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Cutaneous SarcoidosisPhase 1NCT03910543

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

A Phase 1 study testing Tofacitinib 5 mg twice daily in people with Cutaneous Sarcoidosis and Granuloma Annulare, run by Yale 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

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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Cutaneous Sarcoidosis, Granuloma Annulare
What is being tested?
Tofacitinib 5 mg twice daily
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
11 Apr 2019to 1 Jun 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale Center for Clinical Investigation

    New Haven, Connecticut, 06519

Other trials in United States

About this study

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.

Read the detailed description

An open-label clinical trial of tofacitinib in cutaneous sarcoidosis and GA. The hypothesis is that Janus Kinase (JAK) 1/3 inhibition with tofacitinib will be effective for the treatment these two diseases. Tofacitinib will be administered at a dose of 5 mg twice daily and response to therapy will be assessed at months 1, 3, and 6 of therapy. The primary outcomes will be improvement in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Granuloma Activity Scoring Index (GASI) after 6 months of tofacitinib therapy. Secondary outcomes will include improvement in internal organ sarcoidosis (i.e. lung, cardiac) and skin related quality of life. Pre- and on treatment PET-CT scans will be performed in patients with sarcoidosis with internal organ involvement. Pre- and on treatment blood collection and skin biopsies will be performed for correlative scientific studies using RNA sequencing, immunohistochemistry (IHC), and cytokine profiling.

Being tested
Tofacitinib 5 mg twice daily
Medical subject headings
Granuloma Annulare

What participants receive

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

  • Tofacitinib 5 mg twice dailyDrug

    Also called Xeljanz 5 mg twice daily

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

Study groups in NCT03910543
Study groupRoleWhat they receive
Patients with Cutaneous SarcoidosisExperimentalPatients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis
Receives: Drug: Tofacitinib 5 mg twice daily
Patients with Granuloma AnnulareExperimentalPatients with granuloma annulare that is long-standing and/or widespread
Receives: Drug: Tofacitinib 5 mg twice daily

What is being measured

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

  1. 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)

    Measured: 6 - 12 months

  2. 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).

    Measured: 6 - 12 months

Secondary outcomes (5)

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

    For all patients: change in Skindex-16 score after 6 months of treatment with tofacitinib compared to baseline

    Measured: 6 - 12 months

  2. Change in Histologic Findings

    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.

    Measured: 6 -12 months

  3. Change in RNA sequencing markers (gene expression analysis)

    RNA sequencing will be performed on RNA extracted from skin biopsies of lesional skin at baseline and again after 6 months of treatment.

    Measured: 6 - 12 months

  4. Change in cytokine biomarkers

    Luminex-based cytokine analysis using a commercially available service will be performed on plasma collected at baseline and again after 6 months of treatment.

    Measured: 6 - 12 months

  5. Change in activity of internal organ sarcoidosis

    For patients with sarcoidosis: change in PET-CT imaging after 6 months of treatment with tofacitinib compared to baseline

    Measured: 6 - 12 months

Timeline

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

  1. First posted10 Apr 2019
  2. Study start11 Apr 2019
  3. Primary completion1 Jun 2021
  4. Study completion1 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
Non-randomised
Intervention model
Single group
Model description
open-label trial
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03910543
Sponsor's protocol ID
2000023910
Status last verified
Jul 2021
First submitted
4 Apr 2019
Last updated
14 Jul 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 30586518

  • 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.

    PubMed 35668129

  • 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.

    PubMed 33317858

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tofacitinib 5 mg twice daily in people with Cutaneous Sarcoidosis and Granuloma Annulare, run by Yale 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 7 inclusion and 9 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 14 Jul 2021. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) (time frame: 6 - 12 months). The study lists 2 primary outcomes in all. 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 NCT03910543, which also lists 3 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 14 Jul 2021.

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