Evaluation of Tofacitinib in Prevention of Photosensitivity in Lupus

Evaluation of Tofacitinib in Prevention of Photosensitivity in Cutaneous Lupus Erythematosus (ALE11)

This is a single-arm, multi-site, proof-of-concept study that will evaluate the treatment of 10 participants with cutaneous lupus erythematosus (CLE) with Tofacitinib.

Study Overview

• Status: Completed
• Conditions: Cutaneous Lupus
• Intervention / Treatment: Drug: Tofacitinib

Detailed Description

Once consented, study participants meeting all entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally daily). Tofacitinib will be distributed to eligible participants at Visit 2 (Day 1) and the first dose will be taken on Day 2. The last dose is the morning of Visit 5 (Day 26).Ultraviolet B (UVB)-mediated cutaneous apoptosis and ancillary mechanistic studies will be evaluated in phototests, skin biopsies and blood samples collected before and after treatment.

This study will assess whether a 25-day regimen of tofacitinib impacts photosensitivity following UVB exposure in individuals with CLE.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Cutaneous lupus erythematosus based upon all of the following:

   1. a clinical diagnosis made by a rheumatologist or dermatologist of one of the following: acute cutaneous lupus erythematosus, subacute cutaneous lupus, or chronic cutaneous lupus erythematosus;
   2. active skin disease within 5 years prior to screening. Participants may have concomitant SLE.
2. SLEDAI-2K score ≤4 (clinical criteria only, excludes all laboratory criteria) for all participants regardless of whether they have concomitant SLE.
3. If taking oral corticosteroids, the dose must be ≤ 10 mg daily of prednisone (or equivalent), stable dose for at least 4 weeks, and not anticipated to change over the course of the study.
4. If taking oral anti-malarial medications, the dose(s) must be ≤ 100 mg daily for quinacrine or/and ≤ 400 mg daily for hydroxychloroquine, stable for at least 6 months, and not anticipated to change over the course of the study.
5. If taking oral or subcutaneous methotrexate, the dose must be ≤ 25 mg weekly, stable for at least 4 weeks, and not anticipated to change over the course of the study.
6. If taking oral leflunomide, the dose must be ≤ 20 mg daily, stable for at least 4 weeks, and not anticipated to change over the course of the study.
7. If taking oral mycophenolate mofetil (MMF) or mycophenolic acid, the dose must be equivalent to ≤ 3000 mg of MMF daily, stable for at least 4 weeks, and not anticipated to change over the course of the study.
8. Adults 18 to 65 years of age at screening.
9. All participants and/or their sexual partners who engage in sexual activity that could lead to pregnancy must be willing to use complete abstinence or an FDA-regulated form of contraception for the duration of the study and for at least one month after discontinuation of study drug to prevent pregnancy. Highly effective birth control methods include, but are not limited to, hormonal contraception, an intrauterine device, or surgical options. Periodic abstinence and withdrawal are not acceptable methods of birth control.

Exclusion Criteria:

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
2. Current or recent history, within the last year, of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurologic disease or significant impairment that might negatively impact the participant's ability to participate or that may put a participant at increased risk.

3. Potential active nephritis and/or urinary tract infection at screening, defined as any one of the following determined at screening unless otherwise specified:

   1. >10 RBCs /hpf,
   2. >5 WBCs /hpf with either positive nitrites or greater than a trace leukocyte esterase,
   3. Signs or symptoms of a urinary tract infection,
   4. For individuals with no history of nephritis: Urine protein (mg/dL): creatinine (mg/dL) ratio (Pr/Cr)>0.5 at screening or a Pr/Cr level that has exceeded 1.0 in the prior 12 months,
   5. For individuals with a history of nephritis: A rise in Pr/Cr of >0.5 over the prior 3-6 months prior to screening.
4. History of severe gastrointestinal narrowing or strictures.
5. Medically confirmed history of diverticulitis or chronic, ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis, or other symptomatic, lower GI conditions that might predispose a participant to perforations.
6. History of thrombosis, pulmonary embolism, or antiphospholipid syndrome.

7. History of any one of the following anti-phospholipid antibodies:

   1. Positive lupus anticoagulant test, or
   2. Anti-β2-glycoprotein I IgG ELISA titer ≥ 40 GPL, or
   3. Anti-cardiolipin IgG ELISA titer ≥ 40 GPL.
8. History of chronic pulmonary disease requiring supplemental oxygen including chronic obstructive pulmonary disease (COPD) requiring chronic treatment, interstitial lung disease (ILD) requiring immunosuppressive therapy, and asthma requiring chronic steroid (other than inhaled steroid) or biologic therapy.
9. History of moderate to severe atherosclerotic cardiovascular disease as evidenced by prior coronary artery bypass surgery, coronary artery stent placement, myocardial infarction, symptomatic carotid arterial disease, peripheral vascular disease, abdominal aortic aneurysm; or angina within the past 8 weeks prior to Visit 1 (Day 0).
10. History of keloid scarring.
11. History of any lymphoproliferative disorder or other malignancy with the exception of successfully treated or excised basal cell or squamous cell skin cancer or cervical cancer in situ.
12. Other autoimmune diseases likely to require immunosuppression.

13. Any of the following lab results at screening:

    1. Hemoglobin <9.5 g/dL
    2. White Blood Cell count <3.5 x 109/L
    3. Absolute Neutrophil count <1.2 x 109/L
    4. Platelet count <120 x 109/L
    5. Absolute Lymphocyte count <0.75 x 109/L
    6. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 1.5 × the upper limit of normal (ULN)
    7. Total bilirubin > ULN
    8. Estimated glomerular filtration rate [GFR] <60mL/min/1.73 m2
    9. Triglycerides ≥ 300 mg/dL (fasting not required)
    10. Total Cholesterol ≥ 240 mg/dL (fasting not required).
14. Major surgery < 8 weeks prior to Visit 1 (Day 0).
15. Hospitalized for serious infection < 4 weeks prior to Visit 1 (Day 0).
16. Chronic infections other than chronic or intermittent uncomplicated urinary tract infections (including but not limited to tuberculosis, chronic pyelonephritis, osteomyelitis).
17. Presumed or documented COVID-19 infection within 30 days prior to Visit 1 (Day 0).
18. Recent (within one month prior to screening) close contact with a person who has active TB infection.
19. History of untreated active or latent TB infection.
20. History of incompletely treated active or latent TB infection unless at least one month of treatment has been completed prior to screening.
21. Positive Interferon-Gamma Release Assay (IGRA) or positive purified protein derivative tuberculin skin test (PPD) (> 5mm induration) at screening.
22. An indeterminate IGRA at screening unless followed by a subsequent negative IGRA or negative PPD.
23. History of human immunodeficiency virus (HIV).
24. A positive test for HIV antigen/antibody or nucleic acid test (NAT) at screening.
25. History of a hepatitis B infection.
26. A positive test for hepatitis B surface antigen or hepatitis B core antibody at screening.
27. History of a hepatitis C infection.
28. A positive test for hepatitis C antibody (regardless of whether hepatitis C RNA levels are undetectable) at screening.
29. History of recurrent (more than one episode) herpes zoster, one or more episodes of any of the following: herpes zoster ophthalmicus, or disseminated herpes zoster, or disseminated herpes simplex.
30. Current, recent (< 4 weeks prior to Visit 1 (Day 0)) or chronic use of antibiotic medication, except for suppression of chronic/recurrent urinary tract infection, which is allowed.
31. Simultaneous use of more than one of the following: leflunomide, methotrexate and MMF.
32. Any of the following active medications (oral or parenteral): cyclosporine, voclosporin, cyclophosphamide, tacrolimus, rituximab or other anti-CD20s, or any other investigational or marketed biologic with immunomodulatory properties within a year prior to Visit 1 (Day 0).
33. Any of the following medications (oral or parenteral): azathioprine or belimumab within 3 months prior to Visit 1 (Day 0).
34. Any prior treatment with cell-depleting therapies other than anti-CD20s including but not limited to CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 products.
35. Intravenous or intramuscular corticosteroids within 2 weeks prior to Visit 1 (Day 0).
36. Treatment with any investigational agent ≤ 4 weeks or ≤ 5 half-lives of the investigational drug prior to Visit 1 (Day 0), whichever is longer.
37. Treatment with more than one dose of ketoconazole within one week of screening.
38. Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation.
39. Vaccinated or exposed by close contact, e.g., within a household, to a live/attenuated vaccine ≤ 6 weeks prior to Visit 1 (Day 0); or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of study medication.
40. Received a non-live vaccine ≤ 2 weeks prior to initiation of study drug, or unwillingness of a participant to delay non-live vaccination until 1 month after completion of study therapy.
41. Pregnant or breastfeeding females.
42. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug.
43. Past or current medical or psychiatric conditions or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacinitib; 10 participants receiving 11 mg of Tofacitinib administered orally and daily, from Day 2 to Day 26	Drug: Tofacitinib; 10 participants with Cutaneous lupus erythematosus (CLE). Consenting individuals meeting all entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally (PO) daily) with evaluation of UVB-mediated cutaneous apoptosis; Other Names: XELJANZ(R) XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percentage of UVB-induced Apoptotic Epidermal Cells	At Day 0 and Day 25, skin was exposed to 10-80 mJ/cm2 UVB irradiation. At Day 1 and Day 26, erythema levels were measured with a Chroma Meter at each dose site and in an unexposed section. Skin biopsies at Day 1 and Day 26 were taken at the unexposed site and at the minimal erythema dose (MED) at Day 1. The percentage of apoptotic epidermal cells were determined in each skin biopsy sample by TUNEL staining. The percentage of UVB-induced apoptotic cells is defined as the difference between the percentage of apoptotic epidermal cells in the UVB-exposed biopsy at the MED and percentage of apoptotic epidermal cells in the unexposed biopsy at the same visit. Change in percentage of UVB-induced apoptotic epidermal cells is calculated as the difference in the percentage of UVB-induced apoptotic cells at Day 26 and at Day 1.	Day 1 (pre-treatment) to Day 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Minimal Erythema Dose (MED) Due to UVB	At Day 0 and Day 25, skin was exposed to 10-80 mJ/cm2 UVB irradiation. At Day 1 and Day 26, erythema levels were measured with a Chroma Meter at each dose site and in an unexposed section. The MED was defined as the dose that contained the lowest UVB exposure and the average redness reading that was at least 2.5 higher than the average redness reading in the unexposed skin. The possible values for MED ranged from 10 to 80 mJ/cm2.	Day 1 (pre-treatment) to Day 26
Change in UVB-induced Expression of Inflammatory Genes in Skin Based on Enumeration of RNA Transcripts.	Skin biopsies at Day 1 and Day 26 were taken at the unexposed site and at the site corresponding to the next higher UVB dose than the Day 26 MED. RNA was isolated and expression values were analyzed by RNA sequencing. UVB-induced expression is defined as the difference in expression measured in the biopsy exposed at the Visit 2 (Day 1) 1x minimal erythema dose (MED) and that measured in the unexposed biopsy.	Day 1 (pre-treatment) to Day 26
Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score	CLASI is a validated, physician-based assessment tool used to measure cutaneous lupus severity. Severity is calculated based on disease activity (erythema and scale) and damage (dyspigmentation and scarring) for the cumulative areas of involved skin. CLASI activity score ranges from 0 to 70, with higher scores indicating increased disease severity.	Day 0 (pre-treatment) to Day 25
Change in CLASI Damage Score	CLASI is a validated, physician-based assessment tool used to measure cutaneous lupus severity. Damage is calculated based on dyspigmentation and scarring for the cumulative areas of involved skin. The CLASI damage score ranges from 0 to 56, with higher scores indicating worse damage to the skin due to lupus.	Day 0 (pre-treatment) to Day 25
Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score	Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 30 days. SLEDAI-2K total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.	Day 0 (pre-treatment) to Day 25
Change in Severity Grade for Laboratory Tests From Grade 0	The study sites graded the severity of laboratory results for the study participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The NCI-CTCAE manual provides a common language to describe levels of severity, to analyze and interpret data, and to articulate the clinical significance of adverse events. Select laboratory results are incorporated into relevant adverse event criteria.	Screening Visit through Day 40
Treatment-emergent Adverse Events by Severity	The study sites graded the severity of AEs experienced by the study participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The NCI-CTCAE manual provides a common language to describe levels of severity, to analyze and interpret data, and to articulate the clinical significance of all AEs. A treatment-emergent AE is defined as an increase in grade from the last assessment prior to a participant starting treatment at Day 2, or from the last post-baseline value that doesn't meet grading criteria. AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 25.1.	Day 2 to Day 40
Treatment-emergent Adverse Events by Relationship to Tofacitinib	The relationship, or attribution, of an adverse event to the study therapy regimen or study procedure(s) was initially determined by the site investigator and recorded on the appropriate AE/SAE eCRF as not related, possibly related or related. Final determination of attribution for safety reporting was determined by sponsor. An AE assessed as possibly related or related was classified as related to the study therapy or procedure. A treatment-emergent AE is defined as an increase in grade from the last assessment prior to a participant starting treatment at Day 2, or from the last post-baseline value that doesn't meet grading criteria. AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 25.1.	Day 2 to Day 40

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Joanne M Kahlenberg, M.D., Ph.D., University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Autoimmunity Centers of Excellence (ACE)

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Actual): February 15, 2024
• Study Completion (Actual): February 29, 2024

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Lupus; Tofacitinib; Cutaneous Lupus; Systemic Lupus; Ultraviolet; Systematic Lupus Erythematosus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Janus Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: DAIT ALE11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The plan is to share data in ImmPort [https://immport.niaid.nih.gov/ ], a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts, upon completion of the study.
• IPD Sharing Time Frame: After completion of the study
• IPD Sharing Access Criteria: Data will be sent to ImmPort, but not made available to the public, due to small sample size of study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No