Conditions: Lichen Planus
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: no

Brief summary:
To evaluate the safety and efficacy of INCB018424 PHOSPHATE CREAM in cutaneous LP as assessed by the change in Physician Global Assessment (PGA), Body Surface Area (BSA), Index Treatment and Control Lesion by Clinical Assessment Scale of Severity for Index Lesion Signs and Symptoms (CAILS) score, Pruritus Numerical Rating Scale (NRS), and Skindex-16. To predict responses through the identification of unique biomarkers of LP at week 0 and utilizing RNA sequencing on responsive and non-responsive tissue at week 4.

Detailed description:
This is a single center, exploratory, open-label, single-arm design study of 12 patients. Treatment naïve and treatment refractory patients with LP will be treated with INCB018424 PHOSPHATE CREAM. Patients who are non-responders, to physician choice standard of care, will undergo a washout period and will be enrolled in the study. The study consists of 3 epochs: screening/washout period (of at least 1 week and up to 4 weeks), treatment epoch (of 8 weeks from screen/washout), and follow up epoch (of 4 weeks). The screening and washout period will allow for treatment naïve/ new diagnosis LP to undergo evaluation and diagnosis and for treatment refractory to undergo a washout. The total duration of the study will be 13-16 weeks.

Arms:
arm 1: INCB018424 Cream

Interventions: intervention 1: INCB018424
Intervention descriptions: intervention 1: INCB018424 PHOSPHATE CREAM 1.5%, topical application, twice daily on lesions of cutaneous LP.

Protocol document:
Prot_SAP_000.pdf: 
 
 
INCB018424 PHOSPHATE CREAM in the 
Treatment of Cutaneous Lichen Planus 
 
 NCT03697460 
 
29MAY2020 


 
 
 
INCB018424 PHOSPHATE CREAM in the Treatment of Cutaneous Lichen Planus 
 
 
 
 
 
 
Regulatory Sponsor: 
Mayo Clinic  
Aaron Mangold, M.D.   
Department of Dermatology  
13400 E Shea Blvd 
Scottsdale, AZ 85259  
(480)301-5686 
 
Funding Sponsor: 
(Optional) 
Incyte Corporation  
1801 Augustine Cut-Off 
Wilmington, DE 19803 
(302)498-6700 
   
Study Product: 
INCB018424 PHOSPHATE CREAM phosphate cream 
(ruxolitinib)    
Protocol Number: (IRBe) 
  
17-005406   
 
IND Number: 
139162 
 
 
 
 
 
 
Version Date 
Major Changes 
1.0 
11Sep2017 
Initial Protocol 
2.0 
25Apr2018 
Section 9.4 Stopping Rules; Grade 4 reduced to Grade 3 
3.0 
15Apr2019 
Added IND # to cover page 
5.1 Inclusion Criteria revised 
• 
LP up to 20% of the BSA 
• 
Subjects must have a minimum of 4 lesions, ideally 10 lesions of LP 
6.6. Drug labeling clarified 
4.0 
31Oct2019 
ECG removed throughout protocol  
5.0 
08Jan2020 
4.1 Up to 60 biopsies will be taken throughout study for analysis 
4.3 Table 2 and 7.7 Visit 7 Removed Drug Disbursement at Week 8 


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9.1 Supplemental 1: Skin Scoring: Added Lesion Count Methods 
Updated photos to be taken at every visit from Day 0 through Week 12 visit 
throughout protocol 
6.0 
29May2020 Updated CAILS assessment to Modified CAILS throughout protocol 
 
 


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Table of Contents 
 
STUDY SUMMARY ...................................................................................................................................... 6 
1 
INTRODUCTION ................................................................................................................................. 7 
1.1 
BACKGROUND ................................................................................................................................ 7 
1.2 
INVESTIGATIONAL AGENT ............................................................................................................... 8 
1.3 
PRECLINICAL DATA ........................................................................................................................ 8 
1.4 
CLINICAL DATA TO DATE .............................................................................................................. 11 
1.5 
DOSE RATIONALE AND RISK/BENEFITS ........................................................................................... 13 
2 
STUDY OBJECTIVES ........................................................................................................................ 16 
3 
STUDY DESIGN ................................................................................................................................. 16 
3.1 
GENERAL DESIGN ......................................................................................................................... 16 
3.2 
PRIMARY STUDY ENDPOINTS ........................................................................................................... 1 
3.3 
SECONDARY STUDY ENDPOINTS ....................................................................................................... 1 
3.4 
PRIMARY SAFETY ENDPOINTS .......................................................................................................... 1 
4 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL ........................................................ 2 
4.1 
INCLUSION CRITERIA ....................................................................................................................... 2 
4.2 
EXCLUSION CRITERIA ...................................................................................................................... 2 
4.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING .................................................................... 3 
4.4 
EARLY WITHDRAWAL OF SUBJECTS .................................................................................................. 3 
4.4.1 
When and How to Withdraw Subjects .......................................................................................... 3 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects ................................................................ 4 
5 
STUDY DRUG ...................................................................................................................................... 4 
5.1 
DESCRIPTION .................................................................................................................................. 4 
5.2 
TREATMENT REGIMEN ..................................................................................................................... 6 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ............ ERROR! BOOKMARK NOT DEFINED. 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ....................................................................... 6 
5.5 
SUBJECT COMPLIANCE MONITORING ................................................................................................ 6 
5.6 
PRIOR AND CONCOMITANT THERAPY ................................................................................................ 7 
5.7 
PACKAGING .................................................................................................................................... 7 
5.8 
BLINDING OF STUDY ..................................................................... ERROR! BOOKMARK NOT DEFINED. 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN ............................................................................... 7 
5.9.1 
Receipt of Drug Supplies ............................................................................................................ 7 
5.9.2 
Storage ..................................................................................................................................... 7 
5.9.3 
Dispensing of Study Drug ........................................................................................................... 7 
5.9.4 
Return or Destruction of Study Drug ........................................................................................... 8 
6 
STUDY PROCEDURES ........................................................................................................................ 8 
6.1 
VISIT 1 ........................................................................................................................................... 8 
6.2 
VISIT 2 ........................................................................................................................................... 8 
6.3 
VISIT 3, 4, 5, …ETC. ........................................................................................................................ 9 
7 
STATISTICAL PLAN ......................................................................................................................... 11 
7.1 
SAMPLE SIZE DETERMINATION ....................................................................................................... 11 
7.2 
STATISTICAL METHODS ................................................................................................................. 11 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ......................................................................................... 12 
8 
SAFETY AND ADVERSE EVENTS ................................................................................................... 13 
8.1 
DEFINITIONS ................................................................................................................................ 13 


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8.2 
RECORDING OF ADVERSE EVENTS .................................................................................................. 17 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ...................................... 17 
8.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB ............................................................. 17 
8.3.2 
Sponsor-Investigator reporting: Notifying the FDA ..................................................................... 19 
8.4 
UNBLINDING PROCEDURES ............................................................ ERROR! BOOKMARK NOT DEFINED. 
8.5 
STOPPING RULES  .......................................................................................................................... 21 
8.6 
MEDICAL MONITORING ................................................................................................................. 21 
8.6.1 
Internal Data and Safety Monitoring Board ................................. Error! Bookmark not defined. 
8.6.2 
Independent Data and Safety Monitoring Board ........................... Error! Bookmark not defined. 
9 
DATA HANDLING AND RECORD KEEPING .................................................................................. 23 
9.1 
CONFIDENTIALITY ........................................................................................................................ 23 
9.2 
SOURCE DOCUMENTS .................................................................................................................... 23 
9.3 
CASE REPORT FORMS .................................................................................................................... 23 
9.4 
RECORDS RETENTION .................................................................................................................... 24 
10 
STUDY MONITORING, AUDITING, AND INSPECTING ................................................................ 24 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 24 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 25 
11 
ETHICAL CONSIDERATIONS ......................................................................................................... 25 
12 
STUDY FINANCES ............................................................................................................................ 25 
12.1 
FUNDING SOURCE ......................................................................................................................... 25 
12.2 
CONFLICT OF INTEREST ................................................................. ERROR! BOOKMARK NOT DEFINED. 
12.3 
SUBJECT STIPENDS OR PAYMENTS .................................................................................................. 25 
13 
PUBLICATION PLAN ....................................................................................................................... 25 
14 
REFERENCES ................................................................................................................................... 26 
15 
ATTACHMENTS ............................................................................................................................... 27 
 
 
 
 
 
 
 
 


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List of Abbreviations 
 
 
LIST OF ABBREVIATIONS 
AE 
BSA 
CAILS 
 
 
Adverse Event/Adverse Experience 
Body Surface Area  
Clinical Assessment Scale of Severity for Index Lesion Signs & 
Symptoms 
CFR 
Code of Federal Regulations 
CRF 
CXCR3 
CXCL9 
DEGs 
Case Report Form 
Chemokine Receptor-3 
Chemokines Ligands 9 
Differentially Expressed Genes  
DSMB 
Data and Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
GVHD 
Good Clinical Practice 
Graft Versus Host Disease  
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
IL-1 
Investigator’s Brochure 
Interleukin-1 
IND 
IFN 
IFNγ 
Investigational New Drug Application 
Interferon Alpha 
Interferon Gamma 
IRB 
JAK 
LP 
LTR 
MDC 
NRS 
PDC 
PGA 
Institutional Review Board 
Janus Kinase  
Lichen Planus 
Lichenoid Tissue Reaction 
Myeloid Dendritic Cells   
Numerical Rating Scale  
Plasmacytoid Dendritic Cells  
Physician Global Assessment  
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
 
 
 
 
. 
 
 
 


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Study Summary 
Title 
INCB018424 PHOSPHATE CREAM in the Treatment of 
Cutaneous Lichen Planus 
 
Running Title 
INCB018424 PHOSPHATE CREAM in LP 
Protocol Number 
17-005406 
Phase 
Phase II 
Methodology 
Open-Label, Single Arm  
Overall Study 
Duration 
13 to 16 weeks  
Subject Participation 
Duration 
12 weeks  
Single or Multi-Site  
Single Site  
Objectives 
To evaluate the safety and efficacy of INCB018424 PHOSPHATE 
CREAM in cutaneous LP as assessed by the change in Physician Global 
Assessment (PGA), Body Surface Area (BSA), Index Treatment and 
Control Lesion by Modified Clinical Assessment Scale of Severity for 
Index Lesion Signs and Symptoms (Modified CAILS) score, Pruritus 
Numerical Rating Scale (NRS), and Skindex-16. To predict responses 
through the identification of unique biomarkers of LP at week 0 and 
utilizing RNA sequencing on responsive and non-responsive tissue at 
week 4.   
Number of Subjects 
12 
Diagnosis and Main 
Inclusion Criteria 
Non-pregnant adults with cutaneous LP involving less than 20% of the 
body surface area (BSA) 
Study Product, Dose, 
Route, Regimen 
INCB018424 PHOSPHATE CREAM 1.5%, topical application, twice 
daily on lesions of cutaneous LP. 
Duration of 
Administration 
Drug will be administered from Day 0 through Week 8.  
Reference therapy 
INCB018424 PHOSPHATE CREAM is currently being used to treat 
subjects with Plaque Psoriasis  
Statistical 
Methodology 
The statistical analysis will provide descriptive summary statistics for 
categorical and continuous outcomes.  Categorical variables will be 
described by their count and proportion of occurrence while 
continuous, normally distributed variables will be described by their 
mean and standard deviation; and continuous, non-normally distributed 
variables will be described by their median and range 
 


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2 
Introduction 
 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the applicable United States government regulations and Mayo Clinic research 
policies and procedures.  
2.1 
Background 
 
INCB018424 PHOSPHATE CREAM is a topical JAK1/2 inhibitor with potent activity on the 
cytokine IFN-γ. IFN-γ is a critical cytokine in the signaling of LP. This study is aimed at evaluating 
the effects of topical INCB018424 PHOSPHATE CREAM 1.5% twice daily on lesions of 
cutaneous LP.  
 
Lichenoid tissue reaction (LTR) includes: lichen planus (LP) cutaneous lupus, dermatomyositis 
(DM), and graft versus host disease (GVHD). The pathogenesis of LP is incompletely understood; 
however, it is clearly T-cell mediated without a known auto-antigen. Lichen Planus (LP) is an 
inflammatory skin condition characterized by purple, polygonal, pruritic, papules and plaques. LP 
can affect any ectodermally derived tissues including: the skin (most commonly), nails, and 
mucous membranes. LP is thought to affect approximately 1-2% of the general population. Most 
cutaneous LP resolves within one to two years. Disease duration, in ascending order, is: 
generalized cutaneous, non-generalized cutaneous, cutaneous and mucosal, mucosal, 
hypertrophic, and Lichen Planopilaris (hair LP). LP is the prototypical lichen tissue reaction(LTR). 
Modern theories of LP encompass three major stages: antigen recognition, lymphocyte activation, 
and keratinocyte apoptosis. A fourth stage, resolution, is a new and emerging topic. The occurrence 
of triggering factors in a genetically predisposed individual carrying LP-associated genes, results 
in disease development. During the initiation phase, damage to keratinocytes result in the release 
of DNA, RNA, and cathelicidin (LL37). These proteins can stimulate plasmacytoid dendritic cells 
(PDC) via toll like receptors 7, 9 (TLR7,9) which result in the release of interferon alpha (IFN). 
IFN can have both local and distant affects upon myeloid dendritic cells (MDC) as well as 
keratinocytes. Stimulated MDC interact with CD4+ T-helper cells and with the correct antigen. 
The antigen remains unknown but may represent a viral derived peptide. Signaling receptors on 
MDC will stimulate CD4+ T-helper cells via the release of Tumor necrosis factor alpha (TNF), 
Interleukin-1 (IL-1), and -12. In addition, cluster of differentiation- (CD40) and CD40 ligand 
(CD40L) will result in the co-stimulation of the T-helper/MDC interaction. Stimulated CD4+ T-
helper cells then release of interferon gamma (IFNγ) and IL-2. These cytokines stimulate CD8+ 
T-cytotoxic cells. The stimulated CD8+ cells expressing Chemokine receptor-3 (CXCR3) will 
migrate to the dermal-epidermal junction following the release of chemokines ligands 9(CXCL9), 
-10,-11. These chemokines are released by stressed and stimulated keratinocytes. The stimulated 
CD8+ cells will interact with the stressed keratinocytes and can induce apoptosis in with the proper 
and signaling receptors. This antigen also remains unknown but may be a self-antigen released by 
local stress. The major kill signals are TNF, granzyme, and perforin. Fas and Fas ligand (FasL) 
are expressed on both keratinocytes and lymphocytes. Local CXCR3+ DC and T-regulatory cells 
may also modulate the local lichenoid response.  
 
Based upon critical role of CD8+ T-cytotoxic cells and IFN and IFNγ signaling in LP, inhibition 
with topical Janus Kinase (JAK) 1, 2 inhibitors have significant therapeutic potential. The current 


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topical therapeutic options for LP are limited to topical corticosteroids, calcineurin inhibitors, and 
retinoids. Topical therapies are effective with limited disease but refractory disease is frequently 
encountered. Specific variants of LP, such as hypertrophic LP and localized cutaneous disease, are 
often refractory to all topical therapies and require systemic or skin-directed treatment with oral 
acitretin or methotrexate or light therapy. Therefore, additional topical therapies would be highly 
desirable in hypertrophic and refractory localized cutaneous LP. As proof of principle, systemic 
JAK1, 2 inhibition with ruxolitonib was highly effective in steroid refractory graft versus host 
disease (GVHD). (1) Additionally, there was a recent case report of an exceptional responder to 
JAK1, 2 inhibition with ruxolitinib in refractory dermatomyositis (DM). (2) As stated above, DM, 
GVHD, and LP share a similar histological pattern as well as signaling mechanism and, therefore, 
we would expect LP to respond similarly with systemic as well as topical treatment. To test this 
concept, we would propose a single-center, exploratory, open-label, single-arm design study using 
topical JAK1, 2 inhibitor on selected lesions of LP. 
 
2.2 
Investigational Agent 
 
INCB018424 PHOSPHATE (ruxolitinib) is an inhibitor of the JAK family of protein tyrosine 
kinases. Mitogenic and inflammatory cytokines are strongly implicated in the pathogenesis of 
psoriasis, alopecia areata, atopic dermatitis, and lichenoid tissue reactions of the skin including 
LP. INCB018424 PHOSPHATE CREAM also potently inhibited the phosphorylation of STAT 
proteins and the production of pro-inflammatory factors induced by cytokines such as IL-23 and 
IFNγ. (Investigator’s Brochure) IFNγ is a key cytokine in the pathogenesis of LP.  
 
INCB018424 PHOSPHATE CREAM 1.5%, topical application, twice daily on lesions of 
cutaneous LP. 
2.3 
Preclinical Data 
 
The absorption, pharmacokinetics (PK), distribution, and metabolism of INCB018424 were 
characterized in CD-1 mice, rats, cynomolgus monkeys, beagle dogs, and Gottingen minipigs, 
and the metabolism of INCB018424 was characterized in vitro in rat, dog, and human and in 
vivo in CD-1 mouse, rat, dog, minipig, and human. Additional studies include the mass balance 
excretion of 14C-INCB018424 in rats, dogs, and humans after oral dosing, the tissue distribution 
in rats after an oral dose, and the skin distribution in Gottingen minipig after daily topical 
administration. 
 
The relative bioavailability of INCB018424 PHOSPHATE CREAM was markedly (~ 90%) 
lower than that following oral administration. Following intravenous (IV) administration of 
INCB018424, the total systemic clearance was species-dependent, ranging from 26% (dog) to 
450% (minipig) of hepatic blood flow. The primary clearance pathway is via metabolism based 
on the identification of multiple metabolites coupled with negligible renal clearance of parent 
drug in all species studied. In vitro metabolism studies strongly suggest that cytochrome P450 
(CYP) 3A4 is the predominant CYP isozyme responsible for the metabolism of INCB018424.  
 


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The major metabolites in rat, dog, and the minipig were the hydroxylated products and the 
corresponding ketones. All INCB018424 human in vitro metabolites were also present in rat, 
dog, and minipig. Several in vitro and/or in vivo metabolites of INCB018424 found in rat, dog, 
and human retain JAK-related pharmacological activity. 
 
In CD-1 and hairless (CrL:SKH1-hr) mice after topical dosing for up to 3 months, there were 
minimal differences in the plasma toxicokinetics of INCB018424 PHOSPHATE CREAM. The 
distribution and elimination was rapid, while the AUC values for INCB018424 were not 
consistently different between steady state and Day 1. Higher application rates resulted in higher 
exposures, which further increased when administered twice daily (BID) compared to once daily 
(QD). The in vitro transdermal flux of INCB018424 in a solubilized cream formulation across 
mouse skin was about 20-fold higher than with human cadaver skin. 
 
In Gottingen minipigs following a single topical application using either a 1.5% w/w solubilized 
cream or a 1.0% w/w dispersed cream, INCB018424 exhibited an apparent zero-order 
transdermal absorption with an average plasma concentration over 24 hours of about 1 nM. In 
toxicology studies in minipigs up to 9 months using the solubilized cream formulation, plasma 
concentrations of INCB018424 were significantly higher at steady state compared to Day 1. 
There were minimal sex differences in plasma AUC values, which were higher when 
administered BID compared to QD. 
 
In rats, elimination of drug-derived radioactivity after a single oral and IV dose was rapid, with 
excretion in urine, bile, and feces accounting for approximately 50%, 37%, and 12% of the dose, 
respectively. Elimination was rapid in male and female dogs after an oral dose, with excretion in 
urine and feces accounting for 34% to 36% and 55% to 58% of the dose, respectively. These 
results are similar to humans, which after a single oral dose of 14C-INCB018424 PHOSPHATE 
CREAM, recovery of administered radioactivity was 96% (74% in urine and 22% in feces). 
 
The apparent steady-state volume of distribution (Vss) of INCB018424 ranged from 0.81 L/kg 
(monkey) to 6.4 L/kg (minipig), and the terminal elimination half-life ranged from 0.4 hour (rat) 
to 2.5 hours (dog). In Sprague Dawley rats, after oral dosing, the highest concentrations were 
observed in the tissues and contents of the gastrointestinal tract, urinary bladder, renal cortex, 12 
renal medulla, liver, aorta, and adrenal gland. In Long Evans rats, the highest concentrations of 
drug-derived radioactivity were tissues and contents of the gastrointestinal tract, urine, bile, 
uveal tract, liver, renal medulla, renal cortex, skin (pigmented), and kidney. Elimination in 
Sprague Dawley and Long Evans rats was rapid and complete in most tissues. In a male 
Gottingen minipig after 4 consecutive daily topical doses of 1% 14C-INCB018424 cream, 
radiolabeled material penetrated from the site of application into the epidermis, while penetration 
into the underlying dermis was substantially lower. The serum and plasma protein binding of 
INCB018424 was species-dependent, with fraction unbound ranging from 2.7% in CD-1 mice to 
33% in the minipig (human in vitro unbound fraction in plasma was 3.3%). 
 
The toxicologic and toxicokinetic profiles of INCB018424 were characterized in single and 
repeat oral dose studies of up to 4 weeks in mice, 6 months in duration in rats, and 12 months in 
duration in dogs, and in single and repeat topical dose studies of up to 3 months in mice and up 
to 9 months in the Gottingen minipig. INCB018424 was evaluated in acute dermal and ocular 


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irritation studies in rabbits, an acute ocular irritation study in dogs, 10-day ocular toxicity studies 
in rabbits and dogs, the mouse local lymph node assay, and in phototoxicity and photoallergy 
studies in hairless albino guinea pigs. Genetic toxicology, safety pharmacology, and reproductive 
toxicology assessments have also been conducted, and the carcinogenic potential of 
INCB018424 was evaluated in a 6-month Tg.rasH2 transgenic mouse model and in oral and 
topical 2-year carcinogenicity studies in rats and mice, respectively. 
 
INCB018424 PHOSPHATE CREAM applied at concentrations ≤ 1.5% BID, using a 10 mg/cm2 
application rate to 10% body surface area (BSA) was well tolerated in assessments of up to 9 
months in the Gottingen minipig. Decreases in lymphocytes were observed in both male and 
female animals administered INCB018424 but were considered nonadverse in the absence of any 
other findings suggestive of systemic toxicity. INCB018424-associated microscopic skin lesions 
were generally of minimal to mild severity and lacked a clear dose-response relationship. The 
no-observed-adverse-effect level (NOAEL) was 1.5% BID (Day 293 mean unbound AUC 0.064 
μM*h). INCB018424 PHOSPHATE CREAM did not act as a contact sensitizer nor did it 
produce significant dermal or ocular irritation, acute phototoxicity, or photoallergic potential. 
There was no evidence of systemic toxicity following repeated ocular administration to rabbits or 
dogs. 
 
Effects noted in multiple-dose oral toxicity studies were primarily those associated with the 
mechanism of action of INCB018424. Decreases in red blood cells, reticulocytes, eosinophils, 
and lymphocytes have been observed along with lymphoid depletion in bone marrow and 
lymphoid organs. In addition, in dogs, demodectic mange, bacterial pneumonia, and viral-
induced papillomas, expected consequences of the pharmacology of JAK inhibition, were noted. 
INCB018424 doses ≥ 50 mg/kg given to rats as a single oral dose in a central nervous system 
evaluation were associated with decreases in body temperature and transient decreases in 
locomotor activity. Administration of single oral doses of 150 mg/kg INCB018424 was 
associated with decreases in respiratory frequency, increases in tidal volume, and, for females 
only, an adverse decrease in minute volume. The IC50 for inhibition of the human-ether-à-go-go 
related gene (hERG) channel was determined to be 131.6 μM. In a cardiovascular evaluation of 
INCB018424 in radiotelemetry-implanted dogs, electrocardiogram (ECG) parameters were 
unaffected at all doses. Administration of 30 mg/kg INCB018424 resulted in an adverse lowering 
of systolic, diastolic, mean arterial, and pulse pressures with a corresponding increase in heart 
rate. There were no effects on ventricular repolarization at any dose in the study. 
 
In embryo-fetal assessments in rat and rabbit, maternal toxicity and minimal embryo-fetal 
toxicity were noted at the highest doses evaluated. INCB018424 was not teratogenic in either 
species. The NOAEL dose for the rat and rabbit study was 30 mg/kg per day. In an evaluation of 
fertility and early embryonic development, no effects were noted on reproductive performance or 
fertility in male or female rats. Increases in postimplantation loss were noted at the higher doses. 
In a prenatal and postnatal development and maternal function study in rats, there were no 
adverse findings for fertility indices or for maternal and embryo-fetal survival, growth, and 
developmental parameters. INCB018424 passed into the milk of lactating rats with an exposure 
that was 13-fold higher than maternal plasma exposure. 
 


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INCB018424 was not mutagenic or clastogenic, nor did it demonstrate potential for 
carcinogenicity in a 6-month study in Tg.rasH2 mice or in 2-year studies in mice or rats. 
2.4 
Clinical Data to Date 
 
INCB018424 PHOSPHATE CREAM has been evaluated in over 200 subjects with plaque 
psoriasis in 3 clinical studies with dosing of 1 to 3 months' duration. 
 
Study INCB 18424-201 was a double-blind, vehicle-controlled, rising-dose, safety, tolerability, 
PK, and preliminary efficacy study of INCB01824 1% cream applied QD and 1.5% cream 
applied BID. All doses were safe and well tolerated. Preliminary efficacy was consistently 
shown for the 1.0% QD and 1.5% BID cohorts compared with vehicle, with a trend toward a 
dose response. The 1.5% cream BID showed similar responses compared with Dovonex® 
(calcipotriene) 0.005% cream and Diprolene® AF (betamethasone dipropionate) 0.05% cream. 
Systemic bioavailability of INCB018424 was independent of formulation strength. All adverse 
events (AEs) were mild to moderate in intensity and most judged unrelated to study medication, 
with no associated serious AEs (SAEs) or withdrawals. Laboratory and ECG evaluations did not 
suggest any safety issues, specifically no instances of neutropenia, thrombocytopenia, or 
leukopenia. 
 
INCB 18424-202 was an open-label, multicenter, sequential-cohort, dose-escalation, safety, 
tolerability, PK, pharmacodynamic (PD), and preliminary efficacy study of INCB018424 
PHOSPHATE CREAM 1.0% or 1.5% applied to 2% to 20% BSA QD or BID for 4 weeks. 
Application area increased sequentially, and alternative dosing paradigms were explored at the 
highest application area. The efficacy analyses collectively demonstrated efficacy of all 5 
regimens of INCB018424 PHOSPHATE CREAM in psoriasis. The incidence of all reported 
AEs, the clinical laboratory results, vital signs, and ECG findings showed no confirmed safety 
signals or trends. Mean topical bioavailability ranged from 3.4% to 5.2% with no significant 
inhibition of cohort mean PD. Overall, INCB018424 PHOSPHATE CREAM (1.0% or 1.5% ) 
was demonstrated to be safe and well tolerated when applied QD or BID for 28 days to plaque 
psoriasis affecting 2% to 20% of the BSA. 
 
INCB 18424-203 was a double-blind, randomized, multicenter, parallel group, vehicle-controlled 
dose-ranging study with application of INCB018424 PHOSPHATE CREAM or vehicle in 
subjects with stable plaque psoriasis The study was designed to evaluate safety and efficacy of 
INCB018424 PHOSPHATE CREAM 
0.5%, 1.0%, or 1.5% relative to vehicle cream when applied QD for 12 weeks in equal size 
groups. 
 
Overall, 199 subjects were enrolled. A total of 161 (80.9%) completed the Day 84 visit. Within 
each active treatment group, the mean scores for the individual and total psoriasis lesion 
assessments, the Psoriasis Area and Severity Index (PASI), and the Physician's Global 
Assessment (PGA), as well as the mean treatable percent BSA decreased from baseline to each 
subsequent assessment, which indicated an overall lessening of disease severity. Based on a 
review of the extent of exposure, the incidence of all reported AEs, the clinical laboratory results, 
vital signs, and ECG findings, no safety signals or trends were observed. Overall, INCB018424 


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PHOSPHATE CREAM (0.5%, 1.0%, or 1.5%) was demonstrated to be safe and well tolerated 
when applied QD for 12 weeks to plaque psoriasis affecting 2% to 20% of the BSA. 
 
Study INCB 18424-204 is a 2-part study of subjects with alopecia areata with Part A being open-
label and Part B being double-blind, randomized, and placebo-controlled; subjects in both parts 
who meet prespecified criteria are eligible for an additional 24 weeks of open-label treatment. 
Preliminary unaudited data for this study are presented through 28 JUN 2016. Twelve subjects 
were enrolled in Part A, the open-label portion of the study. Of these 12 subjects, 5 subjects 
(41.7%) have completed the study through Week 24, and no subjects have discontinued study 
treatment. Forty-four subjects were randomized in Part B, the double-blind portion of the study. 
Of these 44 subjects, 3 subjects (6.8%) discontinued from the study, 1 subject because of an AE 
(pruritus judged not related to study drug), 1 subject because of subject decision, and 1 subject 
because of abnormal laboratory values at screening. In Part A, 8 subjects (66.7%) had a 
treatment-emergent adverse event (TEAE). One subject had Grade 3 SAEs of noncardiac chest 
pain, pulmonary mass, and sepsis judged as not related to study drug by the investigator that led 
to interruption of study drug; these events resolved, and the subject resumed study drug. All of 
the TEAEs reported in Part A occurred in 1 subject each. In Part B, 7 subjects (16.7%) had 
TEAEs. One subject had an SAE of nausea and vomiting (judged not related by the investigator); 
this event resolved with continuation of study drug. The most frequently reported TEAE in Part 
B was skin exfoliation, which was reported in 3 subjects (7.1%); these events were judged as not 
related by the investigator. 
 
INCB018424 has also been administered orally as single or multiple doses to healthy volunteers 
and subjects with inflammatory, hematologic, and oncologic disease. Oral administration has 
been generally safe and well tolerated. Literature reports also indicate that oral INCB018424 
may restore hair growth in patients with alopecia areata. 
 
INCB018424 PHOSPHATE CREAM appears to pose a low risk of cutaneous toxicity. 
INCB018424 PHOSPHATE CREAM applied at concentrations ≤ 1.5% (10 mg/cm2 application 
rate to 10% BSA corresponding to 434-1099 cm2) was well tolerated in a 9-month assessment in 
the Gottingen minipig. INCB018424 PHOSPHATE CREAM did not act as a contact sensitizer 
nor did it produce significant dermal irritation or demonstrate phototoxicity or photoallergenic 
potential. This lack of adverse cutaneous effects has been supported by clinical trials to date 
where cutaneous AEs have been infrequent and of similar frequency and severity as with vehicle 
control treatment. INCB018424 PHOSPHATE CREAM tested positive in a photoclastogenicity 
assay; hence there may be a risk of skin reaction to the combined exposure of INCB018424 
PHOSPHATE CREAM and sunlight. Subjects should be cautioned to avoid excessive exposure 
to either natural or artificial sunlight (including tanning booths, sun lamps, etc), and, when 
outdoors, should be advised to wear loose-fitting clothing that protects the treated area from the 
sun. 
 
The primary clinical risks noted with orally administered INCB018424 treatment are the 
potential sequelae of decreased hematopoietic proliferation secondary to the inhibition of growth 
factor pathways by JAK2 antagonism. Systemic exposure with topical INCB018424 
PHOSPHATE CREAM is several fold below that which is associated with hematologic changes 
that may be seen following oral dosing. Dose-dependent, reversible thrombocytopenia has been 


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observed in subjects with myelofibrosis (MF), as well as anemia and less frequently neutropenia. 
An increased rate of infection is an additional potential risk of immunomodulation. A few 
subjects have had an apparent worsening of their premorbid disease symptoms following rapid 
cessation of INCB018424 therapy. A gradual tapering and use of steroids in fragile patients may 
be considered when stopping INCB018424 therapy. Leukemic transformation has been observed, 
but was considered to be consistent with the natural history of the underlying disease and 
unrelated to drug. In healthy volunteers and rheumatoid arthritis (RA) patients with greater bone 
marrow reserve, the effects on hematopoietic proliferation appear to be less pronounced. Overall, 
the safety profile of ruxolitinib in the polycythemia vera (PV) population treated was generally 
consistent with what was observed in the MF population. Ruxolitinib was generally well 
tolerated in subjects with PV, and only a small proportion of subjects discontinued ruxolitinib 
due to AEs (3.6%). Most of the AEs have been managed by dose adjustments. Hematologic 
toxicities were less frequent and less severe in subjects with PV as compared to those observed 
in subjects with MF. 
2.5 
Dose Rationale  
 
Topical Dosing: 
In addition to the safety pharmacology and toxicology studies that were completed to support 
development of INCB018424 PHOSPHATE CREAM. The relative bioavailability of 
INCB018424 PHOSPHATE CREAM was markedly (~ 90%) lower than that following oral 
administration. In vitro metabolism studies strongly suggest that cytochrome P450 (CYP) 3A4 is 
the predominant CYP isozyme responsible for the metabolism of INCB018424 PHOSPHATE 
CREAM.  
 
INCB018424 PHOSPHATE CREAM has been evaluated in over 200 subjects with plaque 
psoriasis in 3 clinical studies with dosing of 1 to 3 months' duration. Study INCB 18424-201 was 
a double-blind, vehicle-controlled, rising-dose, safety, tolerability, PK, and preliminary efficacy 
study of INCB01824 1% cream applied QD and 1.5% cream applied BID. All adverse events 
(AEs) were mild to moderate in intensity and most judged unrelated to study medication, with no 
associated serious AEs (SAEs) or withdrawals. Laboratory and ECG evaluations did not suggest 
any safety issues, specifically no instances of neutropenia, thrombocytopenia, or leukopenia.  
 
INCB 18424-202 was an open-label, multicenter, sequential-cohort, dose-escalation, safety, 
tolerability, PK, pharmacodynamics (PD), and preliminary efficacy study of INCB018424 
PHOSPHATE CREAM 1.0% or 1.5% applied to 2% to 20% BSA QD or BID for 4 weeks. 
Application area increased sequentially, and alternative dosing paradigms were explored at the 
highest application area. The efficacy analyses collectively demonstrated efficacy of all 5 regimens 
of INCB018424 PHOSPHATE CREAM in psoriasis. The incidence of all reported AEs, the 
clinical laboratory results, vital signs, and ECG findings showed no confirmed safety signals or 
trends. Mean topical bioavailability ranged from 3.4% to 5.2% with no significant inhibition of 
cohort mean PD. Overall, INCB018424 PHOSPHATE CREAM (1.0% or 1.5%) was demonstrated 
to be safe and well tolerated when applied QD or BID for 28 days to plaque psoriasis affecting 2% 
to 20% of the BSA. 
 






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Chest X-ray: 
Subjects will be exposed to radiation from the chest x-ray. The amount of radiation has a low 
risk of harmful effects. 
 
 
Blood draw:  
The risks of drawing blood include pain, bruising, lightheadedness, and/or fainting, or rarely, 
infection at the site of the needle stick.   
 
Other: 
As with all research, there is a chance that confidentiality could be compromised; however, we 
take precautions to minimize this risk.  
 
3 Study Objectives 
 
Primary Objective: 
To determine the efficacy of INCB018424 PHOSPHATE CREAM as measured by the change in 
Modified CAILS score of the index treatment and control lesion (weeks 0 and 4) and changes in 
lesion count (week 0 and 4) 
  
Secondary Objective: 
To determine the efficacy of INCB018424 PHOSPHATE CREAM and the duration of response 
after discontinuation as measured by the change in Pruritus NRS, (week 0 to week 4, week 0 to 
week 8, weeks 4 to 8, weeks 8 to 12), Change in Skindex-16 (week 0 to week 4, weeks 4 to 8, 
weeks 8 to 12), Change in Physician Global Assessment (PGA) (week 0 to week 4, week 0 to week 
8,  weeks 4 to 8, weeks 8 to 12), Change in BSA (week 0 to week 4, week 0 to week 8, weeks 4 to 
8, weeks 8 to 12), Change in Modified CAILS (week 0 to week 8, weeks 4 to 8, weeks 8 to 12). 
 
Exploratory Objectives:  
To predict responses and examine the pharmacodynamics of treatment through the identification 
of unique biomarkers and transcriptomic changes of LP at week 0 and utilizing RNA sequencing 
on responsive and non-responsive tissue at week 4 To correlate these biomarkers with measures 
of global response: Modified CAILS, PGA, BSA, and lesion count.  
 
 
 
 
4 Study Design 
 
4.1 
General Description 
 


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This is a single center, exploratory, open-label, single-arm design study of 12 patients. Treatment 
naïve and treatment refractory patients with LP will be treated with INCB018424 PHOSPHATE 
CREAM. Patients who are non-responders, to physician choice standard of care, will undergo a 
washout period and will be enrolled in the study. 
 
Multiple safety studies have been conducted with INCB018424 PHOSPHATE CREAM (see 
Safety) and a dose of 1.5% cream BID on up to 20% BSA is deemed safe. (Investigator’s 
Brochure) The Within each cohort, the maximum reduction from baseline in the total psoriasis 
lesion assessment scores for the treated lesions was observed at the end of treatment (Day 28). 
(Investigator’s Brochure) Therefore, we propose a single center, exploratory, open-label, single-
arm design study of 12 patients. Treatment naïve and treatment refractory patients with LP will 
be treated with INCB018424 PHOSPHATE CREAM. 
 
Individuals with LP involving less than 20% of the BSA will be eligible. Individuals must have 4 
lesions at baseline, however, a minimum of 10 lesions is ideal, which are at least 5mm in 
diameter. 10 lesions are ideal as 2 lesions will be index lesions and 8 or more lesions will be 
selected from as responsive or non-responsive at 4 weeks. All lesions except for one index lesion 
will be treated and all lesions will be annotated, photographed, and scored. The rationale for a 
minimum of 8 lesions is based upon the assumption of a 50% response rate at 2 weeks. With 8 
lesions, there would be a less than 1% chance that all 8 lesions would respond. Ideally, the 2 
index lesions will be 10mm in diameter but this is not a requirement. Prior treatment will be 
allowed; however, a washout period of 2 weeks for topical and 4 weeks for systemic agents is 
required. At the washout period, individuals will undergo evaluation with a PGA, BSA 
calculation, and have the 2 largest, representative lesions selected for evaluation using a 
modified CAILS score lesion A- treatment index lesion and B-index control lesion. The 
determination of which lesion receives treatment and which is a control will be determined 
randomly. The additional  lesions will be photographed, measured, scored, and recorded with 
Modified CAILS scores as well. The later calculations will be used for the determination of 
responsive and non-responsive lesions. Additional Pruritus measures using the NRS and 
Skindex-16 will be collected at that time.  
 
Individuals will then initiate treatment on all lesions of LP BID and will be evaluated weekly and 
assessed by PGA, BSA, lesion count; Modified CAILS, Pruritus NRS, and Skindex-16 between 
weeks 0-4 (see Appendix). Week 4 will be the primary endpoint; however therapy will be 
continued for an additional 4 weeks. Therapy will be stopped and the individuals will be 
evaluated at week 8 and assessed by PGA, BSA, lesion count, Modifed CAILS, Pruritus NRS, 
and Skindex-16. Laboratory and safety monitoring will occur at weeks 1, 2, 3, 4, and 8, and 12. 
3D Photographs will be taken at weeks 0, 1, 2, 3, 4, 8, and 12. Individual lesions will be circled 
at that time and the exact volume of each lesion will be measured. Up close photos will be taken 
of the disease and normal tissues attained at weeks 0 & 4.  
 
Tissue will be collected for RNA sequencing at week 0 and 4. Blood collection will include the 
isolation at week 0, 2, and week 4, 5mL vials of blood which will be separated and the serum and 
cell pellet will be stored for future analysis. Five skin biopsies will be taken during the study. At 
week 0, up to two 3mm tissue biopsies will be taken from lesional skin and one biopsy will be 
taken from normal appearing skin. The initial biopsy of lesional tissue and control will be 


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annotated. At week 4, up to two 3mm biopsies will be taken from lesional responsive tissue and 
lesional refractory tissue. Responsive and non-responsive lesions will be determined by the 
change in Modified CAILS between week 0 and 4. Responsive will require a 50% reduction in 
Modified CAILS and non-responsive can have progression, no change, or up to a 50% reduction 
in Modified CAILS. The lesions will be chosen using full body photographs taken at week 0. Up 
to 60 samples will be snap frozen and stored in the tissue biobank. Once completed, RNA 
sequencing will be performed on the 60 tissue samples and analysis will be performed. Paired 
analysis of treatment responsive and refractory lesions will be made as well as treated and 
untreated lesions.  
 
Nucleic Acid Extractions: RNA will be extracted from a total of 50 um of fresh tissue using the 
Qiagen FFPE RNeasy Micro extraction Kit according to manufacturer’s recommendation.  
 
RNA Transcriptome Sequencing: RNA transcriptome sequencing will be carried out using 
commercially available techniques.  Briefly, RNA Libraries will be created using up to 100ng of 
RNA as starting material using the Agilent RNA Access Library kit according to manufacturer’s 
recommendation. Libraries will be QCed for quality and quantity using the Agilent BioAnalyzer 
High Sensitivity Chip. Pair-End sequencing will then be carried out on the Illumina HiSeq 4000 
using 101bp insert fragments.   
 
Primary and Secondary Measures: 
 
All efficacy assessments will be performed prior to the administration of study treatment at each 
visit. The recommended order and the overall outline of measurements for the efficacy assessments 
are described below.  
 
Efficacy measures: PGA, BSA, Modified CAILS, Pruritus NRS, Skindex-16 
To determine the efficacy of INCB018424 PHOSPHATE CREAM as measured by the change in 
Modified CAILS score of the index treatment and control lesion (weeks 0 and 4) and changes in 
lesion count (week 0 and 4) 
 
Secondary Outcome Measures: To determine the efficacy of INCB018424 PHOSPHATE CREAM 
and the duration of response after discontinuation as measured by the change in Pruritus NRS, 
(week 0 to week 4, week 0 to week 8, weeks 4 to 8, weeks 8 to 12), Change in Skindex-16 (week 
0 to week 4, weeks 4 to 8, weeks 8 to 12), Change in Physician Global Assessment (PGA) (week 
0 to week 4, week 0 to week 8,  weeks 4 to 8, weeks 8 to 12), Change in BSA (week 0 to week 4, 
week 0 to week 8, weeks 4 to 8, weeks 8 to 12), Change in Modified CAILS (week 0 to week 8, 
weeks 4 to 8, weeks 8 to 12). 
 
Exploratory Outcome Measures: To predict responses and examine the pharmacodynamics of 
treatment through the identification of unique biomarkers and trasnscriptomic changes of LP at 
week 0 and utilizing RNA sequencing on responsive and non-responsive tissue at week 4 to 
correlate these biomarkers with measures of global response: Modified CAILS, PGA, BSA, and 
lesion count. 


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4.2 
Number of Subjects 
 
12 subjects will be enrolled in this study. 
 
4.3 
Duration of Participation 
 
The study consists of 3 epochs: screening/washout period (of at least 1 week and up to 4 weeks), 
treatment epoch (of 8 weeks from screen/washout), and follow up epoch (of 4 weeks). The 
screening and washout period will allow for treatment naïve/ new diagnosis LP to undergo 
evaluation and diagnosis and for treatment refractory to undergo a washout. The total duration of 
the study will be 13-16 weeks. 
 
Tables: 
• 
Table-1: Prohibited treatment 
Prohibited treatments†, ‡  
 
Washout period  
(before Randomization 
Visit) 
Any concomitant oral or topical JAK inhibitor 
Any biologic drug  
Prohibited 
Stable dose for 3 months  
Immunomodulation treatments for LP§ 
[e.g., methotrexate, cyclosporine A, corticosteroids (oral, i.v., 
intramuscular, s.c., intra-articular, transdermal), 
mycophenolate mofetil, azathioprine ]  
4 weeks 
Topical treatment that is likely to impact signs and symptoms 
of LP (e.g., pimecrolimus, tacrolimus) 
2 weeks 
Non-immunosuppressive agents (tetracycline antibiotics & 
niacinamide) 
2 weeks 
 
Prohibited regimen of Topical Corticosteroids (TCS) 
 
TCS on any location on body (including face, scalp and/or 
genitoanal area) 
2 weeks 
 
 
† If the prohibited treatment is being used during the study for any indication, the subject must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study.  
‡ In case of undue safety risk for the subject, the subject should discontinue study treatment at the 
discretion of the investigator/qualified site staff. If the subject received a live virus vaccination 
during the study, the subject must discontinue study treatment. 
§Inhalative CS with only a topical effect (e.g., to treat asthma) are not considered “systemic 
immunomodulation 
treatments” 
and 
are 
therefore 
acceptable 
as 
co-medication. 
Immunosuppressive medication for conditions other than LP will be allowed.   
 
Table-2: Screening and Visits (+/- 2 day window) 
Screening 
Day 
0 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Week 
8 
Week 
12 


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INCB18424 
X 
X 
X 
X 
X 
 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
X 
X 
X 
X 
X 
X 
X 
Chest X-ray 
X 
 
 
Assessments: PGA, 
BSA, lesional 
number, Modified 
CAILS, Skindex-16, 
Pruritus NRS 
 
X 
X 
X 
X 
X 
X 
X 
Photographer 
X 
X 
X 
X 
X 
X 
X 
Skin Biopsy 
(tissue/serum bank) 
 
X 
 
 
 
X 
 
 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
 
Venipuncture 
X 
X 
X 
X 
X 
X 
X 
X 
Biomarker/RNAseq 
blood (tissue/serum 
bank) 
 
X 
 
X 
 
X 
 
 
CMP 
X 
X 
X 
X 
X 
X 
X 
CBC 
X 
X 
X 
X 
X 
X 
X 
Quantiferon Gold 
X 
 
 
Hepatitis B 
X 
 
 
Hepatitis C 
X 
 
 
 
 
 
 
 
HIV 
X 
 
 
Coccidioidomycosis 
X 
 
 


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4.4 
Primary Study Endpoints 
 
Change in Modified CAILS of index treatment lesion and index control lesion (week 0 and 4) and 
change in lesion count (week 0 and week 4). 
4.5 
Secondary Study Endpoints 
Change in Pruritus NRS, (week 0 to week 4, week 0 to week 8, weeks 4 to 8, weeks 8 to 12), 
Change in Skindex-16 (week 0 to week 4, weeks 4 to 8, weeks 8 to 12), Change in Physician 
Global Assessment (PGA) (week 0 to week 4, week 0 to week 8,  weeks 4 to 8, weeks 8 to 12), 
Change in BSA (week 0 to week 4, week 0 to week 8, weeks 4 to 8, weeks 8 to 12), Change in 
Modified CAILS (week 0 to week 8, weeks 4 to 8, weeks 8 to 12). 
4.6 
Primary Safety Endpoints 
 
A thorough baseline screening will be followed for all patients and is outlined in Table-2. A 
detailed list of the methods in which baseline screening will be performed is outlined in 
Supplemental 2. All blood draws and safety assessments must be performed prior to study 
treatment administration. Appropriate safety assessments (e.g., evaluation of AEs and SAEs) 
should be repeated after dosing with study treatment. A physical examination, including general 
appearance and vital signs, will be performed as indicated in Table-2. If indicated, based on 
medical history and/or symptoms, additional exams will be performed at the discretion of the 
investigator. If possible, the same member of the study site staff throughout the study will perform 
assessments for an individual subject. Information for all physical examinations will be included 
in the source documentation at the study site. Significant findings that are present prior to the 
subject signing informed consent will be included in the Medical History. Significant findings 
made after the signing of the informed consent, which meet the definition of an AE, must be 
recorded as an AE. Vital signs (blood pressure, pulse, height, weight) will be assessed at each 
physical examination as indicated in Table-2 (see Supplemental 2 for details on how to acquire 
vital signs). Whether action needs to be taken to address notable vital signs will be decided by the 
investigator, considering the overall status of the subject. Laboratory studies will be drawn as 
indicated in Table-2. Whether action needs to be taken to address notable laboratory values will 
be decided by the investigator, considering the overall status of the subject. Hematology 
assessments will be measured at all scheduled study visits specified in Table-2. Serum chemistry 
will be a comprehensive metabolic panel will be measured at all scheduled study visits specified 
in Table-2. 
 
If the prohibited treatment is being used during the study for any indication, the subject must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study.  In case of 
undue safety risk for the subject, the subject should discontinue study treatment at the discretion 
of the investigator/qualified site staff. If the subject received a live virus vaccination during the 
study, the subject must discontinue study treatment. 
 


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4.7 
Identification of Source Data 
 
All data in the study will be captured in the case report forms including: 
• Safety measures 
• Efficacy measures 
• Laboratory studies 
• Vital Signs 
• 
Exploratory measures 
5 Subject Selection Enrollment and Withdrawal 
5.1 
Inclusion Criteria 
 
Subjects eligible for inclusion in this study must fulfill all the following criteria: 
 
• Subjects must be able to understand and comply with the requirements of the study and 
communicate with the investigator. Subjects must give written, signed, and dated informed 
consent before any study related activity is performed. When appropriate, a legal representative 
will sign the informed consent according to local laws and regulation 
• Both men and women must be at least 18 years of age at the time of screening 
• Subjects must have clinical and histological features of LP 
• LP up to 20% of the BSA 
• Subjects must have a minimum of 4 lesions, ideally 10 lesions of LP 
• Subjects must have treatment naïve cutaneous LP or treatment refractory disease, as defined 
by failure of at least one established treatment for LP 
o Failure of prior therapy 
▪ Topical treatment 
▪ Systemic immunosuppressant 
▪ Oral metronidazole 
▪ Oral sulfasalazine 
▪ Oral retinoid 
5.2 
Exclusion Criteria 
 
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. To ensure 
the recruitment of a representative sample of all eligible subjects, the investigator may apply no 
additional exclusions. 
• On excluded therapies, not on a stable dose of a therapy, or incompletely washed out for a 
therapy (Table-1.) 
• Known hypersensitivity to any component of INCB018424 PHOSPHATE CREAM 
• Variants of LP deemed by the investigators to be inappropriate for INCB018424 
PHOSPHATE CREAM including by not limited to: 
o Erosive LP 
o Intertriginous LP 
o Oral LP 
o Facial LP 


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o Drug-induced LP  
o Vaginal LP 
• LP involving greater than 20% BSA 
• Pregnant or nursing (lactating) women (pregnancy is defined as the state of a female after 
conception and until the termination of gestation, confirmed by a positive human chorionic 
gonadotropin (hCG) laboratory test) 
• Women of childbearing potential [Post-menopausal or not of child-bearing potential is 
defined by: 1 year of natural (spontaneous) amenorrhea or Surgical bilateral oophorectomy 
(with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks ago. 
Oophorectomy alone must be confirmed by follow up hormone level assessment to be 
considered not of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using basic methods of contraception which includes: 
o Total abstinence (Periodic abstinence and withdrawal are not acceptable methods of 
contraception) 
o Female sterilization (bilateral oophorectomy with or without hysterectomy), total 
hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. 
Oophorectomy alone requires follow up hormone level assessment for fertility.  
o Male sterilization (at least 6 months prior to screening). The vasectomized male 
partner should be the sole partner for that subject. 
o Barrier methods of contraception: condom or occlusive cap.  
o Use of oral, injected or implanted hormonal methods of contraception or other forms 
or hormonal contraception that have complete efficacy (failure <1%). (The dose of 
the contraceptive should be stable for 3 months) 
• Active ongoing inflammatory diseases of the skin other than LP that might confound the 
evaluation of the benefit of INCB018424 PHOSPHATE CREAM 
• Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions) which, 
in the opinion of the investigator, significantly immunocompromised the subject and/or 
places the subject at unacceptable risk for receiving an immunomodulatory therapy 
• Active systemic infections during the 2 weeks prior to randomization (common cold viruses 
not included) or any infection that reoccurs on a regular basis.  
• 
Current severe progressive or uncontrolled disease which the investigator renders the subject 
unsuitable for the trial or puts the subject at increased risk  
 
5.3 
Subject Recruitment, Enrollment and Screening 
 
• From the Principal Investigator or Co-Investigator clinical practices 
• Screening requirements or qualifying lab values 
• Evaluation and documentation of inclusion/exclusion criteria 
 
5.4 
Early Withdrawal of Subjects 
5.4.1 When and How to Withdraw Subjects 
• Subject safety issues 


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• Failure of subject to adhere to protocol requirements 
• Disease progression 
• Subject decision to withdraw from the study (withdrawal of consent) 
Subjects who withdraw from the study for any reason will have their information recorded at the 
time of withdrawal. At the time of withdrawal, the subject will be considered at the final 
treatment date and will move into the treatment observation phase (4 weeks). Subjects will not be 
replaced. Follow up for subjects will continue to follow the normal follow up (Table-2) 
5.4.2 Data Collection and Follow-up for Withdrawn Subjects 
At the time of withdrawal, the reason for withdrawal will be recorded in the CRF. Individuals 
who withdraw will go into the observation phase for 4 weeks. If a subject withdraws consent, 
attempts will be made to obtain permissions to collect follow up information.  
6 Study Drug  
6.1 
Description 
 
The chemical name of INCB018424 phosphate is (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-
pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate (Figure 1). INCB018424 phosphate has a 
molecular formula of C17H21N6O4P and a molecular weight of 404.36. 
 
INCB018424 Phosphate Structural Formula   
 
 
INCB018424 phosphate drug substance is a white to off-white to light pink powder. 
INCB018424 PHOSPHATE CREAM has been formulated in 4 strengths (0.15%, 0.5%, 1.0%, 
and 1.5% w/w free base equivalent) that are actively being investigated. All excipients in both 
the INCB018424 PHOSPHATE CREAM and placebo cream formulations are compendial grade 
or are approved for use in topical products.  
 
INCB018424 PHOSPHATE CREAM is a topical formulation of an investigational product 
under development for the treatment of patients with psoriasis, alopecia areata, atopic dermatitis, 
and other potential autoimmune diseases of the skin. INCB018424 phosphate (ruxolitinib) is an 
inhibitor of the Janus kinase (JAK) family of protein tyrosine kinases. INCB018424 inhibits 
Janus Associated Kinases (JAKs) JAK1 and JAK2 which mediate the signaling of a number of 


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cytokines and growth factors that are important for hematopoiesis and immune function. JAK 
signaling involves recruitment of STATs (signal transducers and activators of transcription) to 
cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to 
modulation of gene expression. Mitogenic and inflammatory cytokines are strongly implicated in 
the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and other potential autoimmune 
diseases of the skin. Inhibition of specific cytokine function using antibodies directed against the 
common p40 subunit of interleukin (IL)-12 and IL-23 has demonstrated proof-of-concept 
validating cytokine signaling as a therapeutic target for the treatment of psoriasis. 
 
INCB018424 PHOSPHATE CREAM has been evaluated in over 200 subjects in 3 clinical 
studies with dosing of 1 to 3 months in duration. One study of 12 subjects with Alopecia Areata.  
 
Pharmacodynamics: 
Ex vivo addition of INCB018424 to the whole blood samples from psoriasis subjects inhibited 
cytokine-induced STAT3p levels with a similar potency to that observed previously in whole 
blood from healthy volunteers (IC50 = 334 nM vs 414 nM, respectively). No significant 
inhibition of mean systemic STAT3p was observed in any cohort following topical INCB018424 
application. 
 
Pharmacokinetics: 
Study 1:  
• Cohort A: INCB018424 PHOSPHATE CREAM 0.5% versus vehicle applied QD. 
• Cohort B: INCB018424 PHOSPHATE CREAM 1.0% versus vehicle applied QD. 
• Cohort C: INCB018424 PHOSPHATE CREAM 1.5% versus vehicle applied BID. 
 
Application of INCB018424 PHOSPHATE CREAM 0.5% to 1.5% QD or BID resulted in mean 
plasma concentrations of INCB018424 ranging from 0.34 ± 0.4 nM (Cohort A) through 2.10 ± 
1.78 nM (Cohort C) at steady state. The mean INCB018424 steady-state concentration increased 
approximately proportional to application dose per day. The size of the lesion areas treated 
ranged from 9 to 63 cm2. Application of INCB018424 PHOSPHATE CREAM 0.5% to 1.5% 
QD or BID resulted in a mean skin flux of INCB018424 ranging from 54 ± 41 ng/cm2/h (Cohort 
A) through 422 ± 200 ng/cm2/h (Cohort C). The mean skin flux of INCB018424 increased with 
increasing application (API) strength. The mean systemic bioavailability was 2.8 ± 3.2%, 3.0 ± 
1.9%, 3.0 ± 1.9%, 2.7 ± 1.1%, and 2.7 ± 2.3% for Cohorts A through E, respectively. The 
systemic bioavailability of INCB018424 applied as a topical cream appears independent of the 
strength of the cream formulation. 
 
Study 2:  
• Cohort A: treat 2%-7% BSA with 1.5% BID in 5 subjects 
• Cohort B: treat 8%-13% BSA with 1.5% BID in 5 subjects 
• Cohort C: treat 14%-20% BSA with 1.5% QD in 5 subjects 
• Cohort D (optional): treat 14%-20% of BSA with 1.0% QD or BID in 5 subjects 
• Cohort E (optional): treat 14%-20% of BSA with 1.5% QD or BID in 5 subjects 
 
The average plasma concentrations of INCB018424 for Cohort A , Cohort B, Cohort C, Cohort 
D, and Cohort E were 7.00 ± 2.11 nM, 29.38 ± 13.10 nM, 24.42 ± 10.07 nM, 34.96 ± 20.43 nM, 


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and 60.99 ± 73.85 nM, respectively, at the steady state. The mean INCB018424 Css increased 
approximately proportional to application dose per day. The mean skin flux of INCB018424 was 
estimated to be 180 ± 126 ng/cm2/h, 131 ± 92 ng/cm2/h, 60 ± 43 ng/cm2/h, 151 ± 126 ng/cm2/h, 
and 152 ± 74 ng/cm2/h, respectively, for Cohorts A, B, C, D, and E. The mean topical 
bioavailability was estimated to be 3.8 ± 2.5%, 4.1 ± 3.4%, 3.4 ± 1.9%, 3.9 ± 1.3%, and 5.2 ± 
1.9%, respectively, for Cohorts A, B, C, D, and E. Based on this result, it is concluded that the 
systemic bioavailability of INCB018424 applied as a topical cream is independent of the strength 
of the cream formulation and %BSA. 
 
Study 3:  
• Treatment A: INCB018424 PHOSPHATE CREAM 0.5% applied QD for 12 weeks 
• Treatment B: INCB018424 PHOSPHATE CREAM 1.0% applied QD for 12 weeks 
• Treatment C: INCB018424 PHOSPHATE CREAM 1.5% applied QD for 12 weeks 
• Treatment D: Vehicle containing placebo cream applied QD for 12 weeks 
 
Application of INCB018424 PHOSPHATE CREAM 0.5%, 1.0%, and 1.5% QD resulted in 
mean steady-state trough plasma concentrations (Css,min) of INCB018424 of 9.19 ± 11.77 nM, 
16.99 ± 19.05 nM, and 19.97 ± 25.13 nM, respectively, for 0.5% QD to 1.5% QD. Thus, the 
mean INCB018424 Css,min increased approximately proportional to application dose. As the 
severity of lesion thickness, erythema, and scale increased, the INCB018424 Css,min appeared 
to be decreased for the same treatment. The subjects with less severe lesion thickness, erythema, 
and scale seemed to have higher trough INCB018424 exposures. 
 
Study 4:  
Twelve subjects were enrolled in Part A (1.5% BID). Pharmacokinetic data were available for 12 
subjects at Week 4 and 5 subjects at Week 12. Application of INCB018424 PHOSPHATE 
CREAM 1.5% BID resulted in mean steady state plasma concentrations of 25.4 ± 15.9 nM at 
Week 4 and 43.0 ± 36.5 nM at Week 12, which are generally consistent with the steady state 
concentrations seen in subjects with psoriasis. Steady state was assumed to be achieved at Day 8. 
6.2 
Treatment Regimen 
 
Subjects will apply the study drug topically to LP lesions twice daily.    Treatment will take place 
from Day 0 to Week 8.    
6.3 
Preparation and Administration of Study Drug 
 
The study drug will be supplied by Incyte to the Mayo Clinic Pharmacy, attn. 
, 
, Scottsdale, AZ 
. The study drug will be stored in 
the Mayo Clinic Pharmacy. The study drug will be labelled in the Mayo Clinic Pharmacy and 
will be dispensed to the subjects. The subjects will be given the appropriate amount of topical 
cream to apply to the disease. Instructions on proper use will be provided to each subject. 
 
6.4 
Subject Compliance Monitoring 
 


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Compliance will be assessed through direct questioning of subjects as well as through drug use 
diaries.  The drug tubes will be weighed, and weight will be documented at each visit to 
determine usage.  
6.5 
Prior and Concomitant Therapy 
 
Individuals on stable doses of medications for chronic illnesses will be allowed. Individuals on 
immunosuppressive agents for LP will not be allowed; however, individuals on stable doses of 
immunosuppressant for other conditions will be allowed if deemed to be safe by the treating 
physicians. Additional exclusionary drugs are included in Table-1. 
 
Individuals using INCB018424 PHOSPHATE CREAM should use topical broad spectrum 
sunscreens with a minimum of SPF30, avoid excess sunlight, and wear sun protective clothing.  
 
6.6 
Packaging 
 
The drug will be packaged in 15 gram single tubes and bubble wrapped for shipment.   The 
entire quantity needed for the study will be provided in one shipment.   The study drug tubes will 
be labeled with a diaper label that fully surrounds the tube.  All applicable US FDA required text 
will be included on the label, included Caution: Limited by U.S. Law to Investigational Use         
6.7 
Receiving, Storage, Dispensing and Return 
6.7.1 Receipt of Drug Supplies 
 
The drug will be obtained or delivered from Incyte Corporation to the pharmacy at each 
investigative site. 
 
Upon receipt of the of the study treatment supplies, an inventory must be performed and a drug 
receipt log filled out by the person accepting the shipment.  It is important that the designated 
study staff counts and verifies that the shipment contains all the items noted in the shipping 
invoice. Any discrepancies, damaged or unusable study drug in a given shipment (active drug or 
comparator) will be documented in the study files. The sponsor-investigator must be notified 
immediately of any discrepancies, damaged or unusable products that are received. 
6.7.2 Storage 
The INCB018424 PHOSPHATE CREAM drug product and placebo cream should be stored 
between 15°C and 30°C (59°F and 86°F). The supplies will be stored in the Mayo Clinic 
Pharmacy.  
6.7.3 Dispensing of Study Drug 
 
Regular study drug reconciliation will be performed to document drug assigned, drug dispensed, 
drug returns, and drug remaining.  This reconciliation will be logged on the drug reconciliation 
form, and signed and dated by the study team. 


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6.7.4 Return or Destruction of Study Drug 
 
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
dispensed, drug returns, and drug remaining.  This reconciliation will be logged on the drug 
reconciliation form, signed and dated.  Any discrepancies noted will be documented and 
investigated, prior to return or destruction of unused study drug.  Drug destroyed on site will be 
documented in the study files. 
 
7 
Study Procedures 
 
7.1 
Visit 1 
 
Screening visit:   
 
During this visit, we will do some tests and procedures to see if subjects are eligible to take part 
in this research study.  The study staff will review the results of these tests and procedures.  If 
subjects aren’t eligible, the Principal Investigator will tell them why.  At this visit we will:  
 
▪ Ask about medical history 
▪ Perform a physical exam, including height, weight, and “vital signs” (blood pressure, 
temperature, heart and breathing rates) 
▪ Perform a chest x-ray  
▪ Draw a blood sample 
▪ We may take swabs to test for certain fungal and bacterial infections 
▪ Test urine for pregnancy if female subject is able to become pregnant 
 
If it isn’t known if subject has HIV, Hepatitis B or C, blood tests will need to be done.   
7.2 
Visit 2 
 
Day 0 Visit we will: 
 
• Perform a physical exam, check vital signs and ask about side effects or health 
problems since last visit 
• Exam skin lesions to note any changes 
• Take photographs of  skin lesions to document any changes 
• Draw a blood sample 
• Perform a skin biopsy (up to 3 tissue samples will be taken)  
• Perform a tap stripping on skin 
• Dispense study drug  
 


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7.3 
Visit 3  
 
Week 1 Visit we will:   
  
• Perform a physical exam, check vital signs and ask about side effects or health problems 
since last visit 
• Exam skin lesions to note any changes 
• Take photographs of skin lesions to document any changes 
• Draw a blood sample 
• Dispense study drug  
 
7.4      Visit 4  
 
Week 2 Visit we will:  
 
• Perform a physical exam, check vital signs and ask about side effects or health 
problems since last visit 
• Exam skin lesions to note any changes 
• Take photographs of  skin lesions to document any changes 
• Draw a blood sample 
• Dispense study drug  
 
7.5       Visit 5 
 
Week 3 Visit we will:  
 
• Give subject a physical exam, check vital signs and ask about side effects or health 
problems since last visit 
• Exam skin lesions to note any changes 
• Take photographs of  skin lesions to document any changes 
• Draw a blood sample 
• Dispense study drug  
 
7.6       Visit 6 
 
Week 4 Visit we will:  
 
• Perform a physical exam, check vital signs and ask about side effects or health problems 
since last visit 
• Exam skin lesions to note any changes 
• Take photographs of  skin lesions to document any changes 
• Draw a blood sample 
• Perform a skin biopsy (up to 2 tissue samples will be taken) 
• Perform a tap stripping on skin 
• Dispense study drug  


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7.7         Visit 7 
 
Week 8 Visit we will:  
 
• Perform a physical exam, check vital signs and ask about side effects or health 
      problems since last visit 
• Exam skin lesions to note any changes 
• Take photographs of skin lesions to document any changes 
• Draw a blood sample 
 
7.8        Visit 8 
 
Week 12 Visit we will:  
 
• Perform a physical exam, check vital signs and ask about side effects or health 
      problems since last visit 
• Exam skin lesions to note any changes 
• Take photographs of  skin lesions to document any changes 
• Draw a blood sample 
 
 


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8 Statistical Plan 
8.1 
Sample Size Determination 
 
 Data analysis: Assuming a medium effect size (0.3) and a target power of 80%, a two-armed study 
would need about 108 subjects and a single arm about 88 subjects. Due to the costs associated with 
a study, we propose a single armed study of 12 subjects with corollary science including RNA 
sequencing. This will reduce costs and provide biomarkers predictive of response. Effect sizes will 
be estimated for the appropriate statistical tests that will be used for group comparisons in future 
studies. This will enable more accurate power and sample size estimates moving forward. 
 
8.2 
Statistical Methods 
 
Descriptive Statistics 
 
Sample Size Computation and Power Analysis: 
The sample size for this pilot study is set at 12 subjects for logistical and financial reasons. This is 
similar in size to other exploratory studies and will provide adequate data for estimation purposes 
for planning future studies.  With 12 subjects, the study is intended to be for estimation purposes 
only.    
 
Statistical Analysis Plan: 
Data Analysis - The statistical analysis will provide descriptive summary statistics for categorical 
and continuous outcomes.  Categorical variables will be described by their count and proportion 
of occurrence while continuous, normally distributed variables will be described by their mean 
and standard deviation; and continuous, non-normally distributed variables will be described by 
their median and range. The paired or unpaired Wilcoxon tests will be used to quantify 
differences in numerical outcomes while the Fisher’s exact test and the McNemar’s or Bowker’s 
tests will be used to quantify changes in categorical variables.  
If missingness occurs at random a mixed model will be utilized to assess the change in the lesion 
over time. A sensitivity analysis will be performed using the last observation carried forward and 
the results will be compared to that of the mixed-model. 
Effect sizes will be estimated for the appropriate statistical tests that will be used for group 
comparisons in future studies. This will enable more accurate power and sample size estimates 
moving forward. 
 
Bioinformatic Analysis:  
RNA-seq analysis: We will use our recently developed LinNorm program 
(https://www.bioconductor.org/packages/release/bioc/html/Linnorm.html) to process RNA-seq 
data and detect differentially expressed genes (DEGs) by comparing the RNA-seq profiles. We 
will first find DEG between responsive and non-responsive samples from the same individual by 
using paired or unpaired Wilcoxon rank-sum test (depending on how the samples are collected). 
We will then rank each gene in the DEGs based on the occurrence frequencies in all 12 subjects 


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to find common DEGs for responsiveness (use permutation test to determine the p value).  For 
the top ranked genes (common DEGs), we will use DAVID (3) and GSEA (4) software to find 
enriched inflammatory pathways and GO terms for the DEGs. By comparing the normal tissue 
with the pathogenic tissue (responsive + non-responsible) using the above approach, we will 
detect a common DEGs for LP pathogenesis. Hierarchical clustering (5) and Principal 
Component Analysis (PCA) (6) will be applied to samples for their hierarchical relationship and 
clustering properties. Ideally normal, responsive and non-responsible tissues should form three 
distinct groups. The PCA analysis will provide us a set of gene signatures that can distinguish 
these three types of tissues. The common DEGs for responsiveness and pathogenesis, as well as 
gene signature from PCA will be used for our pathogenesis or survival prediction. We will 
perform structure variants calling from RNA-seq data with SNPiR (7), and reconstruct gene co-
expression networks with ARACHNE.(8) Additionally, we will perform de-convolutional 
analysis, to compare the immune profiles of responsive and non-responsive tissue and to 
correlate immune profiles. Predictive biomarkers will be correlated with lesional and global 
responses.  
 
8.3 
Subject Population(s) for Analysis 
• All-completed population:  All subjects that receive at least one dose will be considered 
for analysis.  
 


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9 Safety and Adverse Events 
9.1 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  
• Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; (6) 
breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
• Unanticipated: (i.e. unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, not listed in the 
Investigator’s Brochure, or not part of an underlying disease. A problem or event is 
"unanticipated" when it was unforeseeable at the time of its occurrence. A problem or 
event is "unanticipated" when it occurs at an increased frequency or at an increased 
severity than expected, AND 
• Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
Adverse Event 
An untoward or undesirable experience associated with the use of a medical product (i.e. drug, 
device, biologic) in a patient or research subject. 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  Serious problems/events can be well 
defined and include; 
• death 
• life threatening adverse experience 
• hospitalization 
• inpatient, new, or prolonged; disability/incapacity 
• persistent or significant disability or incapacity 
• birth defect/anomaly 
 
and/or per protocol may be problems/events that in the opinion of the sponsor-investigator 
may have adversely affected the rights, safety, or welfare of the subjects or others, or 
substantially compromised the research data. 
 
.  
 


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All adverse events that do not meet any of the criteria for serious, should be regarded as non-
serious adverse events.  
 
Adverse Event Reporting Period 
 
For this study, the study treatment follow-up period is defined as 30 days following the last 
administration of study treatment.  
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
should be recorded as an adverse event if the frequency, intensity, or the character of the 
condition worsens during the study period. 
 
General Physical Examination Findings 
 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an adverse event must also be recorded and documented as an adverse 
event.  
 
A thorough baseline screening will be followed for all subjects and is outlined in Table-2. A 
detailed list of the methods in which baseline screening will be performed is outlined in 
Supplemental 2. All blood draws and safety assessments must be performed prior to study 
treatment administration. Appropriate safety assessments (e.g., evaluation of AEs and SAEs) 
should be repeated after dosing with study treatment. A physical examination, including general 
appearance and vital signs, will be performed as indicated in Table-2. If indicated, based on 
medical history and/or symptoms, additional exams will be performed at the discretion of the 
investigator. If possible, the same member of the study site staff throughout the study will 
perform assessments for an individual subject. Information for all physical examinations will be 
included in the source documentation at the study site. Significant findings that are present prior 
to the subject signing informed consent will be included in the Medical History. Significant 
findings made after the signing of the informed consent, which meet the definition of an AE, 
must be recorded as an AE. Vital signs (blood pressure, pulse, height, weight) will be assessed at 
each physical examination as indicated in Table-2 (see Supplemental 2 for details on how to 
acquire vital signs). Whether action needs to be taken to address notable vital signs will be 
decided by the investigator, considering the overall status of the subject. 
 
Supplemental 1: Appropriateness of Measures 
 
Skin Scoring: 
There are no validated skin scoring systems for LP. Therefore, we will use simple measures of 
BSA which is objective and PGA which is well validated in other inflammatory skin conditions. 
Additionally, we will simply annotate the number of lesions on the individual as a marker of 
total disease burden. The later measure, CAILS was devised for evaluation of cutaneous T-cell 
lymphoma lesions for trial purposes. This system provides accurate measurements of CTCL 
patches, plaques, and tumors. This scoring system captures lesion redness, size, texture, 


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pigmentation and elevation characteristics. We will use a Modified CAILS scoring system that 
discards pigmentation scoring as resolving LP lesion inherently leave behind hyperpigmented 
skin changes which may confound active lesion scoring. This will provide a composite analysis 
of the index lesions as well as the general body involvement of the individual. The Modified 
CAILS system is advantageous over the PASI or EASI system in that in allows for more accurate 
calculation of surface area and incorporates that into the final score.  
 
In cases where some or all of the affected body regions contain such extensive LP disease that 
make counting individual LP lesions unfeasible, the lesion count in these areas will be estimated. 
The palmar surface of the hand equates to approximately 1% BSA. To estimate the lesion count  
in a body region of extensive disease, the number of lesions counted within an area equivalent to 
area the palmar surface of the hand within that extensively diseased body region will be 
multiplied by the representative BSA of that body region to determine the estimated lesion count 
contained in that body region. Representative BSAs of body regions are defined as follows: head 
(7%), neck (2%), anterior trunk (13%), arms (8%), forearms (6%), hands (5%), posterior trunk 
(13%), buttocks (5%), thighs (19%), legs (14%), feet (7%) and groin (1%).  
 
Itch Scoring: 
 
The NRS and Skindex-16 are all well validated measure of itch. The First score measure focuses 
in upon a gestalt of itch. The later scoring system focuses in upon the itch and its impact upon 
quality of life.  
 
Supplemental 2: Safety Measures 
 
Baseline Screening: 
 
A serum β-hCG test will be performed in all pre-menopausal women as indicated. All pre-
menopausal women who are not sterile at screening will also have a urine pregnancy test 
performed locally as indicated. Any woman with a confirmed positive pregnancy test during 
screening is not eligible for the study. A positive urine pregnancy test during the treatment periods 
of the study requires immediate interruption of study treatment until serum β-hCG is performed 
and found to be negative. If the serum β-hCG test is positive, study treatment must be definitively 
discontinued. 
 
Blood Pressure and Pulse: 
 
Height and Weight: 
Height and body weight will be measured in indoor clothing, but without shoes. If possible, body 
weight assessments should be performed by the same study site staff member and using the same 
scale throughout the study. 
 
Blood Draws: 
Subjects should avoid smoking within the hour preceding the blood draws. All laboratory studies 
will be conducted within the Mayo Clinic Health Systems (Mayo Clinic Arizona and Mayo Clinic 
Rochester). Details on the collections, shipment of samples and reporting of results will follow 


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Mayo Clinic’s current protocols. For the identification of notable values, the Mayo Clinic reference 
laboratory should be consulted. 
 
Supplemental 3: Safety Monitoring 
 
Infection monitoring: 
Study subjects will be evaluated at each visit for signs or symptoms of infection.  
• Vitals signs as well as constitutional symptoms will be assessed.  
• Assessment for common infections such as cellulitis as well as oral, vaginal, and cutaneous 
candidiasis will be performed 
 
 
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the sponsor-investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the sponsor-investigator should instruct each subject to report, to the sponsor-
investigator, any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.  
 
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an adverse event if  
 
• they induce clinical signs or symptoms,  
• they are considered clinically significant,  
• they require therapy.  
 
Laboratory studies will be drawn as indicated in Table-2. Whether action needs to be taken to 
address notable laboratory values will be decided by the investigator, considering the overall status 
of the subject. Hematology assessments will be measured at all scheduled study visits specified in 
Table-2. Serum chemistry will be a comprehensive metabolic panel will be measured at all 
scheduled study visits specified in Table-2. 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise in 
this protocol.  Any condition responsible for surgery should be documented as an adverse event 
if the condition meets the criteria for an adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
adverse event in the following circumstances:  
 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures 
for a preexisting condition.  Surgery should not be reported as an outcome of an adverse 
event if the purpose of the surgery was elective or diagnostic and the outcome was 
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9.2 
Recording of Adverse Events 
At each contact with the subject, the study team must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event section of the case report form (CRF).  All clearly related signs, symptoms, and abnormal 
diagnostic, laboratory or procedure results should recorded in the source document. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious adverse event that occurs during the Adverse Event Reporting 
Period and is considered to be at least possibly related to the study treatment or study 
participation should be recorded and reported immediately. 
 
9.3 
Reporting of Serious Adverse Events and Unanticipated Problems 
 
When an adverse event has been identified, the study team will take appropriated action 
necessary to protect the study participant and then complete the Study Adverse Event Worksheet 
and log.  The sponsor-investigator will evaluate the event and determine the necessary follow-up 
and reporting required. 
 
9.3.1 Sponsor-Investigator reporting: notifying the Mayo IRB 
 
The sponsor-investigator will report to the Mayo IRB any UPIRTSOs and Non-UPIRTSOs 
according to the Mayo IRB Policy and Procedures. 
 
Action taken regarding treatment  
 
AE Action: 
All adverse events should be treated appropriately. Treatment may include one or more of the 
following:  
• No action taken (i.e. further observation only)  
• [study/investigational] treatment dosage adjusted/temporarily interrupted  
• [study/investigational] treatment permanently discontinued due to this adverse event  
• concomitant medication given  
• non-drug therapy given  
• patient hospitalized/patient’s hospitalization prolonged  
 
AE Outcome: 
• All AE outcomes should be recorded (not recovered/not resolved; recovered/resolved; 
recovering/resolving, recovered/resolved with sequelae; fatal; or unknown) 
 
 


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Serious Adverse Events (SAE) 
An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the following 
criteria (Life-threatening in the context of a SAE refers to a reaction in which the patient was at 
risk of death at the time of the reaction; it does not refer to a reaction that hypothetically might 
have caused death if more severe.): 
• Is fatal or life-threatening  
• Results in persistent or significant disability/incapacity 
• Constitutes a congenital anomaly/birth defect 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes) 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
o Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission  
o Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
• Is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention. 
 
SAE Reporting: 
 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 30-days after the subject stopped study participation must be 
reported to the Incyte as soon as possible but no later than 5 days from learning of its occurrence 
according to the Mayo Clinic IRB policy. Any SAEs experienced after the 30-days period should 
only be reported to Incyte and the Mayo Clinic IRB if the investigator suspects a causal relationship 
to study treatment. Recurrent episodes, complications, or progression of the initial SAE must be 
reported as follow-up to the original episode, regardless of when the event occurs. This report must 
be submitted as soon as possible but no later than 5 days from the investigator receiving the follow-
up information. SAE should be followed up until resolution or until it is judged to be permanent. 
An SAE that is considered completely unrelated to a previously reported one should be reported 
separately as a new event. 
 
Information collected on the adverse event worksheet (and entered in the research database):  
• Subject’s name:  
• Medical record number:  
• Disease/histology (if applicable):  
• The date the adverse event occurred:  
• Description of the adverse event:  
• Relationship of the adverse event to the research (drug, procedure, or intervention*):  
• If the adverse event was expected:  
• The severity of the adverse event: (use a table to define severity scale 1-5**) 
• If any intervention was necessary:  


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• Resolution: (was the incident resolved spontaneously, or after discontinuing treatment) 
• Date of Resolution:  
 
AE Reporting: 
Its relationship to the:  
• Study treatment (no/yes), or 
• Investigational treatment (no/yes), or 
• The other study treatment (non-investigational) (no/yes), or 
• Both or indistinguishable 
The relationship will be categorized as follows: 
• Unrelated- Clearly due only to extraneous causes, and does not meet criteria listed under 
possible or probable. 
• Unlikely- Does not follow a reasonable temporal sequence from administration. May have 
been produced by the patient’s clinical state or by environmental factors or other therapies 
administered. 
• Possible- Follows a reasonable temporal sequence from administration, but may have been 
also produced by the patient’s clinical state, environmental factors or other therapies 
administered. 
• Probable- Clear-cut temporal association with administration with improvement on cessation 
of investigational medicinal product or reduction in dose. Reappears upon rechallenge. 
Follows a known pattern of response to the investigational medicinal product. 
Its duration (start and end dates) or if the event is ongoing an outcome of not recovered/not 
resolved should be reported. 
Whether it constitutes a serious adverse event(SAE) 
 
Adverse Events (AE): 
The severity grade/Common Toxicity Criteria (CTC) AE Version 4.0 grade 
• Mild: usually transient in nature and generally not interfering with normal activities 
• Moderate: sufficiently discomforting to interfere with normal activities 
• Severe: prevents normal activities 
 
If CTCAE grading does not exist for an adverse event, use  
1=mild, 2=moderate, 3=severe, 4=life-threatening, CTCAE Grade 5 (death) is not used, but is 
collected in other CRFs (Study Completion, Death/Survival). 
 
9.3.2 Sponsor-Investigator reporting: Notifying the FDA and Funding Sponsor  
 
The sponsor-investigator will report to the FDA all unexpected, serious suspected adverse 
reactions according to the required IND Safety Reporting timelines, formats and requirements. 
 
Unexpected fatal or life threatening suspected adverse reactions where there is evidence to 
suggest a causal relationship between the study drug/placebo and the adverse event, will be 
reported as a serious suspected adverse reaction.  This will be reported to the FDA on FDA Form 
3500A, no later than 7 calendar days after the sponsor-investigator’s initial receipt of the 
information about the event. 




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Within 30 days of learning of the pregnancy, the investigational site completes the Clinical Trial 
Pregnancy Form (sections I, II, and question 18 in section III) or equivalent, and e-mails the report 
to Incyte at 
  
 
Within 30 days of learning of the outcome of the pregnancy (delivery, termination, or miscarriage), 
the investigational site completes the Clinical Trial Pregnancy Form (sections II, III, IV, and V) 
or equivalent, and e-mails the report to Incyte at 
 
NOTE:  If a woman has a positive pregnancy test at Baseline, the investigational site completes 
Clinical Trial Pregnancy Form (sections I, II, and III (question 18)) or equivalent and e-mails the 
report to Incyte at 
 as per established timelines.  
 
Any SAE occurring during pregnancy must be reported to Incyte as an SAE, in accordance with 
Section 3 of the Serious Adverse Event Reporting Plan, as provided by Incyte. 
 
9.4 
Stopping Rules  
 
The stopping rules specified below are based on the knowledge available at study development. 
The stopping rule applies to the overall study. We note that the Adverse Event Stopping Rule 
may be adjusted in the event of either (1) the study re-opening to accrual or (2) at any time 
during the conduct of the trial and in consideration of newly acquired information regarding the 
adverse event profile of the treatment(s) under investigation. The study team may choose to 
suspend accrual because of unexpected adverse event profiles that have not crossed the specified 
rule below. 
 
Accrual will be temporarily suspended to this study if at any time we observe events considered 
at least possibly related to study treatment (i.e. an adverse event with attribute specified as 
“possible”, “probable”, or “definite”) that satisfy the following: 
 
• If 2 or more patients in the first 6 treated patients (or 30% after the first 6 treated patients have 
been accrued) experience a grade 3 or higher non-hematologic adverse event. 
 
We note that we will review grade 4 and 5 adverse events deemed “unrelated” or “unlikely to be 
related”, to verify their attribution and to monitor the emergence of a previously unrecognized 
treatment-related adverse event. 
9.5 
Medical Monitoring 
 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan (see section 10  “Study Monitoring, Auditing, and Inspecting”).  Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
 
The occurrence of adverse events will be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when the patient volunteers them 


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during or between visits or through physical examination, laboratory test, or other assessments. 
Please see Supplemental 3 for a detailed description of safety monitoring. Clinically significant 
abnormal laboratory values or test results will be identified through a review of values outside of 
normal ranges/clinically notable ranges, significant changes from baseline or the previous visit, or 
values which are non-typical in patient with underlying disease. Investigators have the 
responsibility for managing the safety of individual patient and identifying adverse events. Alert 
ranges for labs and other test abnormalities are included determined by the Mayo Clinic Arizona 
and Mayo Medical Laboratory. Adverse events will be recorded in the Adverse Events Case Report 
Form (CRF) under the signs, symptoms or diagnosis associated with them, and severity. All 
adverse events will be treated appropriately. Once an adverse event is detected, it should be 
followed until its resolution or until it is judged to be permanent, and 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 it, and the outcome (see 
Supplemental 3). Information about common side effects already known about the investigational 
drug can be found in the package insert. This information will be included in the patient informed 
consent and should be discussed with the patient during the study as needed. The investigator will 
also instruct each patient to report any new adverse event (beyond the protocol observation period) 
that the patient, or the patient’s personal physician, believes might reasonably be related to study 
treatment. This information should be recorded in the investigator’s source documents, however, 
if the AE meets the criteria of an SAE. To ensure patient safety, every SAE (see Supplemental 3 
for definition), regardless of suspected causality, occurring after the patient has provided informed 
consent and after the patient begins taking study drug and until 30 days after the patient has stopped 
study participation will be recorded and reported to Incyte. Any SAEs experienced after this 30-
day period should only be reported to Incyte if the investigator suspects a causal relationship to 
the study drug. All malignant neoplasms will be assessed as serious under “medically significant” 
if other seriousness criteria are not met. Medical and scientific judgment will be exercised in 
deciding whether other situations should be considered serious reactions, such as important 
medical events that might not be immediately life threatening or result in death or hospitalization 
but might jeopardize the patient or might require intervention to prevent one of the outcomes listed 
in SAE. Any suspected transmission via a medicinal product of an infectious agent is also 
considered a serious adverse reaction. All AEs (serious and non-serious) are captured and 
recorded, SAEs also require individual reporting (see Supplemental 3). To ensure patient safety, 
each pregnancy occurring while the patient is on study treatment must be reported to the sponsor-
investigator within 24 hours of learning of its occurrence. The pregnancy should be followed up 
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. Pregnancy follow-up should be recorded on the same form and should include an 
assessment of the possible relationship to the study treatment. Any SAE experienced during the 
pregnancy and unrelated to the pregnancy must be reported on a SAE form.  
 


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10 Data Handling and Record Keeping 
10.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
The rights of a research subject to revoke their authorization for use of their PHI. (This information 
is contained within the Mayo IRB Informed Consent Template SectioStudy data will be securely 
stored on a password protected computer that only the research study team will have access to.  
Any study related paper documents will be stored in a locked cabinet that only the research study 
team will have access to.  
• 14) 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (long term survival status that 
the subject is alive) at the end of their scheduled study period. 
10.2 Source Documents 
Source data is all information, 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.  Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
10.3 Case Report Forms 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All 
data requested on the CRF must be recorded.  All missing data must be explained.  If a space on 
the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”.  If the item is not applicable to the individual case, write “N/A”.  All entries should be 
printed legibly in black ink.  If any entry error has been made, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it.  All such 
changes must be initialed and dated.  Do not erase or use “white-out” for errors.  For clarification 
of illegible or uncertain entries, print the clarification above the item, then initial and date it.  If 
the reason for the correction is not clear or needs additional explanation, neatly include the 
details to justify the correction. 
 
 


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Data Security and Confidentiality 
 
All study data will be collected by the research team, reviewed by the PI, and stored in secure, 
locked files and/or databases in order to protect it from inadvertent loss or improper access. All 
laboratory specimens, evaluation forms, reports, and other records will be identified by coded 
number only to maintain subject confidentiality. Information gained from this study that can be 
linked to the subject's identity will not be released to anyone other than the investigators, the 
subject and the subject's physician. All the information obtained in connection with these studies 
will remain confidential as far as possible within state and federal law. The results of these 
studies will be published in scientific journals without identifying the subjects by name. 
 
Data Quality Assurance 
 
Source document verification will be performed to ensure that the database accurately reflects 
data on the CRFs.  
 
Data Clarification Process 
 
10.4 Records Retention 
 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents. These will include 
subject case histories and regulatory documents. There will be a subject code master list that will 
be stored so as to protect subjects’confidentiality. Case Report Forms will be coded. There will 
be no subject names or other directly identifiable information will not appear on any reports, 
publications, or other disclosures of clinical study outcomes. 
 
The sponsor-investigator will retain the specified records and reports for; 
1. Up to 2 years after the marketing application is approved for the drug; or, if a marketing 
application is not submitted or approved for the drug, until 2 years after shipment and 
delivery of the drug for investigational use is discontinued and the FDA has been so 
notified. OR 
2. As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy” 
   
Whichever is longer 
 
11 Study Monitoring, Auditing, and Inspecting 
11.1 Study Monitoring Plan 
 
The investigator will allocate adequate time for such monitoring activities.  The Investigator will 
also ensure that the monitor or other compliance or quality assurance reviewer is given access to 
all the study-related documents and study related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.), and has adequate space to conduct the monitoring visit. 


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11.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, and government regulatory agencies, of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 
12 Ethical Considerations 
This study is to be conducted according to United States government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the Approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject or the subject’s legally authorized representative, and the individual obtaining the 
informed consent. 
13 Study Finances 
13.1 Funding Source 
 
Incyte Corporation is funding this research study.  
 
13.2 Subject Stipends or Payments 
 
Subjects will receive $50 for each biopsy visit they complete (Day 0 and Wk4).  They will 
receive $25 for all other visits that they complete.   If they complete all study visits they will 
receive a total of $250.    
 
14 Publication Plan 
 
The key design elements of this protocol will be posted in a publicly accessible database such as 
clinicaltrials.gov. In addition, upon study completion and finalization of the study report the results 


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of this trial will be either submitted for publication and/or posted in a publicly accessible database 
of clinical trial results. 
 
15 References 
 
1. 
Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. 
Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell 
transplantation: a multicenter survey. Leukemia. 2015;29(10):2062-8. 
2. 
Hornung T, Janzen V, Heidgen FJ, Wolf D, Bieber T, Wenzel J. Remission of recalcitrant 
dermatomyositis treated with ruxolitinib. N Engl J Med. 2014;371(26):2537-8. 
3. 
Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG, Roayaei J, et al. The DAVID 
Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally 
analyze large gene lists. Genome Biol. 2007;8(9):R183. 
4. 
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. 
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide 
expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-50. 
5. 
Yeung KY, Haynor DR, Ruzzo WL. Validating clustering for gene expression data. 
Bioinformatics. 2001;17(4):309-18. 
6. 
Yeung KY, Ruzzo WL. Principal component analysis for clustering gene expression data. 
Bioinformatics. 2001;17(9):763-74. 
7. 
Piskol R, Ramaswami G, Li JB. Reliable identification of genomic variants from RNA-
seq data. Am J Hum Genet. 2013;93(4):641-51. 
8. 
Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Dalla Favera R, et al. 
ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian 
cellular context. BMC Bioinformatics. 2006;7 Suppl 1:S7. 
9. 
Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, et al. Clinical end 
points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement 
of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma 
Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for 
Research and Treatment of Cancer. Journal of clinical oncology : official journal of the 
American Society of Clinical Oncology. 2011;29(18):2598-607. 
10. 
Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, et al. Phase 2 and 3 
clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent 
early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001;137(5):581-93. 
11. 
Rogers LC, Bevilacqua NJ, Armstrong DG, Andros G. Digital planimetry results in more 
accurate wound measurements: a comparison to standard ruler measurements. J Diabetes Sci 
Technol. 2010;4(4):799-802. 
12. 
Phan NQ, Blome C, Fritz F, Gerss J, Reich A, Ebata T, et al. Assessment of pruritus 
intensity: prospective study on validity and reliability of the visual analogue scale, numerical 
rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 
2012;92(5):502-7. 
13. 
Reich A, Heisig M, Phan NQ, Taneda K, Takamori K, Takeuchi S, et al. Visual analogue 
scale: evaluation of the instrument for the assessment of pruritus. Acta Derm Venereol. 
2012;92(5):497-501. 


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14. 
Chren MM, Lasek RJ, Sahay AP, Sands LP. Measurement properties of Skindex-16: a 
brief quality-of-life measure for patients with skin diseases. J Cutan Med Surg. 2001;5(2):105-
10. 
15. 
Atherton PJ, Burger KN, Loprinzi CL, Neben Wittich MA, Miller RC, Jatoi A, et al. 
Using the Skindex-16 and Common Terminology Criteria for Adverse Events to assess rash 
symptoms: results of a pooled-analysis (N0993). Support Care Cancer. 2012;20(8):1729-35. 
 
16 Attachments 
 
Appendix: 
 
Physician Global Assessment: (9, 10) 
Grade 0 Completely clear: no evidence of disease (100% improvement) CCR 
Grade 1 Almost clear: very significant clearance (≥90% to <100%) PR 
Grade 2 Marked Improvement: significant improvement (≥75% to <90%)PR 
Grade 3 Moderate improvement: intermediate between slight and marked (≥50% to <75%) PR 
Grade 4 Slight improvement: some improvement (≥25% to <50%); however, significant 
evidence of disease remains SD 
Grade 5 No change; disease has not changed from baseline condition (+/-<25%) SD 
Grade 6 Worse, disease is worse than at baseline evaluation by (≥25%) or more PD 
 
CCR- Complete clinical response 
PR- Partial response 
SD- Stable disease 
PD- Progressive Disease 
 
 
 
 


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Modified CAILS- 
Clinical Assessment Scale of Severity for Index Lesion Signs and Symptoms (CAILS) (9, 10) 
 
Scale      Grade 
0             No evidence of sign or symptom 
1             Intermediate interval 
2             Mild: less than average presentation of sign or symptom 
3             Intermediate interval 
4             Moderate: average disease presentation of sign or symptom 
5             Intermediate interval 
6             Severe: greater than 25% worse than average severity of sign or symptom 
7             Intermediate interval 
8             Very severe: the near worst severity sign or symptom 
A scale of 0 to 18 was used to grade lesion size by square centimeter (0, 0 [no measurable area]; 
1, >0 and ≤4; 2, >4 and ≤10; 3, >10 and ≤16; 4, >16 and ≤25; 5, >25 and ≤35; 6, >35 and ≤45; 7, 
>45 and ≤55; 8, >55 and ≤70; 9, >70 and ≤90; 10, >90 and ≤110; 11, >110 and ≤130; 12, >130 
and ≤155; 13, >155 and ≤180; 14, >180 and ≤210; 15, >210 and ≤240; 16, >240 and ≤270; 17, 
>270 and ≤300; and 18, >300). The area of the lesion will be measured with digital planimetry. 
(9-11) 
 
 
Modified CAILS index lesion score: 
1. 
Erythema(0-8) 
2. 
Scaling (0-8) 
3. 
Plaque elevation (0-8) 
4. 
Size (0-18) 
o 
Trained clinical evaluators assessed the same patients throughout the study. 
o 
The CA (the ratio of summation (Σ) of all clinical signs for these index lesion at each 
visit compared with baseline) included cutaneous tumors and all extra cutaneous manifestations 
of disease.  
o 
Complete clinical remission (CCR) required a CA ratio of 0 with no evidence of disease  
o 
Partial remission (PR) was defined as  
o 
A CA ratio of 0.5 or lower without new clinically abnormal lymph nodes 
o 
Progressive disease was defined as  
o 
A 25% or higher increase in CA ratio 
(Olsen et al., 2011b, Duvic et al., 2001b) 
 
 
 


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Itch-  
Numerical Rating Scale (NRS) (bottom)- (12, 13) 
 
0- No itch 
1-4 Mild itch 
4-7 Moderate itch 
7-9 Severe itch 
10- Very severe itch  
 
 
 
 


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Skindex-16- 
 
Skindex 16 (14, 15)- 
 
Scoring (0=never bothered to 6=always bothered), Total 0 to 96 
 
Symptom Subscale 
1. 
Skin itching 
2. 
Skin burning or stinging 
3. 
Skin hurting 
4. 
Skin irritated 
 
Emotional Subscale 
5. 
Persistence or recurrence of condition 
6. 
Worry about condition 
7. 
Appearance of skin 
8. 
Frustration about skin 
9. 
Embarrassment about skin 
10. 
Annoyed about skin 
11. 
Feeling depressed 
 
Functional Subscale 
12. 
Effect of skin on interaction with others 
13. 
Effect of skin on desire to be with people 
14. 
Skin making it hard to show affection 
15. 
Effect of skin on daily activity 
16. 
Skin making it hard to work/have enjoyment