Effects of Tralokinumab in the Skin: an Immunologic and Molecular Investigation

Study Overview
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Brief Summary
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The clinical efficacy of tralokinumab has been demonstrated in the treatment of AD; its MOA however remains insufficiently understood. A better understanding of the mechanisms underlying the clinical effects of tralokinumab would be of great clinical benefit since it may ultimately help us to identify more precisely candidate patients who may benefit from a therapy with tralokinumab.

Detailed Description
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Primary objective: To detect and quantify Tralokinumab in the skin of treated AD patients and concurrently characterize the cellular and molecular changes of the cutaneous and systemic immune response Secondary objectives: Clinical response analysed by SCORAD, IG, DLQI and worst daily pruritus NRS To identify immunologic changes on a cellular and molecular level in the skin and in the blood in correlation with Tralokinumab levels over the treatment course. Changes in the skin barrier function over the treatment course Primary outcome: Detection of Tralokinumab in lesional skin after 16 weeks of treatment in comparison to the begin of the study assessed by mass spectrometry with Parallel Reaction Monitoring (PRM) using the Orbitrap ECLIPSE mass spectrometer Secondary outcome: Clinical response analysed by SCORAD, IG, DLQI and worst daily pruritus NRS Detection and quantification of Tralokinumab levels in skin biopsies and skin swabs using mass spectrometer-based proteomics. Immunologic changes on a cellular and molecular level in the skin (assessed by IMC and mass spectrometer-based proteomics) and in the blood (OLINK targeted proteomics) in correlation with Tralokinumab levels over the treatment course. Changes in skin impedance (as a parameter for barrier changes) measured by NeviSense Levels of free IL-13 in blood serum and in skin biopsies Levels of serum IgE (total, specific) Blood eosinophil counts

Official Title
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Effects of Tralokinumab in the Skin: an Immunologic and Molecular Investigation (TRALIS)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Application of Tralokinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria (patients): Moderate to severe AD EASI < 50 18-65 years old Subject is capable of giving informed consent Signed informed consent Inclusion criteria (Healthy controls): No diagnosis or history of atopic dermatitis 18-65 years old Subject is capable of giving informed consent Signed informed consent Exclusion Criteria: Use of systemic corticosteroids or systemic immunosuppressive/immunomodulating drugs within four weeks prior to start of the study Use of tanning beds or phototherapy within 6 weeks prior to start of the study History of cancer except for treated basal cell or spinal cell carcinoma of the skin Active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection, active or untreated latent tuberculosis. Female patients of childbearing potential who are pregnant or breast feeding or planning a pregnancy during the duration of the trial and/or not practicing acceptable birth control for the duration of the trial Known or suspected non-compliance, drug or alcohol abuse, Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant, Previous enrolment into the current study, Enrolment of the investigator, his/her family members, employees and other dependent persons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-randomized treatment study involving state of the art technique such as imaging mass spectrometry, classical mass spectroscopy and proteomics in patients treated with Tralokinumab during 16 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy arm<br>Healthy controls | |
| Active Comparator: Tralokinumab<br>Patients with AD | Drug: Application of Tralokinumab<br>* 2 Arms 20 patients 5 healthy controls<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Tralokinumab in lesional skin after 16 weeks of treatment | Concentration of Tralokinumab in lesional skin after 16 weeks of treatment in comparison to the begin of the study assessed by mass spectrometry with Parallel Reaction Monitoring (PRM) using the Orbitrap ECLIPSE mass spectrometer | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome analysed by SCORAD | Clinical response analysed by SCORAD (SCORing Atopic Dermatitis, 0-103, higher scores worse outcome) | 2 years | 
| Clinical outcome analysed by IGA | Clinical response analysed by IGA (Investigator Global Assessment, 0-4, higher scores worse outcome) | 2 years | 
| Clinical outcome analysed by DLQI | Clinical response analysed by DLQI (Dermatology Life Quality Index, 0-30, higher scores wose outcome | 2 years | 
| Clinical outcome analysed by worst daily pruritus NRS | Clinical response analysed by worst daily pruritus NRS Numerating Rating Scale, 0-10, higher values worse outcome) | 2 years | 
| Detection and quantification of Tralokinumab levels in skin biopsies | Detection and quantification of Tralokinumab levels in skin biopsies using mass spectrometer-based proteomics | 2 years | 
| Detection and quantification of Tralokinumab levels in skin swabs | Detection and quantification of Tralokinumab levels in skin swabs using mass spectrometer-based proteomics. | 2 years | 
| Immunologic changes on a cellular level in the skin | Immunologic changes on a cellular level in the skin (assessed by IMC and mass spectrometer-based proteomics) in correlation with Tralokinumab levels over the treatment course | 2.5 years | 
| Immunologic changes on a molecular level in the skin | Immunologic changes on molecular level in the skin (assessed by IMC and mass spectrometer-based proteomics) in correlation with Tralokinumab levels over the treatment course. | 2.5 years | 
| Immunologic changes on a cellular and molecular level in the blood | Immunologic changes on a cellular level in the blood (OLINK targeted proteomics) in correlation with Tralokinumab levels over the treatment course. | 2.5 years | 
| Immunologic changes on a molecular level in the blood | Immunologic changes on a molecular level in the blood (OLINK targeted proteomics) in correlation with Tralokinumab levels over the treatment course. | 2.5 years | 
| Changes in skin impendance asessed by NeviSense | Changes in skin impedance (as per parameter for barrier changes) | 2.5 years | 
| Levels of IL-13 in blood serum | Levels of IL-13 in blood serum | 2.5 years | 
| Levels of IL-13 in skin biopsies | Levels of IL-13 in skin biopsies | 2.5 years | 
| Blood eosinophil counts | Eosinophil counts in peripheral blood; normal < 0.4 g/l | 2 years | 
| Levels of total serum IgE | Levels of total serum IgE (kU/l) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tralokinumab