Scientific Substantiation and Assessment of the Effectiveness of Pathogenetic Methods of Therapy for Congenital Ichthyosis in Children
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Ichthyosis Area Severity Index (IASI)
研究概览
简要总结
This is an experimental non-randomized clinical study aimed at expanding the indications for the use of biological drugs with the aim of using them for the pathogenetic therapy of children with congenital ichthyosis.
详细描述
This is an experimental non-randomized clinical study aimed at expanding the indications for the use of biological drugs with the aim of using them for the pathogenetic therapy of children with congenital ichthyosis.
The study will include 50 children aged 6 months to 18 years with a clinically and genetically confirmed diagnosis of congenital ichthyosis. Patients will be divided into 4 groups who will receive symptomatic therapy (using active external agents, emollients and / or systemic retinoids) or biologics targeting the cytokines IL-12 / IL-23, IL-4 / IL-13 and IL -17A. Immunophenotyping of all patients will be performed, the cytokine profile and spectrum of sensitization and the degree of NF-kB activation in lymphocytes will be determined. In experimental group №3, 10 patients with Netherton syndrome will receive dupilumab, in experimental group №2, 10 patients will receive ustekinumab, and in experimental group №1 10 patients will receive secukinumab. Efficiency will be assessed using the Ichthyosis Area Severity Index (IASI), determination of the level of TEWL, and the change in quality of life will also be assessed using the Children's Dermatological Life Quality Index (CDLQI) in comparison from baseline, than at 16 and 52 weeks. Throughout the study, the safety profile (registration of the development of infectious diseases) will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The subject has signed an informed consent; parental or legal representative consent for patients under 18 years of age, as well as additional consent for patients aged ≥ 15 and <
- •At the time of participation in the study, the age of the subject is not less than 6 months and not more than 18 years.
- •At the time of participation in the study, a clinical diagnosis was established: Congenital ichthyosis with various clinical forms, with the exception of vulgar and X - linked congenital ichthyosis (genetic research is not a prerequisite for participation in the study).
- •Subjects should have at least moderate IASI erythema associated with his / her ichthyosis, and a decrease in the quality of life according to CDLQI ≥ 10
- •Absence of signs of severe infectious diseases (pneumonia, tuberculosis, etc.)
- •No previous history of the use of the following genetically engineered biological drugs: ustekinumab, secukinumab, dupilumab
排除标准
- •Subjects who have an allergic reaction to ustekinumab, secukinumab or other components of the drugs.
- •Subjects who have bacterial and/or fungal diseases.
- •Subjects who have problems in dynamic observation.
- •Subjects who will have a worsening of clinical symptoms
研究组 & 干预措施
Experimental group №1 (Secukinumab )
Secukinumab - subcutaneous injections into the shoulder according to the schedule of 0,1,2,3 weeks, then injections 1 time in 3 months up to 52 weeks of therapy.
干预措施: Secukinumab Injection (Drug)
Experimental group №2 (Ustekinumab)
Ustekinumab - subcutaneous injections in the shoulder on schedule 0; 1 month, then every 2 months up to 52 weeks of therapy.
干预措施: Ustekinumab Injection (Drug)
Experimental group №3 (Dupilumab)
Dupilumab - subcutaneous injections in the shoulder:
for patients weighing from 15 to <30 kg: initial dose - 600 mg (2 injections of 300 mg), then 300 mg every 4 weeks; for patients weighing from 30 to <60 kg: initial dose - 400 mg (2 injections of 200 mg), then 200 mg every 2 weeks; for patients weighing 60 kg or more: the initial dose is 600 mg (2 injections of 300 mg), then 300 mg every 2 weeks.
干预措施: Dupilumab Injection (Drug)
Control group (Symptomatic therapy)
symptomatic therapy with emollients + systemic retinoids
干预措施: Symptomatic therapy (Other)
结局指标
主要结局
Change in Ichthyosis Area Severity Index (IASI)
时间窗: 52 weeks
Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S)
次要结局
- Change in the Children's Dermatology Life Quality Index (CDLQI)(52 weeks)
- Transepidermal water loss (TEWL) level change(52 weeks)