Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare

NCT03910543 | Completed Phase 1 FDA Drug

• 1 other identifier: 2000023910
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the ability of tofacitinib, a Janus kinase (JAK) inhibitor, to treat patients with cutaneous sarcoidosis and granuloma annulare during 6 months of therapy.

Conditions

Cutaneous Sarcoidosis; Granuloma Annulare

Outcome Measures

Primary Outcomes (2)

• Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI)

  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

  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 Outcomes (5)

• Change in Skindex-16: a skin-related quality of life metric

  6 - 12 months

• Change in Histologic Findings

  6 -12 months

• Change in RNA sequencing markers (gene expression analysis)

  6 - 12 months

• Change in cytokine biomarkers

  6 - 12 months

• Change in activity of internal organ sarcoidosis

  6 - 12 months

Study Arms (2)

Patients with Cutaneous Sarcoidosis

EXPERIMENTAL

Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis

Drug: Tofacitinib 5 mg twice daily

Patients with Granuloma Annulare

EXPERIMENTAL

Patients with granuloma annulare that is long-standing and/or widespread

Drug: Tofacitinib 5 mg twice daily

Interventions

Tofacitinib 5 mg twice daily DRUG

Tofacitinib will be administered at a dose of 5 mg twice daily

Also known as: Xeljanz 5 mg twice daily

Patients with Cutaneous Sarcoidosis; Patients with Granuloma Annulare

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• Pfizer: collaborator

Study Sites (1)

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

Related Publications (3)

• 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.

  PMID: 30586518 BACKGROUND

• 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.

  PMID: 35668129 DERIVED

• 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.

  PMID: 33317858 DERIVED

MeSH Terms

Conditions

Granuloma Annulare

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Necrobiotic Disorders; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Granuloma; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• William Damsky, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label trial

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 10, 2019
• Study Start: April 11, 2019
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: July 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)