Role of Immunoglobulin E (IgE) Bearing Cells in Chronic Idiopathic Urticaria
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Time to 50% Decline in Clinical Symptoms Measured by the Urticaria Activity Score Seven Day(UAS7)
研究概览
简要总结
This is a Phase IV, single-site study that will examine blood cells or tissue obtained from CIU ( chronic idiopathic Urticaria) patients receiving open-label treatment with omalizumab at the current FDA-approved dose of 300 mg/month for 12 weeks in addition to standard therapy with anti-histamines. Results from the 3 Phase III studies in CIU patients provide evidence that a meaningful change in symptoms is apparent at 1-2 wks. The Minimal Important Difference (MID) is achieved by 70% of patients by 2 wks on multiple background drugs for hives. The goal is to identity the IgE bearing cell type associated with clinical symptom change.
详细描述
Primary Objective
This will be a study of the kinetics of clinical symptom relief during treatment of patients with CIU. The purpose is to determine if the rate of clinical remission is concordant with the rate that IgE-dependent functions of basophil change or mast cell changes during treatment.
Secondary Objectives
- Basophil surface IgE, Fc epsilon Receptor I alpha (FcεRI) and Syk by flow cytometry
- Dendritic cell surface IgE, FcεRI, functions
- Basophil anti-IgE, anti FcεRI, C5a, N-Formylmethionyl-leucyl-phenylalanine (FMLP) mediated histamine along with sensitivity measures
- Serum free IgE measures
- Characterization of presence of serum autoantibody presence ± Syk inhibitors
- Basophil enumeration
- Basophil Messenger RNA (mRNA) profiling baseline at 3 timepoints (baseline, meaningful clinical changes, and 30 days)
- To assess the rate of IgE and FcεRI change in skin mast cells at day 0, 6, 90, via a small punch biopsy as well as the Mas-Related gpr Family Member X2 (MrgX2) receptor expression
Study Design
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age >18 years old
- •Females must be surgically sterile or postmenopausal or using a highly effective form of birth control throughout the duration of the study.
- •Females must have a negative urine pregnancy test at screening and other visits specified in this protocol unless documented to have a hysterectomy or be postmenopausal.
- •Clinical history of CIU at the time of screening, as defined by pruritus and hives for > 3 days in a 7-day period for > 6 consecutive weeks despite treatment with H1 antihistamine.
- •CIU diagnosis > 3 months (by history)
- •No underlying etiology clearly defined for urticaria (main manifestation cannot be physical urticaria).
- •Non-diary based UAS scores ≥ 2 at either the screening visit (Week -3), at the run-in visit (Week -2), or on Day
- •Compliance with study procedures during run-in period (e.g., completion of the study diary).
排除标准
- •Pregnant females, Recent history of drug or alcohol abuse (within 3 years prior to screening visit).Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- •Use of any investigational drugs within 30 days of screening.
- •Active atopic dermatitis or other skin disease associated with pruritus during the time of the study, which require treatment with topical corticosteroids.
- •Clinically relevant major systemic disease (making interpretation of the study results difficult) including a history of anaphylaxis.
- •Inability to comply with study and follow-up procedures
- •Patients may not use oral or systemic steroids during the study or within 4 weeks prior to enrollment.
- •Patients may not take H2 antihistamines and leukotriene receptor antagonists within 7 days before screening, during the screening, run-in, or treatment phases. The exception will be if they are already on these medications for the treatment of Gastro-Esophageal Reflux Disease (GERD), asthma or allergic rhinitis.
- •Any clinically relevant abnormal findings in clinical chemistry, hematology, urinalysis, physical examination, pulse, blood pressure at baseline, which, in the opinion of the investigator, could put the patient at risk because of his/her participation in the study.
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may compromise the quality of the data obtained from the study.
研究组 & 干预措施
Omalizumab
Omalizumab 300mg every month for 3 doses
干预措施: Omalizumab (Drug)
结局指标
主要结局
Time to 50% Decline in Clinical Symptoms Measured by the Urticaria Activity Score Seven Day(UAS7)
时间窗: From first injection to time of meaningful change, up to 12 Weeks
The time (in days) to meaningful change in diary-based clinical symptoms as measured by the Urticaria Activity Score (UAS) from baseline (Wk -7 to Day -1) to the date at which an Minimally Important Difference (5 point change in weekly UAS 7) or achievement of \> 50% reduction in daily symptom score for 3 days if in the first week. The UAS score, which is the sum of pruritus and hives, will be used to calculate the UAS7. The UAS7 score obtained 1 week prior to randomization will be used as the baseline. The UAS is a validated measure of CIU disease activity calculated from the average of twice daily recorded itch (0 - 3; 0= no itch, 1= mild itch, 2= moderate itch, 3= severe itch) and hives (0 - 3, 0= no hives, 1= 1-6 hives, 2= 7-12 hives, 3= \> 12 hives in the past 12 hours) scores with a daily maximum of 6. The UAS-7 is the sum of 7 daily average UAS scores with a maximum value of 42 The UAS-7 is the sum of 7 daily average UAS scores with a maximum value of 42.
次要结局
未报告次要终点