Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
Condition: Sarcoidosis, Pulmonary; Sarcoidosis Lung; Sarcoidosis
MeSH terms: Sarcoidosis, Pulmonary; Sarcoidosis
Intervention: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial; Spirometry; RNA Sequencing; Laboratory testing; Corticosteroid; Tofacitinib 5mg [Xeljanz] 1 year open-label extension
Intervention description: Tofacitinib 5mg oral table twice daily for 16 weeks; Spirometry testing at baseline, week 4, week 8, week 12, and week 16; RNA sequencing test at baseline and week 16; Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16; Taper corticosteroids starting at week 4; After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
Intervention MeSH terms: Prednisone; Tofacitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open-label, interventional, proof of concept, hypothesis-generating study
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 89 Years
Healthy volunteers: No
Keywords: Sarcoidosis; Corticosteroid dependent sarcoidosis

Summary:

      This is a pilot study to determine whether further research is warranted to assess whether
      tofacitinib is an effective steroid sparing treatment for pulmonary sarcoidosis. The primary
      endpoint for this study is a 50% or greater reduction in corticosteroid requirement.
    

Eligibility criteria:

        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

          -  Forced vital capacity 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).