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

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Ichthyosis
• Intervention / Treatment: Drug: Secukinumab Injection; Drug: Ustekinumab Injection; Drug: Dupilumab Injection; Other: Symptomatic therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Karine O. Avetisyan, MD; Phone Number: +79260869259; Email: avetisyan.karine@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119296
    • Recruiting
    • National Medical Research Center for Children's Health
    • Contact: Karine Avetisyan, MD; Phone Number: +79260869259; Email: Avetisyan.karine@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Secukinumab Injection; Pathogenetic therapy with biologic drugs
Experimental: 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.	Drug: Ustekinumab Injection; Pathogenetic therapy with biologic drugs
Experimental: 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.	Drug: Dupilumab Injection; Pathogenetic therapy with biologic drugs
Active Comparator: Control group (Symptomatic therapy); symptomatic therapy with emollients + systemic retinoids	Other: Symptomatic therapy; Active external agents, Emollients, systemic retinoids if needed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ichthyosis Area Severity Index (IASI)	Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S)	From Baseline up to 16 weeks
Change in Ichthyosis Area Severity Index (IASI)	Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S)	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transepidermal water loss (TEWL) level change	Change in transepidermal water loss (TEWL) while rebuilding the epidermal barrier of the skin (an indicator of the effectiveness of the therapy). Measured in g/hm2.	From Baseline up to 16 weeks
Transepidermal water loss (TEWL) level change	Change in transepidermal water loss (TEWL) while rebuilding the epidermal barrier of the skin (an indicator of the effectiveness of the therapy). Measured in g/hm2.	52 weeks
Change in the Children's Dermatology Life Quality Index (CDLQI)	increasing The Children's Dermatology Life Quality Index, as an indicator of the effectiveness of therapy. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The CDLQI can also be expressed as a percentage of the maximum possible score of 30.	From Baseline up to 16 weeks
Change in the Children's Dermatology Life Quality Index (CDLQI)	Change in the Children's Dermatology Life Quality Index (CDLQI), as an indicator of the effectiveness of therapy. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The CDLQI can also be expressed as a percentage of the maximum possible score of 30.	52 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 9, 2021
• Last Update Submitted That Met QC Criteria: July 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Netherton syndrome; Biologic therapy; Congenital ichthyosis; Autosomal recessive congenital ichthyosis
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosis; Ichthyosis, Lamellar; Ichthyosiform Erythroderma, Congenital; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: 12269723

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No