Clinical trial NCT05378698: Effects of Tralokinumab in the Skin: an Immunologic and Molecular Investigation
Official title: Effects of Tralokinumab in the Skin: an Immunologic and Molecular Investigation (TRALIS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Atopic Dermatitis
Keywords: Tralokinumab
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Hochgebirgsklinik Davos-Wolfgang
First posted: 2022-05-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Concentration of Tralokinumab in lesional skin after 16 weeks of treatment
timeFrame: 2 years
Secondary outcomes:
measure: Clinical outcome analysed by SCORAD
timeFrame: 2 years
measure: Clinical outcome analysed by IGA
timeFrame: 2 years
measure: Clinical outcome analysed by DLQI
timeFrame: 2 years
measure: Clinical outcome analysed by worst daily pruritus NRS
timeFrame: 2 years
measure: Detection and quantification of Tralokinumab levels in skin biopsies
timeFrame: 2 years
measure: Detection and quantification of Tralokinumab levels in skin swabs
timeFrame: 2 years
measure: Immunologic changes on a cellular level in the skin
timeFrame: 2.5 years
measure: Immunologic changes on a molecular level in the skin
timeFrame: 2.5 years
measure: Immunologic changes on a cellular and molecular level in the blood
timeFrame: 2.5 years
measure: Immunologic changes on a molecular level in the blood
timeFrame: 2.5 years
measure: Changes in skin impendance asessed by NeviSense
timeFrame: 2.5 years
measure: Levels of IL-13 in blood serum
timeFrame: 2.5 years
measure: Levels of IL-13 in skin biopsies
timeFrame: 2.5 years
measure: Blood eosinophil counts
timeFrame: 2 years
measure: Levels of total serum IgE
timeFrame: 2 years
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: Allergy Unit, Dept. of Dermatology, Unviersity Hosptial of Zurich
Study officials:
affiliation: University of Zurich
name: Peter Schmid-Grendelmeier, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: