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

December 3, 2021 updated by: Jim Rosenbaum, Oregon Health and Science University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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:
  • Xeljanz
  • tofacitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With 50% Reduction in Corticosteroid Requirement
Time Frame: 16 weeks
50% reduction in corticosteroid requirement 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
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing
Time Frame: 16 weeks
Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of < 0.05.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Collaborators

Pfizer

Investigators

  • Principal Investigator: Jim Rosenbaum, MD, Oregon Health and Science University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2019

Primary Completion (Actual)

June 24, 2020

Study Completion (Actual)

June 24, 2021

Study Registration Dates

First Submitted

January 2, 2019

First Submitted That Met QC Criteria

January 2, 2019

First Posted (Actual)

January 4, 2019

Study Record Updates

Last Update Posted (Actual)

February 18, 2022

Last Update Submitted That Met QC Criteria

December 3, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00017902

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified individual participant data for all primary and secondary outcomes will be made available.

IPD Sharing Time Frame

January 1, 2022 until December 31, 2023

IPD Sharing Access Criteria

Email friedmam@ohsu.edu

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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