Clinical trial NCT05593432
Conditions: Cutaneous Lichen Planus
Keywords: Lichen Planus Skin Diseases 18424 Ruxolitinib topical cream
Sponsor: Incyte Corporation
Start date: 2022-11-23; Completion date: 2024-02-26
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study will be to evaluate efficacy and safety of Ruxolitinib cream in participants With Cutaneous Lichen Planus. This is randomized, double-blind, vehicle-controlled (DBVC) study with a DBVC period of 16 weeks followed by an open label period (OLE) period of 16 weeks.

Detailed description:

Arms: arm 1: Ruxolitinib 1.5% cream BID for 16 weeks, followed by ruxolitinib cream BID 16-week open-label extension. arm 2: Vehicle cream BID for 16 weeks, followed by ruxolitinib 1.5% cream BID in a 16-week 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 Randomized, Double-Blind, Vehicle-Controlled Study of the Efficacy and Safety of 
Ruxolitinib Cream in Participants With Cutaneous Lichen Planus
NCT Number: NCT05593432   
 Document Date: Clinical Study Protocol: 27-March-2023 


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Protocol INCB 18424-216 Am 1 
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Clinical Study Protocol 
TITLE PAGE 
INCB 18424-216 
A Phase 2, Randomized, Double-Blind, Vehicle-Controlled Study of the 
Efficacy and Safety of Ruxolitinib Cream in Participants With 
Cutaneous Lichen Planus 
Product: 
Ruxolitinib Cream 
IND Number: 
77101 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 USA 
Original Protocol: 
02 MAY 2022 
Protocol Amendment 1: 
27 MAR 2023 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki (Brazil 2013) and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and 
applicable laws and country-specific regulations, including WMO (Medical Research Involving Human Participants 
Act) and Clinical Trials Regulation (EU) No. 536/2014, 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 18424-216 Protocol Amendment 1 (dated 27 MAR 2023) 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 ......................................................................................................17 
2.1. 
Background .................................................................................................................17 
2.1.1. 
Scientific Rationale for Study Design ........................................................................19 
2.1.2. 
Justification for Dose ..................................................................................................20 
2.2. 
Benefit/Risk Assessment ............................................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................21 
4. 
STUDY DESIGN .......................................................................................................23 
4.1. 
Overall Design ............................................................................................................23 
4.2. 
Overall Study Duration ...............................................................................................23 
4.3. 
Study Termination ......................................................................................................23 
5. 
STUDY POPULATION .............................................................................................24 
5.1. 
Inclusion Criteria ........................................................................................................24 
5.2. 
Exclusion Criteria .......................................................................................................25 
5.3. 
Lifestyle Considerations .............................................................................................27 
5.4. 
Screen Failures ............................................................................................................27 
5.5. 
Replacement of Participants .......................................................................................27 
6. 
STUDY TREATMENT ..............................................................................................28 
6.1. 
Study Treatments Administered .................................................................................28 
6.2. 
Preparation, Handling, and Accountability ................................................................29 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................30 
6.4. 
Study Treatment Compliance .....................................................................................30 
6.5. 
Dose Modifications .....................................................................................................31 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................31 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug Due to an Adverse 
Event ...........................................................................................................................32 
6.6. 
Concomitant Medications and Procedures .................................................................33 


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6.6.1. 
Permitted Medications and Procedures ......................................................................33 
6.6.2. 
Restricted Use Medications and Procedures ...............................................................34 
6.6.3. 
Prohibited Medications and Procedures .....................................................................34 
6.7. 
Treatment After the End of the Study .........................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Reasons for Discontinuation .......................................................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................36 
7.2. 
Participant Withdrawal from the Study ......................................................................36 
7.3. 
Lost to Follow-Up.......................................................................................................36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................37 
8.1. 
Administrative and General Procedures .....................................................................37 
8.1.1. 
Informed Consent Process ..........................................................................................37 
8.1.2. 
Screening Procedures ..................................................................................................38 
8.1.3. 
Interactive Response Technology Procedure ..............................................................38 
8.1.4. 
Distribution of Reminder Cards and eDiaries ............................................................38 
8.1.5. 
Demography and Medical History ..............................................................................39 
8.1.5.1. 
Demographics and General Medical History .............................................................39 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................39 
 
39 
8.2. 
Efficacy Assessments .................................................................................................40 
8.2.1. 
Health Economics .......................................................................................................40 
8.2.2. 
Investigator's Global Assessment ...............................................................................40 
 
41 
 
41 
 
42 
 
42 
 
42 
 
42 
8.2.8.1. 
eDiary Assessments ....................................................................................................42 
 
43 


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43 
 
43 
 
44 
 
44 
8.3. 
Safety Assessments .....................................................................................................44 
8.3.1. 
Adverse Events ...........................................................................................................44 
8.3.2. 
Physical Examinations ................................................................................................45 
8.3.3. 
Vital Signs ..................................................................................................................45 
8.3.4. 
Laboratory Assessments .............................................................................................45 
8.3.4.1. 
Pregnancy Testing ......................................................................................................46 
8.3.4.2. 
Serology ......................................................................................................................46 
 
47 
 
47 
 
47 
 
47 
8.6. 
Unscheduled Visits .....................................................................................................47 
8.7. 
End of Treatment and Early Termination ...................................................................48 
8.8. 
Follow-Up ...................................................................................................................48 
8.8.1. 
Safety Follow-Up ........................................................................................................48 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................49 
9.1. 
Definition of Adverse Event .......................................................................................49 
9.2. 
Definition of Serious Adverse Event ..........................................................................50 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........51 
9.4. 
Reporting of Serious Adverse Events .........................................................................53 
9.5. 
Potential Drug-Induced Liver Injury ..........................................................................54 
9.6. 
Events of Clinical Interest ..........................................................................................54 
9.7. 
Emergency Unblinding of Treatment Assignment .....................................................54 
9.8. 
Pregnancy ...................................................................................................................55 
9.9. 
Warnings and Precautions ..........................................................................................55 
9.10. 
Product Complaints ....................................................................................................56 
9.11. 
Treatment of Overdose ...............................................................................................56 
10. 
STATISTICS ..............................................................................................................56 


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10.1. 
Sample Size Determination ........................................................................................56 
10.2. 
Populations for Analysis .............................................................................................56 
10.3. 
Level of Significance ..................................................................................................57 
10.4. 
Statistical Analyses .....................................................................................................57 
10.4.1. 
Primary Analysis ........................................................................................................57 
10.4.2. 
Secondary Analysis ....................................................................................................58 
10.4.3. 
Safety Analyses ..........................................................................................................58 
 
59 
10.5. 
Interim Analysis ..........................................................................................................59 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................60 
11.1. 
Investigator Responsibilities .......................................................................................60 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................61 
11.2. 
Data Management .......................................................................................................61 
11.3. 
Data Quality Assurance ..............................................................................................63 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................63 
11.5. 
Financial Disclosure ...................................................................................................64 
11.6. 
Publication Policy .......................................................................................................64 
11.7. 
Study and Site Closure................................................................................................65 
12. 
REFERENCES ...........................................................................................................66 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................68 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................70 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................73 
 


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LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................11 
Table 2: 
Key Study Design Elements .......................................................................................12 
Table 3: 
Schedule of Activities .................................................................................................14 
Table 4: 
Objectives and Endpoints ...........................................................................................21 
Table 5: 
Study Treatment Information .....................................................................................29 
Table 6: 
Guidelines for Interruption of Study Drug for Treatment-Related Adverse 
Events and Restarting of Study Drug .........................................................................32 
 
41 
Table 8: 
Schedule of Laboratory Assessments .........................................................................46 
Table 9: 
Populations for Analysis .............................................................................................57 
Table 10: Summary of Primary Analysis....................................................................................58 
 
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 
AST 
aspartate aminotransferase 
BID  
twice daily 
BSA 
body surface area 
CCL 
C-C motif chemokine ligand 
CCR 
C-C motif chemokine receptor 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
CXCL 
C-X-C chemokine ligand 
CXCR 
C-X-C chemokine receptor 
CYP 
cytochrome P450 
DBVC 
double-blind, vehicle-controlled 
 
 
DNA 
deoxyribonucleic acid 
EASI 
Eczema Area and Severity Index 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOT 
end of treatment 
ET 
early termination 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 


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Abbreviations and 
Special Terms 
Definition 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV  
human immunodeficiency virus 
HRT 
hormone replacement therapy 
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 
IFN 
interferon 
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 
IRB 
institutional review board 
IRT 
interactive response technology  
ITCH4 
≥ 4-point improvement in WI-NRS score 
ITT 
intent-to-treat 
JAK 
Janus kinase 
 
 
 
 
 
 
 
 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
numeric rating scale 
OLE 
open-label extension 
 
 
 
 
 
 
 
 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
schedule of activities 


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Abbreviations and 
Special Terms 
Definition 
SOP 
standard operating procedure 
STAT 
signal transducer and activator of transcription 
STD 
standard deviation 
TEAE 
treatment-emergent adverse event, AEs reported for the first time or worsening 
of a pre-existing event after first dose of study treatment 
ULN 
upper limit of normal 
VC 
vehicle-controlled 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Vehicle-Controlled Study of the Efficacy and Safety of 
Ruxolitinib Cream in Participants with Cutaneous Lichen Planus 
Protocol Number: INCB 18424-216 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% cream 
BID in participants with cutaneous LP. 
IGA-TS response (defined as an IGA score of 0 or 1 
with ≥ 2-grade improvement from baseline) at 
Week 16. 
[Proportion of participants achieving IGA-TS at 
Week 16] 
Secondary 
To further assess the treatment effects of ruxolitinib 
1.5% cream BID in participants with cutaneous LP. 
• IGA-TS response at each scheduled postbaseline 
visit up to and including Week 32. 
[Proportion of participants achieving IGA-TS at 
each scheduled postbaseline visit] 
• ITCH4 response (defined as a ≥ 4-point 
improvement in Itch NRS score from baseline) at 
each scheduled postbaseline visit up to and 
including Week 32. 
[Proportion of participants with ITCH4 at each 
scheduled postbaseline visit] 
• Time to achieve ITCH4. 
• Change from baseline in the Skin Pain NRS score at 
each scheduled postbaseline visit up to and 
including Week 32.  
To evaluate the safety and tolerability of ruxolitinib 
1.5% cream BID. 
• The type, frequency, and severity of AEs, including 
changes in vital signs and clinical laboratory blood 
samples. 
Overall Design: 
Table 2 presents the key study design elements. Further study details are presented after the 
table. 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of patients with cutaneous LP 
Population 
Male and female participants at least 18 years of age who have 
predominantly cutaneous LP (covering ≤ 20% BSA) and baseline IGA 
score ≥ 3. 
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 16-week, randomized, DBVC study with a 16-week OLE period 
with a crossover to active treatment for participants who complete the 
16-week DBVC period (vehicle cream), followed by a 30-day 
post-treatment, safety follow-up visit. Participants initially randomized to 
the active treatment arm will continue with ruxolitinib 1.5% cream during 
the OLE period.  
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 
Treatment Groups and Duration: 
This is a Phase 2, randomized, DBVC study with a DBVC period of 16 weeks followed by an 
OLE period of 16 weeks. Participants who were initially assigned to ruxolitinib 1.5% cream will 
continue with active treatment during the OLE period, while those participants who were initially 
assigned to vehicle will cross over to active treatment. 
Approximately 60 participants will be randomized 1:1 to either ruxolitinib 1.5% cream or vehicle 
cream (see Figure 1). Participants will be stratified by baseline IGA score (3 or 4). Participants 
will apply either ruxolitinib 1.5% cream or vehicle cream (both 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 in the VC period will be crossed over to ruxolitinib 1.5% cream, and 
participants randomized to ruxolitinib 1.5% cream at baseline will continue to apply ruxolitinib 
cream through Week 32. In the OLE period, participants will only treat active lesions. At 
Week 16, the LP treatment area will be evaluated by the investigator to assess the disease and 
confirm whether treatment continuation is required (IGA score ≥ 1) during the OLE period or 
can otherwise (re)enter an observation/no treatment cycle (IGA score = 0). Treatment assignment 
during the DBVC period will remain blinded until all participants have completed treatment or 
discontinued. 
Table 3 presents the SoA. Adherence to the study design requirements, including those specified 
in the SoA, is essential and required for study conduct.  


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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: 
Study Design Schema 
 
 


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Table 3: 
Schedule of Activities 
 
Days 
−28 to −1 
DBVC Period 
OLE Period 
Unscheduled 
Visit 
Safety 
Follow-Up 
Visit Day (Range) 
Screening 
Baseline/ 
Day 1 
Wk 2a 
(± 3 d) 
Wk 4a 
(± 3 d) 
Wk 8a 
(± 3 d 
Wk 12a 
(± 3 d) 
Wk 16/ 
EOT1b 
(± 3 d) 
Wk 18a 
(± 3 d) 
Wk 20a 
(± 3 d) 
Wk 24a 
(± 3 d) 
Wk 28a 
(± 3 d) 
Wk 32 
EOT2/ETc 
(± 3 d) 
30 Days 
(+ 7 Days After 
Last 
Application) 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
review 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and medical 
history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
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 
X 
 
 
Distribute reminder cards 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Distribute eDiary 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Apply study drug in clinic 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Weigh/dispense study drug  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Collect/weigh study drug  
 
 
X 
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 
X 
Comprehensive physical 
examinationd 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Height and body weight 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physician-reported outcomes 
IGA  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
%BSAe 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Target lesion assessmentf 
 
X 


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Table 3: 
Schedule of Activities (Continued) 
 
Days 
−28 to −1 
DBVC Period 
OLE Period 
Unscheduled 
Visit 
Safety 
Follow-Up 
Visit Day (Range) 
Screening 
Baseline/ 
Day 1 
Wk 2a 
(± 3 d) 
Wk 4a 
(± 3 d) 
Wk 8a 
(± 3 d 
Wk 12a 
(± 3 d) 
Wk 16/ 
EOT1b 
(± 3 d) 
Wk 18a 
(± 3 d) 
Wk 20a 
(± 3 d) 
Wk 24a 
(± 3 d) 
Wk 28a 
(± 3 d) 
Wk 32 
EOT2/ETc 
(± 3 d) 
30 Days 
(+ 7 Days After 
Last 
Application) 
Patient-reported outcomes 
Itch NRS 
Completed each evening through the last application of study drug. 
 
 
 
Skin Pain NRS 
 
 
Laboratory assessments 
Chemistry assessments 
X 
Xh 
 
 
X 
 
X 
 
 
X 
 
X 
Xi 
X 
Hematology assessments 
X 
Xh 
 
 
X 
 
X 
 
 
X 
 
X 
Xi 
X 
FSHj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy testk 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy testk 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hepatitis/HIV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug exposure assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Visits at Weeks 2, 4, 8, 12, 18, 20, 24, and 28 can be performed virtually (through telemedicine if applicable) only due to COVID-19–related reasons. No efficacy assessments 
can be performed virtually (see Appendix B). 
b All Week 16 assessments must be completed before the participant can continue in the OLE period. Study drug will not be applied in the clinic at Week 16 for participants not 
continuing into the OLE period. 
c Participants who withdraw from the study early should complete the ET and the safety follow-up visits. 
d Targeted physical examinations can be performed for assessment of AEs and during other visits, including unscheduled visits, as per discretion of the investigator. 


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e The total %BSA affected should be ≤ 20% to be eligible for study entry and continued participation. 
f Target lesions typical of LP (3 or more) will be identified at baseline. 
  
h Not necessary if screening assessment is performed within 14 days of Day 1. 
i Laboratory assessments are optional during unscheduled visits based on investigator's discretion and clinical judgment. 
j Women of nonchildbearing potential only. FSH is not needed in women with documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. 
k Female participants of childbearing potential will have a serum test at screening, a urine pregnancy test before Day 1 study cream application, 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 
Lichen planus is an inflammatory skin condition characterized by purple, polygonal, pruritic 
papules, and plaques. The lesions are often covered by lacy, reticular, white lines known as 
Wickham striae. Lichen planus can affect any ectodermally derived tissues, including the skin 
(most commonly), nails, and mucous membranes. Onset is usually acute, affecting the flexor 
surfaces of the wrists, forearms, and legs. Oral LP can be the sole clinical presentation of the 
disease or accompanied by cutaneous or other mucosal manifestations, including the genital area, 
gastrointestinal tract, and eyes. Classic cases of LP may be diagnosed clinically, but a biopsy is 
often helpful and is required for more atypical cases (Usatine and Tinitigan 2011). Itch is present 
in most patients and is considered the most bothersome symptoms of LP (Welz-Kubiak and 
Reich 2013). Lichen planus is associated with relatively high rates of depression and anxiety. 
A recent meta-analysis showed a high prevalence of signs of depression (27%) and anxiety 
(28%) in patients with LP (Jalenques et al 2020). 
The prevalence of LP is 0.89% in the general population and 0.98% in patients seeking 
dermatological care, according to a recent meta-analysis of 46 studies (Li et al 2020). The 
prevalence of cutaneous LP is reported to range between 0.2% and 1.0% of the adult population, 
and it is outnumbered by oral LP in most study populations (Boyd and Neldner 1991, Le Cleach 
and Chosidow 2012). Patients with LP are usually between the ages of 30 and 60 years, and there 
appears to be a slightly higher prevalence in women (60%; Axéll and Rundquist 1987). While 
oral LP affects females more frequently than males (Axéll and Rundquist 1987, Li et al 2020), 
cutaneous LP does not demonstrate a prominent sex predilection (Irvine et al 1991). Cutaneous 
LP tends to manifest during the fifth and sixth decades of life, with almost two-thirds of patients 
presenting with the disease between the ages of 30 and 60 years (Schwager et al 2019, Wagner 
et al 2013). The majority of cutaneous LP lesions resolve spontaneously over 1 to 2 years, often 
with a residual hyperpigmented macule (Weston and Payette 2015). 
Lichen planus is a T cell–mediated disease affecting the stratified squamous epithelia of the skin 
and/or mucous membrane. Histologically, the disease is characterized by a lichenoid 
inflammatory infiltrate and vacuolar degeneration of the basal layer of the epidermis. Several 
alterations in the expression of cytokines and chemokines in lesions or serum of patients with LP 
have been described. Serum levels of IL-5, IL-6, IL-8, IL-9, IL-10, IL-12 IL-17, IL-22, tumor 
necrosis factor α, transforming growth factor β, IFN-γ, CXCR-3, CXCR-4, CXCL-10, CXCL-12, 
CCR1, CCR3, CCR4, CCL5-CCR5, and CCL17-CCR4 have been found to be elevated (Chen 
et al 2013, Kurago 2016, Weber et al 2017, Zychowska et al 2020). Recent studies demonstrated 
that the inflammation in cutaneous LP is dominated by IFN-γ, IL-6, and IL-21 and the 
proinflammatory milieu is dominated by STAT1 activation (Boch et al 2021, Shao et al 2019). 
All of these cytokines, IL-21, IFN-γ, IL-6, and Type I IFN, use JAK1 for signal transduction. Of 
note, JAK1 has been reported to be overexpressed in dermal skin of LP (Alves de Medeiros et al 
2016). Therefore, JAK1 blockade could be beneficial for cutaneous LP. 
Patients with LP currently have limited treatment options, which include irritant avoidance and 
first-line treatment with topical corticosteroids. Topical calcineurin inhibitors are the second line 
of choice when topical corticosteroids are not effective or not tolerated. 


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Ruxolitinib is a small molecule inhibitor of the JAKs, which play an important role in signal 
transduction following cytokine and growth factor binding to their receptors. Increased 
production of cytokines and growth factors has been associated with a number of chronic 
inflammatory conditions, including AD, vitiligo, and other autoimmune diseases of the skin. 
Therefore, JAK inhibition may be expected to be efficacious in these diseases (refer to the IB for 
more information). 
The efficacy of ruxolitinib cream, a JAK1/2 inhibitor, has been demonstrated in inflammatory 
dermatoses such as 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% affected BSA (excluding the scalp; 
Papp et al 2020). In both AD Phase 3 studies, more than 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 score of 0 or 1 with ≥ 2-grade improvement from baseline) compared with 15.1% and 
7.9% of participants who applied vehicle cream, respectively. 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 vs 16.3% and 
15.4% for vehicle cream, respectively). 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 in the US as Opzelura™ for the topical short-term and noncontinuous chronic 
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. 
Ruxolitinib 1.5% cream has demonstrated efficacy in vitiligo. Studies INCB 18424-306 and -307 
were identically designed randomized, VC, Phase 3 studies 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 studies 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 Face Vitiligo 
Area Scoring Index at Week 24 compared to participants treated with a vehicle control. In 
addition, ruxolitinib 1.5% cream was safe and well-tolerated in both adolescents and adults with 
vitiligo. 
Recently, the potential benefit of ruxolitinib 1.5% cream BID was reported in a single-arm, 
open-label study in participants with cutaneous LP treated for 8 weeks (Mangold et al 2021). 
Twelve patients with a median age of 63 years (range: 34-81 years) participated in the study. At 
Week 4 (primary endpoint), total body lesion number decreased by a median of 50 lesions 
(interquartile range: 25-723; p < 0.001). Mean (STD) mCAILS scores decreased by 11.0 (6.2) in 
index treatment lesions and 3.4 (5.6) in index controls, for a mean difference of 7.6 (8.8; 
p = 0.016). Ten of 12 index treatment lesions (83.3%) achieved treatment response, as defined by 
≥ 50% reduction in mCAILS score, compared to 4 of 12 controls (33.3%; p = 0.077). Post hoc 
analysis, which excluded 4 participants who unintentionally treated their control lesions at any 
point during the study, revealed response of 7 of 8 treatment lesions (87.5%) compared to 1 of 
8 control lesions (12.5%; p = 0.04). All participants were responsive (≥ 50% improvement) 
based on Patient Global Assessment score at Week 4; 2 of 12 were 100% clear, 5 of 12 had 
≥ 90% improvement, 4 of 12 had marked (≥ 75% to 90%) improvement, and 1 of 12 had 


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moderate (≥ 50% to 75%) improvement. A significant reduction (p = 0.006) in mean pruritus 
NRS scores was reported at Week 4. Only 1 AE was deemed to be possibly related to the study 
treatment ("abnormal taste" reported at Week 1) and was classified as mild. All other AEs were 
judged as mild to moderate and were determined to be unrelated to the study medication. 
This study is designed to evaluate the efficacy and safety of ruxolitinib 1.5% cream in 
participants with cutaneous LP. 
2.1.1. 
Scientific Rationale for Study Design 
Similar to AD and vitiligo, LP is considered to be an inflammatory dermatosis. The pathogenesis 
of LP involves autoimmunity and several cytokines that are dependent on the JAK-STAT 
pathway for signal transduction. Similar to AD and vitiligo, JAK1- and JAK2-associated 
cytokines are involved in the pathogenesis of cutaneous LP. Prior studies have shown 
overexpression of IFN-γ, IL-21, IL-4, IL-12A, and tumor necrosis factor in LP (Pietschke et al 
2021, Shao et al 2019). Ruxolitinib is a selective inhibitor of JAK1 and JAK2, and based on its 
demonstrated efficacy in both AD and vitiligo in well-designed pivotal Phase 3 trials 
(INCB 18424-303/-304 and INCB 18424-306/-307) and data from Mangold et al (2021), 
ruxolitinib 1.5% cream is expected to have potential activity in cutaneous LP. 
While the study by Mangold et al (2021) provides preliminary evidence of the efficacy of 
ruxolitinib 1.5% cream in patients with LP, this was a single-arm study with a small sample size, 
and these findings need to be replicated in a larger randomized controlled trial as a proof of 
concept. Lichen planus lesions mostly resolve spontaneously over a period of 1 to 2 years, and 
the aim of treatment is to hasten recovery and reduce associated symptoms such as itching. 
Given the high rate of spontaneous resolution, it is important to demonstrate the efficacy of 
ruxolitinib 1.5% cream against a VC arm. Although ruxolitinib 1.5% cream has been 
demonstrated to improve AD at 8 weeks, LP lesions involve significantly more skin changes. 
Mangold et al (2021) demonstrated reduction in lesion count by 50% after 4 weeks of open-label 
treatment with ruxolitinib 1.5% cream. However, concern with spontaneous resolution of LP 
remains. In the study by Mangold et al (2021), approximately 33% of control lesions achieved 
treatment response, as defined by ≥ 50% reduction in mCAILS score at Week 4. Based on these 
findings, it is crucial to demonstrate the efficacy of ruxolitinib 1.5% cream in participants with 
cutaneous LP as a proof-of-concept Phase 2 study with a longer treatment period (16 weeks was 
chosen for this study) before moving to confirmatory Phase 3 studies. In addition, there is a need 
to demonstrate the long-term safety and efficacy of ruxolitinib 1.5% cream in LP by including an 
OLE period. 
This study will evaluate the efficacy and safety of ruxolitinib 1.5% cream BID versus vehicle in 
participants with LP. The VC period is 16 weeks. Participants who are randomly assigned to 
ruxolitinib 1.5% cream will continue to treat active LP areas during the OLE period for an 
additional 16 weeks. Participants assigned to vehicle initially will then be crossed over to receive 
active treatment for an additional 16 weeks. This design will provide a well-controlled 
assessment of the efficacy of ruxolitinib 1.5% cream in participants with LP compared to 
vehicle. 


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2.1.2. 
Justification for Dose 
The ruxolitinib cream strength and application frequency for this study (ruxolitinib 1.5% cream 
BID) was selected primarily based on preliminary evidence from the open-label study by 
Mangold et al (2021) and 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. Overall, ruxolitinib 1.5% cream was found to be 
more efficacious than ruxolitinib 0.75% cream, while the safety and tolerability profiles of both 
treatment arms were comparable and nondifferentiating. Of note, the Phase 3 efficacy and safety 
findings were on par and thus fully confirmatory of the outcomes of the earlier Phase 2 
(INCB 18424-206) dose range–finding study. Similarly, Phase 3 pivotal studies in vitiligo 
(INCB 18424-306 and -307) provide further support for the superior efficacy of ruxolitinib 1.5% 
cream versus vehicle cream. 
Given the known data and the pathogenic and clinical manifestations of LP, ruxolitinib 1.5% 
cream BID was selected as the treatment regimen for this study. 
2.2. 
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 itch 
(Papp et al 2020). Given that LP has an itch component to the disease, it is likely that participants 
with LP will benefit from ruxolitinib cream in treating itch.  
Safety data from the Phase 3 AD studies (INCB 18424-303 and-304) demonstrated that 
ruxolitinib 1.5% cream BID applied continuously for 8 weeks followed by prolonged (44 weeks) 
intermittent use is 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. 
In the study by Mangold et al (2021), all AEs were mild to moderate in severity and, with 
1 exception, all were unrelated to the study medication. This provides some evidence of the 
safety of ruxolitinib 1.5% cream in participants with LP. 
Results from dermal safety studies in healthy adult participants (INCB 18424-104, -105, -106, 
-107, and -108) to evaluate local tolerability demonstrated that ruxolitinib 1.5% cream did not 
cause sensitization and was only slightly irritating under exaggerated testing conditions 
(occlusive application). In addition, ruxolitinib 1.5% cream was not phototoxic and did not 
induce photosensitization. This was further confirmed by the Phase 3 (INCB 18424-303 and 
-304) safety data, where ruxolitinib 1.5% cream BID was well-tolerated at the application sites 
with infrequently reported application site reactions. The most frequently reported application 
site reaction events were application site pain (lowest-level terms were primarily application site 
burning or application site stinging) and application site pruritus. Each of these events occurred 
in a lower proportion of participants in the ruxolitinib 1.5% cream BID treatment group (< 1%) 
compared with the vehicle cream treatment group (3%-5%) during the 8-week VC period, which 


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may be attributable to worsening of the underlying disease in the absence of active drug 
treatment. More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of ruxolitinib cream may be found in the IB. 
The efficacy and safety data from AD and vitiligo studies as well as data from the study by 
Mangold et al (2021) in cutaneous LP provide support of the expected positive benefit-risk ratio 
of ruxolitinib cream in LP. Furthermore, given that LP has an itch component to the disease, it is 
anticipated that participants with LP will benefit from ruxolitinib cream in treating itch. 
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 cutaneous LP. 
IGA-TS response (defined as an IGA score of 0 or 1 
with ≥ 2-grade improvement from baseline) at 
Week 16. 
[Proportion of participants achieving IGA-TS at 
Week 16] 
Secondary 
To further assess the treatment effects of ruxolitinib 
1.5% cream BID in participants with cutaneous LP. 
• IGA-TS response at each scheduled postbaseline 
visit up to and including Week 32. 
[Proportion of participants achieving IGA-TS at 
each scheduled postbaseline visit] 
• ITCH4 response (defined as a ≥ 4-point 
improvement in Itch NRS score from baseline) at 
each scheduled postbaseline visit up to and 
including Week 32. 
[Proportion of participants with ITCH4 at each 
scheduled post-baseline visit] 
• Time to achieve ITCH4. 
• Change from baseline in the Skin Pain NRS score at 
each scheduled postbaseline visit up to and 
including Week 32.  
To evaluate the safety and tolerability of ruxolitinib 
1.5% cream BID. 
The type, frequency, and severity of AEs, including 
changes in vital signs and clinical laboratory blood 
samples. 


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Table 4: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, randomized, DBVC study in participants at least 18 years of age who have 
predominantly cutaneous LP (covering ≤ 20% BSA) and baseline IGA score ≥ 3. The study will 
consist of a 16-week DBVC period followed by a 16-week OLE period. Participants who were 
initially assigned to ruxolitinib 1.5% cream will continue with active treatment during the OLE 
period, while those participants who were initially assigned to vehicle will cross over to active 
treatment. 
Approximately 60 participants will be randomized 1:1 to either ruxolitinib 1.5% cream or vehicle 
cream (see Figure 1). Participants will be stratified by baseline IGA score (3 or 4). Participants 
will apply either ruxolitinib 1.5% cream or vehicle cream (both 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 in the VC period will be crossed over to ruxolitinib 1.5% cream, and 
participants randomized to ruxolitinib 1.5% cream at baseline will continue to apply ruxolitinib 
cream through Week 32. In the OLE period, participants will only treat lesions that are 
symptomatic. At Week 16, the LP treatment area will be evaluated by the investigator to assess 
the disease and confirm whether treatment continuation is required (IGA score ≥ 1) during the 
OLE period or can otherwise (re)enter an observation/no treatment cycle (IGA score = 0; see 
also Section 6.1). Treatment assignment during the DBVC period will remain blinded until all 
participants have completed treatment or discontinued. Table 3 presents the SoA.  
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. 
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. 


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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 aged 18 years or older. 
3. Clinical diagnosis of LP with predominant cutaneous involvement. 
4. IGA score of 3 or 4 at screening and baseline. 
5. LP affecting ≤ 20% of the BSA at screening and baseline.  
6. Baseline LP-related Itch NRS score ≥ 4. Baseline Itch NRS is defined as the 7-day 
average of Itch NRS score before Day 1 (data from a minimum of 4 out of 7 days directly 
prior to Day 1 is needed).  
7. 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 study treatment 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 a negative urine pregnancy test before the first study cream 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 
treatment 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. A female participant not considered to be of childbearing potential as defined in 
Appendix A is eligible. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Concurrent conditions and history of other diseases: 
a. Variants of LP deemed by the investigators to be inappropriate for topical treatment, 
including but not limited to predominant mucosal (such as oral or vaginal) LP. 
Note: Participants with mucosal LP can be eligible if they have predominant 
cutaneous LP and agree to not treat mucosal LP during the study.  
b. Active ongoing inflammatory diseases of the skin other than LP that might confound 
the evaluation of LP lesions or compromise participant safety. 
c. 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 LP lesions or compromise 
participant safety. 
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. 
f. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chickenpox, clinically infected AD, or impetigo) within 1 week before 
baseline.  
2. Participants with the following conditions:  
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 mm Hg) unless approved by the medical monitor/sponsor. 
b. Current or previous malignancy within 5 years of study entry, except for adequately 
treated nonmetastatic nonmelanoma skin cancer. 
c. Unstable asthma or COPD requiring systemic treatment (such as intravenous steroids) 
or hospital admission or emergency department treatment within 3 months from 
baseline or stable asthma or COPD requiring budesonide more than 720 µg/day 
(2 puffs BID of 180-μg dose) or fluticasone more than 440 μg/day (2 puffs BID of 
110-μg dose) or other equivalent inhaled corticosteroids.  
d. Current and/or history of arterial or venous thrombosis, including deep venous 
thrombosis and pulmonary embolism. 
e. Current and/or history of active tuberculosis or current and/or history of latent 
tuberculosis unless adequately treated. 
f. History of severe anemia, severe thrombocytopenia, or severe neutropenia. 
g. 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. Investigator 
should consult with the medical monitor to clarify eligibility when in doubt. 


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3. Any of the following clinical laboratory test results at screening: 
a. Cytopenias, defined as follows: 
− Hemoglobin < 100 g/L (ie, 10 g/dL) 
− Absolute neutrophil count < 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 glomerular filtration rate < 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 of acute or chronic active hepatitis B or C virus infection. Participants who 
have recovered or have been successfully treated with no evidence of active hepatitis 
B or C 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.  
4. Use of any of the following treatments within the indicated washout period before the 
baseline visit: 
a. 5 half-lives or 12 weeks, whichever is longer – biologic agents (eg, dupilumab). For 
biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult 
the medical monitor. 
b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs, 
cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or 
immunomodulating agents (eg, mycophenolate or tacrolimus).  
c. 2 weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. 
d. 2 weeks – systemic antibiotics and immunizations with live-attenuated vaccines, 
sedating antihistamines unless on a long-term stable regimen (nonsedating 
antihistamines are permitted).  
e. Note: Live-attenuated vaccines are prohibited during the DBVC period. COVID-19 
vaccination is permitted.  
f. 2 weeks – treatment with topical therapy (eg, topical corticosteroids, pimecrolimus, 
and tacrolimus).  
5. 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. 
6. Pregnant or lactating participants, or those considering pregnancy during the period of 
their study participation. 
7. 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. 


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8. Previous treatment with systemic or topical JAK inhibitors (eg, ruxolitinib, tofacitinib, 
baricitinib, filgotinib, lestaurtinib, pacritinib). 
9. Inadequate venous access in nonlesional areas or in areas not treated by the study drug.  
10. Known allergy or reaction to any of the components of the study drug. 
11. In the opinion of the investigator, are unable or unlikely to comply with the 
administration schedule and study evaluations. 
12. Committed to a mental health institution by virtue of an order issued either by the judicial 
or the administrative authorities. 
13. Employees of the sponsor or investigator or otherwise dependents of them. 
5.3. 
Lifestyle Considerations 
Participants should be cautioned to avoid excessive 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 1 hour before or 2 hours after the planned study drug application. Participants should not 
wash the area where study cream has been applied for at least 2 hours after application of study 
cream. 
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 Treatments Administered 
Ruxolitinib cream or matching vehicle will be applied as a thin film BID, with applications 
approximately 8 to 12 hours apart in the morning and in the evening at least 1 hour before 
bedtime.  
At the baseline visit, an estimate of the %BSA to be treated will be used by the IRT system to 
calculate the number of tubes of study cream to be dispensed. During clinic visits, the participant 
should apply a thin film of study cream in front of site staff until all the affected areas to be 
treated are covered. This supervised application will be limited to 1 application of the study drug 
during the clinic visit. 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 
cream. If there are new areas to be treated, including expansion of existing areas or development 
of new areas, after consultation with the investigator, study cream should be applied to these 
areas in addition to the areas treated at baseline (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 cream to be dispensed. 
Participants whose 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 the EOT assessment should 
be completed.  
During the OLE period, starting at the Week 16 visit, the LP treatment areas will be evaluated by 
the investigator to assess if they still have disease and confirm whether the participant requires 
continuation of therapy (IGA score ≥ 1) or can otherwise (re)enter the observation/no treatment 
cycle (IGA score = 0). Participants will stop treatment applications 3 days after all LP signs and 
symptoms have resolved. Multiple cycles of treatment/no treatment may be utilized as needed 
and treatment start/stop dates should be recorded by the participant in their eDiary. At any time 
during the OLE period, if a participant's new areas to be treated in addition to the areas identified 
at the previous visit exceed 20% BSA, then the participant should be discontinued from study 
treatment and the EOT assessment should be completed.  
The amount of study cream 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. 


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Table 5: 
Study Treatment Information 
 
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 8-12 hours apart for 16 weeks. 
OLE period: Apply a thin film to affected areas in the morning and at 
least 1 hour before bedtime with applications approximately 8-12 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. 
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. Participants should store study treatment at ambient 
temperature conditions. 
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. 


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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 IGA score (3, 4), 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). 
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 period of the 
study. Participants who are noncompliant during the DBVC period and OLE period (if on a 


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treatment cycle) will be reinstructed by the investigator (or designee), and the sponsor should be 
consulted by the investigator for instruction on the proper handling of the participant. 
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 study drug interruption or permanent discontinuation if 
needed (eg, for management of an AE).  
Temporary interruption could be due to an AE during the DB VC or OLE period or clearance of 
the LP during the OLE period. 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
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 as a result of AEs 
or laboratory abnormalities that may have an unclear relationship to study drug (see Table 6). 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 
consult with the medical monitor before interrupting study drug applications. Additionally, the 
investigator should 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. 


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Table 6: 
Guidelines for Interruption of Study Drug for Treatment-Related Adverse 
Events 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. 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug Due to an Adverse Event 
The occurrence of unacceptable severity of an AE, such that it would interfere with study drug 
treatment or study procedures, 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, compromises the 
participant's ability to continue study-specific procedures, or continuing in the study 
is considered to not be in the participant's best interest.  
• Worsening of LP that requires treatment with a prohibited concomitant medication. 
• Adverse event requiring an interruption of study drug for more than 2 weeks. 
• Confirmed Grade 4 laboratory abnormalities deemed related to study drug. 


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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-LP medications received up to 28 days before the first application of study treatment will be 
recorded in the eCRF. Any prior LP 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 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 application 
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. 
6.6.1. 
Permitted Medications and Procedures 
The following are permitted during the study if, in the judgment of the investigator, the intake of 
these medications and procedures will not impact the safety of the participant or efficacy of the 
treatment: 
• Participants may use/continue to use bland emollients. Participants may not change or 
introduce a new emollient within 4 weeks of the baseline visit. 
Note: Emollients should not be used within 2 hours before and 1 hour after 
application of study drug. 
• Participants may use nonsedating, over-the-counter antihistamines. 
• Established and stable treatment with sedating antihistamines (≥ 28 days prior to 
baseline) may be continued. 
• Use of inhaled corticosteroids for bronchial asthma or COPD is allowed with the dose 
equivalent of budesonide (not to exceed 720 µg/day or 2 puffs BID of a 180-μg dose) 
or fluticasone (not to exceed 440 μg/day or 2 puffs BID of a 110-μg dose) or other 
equivalent inhaled corticosteroids.  
• Use of any over-the-counter, nonprescription vitamins, minerals, and 
phytotherapeutic, herbal, or plant-derived preparations is permitted.  


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6.6.2. 
Restricted Use 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 the 
follow-up visit: 
• Use of any prescription medication to treat chronic medical conditions (such as 
hypertension) if on a stable regimen in the judgment of the investigator. 
• Short course of topical anti-infectives (including antibacterial, antifungal, and 
antivirals) if used ≤ 5 days on active LP lesions to treat skin infection. Anti-infective 
treatment should not be used for at least 2 hours before and 1 hour after application of 
study cream. 
6.6.3. 
Prohibited Medications and Procedures 
No rescue treatment or therapy is allowed during the study. In addition, the following are not 
permitted during the study:  
• Any investigational medication other than the study drug. 
• Medications to treat LP (such as retinoids, methotrexate, thalidomide, heparin, 
griseofulvin, cyclosporine, sulfasalazine, mycophenolate, hydroxychloroquine or 
metronidazole, etc). Other treatments known to affect the course of LP are also 
prohibited. 
• Topical corticosteroids or calcineurin inhibitors. 
• Systemic corticosteroids, methotrexate, cyclosporin A, azathioprine and biological 
therapies, or other immunosuppressant/immunomodulator agents. 
• Any other topical or systemic treatment for LP. 
• Concomitant use of strong inhibitors of CYP3A4. 
• Phototherapy (such as ultraviolet B) or tanning beds. 
• Live-attenuated vaccination during the DBVC period.  
Note: COVID-19 vaccination (not live-attenuated) is permitted. 
6.7. 
Treatment After the End of the Study 
There will be no treatment provided after the end of the study. 


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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. 
• Worsening LP and treatment with a prohibited medication 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 for the following reasons: 
• 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 administration 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/EOT2 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. 
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. 


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• 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. 
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 [example only; not applicable to this 
Protocol]) 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 study-related data will be used 
by the sponsor 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. 


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• 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. 
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 eDiaries 
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 
and will also remind the participant that their morning application of study cream (if applicable) 


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will take place at the clinic under site supervision after blood draws for
 safety 
evaluations have been completed. 
Participants will be provided with a handheld device at the screening visit. The participant will 
start using the eDiary function of the handheld device on Day 1. The date and time of the last 
application of study drug 
 will be recorded in the 
eDiary. 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 
history, and current illnesses. Medical history will include relevant medical or surgical treatment 
within the last 2 years that are considered to be clinically significant by the investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
Relevant medical and treatment history for the past year will be collected at screening by the 
investigator or qualified designee. Details regarding the participant's history of LP, including 
date of diagnosis, relevant disease characteristics, and prior treatments with outcome (eg, 
inadequate response) and reason for stopping treatment, will be recorded.  


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8.2. 
Efficacy Assessments 
8.2.1. 
Health Economics 
Health economics parameters are not evaluated in this study. 
8.2.2. 
Investigator's Global Assessment  
The IGA to assess cutaneous LP has been modified by the sponsor to appropriately assess LP. 
The investigator/rater will assess the lesions at the study visits indicated in Table 3 by using the 
descriptors 
 that best describe the overall appearance of the lesions at a given 
timepoint. It is not necessary that all characteristics under the morphological description be 
present.  
IGA-TS is defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline. 


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8.2.8. 
Patient-Reported Outcomes 
Patient-reported outcomes will be collected and assessed as outlined in the SoA (see Table 3). 
For all patient-reported outcome assessments conducted at the study site, in order to avoid bias in 
the participants' responses to the questionnaires, assessments should be completed before any 
other evaluations or study procedures on the day of the study visit and prior to treatment-related 
discussions with the investigator or study site staff. 
8.2.8.1. 
eDiary Assessments 
The participant will be instructed to complete and record their Itch NRS and Skin Pain NRS 
scores via eDiary every evening beginning on the day of screening through Week 32 or ET. 
Both the Itch NRS and Skin Pain NRS are a daily participant-reported measure (24-hour recall) 
of the worst level of itch or skin pain intensity related to LP. 
The participants will rate the following:  
• Itch NRS: Itch severity of their LP 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.  
• Skin Pain NRS: Pain severity of their LP 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.  


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The average of the 7-day Itch NRS score prior to the baseline visit (minimum 4 out of 7 days' 
data required) will be used to determine if a participant meets the inclusion criteria. 
Detailed directions for the administration of the eDiary will be provided in the Study Manual. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see 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. 


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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 (EOT2)/ET 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. Fitzpatrick skin classification will be included as part of the physical 
examination at screening.  
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. 
Height and body weight will be assessed at screening and the Week 32 (EOT2)/ET visit.  
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 8 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) and will store the samples for 
 PD 
analysis. 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 8: 
Schedule of Laboratory Assessments 
Chemistry 
Hematology 
Serology 
Pregnancy Testing 
Alkaline phosphatase 
ALT 
AST 
Blood urea nitrogen or 
urea 
Creatinine 
Creatine kinase 
Glucose 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is elevated 
above ULN) 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell 
count 
• Reticulocyte count 
• White blood cell 
count 
Differential count 
(absolute and %), 
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 screeningc and a 
urine pregnancy test at 
all other visits. A 
positive urine test will 
be confirmed by a 
serum test. 
Pregnancy tests (serum 
or urine) should be 
repeated if required by 
local regulations. 
Note: Additional tests may be required, as agreed upon by the 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. 
c A negative urine pregnancy test at baseline is required prior to initiating Day 1 study cream application. 
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 and 
Table 8). 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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8.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time medically warranted, including when participants 
develop new areas of LP. Any assessments performed at those visits should be recorded in the 
eCRF. 


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8.7. 
End of Treatment and Early Termination 
The EOT coincides with the Week 32 visit. A participant that completes the Week 32/EOT2 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/EOT2 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.  
8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the Week 32 (EOT2)/ET visit and the 
scheduled follow-up visit, which should occur 30 days (+ 7 days' visit window) after the 
Week 32 (EOT2)/ET visit (or 30 days after the last application of study drug if the Week 32 
(EOT2)/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 or 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 or thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin or 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, or diagnostic reports) related to the event. 
• The investigator (or delegate) 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 Grades 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, or unknown). 
• The seriousness, 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). 


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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: 
• 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 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. 


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• 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. 
• 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 


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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. 
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 Event 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 Event 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. 


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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 
continue in the study. 
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. 
There are no study-specific warnings or precautions in this study. 


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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. 
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. 
10. 
STATISTICS 
10.1. 
Sample Size Determination 
Approximately 60 participants will be randomized 1:1 to ruxolitinib 1.5% cream BID or vehicle 
cream BID. The sample size calculation is based on the Fisher exact test for the primary efficacy 
endpoint, the proportion of participants achieving IGA-TS at Week 16. Based on previous 
studies (INCB 18424-303 and -304) and the results from an investigator sponsored trial 
(Mangold et al 2021) with topical ruxolitinib (NCT03697460), the preliminary assumption of 
response rates is 58% for ruxolitinib 1.5% cream and 20% for vehicle cream. Using a 2-sided 
alpha of 0.05, the sample size based on the current setup will have > 80% power to detect a 
difference between active treatment and vehicle.  
In addition to providing adequate power for efficacy variables, the sample size is determined to 
provide an adequate database for safety evaluations. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 9. 


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Table 9: 
Populations for Analysis 
Population 
Description 
ITT 
The ITT population includes all randomized participants. 
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. 
OLE evaluable 
All analyses for the OLE period will be conducted with the OLE evaluable 
population, which includes all participants who applied ruxolitinib 1.5% 
cream at least once during the OLE period. 
 
 
 
 
 
 
 
 
10.3. 
Level of Significance 
The significance level for primary efficacy analysis will be 0.05 for a 2-sided test. 
10.4. 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the participant 
populations to be included in the analyses and procedures for accounting for missing, unused, 
and spurious data. This section is a summary of the planned statistical analyses of the primary 
and secondary endpoints. 
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 10. 


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Table 10: 
Summary of Primary Analysis 
Parameter 
Definition 
Treatment 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population  
ITT population 
Variable 
IGA-TS response at Week 16: achieving an IGA score of 0 or 1 with ≥ 2-grade 
improvement from baseline at Week 16 
Population-level 
summary 
IGA-TS response rate difference with 95% CI 
Note: Participants with missing Week 16 data, as well as all participants who discontinue study treatment at any 
time before the timepoint of interest, or discontinue from the study for any reason, will be defined as 
nonresponders. No rescue therapy or treatment switch is allowed in this study. 
The primary alternative hypothesis (superiority of ruxolitinib 1.5% cream BID compared with 
vehicle) will be tested at a 2 sided α = 0.05 level using a Cochran-Mantel-Haenszel test stratified 
by baseline IGA score (3 or 4). The p-value and stratum-adjusted IGA-TS response rate 
difference with 95% CI will be provided. A summary of IGA-TS rates will be reported for each 
treatment group. Subgroup analysis by baseline characteristics will be performed. Details will be 
provided in the SAP. 
10.4.2. 
Secondary Analysis 
All secondary 
 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, STD, 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 Itch NRS score as well as the Skin Pain NRS score for each visit will be 
determined by averaging the 7 daily scores for Itch or Skin Pain before the corresponding visit 
day. If 4 or more daily scores are missing (out of the 7), the Itch NRS or Skin Pain NRS score at 
the visit will be set to missing. 
For the time to achieve ITCH4, a log-rank test stratified by randomization stratification factor 
will be used for between-treatment group comparisons. The hazard ratio and its 95% CI will be 
estimated based on the stratified Cox regression model using Efron's method accounting for ties. 
Kaplan-Meier curves will be presented by treatment groups. The number of participants, number 
of events, and number of censorings will be summarized by treatment groups. The Kaplan-Meier 
estimate of median time will be presented with its 95% CI. The 95% CI will be calculated using 
the method by Brookmeyer and Crowley (1982). 
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 


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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 
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 sponsor will be unblinded after the primary 
database lock; however, investigators and participants will remain blinded to the 
individual study treatment assignment. 
• 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 the 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 their 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, 
, 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;
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, 
, 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, 
 
 
 
 
 


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• 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/or the Monitoring Plan. 
Quality tolerance limits will be predefined in the Quality Risk Management Plan or Integrated 
Project Management Plan to identify systematic issues that can impact participants' 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 quality tolerance limits and remedial actions taken, including reporting to 
IRBs/IECs and health authorities if applicable, will be summarized in the CSR. 
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, and the sponsor operates comprehensive data 
privacy and data security programs that are applicable to this study. Appropriate notice, or notice 
and consent (as may be required by each applicable jurisdiction), for collection, use, disclosure, 


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and/or transfer (if applicable) of personal information must be obtained in accordance with local 
data protection laws. Appropriate data protection terms that comply with applicable laws will be 
included in relevant study agreements. 
To ensure confidentiality of records and protect personal data, 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. 
In the event of a data breach involving participant data, the sponsor or its designee will follow 
the sponsor's incident response procedures. The precise definition of a data breach varies in 
accordance with applicable law but may generally be understood as a breach of security leading 
to the accidental or unlawful destruction, loss, alteration, unauthorized disclosure of, or access to, 
personal data. In accordance with its incident response procedures, the sponsor will assess the 
breach to consider its notification and remediation obligations under applicable law. 
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 Clinical 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 
Alves de Medeiros AK, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J. JAK3 
as an emerging target for topical treatment of inflammatory skin diseases. PLoS One 
2016;11:e0164080. 
Axéll T, Rundquist L. Oral lichen planus—a demographic study. Community Dent Oral 
Epidemiol 1987;15:52-56. 
Boch K, Langan EA, Kridin K, Zillikens D, Ludwig RJ, Bieber K. Lichen planus. Front Med 
(Lausanne) 2021;8:737813.  
Boyd AS, Neldner KH. Lichen planus. J Am Acad Dermatol 1991;25:593-619.  
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
 
 
Chen J, Feng J, Chen X, et al. Immunoexpression of interleukin-22 and interleukin-23 in oral and 
cutaneous lichen planus lesions: a preliminary study. Mediators Inflamm 2013;2013:801974. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
Irvine C, Irvine F, Champion RH. Long-term follow-up of lichen planus. Acta Derm Venereol 
1991;71:242-244. 
Jalenques I, Lauron S, Almon S, Pereira B, D'Incan M, Rondepierre F. Prevalence and odds of 
signs of depression and anxiety in patients with lichen planus: systematic review and 
meta-analyses. Acta Derm Venereol 2020;100:adv00330. 
 
 
 
Kurago ZB. Etiology and pathogenesis of oral lichen planus: an overview. Oral Surg Oral Med 
Oral Pathol Oral Radiol 2016;122:72-80. 
Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med 2012;366:723-732. 
Li C, Tang X, Zheng X, et al. Global prevalence and incidence estimates of oral lichen planus: a 
systematic review and meta-analysis. JAMA Dermatol 2020;156:172-181. 
Mangold A, Brumfiel CM, Patel MH, Severson KJ, Zhang N, Pittelkow MR. Ruxolitinib cream 
in the treatment of cutaneous lichen planus. J Am Acad Dermatol 2021;85(suppl):AB10 [abstract 
25713]. 


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Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the 
treatment of atopic dermatitis: pooled analysis of two Phase 3, randomized, double-blind studies. 
Poster presented at: Revolutionizing Atopic Dermatitis Virtual Conference; December 2020. 
Pietschke K, Holstein J, Meier K, et al. The inflammation in cutaneous lichen planus is 
dominated by IFN-γ and IL-21—a basis for therapeutic JAK1 inhibition. Exp Dermatol 
2021;30:262-270. 
Ruxolitinib Cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
 
 
Schwager Z, Stern M, Cohen J, Femia A. Clinical epidemiology and treatment of lichen planus: 
a retrospective review of 2 tertiary care centers. J Am Acad Dermatol 2019;81:1397-1399. 
Shao S, Tsoi LC, Sarkar MK, et al. IFN-γ enhances cell-mediated cytotoxicity against 
keratinocytes via JAK2/STAT1 in lichen planus. Sci Transl Med 2019;11:eaav7561. 
 
 
Usatine RP, Tinitigan M. Diagnosis and treatment of lichen planus. Am Fam Physician 
2011;84:53-60. 
Wagner G, Rose C, Sachse MM. Clinical variants of lichen planus. J Dtsch Dermatol Ges 
2013;11:309-319. 
Weber B, Schlapbach C, Stuck M, et al. Distinct interferon-gamma and interleukin-9 expression 
in cutaneous and oral lichen planus. J Eur Acad Dermatol Venereol 2017;31:880-886. 
Welz-Kubiak K, Reich A. Mediators of pruritus in lichen planus. Autoimmune Dis 
2013;2013:941431. 
Weston G, Payette M. Update on lichen planus and its clinical variants. Int J Womens Dermatol 
2015;1:140-149. 
Żychowska M, Batycka-Baran A, Baran W. Increased serum level and high tissue 
immunoexpression of interleukin 17 in cutaneous lichen planus: a novel therapeutic target for 
recalcitrant cases? Dis Markers 2020;2020:6521274. 


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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 woman of childbearing potential 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, post ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea 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, 
 
). 
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, subject 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 
Document 
Date 
Amendment 1 
27 MAR 2023 
Amendment 1 (27 MAR 2023) 
Overall Rationale for the Amendment: 
 
 
 
 
 
 
 
 
 
2. Section 5.1, Inclusion Criteria (Criterion 7b) 
Description of change: Updated to include that WOCBP must have a negative serum 
pregnancy test at screening and a negative urine pregnancy test before the first study drug 
application on Day 1. 
Rationale for change: To be consistent with the pregnancy test requirements in the SoA. 
3. Section 5.2, Exclusion Criteria (Criterion 2b) 
Description of change: Updated to cover current or previous malignancy within 5 years 
of study entry, except for adequately treated nonmetastatic nonmelanoma skin cancer. 
Rationale for change: To be consistent with other ruxolitinib cream study protocols. 
4. Section 5.2, Exclusion Criteria (Criterion 2g) 
Description of change: Updated exclusion criterion 2 to relocate the investigator's 
opinion of conditions into new criterion 2g as one of the listed conditions. 
Rationale for change: To allow the investigator's opinion to determine additional 
exclusions. 
5. Section 10.4.2, Secondary Analysis 
Description of change: Updated to include Skin Pain NRS analysis from daily diary 
data. 
Rationale for change: Not specified in the original protocol. 
6. Incorporation of administrative changes. Other regulatory guidance and administrative 
changes have been incorporated in the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-019787 v4.0
Signature Page for VV-CLIN-019787 v4.0
Approval Task
Approval Task
Approval Task
Approval Task
Approver
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Approver

SAP_001.pdf: 
Official Title: A Randomized, Double-Blind, Vehicle-Controlled Study of the Efficacy and Safety of 
Ruxolitinib Cream in Participants With Cutaneous Lichen Planus
NCT Number: NCT05593432
Document Date: Statistical Analysis Plan: 30-Aug-2023


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Statistical Analysis Plan 
TITLE PAGE 
INCB 18424-216 
A Phase 2, Randomized, Double-Blind, Vehicle-Controlled, Study of the 
Efficacy and Safety of Ruxolitinib Cream in Participants With 
Cutaneous Lichen Planus 
IND Number: 
77,101 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 1 dated 27 MAR 2023 
CRF Approval Date: 
20 JUL 2023 
SAP Version: 
Original 
SAP Author: 
 PhD 
 
Date of Plan: 
30 AUG 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 ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................9 
2.1. 
Protocol and Case Report Form Version ......................................................................9 
2.2. 
Study Objectives and Endpoints ...................................................................................9 
3. 
STUDY DESIGN .......................................................................................................12 
3.1. 
Randomization ............................................................................................................12 
3.2. 
Control of Type I Error ...............................................................................................12 
3.3. 
Sample Size Considerations .......................................................................................13 
3.4. 
Schedule of Assessments ............................................................................................13 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................14 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................14 
4.1.1. 
Day 1 ...........................................................................................................................14 
4.1.2. 
Study Day ...................................................................................................................14 
4.1.3. 
Baseline Value ............................................................................................................14 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................15 
4.2. 
Variable Definitions ....................................................................................................15 
4.2.1. 
Body Mass Index ........................................................................................................15 
4.2.2. 
Prior and Concomitant Medication .............................................................................15 
5. 
STATISTICAL METHODOLOGY ...........................................................................16 
5.1. 
General Methodology .................................................................................................16 
5.2. 
Treatment Groups .......................................................................................................16 
5.3. 
Analysis Populations ..................................................................................................16 
5.3.1. 
Intent-to-Treat Population ..........................................................................................16 
5.3.2. 
Safety Population ........................................................................................................16 
5.3.3. 
Open-Label Extension Evaluable Population .............................................................16 
 
17 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................17 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................17 


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6.1.1. 
Demographics and Baseline Characteristics ...............................................................17 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................17 
6.1.3. 
Disease History ...........................................................................................................18 
6.1.4. 
Medical History ..........................................................................................................18 
6.2. 
Disposition of Participant ...........................................................................................18 
6.3. 
Protocol Deviations ....................................................................................................18 
6.4. 
Exposure .....................................................................................................................18 
6.5. 
Study Drug Compliance .............................................................................................19 
6.6. 
Prior and Concomitant Medication .............................................................................19 
7. 
EFFICACY .................................................................................................................20 
7.1. 
Efficacy Hypotheses ...................................................................................................20 
7.2. 
Efficacy Measures ......................................................................................................20 
7.2.1. 
Investigator's Global Assessment ...............................................................................20 
 
21 
 
21 
 
 
22 
7.2.5. 
Body Surface Area ......................................................................................................22 
7.2.6. 
Patient-Reported Outcomes ........................................................................................23 
7.2.6.1. 
Itch Numerical Rating Scale .......................................................................................23 
7.2.6.2. 
Skin Pain Numerical Rating Scale ..............................................................................23 
 
24 
 
24 
 
25 
 
25 
 
25 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................26 
7.3.1. 
Primary Efficacy Analysis ..........................................................................................26 
7.3.2. 
Subgroup Analyses for Primary Endpoint ..................................................................26 
7.4. 
Analysis of the Secondary Efficacy Parameters .........................................................26 
7.4.1. 
Continuous Efficacy Endpoints ..................................................................................26 
7.4.2. 
Categorical Efficacy Endpoints ..................................................................................26 
7.4.3. 
Time-To-Event Efficacy Endpoint .............................................................................27 


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27 
 
29 
 
29 
 
29 
9. 
SAFETY AND TOLERABILITY ..............................................................................30 
9.1. 
General Considerations ...............................................................................................30 
9.2. 
Adverse Events ...........................................................................................................30 
9.2.1. 
Adverse Event Definitions ..........................................................................................30 
9.2.2. 
Adverse Event Summaries ..........................................................................................31 
9.3. 
Clinical Laboratory Tests ...........................................................................................32 
9.3.1. 
Laboratory Value Definitions .....................................................................................32 
9.3.2. 
Laboratory Value Summaries .....................................................................................32 
9.4. 
Vital Signs ..................................................................................................................33 
10. 
PLANNED ANALYSES ............................................................................................33 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................34 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................34 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................34 
12. 
REFERENCES ...........................................................................................................35 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................36 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................9 
 
20 
 
22 
Table 4: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................33 
Table 5: 
Statistical Analysis Plan Versions ..............................................................................34 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
AIF 
area involvement factor 
ASR 
application site reaction 
BID 
twice daily 
BSA  
body surface area 
CI 
confidence interval 
CRF  
case report form 
CTCAE  
Common Terminology Criteria for Adverse Events 
DBVC  
double-blind, vehicle-controlled 
  
 
eCRF 
electronic case report form 
Ep 
erythematous papules 
Hp 
hyperpigmented hypertrophic papules and plaques 
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) 
ITCH4  
≥ 4-Point improvement in Itch NRS score 
ITT  
intent-to-treat 
  
 
  
 
  
 
  
 
 
 
  
 
MedDRA  
Medical Dictionary for Regulatory Activities 
MF 
multiplication factor 
NCI 
National Cancer Institute 
NRS  
numeric rating scale 
OLE  
open-label extension 
  
 
PIH 
postinflammatory hyperpigmentation 
 
 
 
 
PT 
preferred term 
rux 
ruxolitinib 


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Abbreviation 
Term 
SAP  
Statistical Analysis Plan 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
VC  
vehicle-controlled 
Vp 
violaceous flat papules 
Vpl 
violaceous flat plaques 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
INCB 18424-216 is a Phase 2, randomized, DBVC study to evaluate the efficacy and safety of 
ruxolitinib 1.5% cream BID in participants with cutaneous LP over a 16-week treatment 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 18424-216 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 18424-216 Protocol Amendment 1 dated 27 MAR 2023 and CRFs 
approved 20 JUL 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 cutaneous LP. 
• 
IGA-TS response is defined as an IGA score of 
0 or 1 with ≥ 2-grade improvement from baseline 
at Week 16; this is the proportion of participants 
achieving IGA-TS at Week 16. 
Secondary 
To further access the treatment effects of 
ruxolitinib 1.5% cream BID in participants with 
cutaneous LP. 
• 
IGA-TS response at each scheduled postbaseline 
visit up to and including Week 32 will be the 
proportion of participants achieving IGA-TS at 
each scheduled postbaseline visit. 
• 
ITCH4 response is defined as a ≥ 4-point 
improvement in Itch NRS score from baseline at 
each scheduled postbaseline visit, up to and 
including Week 32; it is the proportion of 
participants with ITCH4 at each scheduled 
postbaseline visit. 
• 
Time to achieve ITCH4. 
• 
Change from baseline in the Skin Pain NRS score 
at each scheduled postbaseline visit, up to and 
including Week 32. 
To evaluate the safety and tolerability of 
ruxolitinib 1.5% cream BID. 
• 
The type, frequency, and severity of AEs, 
including changes in vital signs and clinical 
laboratory blood samples. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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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 who have 
predominantly cutaneous LP (covering ≤ 20% BSA) and baseline IGA score ≥ 3. The study will 
consist of a 16-week DBVC period followed by a 16-week OLE period. 
Approximately 60 participants will be randomized 1:1 to either ruxolitinib 1.5% cream BID or 
vehicle cream BID. Participants will be stratified by baseline IGA score (3 or 4). 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 initially to vehicle cream 
in the DBVC period will be crossed over to ruxolitinib 1.5% cream BID and participants 
randomized to ruxolitinib 1.5% cream at baseline will continue to apply ruxolitinib 1.5% cream 
BID through Week 32. In the OLE period, participants will only treat active lesions up to 
20% BSA. At Week 16, the LP treatment area will be evaluated by the investigator to assess the 
disease and confirm whether treatment continuation is required (IGA score ≥ 1) during the 
OLE period or can otherwise (re)enter an observation/no treatment cycle (IGA score = 0). 
The study schema is shown below in Figure 1. 
Figure 1: 
Study Design Schema 
 
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. 
3.1. 
Randomization 
Approximately 60 participants will be randomized 1:1 to either ruxolitinib 1.5% cream BID or 
vehicle cream BID, stratified by baseline IGA score (3 or 4). 
3.2. 
Control of Type I Error 
The significance level for primary efficacy analysis will be 0.05 for a 2-sided test.  


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3.3. 
Sample Size Considerations 
Approximately 60 participants will be randomized 1:1 (ie, ruxolitinib 1.5% cream BID or 
vehicle cream BID) and stratified by baseline IGA (3 or 4). The sample size calculation is based 
on the Fisher exact test for the statistical comparison on the primary efficacy endpoint: the 
proportion of participants achieving IGA-TS at Week 16. Based on previous studies 
(INCB 18424-303 and -304) and the results from an investigator sponsored trial (Mangold 
et al 2021) with topical ruxolitinib (NCT03697460), the preliminary assumption of response 
rates is 58% for ruxolitinib 1.5% cream and 20% for vehicle cream. Using a 2-sided alpha of 
0.05, the sample size, based on the current setup, will have > 80% power to detect a difference 
between active treatment and vehicle. In addition to providing adequate power for efficacy 
variables, the sample size is determined to provide an adequate database for safety evaluations. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 1 dated 27 MAR 2023 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 cream or vehicle cream in the specific 
period. 
For randomized participants not treated with any study drug, Day 1 is defined as the date of 
randomization. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before or on the day of the first 
application of ruxolitinib cream or vehicle cream for the DBVC period. 
For randomized participants not treated with any study drug, baseline is defined as the last 
nonmissing assessment before randomization for all parameters. 
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: 
− For participants who cross over from vehicle group to ruxolitinib cream, the 
baseline is the last nonmissing measurement obtained before or on the day of first 
application of ruxolitinib cream in the OLE period. 
− For participants who apply ruxolitinib cream in both periods, baseline is the last 
nonmissing measurement obtained before or on the day of first application of 
study treatment in the DBVC period. 


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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 dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first application, but an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
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 LP diagnosis date will be handled as follows: 
• If only the day is missing, then the fifteenth of the month will be used. 
• If both the month and day are missing, then 01 JUL of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
Body mass index (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first application of 
ruxolitinib 1.5% cream BID or vehicle cream BID. 
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 study. 
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.  


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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, DBVC study followed by an OLE period. Table summaries, unless 
otherwise indicated, will present data by treatment group. 
For the DBVC period, the treatment groups will be vehicle cream and ruxolitinib 1.5% cream. 
For the OLE period, the participants will be grouped according to the treatment they received 
during the DBVC period: 
• Vehicle cream to ruxolitinib 1.5% cream 
• Ruxolitinib 1.5% cream 
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, and analyses of all efficacy data. 
5.3.2. 
Safety Population 
The safety population will include all participants who applied ruxolitinib 1.5% cream BID or 
vehicle cream BID 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 study 
drug treatment. 
All safety analyses will be conducted using the safety population. 
5.3.3. 
Open-Label Extension Evaluable Population 
All analyses for the OLE period will be conducted with the OLE evaluable population, which 
includes all participants who applied ruxolitinib 1.5% cream at least once during the OLE period. 


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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 
groups and overall for the ITT population in the DBVC period and for the OLE evaluable 
population in the OLE period: age, sex, race, ethnicity, weight, height, and body mass index. 
6.1.2. 
Baseline Disease Characteristics and Disease History 
For the ITT population, the baseline disease characteristics will be summarized by treatment 
group and will include, but not limited to, the following: 
• Disease duration (years) 
• LP diagnosis confirmed by previous biopsy (yes/no) 
• Anatomic location (hands/wrists, forearms/arms, neck, face, ankle/feet, legs, 
back/buttocks, chest, abdomen, mucosal-mouth, mucosal-nose, mucosal-
vulva/vagina, mucosal-esophagus, or other) 
• Variant (type) of LP (hypertrophic LP, annular LP, bullous LP, actinic LP, LP 
pigmentosus, inverse LP, atrophic LP, lichen planopilaris [follicular LP], nail LP, 
mucosal LP-oral, mucosal LP-genital, mucosal LP-esophageal, mucosal LP-otic, 
indeterminate/unspecified, unknown, or other) 
• Family history of LP (yes/no) 
• History of skin infection related to LP requiring antibiotic treatment (yes/no) 
• History of other skin diseases (yes/no) 
• Days since onset of current episode of LP flare/activity 
• Number of flares/episodes of LP in the past year other than current flare the 
participant experienced 
• Clinical manifestations related to LP (% participants with each of the manifestations) 
• Prior treatment received for LP (yes/no) 
 
 


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• Skin type using Fitzpatrick classification (Type I through VI) 
• Total % BSA affected  
• Baseline IGA score 
• Baseline Itch NRS score 
• Baseline Skin Pain NRS 
6.1.3. 
Disease History 
The time since disease duration will be summarized for all participants in the ITT population. 
Time since diagnose (ie, disease duration [years]) will be calculated as follows: 
Disease duration (years) = (date of randomization – date of initial LP diagnosis +1) / 
365.25. 
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 as part of 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 as part of the OLE evaluable 
population. 
6.3. 
Protocol Deviations 
Protocol deviations will be summarized and listed by treatment group and overall for ITT and 
OLE populations. 
6.4. 
Exposure 
For participants in the safety population in the DBVC period, the OLE evaluable population in 
the OLE period, and those who applied ruxolitinib 1.5% cream BID throughout the study, study 
drug exposure will be summarized by treatment group, descriptively, as follows: 
• Duration of treatment (days): 
Date of last application of ruxolitinib cream or vehicle cream in the specific period –  
date of first application of ruxolitinib cream or vehicle cream in the specific period + 1 


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• Total amount of cream applied (g): 
Total weight of ruxolitinib cream or vehicle cream dispensed in the specific period –  
total weight of ruxolitinib cream or vehicle cream returned in the specific period 
• Average daily application: 
Total amount of cream applied in the specific period (g) / [duration of treatment with 
study cream in the specific period (days) – number of interrupted days with study cream 
in the specific period].  
6.5. 
Study Drug Compliance 
The overall compliance (%) for the application of ruxolitinib 1.5% cream BID or vehicle cream 
BID during the DBVC period will be calculated for all participants in the safety population as 
follows:  
Cream application compliance (%) = 100 × [total number of nonmissing applications] / [total 
number of intended applications], where  
Total number of nonmissing applications = number of applications that the participants 
actually applied during the study, and 
Total number of intended applications = 2 × duration of treatment (days) – number of 
interrupted applications. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
The number and percentage of participants with prior and concomitant medication will be 
summarized by treatment group, as well as overall for the ITT population during the DBVC 
period by WHO drug class and WHO drug preferred term. For the OLE period, only concomitant 
medications will be summarized based on OLE evaluable 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 Hypotheses 
The primary hypothesis is the superiority of ruxolitinib 1.5% cream BID compared with vehicle 
cream BID in the proportion of participants achieving IGA-TS at Week 16.  
7.2. 
Efficacy Measures 
7.2.1. 
Investigator's Global Assessment 
The IGA to assess cutaneous LP has been modified by the sponsor to appropriately assess LP. 
The investigator/rater will assess the lesions at the study visits by using the descriptors 
 
that best describe the overall appearance of the lesions at a given timepoint. It is not necessary 
that all characteristics under the morphological description be present. 
The IGA-TS is defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline. 
Nonresponder imputation will be used to handle missing postbaseline values in the 
DBVC period. 
 
 


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7.2.5. 
Body Surface Area 
The total % BSA affected will be estimated at each visit. The BSA assessment will be 
approximated to the nearest 0.1% using the Palmar Method as a guide, which is the palm plus 
5 digits, with fingers tucked together and thumb tucked to the side (handprint) as 1% BSA and 
the thumb as 0.1% BSA. 


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7.2.6. 
Patient-Reported Outcomes 
Patient-reported outcomes will be collected and assessed. For all patient-reported outcome 
assessments conducted at the study site, in order to avoid bias in the participants' responses to the 
questionnaires, assessments will be completed before any other evaluations or study procedures 
on the day of the study visit and prior to any treatment-related discussions with the investigator 
or study site staff. 
7.2.6.1. 
Itch Numerical Rating Scale 
The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch 
intensity (Kimball et al 2016, Silverberg et al 2021). Participants will be instructed to complete 
and record their Itch NRS in a diary each evening beginning on the day of screening through 
Week 32 or treatment discontinuation, whichever comes first. Participants will rate itch severity 
of their LP by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best 
describes the worst level of itch they experienced in the past 24 hours. 
The participant's baseline Itch NRS score will be determined by averaging the 7 daily NRS 
scores before Day 1 (ie, Days –7 to –1) for all the 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 (out of the 7) are missing, the by-visit Itch NRS score will be 
set to missing. For all daily itch-related analyses, including time to achieve Itch NRS score 
improvement of at least 4 points analysis, baseline will be defined as the last available Itch NRS 
score during the week prior to Day 1 (ie, Days −7 to −1). Nonresponder imputation will be used 
to handle missing postbaseline values in the DBVC period.  
A participant is said to have an ITCH4 response if they achieved a ≥ 4-point improvement in 
Itch NRS score from baseline. For determining ITCH4 response at a visit, the by-visit Itch NRS 
score will be compared with the baseline Itch NRS score. For the endpoint time to achieve 
ITCH4, the daily Itch NRS score will be compared with the baseline Itch NRS score. 
7.2.6.2. 
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. Participants 
will rate their pain, which will include all types of pain (eg, burning, tearing, pulling, stabbing, 
etc) severity of the LP by selecting a number from 0 (no pain) to 10 (worst imaginable pain) that 
best describes the worst level of pain they experienced in the past 24 hours. 
The participant's baseline Skin Pain NRS score will be determined by averaging the 7 daily NRS 
scores before Day 1 (ie, Days –7 to –1). 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 (out of the 7) are missing, the Skin Pain NRS score at the visit will be set to missing. No 
imputation will be performed for missing values. 


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7.3. 
Analysis of the Primary Efficacy Parameter 
7.3.1. 
Primary Efficacy Analysis 
The primary efficacy analysis will be based on the ITT population. The primary efficacy 
endpoint is the IGA-TS response, defined as an IGA score of 0 or 1 with ≥ 2-grade improvement 
from baseline, at Week 16. The comparison of the proportions of participants achieving IGA-TS 
at Week 16 will be made between the ruxolitinib 1.5% cream BID arm and the vehicle cream 
BID arm. The primary hypothesis (the superiority of ruxolitinib 1.5% cream BID compared with 
vehicle cream BID in participants with cutaneous LP) will be tested using a 
Cochran-Mantel-Haenszel test stratified by baseline IGA score (3 or 4) at a 2-sided 
α =  0.05 level. The p-value and stratum-adjusted IGA-TS response rate difference with 95% CI 
will be provided. A summary of IGA-TS rates will be reported for each treatment group. 
Nonresponder imputation will be used to handle missing postbaseline values in the 
DBVC period. 
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: 
• Sex: female versus male 
• Baseline categorical age: ≥ 18 and < 65 versus ≥ 65 
• Baseline duration of disease: ≤ 1, > 1 and ≤ 5, > 5 
• Race: Black/African American versus White/Asian/other 
The primary efficacy endpoint will be summarized 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 
Summary statistics for the following continuous measurements, including change from baseline, 
will be presented for each treatment arm: 
• By-visit Skin Pain NRS score 
The summary statistics, including sample size, mean, median, standard deviation, minimum, 
maximum, first quartile, third quartile, and 95% CI, will be presented by visit. 
7.4.2. 
Categorical Efficacy Endpoints 
For the following categorical parameters, summary statistics, including sample size, frequency, 
and percentages, will be presented by visit. 
• IGA-TS response 
• By-visit ITCH4 response 


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In addition, a Cochran-Mantel-Haenszel test stratified by baseline IGA score (3 or 4) at a 2-sided 
α = 0.05 level will be used for the comparison between ruxolitinib 1.5% cream BID and vehicle 
cream BID at Week 16 for ITCH4 response. The p-value and stratum-adjusted response rate 
difference with 95% CI will be provided. 
7.4.3. 
Time-To-Event Efficacy Endpoint 
The time to achieve Itch NRS score improvement of at least 4 points from baseline (ie, ITCH4) 
will use the daily Itch NRS score in comparison to baseline Itch NRS score in the DBVC period. 
A log-rank test stratified by randomization stratification factor, baseline IGA score (3 or 4), will 
be used for between-treatment group comparisons. The hazard ratio and its 95% CI will be 
estimated based on the stratified Cox regression model using Efron's method accounting for ties. 
Kaplan-Meier curves will be presented by treatment groups. The number of participants, number 
of participants with events, and number of participants censored will be summarized by 
treatment group. The Kaplan-Meier estimate of median time will be presented with its 95% CI. 
The 95% CI will be calculated using the method by Brookmeyer and Crowley (1982). 
The last available value for time to ITCH4 during the DBVC period is the last nonmissing 
measurement obtained after the first application of study cream and within 30 days after the last 
application of study cream in DBVC period, or before the first application of study cream in the 
OLE period, whichever is earlier. 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. 
9.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the DBVC period and 
the OLE evaluable population in the OLE period, 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; however, 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 NCI CTCAE v5. 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. 
Application site reactions are AEs that occur at the site of drug application. A summary of ASRs 
will be provided. 


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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 
• Number (%) of participants reporting any treatment-related TEAEs  
• 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 


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9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
All laboratory assessments will be performed using a central laboratory with the exception of 
urine pregnancy tests. 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. 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. 


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9.4. 
Vital Signs 
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. 
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 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 20 breaths/min 
< 8 breaths/min 
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 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 
30 AUG 2023 
11.1. 
Changes to Protocol-Defined Analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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12. 
REFERENCES 
 
 
 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
 
 
 
 
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. 
Mangold A, Brumfiel CM, Patel MH, Severson KJ, Zhang N, Pittelkow MR. Ruxolitinib cream 
in the treatment of cutaneous lichen planus. J Am Acad Dermatol 2021;85(suppl):AB10 [abstract 
25713]. 
Ruxolitinib Cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
 
 
 
 
 
 
 


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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 
ITT 
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 in the DBVC 
Period 
ITT 
X 
1.2.2 
Summary of Demographics and Baseline Characteristics in the OLE 
Period 
OLE 
X 
1.3 Baseline Disease Characteristics 
1.3.1 
Summary of Baseline Disease Characteristics in the DBVC Period 
ITT  
X 
1.3.2 
Summary of Baseline Disease Characteristics in the OLE Period 
OLE 
X 
1.4 Prior and Concomitant Medication 
1.4.1 
Summary of Prior Medications in the DBVC Period 
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 in the DBVC Period 
ITT 
X 
Efficacy 
2.1 IGA Score 
2.1.1 
Summary and Analysis of Participants Achieving IGA-TS in Treatment 
Periods 
ITT 
 
2.1.2 
Summary and Analysis of Participants Achieving IGA-TS by Sex in 
Treatment Periods 
ITT 
 
2.1.3 
Summary and Analysis of Participants Achieving IGA-TS by Categorical 
Age in Treatment Periods 
ITT 
 
2.1.4 
Summary and Analysis of Participants Achieving IGA-TS by Duration 
of Disease in Treatment Periods 
ITT 
 


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Table No. 
Title 
Population 
Standard 
2.1.5 
Summary and Analysis of Participants Achieving IGA-TS by Race in 
Treatment Periods 
ITT 
 
2.1.6 
Summary of Participants in Each Category of IGA in Treatment Periods 
ITT 
 
2.2 Itch NRS Score 
2.2.1 
Summary of Participants Achieving ITCH4 in Treatment Periods 
ITT 
 
2.2.2 
Summary of By-Visit Itch NRS Score in Treatment Periods 
ITT 
 
2.2.3 
Summary of Daily Itch NRS Score from Day 1 to Day 28 
ITT 
 
2.2.4 
Summary of Time to ITCH4 in the DBVC Period 
ITT 
 
2.3 Skin Pain NRS Score 
2.3.1 
Summary of By-Visit Skin Pain NRS Score in Treatment Periods 
ITT 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.13 BSA 
2.13.1 
Summary of Total % BSA in Treatment Periods 
ITT 
 
Safety 
3.1 Exposure & 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 


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Table No. 
Title 
Population 
Standard 
3.1.1.3 
Summary of Exposure in Treatment Periods 
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 
X 
3.2.14.x 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome 
by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.16.x 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Interruption by MedDRA System Organ Class and Preferred Term  
Safety 
X 
3.2.17.x 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ Class and 
Preferred Term  
Safety 
X 
3.2.18.x 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety 
X 
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 
X 
3.3.2.2.x 
Shift Summary of Chemistry Laboratory Values – to the Worst 
Abnormal Value  
Safety 
X 


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Table No. 
Title 
Population 
Standard 
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, OLE period, and the treatment 
periods (DBVC and OLE periods). 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 
Proportion of Participants Achieving IGA-TS in Treatment Periods 
ITT 
4.1.1.2 
Proportion of Participants Achieving IGA-TS by Sex in Treatment Periods 
ITT 
4.1.1.3 
Proportion of Participants Achieving IGA-TS by Baseline Age Group in Treatment 
Periods 
ITT 
4.1.1.4 
Proportion of Participants Achieving IGA-TS by Baseline Duration of Disease in 
Treatment Periods 
ITT 
4.1.1.5 
Proportion of Participants Achieving IGA-TS by Race in Treatment Periods 
ITT 
4.1.1.5 
Forest Plot of Response Rate Difference in Achieving IGA-TS at Week 16 
ITT 
4.2.1.1 
Proportion of Participants Achieving ITCH4 in Treatment Periods 
ITT 
4.2.2.1 
Mean and Standard Error Plot of By-Visit Itch NRS Score in Treatment Periods 
ITT 
 
 
 
 
4.2.3.1 
Mean and Standard Error Plot of Daily Itch NRS Score from Day 1 to Day 28 
ITT 
 
 
 
 
4.2.4 
Kaplan-Meier Curve of Time to ITCH4 in the DBVC Period 
ITT 
4.3.1.1 
Mean and Standard Error Plot of By-Visit Skin Pain NRS Score in Treatment 
Periods 
ITT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listings 
Listing No. 
Title 
2.1 Demographic and Baseline Characteristics 
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 Data Excluded From 
, Efficacy, and/or Safety Analyses 
2.3 
Analysis Populations 
2.4 Demographic and Baseline Characteristics (Including Prior and Concomitant Medications) 
2.4.1 
Demographic and Baseline Characteristics  
2.4.2 
Baseline Disease Characteristics  
2.4.3 
Medical History  
2.4.4 
Prior and Concomitant Medications 
2.4.5 
Prior Medications for Cutaneous Lichen Planus 
2.5 Drug Exposure and Compliance 
2.5.1 
Study Drug Exposure and Compliance in the DBVC Period 
2.5.2 
Study Drug Exposure in the OLE Period 
2.6 Efficacy  
2.6.1 
IGA Score 
2.6.2.1 
By-Visit Itch NRS Score 
2.6.2.2 
Daily Itch NRS Score 
2.6.3.1 
By-Visit Skin Pain NRS Score 
2.6.3.2 
Daily Skin Pain NRS Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.7 Adverse Events 
2.7.1 
Adverse Events 


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Listing No. 
Title 
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 Interruption of Study Drug 
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 
2.8.1.4 
Abnormal Clinical Laboratory Values – Hematology 
2.8.1.5 
Abnormal Clinical Laboratory Values – Chemistry 
Vital Signs 
2.8.2.1 
Vital Signs 
2.8.2.2 
Abnormal Vital Sign Values 
2.8.2.3 
Alert Vital Sign Values