Clinical trial NCT03793439: Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
Official title: Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoidosis, Pulmonary
Sarcoidosis Lung
Sarcoidosis
Keywords: Sarcoidosis
Corticosteroid dependent sarcoidosis
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2019-01-04
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, interventional, proof of concept, hypothesis-generating study
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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).

Primary outcomes:
measure: Number of Participants With 50% Reduction in Corticosteroid Requirement
timeFrame: 16 weeks
Secondary outcomes:
measure: Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Jim Rosenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenbaum JT, Choi D, Wilson DJ, Grossniklaus HE, Harrington CA, Sibley CH, Dailey RA, Ng JD, Steele EA, Czyz CN, Foster JA, Tse D, Alabiad C, Dubovy S, Parekh P, Harris GJ, Kazim M, Patel P, White V, Dolman P, Korn BS, Kikkawa D, Edward DP, Alkatan H, Al-Hussain H, Yeatts RP, Selva D, Stauffer P, Planck SR. Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood. JAMA Ophthalmol. 2015 Jul;133(7):770-7. doi: 10.1001/jamaophthalmol.2015.0726.
citation: Friedman MA, Le B, Stevens J, Desmarais J, Seifer D, Ogle K, Choi D, Harrington CA, Jackson P, Rosenbaum JT. Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study. Lung. 2021 Apr;199(2):147-153. doi: 10.1007/s00408-021-00436-8. Epub 2021 Apr 7.