Evaluation of the Effectiveness and Safety of Immunosuppressive and Biological Therapy of Atopic Dermatitis in Childhood

This comparative study analyzes the efficacy and safety of treatment of children from 6 years of age suffering from moderate to severe atopic dermatitis using an inhibitor of IL4, IL13 and classical immunosuppressants.

Study Overview

• Status: Not yet recruiting
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Methotrexate therapy; Drug: Mycophenolate mofetil therapy; Drug: Cyclosporine therapy; Drug: Dupilumab therapy

Detailed Description

This is a prospective study aimed at direct comparative analysis of the efficacy and safety of treatment of children from 6 years of age suffering from moderate and severe atopic dermatitis using a genetically engineered biological drug and classical immunosuppressants.

Based on clinical and anamnestic data, compliance with the inclusion / exclusion criteria, the study included 160 patients from 6 years old, with moderate / severe atopic dermatitis.

The initial indices were assessed: SCORAD- Scoring of Atopic Dermatitis (index for assessing the severity of atopic dermatitis); NRS- numeric rating scale for itch; CDLQI - The Children's Dermatology Life Quality Index; POEM- Patient-Oriented Eczema Measure (personalized assessment of eczema) and laboratory parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, total bilirubin, direct bilirubin, serum albumin, blood urea specific IgE to food and household allergens, indicators of a clinical blood test, indicators of a general analysis of urine, indicators of a biochemical analysis of urine (creatinine, urea).

In the presence of concomitant allergic pathology (bronchial asthma, allergic rhinitis), the CSMS [Combined Symptom and Medication Score] were additionally assessed (Scale for assessing nasal symptoms of rhinitis, taking into account the need for medication); VAS - Visual Analog Scale (visual analog scale); ACT- Asthma Control Test. Subsequently, systemic therapy was prescribed: metorexat (40 people), mycophenolate mofetil (40 people), cyclosporine (40 people) dupilumab (40 people).

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119296
    • National Medical Research Center for Children's Health
    • Contact: Nikolay Murashkin, DMS; Phone Number: +79184951122; Email: m_nn2001@mail.ru
    • Principal Investigator: Mariam Edwardovna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age over 6 years inclusive;
2. Atopic dermatitis diagnosed at least 12 months before the start of the study;
3. Atopic dermatitis of moderate or severe course;

4. Consent to discontinue the use of the following prohibited drugs or any of the following therapies at least 4 weeks before the start of the study and not to use them throughout the study, unless otherwise specified below:

   1. Oral systemic corticosteroids;
   2. Other systemic immunosuppressive drugs;
   3. Phototherapy, including therapeutic phototherapy (psoralen plus ultraviolet A, ultraviolet B), excimer laser, and self-medication using a tanning bed;
5. A signed and dated informed consent received from the patient's parents (guardians), as well as from a patient over 14 years of age, to participate in the study.
6. Ability to attend control visits within the specified time frame

Exclusion Criteria:

1. Use of other genetically engineered biological preparations in therapy;
2. Participation in other clinical trials;
3. The presence of other concomitant skin diseases in the present or in the past, which could affect the assessment of the effect of the study drugs on the course of atopic dermatitis;
4. The presence of herpetic eczema within 12 months before the start of the study;
5. A history of two or more cases of herpetic eczema;
6. The presence in the present of a skin infection for which is required or is being treated with antibiotics for topical use or systemic antibiotics;

7. Therapy with the following drugs:

   1. Other genetically engineered biological preparations less than 5 half-lives before the start of the study.
   2. Any corticosteroid for oral and parenteral administration and administration, which were in therapy for 2 weeks before enrollment in the study, or the possible need for parenteral injection of corticosteroids during the course of the study.
   3. Intra-articular corticosteroid injection within 2 weeks prior to study enrollment; Note: The use of intranasal or inhaled steroids is permitted throughout the study.
8. Extensive or complete disability, significantly limiting personal care or determining the inability to carry it out.
9. Immunodeficiency disease;
10. The presence in the past or present of any serious and / or unstable disease, which, in the opinion of the investigator, may pose an unacceptable risk to the patient in the case of the use of the investigational drug or interfere with the interpretation of the data;
11. History of lymphoproliferative disease; or manifestations or symptoms suggesting the possible presence of lymphoproliferative disease, including lymphadenopathy or splenomegaly; either primary or recurrent malignant disease in active form; or remission after a clinically significant malignant disease lasting less than 5 years;
12. The course of a viral, bacterial, fungal or parasitic infection;
13. Failure or unwillingness of the patient or patient's parent / caregiver / patient legal guardian to comply with the requirements of research participants throughout the study and / or unwillingness to follow research restrictions / procedures, including the use of data loggers.
14. Contraindications to the use of adrenaline.

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: Group №1: Methotrexate therapy	Drug: Methotrexate therapy; Methotrexate subcutaneously 10-15 mg/m2 once every 7 days within 12 months
Experimental: Group №2: Mycophenolate mofetil therapy	Drug: Mycophenolate mofetil therapy; Mycophenolate mofetil per os 500-700 mg/m2 2 times a day within 12 months
Experimental: Group №3: Cyclosporine therapy	Drug: Cyclosporine therapy; Cyclosporine per os 3 mg/m2 2 times a day within 12 months
Experimental: Group №4: Dupilumab therapy	Drug: Dupilumab therapy; Patients weighing <30 kg received an initial dose of 600 mg (2 injections of 300 mg subcutaneously), then 300 mg every 4 weeks. Patients weighing 30 to <60 kg received an initial dose of 400 mg (2 injections of 200 mg subcutaneously), then 200 mg every 2 weeks; Patients weighing 60 kg or more, the initial dose is 600 mg (2 injections of 300 mg subcutaneously), then 300 mg every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SCORAD (Scoring of Atopic Dermatitis)	change of the SCORAD index	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
NRS (Numeric rating scale for itch)	change of the NRS	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
Adverse events	Adverse events monitoring	screening (baseline), 3, 4, 6 and 12 months from the start of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDLQI (The Children's Dermatology Life Quality Index)	change of the CDLQI	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
POEM (Patient-Oriented Eczema Measure)	change of the POEM	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
CSMS (Combined Symptom and Medication Score)	change of the CSMS	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
VAS (Visual Analog Scale)	change of the VAS	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
ACT (Asthma Control Test)	change of the ACT	screening (baseline), 3, 4, 6 and 12 months from the start of therapy
Concentration in the biochemical blood test of total IgE and specific IgE for food and household allergens	change in the Concentration in the biochemical blood test of total IgE, specific IgE-method ImmunoCap to food and household allergens	screening (baseline), 3, 4, 6 and 12 months from the start of therapy

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): November 25, 2021
• Primary Completion (Anticipated): July 25, 2023
• Study Completion (Anticipated): July 25, 2023

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Methotrexate; dupilumab; Glucocorticoids; Cyclosporine; Biologic Drugs
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Reproductive Control Agents; Antitubercular Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antibiotics, Antitubercular; Calcineurin Inhibitors; Methotrexate; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 04532781

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