Exploratory Study of Ruxolitinib Cream for the Treatment of Discoid Lupus Erythematosus
Phase: PHASE2
Conditions: Discoid Lupus Erythematosus
Sponsor: University of Rochester

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NCT04908280
Exploratory Study of Ruxolitinib Cream for the Treatment 
of Discoid Lupus Erythematosus 
Principal Investigator – Christopher T. Richardson MD, PhD 
TABLE OF CONTENTS 
Glossary of Abbreviations..................................................................................................... 3 
1. Purpose of Study.............................................................................................................. 4 
2. Background and Rationale............................................................................................... 4 
3. Administrative Organization............................................................................................ 5 
4. Study Design.................................................................................................................... 5 
4.1. Subject Population.................................................................................................... 5 
4.1.1. Number of Subject......................................................................................... 5 
4.1.2. Gender and Age............................................................................................. 5 
4.1.3. Racial and Ethnic Origin................................................................................ 5 
4.1.4. Vulnerable Subject......................................................................................... 5 
4.2. Study Interventions................................................................................................... 6 
5. Inclusion and Exclusion Criteria...................................................................................... 6 
5.1. Inclusion Criteria...................................................................................................... 6 
5.2. Exclusion Criteria..................................................................................................... 6 
6. Recruitment Methods....................................................................................................... 7 
7. Consent Process............................................................................................................... 8 
7.1. Process of Consent.................................................................................................... 8 
7.2. Consent Forms.......................................................................................................... 8 
7.3. Documentation of Consent....................................................................................... 8 
8. Study Procedures............................................................................................................. 8 
8.1. Subject Visits............................................................................................................ 9 
8.2. Study Procedures...................................................................................................... 9 
8.2.1. Clinical Assessments..................................................................................... 9 
8.2.2. Safety Monitoring........................................................................................ 10 

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8.2.3. Research Procedures...................................................................................... 10 
8.2.4. Schedule of Activities ................................................................................... 12 
8.2.5. Data Analysis................................................................................................. 13 
9. Risks to Subjects.............................................................................................................. 13 
9.1. Risks of Participation................................................................................................ 13 
9.2. Alternatives to Participation..................................................................................... 14 
10. Potential Benefits to Subjects.......................................................................................... 14 
11. Costs for Participation......................................................................................................14 
12. Payment for Participation................................................................................................ 15 
13. Subject Withdrawals........................................................................................................ 15 
14. Privacy and Confidentiality of Subjects and Research Data........................................... 16 
15. Data / Sample Storage for Future Use............................................................................. 16 
16. Data and Safety Monitoring Plan..................................................................................... 17 
16.1. 
Data Safety and Monitoring........................................................................... 17 
16.2. 
SAE Reporting to Incyte................................................................................ 17 
16.3. 
Reporting of Pregnancy to Incyte.................................................................. 18 
17. Data Analysis Plan........................................................................................................... 18 
18. References........................................................................................................................ 18 
 
 
 
 
 
 
 
 
 
 
 
 
 

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GLOSSARY OF ABBREVIATIONS 
 
 
AE 
Adverse event 
AIR 
Allergy, Immunology and Rheumatology 
BSA 
Body surface area 
CBC 
Complete blood count 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CMP 
Comprehensive metabolic panel 
CTU 
Clinical trials unit 
DLE  
Discoid lupus erythematosus 
EI 
Erythema index 
FDA 
U.S. Food and Drug Administration 
IFM 
Immunofluorescence microscopy 
IFN 
Interferon 
IGA 
Investigator’s Global Assessment 
IHC 
Immunohistochemistry 
IND 
Investigational new drug 
IRB 
Institutional review board 
JAK 
Janus kinase 
MACE 
Major adverse cardiovascular event 
MI 
Melanin index 
NRS 
Numeric rating scale 
PHI 
Protected health information 
PI 
Principal investigator 
RSRB 
Research subjects review board 
SAE 
Serious adverse event 
STAT 
Signal transducer and activator of transcription  
URMC 
University of Rochester Medical Center 
 
 
 

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1. PURPOSE OF STUDY 
 
The primary objective of this study is to assess the potential efficacy of topical ruxolitinib for 
the treatment of discoid lupus erythematosus (DLE). We propose a 12-week open-label clinical 
trial. An exploratory objective of this study is to analyze cellular and molecular features of 
discoid lesions before and after treatment with topical ruxolitinib to assess 1) predictors of 
treatment response, and 2) treatment response to ruxolitinib. 
 
 
2. BACKGROUND AND RATIONALE  
 
Standard of care for patients with DLE depends on disease severity, but can include topical 
steroids, 
topical 
calcineurin 
inhibitors, 
systemic 
antimalarials, 
and 
systemic 
immunosuppressive medications. The only FDA-approved medication for DLE is 
hydroxychloroquine. Consequently, topical steroids and calcineurin inhibitors, as well as a 
number of systemic immunosuppressive medications, are also used to treat DLE. Systemic 
immunosuppression is used infrequently. Topical calcineurin inhibitors are generally less 
effective than topical steroids, but arguably may have a more favorable safety profile. Topical 
steroids have the potential to induce skin atrophy, an especially devastating side effect on the 
face, head and neck, the most commonly affected areas in DLE. Though not often used on the 
face to treat other skin conditions, due to the severe nature of the disease, class I superpotent 
topical steroids are used in DLE for short periods of time (< 2 weeks), while weaker topical 
steroids are generally not very effective. Antimalarials and other systemic immunosuppressive 
medications are effective in some DLE patients, but have significant potential side effects 
including retinopathy, cytopenias, liver toxicity, and increased infection risk.  
  
Type I interferons are key inflammatory cytokines in DLE pathogenesis.1 These inflammatory 
mediators signal through the JAK-STAT pathway. Janus kinase (JAK) inhibitors, which block 
interferon (IFN) signaling, are a new class of therapeutics with potential efficacy in lupus. 
Systemic JAK inhibitors have been effective in murine models of lupus.2-4 Of particular 
interest is one murine study in which oral ruxolitinib, a potent JAK1/2 inhibitor, attenuates 
cutaneous lupus development, without much effect on systemic disease.2 This study suggests 
that ruxolitinib may be more selective in treating lupus skin disease. 
 
Oral ruxolitinib is FDA-approved for the treatment of polycythemia vera, myelofibrosis and 
acute graft-versus-host disease. Topical ruxolitinib has been shown to be effective in a number 
of inflammatory human skin diseases including alopecia areata/universalis, vitiligo, and atopic 
dermatitis.5-7 Systemic side effects have not been reported with topical use. The most common 
side effects from topical JAK inhibitors are mild and include local irritation, erythema, acne, 
or papular eruptions. In summary, we hypothesize that topical ruxolitinib may be both more 
effective and safer than topical steroids for the treatment of DLE. 
 
 
 
 
 

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3. ADMINISTRATIVE ORGANIZATION   
 
This is a single-center study in the Department of Dermatology at the University of Rochester 
Medical Center (URMC). Dr. Christopher Richardson, who is a medical dermatologist with 
clinical and research expertise in lupus, will be the principal investigator (PI). The study will 
be performed in the URMC Dermatology Clinical Trials Unit (CTU), which will provide both 
administrative and coordinator support for the trial. Medication management will be handled 
by the Investigational Drug Service of the URMC Department of Pharmacy. Safety laboratory 
monitoring will be done through URMC labs. Laboratory analyses of deidentified skin samples 
will be performed in the Richardson laboratory and URMC core facilities.  
 
 
4. STUDY DESIGN 
 
This is a 12-week, single-center, open-label study of ruxolitinib 1.5% cream for the treatment 
of discoid lupus. The primary endpoint is a ≥ 2-point reduction in Investigator’s Global 
Assessment (IGA) score at Week 12 compared to baseline. Secondary endpoints at Week 12 
include the mean percentage change from baseline in the Cutaneous Lupus Erythematosus 
Disease Area and Severity Index (CLASI), CLASI-A (activity) and CLASI-D (damage) 
scores; the change in erythema and pigmentation as determined by quantitative photographic 
analysis; and the change in numeric rating scale (NRS) for pain and pruritus. Exploratory 
endpoints of skin biopsies will evaluate cellular and molecular features of discoid lesions pre- 
and post-treatment for 1) predictors of treatment response, and 2) treatment response to 
ruxolitinib. Quantitative and qualitative measures of the cutaneous inflammatory response, 
including evaluation of the immune cell infiltrate and IFN signature, will be assessed.  
 
4.1. SUBJECT POPULATION 
 
4.1.1 Number of Subjects 
Fifteen subjects will be consented to enroll in this study. This small sample size is justified 
by the rarity of this condition and the exploratory nature of the study.  
 
4.1.2 Gender and Age 
DLE has a female predominance, but both men and women may participate. Subjects will 
be 18 years old or older. 
 
4.1.3 Racial and Ethnic Origin 
DLE affects all racial and ethnic groups, but is more frequent and more severe among 
African Americans than among Caucasians. Racial and ethnic origin of subjects will be 
monitored to reflect the diversity of our community. However, no subjects will be excluded 
based on race or ethnic origin. 
 
4.1.4 Vulnerable Subjects 
Vulnerable subjects will not be targeted, including children, pregnant women, prisoners, 
and decisionally impaired adults. Employees and students of the University may participate 
but will not be targeted or coerced. 
 

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4.2. STUDY INTERVENTIONS 
 
The active drug used in this trial will be ruxolitinib 1.5% cream. Ruxolitinib cream will be 
applied topically twice daily to areas of active disease.  Ruxolitinib cream will be supplied 
by Incyte. Incyte’s IND number for ruxolitinib is #77,101. Inventory control and storage, 
drug accountability, packaging and labeling, and dispensing will be managed by the 
URMC Investigational Drug Services. Standard topical therapies will be replaced with the 
study drug, and only systemic antimalarials will be continued as standard of care during 
this study. Details of potential risks associated with this drug is discussed in detail in 
Section 9, Risks to Subjects. Subjects are free to withdraw from the study at any time.  
 
 
5. INCLUSION AND EXCLUSION CRITERIA 
 
5.1 Inclusion Criteria 
 
Individuals who meet all of the following criteria are eligible for enrollment as study 
participants: 
● Ability to understand and comply with the protocol and provide informed consent. 
● Speaks English. 
● Age ≥ 18 years. 
● Clinical diagnosis of discoid lupus as assessed by the PI. 
● At least one active (inflamed) discoid lesion with an IGA score of ≥ 3 and with a 
diameter ≥ 1cm at screening and baseline. Two lesions with equal scores will be 
necessary if consenting to pre-and post-treatment biopsies. 
● Maximum body surface area of 20%. 
 
     5.2 Exclusion Criteria 
 
Individuals who meet any of these criteria are not eligible for enrollment as study 
participants: 
● Unwillingness or inability to complete informed consent process or comply with the 
study protocol. 
● Pregnant or breast-feeding women, or women planning to become pregnant or 
breastfeed during the study. 
● History of coagulopathy, pulmonary embolism or deep venous thrombosis. 
● History of cutaneous squamous cell carcinoma localized to the treatment area. 
● Serum creatinine > 1.5 mg/dL, or alanine aminotransferase or aspartate 
aminotransferase  > 1.5 × upper limit of normal. 
● Other dermatologic disease besides discoid lupus whose presence or treatments could 
complicate assessments. 
● Other diseases besides dermatologic disorders whose treatment could complicate 
assessments. Subjects with systemic lupus erythematosus are permitted as long as they 

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do not have unstable disease and meet all other criteria, including the exclusion criteria 
for systemic immunosuppressive or immunomodulating drugs (below). 
● Topical treatments for discoid lupus within 2 weeks of Visit 2. 
● Systemic immunosuppressive or immunomodulating drugs (e.g. oral or injectable 
corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) 
other than antimalarials (hydroxychloroquine, chloroquine, quinacrine) within 4 weeks 
or 5 half-lives of Visit 2 (whichever is longer). 
● Potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 
half-lives, whichever is longer, before Visit 2 (topical agents with limited systemic 
availability are permitted). 
● Prior use of JAK inhibitors, systemic or topical, within the last 12 months. 
● Ultraviolet (UV) therapy or tanning within 2 weeks prior to Visit 2 or during the 
duration of the treatment period. 
● Any systemic or local infection that, in the opinion of the investigator, may compromise 
the safety of the subject or complicate assessments. 
● Subjects allergic to lidocaine or with a history of keloids will not be allowed to provide 
an optional skin biopsy, but will be eligible for the remainder of the study. 
 
 
6. RECRUITMENT METHODS 
 
Eligible subjects will be identified and recruited in the following ways:  
● Subjects with DLE may be recruited from the contact database of Med/AIR Subject 
Database and Tissue Repository (RSRB#276) or the Evaluation of the Pathogenesis of 
Cutaneous Lupus Erythematosus study (RSRB#3215) if subjects have previously 
indicated their interest in being contacted for future studies. The PI of this study (Dr. 
Richardson) is also the PI of RSRB#3215 and a sub-investigator on RSRB#276. 
● This study will identify potential subjects for recruitment using the UR CTSI Research 
Participant Registry, STUDY00001978. Subjects enrolled in the URMC Research 
Participant Registry may be contacted to enroll in this study.  
● Subjects may be recruited during routine clinic visits by providers and staff involved 
in their care. These providers may also include the PI and Sub-investigators. To assist 
in identifying subjects who have not yet been recruited into this study, the study 
coordinators may review eRecord charts of individuals prior to their clinic visits to 
prompt the provider to discuss research with them. Subjects will be approached by staff 
providing care to obtain the subject’s agreement to be contacted by the study team. 
● As standard of care, subjects who have been evaluated in the Department of 
Dermatology or Allergy, Immunology and Rheumatology (AIR) Division, and who 
have been coded with a lupus specific ICD-9 or ICD-10 code, may have providers reach 
out and offer for them to be seen in a Dermatology or AIR clinic. They may also be 

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offered enrollment in this study. Subjects who do not want to be seen in clinic will still 
have the option to enroll into this study. 
Potential subjects may be contacted via telephone call to discuss the study, field questions and assess 
interest; an IRB approved Telephone Script will be followed.  If the potential subject is interested in 
participating in the study they will be offered to have the consent form mailed or emailed to them to READ 
ONLY with an IRB approved Information Sheet with instructions that the consent is for review only.  Prior 
to the consent being mailed or emailed to the potential subject a study team member will cross out the 
signature page to eliminate confusion.  The potential subject will sign a NEW clean consent upon their 
clinic and/or study visit along with the study team member.  
 
7. CONSENT PROCESS 
 
7.1 Process of Consent 
The consent process will provide information about the study to a prospective participant 
and will allow adequate time for review and discussion prior to his/her decision. The PI or 
a qualified study member listed in the CLICK IRB protocol will review the consent form 
with the participant and answer questions. Consent designees will be listed on the site 
delegation of responsibilities log, complete consenting certification, and have knowledge 
of the protocol and study procedures. The PI or designee will meet directly with subjects 
in a private room and the consent form will be read in its entirety. Any questions will be 
answered to the subject’s satisfaction. The subject’s capacity to comprehend the 
information in the consent form will be assessed by asking questions about the content and 
encouraging the subject to describe briefly the study procedures. Subjects will be assured 
that enrollment is voluntary and that they are free to not participate or to withdraw at any 
time, without risking loss of present or future care that they would otherwise receive. It 
will be explained to the subject that those who consent to participate in this study will have 
their contact information and medical history stored in the database. Subjects will be 
informed that if they withdraw consent, no new information will be collected, and they can 
choose to have any stored samples discarded. However, data generated from previously 
used samples may be retained. Subjects will be allowed as much time as necessary to 
provide consent. Subjects will provide consent by signing the informed consent form for 
this study. Subjects will receive a signed copy of the consent form. The consent process 
will be ongoing. The consent form will be revised, and the subjects re-consented, when 
important new safety information is available, the protocol is amended, and/or new 
information becomes available that may affect participation in the study.   
 
7.2 Consent Forms 
Attached in the RSRB application. 
 
7.3 Documentation of Consent 
Both the study subject and the person obtaining consent will sign and date the consent form 
in order to document consent.  
 
 
 
8. STUDY PROCEDURES 
 

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This study will be a single-arm trial of ruxolitinib 1.5% cream applied twice daily for 12 weeks. 
Only active lesions will be treated, defined as those with erythema, scale, pain, or pruritus. 
Each subject will be provided with ruxolitinib cream. 
 
8.1 Subject Visits 
Each subject will have a total of 7 visits. The initial visit will be the Screening visit, which 
will occur 7 to 28 days before the start of the trial. Treatment visits will be at weeks 0, 2, 
4, 8, and 12, at which times the subject will have assessments performed to document DLE 
severity and assess safety. A follow-up visit to assess safety will be performed at 16 weeks. 
 
 
8.2 Study Procedures 
Clinical assessments, safety procedures, and research procedures will be performed as 
outlined below per the schedule of activities. In the event that one of these is not able to be 
completed, disease activity increases or other concerns arise, the subject may be asked to 
return to the clinic for an “unscheduled visit” to reassess the subject and perform as needed 
any clinical assessments, safety procedures, or research procedures as outlined below. 
 
8.2.1 Clinical Assessments 
Clinical Assessments: A detailed physical exam, past medical history and vital signs will 
be performed at study visit 1. A problem-focused physical exam, interval history and vital 
signs (heart rate, blood pressure, temperature, weight) will be performed at visits 2-7. 
Adverse events will be assessed at study visits 2-7. 
 
IGA: The Investigator’s Global Assessment will be performed at study visits 2-6. The IGA 
is an instrument to rate the severity of the subject's global disease. This IGA is comprised 
of a 5-point scale of disease activity ranging from 0 to 4 as follows: 
 
0: “clear,” no erythema or scale 
1: “almost clear,” pink erythema without scale 
2: “mild,” pink erythema with scale 
3: “moderate,” red erythema with scale 
4: “severe,” purple/violaceous or hemorrhagic/crusted erythema OR hypertrophic/ 
 
verrucous scale 
 
CLASI: The Cutaneous Lupus Area and Severity Index will be performed at study visits 
2-6. This is a validated measurement instrument designed for use in clinical trials to assess 
disease activity and damage in subjects with cutaneous lupus. The CLASI is comprised of 
two parts, CLASI-A that measures disease activity (erythema and scale), and CLASI-D 
that measures disease damage (pigmentation and scarring). 
 
NRS: Subjects will maintain a symptom diary every day for 12 weeks. Specifically, 
subjects will rate pain and itch separately using a numeric rating scale (NRS) and the 
questions below. Symptom diaries will be reviewed at study visits 2-6.  
 
On a scale of no itch (0) to worst imaginable itch (10), how itchy was the worst discoid 

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lupus lesion in the last 24 hours? 
 
On a scale of no pain (0) to worst imaginable pain (10), how painful was the worst discoid 
lupus lesion in the last 24 hours?  
Photography: Photographs of all discoid lesions will be taken at study visits 2-6. The Haiku 
app or Canto app will be used to directly load photos into the secure Epic medical record 
system. Images will be extracted from Epic, and analyzed as described.8 In brief, a melanin 
index (MI) and an erythema index (EI) will be generated for each lesion using Image J 
software analysis. The analysis uses perilesional skin to normalize the photograph. Images 
from serial visits will then be compared, as well as between treatment groups. 
 
Compliance: Tubes of cream will be weighed at each visit. Additional jars/tubes will be 
supplied as needed at study visits, which will vary depending on the percent body surface 
area (BSA) involved. 
 
8.2.2 Safety Monitoring 
History & Exam: An interval history and problem focused physical exam will be performed 
at each visit. Subjects will also be asked about recent systemic infections. The focused 
exam will also include an assessment of the skin immediately surrounding the DLE lesion 
for irritation using a standard 8-pt scale. This scale was developed by Berger and Bowman9 
to assess the effect of topicals on normal skin; any visual assessment methodology for 
irritation on an already inflamed DLE lesion would not be informative. 
 
Phlebotomy: Blood draws will be performed by a trained phlebotomist. A complete blood 
count (CBC), comprehensive metabolic panel (CMP), and lipid panel will be assessed at 
the screening visit. Additional labs will be drawn as follows: CBC and CMP at 4 and 12 
weeks, lipid panel at 12 weeks. Standard of care laboratories may be drawn at the same 
time for subject convenience. The venipuncture site will be covered with gauze and a band-
aid. 
 
Urine pregnancy test: Urine pregnancy tests will be performed at screening and monthly 
during treatment for all females of childbearing potential. Menopause is defined as at least 
12 consecutive months without menses; if in question, a follicle stimulating hormone of 
≥25 U/mL must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal 
ligation must be documented, as applicable; if documented, a urine pregnancy test is not 
required for women with these conditions. 
 
 
8.2.3 Research Procedures 
Optional skin biopsies at weeks 0 and 12 will be analyzed as follows: 
● Histology: H&E, immunohistochemistry (IHC), and/or immunofluorescence 
microscopy (IFM) 
● Flow cytometry/cell sorting: composition of inflammatory infiltrate 
● RNAseq: IFN signature 

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Biopsy: For subjects that are willing to provide an optional skin biopsy, two discoid lesions 
with equal IGA scores (3 or 4) will be selected at Visit 2, one of which will be biopsied at 
that visit. At visit 6, the other lesion will be biopsied.  
 
After obtaining informed consent, a skin biopsy will be obtained by a study practitioner 
trained in this procedure. A biopsy will consist of removing a piece of skin with a 4-mm 
skin biopsy punch. The biopsy will be performed after injecting a local anesthetic 
(lidocaine with epinephrine) to minimize pain and blood loss. At the biopsy site one or two 
sutures may be placed to improve healing, reduce blood loss and scar formation. A pressure 
bandage will be applied to the biopsy site to minimize the risk of bleeding and infection. 
The biopsy will be divided as appropriate for subsequent analysis. 
  
All study subjects will be given the option to visit the study center for suture removal 7-14 
days after the biopsy was taken. Our experience is that some of our study subjects, 
especially the ones who live far from the study center, prefer to have their sutures removed 
by a local physician, health care provider, family member or friend trained on removing 
sutures.  Nevertheless, we will strongly recommend in each case that the study subject 
return to the study center for removal of suture so that we can evaluate whether the biopsy 
site is healing well. 
  
We will provide each subject with a wound care instruction sheet which says: 
“If non-absorbable stitches were placed, they should be removed either by returning to the 
University of Rochester Department of Dermatology or by a local physician, health care 
provider, family member or friend with experience removing sutures in 7 to 10 days from 
their placement.  If possible, keep the biopsy site completely dry for the first 24 hours after 
the biopsy. After that, change the band-aid and apply petroleum jelly to the site on a daily 
basis. We have provided you with the supplies to do this.  The site will appear a bit red and 
may be itchy after several days and that is a normal healing response.  Please contact us if 
at the site of the skin biopsy the pain increases, the dressing continues to be saturated with 
blood or there is foul-smelling, pus-like drainage from the site (after the first 2 days).  For 
any questions or concerns, or to arrange for stitch removal, call the Clinical Coordinators 
- at 585-273-2909 or 585-273-4195.” 
 
Histology: We will analyze the DLE skin tissue using IHC and/or IFM. Common features 
of DLE histology will be evaluated, including hyperkeratosis, epidermal atrophy, follicular 
plugging, interface change, and immunoglobulin deposition. A quantitative analysis of 
immune cell counts will be performed. Markers of IFN response will be analyzed. 
 
Flow Cytometry: We will evaluate the immune and other cell types from disaggregated 
DLE skin tissue by multi-color flow cytometry per lab protocols. 
 
Transcriptomics: The IFN signature will be evaluated by RNAseq.  
 
 
8.2.4 Schedule of Activities 
 

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Study Procedure 
Screening 
Treatment 
 
F/U 
Unscheduled 
Visit 
1 
2 
3 
4 
5 
6 
7 
  
Week 
-4 to -1 
0 
2 
4 
8 
12 
16 
  
Study day 
-28 to -7 
0 
14 
28 
56 
84 
112 
  
Window in days 
  
  
+/-3 
+/-3 
+/-3 
+/-3 
+/-3 
  
Screening/Baseline 
  
  
  
  
  
  
  
  
Informed Consent 
X 
  
  
  
  
  
  
  
Review eligibility  
X 
  
  
  
  
  
  
  
Medical history 
X 
  
  
  
  
  
  
  
Detailed physical exam 
X 
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
Confirm eligibility/Enroll 
  
X 
  
  
  
  
  
  
Assessment 
  
  
  
  
  
  
  
  
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
Interval history 
  
X 
X 
X 
X 
X 
X 
X 
Problem-focused Exam  
  
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
  
X 
X 
X 
X 
X 
X 
X 
IGA 
 
X 
X 
X 
X 
X 
  
X 
CLASI 
  
X 
X 
X 
X 
X 
  
X 
Symptom Diary Review 
  
X 
X 
X 
X 
X 
  
X 
Photography 
  
X 
X 
X 
X 
X 
  
X 
Laboratory Testing 
  
  
  
  
  
  
  
  
CBC, CMP 
X 
  
  
X 
 
X  
 
X 
Lipid panel 
X 
 
 
 
 
X 
 
X 
Urine Pregnancy 
X 
X 
 
X 
X 
X 
 
X 
Treatment 
  
  
  
  
  
  
  
  
Weigh product 
  
X 
X 
X 
X 
X 
  
X 
Dispense product (as 
needed) 
  
X 
X 
X 
X 
 
  
X 
Return product 
  
  
  
  
  
X  
  
X 
Research Procedure 
  
  
  
  
  
  
  
  
Skin biopsy (optional) 
  
X 
  
  
  
X 
  
X 
8.2.5 Data Analysis 
 
Primary Endpoint: A ≥ 2-point reduction in IGA score at Week 12 compared to baseline. 
 
 
 
Secondary Endpoints: The mean percentage change at Week 12 from baseline in CLASI, 
CLASI-A and CLASI-D scores; erythema (EI) and melanin indices (MI); and NRS for pain 
and pruritus.  

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Exploratory Endpoints: The change in inflammatory response, which includes the degree 
of inflammation, composition of inflammatory infiltrate, and interferon (IFN) signature. 
 
 
9. RISKS TO SUBJECTS 
 
9.1 Risks of Participation 
 
As with any change in treatment, there is a risk of no change or worsening of disease. All 
subjects in this study will have active discoid lesions. This means that their current therapeutic 
regimen is inadequate to control their disease. Stopping any current topical therapies may lead 
to worsening of disease, but continuing the same treatment regimen will not lead to clearance 
of disease activity. 
 
Ruxolitinib cream: Skin-related side effects of ruxolitinib 1.5% cream are rare, but local 
irritation, pain, itch, erythema, acne, or papular eruptions have been observed.5, 6, 11 Systemic 
side effects are not expected. In the largest trial of ruxolitinib cream to date (307 patients with 
atopic dermatitis, 3-20% BSA), no clinically significant laboratory changes were observed.11 
As of June 28, 2020, a total of 2350 study participants have been exposed to topical ruxolitinib, 
with no serious adverse events or fatal or life-threatening serious adverse reactions identified 
as treatment-related (Incyte, Global Investigator’s Brochure v9, Aug 2020). In this study, we 
anticipate few effects from systemic absorption since most patients with DLE have even less 
cutaneous involvement than in prior studies, typically only 1-2% BSA.  
 
While systemic side effects have not been seen with topical ruxolitinib, and the amount 
applied to the skin will be limited given the small area of treatment, there is a theoretical risk 
of side effects that have been observed with much higher oral doses. The most common side 
effects of oral ruxolitinib include increased risk of infection, laboratory abnormalities 
(cytopenias, elevated transaminases, and elevated cholesterol & triglycerides), and mild 
neurologic and gastrointestinal symptoms (dizziness, headache, fatigue, insomnia, diarrhea, 
abdominal pain). Ruxolitinib is a pregnancy Category C drug. 
 
As with any treatment, there is a small risk of an allergic reaction, though this has not been 
documented for ruxolitinib cream. There is no known risk of interaction between antimalarials 
and the study drug ruxolitinib. 
 
Safety monitoring and mitigating risk associated with the use of ruxolitinib cream is addressed 
in Section 8.2.2. 
 
Phlebotomy: The risks of having blood drawn include some pain with needle insertion and a 
small risk of bruising and/or infection at that site.  Some people may get lightheaded, nauseous, 
or faint.  The risks of phlebotomy will be reduced by its performance by trained phlebotomists. 
 
Skin Biopsy: The skin punch biopsy procedure involves the momentary pain of the needle 
prick used to insert the local anesthetic. There is a low risk of having an allergic reaction to the 
anesthetic used (lidocaine with epinephrine), which could result in a rash, itching, swelling, 

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dizziness, or trouble breathing. There is also a low risk of skin discoloration, temporary 
bleeding/bruising, and infection. Subjects may have a scar at the site of each biopsy and there 
is a risk of delayed or difficult healing at the site of the biopsy. Standard precautions will be 
taken to minimize these risks. For example, the procedure will be performed by a trained 
professional who will discuss the risks of the procedure and actions to be taken in the event of 
a complication. Participants will be given a handout with wound care instructions and a number 
to call in the unlikely event that a complication arises. Additionally, subjects will be asked if 
they have any allergies to lidocaine. If the subject does not return for suture removal, a member 
of the study team will call the participant to check on the healing of the skin biopsy, and to see 
if there are additional questions or concerns. 
 
9.2 Alternatives to Participation 
Non-participation. Study participation is voluntary. Subjects are free to not participate or to 
withdraw at any time, without risking loss of present or future care that they would otherwise 
receive. If they choose not to participate, standard of care treatment will be available. 
 
 
10. POTENTIAL BENEFITS TO SUBJECTS 
 
There may or may not be any direct benefits for the participants who elect to enroll in this 
study. The potential direct benefits to the subjects include more frequent provider evaluation 
and management of their disease as well as potential efficacy of a new therapy (ruxolitinib). 
 
 
11. COSTS FOR PARTICIPATION 
 
There will be no additional costs to the subject due to this study in addition to those incurred 
as part of routine standard of care. Insurance will not be billed for any study-specific visits or 
procedures associated with the study. The normal costs related to the subject’s care during 
the course of the study will be up to the subject’s insurer: 
• Physician visits outside of study visits 
• Emergency room or urgent care visits 
• Hospitalizations 
 
 
12. PAYMENT FOR PARTICIPATION  
 
Subjects enrolled in this protocol will receive $35 for each visit and $100 for each individual 
skin biopsy. Subjects will only be compensated for the activities they complete. For subjects 
who will complete all of the visits (#7) and optional biopsies (#2), the total compensation will 
be $445. Subjects will be reimbursed $35 if they are asked to come in for an unscheduled visit 
(and compensated an additional $100 if a skin biopsy is performed).  
 
For this study we use a subject payment system called Advarra Participant Payments. The 
system allows three ways to provide payment. Subjects can choose: a reloadable debit card; 
direct deposit; or mailed paper checks. The study team will help the subject create a “subject 

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profile” in the system.  In order to provide payment, the subject will need to enter their name 
and date of birth into their subject profile which is required to set up a subject account and for 
customer service purposes.  Depending on which payment method they choose, they may also 
need to enter their email address and banking information. If they already have an Advarra 
account (because they are in another study that uses this system), their existing profile will be 
used to provide payment.  See the ‘Information Sheet for Advarra Participant Payments” for 
additional information.  
 
Payment  received  for  participation  in  research  is  considered  taxable  income. If  the subject 
receives  payment  for  their  participation  in studies  at  the  University  of Rochester and  its 
affiliates of $600.00 or more in any one calendar year, the University is required to report this 
information to the Internal Revenue Service (IRS) in a 1099 (Miscellaneous Income) form.  They 
will be sent a copy of this form and a copy will be sent to the IRS. Depending on the amount 
they are paid, they may be asked to submit a W-9 form, which includes their Social Security 
Number. 
 
 
13. SUBJECT WITHDRAWALS 
 
Subjects will be notified by the study coordinator and advised in the written informed consent 
provided that they have the right to withdraw from the study at any time without prejudice.  
 
If participants of the study at any point meet the exclusion criteria established in this protocol, 
including pregnancy, study drug will be discontinued. In addition, study drug will be 
discontinued for any subject who experiences any of the following (per Common Terminology 
Criteria for Adverse Events v5.0): 
• Grade 2 event in Cardiac Disorders 
• Grade 3 event in any other System Organ Class 
Current research does not suggest a treatment-associated increased risk for these events. 
Standard treatment will proceed as necessary to ensure optimal health for the subject. In this 
situation, long term data will no longer be collected, and only the data collected during the 
duration of participation of the clinical trial will be included in the data analysis and 
conclusions of the study.   
  
 
14. PRIVACY AND CONFIDENTIALITY OF SUBJECTS AND RESEARCH DATA 
 
Steps to ensure privacy and confidentiality of subjects and research data will include: 
 
• The PI will be responsible for all aspects of this study, including privacy and 
confidentiality of subjects and research data. 
• All study personnel will be appropriately trained in Good Clinical Practice. 
• Study investigators or coordinators will meet with subjects in a private room, where 
they will conduct all aspects of this study that involves direct subject interaction. 

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• Subjects will not be re-contacted without prior consent. During the process of consent, 
subjects will be given the option to be re-contacted regarding opportunities to 
participate in future studies. 
• All electronic and physical documentation that includes protected health information 
(PHI) will be stored in files and/or folders with access limited to authorized study 
personnel only. 
• Physical files will be kept in a locked secure area of the URMC Dermatology CTU. 
• Computers on which electronic PHI data is accessed will be password protected and 
will not be left unattended while in use. 
• Passwords and system IDs will not be shared. 
• Physical security of computers/files will be maintained. 
• Subjects and samples will be assigned a unique code to facilitate deidentification of the 
data. Codes will not be generated from existing identifiers, such as initials or enrollment 
date.  
• Only authorized study personnel will have access to data containing PHI.  
• Other research personnel conducting experiments on tissue samples and analyzing data 
will have access to deidentified samples and data only. 
• Data will be stored for at least 6 years after the completion of the study, or for at least 
two years following marketing approval (or, if not approved, 2 years following 
shipment and delivery of the investigational product is discontinued), whichever is 
longer.    
       
 
15. DATA / SAMPLE STORAGE FOR FUTURE USE 
 
Clinical labs drawn as standard of care and as part of this study will be recorded in the subject’s 
medical record and will be available to the subject. Since the non-clinical testing is being done 
strictly for research purposes, the results of these tests will not be recorded in the subject’s 
medical record and subjects will not be informed of the results of these research assays.  
 
Data and samples collected as part of this protocol will be used to perform the studies related 
to the primary, secondary and exploratory endpoints of this study. Any tissue that remains after 
these analyses have been performed will be deidentified and may be stored and used for future 
studies. These stored samples may also be shared with companies that are providing support 
for this study; this includes Incyte and their affiliates. 
 
 
16. DATA AND SAFETY MONITORING PLAN 
 
16.1 Data and Safety Monitoring 
During the conduct of the study, the PI and his designee(s) will continually monitor the study 
to ensure that the study is conducted in compliance with the IRB-approved study protocol and 
that subject safety is maintained. Safety data will be reviewed by the PI or designee as soon as 
it is received. The review will include: the number of subjects consented/enrolled/completed, 
possible adverse events, and any other responses observed.  
 

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The FDA defines an adverse event (AE) as “any untoward medical occurrence associated with 
the use of a drug in humans, whether or not considered drug related” and a serious adverse 
event (SAE) as an AE that “results in any of the following outcomes: Death, a life-threatening 
adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent 
or significant incapacity or substantial disruption of the ability to conduct normal life functions, 
or a congenital anomaly/birth defect” (Electronic Code of Federal Regulations, 13 Jan 2020). 
 
The PI and study coordinator are the primary individuals charged with identification and 
reporting of all AE and SAE occurrences as well as protocol deviations. All SAEs that are 
considered serious, unexpected and related to the study participation will be reported to the 
IRB within 10 calendar days and all non-serious adverse events will be reported annually with 
the continuing review. The investigator will also notify the IRB of any serious deviations from 
the protocol, and any new information indicating added risk to subjects.  
 
16.2 SAE Reporting to Incyte 
The Principal Investigator (PI) must report all Serious Adverse Events (SAEs) to Incyte within 
24 hours of learning of an event, regardless of the PI’s causality assessment. This notification 
should be provided on a completed Serious Adverse Event (SAE) form.  SAE reporting for 
each subject begins the day the informed consent is signed by the patient and within 30 days 
after subject has completed or discontinued from the study or has taken last dose of the study 
drug, or as described in the protocol. 
 
SAEs, occurring using Incyte study drug, are reported in accordance with the effective 
protocol.  SAEs occurring with any other commercial drug are reported to the manufacturer of 
that drug in accordance with regulations and protocol.  
 
Initial SAEs and/or subsequent follow-up reports should be reported via email to 
SafetyReporting@Incyte.com  or fax (+) 1-866-981-2057.  SAE reports should be for a single 
subject.  SAE forms should be sent with a cover sheet and any additional attachments. 
 
All adverse event information is reported to Incyte on the Principal Investigator’s/Institution’s 
Adverse Event Report Form, or a CIOMS-I or MedWatch Form FDA 3500A, or on an Adverse 
Event Report Form which may be provided by Incyte upon request. The Principal Investigator 
does not provide medical records (e.g., discharge summary) to Incyte, unless specifically 
requested. 
 
 
16.3 Reporting of Pregnancy to Incyte 
An “Initial Pregnancy Report” or equivalent must be completed in full and emailed to 
SafetyReporting@Incyte.com or faxed to (+) 1-866-981-2057 within 24 hours of discovery of 
a pregnancy of a subject who has taken the Incyte product or the pregnancy of a partner for a 
subject who has taken the Incyte product.  The “Follow-up Pregnancy Report Form” or 
equivalent must be completed and emailed to SafetyReporting@Incyte.com or faxed to (+) 1-
866-981-2057 within 30 days after delivery, so that Incyte is provided with information 
regarding the outcome of the pregnancy.  If the pregnancy results in any events which meet 

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the serious criteria (i.e., miscarriage or termination), the SAE reporting process needs to be 
followed and the timelines associated with a SAE should be followed. 
 
 
17. DATA ANALYSIS PLAN 
 
This exploratory study has a sample size of 15 subjects. Given the small sample size, a robust 
statistical analysis will be limited. The primary endpoint will be a ≥ 2-point reduction in IGA 
score. The mean percentage change from baseline will be assessed for the secondary endpoints 
(CLASI, CLASI-A, CLASI-D, NRS, EI, MI). Statistical analysis of exploratory endpoints 
comparing skin tissue before and after ruxolitinib treatment will be performed in accordance 
with the technique being used (histology, flow cytometry, RNAseq). Analyses of DLE 
histology (H&E, IHC, IFM) will include common histologic features (follicular plugging, 
interface change, etc.), cell counts of the immune infiltrate, and markers of IFN response. Flow 
cytometric analysis will evaluate the immune infiltrate, including T and B cell subsets. The 
focus of the RNAseq analysis will be on interferon expression, though other analyses may be 
performed. Differences will be considered significant at p < 0.05.   
 
 
18. REFERENCES 
 
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2. Chan ES, Herlitz LC, Jabbari A. Ruxolitinib Attenuates Cutaneous Lupus Development in a 
Mouse Lupus Model. Journal of Investigative Dermatology. 2015;135(7):1912-5. 
3. Ikeda K, Hayakawa K, Fujishiro M, Kawasaki M, Hirai T, Tsushima H, et al. JAK inhibitor 
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