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

Phase 2

Not yet recruiting

• Conditions: Atopic Dermatitis
• Interventions: Drug: Application of Tralokinumab

• Registration Number: NCT05378698
• Lead Sponsor: University of Zurich

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

Study Timeline

• Study First Submitted: 2022-02-17
• Status Verified: 2022-05
• Study First Submitted QC: 2022-05-13
• Last Update Submitted: 2022-05-13
• Study First Posted: 2022-05-18
• Last Update Posted: 2022-05-18
• Study Start: 2022-06
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tralokinumab	Application of Tralokinumab	Patients with AD

Primary Outcome Measures

Name	Time	Method
Concentration of Tralokinumab in lesional skin after 16 weeks of treatment	2 years	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Allergy Unit, Dept. of Dermatology, Unviersity Hosptial of Zurich; 🇨🇭 Zürich, Switzerland