Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis

Primary Objectives:

Objective 1: Test the hypothesis that the addition of tofacitinib will allow patients with sarcoidosis to have 50% or greater reduction in their corticosteroid requirement without a significant decrease in pulmonary function testing, and with a similar quality of life as measured by a validated questionnaire (1).

Objective 2: Test the hypothesis that the addition of tofacitinib will result in significantly decreased expression of signal transducer and activator of transcription (STAT)-1 dependent gene expression.

Outline:

This is a 16-week open-label, interventional, proof of concept, hypothesis-generating study. All subjects will receive Tofacitinib 5mg twice daily for 16 weeks. After four weeks on Tofacitinib, the corticosteroid will be tapered per a pre-defined protocol; once a reduction of 50% has been achieved, any further taper will be per physician discretion. After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.

• Sarcoidosis, Pulmonary
• Sarcoidosis Lung
• Sarcoidosis

• Drug: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial
  Tofacitinib 5mg oral table twice daily for 16 weeks
  Other Names:

  • Xeljanz
  • tofacitinib
• Diagnostic Test: Spirometry
  Spirometry testing at baseline, week 4, week 8, week 12, and week 16
  Other Name: Pulmonary function test
• Genetic: RNA Sequencing
  RNA sequencing test at baseline and week 16
• Diagnostic Test: Laboratory testing
  Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16
  Other Name: Blood work
• Drug: Corticosteroid
  Taper corticosteroids starting at week 4
  Other Names:

  • Corticosteroid taper
  • Prednisone taper
  • Steroid taper
• Drug: Tofacitinib 5mg [Xeljanz] 1 year open-label extension
  After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
  Other Names:

  • tofacitinib
  • Xeljanz

• Experimental: Open-label treatment
  All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
  Interventions:

  • Drug: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial
  • Diagnostic Test: Spirometry
  • Genetic: RNA Sequencing
  • Diagnostic Test: Laboratory testing
  • Drug: Corticosteroid
• Experimental: Open-label extension
  After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
  Interventions:

  • Diagnostic Test: Laboratory testing
  • Drug: Tofacitinib 5mg [Xeljanz] 1 year open-label extension

Inclusion Criteria:

• Meet World Association of Sarcoidosis and other Granulomatous Disorders (WASOG) definition of pulmonary sarcoid
• Histologically proven sarcoid
• Evidence of pulmonary sarcoid on chest radiograph
• FVC of > 50%
• Require 15-30mg/day of prednisone or equivalent corticosteroid to control sarcoidosis.
• Stable dose of prednisone or equivalent corticosteroid for 4 weeks prior to enrollment.

Exclusion Criteria:

• May be taking methotrexate but not other immunosuppressive or immunomodulatory treatments in the two months prior to study period. This includes but is not limited to azathioprine, cyclophosphamide, leflunomide, mycophenolate mofetil, cyclosporine, tacrolimus, and biologic medications.
• Patients requiring >30mg/day prednisone or equivalent.
• Pregnant or lactating women.
• Hemoglobin < 9g/dL or hematocrit < 30%
• White blood cell count <3.0 K/cu mm
• Absolute neutrophil count <1.2 K/cu mm
• Platelet count <100 K/cu mm
• Subjects with an estimated glomerular filtration rate (GFR) ?40 ml/min
• Subjects with a total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal at screening.
• Severe, progressive, or uncontrolled chronic liver disease including fibrosis, cirrhosis, or recent or active hepatitis.
• History of any lymphoproliferative disorder such as Epstein Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggest of current lymphatic disease.
• Current malignancy or history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
• Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
• Have a known infection with human immunodeficiency virus (HIV)
• Have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac (New York Heart Association class III or IV), neurologic, or cerebral diseases (with the exception of sarcoidosis).