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

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ClinicalTrials.gov Identifier: NCT03910543
Recruitment Status : Recruiting
First Posted : April 10, 2019
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Cutaneous Sarcoidosis Granuloma Annulare Drug: Tofacitinib 5 mg twice daily Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: open-label trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare
Actual Study Start Date : April 11, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sarcoidosis

Arm Intervention/treatment
Experimental: Patients with Cutaneous Sarcoidosis
Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis
Drug: Tofacitinib 5 mg twice daily
Tofacitinib will be administered at a dose of 5 mg twice daily
Other Name: Xeljanz 5 mg twice daily

Experimental: Patients with Granuloma Annulare
Patients with granuloma annulare that is long-standing and/or widespread
Drug: Tofacitinib 5 mg twice daily
Tofacitinib will be administered at a dose of 5 mg twice daily
Other Name: Xeljanz 5 mg twice daily




Primary Outcome Measures :
  1. 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)


  2. 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).



Secondary Outcome Measures :
  1. Change in Skindex-16: a skin-related quality of life metric [ Time Frame: 6 - 12 months ]
    For all patients: change in Skindex-16 score after 6 months of treatment with tofacitinib compared to baseline

  2. Change in Histologic Findings [ Time Frame: 6 -12 months ]
    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.

  3. Change in RNA sequencing markers (gene expression analysis) [ Time Frame: 6 - 12 months ]
    RNA sequencing will be performed on RNA extracted from skin biopsies of lesional skin at baseline and again after 6 months of treatment.

  4. Change in cytokine biomarkers [ Time Frame: 6 - 12 months ]
    Luminex-based cytokine analysis using a commercially available service will be performed on plasma collected at baseline and again after 6 months of treatment.

  5. Change in activity of internal organ sarcoidosis [ Time Frame: 6 - 12 months ]
    For patients with sarcoidosis: change in PET-CT imaging after 6 months of treatment with tofacitinib compared to baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03910543


Contacts
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Contact: Yvette Strong 203-737-2506 yvette.strong@yale.edu
Contact: William Damsky, MD, PhD 203-737-2506 william.damsky@yale.edu

Locations
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United States, Connecticut
Yale Center for Clinical Investigation Recruiting
New Haven, Connecticut, United States, 06519
Contact: Yvette Strong    203-737-2506    yvette.strong@yale.edu   
Principal Investigator: William Damsky, MD, PhD         
Sponsors and Collaborators
Yale University
Pfizer
Investigators
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Principal Investigator: William Damsky, MD, PhD Yale University

Publications:
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03910543    
Other Study ID Numbers: 2000023910
First Posted: April 10, 2019    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Sarcoidosis
Granuloma
Granuloma Annulare
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Necrobiotic Disorders
Collagen Diseases
Connective Tissue Diseases
Skin Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action