Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants With 50% Reduction in Corticosteroid Requirement
研究概览
简要总结
This is a pilot study to determine whether further research is warranted to assess whether tofacitinib is an effective steroid sparing treatment for pulmonary sarcoidosis. The primary endpoint for this study is a 50% or greater reduction in corticosteroid requirement.
详细描述
Primary Objectives:
Objective 1: Test the hypothesis that the addition of tofacitinib will allow patients with sarcoidosis to have 50% or greater reduction in their corticosteroid requirement without a significant decrease in pulmonary function testing, and with a similar quality of life as measured by a validated questionnaire (1).
Objective 2: Test the hypothesis that the addition of tofacitinib will result in significantly decreased expression of signal transducer and activator of transcription (STAT)-1 dependent gene expression.
Outline:
This is a 16-week open-label, interventional, proof of concept, hypothesis-generating study. All subjects will receive Tofacitinib 5mg twice daily for 16 weeks. After four weeks on Tofacitinib, the corticosteroid will be tapered per a pre-defined protocol; once a reduction of 50% has been achieved, any further taper will be per physician discretion. After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet World Association of Sarcoidosis and other Granulomatous Disorders (WASOG) definition of pulmonary sarcoid
- •Histologically proven sarcoid
- •Evidence of pulmonary sarcoid on chest radiograph
- •Forced vital capacity of > 50%
- •Require 15-30mg/day of prednisone or equivalent corticosteroid to control sarcoidosis.
- •Stable dose of prednisone or equivalent corticosteroid for 4 weeks prior to enrollment.
排除标准
- •May be taking methotrexate but not other immunosuppressive or immunomodulatory treatments in the two months prior to study period. This includes but is not limited to azathioprine, cyclophosphamide, leflunomide, mycophenolate mofetil, cyclosporine, tacrolimus, and biologic medications.
- •Patients requiring >30mg/day prednisone or equivalent.
- •Pregnant or lactating women.
- •Hemoglobin < 9g/dL or hematocrit < 30%
- •White blood cell count <3.0 K/cu mm
- •Absolute neutrophil count <1.2 K/cu mm
- •Platelet count <100 K/cu mm
- •Subjects with an estimated glomerular filtration rate (GFR) ≤40 ml/min
- •Subjects with a total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal at screening.
- •Severe, progressive, or uncontrolled chronic liver disease including fibrosis, cirrhosis, or recent or active hepatitis.
- •History of any lymphoproliferative disorder such as Epstein Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggest of current lymphatic disease.
- •Current malignancy or history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
- •Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
- •Have a known infection with human immunodeficiency virus (HIV)
- •Have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac (New York Heart Association class III or IV), neurologic, or cerebral diseases (with the exception of sarcoidosis).
研究组 & 干预措施
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial (Drug)
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: Spirometry (Diagnostic Test)
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: RNA Sequencing (Genetic)
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: Laboratory testing (Diagnostic Test)
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: Corticosteroid (Drug)
Open-label treatment
All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
干预措施: Tofacitinib 5mg [Xeljanz] 1 year open-label extension (Drug)
结局指标
主要结局
Number of Participants With 50% Reduction in Corticosteroid Requirement
时间窗: 16 weeks
50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a \>15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value
次要结局
- Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing(16 weeks)
研究者
Jim Rosenbaum
Professor of Ophthalmology, Medicine, and Cell Biology, OHSU
Oregon Health and Science University