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

NCT03793439

Last updated date
Study Location
Oregon Health & Science University
Portland, Oregon, 97239, United States
Contact
5034948637

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

5034948637

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Pulmonary Sarcoidosis, Sarcoidosis Lung, Sarcoidosis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-89 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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).

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Pulmonary Sarcoidosis, Sarcoidosis Lung, SarcoidosisTofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
NCT03793439
  1. Portland, Oregon
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
Official Title  ICMJE Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE
  • Sarcoidosis, Pulmonary
  • Sarcoidosis Lung
  • Sarcoidosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 2, 2019)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2022
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marcia A Friedman, MD5034948637[email protected]
Contact: Kimberly Ogle503-494-5711[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03793439
Other Study ID Numbers  ICMJE STUDY00017902
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Undecided
Plan Description:De-identified individual participant data for all primary and secondary outcomes will be made available.
Responsible Party Jim Rosenbaum, Oregon Health and Science University
Study Sponsor  ICMJE Oregon Health and Science University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Jim Rosenbaum, MDOregon Health and Science University
PRS Account Oregon Health and Science University
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP