A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 319
- 主要终点
- Change From Baseline to Week 12 in the Weekly Itch Severity Score
研究概览
简要总结
The study is a global Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory CIU and who remain symptomatic despite standard-dose H1 antihistamine treatment.
详细描述
Type I Error Rate Control Plan
Primary Outcome Measure
In order to maintain an overall type I error rate of 0.05 (2-sided) across the 3 omalizumab dose levels, the testing of the primary Outcome Measure was conducted in the following hierarchical order. A p-value < 0.05 is only considered statistically significant if statistical significance was claimed at the previous stage.
- Stage 1: Omalizumab 300-mg group vs. placebo
- Stage 2: Omalizumab 150-mg group vs. placebo
- Stage 3: Omalizumab 75-mg group vs. placebo
Secondary Outcome Measures
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) refractory to H1 antihistamines at the time of randomization.
排除标准
- •Treatment with an investigational agent within 30 days prior to screening.
- •Weight < 20 kg (44 lbs).
- •Clearly defined underlying etiology for chronic urticarias other than CIU.
- •Evidence of parasitic infection.
- •Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
- •Previous treatment with omalizumab within a year prior to screening.
- •Routine doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
- •Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.
- •Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening.
- •Any H2 antihistamine use within 7 days prior to screening.
- •Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to screening.
- •Any H1 antihistamines at greater than approved doses within 3 days prior to screening.
- •Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved.
- •Hypersensitivity to omalizumab or any component of the formulation.
- •History of anaphylactic shock.
- •Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
- •Evidence of current drug or alcohol abuse.
- •Nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.
研究组 & 干预措施
Placebo
Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
干预措施: Placebo (Drug)
Omalizumab 75 mg
Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.
干预措施: Omalizumab (Drug)
Omalizumab 150 mg
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.
干预措施: Omalizumab (Drug)
Omalizumab 300 mg
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
干预措施: Omalizumab (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in the Weekly Itch Severity Score
时间窗: Baseline to Week 12
The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.
次要结局
- Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12(Baseline to Week 12)
- Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)(Baseline to Week 12)
- Percentage of Complete Responders (UAS7 = 0) at Week 12(Week 12)
- Change From Baseline to Week 12 in the Weekly Number of Hives Score(Baseline to Week 12)
- Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12(Baseline to Week 12)
- Percentage of Participants With a UAS7 Score ≤ 6 at Week 12(Week 12)
- Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score(Baseline to Week 12)
- Percentage of Weekly Itch Severity Score MID Responders at Week 12(Baseline to Week 12)
- Percentage of Angioedema-free Days From Week 4 to Week 12(Week 4 to Week 12)