Scientific Substantiation and Assessment of the Effectiveness of Pathogenetic Methods of Therapy for Congenital Ichthyosis in Children

NCT ID: NCT04996485

Last Updated: 2021-08-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2023-06-01

Brief Summary

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.

Detailed Description

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.

Conditions

Congenital Ichthyosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Secukinumab Injection

Intervention Type: DRUG

Pathogenetic therapy with biologic drugs

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.

Group Type: EXPERIMENTAL

Ustekinumab Injection

Intervention Type: DRUG

Pathogenetic therapy with biologic drugs

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.

Group Type: EXPERIMENTAL

Dupilumab Injection

Intervention Type: DRUG

Pathogenetic therapy with biologic drugs

Control group (Symptomatic therapy)

symptomatic therapy with emollients + systemic retinoids

Group Type: ACTIVE_COMPARATOR

Symptomatic therapy

Intervention Type: OTHER

Active external agents, Emollients, systemic retinoids if needed

Interventions

Secukinumab Injection

Pathogenetic therapy with biologic drugs

Intervention Type: DRUG

Ustekinumab Injection

Pathogenetic therapy with biologic drugs

Intervention Type: DRUG

Dupilumab Injection

Pathogenetic therapy with biologic drugs

Intervention Type: DRUG

Symptomatic therapy

Active external agents, Emollients, systemic retinoids if needed

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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 <18.

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Medical Research Center for Children's Health, Russian Federation

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National Medical Research Center for Children's Health

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Karine O. Avetisyan, MD

Role: CONTACT

avetisyan.karine@mail.ru

+79260869259

Facility Contacts

Karine Avetisyan, MD

Role: primary

Avetisyan.karine@mail.ru

+79260869259

Other Identifiers

12269723

Identifier Type: -

Identifier Source: org_study_id