NCT05048238已完成1 期
Evaluation of Tofacitinib in Prevention of Photosensitivity in Cutaneous Lupus Erythematosus (ALE11)
National Institute of Allergy and Infectious Diseases (NIAID)2 个研究点 分布在 1 个国家目标入组 7 人开始时间: 2022年9月30日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Change in Percentage of UVB-induced Apoptotic Epidermal Cells
研究概览
简要总结
This is a single-arm, multi-site, proof-of-concept study that will evaluate the treatment of 10 participants with cutaneous lupus erythematosus (CLE) with Tofacitinib.
详细描述
Once consented, study participants meeting all entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally daily). Tofacitinib will be distributed to eligible participants at Visit 2 (Day 1) and the first dose will be taken on Day 2. The last dose is the morning of Visit 5 (Day 26).Ultraviolet B (UVB)-mediated cutaneous apoptosis and ancillary mechanistic studies will be evaluated in phototests, skin biopsies and blood samples collected before and after treatment.
This study will assess whether a 25-day regimen of tofacitinib impacts photosensitivity following UVB exposure in individuals with CLE.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cutaneous lupus erythematosus based upon all of the following:
- •a clinical diagnosis made by a rheumatologist or dermatologist of one of the following: acute cutaneous lupus erythematosus, subacute cutaneous lupus, or chronic cutaneous lupus erythematosus;
- •active skin disease within 5 years prior to screening. Participants may have concomitant SLE.
- •SLEDAI-2K score ≤4 (clinical criteria only, excludes all laboratory criteria) for all participants regardless of whether they have concomitant SLE.
- •If taking oral corticosteroids, the dose must be ≤ 10 mg daily of prednisone (or equivalent), stable dose for at least 4 weeks, and not anticipated to change over the course of the study.
- •If taking oral anti-malarial medications, the dose(s) must be ≤ 100 mg daily for quinacrine or/and ≤ 400 mg daily for hydroxychloroquine, stable for at least 6 months, and not anticipated to change over the course of the study.
- •If taking oral or subcutaneous methotrexate, the dose must be ≤ 25 mg weekly, stable for at least 4 weeks, and not anticipated to change over the course of the study.
- •If taking oral leflunomide, the dose must be ≤ 20 mg daily, stable for at least 4 weeks, and not anticipated to change over the course of the study.
- •If taking oral mycophenolate mofetil (MMF) or mycophenolic acid, the dose must be equivalent to ≤ 3000 mg of MMF daily, stable for at least 4 weeks, and not anticipated to change over the course of the study.
- •Adults 18 to 65 years of age at screening.
- •All participants and/or their sexual partners who engage in sexual activity that could lead to pregnancy must be willing to use complete abstinence or an FDA-regulated form of contraception for the duration of the study and for at least one month after discontinuation of study drug to prevent pregnancy. Highly effective birth control methods include, but are not limited to, hormonal contraception, an intrauterine device, or surgical options. Periodic abstinence and withdrawal are not acceptable methods of birth control.
排除标准
- •Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- •Current or recent history, within the last year, of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurologic disease or significant impairment that might negatively impact the participant's ability to participate or that may put a participant at increased risk.
- •Potential active nephritis and/or urinary tract infection at screening, defined as any one of the following determined at screening unless otherwise specified:
- •>10 RBCs /hpf,
- •>5 WBCs /hpf with either positive nitrites or greater than a trace leukocyte esterase,
- •Signs or symptoms of a urinary tract infection,
- •For individuals with no history of nephritis: Urine protein (mg/dL): creatinine (mg/dL) ratio (Pr/Cr)>0.5 at screening or a Pr/Cr level that has exceeded 1.0 in the prior 12 months,
- •For individuals with a history of nephritis: A rise in Pr/Cr of >0.5 over the prior 3-6 months prior to screening.
- •History of severe gastrointestinal narrowing or strictures.
- •Medically confirmed history of diverticulitis or chronic, ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis, or other symptomatic, lower GI conditions that might predispose a participant to perforations.
- •History of thrombosis, pulmonary embolism, or antiphospholipid syndrome.
- •History of any one of the following anti-phospholipid antibodies:
- •Positive lupus anticoagulant test, or
- •Anti-β2-glycoprotein I IgG ELISA titer ≥ 40 GPL, or
- •Anti-cardiolipin IgG ELISA titer ≥ 40 GPL.
- •History of chronic pulmonary disease requiring supplemental oxygen including chronic obstructive pulmonary disease (COPD) requiring chronic treatment, interstitial lung disease (ILD) requiring immunosuppressive therapy, and asthma requiring chronic steroid (other than inhaled steroid) or biologic therapy.
- •History of moderate to severe atherosclerotic cardiovascular disease as evidenced by prior coronary artery bypass surgery, coronary artery stent placement, myocardial infarction, symptomatic carotid arterial disease, peripheral vascular disease, abdominal aortic aneurysm; or angina within the past 8 weeks prior to Visit 1 (Day 0).
- •History of keloid scarring.
- •History of any lymphoproliferative disorder or other malignancy with the exception of successfully treated or excised basal cell or squamous cell skin cancer or cervical cancer in situ.
- •Other autoimmune diseases likely to require immunosuppression.
- •Any of the following lab results at screening:
- •Hemoglobin <9.5 g/dL
- •White Blood Cell count <3.5 x 109/L
- •Absolute Neutrophil count <1.2 x 109/L
- •Platelet count <120 x 109/L
- •Absolute Lymphocyte count <0.75 x 109/L
- •Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 1.5 × the upper limit of normal (ULN)
- •Total bilirubin > ULN
- •Estimated glomerular filtration rate [GFR] <60mL/min/1.73 m2
- •Triglycerides ≥ 300 mg/dL (fasting not required)
- •Total Cholesterol ≥ 240 mg/dL (fasting not required).
- •Major surgery < 8 weeks prior to Visit 1 (Day 0).
- •Hospitalized for serious infection < 4 weeks prior to Visit 1 (Day 0).
- •Chronic infections other than chronic or intermittent uncomplicated urinary tract infections (including but not limited to tuberculosis, chronic pyelonephritis, osteomyelitis).
- •Presumed or documented COVID-19 infection within 30 days prior to Visit 1 (Day 0).
- •Recent (within one month prior to screening) close contact with a person who has active TB infection.
- •History of untreated active or latent TB infection.
- •History of incompletely treated active or latent TB infection unless at least one month of treatment has been completed prior to screening.
- •Positive Interferon-Gamma Release Assay (IGRA) or positive purified protein derivative tuberculin skin test (PPD) (> 5mm induration) at screening.
- •An indeterminate IGRA at screening unless followed by a subsequent negative IGRA or negative PPD.
- •History of human immunodeficiency virus (HIV).
- •A positive test for HIV antigen/antibody or nucleic acid test (NAT) at screening.
- •History of a hepatitis B infection.
- •A positive test for hepatitis B surface antigen or hepatitis B core antibody at screening.
- •History of a hepatitis C infection.
- •A positive test for hepatitis C antibody (regardless of whether hepatitis C RNA levels are undetectable) at screening.
- •History of recurrent (more than one episode) herpes zoster, one or more episodes of any of the following: herpes zoster ophthalmicus, or disseminated herpes zoster, or disseminated herpes simplex.
- •Current, recent (< 4 weeks prior to Visit 1 (Day 0)) or chronic use of antibiotic medication, except for suppression of chronic/recurrent urinary tract infection, which is allowed.
- •Simultaneous use of more than one of the following: leflunomide, methotrexate and MMF.
- •Any of the following active medications (oral or parenteral): cyclosporine, voclosporin, cyclophosphamide, tacrolimus, rituximab or other anti-CD20s, or any other investigational or marketed biologic with immunomodulatory properties within a year prior to Visit 1 (Day 0).
- 另有 11 项未显示
研究组 & 干预措施
Tofacinitib
Experimental
10 participants receiving 11 mg of Tofacitinib administered orally and daily, from Day 2 to Day 26
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Change in Percentage of UVB-induced Apoptotic Epidermal Cells
时间窗: Day 1 (pre-treatment) to Day 26
At Day 0 and Day 25, skin was exposed to 10-80 mJ/cm2 UVB irradiation. At Day 1 and Day 26, erythema levels were measured with a Chroma Meter at each dose site and in an unexposed section. Skin biopsies at Day 1 and Day 26 were taken at the unexposed site and at the minimal erythema dose (MED) at Day 1. The percentage of apoptotic epidermal cells were determined in each skin biopsy sample by TUNEL staining. The percentage of UVB-induced apoptotic cells is defined as the difference between the percentage of apoptotic epidermal cells in the UVB-exposed biopsy at the MED and percentage of apoptotic epidermal cells in the unexposed biopsy at the same visit. Change in percentage of UVB-induced apoptotic epidermal cells is calculated as the difference in the percentage of UVB-induced apoptotic cells at Day 26 and at Day 1.
次要结局
- Change in Minimal Erythema Dose (MED) Due to UVB(Day 1 (pre-treatment) to Day 26)
- Change in UVB-induced Expression of Inflammatory Genes in Skin Based on Enumeration of RNA Transcripts.(Day 1 (pre-treatment) to Day 26)
- Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score(Day 0 (pre-treatment) to Day 25)
- Change in CLASI Damage Score(Day 0 (pre-treatment) to Day 25)
- Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score(Day 0 (pre-treatment) to Day 25)
- Change in Severity Grade for Laboratory Tests From Grade 0(Screening Visit through Day 40)
- Treatment-emergent Adverse Events by Severity(Day 2 to Day 40)
- Treatment-emergent Adverse Events by Relationship to Tofacitinib(Day 2 to Day 40)
研究者
研究点 (2)
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