ECs and health authorities if applicable, will 
be summarized in the clinical study report. 


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11.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations. The investigator and the sponsor or its designee are responsible for ensuring that 
personal information is handled in accordance with local data protection laws (including but not 
limited to HIPAA and GDPR) as applicable. Appropriate notice, or notice and consent (as may 
be required by each applicable jurisdiction), for collection, use, disclosure and/or transfer (if 
applicable) of personal information must be obtained in accordance with local data protection 
laws. 
Participant names will not be supplied to the sponsor or its designee. Only the participant number 
will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee. Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
11.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply. For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator. These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form. During a covered clinical study, any 
changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee. At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations. In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.6. 
Publication Policy 
By signing the study Protocol, the investigator and their institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals. Study results will be published in accordance with applicable local and national 
regulations. If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement. The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee. A signed agreement will 
be retained by the sponsor or its designee. 


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The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.7. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
Alavi A, Hamzavi I, Brown K, et al. Janus kinase 1 inhibitor INCB054707 for patients with 
moderate-to-severe hidradenitis suppurativa: results from two phase II studies. Br J Dermatol 
2022;186:803-813. 
Canoui-Poitrine F, Le Thuaut A, Revuz JE, et al. Identification of three hidradenitis suppurativa 
phenotypes: latent class analysis of a cross-sectional study. J Invest Dermatol 
2013;133:1506-1511. 
Chapman S, Kwa M, Gold LS, Lim HW. Janus kinase inhibitors in dermatology: Part I. A 
comprehensive review. J Am Acad Dermatol 2022;86:406-413. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
 
 
Frew JW. Therapeutic biomarkers in hidradenitis suppurativa: one step closer to the clinic. Br J 
Dermatol 2021;185:696-697. 
Frew JW, Jiang CS, Singh N, et al. Clinical response rates, placebo response rates, and 
significantly associated covariates are dependent on choice of outcome measure in hidradenitis 
suppurativa: a post hoc analysis of PIONEER 1 and 2 individual patient data. J Am Acad 
Dermatol 2020;82:1150-1157. 
 
 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
Jemec GBE, Kimball AB. Hidradenitis suppurativa: epidemiology and scope of the problem. J 
Am Acad Dermatol 2015;73(suppl 1):S4-S7. 
Kelly G, Prens EP. Inflammatory mechanisms in hidradenitis suppurativa. Dermatol Clin 
2016;34:51-58. 
Kimball AB, Sobell JM, Zouboulis CC, 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. 
 
 
 
Kurek A, Johanne Peters EM, Sabat R, Sterry W, Schneider-Burrus S. Depression is a frequent 
co-morbidity in patients with acne inversa. J Dtsch Derm Ges 2013;11:743-750. 
Opzelura (ruxolitinib) cream 1.5% [prescribing information]. Incyte Corporation; September 
2021. 


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Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the 
treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am 
Acad Dermatol 2021;85:863-872 
 
 
Rumberger BE, Boarder EL, Owens SL, Howell MD. Transcriptomic analysis of hidradenitis 
suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis. 
Inflamm Res 2020;69:967-973. 
Ruxolitinib Cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Sabat R, Jemec GBE, Matusiak Ł, Kimball AB, Prens E, Wolk K. Hidradenitis suppurativa. Nat 
Rev Dis Primers 2020;6:18. 
Saunte DML, Jemec GBE. Hidradenitis suppurativa: advances in diagnosis and treatment. JAMA 
2017;318:2019-2032. 
Schneider-Burrus S, Jost A, Peters EMJ, Witte-Haendel E, Sterry W, Sabat R. Association of 
hidradenitis suppurativa with body image. JAMA Dermatol 2018;154:447-451. 
Zouboulis CC, Benhadou F, Byrd AS, et al. What causes hidradenitis suppurativa? — 15 years 
after. Exp Dermatol 2020;29:1154-1170. 
Zouboulis CC Desai N, Emtestam L, et al. European S1 guideline for the treatment of 
hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol 2015;29:619-644. 
Zouboulis CC, Frew JW, Giamarellos-Bourboulis EJ, et al. Target molecules for future 
hidradenitis suppurativa treatment. Exp Dermatol 2021;30(suppl 1):8-17. 
Zouboulis CC, Tzellos T, Kyrgidis A, et al. 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. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS 
Definitions 
WOCBP: A woman who is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal with 1 of the following:a 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
• Postmenopausal 
− A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or HRT. However, in the absence of 12 months of 
amenorrhea, confirmation with 2 FSH measurements in the postmenopausal range is required.  
Female participants on HRT and whose menopausal status is in doubt will be required to use 1 of the 
nonhormonal, highly effective contraception methods if they wish to continue their HRT during the study. 
Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. 
For male participants of reproductive potentialb 
The following methods during the Protocol-defined timeframe in Section 5.1 are highly effective: 
• Use of a male condom plus partner use of an additional contraceptive method when having penile-vaginal 
intercourse with a WOCBP who is not currently pregnant 
• Vasectomy with medical assessment of the surgical success (verified by site personnel's review of the 
participant's medical records) 
• Sexual abstinencec 
− Abstinence from penile-vaginal intercourse 
The following are not acceptable methods of contraception: 
• Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method 
• Male condom with cap, diaphragm, or sponge with spermicide 
• Male and female condom used together 
Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration. 


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 that can achieve a failure rate of less 
than 1% per year when used consistently and correctly are considered as highly effective birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationd 
− oral 
− intravaginal  
− transdermal  
• Progestogen-only hormonal contraception associated with inhibition of ovulationd 
− oral 
− injectable 
− implantablee 
• Intrauterine devicee 
• Intrauterine hormone-releasing systeme 
• Bilateral tubal occlusione 
• Vasectomized partnere,f 
• Sexual abstinencec 
a Documentation can come from the site personnel's review of the participant's medical records, medical examination, or medical 
history interview. 
b If the male participant has a partner of childbearing potential, the partner should also use contraceptives. 
c In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. 
d Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may reduce the 
efficacy of the contraception method. In this case, 2 methods of contraception should be used. 
e Contraception methods that in the context of this guidance are considered to have low user dependency. 
f Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success. 
Source: Clinical Trials Facilitation and Coordination Group 2020. 


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APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical trials. The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the investigational 
product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the trial. Because of this risk and 
in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines: 
In addition to the remote visits already specified in the Protocol, the evolving situation of the 
pandemic may require further travel restrictions and isolation requirements, or the investigator's 
benefit/risk assessment may determine it to be unsafe for participants to attend study visits at the 
investigational site. In such cases, the site staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video calls). At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed. Periodic on-site visits 
should be conducted whenever feasible, in addition to the mandatory on-site visits 
outlined below. 
• No efficacy assessments can be performed via telemedicine (video call or phone call). 
• Laboratory sampling: in order to support investigator oversight of participant safety 
and disease management, off-site laboratory sampling (in accordance with the SoA, 
see Table 3) may be allowed in 1 of 2 ways: 
− Use of home nursing services. 
− Instruct the participant to undergo some laboratory tests at a local (nearby) 
hospital laboratory or facility closer to the participant's residence rather than at the 
investigational site. In this case, the study physician will provide the participant 
with the list of parameters to be checked. These tests should be performed at 
certified laboratories and copies of results provided to the site. 


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Mandatory On-Site Visits: 
The visits outlined below must be performed in person in order to capture the investigator's 
efficacy assessments and the patient-reported outcomes, even if the date that the participant 
eventually comes into the clinic deviates from the visit window. 
No efficacy assessments can be performed via telemedicine (video call, phone call, or 
photography). 
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic. Further instructions 
will be provided if needed. 
During the DBVC period, the following visits must be performed in person: 
• Screening 
• Day 1 (baseline) 
• Week 16 visit 
During the OLE period, the following visits must be performed in person: 
• Week 32 visit 
Investigational Medicinal Product Dispensing and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug via shipment 
to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study drug 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant. 
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the site monitor will continue to employ off-site monitoring practices such as routine 
communication methods (eg, phone calls, e-mails, video visits) with the sites to get information 
on trial progress, participant status, and information on issue resolution. The study monitor may 
remotely review data entered into the EDC for accuracy and completeness. If allowed by local 
regulations, remote source data verification may be implemented with agreement of the principal 
investigator and institution, as applicable. 
If the study-site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 


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training. The study drug can be returned to the sponsor by the hospital pharmacy directly or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Other Considerations 
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight. In such situations, the investigator is required to provide the 
local physician with a delegation letter listing all delegated activities. The sponsor, through the 
study investigator or institution, will reimburse the local physician for the tests/procedures 
conducted outside of the standard of care. 
• In case of need, participants may refer to the local health care provider. Participants will 
be requested to obtain certified copies of the source data at the local health facility with 
the outcome of the contact and provide those to the investigator for appropriate oversight. 
The investigator/delegate will be requested to enter any relevant information into the 
EDC. 
• Should COVID-19–related restrictions be localized and have an effect on a limited 
number of sites, the affected sites may utilize direct contracting of third parties to support 
continuous study conduct (eg, home nursing services, couriers, etc). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [nearby] laboratory tests). 


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APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Not applicable. 


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SAP_001.pdf: 
Official Title: A Phase 2, Double-Blind, Randomized, Vehicle Controlled, Efficacy, 
and Safety Study of Ruxolitinib Cream in Participants With Hidradenitis Suppurativa
NCT Number: NCT05635838
Document Date: Statistical Analysis Plan: 12 SEP 2023


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Statistical Analysis Plan 
TITLE PAGE 
INCB 18424-221
A Phase 2, Double-Blind, Randomized, Vehicle-Controlled, Efficacy, 
and Safety Study of Ruxolitinib Cream in Participants With 
Hidradenitis Suppurativa 
IND Number: 
77,101 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol dated 19 AUG 2022 
CRF Approval Date: 
14 AUG 2023 
SAP Version: 
Original 
SAP Author: 
Biostatistician 
Date of Plan: 
12 SEP 2023 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
3. 
STUDY DESIGN .......................................................................................................10 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Considerations .......................................................................................11 
3.4. 
Schedule of Assessments ............................................................................................11 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................12 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................12 
4.1.1. 
Day 1 ...........................................................................................................................12 
4.1.2. 
Study Day ...................................................................................................................12 
4.1.3. 
Baseline Value ............................................................................................................12 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................13 
4.2. 
Variable Definitions ....................................................................................................13 
4.2.1. 
Body Mass Index ........................................................................................................13 
4.2.2. 
Prior and Concomitant Medications ...........................................................................13 
5. 
STATISTICAL METHODOLOGY ...........................................................................14 
5.1. 
General Methodology .................................................................................................14 
5.2. 
Treatment Groups .......................................................................................................14 
5.3. 
Analysis Populations ..................................................................................................14 
5.3.1. 
Intent-to-Treat Population ..........................................................................................14 
5.3.2. 
Safety Population ........................................................................................................15 
5.3.2.1. 
Open-Label Extension Safety Population ...................................................................15 
 
15 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................16 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................16 


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6.1.1. 
Demographics and Baseline Characteristics ...............................................................16 
6.1.2. 
Baseline Disease Characteristics ................................................................................16 
6.1.3. 
Disease History ...........................................................................................................17 
6.1.4. 
Medical History ..........................................................................................................17 
6.2. 
Disposition of Participant ...........................................................................................17 
6.3. 
Protocol Deviations ....................................................................................................17 
6.4. 
Exposure .....................................................................................................................17 
6.5. 
Study Drug Compliance .............................................................................................18 
6.6. 
Prior and Concomitant Medications ...........................................................................18 
7. 
EFFICACY .................................................................................................................19 
7.1. 
Efficacy Hypothesis ....................................................................................................19 
7.2. 
Efficacy Measures ......................................................................................................19 
7.2.1. 
Lesion Counts .............................................................................................................19 
7.2.1.1. 
Abscess and Inflammatory Nodule Counts ................................................................19 
7.2.1.2. 
Hidradenitis Suppurativa Clinical Response ..............................................................19 
7.2.1.3. 
International Hidradenitis Suppurativa Severity Score System ..................................19 
 
20 
7.2.2. 
Hurley Stages of Hidradenitis Suppurativa ................................................................20 
7.2.3. 
Body Surface Area ......................................................................................................20 
7.2.4. 
Patient-Reported Outcomes ........................................................................................20 
7.2.4.1. 
Skin Pain Numerical Rating Scale ..............................................................................20 
7.2.4.2. 
Itch Numerical Rating Scale .......................................................................................21 
 
21 
 
.21 
 
.22 
 
23 
 
23 
 
24 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................24 
7.3.1. 
Primary Efficacy Analysis ..........................................................................................24 
7.3.2. 
Subgroup Analyses for Primary Endpoint ..................................................................25 
7.4. 
Analysis of the Secondary Efficacy Parameters .........................................................25 
7.4.1. 
Continuous Efficacy Endpoints ..................................................................................25 


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7.4.2. 
Categorical Efficacy Endpoints ..................................................................................25 
 
26 
 
27 
 
27 
 
27 
9. 
SAFETY AND TOLERABILITY ..............................................................................28 
9.1. 
General Considerations ...............................................................................................28 
9.2. 
Adverse Events ...........................................................................................................28 
9.2.1. 
Adverse Event Definitions ..........................................................................................28 
9.2.2. 
Adverse Event Summaries ..........................................................................................28 
9.3. 
Clinical Laboratory Tests ...........................................................................................29 
9.3.1. 
Laboratory Value Definitions .....................................................................................30 
9.3.2. 
Laboratory Value Summaries .....................................................................................30 
9.4. 
Vital Signs ..................................................................................................................30 
10. 
PLANNED ANALYSES ............................................................................................32 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................33 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................33 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................33 
12. 
REFERENCES ...........................................................................................................34 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................35 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Hurley Stages of Hidradenitis Suppurativa ................................................................20 
Table 3: 
Summary of Primary Analysis....................................................................................24 
Table 4: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................31 
Table 5: 
Statistical Analysis Plan Versions ..............................................................................33 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................10 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
AN 
abscess and inflammatory nodule 
ASR 
application site reaction 
BID 
twice daily 
BMI 
body mass index 
BSA 
body surface area 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBVC 
double-blind, vehicle-controlled 
 
 
eCRF 
electronic case report form 
 
 
EQ VAS 
EuroQol visual analogue scale 
HiSCR 
hidradenitis suppurativa clinical response 
 
 
HS 
hidradenitis suppurativa 
IHS4 
International Hidradenitis Suppurativa Severity Score System 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measures 
NRS 
numeric rating scale 
OLE 
open-label extension 
 
 
 
 
PRO 
patient-reported outcome 
PT 
preferred term 
Q# 
Question <number> 
SAP 
Statistical Analysis Plan 
SI 
International System of Units 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WHO 
World Health Organization 
 
 


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1. 
INTRODUCTION 
INCB 18424-221 is a Phase 2, randomized, DBVC, efficacy, and safety study in participants 
aged ≥ 18 years with a diagnosis of HS. The study will consist of a 16-week DBVC period 
followed by a 16-week OLE period. A 30-day post-treatment safety follow-up visit will be 
conducted after the OLE period. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 18424-221 Protocol. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 18424-221 Protocol dated 19 AUG 2022 and CRFs approved 
14 AUG 2023. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% cream 
BID in participants with HS. 
Change from baseline in AN count at Week 16. 
Secondary 
To further evaluate the treatment effect of ruxolitinib 
1.5% cream BID in participants with HS. 
• Change from baseline to Week 16 in total 
AN count in anatomical areas with pre-existing 
AN at baseline. 
Note: Pre-existing AN at baseline are defined as 
abscesses and/or inflammatory nodules present at 
baseline. 
• Proportion of participants achieving AN50, 
AN75, AN90, and AN100 (at least 50%, 75%, 
90%, and 100% reduction, respectively, in 
AN count relative to baseline) at Week 16. 
• Change from baseline in the Skin Pain NRS score 
at Week 16. 
• Change from baseline in the Itch NRS score at 
Week 16. 
• Proportion of participants who achieve HiSCR at 
Week 16. 
Note: HiSCR is defined as at least 50% reduction 
in AN count with no increase in either abscess or 
draining fistula counts, relative to baseline. 
• Change from baseline in the IHS4 score at 
Week 16. 
• Note: IHS4 score is calculated by the number of 
inflammatory nodules (multiplied by 1) plus the 
number of abscesses (multiplied by 2) plus the 
number of draining tunnels (multiplied by 4). 
To evaluate the safety and tolerability of ruxolitinib 
1.5% cream BID in participants with HS. 
The type, frequency, and severity of AEs, and 
changes in vital signs and hematology and serum 
chemistry parameters. 


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Table 1: 
Objectives and Endpoints (Continued) 


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3. 
STUDY DESIGN 
This is a Phase 2, randomized, DBVC study in participants aged ≥ 18 years with confirmed 
diagnosis of HS. The study will consist of a 16-week DBVC period followed by a 16-week 
OLE period.  
Participants will be screened for up to 28 days prior to the first application of ruxolitinib 
1.5% cream or vehicle cream. Approximately 60 eligible participants aged ≥ 18 years will be 
randomized 1:1 to either ruxolitinib 1.5% cream or vehicle cream. Participants will be stratified 
by baseline AN count (ie, ≥ 3 to 4 or ≥ 5 to 10). Participants will apply either ruxolitinib 
1.5% cream BID or vehicle cream BID through Week 16 to all affected areas identified at 
baseline. At Week 16, participants who meet the criteria (compliant with the Protocol and 
without safety concerns) will enter the 16-week OLE period. Participants randomized to 
vehicle BID in the DBVC period will be crossed over to ruxolitinib 1.5% cream BID and 
participants randomized to ruxolitinib 1.5% cream BID at baseline will remain on ruxolitinib 
1.5% cream BID through Week 32 in an open-label fashion. Participants will enter the 30-day 
safety follow-up period after the last application of study treatment. 
The study schema is shown below in Figure 1. 
Figure 1: 
Study Design Schema 
 
Abbreviations: Rux = ruxolitinib. 
The primary analysis will occur after the primary database lock, when all participants have 
completed or discontinued from the DBVC period. The final analysis will occur when all 
participants have completed or withdrawn from the study, whichever comes first. 
3.1. 
Randomization 
Approximately 60 participants will be randomized 1:1 to either ruxolitinib 1.5% cream BID or 
vehicle cream. Participants will be stratified by baseline AN count (ie, ≥ 3 to 4 or ≥ 5 to 10). 
3.2. 
Control of Type I Error 
The significance level for primary efficacy analysis will be 0.1 for a 2-sided test.  
16 weeks
Vehicle cream BID
(N = 30 patients)
RUX 1.5% BID
(N = 30 patients)
-
Open-Label
Extension
16 weeks
• Age ≥ 18 years
• Diagnosis of HS ≥ 3 months
• 3 to ≤ 10 AN
Randomization (1:1)
Safety Follow-Up (30 days)
Investigator’s Assessment 
Recurrence 
of AN
Triggers for 
starting/ending 
cycles
Clearance of 
AN
RUX 1.5% 
BID
No 
treatment
Double-Blind, Vehicle-Controlled 
Treatment Period
Open Label Extension 
Treatment Period
Enrollment


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3.3. 
Sample Size Considerations 
Approximately 60 participants will be randomized 1:1 to ruxolitinib 1.5% cream BID or 
vehicle BID. The sample size was not calculated based on statistical power calculations, but for 
demonstration of preliminary findings of clinical response. It is anticipated that a sample size of 
approximately 60 participants will 1) generate sufficient data to assess whether ruxolitinib 
1.5% cream warrants further investigation in HS, and 2) be sufficient to provide enough data for 
an initial evaluation of the safety profile of ruxolitinib 1.5% cream in HS. 
3.4. 
Schedule of Assessments 
Refer to Protocol dated 19 AUG 2022 for a full description of all study procedures and 
assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first application of ruxolitinib 1.5% cream or vehicle cream is 
administered to the participants in the specific period. 
For randomized participants not treated with any study drug, Day 1 is defined as the date of 
randomization. 
 
 
 
 
 
 
 
 
 
4.1.3. 
Baseline Value 
For the DBVC period, baseline is the last nonmissing measurement obtained before or on the day 
of the first application of ruxolitinib 1.5% cream or vehicle cream in the DBVC period, unless 
otherwise defined. 
For randomized participants not treated with any study drug, baseline is defined as the last 
nonmissing assessment before or on the date of randomization. 
For participants who continue in the OLE period, baseline is defined as follows: 
• For efficacy evaluation in the OLE period, baseline is the last nonmissing 
measurement obtained before or on the day of first application of study treatment in 
the DBVC period. 
• For safety evaluation in the OLE period, baseline is the last nonmissing measurement 
obtained before or on the day of first application of ruxolitinib 1.5% cream in the 
study. 
When a scheduled assessment and an unscheduled assessment occur on the same day and the 
times of the assessments are not available, use the following convention to determine baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first 
application and the time is missing, use the scheduled assessment as baseline. 
• If the scheduled assessment is missing on the day of the first application and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 


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4.1.4. 
Handling of Missing and Incomplete Dates 
In general, values for missing dates will not be handled unless methods for handling missing 
dates are specified in this section or relevant sections. The original reported dates collected on 
the eCRF should be used in all relevant listings. The following rules will be used for handling 
partial dates for analyses requiring dates. 
Partial HS diagnosis date will be handled, as follows, in the calculation: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 
When the date of the last application is used in deriving variables, such as duration of treatment 
or TEAE flag, a missing date of the last application in the specified treatment period will be 
handled as follows: 
• If the last application date is missing, then the end date of the specified treatment 
period will be used as the date of the last application. 
• If the last application date and the end date of the specified treatment period are both 
missing and the participant is lost to follow-up, then the date of last contact will be 
used as the date of the last application. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.2. 
Prior and Concomitant Medications 
A prior medication is defined as any nonstudy medication started before the first application of 
ruxolitinib 1.5% cream or vehicle cream. 
A concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first application of ruxolitinib 1.5% cream or vehicle cream and is 
ongoing throughout the study or ends on/after the date of first study drug application. 
• On/after the date of first application of ruxolitinib 1.5% cream or vehicle cream and is 
ongoing or ends during the course of the study. 


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A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first application of ruxolitinib 1.5% cream or vehicle cream. In the listing, it 
will be indicated whether a medication is only prior, only concomitant, or both prior and 
concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 
5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9.4 or later) will be used 
for the generation of all tables, graphs, and statistical analyses. Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum. Descriptive summaries for categorical 
variables will include the number and percentage of participants in each category. 
5.2. 
Treatment Groups 
This is a randomized study with DBVC and OLE periods. 
Efficacy data will be presented by treatment group assigned at study entry for the 
ITT population. The treatment groups will be 1.5% BID (ie, ruxolitinib 1.5% cream BID) and 
vehicle BID. 
Safety data will be presented by treatment group that participants actually applied. 
• For safety data in the DBVC period, the treatment groups will be 1.5% BID and 
vehicle BID. 
• For safety data in the OLE period, the treatment groups will be 1.5% BID to 
1.5% BID and vehicle BID to 1.5% BID. 
• For safety data throughout the study, the only treatment group will be 1.5% BID, 
including participants who applied ruxolitinib 1.5% cream BID from Day 1 through 
Week 32 or end of study treatment. 
5.3. 
Analysis Populations 
5.3.1. 
Intent-to-Treat Population 
All participants who are randomized will constitute the ITT population. Treatment groups for 
this population will be defined according to the treatment assignment at the time of 
randomization regardless of the actual study drug the participant might take during their 
participation in the DBVC period. 
The ITT population will be used for the summary of demographics, baseline characteristics, 
participant disposition, medical history, prior and concomitant medications, and analyses of all 
efficacy data, unless otherwise specified. 


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5.3.2. 
Safety Population 
The safety population will include all participants who applied ruxolitinib 1.5% cream or vehicle 
cream at least once. Treatment groups for this population will be determined according to the 
actual treatment the participant applied on Day 1 regardless of assigned treatment group. 
The safety population will be used for safety summaries in the DBVC period. 
5.3.2.1. 
Open-Label Extension Safety Population 
The OLE safety population includes all participants who applied ruxolitinib 1.5% cream BID at 
least once during the OLE period. 
All safety analyses conducted specifically for the OLE period will use the OLE safety 
population. 
 
 
 
 
 
 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of planned tables, figures, and listings. Sample data displays are 
included in a separate document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics and baseline characteristics will be summarized by treatment group 
and overall for the ITT population in the DBVC period and for the OLE safety population in the 
OLE period: age, sex, race, ethnicity, weight, height, and BMI. 
6.1.2. 
Baseline Disease Characteristics  
For the ITT population, the baseline disease characteristics will be summarized and analyzed by 
treatment group and will include, but not be limited to the following:  
• Disease duration (months) 
• Prior surgical treatment for HS (yes [incision and drainage, deroofing, or other]/no) 
• Prior therapy received for HS 
• HS family history (yes/no) 
• Selected comorbidities 
• Number of anatomical areas with HS 
• Days since onset of current episode of HS flare/activity 
• Number of HS flares since diagnosis 
• Hurley stage 
• AN count category (≥ 3 to 4 or ≥ 5 to 10) 
• AN count 
• Inflammatory nodule count 
• Abscess count 
• Nondraining tunnel count 
• Draining tunnel count 
• Skin Pain NRS score 
• Itch NRS score 
• Total BSA involvement 


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6.1.3. 
Disease History 
The time since diagnosis will be summarized for all participants in the ITT population. 
Time since diagnosis will be calculated as follows: 
Disease duration (months) = (date of randomization – date of initial HS diagnosis +1) / 
30.4375. 
6.1.4. 
Medical History 
For participants in the ITT population during the DBVC period, medical history will be 
summarized by assigned treatment groups. This summary will include the number and 
percentage of participants with medical history for each body system/organ class as documented 
on the eCRF. 
6.2. 
Disposition of Participant 
The number and percentage of participants who were randomized, treated, and completed the 
DBVC period, as well as the number and percentage of participants who discontinued the 
treatment or withdrew from the study during the DBVC period with a primary reason for 
discontinuation, will be summarized for the ITT population. 
The number and percentage of participants who completed the OLE period, in addition to those 
participants who discontinued treatment or withdrew from the study during the OLE period with 
a primary reason for discontinuation, will be summarized for the OLE safety population. 
6.3. 
Protocol Deviations 
For participants in the ITT population in the DBVC period, as well as the OLE safety population 
in the OLE period, Protocol deviations recorded on the eCRF will be summarized and listed by 
category (critical, major, or minor) for each treatment group and overall. 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.6. 
Prior and Concomitant Medications 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
The number and percentage of participants with prior and concomitant medications will be 
summarized by treatment group and overall for the ITT population during the DBVC period by 
WHO drug class and the WHO drug preferred term. For the OLE period, only concomitant 
medications will be summarized based on OLE safety population. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
Efficacy Hypothesis 
The primary hypothesis is that ruxolitinib 1.5% cream BID, compared with vehicle cream BID, 
will improve change in AN count from baseline to Week 16 in participants with HS. 
7.2. 
Efficacy Measures 
7.2.1. 
Lesion Counts 
The HS lesion counts will be assessed at each study visit by the investigator and used for 
calculation of efficacy parameters as follows: AN counts, HiSCR, IHS4, and flare incidence. 
Lesion count and assessment will be recorded in the lesion count worksheet; the assessment of 
anatomical regions includes, but is not limited to the left and right axilla and the left and right 
inguinocrural fold or inframammary areas. 
7.2.1.1. 
Abscess and Inflammatory Nodule Counts 
The AN counts will be recorded at all visits. The AN results will be used to calculate change in 
AN count relative to baseline, as well as AN50, AN75, AN90, and AN100, which are defined as, 
at least, a 50%, 75%, 90%, and 100% decrease, respectively, in AN count relative to baseline. 
7.2.1.2. 
Hidradenitis Suppurativa Clinical Response 
The HiSCR was originally developed based on the underlying Phase 2 trial of adalimumab and 
validated against meaningful changes in pain score and DLQI (Kimball et al 2016, Sabat 
et al 2020). The achievement of HiSCR is defined as at least 50% reduction in AN count with no 
increase in either abscess or draining fistula counts, relative to baseline. In this study, 
participants with draining fistulas (tunnels) will be excluded from the study. Should a 
randomized participant develop a draining tunnel during the study, the participant will be 
discontinued from the study. 
7.2.1.3. 
International Hidradenitis Suppurativa Severity Score System 
The IHS4 (Zouboulis et al 2017) is a composite, dynamic score, and validated tool, used to 
determine HS severity. It employs a weighted scale using the number of inflammatory nodules, 
the number of abscesses, and the number of draining tunnels (eg, fistulas or sinuses), with 
respective weight factors of 1, 2, and 4. For example, IHS4 score equals the number of 
inflammatory nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the 
number of draining tunnels (multiplied by 4). 


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7.2.2. 
Hurley Stages of Hidradenitis Suppurativa 
The Hurley classification is a static score and was originally designed for selection of the 
appropriate treatment modality in a certain body location (Zouboulis et al 2017): medical therapy 
for Stage I, local surgery for Stage II, and wide surgical excision for Stage III (see Table 2). 
Participants who have been diagnosed with HS, Hurley Stage I or II, as per inclusion criterion, 
will be enrolled into the study. The investigator (or designee) will determine the Global Hurley 
Stage in each affected anatomical region at the designated study visits. For each participant, an 
overall Hurley Stage will be derived as the stage of the worst involved anatomical region. The 
number and proportion of participants in each Hurley Stage will be summarized at baseline and 
each postbaseline visit. 
Table 2: 
Hurley Stages of Hidradenitis Suppurativa 
Hurley Stage 
Description 
I 
Abscess formation, single or multiple, without sinus tracts and cicatrization/scarring. 
II 
One or more widely separated recurrent abscesses with tract formation and 
cicatrization/scarring. 
III 
Multiple interconnected tracts and abscesses across the entire area, with diffuse or near 
diffuse involvement. 
7.2.3. 
Body Surface Area 
Total %BSA affected by HS will be used to determine the number of tubes of study drug 
dispensed at each visit. Total %BSA affected will be estimated at each visit as outlined in the 
Protocol. The BSA assessment will be approximated to the nearest 0.1% using the Palmar 
Method as a guide, with the palm plus 5 digits, with fingers tucked together and thumb tucked to 
the side (handprint), considered as 1% BSA and the thumb as 0.1% BSA. 
7.2.4. 
Patient-Reported Outcomes 
Patient-reported outcomes will be assessed at designated visits as outlined in the Protocol. 
For those PROs scheduled to be completed at study visits, on Day 1, the participant will 
complete their PRO after eligibility is met. For subsequent visits after randomization, 
questionnaires will be completed by the participant before site personnel perform any clinical 
assessments to prevent participant bias in their response. 
7.2.4.1. 
Skin Pain Numerical Rating Scale 
Participants will be instructed to complete and record the Skin Pain NRS in a diary each evening, 
beginning on the day of screening through Week 32 or treatment discontinuation, whichever 
comes first. The participants will rate the severity of their pain associated with HS (ie, burning, 


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tearing, pulling, stabbing, etc) by selecting a number from 0 (no pain) to 10 (worst imaginable 
pain) that best describes their worst level of pain in the past 24 hours. 
The Skin Pain NRS score for baseline will be determined by averaging the 7 daily NRS scores 
before Day 1 (ie, Days –7 to –1) for all by-visit summaries. The by-visit Skin Pain NRS score for 
postbaseline visits will be determined by averaging the 7 daily NRS scores before the visit day. 
If 4 or more daily scores are missing (out of the 7), the Skin Pain NRS score at the visit will be 
set to missing. For all the daily pain-related analyses, baseline will be defined as the last 
available daily pain NRS score during the last week prior to Day 1 (ie, Days −7 to −1). 
7.2.4.2. 
Itch Numerical Rating Scale  
The participant will be instructed to complete and record the Itch NRS in a diary each evening 
beginning on the day of screening through Week 32 or treatment discontinuation, whichever 
comes first. The participant will rate the severity of their itch associated with HS by selecting a 
number from 0 (no itch) to 10 (worst imaginable itch) that best describes the worst level of 
itching in the past 24 hours. 
The Itch NRS score for baseline will be determined by averaging the 7 daily NRS scores before 
Day 1 (ie, Days –7 to –1) for all by-visit summaries. The by-visit Itch NRS score for 
postbaseline visits will be determined by averaging the 7 daily NRS scores before the visit day. 
If 4 or more daily scores are missing (out of the 7), the Itch NRS score at the visit will be set to 
missing. For all the daily itch-related analyses, baseline will be defined as the last available daily 
Itch NRS score during the last week prior to Day 1 (ie, Days −7 to −1). 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 


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7.3. 
Analysis of the Primary Efficacy Parameter 
7.3.1. 
Primary Efficacy Analysis 
The primary analysis will be based on the ITT population. The summary of primary endpoint 
analysis is provided in Table 3. 
Table 3: 
Summary of Primary Analysis 
Parameter 
Definition 
Treatment effect 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population 
ITT population 
Variable 
Change from baseline in AN count at Week 16 
Population-level summary 
Mean change from baseline in AN count at Week 16 
Note: All randomized participants, including those with missing Week 16 data, and those who discontinue study treatment at any 
time before the timepoint of interest, or discontinue from the study for any reason, will be included for the primary analysis. No 
rescue therapy or treatment switch is allowed in this study. 
The primary efficacy analysis will compare ruxolitinib 1.5% cream versus vehicle cream in the 
mean change from baseline in AN count using an MMRM. The MMRM will include the fixed 
effect of the treatment group (ruxolitinib 1.5% and vehicle cream), stratification factor 
(AN count ≥ 3 to 4 or AN count ≥ 5 to 10 at baseline), visit, and visit by treatment interaction. 
The variance-covariance matrix of the within-participant errors in MMRM will be modeled as 
unstructured. 
The primary alternative hypothesis (superiority of active ruxolitinib 1.5% cream group compared 
with vehicle cream) will be tested at a 2-sided α = 0.1 level using the least square mean estimate 
of the change from baseline in AN count at Week 16 from the aforementioned MMRM specified. 


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7.3.2. 
Subgroup Analyses for Primary Endpoint 
Subgroups will be formed based on the following participant characteristics and baseline 
variables for those participants whose data are available: 
• Baseline AN count: ≥ 3 to 4 or ≥ 5 to 10 
• Age group: 18 to 29 years or ≥ 30 years 
The primary efficacy endpoint will be summarized and analyzed using descriptive statistics 
based on the ITT population for the aforementioned subgroups. 
7.4. 
Analysis of the Secondary Efficacy Parameters 
All secondary efficacy analyses will be conducted for the ITT population. 
7.4.1. 
Continuous Efficacy Endpoints 
The summary and analysis of statistics for the following continuous measurements, including 
change from baseline, will be presented for each treatment group: 
• Total AN count in anatomical areas with pre-existing AN at Week 16 
• By-visit Skin Pain NRS score at Week 16 
• By-visit Itch NRS score at Week 16 
• IHS4 score at Week 16 
The summary statistics include sample size, mean, median, standard deviation, minimum, 
maximum, first quartile, third quartile, and 95% confidence interval. A similar MMRM, as 
specified in the primary efficacy analysis, may be fit for the comparison between ruxolitinib 
1.5% cream and vehicle cream at Week 16. 
For the endpoint change from baseline in total AN count in anatomical areas with pre-existing 
AN (ie, not including new AN identified after baseline), only the anatomical areas with an 
AN count > 0 will be considered for each participant. At baseline, the anatomical areas with 
abscesses and/or inflammatory nodules will be identified and AN counts in these areas will be 
summed. At each postbaseline visit, the sum of AN counts in only the pre-existing areas (that 
were identified at baseline) will be used to calculate the change relative to baseline. 
7.4.2. 
Categorical Efficacy Endpoints 
For the following categorical parameters, summary statistics, including sample size, frequency, 
and percentages will be presented. 
• Proportion of participants achieving AN50/75/90/100 at Week 16 
• Proportion of participants achieving HiSCR at Week 16 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the DBVC period, 
OLE safety population in the OLE period, and those who applied ruxolitinib 1.5% cream 
throughout the study, unless otherwise specified. Summary tables may be replaced with listings 
when appropriate. For instance, an AE frequency table may be replaced with a listing if it only 
contains a few unique preferred terms reported on relatively few participants. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first application of study drug and within 30 days of the last application of study drug. For 
participants who cross over treatments, the first application date is period-specific; the end date 
is 30 days after the last application date in this period, or the first application date in the next 
period, whichever comes first. Analysis of AEs (as discussed below) will be limited to TEAEs, 
but data listings will include all AEs regardless of their timing in relation to study drug 
application. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the National Cancer Institute CTCAE v5.0. The CTCAE reporting guidelines and grading 
details are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. In addition, serious TEAEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution. Unresolved missing 
causality and severity will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 
9.2.2. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 


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• Number (%) of participants reporting any treatment-related TEAEs  
• Number(%) of participants reporting any ASRs 
• Number (%) of participants who temporarily interrupted study treatment because of 
TEAEs 
• Number (%) of participants who permanently discontinued study treatment because 
of TEAEs 
• Number (%) of participants who had any fatal TEAEs 
The following summaries will be produced by MedDRA term (if 2 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by MedDRA SOC and PT 
• Summary of TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of TEAEs by MedDRA SOC, PT, and maximum severity 
• Summary of TEAEs by MedDRA SOC, PT, and CTCAE grade category 
• Summary of Grade 3 or higher TEAEs by MedDRA SOC and PT 
• Summary of Grade 3 or higher TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of serious TEAEs by MedDRA SOC and PT 
• Summary of serious TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of Grade 3 or higher treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related serious TEAEs by MedDRA SOC and PT 
• Summary of TEAEs with a fatal outcome by MedDRA SOC and PT 
• Summary of TEAEs leading to dose interruption by MedDRA SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by MedDRA SOC and 
PT 
• Summary of ASR by MedDRA PT in decreasing order of frequency 
9.3. 
Clinical Laboratory Tests 
The analyses in this section will be provided for the safety population in the DBVC period, as 
well as the OLE safety population in the OLE period, unless otherwise specified. 


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9.3.1. 
Laboratory Value Definitions 
All laboratory assessments will be performed using a central laboratory, with the exception of 
urine pregnancy tests (as applicable). Laboratory values and change from baseline values will be 
summarized descriptively by visit; non-numeric test values will be tabulated when necessary. 
Baseline will be determined according to Section 4.1.3, using the last nonmissing value collected 
before the first application, prioritizing scheduled assessments for baseline identification over 
unscheduled visits. The last record before application in the highest priority will be considered 
the baseline record. For baseline laboratory candidates with the same date and time in the same 
priority category, additional rules may be provided after consultation with the medical monitor to 
delineate which value will be defined as baseline. 
9.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in 
SI units. All tests with numeric values will have a unique unit per test. Any laboratory test results 
and associated normal ranges from local laboratories will be converted to SI units. 
When there are multiple laboratory nonmissing values for a participant's particular test at a 
scheduled visit, central laboratory values have higher priority over local laboratory values. If a 
tie still exists, the laboratory value with the smallest laboratory sequence number will be used in 
by visit summaries.  
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low (but never high), normal, high (but never 
low) and both low and high will be calculated for each test. A shift summary will be produced 
for each test. The denominator for the percentage calculation will use the number of participants 
in the baseline category (ie, low, high, normal, or missing) as the denominator for the percentage 
in each of the categories during the study. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5.0. Shift tables will also be presented showing change in CTCAE grade from baseline 
to the worst grade postbaseline. Separate summaries for abnormally high and abnormally low 
laboratory values will be provided when the laboratory parameter has both high and low grading 
criteria. The denominator for the percentage calculation will be the number of participants in the 
baseline category. The number of participants who experienced worsening of laboratory 
abnormalities will be summarized by maximum severity. 
9.4. 
Vital Signs 
The analyses in this section will be provided for the safety population in the DBVC period, as 
well as the OLE safety population in the OLE period, unless otherwise specified. Values at each 
scheduled visit, change, and percentage change from baseline for vital signs, including systolic 
blood pressure, diastolic blood pressure, pulse, temperature, and respiratory rate will be 
summarized descriptively. 


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Normal ranges for vital sign values are defined in Table 4. For participants exhibiting vital sign 
abnormalities, the abnormal values will be listed along with their assigned treatment group. Alert 
vital signs are defined as an absolute value outside the defined normal range and percentage 
change greater than 25%. The abnormal values for participants exhibiting alert vital sign 
abnormalities will be listed. 
Table 4: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
 > 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35.5°C 
Respiratory rate 
> 20 breaths/min 
< 8 breaths/min 


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10. 
PLANNED ANALYSES 
No formal interim analysis is planned in this study. 
There are 2 formal planned analyses: 
• The primary analysis will occur after the primary database lock, when all participants 
have completed or discontinued from the DBVC period. The sponsor will be 
unblinded after the primary database lock; however, investigators and participants 
will remain blinded to the individual study treatment assignment after the primary 
database lock. 
• The final analysis will occur when all participants have completed or withdrawn from 
the study. 


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11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 5. 
Table 5: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
12 SEP 2023 
11.1. 
Changes to Protocol-Defined Analyses 
1. Section 2.2, Study Objectives and Endpoints 
Description of change: Added the secondary endpoint, "Change from baseline to Week 16 
in total AN count in anatomical areas with pre-existing AN at baseline." 
Rationale for change: To further evaluate the treatment effect of ruxolitinib 1.5% cream 
BID in participants with HS. 
  
 
 
 
 
 
 
 
 
11.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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12. 
REFERENCES 
 
 
 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
Kimball AB, Naegeli AN, Edson-Heredia E, et al. Psychometric properties of the Itch Numeric 
Rating Scale in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 
2016;175:157-162. 
 
 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. Pharmacoeconomics 1993;4:353-365. 
Sabat R, Jemec GBE, Lukasz M, Kimball AB, et al. Hidradenitis suppurativa. Nat Rev Dis Prim 
2020;6:1-20. 
Zouboulis CC, Tzellos T, Kyrgidis A, et al. 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. 


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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report. Shells are provided in a separate document for tables that are not in the most current 
Standard Safety Tables v1.13. 
The lists of tables, figures, and listings are to be used as guidelines. Modifications of the lists that 
do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
Baseline and Demographics Characteristics 
1.1 Disposition 
1.1.1 
Analysis Populations 
All 
randomized 
X 
1.1.2.1 
Summary of Participant Disposition in the DBVC Period 
ITT 
X 
1.1.2.2 
Summary of Participant Disposition in the OLE Period 
OLE 
X 
1.1.3 
Summary of Number of Participants Enrolled by Country and 
Site 
ITT 
X 
1.1.4.1 
Summary of Protocol Deviations in the DBVC Period 
ITT 
X 
1.1.4.2 
Summary of Protocol Deviations in the OLE Period 
OLE 
X 
1.2 Demographics and Baseline Characteristics 
1.2.1 
Summary of Demographics and Baseline Characteristics 
ITT 
X 
1.2.2 
Summary of Demographics and Baseline Characteristics 
OLE 
X 
1.3 Baseline Disease Characteristics 
1.3 
Summary of Baseline Disease Characteristics 
ITT  
X 
1.4 Prior and Concomitant Medications 
1.4.1 
Summary of Prior Medications 
ITT 
X 
1.4.2.1 
Summary of Concomitant Medications in the DBVC Period 
ITT 
X 
1.4.2.2 
Summary of Concomitant Medications in the OLE Period 
OLE 
X 
1.5 Others 
1.5 
Summary of General Medical History 
ITT 
X 
Efficacy 
2.1 AN Count 
2.1.1 
Summary and Analysis of AN Count During the Study Period 
ITT 
 
2.1.1.2 
Summary and Analysis of AN Count by Baseline AN Count 
During the Study Period 
ITT 
 
2.1.1.3 
Summary and Analysis of AN Count by Age Group During the 
Study Period 
ITT 
 
2.1.2 
Summary and Analysis of AN Count in Anatomical Areas With 
Pre-Existing AN at Baseline During the Study Period 
ITT 
 
2.1.3 
Summary and Analysis of Participants Achieving AN50 During 
the Study Period 
ITT 
 
2.1.4 
Summary and Analysis of Participants Achieving AN75 During 
the Study Period 
ITT 
 
2.1.5 
Summary and Analysis of Participants Achieving AN90 During 
the Study Period 
ITT 
 


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INCB 18424-221 Statistical Analysis Plan 
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Table No. 
Title 
Population 
Standard 
2.1.6 
Summary and Analysis of Participants Achieving AN100 
During the Study Period 
ITT 
 
2.2 Skin Pain NRS 
2.2.1 
Summary and Analysis of By-Visit Skin Pain NRS Score 
During the Study Period 
ITT 
 
2.2.2 
Summary and Analysis of Daily Skin Pain NRS Score From 
Baseline to Day 28  
ITT 
 
2.2.3 
Summary of Participants Achieving ≥ 2-Point Reduction From 
Baseline in By-Visit Skin Pain NRS Score During the Study 
Period 
ITT (baseline 
Skin Pain NRS 
score ≥ 2) 
 
2.2.4 
Summary of Participants Achieving ≥ 4-Point Reduction From 
Baseline in By-Visit Skin Pain NRS Score During the Study 
Period 
ITT (baseline 
Skin Pain NRS 
score ≥ 4) 
 
2.3 Itch NRS 
2.3.1 
Summary and Analysis of By-Visit Itch NRS Score During the 
Study Period 
ITT 
 
2.3.2 
Summary and Analysis of Daily Itch NRS Score From Baseline 
to Day 28 
ITT 
 
2.3.3 
Summary of Participants Achieving ≥ 4-Point Reduction From 
Baseline in By-Visit Itch NRS Score During the Study Period 
ITT (baseline 
Itch NRS 
score ≥ 4) 
 
2.4 HiSCR 
2.4.1 
Summary and Analysis of Participants Achieving HiSCR 
During the Study Period 
ITT 
 
2.5 IHS4 
2.5.1 
Summary and Analysis of IHS4 During the Study Period 
ITT 
 


Incyte Corporation 
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INCB 18424-221 Statistical Analysis Plan 
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Table No. 
Title 
Population 
Standard 
2.13 Hurley Stage 
2.13.1 
Summary of Participants in Each Hurley Stage During the Study 
Period 
ITT 
 
Safety 
3.1 Exposure and Compliance 
3.1.1.1 
Summary of Exposure in the DBVC Period 
Safety 
X 
3.1.1.2 
Summary of Exposure in the OLE Period 
OLE 
X 
3.1.1.3 
Summary of Exposure During Study Period 
Safety 
X 
3.1.2.1 
Summary of Study Drug Compliance in the DBVC Period 
Safety 
 
3.2 Adverse Events 
3.2.1.X 
Overall Summary of Treatment-Emergent Adverse Events  
Safety 
X 
3.2.2.X 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term  
Safety 
X 
3.2.3.X 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency  
Safety 
X 
3.2.4.X 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity 
Safety 
X 
3.2.5.X 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and CTCAE Grade 
Category  
Safety 
 
3.2.6.X 
Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.7.X 
Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of 
Frequency 
Safety 
X 
3.2.8.X 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.9.X 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency  
Safety 
X 
3.2.10.X 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term  
Safety 
X 
3.2.11.X 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of 
Frequency 
Safety 
X 
3.2.12.X 
Summary of Grade 3 or Higher Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety 
 
3.2.13.X 
Summary of Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred 
Term 
Safety 
 
3.2.14.X 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term 
Safety 
 
3.2.16.X 
Summary of Treatment-Emergent Adverse Events Leading to 
Dose Interruption in Some or All Treated Areas by MedDRA 
System Organ Class and Preferred Term  
Safety 
X 


Incyte Corporation 
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INCB 18424-221 Statistical Analysis Plan 
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Table No. 
Title 
Population 
Standard 
3.2.17.X 
Summary of Treatment-Emergent Adverse Events Leading to 
Dose Interruption in All Treated Areas by MedDRA System 
Organ Class and Preferred Term  
Safety 
 
3.2.18.X 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ 
Class and Preferred Term  
Safety 
 
3.2.19.X 
Summary of Application Site Reactions by MedDRA Preferred 
Term in Decreasing Order of Frequency 
Safety 
 
3.3 Laboratory 
3.3.1.1.X 
Summary of Laboratory Values – Hematology  
Safety 
X 
3.3.1.2.X 
Summary of Laboratory Values – Chemistry  
Safety 
X 
3.3.2.1.X 
Shift Summary of Hematology Laboratory Values – to the 
Worst Abnormal Value  
Safety 
 
3.3.2.2.X 
Shift Summary of Chemistry Laboratory Values – to the Worst 
Abnormal Value  
Safety 
 
3.3.3.1.X 
Shift Summary of Hematology Laboratory Values in CTCAE 
Grade – to the Worst Grade Abnormal Value  
Safety 
X 
3.3.3.2.X 
Shift Summary of Chemistry Laboratory Values in CTCAE 
Grade – to the Worst Grade Abnormal Value  
Safety 
X 
3.4 Vital Signs 
3.4.1.x 
Summary of Systolic Blood Pressure  
Safety 
X 
3.4.2.x 
Summary of Diastolic Blood Pressure  
Safety 
X 
3.4.3.x 
Summary of Pulse  
Safety 
X 
3.4.4.x 
Summary of Respiratory Rate  
Safety 
X 
3.4.5.x 
Summary of Body Temperature 
Safety 
X 
Note: For AE tables ending with "x," separate tables will be provided for the DBVC period, the OLE period, and the entire study 
period. For Laboratory and Vital Sign tables ending with "x," separate tables will be provided for the DBVC period and the 
OLE period. 
Figures 
Figure No. 
Title 
Population 
Efficacy 
4.1.1.1 
Mean and Standard Error Plot of AN Count During the Treatment Period 
ITT 
4.1.1.2 
Mean and Standard Error Plot of Change From Baseline in AN Count During the 
Treatment Period 
ITT 
4.1.1.3 
Mean and Standard Error Plot of Percent Change From Baseline in AN Count 
During the Treatment Period 
ITT 
4.1.2.1 
Mean and Standard Error Plot of AN Count in Anatomical Areas With 
Pre-Existing AN at Baseline During the Treatment Period 
ITT 
4.1.2.2 
Mean and Standard Error Plot of Change From Baseline in AN Count in 
Anatomical Areas with Pre-Existing AN During the Treatment Period 
ITT 
4.1.2.3 
Mean and Standard Error Plot of Percent Change From Baseline in AN Count in 
Anatomical Areas with Pre-Existing AN During the Treatment Period 
ITT 
4.1.3 
Proportion of Participants Achieving AN50 During the Treatment Period 
ITT 
4.1.4 
Proportion of Participants Achieving AN75 During the Treatment Period 
ITT 
4.1.5 
Proportion of Participants Achieving AN90 During the Treatment Period 
ITT 
4.1.6 
Proportion of Participants Achieving AN100 During the Treatment Period 
ITT 


Incyte Corporation 
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INCB 18424-221 Statistical Analysis Plan 
12 SEP 2023 
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CONFIDENTIAL 
Figure No. 
Title 
Population 
4.2.1.1 
Mean and Standard Error Plot of By-Visit Skin Pain NRS Score During the 
Treatment Period 
ITT 
4.2.1.2 
Mean and Standard Error Plot of Change From Baseline in By-Visit Skin Pain 
NRS Score During the Treatment Period 
ITT 
4.2.3.1 
Mean and Standard Error Plot of Daily Skin Pain NRS Score From Baseline to 
Day 28 
ITT 
4.2.3.2 
Mean and Standard Error Plot of Change From Baseline in Daily Skin Pain NRS 
Score From Baseline to Day 28 
ITT 
4.3.1.1 
Mean and Standard Error Plot of By-Visit Itch NRS Score During the Treatment 
Period 
ITT 
4.3.1.2 
Mean and Standard Error Plot of Change From Baseline in By-Visit Itch NRS 
Score During the Treatment Period 
ITT 
4.3.2 
Proportion of Participants Achieving ≥ 4-Point Improvement in By-Visit Itch NRS 
Score During the Treatment Period 
ITT 
(baseline 
Itch NRS 
score ≥ 4) 
4.3.3.1 
Mean and Standard Error Plot of Daily Itch NRS Score From Baseline to Day 28 
ITT 
4.3.3.2 
Mean and Standard Error Plot of Change From Baseline in Daily Itch NRS Score 
From Baseline to Day 28 
ITT 
4.4.1 
Proportion of Participants Achieving HiSCR During the Treatment Period 
ITT 
4.5.1 
Mean and Standard Error Plot of IHS4 Score During the Treatment Period 
ITT 
4.5.2 
Mean and Standard Error Plot of Change From Baseline in IHS4 Score During the 
Treatment Period 
ITT 
4.12.1 
Box Plot of Selected Laboratory Values in the DBVC Period 
ITT 
4.12.2 
Box Plot of Change From Baseline in Selected Laboratory Values During the 
DBVC Period 
ITT 
4.12.3 
Box Plot of Percent Change From Baseline in Selected Laboratory Values During 
the DBVC Period 
ITT 


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INCB 18424-221 Statistical Analysis Plan 
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CONFIDENTIAL 
Listings 
Listing No. 
Title 
2.1 Enrollment and Disposition 
2.1.1 
Participant Enrollment and Disposition Status 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2 Protocol Deviations 
2.2.1 
Protocol Deviations  
2.3 Analysis Populations 
2.3 
Analysis Populations 
2.4 Demographic and Baseline Characteristics (Including Prior and Concomitant Medications) 
2.4.1 
Demographic Characteristics  
2.4.2 
Baseline Disease Characteristics 
2.4.3 
Disease History 
2.4.4 
Medical History  
2.4.5 
Prior and Concomitant Medications 
2.4.6 
Prior Medications for HS 
2.5 Drug Compliance 
2.5.1 
Study Drug Exposure and Compliance  
2.6 Efficacy  
2.6.1.1 
Lesion Count 
2.6.1.2 
AN Count 
2.6.2 
Skin Pain NRS Score 
2.6.3 
Itch NRS Score 
 
 
 
 
 
 
 
 
 
 
 
 
2.7 Adverse Events 
2.7.1 
Adverse Events 
2.7.2 
Adverse Events Leading to Study Drug Discontinuation 
2.7.3 
Serious Adverse Events 
2.7.4 
Treatment-Related Adverse Events 
2.7.5 
Adverse Events With a Fatal Outcome 
2.7.6 
Adverse Events Leading to Dose Interruption 
2.7.8 
Grade 3 or Higher Adverse Events 
2.7.9 
Application Site Reactions 
2.8 Laboratory Data 
2.8.1.1 
Clinical Laboratory Values – Hematology 
2.8.1.2 
Clinical Laboratory Values – Chemistry 
2.8.1.3 
Abnormal Clinical Laboratory Values – Hematology 
2.8.1.4 
Abnormal Clinical Laboratory Values – Chemistry 
Vital Signs 
2.8.2.1 
Vital Signs 


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INCB 18424-221 Statistical Analysis Plan 
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Listing No. 
Title 
2.8.2.2 
Abnormal Vital Sign Values 
2.8.2.3 
Alert Vital Sign Values