- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03910543
Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Connecticut
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New Haven, Connecticut, United States, 06519
- Yale Center for Clinical Investigation
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 18 years old or older
- Diagnosis of cutaneous sarcoidosis or granuloma annulare with supportive skin biopsies in which other causes of granulomas (infectious, foreign body) have been ruled out
- Patients with either: Cutaneous Sarcoidosis Activity and Morphology (CSAMI) activity score greater than or equal to 10 (patients with a CSAMI greater than or equal to 10 have active cutaneous sarcoidosis involving several distinct cutaneous sites and would otherwise be considered candidates for systemic therapy), or any CSAMI score and sarcoidosis involvement causing functional impairment (i.e. nasal or visual field obstruction).
- For patients with granuloma annulare, patients with 5% or greater Body Surface Area (BSA) will be enrolled.
- If patients are on other systemic therapies for their sarcoidosis or granuloma annulare, they must be taking a stable dose of the other medication(s) for at least 3 months with no plans to change the regimen in the next 6 months. With the exception of methotrexate and/or low dose prednisone, use of concomitant immunosuppressants, e.g. infliximab, azathioprine, etc., will not be permitted.
- Females of childbearing potential must agree to use birth control during the study and there must be a negative pregnancy test documented prior to starting the medication.
- Patients must be willing to undergo skin biopsies, blood collection, and total body photography and comply with clinic visits
Exclusion Criteria:
- Age <18 years old
- Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin)
- Patients known to be HIV or hepatitis B (HBV) or C (HCV) positive (prior exposure to but clearance of HBV and HCV is acceptable for study entry as long as patient is being monitored by hepatology)
- Patients with active tuberculosis or untreated latent tuberculosis as determined by positive tuberculin skin test or positive QuantiFERON® Tuberculosis (TB) test and, as necessary, chest X-ray
- Patients with significant hepatic impairment
- Patients with untreated peptic ulcer disease
- Patients taking immunosuppressive medications, with the exception of methotrexate and/or low- dose prednisone, including but not limited to mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or Tumor Necrosis Factor (TNF-α) inhibitors
- Women of childbearing potential who are unable or unwilling to use birth control while taking the medication
- Women who are pregnant or nursing. If a woman becomes pregnant during the study, she will stop study medication and be removed from the study. She will be urged to follow up with her Primary Care Physician or OB/GYN. The study doctors will ask to follow the pregnancy to its outcome.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients with Cutaneous Sarcoidosis
Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis
|
Tofacitinib will be administered at a dose of 5 mg twice daily
Other Names:
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Experimental: Patients with Granuloma Annulare
Patients with granuloma annulare that is long-standing and/or widespread
|
Tofacitinib will be administered at a dose of 5 mg twice daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI)
Time Frame: 6 - 12 months
|
For patients with sarcoidosis: change in CSAMI score after 6 months of treatment with tofacitinib compared to baseline. The activity portion of the CSAMI score will be utilized. The range of scores is from 0 to 165. Higher scores correspond with higher cutaneous disease burden. The percentage change in CSAMI score will be calculated as follows: change in CSAMI score = [baseline CSAMI - final CSAMI] / baseline CSAMI Higher percentage change corresponds to more improvement on therapy (0% = no change, 100% = complete disease resolution) Negative percentage change corresponds to disease worsening (-25% = 25% worsening of disease) |
6 - 12 months
|
Percent Change in Body Surface Area (BSA) involvement by GA lesions
Time Frame: 6 - 12 months
|
For patients with GA: change in BSA involvement after 6 months of treatment with tofacitinib compared to baseline. The range of BSA involvement for this study is from 5% to 100%. Higher BSA involvement corresponds with higher cutaneous disease burden. The percentage change in BSA will be calculated as follows: Change in BSA = [baseline BSA- final BSA] / baseline BSA Higher percentage change corresponds to more improvement on therapy (0% = no change, 100% = complete disease resolution) Negative percentage change corresponds to disease worsening (-25% = 25% worsening of disease). |
6 - 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Skindex-16: a skin-related quality of life metric
Time Frame: 6 - 12 months
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For all patients: change in Skindex-16 score after 6 months of treatment with tofacitinib compared to baseline
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6 - 12 months
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Change in Histologic Findings
Time Frame: 6 -12 months
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Skin biopsies of lesional skin will be performed at baseline and again after 6 months of treatment.
Standard hematoxylin and eosin (H&E) and immunohistochemistry for CD68, phospho-STAT1, and phospho-STAT3 will be performed.
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6 -12 months
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Change in RNA sequencing markers (gene expression analysis)
Time Frame: 6 - 12 months
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RNA sequencing will be performed on RNA extracted from skin biopsies of lesional skin at baseline and again after 6 months of treatment.
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6 - 12 months
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Change in cytokine biomarkers
Time Frame: 6 - 12 months
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Luminex-based cytokine analysis using a commercially available service will be performed on plasma collected at baseline and again after 6 months of treatment.
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6 - 12 months
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Change in activity of internal organ sarcoidosis
Time Frame: 6 - 12 months
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For patients with sarcoidosis: change in PET-CT imaging after 6 months of treatment with tofacitinib compared to baseline
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6 - 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: William Damsky, MD, PhD, Yale University
Publications and helpful links
General Publications
- Damsky W, Thakral D, Emeagwali N, Galan A, King B. Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis. N Engl J Med. 2018 Dec 27;379(26):2540-2546. doi: 10.1056/NEJMoa1805958.
- Damsky W, Wang A, Kim DJ, Young BD, Singh K, Murphy MJ, Daccache J, Clark A, Ayasun R, Ryu C, McGeary MK, Odell ID, Fazzone-Chettiar R, Pucar D, Homer R, Gulati M, Miller EJ, Bosenberg M, Flavell RA, King B. Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nat Commun. 2022 Jun 6;13(1):3140. doi: 10.1038/s41467-022-30615-x.
- Wang A, Rahman NT, McGeary MK, Murphy M, McHenry A, Peterson D, Bosenberg M, Flavell RA, King B, Damsky W. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. J Allergy Clin Immunol. 2021 May;147(5):1795-1809. doi: 10.1016/j.jaci.2020.10.012. Epub 2020 Dec 11.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2000023910
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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