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

NCT03793439 | Completed Phase 1 Results FDA Drug

• 1 other identifier: STUDY00017902
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis Lung; Sarcoidosis

Keywords

Sarcoidosis; Corticosteroid dependent sarcoidosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 50% Reduction in Corticosteroid Requirement

  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 Outcomes (1)

• Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing

  16 weeks

Study Arms (1)

Open-label treatment

EXPERIMENTAL

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; Diagnostic Test: Spirometry; Genetic: RNA Sequencing; Diagnostic Test: Laboratory testing; Drug: Corticosteroid; Drug: Tofacitinib 5mg [Xeljanz] 1 year open-label extension

Interventions

Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial DRUG

Tofacitinib 5mg oral table twice daily for 16 weeks

Also known as: Xeljanz, tofacitinib

Open-label treatment

Spirometry DIAGNOSTIC_TEST

Spirometry testing at baseline, week 4, week 8, week 12, and week 16

Also known as: Pulmonary function test

Open-label treatment

RNA Sequencing GENETIC

RNA sequencing test at baseline and week 16

Open-label treatment

Laboratory testing DIAGNOSTIC_TEST

Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16

Also known as: Blood work

Open-label treatment

Corticosteroid DRUG

Taper corticosteroids starting at week 4

Also known as: Corticosteroid taper, Prednisone taper, Steroid taper

Open-label treatment

Tofacitinib 5mg [Xeljanz] 1 year open-label extension DRUG

After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.

Also known as: tofacitinib, Xeljanz

Open-label treatment

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Pfizer: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (2)

• 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.

  PMID: 25880323 BACKGROUND

• 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.

  PMID: 33825964 DERIVED

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

tofacitinib; Tablets; Clinical Trials as Topic; Spirometry; Respiratory Function Tests; Sequence Analysis, RNA; Clinical Laboratory Techniques; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Sequence Analysis; Genetic Techniques; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Marcia Friedman
• Organization: Oregon Health & Science University

friedmam@ohsu.edu

5034948637

Study Officials

• Jim Rosenbaum, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Ophthalmology, Medicine, and Cell Biology, OHSU

Model Details: Open-label, interventional, proof of concept, hypothesis-generating study

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 4, 2019
• Study Start: May 15, 2019
• Primary Completion: June 24, 2020
• Study Completion: June 24, 2021
• Last Updated: February 18, 2022
• Results First Posted: February 18, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: January 1, 2022 until December 31, 2023
• Access Criteria: Email friedmam@ohsu.edu

Locations

US (1)