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Trial record 2 of 2 for:    tofacitinib | Sarcoidosis

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

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ClinicalTrials.gov Identifier: NCT03910543
Recruitment Status : Completed
First Posted : April 10, 2019
Last Update Posted : July 14, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE April 4, 2019
First Posted Date  ICMJE April 10, 2019
Last Update Posted Date July 14, 2021
Actual Study Start Date  ICMJE April 11, 2019
Actual Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2019)
  • 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)
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
  • Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) [ Time Frame: 6 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)
  • Change in Granuloma Annulare Severity Index (GASI) [ Time Frame: 6 months ]
    For patients with GA: change in GASI score after 6 months of treatment with tofacitinib compared to baseline. The range of scores is from 0 to 50. Higher scores correspond with higher cutaneous disease burden. The percentage change in GASI score will be calculated as follows: change in GASI score = [baseline GASI - final GASI] / baseline GASI 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)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2019)
  • 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
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
  • Change in Skindex-16: a skin-related quality of life metric [ Time Frame: 6 months ]
    For all patients: change in Skindex-16 score after 6 months of treatment with tofacitinib compared to baseline
  • Change in Histologic Findings [ Time Frame: 6 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.
  • Change in RNA sequencing markers (gene expression analysis) [ Time Frame: 6 months ]
    RNA sequencing will be performed on RNA extracted from skin biopsies of lesional skin at baseline and again after 6 months of treatment.
  • Change in cytokine biomarkers [ Time Frame: 6 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.
  • Change in activity of internal organ sarcoidosis [ Time Frame: 6 months ]
    For patients with sarcoidosis: change in PET-CT imaging after 6 months of treatment with tofacitinib compared to baseline
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare
Official Title  ICMJE Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
open-label trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cutaneous Sarcoidosis
  • Granuloma Annulare
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Patients with Cutaneous Sarcoidosis
    Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis
    Intervention: Drug: Tofacitinib 5 mg twice daily
  • Experimental: Patients with Granuloma Annulare
    Patients with granuloma annulare that is long-standing and/or widespread
    Intervention: Drug: Tofacitinib 5 mg twice daily
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 8, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 1, 2021
Actual Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03910543
Other Study ID Numbers  ICMJE 2000023910
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: William Damsky, MD, PhD Yale University
PRS Account Yale University
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP