Effects of Tralokinumab treatment of atopic dermatitis on skin barrier function (TraSki)

Phase 1

Conditions: Patients with moderate to severe atopic dermatitis
MedDRA version: 20.0Level: PTClassification code 10012438Term: Dermatitis atopicSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2019-000598-22-DE

Lead Sponsor: niversity Hospital Schleswig Holstein, Represented by the Board of Directors which is represented by the chairman

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 16

Inclusion Criteria

1.Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening Evaluations.
2.Age = 18 years at time of study entry.
3.Diagnosis of chronic atopic dermatitis for at least 1 year prior to enrollment based on American Academy Criteria.
4.Subjects who have a recent history (within 1 year before the screening visit) of inadequate response to treatment with topical medications. Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0=clear to 2=mild) despite treatment with a daily regimen of TCS of medium to higher potency (±TCI as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g. 14 days for super-potent TCS), whichever is shorter. Subjects with documented systemic treatment for AD in the past year are also considered as inadequate responders to topical treatments and are potentially eligible for treatment with Tralokinumab after appropriate washout.
5.Eczema Area and Severity Index (EASI) score =12 at screening (Week0 minus 7d) and baseline visit (Week0).
6.Investigator Global Assessment (IGA) =3 at screening and baseline visit.
7.Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
8.Female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at Screening.
9.Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1.Subject is unable to provide written informed consent or comply with the protocol.
2.Concurrent enrolment in another clinical trial where the subject is receiving an IMP or participation in another clinical trial with investigational product during the last 30 days before inclusion or 7 half-lives of previously used trial medication, whichever is longer.
3.Previous enrollment in a Tralokinumab clinical trial.
7.Having used immunosuppressive/immunomodulating therapy.
8.Treatment of selected skin areas (non-lesional skin at volar forearm and extensor forearm, lesional skin) with topical corticosteroid or topical calcineurin inhibitor 1 week prior to baseline visit and throughout the study.
9.Treatment of skin areas of examination with emollients 24 hours prior to baseline visit and throughout the study.
11.Dementia or significantly altered mental status that would prohibit the understanding or rendering of information, consent and compliance with the requirements of the protocol and patients who are legally institutionalized.
14.Receipt of live attenuated vaccines 30 days prior to the date of baseline and during the trial including the safety follow-up period.
15.Receipt of any marketed biological therapy (i.e. immunoglobulin, anti-IgE) including dupilumab or investigational biologic agents:
21.History of a helminthic parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
22.History of anaphylaxis following any biological therapy.
23.History of immune complex disease.
24.History of cancer:
25.History of tuberculosis 26.History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject’s verbal report.
27.History of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator.
28.Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could:
29.Any clinically significant abnormal findings in physical examination, vital signs, hematology or clinical chemistry during the screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the trial, or may influence the results of the trial, or the subject’s ability to complete entire duration of the trial.
30.Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening.
31.Pregnant, breastfeeding, or lactating women.
32.Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial or immediate family members of such individuals.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary Objective: To explore the effect of Tralokinumab treatment on skin barrier function in patients with moderate to severe Atopic Dermatitis (AD). ;Secondary Objective: Secondary Objectives:<br>1.To explore the effect of Tralokinumab treatment on skin irritability of non-lesional skin.<br>2.To explore the effect of Tralokinumab treatment on epidermal differentiation.<br>3.To examine the efficacy of Tralokinumab on severity of AD. <br>Exploratory Objectives:<br>1.To investigate the effect of Tralokinumab treatment on the skin transcriptome.<br>2.To investigate the effect of Tralokinumab treatment on the skin proteome.<br>3.To investigate the effect of Tralokinumab treatment on the skin microbiome.<br>;Primary end point(s): Primary Endpoint: Is the change in transepidermal water loss (TEWL) at one non-lesional and one lesional marker skin area at week 16 (day 112) compared to baseline (day 0).;Timepoint(s) of evaluation of this end point: at week 16 (day 112) compared to baseline (day 0)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints<br>1.Skin irritability: Change in clinical score of sodium lauryl sulfate irritant reaction of non-lesional skin at week 16 compared to baseline.<br>2.Epidermal differentiation: Change of epidermal thickness and epidermal differentiation markers (Keratin 16, Ki67, Filaggrin) of one lesional and one non-lesional marker skin area at week 16 compared to baseline.<br>3.Mean percent change at week 16 from baseline in Eczema Area and Severity Index (EASI).<br>;Timepoint(s) of evaluation of this end point: at week 16 (day 112) compared to baseline (day 0)

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