EUCTR2021-005406-96-BE进行中（未招募）1 期
A 24-week, multicenter, randomized, double blind, placebo-controlled, dose-range finding phase II study to compare efficacy and safety of oral masitinib to placebo in treatment of patients with severe mast cell activation syndrome (MCAS) with handicap unresponsive to optimal symptomatic treatment
AB Science0 个研究点目标入组 78 人开始时间: 2022年7月5日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 78
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1.Patient with severe Mast cell activation syndrome (MCAS)
- •For diagnosis of MCAS, the patients must fulfil the following criteria:
- •a)Clinical Criteria:
- •Episodic occurrence of typical MCAS-related clinical symptoms (urticaria, angioedema, flushing, pruritus, nausea, hoarseness, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, nasal congestion, and headache) affecting 2 or more organ systems
- •b)Biomarker Criteria:
- •Increase in serum total tryptase by at least 20% above baseline plus 2 ng/ml during or within 4 h after a symptomatic period
- •Documented evidence of above-normal levels for one of the following MC mediators according to local laboratory criteria:
- •-Random serum tryptase, prostaglandin D2, histamine
- •-Random urinary histamine, N-methylhistamine, prostaglandin D2 and its metabolite 11F2 alpha
- •-24-hour urinary histamine, N-methylhistamine, prostaglandin D2 and its metabolite 11F2 alpha
- •2.Patient with severe symptoms over the 14-day run-in period defined as at least one of the following:
- •Pruritus score = 9
- •Number of flushes per week = 8
- •Hamilton rating scale for depression (HAMD-17) score = 19
- •Fatigue scales FSS = 36
- •Patients with depression should receive a psychiatric assessment in order to confirm the failure of standard treatment.
- •3.Patient with documented treatment failures of his/her symptom (s) (within last two years) with at least two of the symptomatic treatments used at optimized dose (Minimal duration of each treatment should be at least 8 weeks):
- •Corticosteroids
- •Antidepressants
- •Cromoglycate sodium
- •Antileukotrienes
- •4.Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period. For other symptomatic treatments, if the patient takes corticosteroids, anti-H2, PPI, antidepressants, cromoglycate sodium, or an antileukotriene, the treatment must have started at least 4 weeks before screening and must be stable throughout the study.
- •5.Age between 18 to 75 years (inclusive).
- •6.Weight > 45 kg and BMI between 18 and 35 kg/m2
- •7.Contraception:
- •Female patients of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agree to use a highly effective method of contraception and an effective method of contraception by their male partner during the study and for 8 months after the last treatment intake
- •Male patients with a female partner of childbearing potential who agree to use a highly effective method of contraception and an effective method of contraception by their female partner during the study and for 5 months after the last treatment intake OR who agree to use an effective method of contraception and a highly effective method of contraception by their female partner during the study and for 5 after the last treatment intake.
- •Highly effective and effective methods of contraception are detailed in the Appendix 15.3 of the protocol.
- •8.Patient must be able and willing to comply with study visits and procedures.
- •9.Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures.
- •10.Patient able to understand the patient card and follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity.
- •Are the trial subjects under 18? no
排除标准
- •1.Previous treatment with any Tyrosine Kinase Inhibitor.
- •2.Any change in the symptomatic treatment of MCAS, including systemic corticosteroids, or administration of any new treatment for MCAS within 4 weeks prior to screening.
- •3.Treatment with any investigational agent within 8 weeks prior to screening.
- •4.Patients with current or history of severe cardiovascular disease.
- •Myocardial infarction
- •Unstable angina pectoris
- •Coronary revascularization procedure
- •Congestive heart failure of NYHA Class III or IV
- •Stroke, including a transient ischemic attack
- •Second degree or third-degree atrioventricular block not successfully treated with a pacemaker
- •Bi-fascicular block
- •QTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females
- •Drug induced heart failure or ischemic heart disease
- •Radiotherapy induced cardiomyopathy
- •Family history of unexpected death of cardiovascular origin.
- •Edema of cardiac origin and left ventricular ejection fraction =50%
- •5.Patient with two or more of the risk factors listed below assessed by cardiologist as Very High Risk (calculated SCORE =10%.) or High Risk calculated SCORE =5% and <10%) according to the Systematic Coronary Risk Estimation (SCORE):
- •Hypertension (uncontrolled)
- •Kidney disease,
- •Current tabagism (= 10 Pack-year: equivalent to 1 pack of 20 cigarettes per 10 years with the formula N (number of packs of 20 cigarettes smoked daily) x T (number years smoking)). Patients who stopped smoking 6 months prior to evaluation are not concerned.
- •Hypercholesterolemia
- •This assessment is done according to the Systematic Coronary Risk Estimation (SCORE) using the country specific free full version of HeartScore, the interactive tool for predicting and managing the risk of heart attack and stroke in Europe, available at https://www.heartscore.org/en_GB/access. If country specific version is not available, EU one should be used.
- •6.Patient with systemic indolent mastocytosis.
- •7.Patient who had major surgery within 2 weeks prior to screening visit.
- •8.Known hypersensitivity to masitinib or to any of its excipients.
- •9.Patient with concomitant treatment or therapies associated with severe drug-induced skin toxicity.
- •10.Female patients who are pregnant or are breastfeeding.
- •11.Patient with following laboratory results out of the ranges detailed below at screening:
- •Absolute neutrophil count (ANC) = 1.5 x 109/L
- •Haemoglobin = 10 g/dL
- •Platelets (PLT) = 100 x 109/L
- •Albuminemia = 1 x LLN
- •12.Patients with history of severe bone marrow disorders such as agranulocytosis or aplasia
- •13.Patient with history of hepatic disorders, recent alcohol abuse or recent history of hepatic impairment defined as hepatic transaminase levels >1.5 x ULN or total bilirubin level > 1 x ULN
- •14.Patient with severe pre-existing renal impairment, or with abnormal laboratory results from local laboratory assessments at screening:
- •Creatinine clearance < 60 mL/min (Cockcroft and Gault formula)
- •Proteinuria > 30 mg/dL (1+) on dipstick; in case of the proteinuria = 1+ on the dipstick, 24 hours proteinuria must be > 1.5g/24 hours
- •15.Vulnerable population defined as:
- •Life expectancy < 6 months
- •Patient with < 5 years free of malignancy.
- •16.Patient with history of poor compliance, or current or past psychiatric disease that might interfere with the ability to comply with the study procedures or give informed consent according to the judgment of the investigator or in
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