Multicenter Randomized, Double-blind, Placebo-controlled Parallel Clinical Trial to Assess Efficacy and Safety of Omalizumab (Xolair®) in a New Indication: Cholinergic Urticarial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Negativization of the exercise challenge test
研究概览
简要总结
To demonstrate the efficacy and safety of Omalizumab in a new indication, that is cholinergic urticaria.
详细描述
Physical urticarias, such as delayed pressure, cholinergic, dermatographism and cold urticaria, are highly disabling conditions[1]. Cholinergic urticaria occurs due to an active (e.g. exercise) or passive (e.g. hot bath) increase in core body temperature, causing itching and small hives with flare reaction on the trunk and limps that fade away upon cooling of the body[2].
As it is the case of chronic urticaria, physical urticarias have a great impact on patients' quality of life[3, 4]. However, these types of urticarias cause even more alteration on quality of life because of the limitations they cause in daily life activities, sports practicing[5] or work performance.
In spite of the high morbidity of this disease and the impact on quality of life, there is no available treatment. Antihistamines that usually control other types of urticaria could only partially alleviate cholinergic urticaria. There is only one paper[6] that shows efficacy doubling the dose of cetirizine above the recommended dosage on the Summary of Product Characteristics (off-label dosage). The poor response to antihistamine is justified by the minimal role of histamine in its physiopathology and only after employing very high doses[7].
The etiology and pathogenesis of hive formation remains unknown, though it is recognized that mast cells are clearly involved[8]. On the other hand, it seems that desensitization or tolerance could be induced in cholinergic urticaria[9]. Thus as it is the case of drug desensitization, Immunoglobulin E (IgE) receptor must also play a role in the development of this physical urticaria[10].
In the past years, the monoclonal humanized anti-IgE antibody (Omalizumab) was shown to be effective in control cholinergic urticaria[11] not respondent to conventional therapies at maximum or off-label doses. A negative response was also reported for cholinergic urticaria[12].
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult female and male patients (age 14 years or older). Diagnosis of cholinergic urticaria trough clinical history and positive challenge test.
- •Non-respondent to supra therapeutic doses of antihistamines (defined as 2x the maximal dose included in the drug labeling) Written informed consent.
排除标准
- •Pruritus related to dermatitis or other skin condition. Any systemic disease that hampers follow up or interpretation of data. Omalizumab treatment within the previous 12 months. Any exclusion criteria included in the drug labeling. Any other conditions that do not allow the accomplishment of the clinical trial requisites, such as the abuse of drugs or alcohol.
研究组 & 干预措施
Active
Omalizumab 300 mg Subcutaneous route 300 mg dose (independent from total IgE, weight or high)
干预措施: Active (Biological)
Placebo
Placebo Saline serum Subcutaneous route 0.6 ml saline serum with same volume as an active treatment
干预措施: Placebo (Biological)
Open labeled
After the double blinded period, all patients from both arms will receive the active drug for 8 more months.
干预措施: Open labeled (Biological)
结局指标
主要结局
Negativization of the exercise challenge test
时间窗: It will be assessed prior to the study, and subsequently each 4 weeks up to 12 months.
a. Our primary endpoint will be the negativization of the exercise challenge test: We will perform the exercise challenge test following the European Guidelines\[14\] for cholinergic urticaria. According with such guidelines, all centers will follow the same center standardized protocol. The patient will exercise in treadmill or running to the point of sweating and following for 15 more minutes, wearing warm clothing in a warm room. The test will be considered positive if exercise challenge leads to the typical rash over 10 minutes.
次要结局
- Chonic Urticaria Quality of life(It will be evaluated up to 48 weeks.)
- Patients' card(It will be assessed up to 48 weeks.)
- Treatment drop offs in each sequence(Up to 48 weeks.)