Open-label Trial of Tofacitinib in Cutaneous Sarcoidosis and Granuloma Annulare
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Patients with Cutaneous Sarcoidosis
Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis
干预措施: Tofacitinib 5 mg twice daily (Drug)
Patients with Granuloma Annulare
Patients with granuloma annulare that is long-standing and/or widespread
干预措施: Tofacitinib 5 mg twice daily (Drug)
结局指标
主要结局
Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI)
时间窗: 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
时间窗: 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).
次要结局
- Change in Histologic Findings(6 -12 months)
- Change in Skindex-16: a skin-related quality of life metric(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)