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

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ClinicalTrials.gov Identifier: NCT03793439
Recruitment Status : Not yet recruiting
First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Jim Rosenbaum, Oregon Health and Science University

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.

Condition or disease Intervention/treatment Phase
Sarcoidosis, Pulmonary Sarcoidosis Lung Sarcoidosis Drug: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial Diagnostic Test: Spirometry Genetic: RNA Sequencing Diagnostic Test: Laboratory testing Drug: Corticosteroid Drug: Tofacitinib 5mg [Xeljanz] 1 year open-label extension Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, interventional, proof of concept, hypothesis-generating study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
Estimated Study Start Date : March 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sarcoidosis Steroids

Arm Intervention/treatment
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.
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

Experimental: Open-label extension
After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
Diagnostic Test: Laboratory testing
Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16
Other Name: Blood work

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




Primary Outcome Measures :
  1. 50% reduction in corticosteroid requirement in at least 60% of subjects. [ Time Frame: 16 weeks ]
    50% reduction in corticosteroid requirement in at least 60% subjects (or 3/5 of the subjects) by week 16, without significant decline in their pulmonary function—defined as a >15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value


Secondary Outcome Measures :
  1. Significant decreases in of peripheral markers of STAT pathway activity [ Time Frame: 16 weeks ]
    Significant decreases in of peripheral markers of STAT pathway activity using RNA sequencing and CXCL10 levels, both measured before and after 16 weeks of tofacitinib treatment.



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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03793439


Contacts
Contact: Marcia A Friedman, MD 5034948637 friedmam@ohsu.edu
Contact: Kimberly Ogle 503-494-5711 oglki@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Marcia A Friedman, MD    503-494-8637    friedmam@ohsu.edu   
Contact: Kim Ogle    503-494-5711    oglki@ohsu.edu   
Sub-Investigator: Janelle Stevens, DO         
Sub-Investigator: Marcia Friedman, MD         
Principal Investigator: Jim Rosenbaum, MD         
Sponsors and Collaborators
Oregon Health and Science University
Pfizer
Investigators
Principal Investigator: Jim Rosenbaum, MD Oregon Health and Science University

Publications:
Responsible Party: Jim Rosenbaum, Professor of Ophthalmology, Medicine, and Cell Biology, OHSU, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03793439     History of Changes
Other Study ID Numbers: STUDY00017902
First Posted: January 4, 2019    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified individual participant data for all primary and secondary outcomes will be made available.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jim Rosenbaum, Oregon Health and Science University:
Sarcoidosis
Corticosteroid dependent sarcoidosis

Additional relevant MeSH terms:
Sarcoidosis
Sarcoidosis, Pulmonary
Tofacitinib
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action