Tofacitinib in Prevention of Photosensitivity in Lupus

• Status: Not yet recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will determine whether the treatment intervention, tofacitinib:

• Impacts photosensitivity following ultraviolet light B (UVB) exposure in individuals with systemic lupus and a history of cutaneous disease

• Is associated with changes in cutaneous disease activity in individuals with systemic lupus and a history of cutaneous disease after a 25-day regimen of tofacitinib

• Is associated with changes in systemic lupus erythematosus (SLE) disease activity in individuals with systemic lupus and a history of cutaneous disease after a 25-day regimen of tofacitinib, and

• Is well tolerated in individuals with systemic lupus and a history of cutaneous disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Autoimmunity Centers of Excellence; Rho Federal Systems Division, Inc.
• Treatments: Tofacitinib

Criteria

Inclusion Criteria:

Individuals must meet all of the following inclusion criteria to be eligible for enrollment in the study:

1. Meets European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria for Systemic Lupus Erythematosus (SLE)

2. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4 (clinical criteria only, excludes all laboratory criteria)

3. History of documented cutaneous flare (acute, subacute, discoid, or tumid) proven by biopsy or documented by physician

4. 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

5. If taking 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

6. If taking 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

7. If taking 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

8. All participants and their sexual partners who engage in sexual activity that could lead to pregnancy must be willing to use complete abstinence or an FDA-approved contraception for the duration of the study and for at least 28 days 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.

• Note: Periodic abstinence and withdrawal are not acceptable methods of birth control.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

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. Active nephritis, defined as:

1. Active urinary sediment (i.e., >5 RBCs /hpf and >5 WBCs /hpf, in the absence of infection), or

2. (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, or

3. (For individuals with a history of nephritis): A rise in Pr/Cr of >0.5 over the prior 3-6 months.

4. History of severe gastrointestinal narrowing or strictures

5. 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-Beta2-glycoprotein I IgG enzyme-linked immunosorbent assay (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 10^9/L

3. Absolute Neutrophil count <1.2 x 10^9/L

4. Platelet count <120 x 10^9/L

5. Absolute Lymphocyte count <0.75 x 10^9/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 m^2

9. Triglycerides ≥300 mg/dL (non-fasting)

10. Total Cholesterol ≥240 mg/dL (non-fasting)

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 (TB), chronic pyelonephritis, osteomyelitis)

17. Coronavirus disease 2019 (COVID-19) infection

a. Presumed or documented COVID-19 infection in the past 30 days

18. Participants at risk for tuberculosis (TB)

1. History of active TB within the last 3 years, even if it was treated

2. History of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type

3. Current clinical, radiographic, or laboratory evidence of active TB (i.e., evaluated at or within 30 days prior to screening)

4. Latent TB at or within 30 days prior to screening

5. History of or current positive purified protein derivative tuberculin skin test (PPD) (> 5mm induration, regardless of Bacille Calmette Guerin [BCG] vaccine and/or QuantiFERON Gold, a negative chest x-ray, and no symptoms or risk factors), unless one month of prophylaxis has been completed prior to inclusion

6. An indeterminate QuantiFERON(R) unless followed by a subsequent negative PPD or negative QuantiFERON(R) or a consultation with and clearance by local infectious disease (ID) department is required

19. History of human immunodeficiency virus (HIV) (as determined by medical records or participant report) or a positive test for HIV antigen/antibody or nucleic acid test (NAT)

20. History of a hepatitis B infection or a positive test for hepatitis B surface antigen or hepatitis B core antibody

21. History of a hepatitis C infection or a positive test for hepatitis C antibody (regardless of whether hepatitis C RNA levels are undetectable)

22. 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

23. 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

24. Simultaneous use of leflunomide and methotrexate

25. Any of the following active medications:

• cyclosporine,

• azathioprine,

• cyclophosphamide,

• tacrolimus,

• belimumab,

• mycophenolate mofetil (MMF),

• rituximab or other anti-CD20s, or

• any other investigational or marketed biologic with immunomodulatory properties within a year prior to Visit 1 (Day 0).

26. 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

27. Intravenous or intramuscular corticosteroids within 2 weeks prior to Visit 1 (Day 0)

28. Treatment with any investigational agent ≤4 weeks or ≤5 half-lives of the investigational drug prior to Visit 1 (Day 0),whichever is longer

29. Treatment with more than one dose of ketoconazole within one week of screening

30. Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation

31. 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

32. Received a COVID-19 vaccine or other non-live vaccines ≤2 weeks prior to Visit 1 (Day 0), or unwillingness of a participant to delay COVID-19 or other non-live vaccination until 1 month after completion of study therapy

33. Pregnant or breastfeeding females

34. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug

35. 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,

• 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.