Optimization of Cyclosporin in Atopic Dermatitis Through Multiomic Predictive Models of Treatment Response

Study Overview
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Brief Summary
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This is a low-intervention phase IV trial. The main objective is to optimize the treatment of patients with moderate-severe atopic dermatitis who require systemic treatment.

Detailed Description
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Primary outcome is the percentage of patients with primary non- response to treatment with cyclosporin. Defined as fail to achieve EASI-75 (a 75% improvement in EASI score) at week 16 of follow-up. A 12-month recruitment period is planned and about of 100 patients with moderate-severe atopic dermatitis will be recruited. The study is divided into two cohorts. All patients diagnosed with moderate-severe atopic dermatitis who are going to receive treatment with cyclosporin in the Dermatology Service of La Paz University Hospital and associated Specialty Centers are selected in cohort 1. Patients will receive the starting dose used in routine clinical practice. All patients diagnosed with moderate-severe atopic dermatitis who are receiving or have received cyclosporin therapy in the Dermatology Service of La Paz University Hospital and associated Specialty Centers are selected in cohort 2.

Official Title
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Optimization of Cyclosporin Therapy in Atopic Dermatitis Through Multiomic Predictive Models of Treatment Response (DermAtOmics)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Cyclosporin A
* Other: Follow-up of Cyclospoin treatment already started


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Subjects diagnosed with moderate-severe atopic dermatitis who are going to receive treatment with cyclosporine. Participants must be willing and able to provide written informed consent prior the initiation of any study procedures. For children, parent/legal guardian must provide written informed consent. If age >11 years old, the minor must give assent. Participant is willing and able to adhere to the procedures specified in this protocol. Cohort 2: Subjects diagnosed with moderate-severe atopic dermatitis who are receiving or have received in the past treatment with cyclosporine. Participants must be willing and able to provide written informed consent prior the initiation of any study procedures. For children, parent/legal guardian must provide written informed consent. If age >11 years old, the minor must give assent. Participant is willing and able to adhere to the procedures specified in this protocol. Exclusion Criteria: Subjects participating in a clinical trial in the last three months. Any condition or situation precluding or interfering the compliance with the protocol. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day 0. Women of childbearing potential must commit not to become pregnant. They must be willing to use highly effective contraceptive methods or have practiced sexual abstinence during the study. Highly effective contraceptive methods include oral, intravaginal, or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner and sexual abstinence.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Non-randomized clinical trial. The intervention consists in additional follow-up visits out of usual clinical practice. According to RD 1090/2015 of December 4, which regulates clinical trials with drugs, it is considered a low level intervention clinical.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Start of Cyclosporin treatment<br>Patients will receive the starting dose used in routine clinical practice (maximum dose of 3 mg/kg/day is standard practice in our center). Once the patient is included in the clinical trial their therapeutic management will be carried out according to usual clinical practice, but additional procedures will be performed: The frequency of follow-up visits will be increased in order to collect data related to clinical efficacy, safety and quality of life; Biological samples will be obtained (blood and urine) for biochemical, kinetic, pharmacogenetic and immunological biomarker analysis to identify variables associated to CsA treatment. | Drug: Cyclosporin A<br>* Once the patient is included in the clinical trial their therapeutic management will be carried out according to usual clinical practice, but additional procedures will be performed: The frequency of follow-up visits will be increased in order to collect data related to clinical efficacy, safety and quality of life; Biological samples will be obtained (blood and urine) for biochemical, kinetic, pharmacogenetic and immunological biomarker analysis to identify variables associated to CsA treatment.<br>* Other names: Prospective;|
| Other: Receiving or received cyclosporin<br>If the patient is receiving cyclosporine therapy, a blood sample for pharmacogenetic analysis will be obtained at screening; also, at discretion of the treating physician, biological samples will be obtained (blood and urine) in this visit and in the follow-up visits to assess biochemical and kinetic variables. Clinical data (scales) will be collected from clinical records from treatment start until study inclusion and prospectively after study inclusion. If the patient received cyclosporine previously but is no longer under CsA therapy, a blood sample will be extracted at screening for pharmacogenetic analysis. Clinical data (scales) will be collected from clinical records. | Other: Follow-up of Cyclospoin treatment already started<br>* If the patient is receiving cyclosporine therapy, a blood sample for pharmacogenetic analysis will be obtained at screening; also, at discretion of the treating physician, biological samples will be obtained (blood and urine) in this visit and in the follow-up visits to assess biochemical and kinetic variables. Clinical data (scales) will be collected from clinical records from treatment start until study inclusion and prospectively after study inclusion. If the patient received cyclosporine previously but is no longer under CsA therapy, a blood sample will be extracted at screening for pharmacogenetic analysis. Clinical data (scales) will be collected from clinical records.<br>* Other names: Ambispective;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with primary non-response to treatment with cyclosporine. | Fail to achieve EASI-75 (a 75% improvement in EASI score) | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving EASI-75 | Fail to achieve EASI-75 (a 75% improvement in EASI score) | week 6 | 
| Percentage of patients reaching EASI-90 | Percentage of patients reaching 90 percentage (EASI-90) improvement from baseline during follow-up | through study completion, an average of 1 year | 
| Time to treatment failure after week 16 | Time to treatment failure with cyclosporine defined as EASI ≤ 50 during follow-up after week 16. | Week 24, week 32, week 40, week 48. | 
| Mean percentage of change in EASI score | Mean percentage of change in EASI score from baseline to week 16 | Week 16 | 
| Percentage of change in SCORAD | The Scoring of Atopic Dermatitis (SCORAD) is the score of the severity of atopic dermatitis. It includes the evaluation of the affected areas. The intensity of the lesions and the subjective symptoms of the patient. Classifies AD as Mild >25, Moderate 25-50, and Severe >50 | Week 16 | 
| improvement of at least 75% in SCORAD | Percentage of patients experiencing an improvement of at least 75% in SCORAD from the baseline value | through study completion, an average of 1 year | 
| Change of IGA | Investigator Global Assessment (IGA) is a simple objective measure providing an overall evaluation. It uses a 5-point scale (clear=0; almost clear=1; mild=2; moderate=3; severe=4). | week 16 | 
| Time to IGA score of 0/1 | Time to IGA score of 0/1 (clear or almost clear) | through study completion, an average of 1 year | 
| Change of BSA | Change of BSA (Body surface area) involment | week 16 | 
| Change in NRS | NRS (Numerical Rating Scale) is a numerical scale that measures the intensity of pruritus, with 10 being the greatest intensity | week 16 | 
| Change in POEM | The Patient-Oriented Eczema Measure (POEM) is a validated tool in which the patient self-assesses how many days they experienced seven distinct items (itch, sleep disturbance, bleeding, weeping/oozing, cracking, flaking, dryness of the skin) during a period of 1 week. The maximum score is 28 points. | week 16 | 
| Change in DLQI | Dermatology Life Quality Index is a validated and widely used 10-item questionnaire with paediatric versions (0-3 and 4-16 years). A variation of 4 points is considered a clinically meaningful endpoint. | week 16 | 
| Percentage of patients having a variation of 4 points in their improvement in DLQI | Dermatology Life Quality Index is a validated and widely used 10-item questionnaire with paediatric versions (0-3 and 4-16 years). A variation of 4 points is considered a clinically meaningful endpoint. | through study completion, an average of 1 year | 
| Rate of adverse events associated to CsA treatment | Any untoward medical occurrence in a patient or clinical trial participant, which does not necessarily have a causal relationship with the research procedures or the investigational medicinal product | through study completion, an average of 1 year |