Multicenter, Double- Blinded, Placebo- Controlled, Randomized, Cross-over (2x2) Clinical Trial, to Assess Efficacy and Safety of a New Indication for Omalizumab (Xolair®, Novartis) in Autoimmune and no Autoimmune Chronic Urticaria.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Symptom's control as measured by the UAS7
研究概览
简要总结
Chronic urticaria can be defined as the occurrence of widespread daily or almost daily wheals for at least 6 weeks, which may be accompanied by angioedema. While the wheals are transient, the resolution of angioedema is slower than wheals and could take up to 72 hours. The natural course of chronic urticaria is self-limited, with spontaneous remissions and occasional relapses. The investigators calculated a 0.6% (95% CI(Confidence Interval): 0.4-0.8) prevalence in a population study. It has a great impact on patients' quality of life. In a recent national survey on patients attending Allergy Department, chronic urticaria was the disease with greater impact on mental quality of life out of all allergic diseases.
In spite of the high morbidity of this disease and the impact in quality of life, there is no available treatment. Last guidelines recommend initiating treatment with antihistamine and if there is no response to increase the dose off-label up to four-fold; systemic corticosteroids are also recommended in short tapering and if no response, the only treatment with clinical evidence to be employed is cyclosporine. As additional data, the treatment cost of this disease has been calculated in 2047$/year.
In past years it has been employed the monoclonal humanized anti-Immunoglobulin IgE (iGE) antibody (Omalizumab) to treat moderate to severe asthma with good results. The rationale for this approach in chronic urticaria is that Omalizumab inhibits the binding of IgE to the high affinity IgE receptor (FceRI) which decreases the FceRI expression on the surface of mast cells and basophils so that immunoglobulin G cross linking of the alpha subunit and basophil degranulation is prevented.The hypothesis the investigators are working on is that monoclonal IgE antibody Omalizumab could be effective in controlling chronic urticaria symptoms in patients non respondent to conventional therapy. The investigators hypothesize that Omalizumab is able to revert the basophil or mast cell activation present in chronic urticaria.
详细描述
The objective of the present study is to demonstrate with an adequate methodology the efficacy and safety of Omalizumab for a new indication that is chronic autoimmune and no autoimmune urticaria. For that purpose, The investigators will perform a Multicenter double- blinded, placebo- controlled, randomized cross-over (2x2) trial. The investigators will include 20 patients including both female and male adults non respondent to antihistamines at supra therapeutic dose. Efficacy will be evaluated through the Urticaria Activity Score 7 (UAS7), Chronic Urticaria Quality of Life validated questionnaire, patients' symptoms card and use of medication. Dropouts in each treatment group will be also evaluated. The investigators will also record leave days because of urticaria and Emergency Department visits, as well as adverse reactions during treatment.
The present study would allow to offer to the Health System an evidence to evaluate the convenience or not to approve the use of Omalizumab for the new indication of chronic urticaria treatment. It is important to take into account that in the present study the investigators will include both autoimmune and non-autoimmune urticaria, since the efficacy could differ between both urticaria types. In the same way, the Health Authorities (AEMPS) would have independent additional information obtained through adequate methodology in the case that a new indication is requested. The investigators also want to stress that in the near future the company that manufactures this antibody could ask for a new indication for chronic urticaria.
A third outcome expected is to offer information on the lasting effect of the drug that is symptoms' free weeks after the dose. This information would be provided from the washing period data and from those patients who were allocated of placebo after the active drug arm. This would give much needed information on the best dosing scheduling protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Adult female and male patients
- •Diagnosis of chronic autoimmune or non autoimmune urticaria
- •The investigators defined chronic urticarial as the occurrence of widespread daily or almost daily wheals for at least 6 weeks, which may be accompanied by angioedema. While the wheals are transient, the resolution of angioedema is slower than wheals and could take up to 72 hours.
- •No response to therapeutic doses of antihistamines
- •The investigators define therapeutic doses of antihistamines the maximal dose included in the drug labeling
- •Written informed consent.
排除标准
- •Urticaria vasculitis or any kind of physical urticaria
- •Total IgE value above 700 UI/l
- •Pruritus related to dermatitis or other skin condition
- •Any systemic disease that do not allow to follow up or interpretation data
- •Omalizumab treatment within the previous 12 months
- •Treatment with corticosteroids or immunosuppressive drugs within the previous 4 weeks
- •Any exclusion criteria included in the drug labeling
- •Any other condition that do not allow to accomplish the clinical trial requisites as use of drugs, alcohol.
研究组 & 干预措施
Omalizumab 300 mg
- Subcutaneous route
- 300 mg dose (independent from total IgE, weight or high)
干预措施: Placebo (Biological)
Placebo
- Saline serum
- Subcutaneous route
- 0.6 ml saline serum with same volume as an active treatment
干预措施: Placebo (Biological)
Placebo
- Saline serum
- Subcutaneous route
- 0.6 ml saline serum with same volume as an active treatment
干预措施: Omalizumab (Biological)
Omalizumab 300 mg
- Subcutaneous route
- 300 mg dose (independent from total IgE, weight or high)
干预措施: Omalizumab (Biological)
结局指标
主要结局
Symptom's control as measured by the UAS7
时间窗: One year
The Urticaria Activity Score 7 measures number the weekly average of hives and pruritus measured twice a day. It scores from 0 to 42
次要结局
- Use of Medication(One year)
- Quality of life score (CU-Q2oL)(One year)