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Sarcoidosis, PulmonaryPhase 1NCT03793439

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

A Phase 1 study testing Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial, Spirometry and RNA Sequencing in people with Sarcoidosis, Pulmonary and Sarcoidosis Lung, run by Oregon Health and Science University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 89 years
What is being tested?
Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial, Spirometry and RNA Sequencing
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
15 May 2019to 24 Jun 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 89 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 15Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Oregon Health & Science University

    Portland, Oregon, 97239

Other trials in United States

About this study

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.

Read the 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.

Being tested
Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial, Spirometry, RNA Sequencing, Laboratory testing, Corticosteroid
Keywords
Sarcoidosis, Corticosteroid dependent sarcoidosis
Medical subject headings
Sarcoidosis, Pulmonary, Sarcoidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trialDrug

    Also called Xeljanz, tofacitinib

    Tofacitinib 5mg oral table twice daily for 16 weeks

  • SpirometryDiagnostic test

    Also called Pulmonary function test

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

  • RNA SequencingGenetic

    RNA sequencing test at baseline and week 16

  • Laboratory testingDiagnostic test

    Also called Blood work

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

  • CorticosteroidDrug

    Also called Corticosteroid taper, Prednisone taper, Steroid taper

    Taper corticosteroids starting at week 4

  • Tofacitinib 5mg [Xeljanz] 1 year open-label extensionDrug

    Also called tofacitinib, Xeljanz

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

Study groups in NCT03793439
Study groupRoleWhat they receive
Open-label treatmentExperimentalAll 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 16 weeks

Secondary outcomes (1)

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

    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.

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2019
  2. Study start15 May 2019
  3. Primary completion24 Jun 2020
  4. Study completion24 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open-label, interventional, proof of concept, hypothesis-generating study
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03793439
Sponsor's protocol ID
STUDY00017902
Status last verified
Dec 2021
First submitted
2 Jan 2019
Last updated
18 Feb 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data for all primary and secondary outcomes will be made available.

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.

    PubMed 25880323

  • 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.

    PubMed 33825964

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial, Spirometry and RNA Sequencing in people with Sarcoidosis, Pulmonary and Sarcoidosis Lung, run by Oregon Health and Science University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 50% Reduction in Corticosteroid Requirement (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03793439, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2022.

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