Effects of Tralokinumab Treatment of Atopic Dermatitis on Skin Barrier Function

Inclusion Criteria:

1. Written informed consent obtained from the subject prior to performing anyprotocol-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 basedon American Academy Criteria
4. Subjects who have a recent history (within 1 year before the screening visit) ofinadequate response to treatment with topical medications. Inadequate response isdefined 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 ofmedium to higher potency (±TCI as appropriate), applied for at least 28 days or forthe maximum duration recommended by the product prescribing information (e.g. 14 daysfor super-potent TCS), whichever is shorter. Subjects with documented systemictreatment for AD in the past year are also considered as inadequate responders totopical treatments and are potentially eligible for treatment with Tralokinumab afterappropriate washout.
5. Eczema Area and Severity Index (EASI) score ≥12 at screening (Week0 minus 7d) andbaseline 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 serumpregnancy test within 7 days prior to start of trial.
8. Female participants who are not capable of bearing children or who use a method ofcontraception that is medically approved by the health authority of the respectivecountry at screening This includes:

• A woman who is not capable of bearing a child is defined as follows:post-menopausal (12 months natural (spontaneous) amenorrhea or 6 monthsspontaneous amenorrhea with serum-FSH-values (follicle-stimulating hormone) of >40 mIU/mL); 6 weeks after a bilateral ovariectomy with or without hysterectomyor sterilization by means of tubal ligation
• A woman capable of bearing child is defined as follows: a woman who isphysiologically capable of becoming pregnant, including women whose occupation,lifestyle or sexual orientation exclude sexual intercourse with a male partnerand women whose partners have been sterilized by vasectomy or other measures.
• Medically-approved methods of contraception can include the following: hormonalcontraceptives or, intrauterine device and double barrier method. Acceptablepreventive measures can include total abstinence at the discretion of theinvestigator, in cases where compliance is ensured because of the studyparticipant's age, occupation, lifestyle or sexual orientation. Periodicalabstinence (e.g. calendar, ovulation, symptothermal methods or abstinence untilthe 4th day after the ovulation) as well as coitus interruptus are not acceptablemethods of contraception.
• A reliable method of contraception (CTFG guideline) must be used for the entireduration of the study.

9. Subject is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations including followup.

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 IMPor participation in another clinical trial with investigational product during thelast 30 days before inclusion or 7 half-lives of previously used trial medication,whichever is longer.
3. Previous enrollment in a Tralokinumab clinical trial.
4. Active dermatologic conditions that may confound the diagnosis of AD or wouldinterfere with assessment of treatment, such as scabies, cutaneous lymphoma, orpsoriasis.
5. Known active allergic or irritant contact dermatitis that is likely to interfere withthe assessment of severity of AD.
6. Subject with mild atopic dermatitis (EASI<12 and IGA<3) or is not a candidate or isnot eligible for Tralokinumab treatment, because of a known or suspected allergy orreaction to any component of the IMP formulation or other possible contraindicationslike trypanophobia
7. Having used immunosuppressive/immunomodulating therapy (Systemicimmunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine,azathioprine, mycophenolate mofetil, Janus kinase inhibitors), systemic corticosteroiduse (excludes topical, inhaled, or intranasal delivery, bleach baths) during any weekwithin the 4 weeks or tanning beds or phototherapy (narrow band ultraviolet B [NBUVB],ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), within 4weeks before the baseline visit
8. Treatment of selected skin areas (non-lesional skin at volar forearm and extensorforearm, lesional skin) with topical corticosteroid or topical calcineurin inhibitor 1week prior to baseline visit and throughout the study.
9. Treatment of skin areas of examination with emollients 24 hours prior to baselinevisit and throughout the study.
10. Involvement in the planning and/or conduct of the study.
11. Dementia or significantly altered mental status that would prohibit the understandingor rendering of information, consent and compliance with the requirements of theprotocol and patients who are legally institutionalized.
12. Pregnancy and breastfeeding are exclusion factors. The effects of Tralokinumab on thedeveloping human fetus are unknown. Enrolled patients must agree to use adequatecontraception prior to study entry, the duration of study participation. Should awoman become pregnant or suspect she is pregnant while she or her partner isparticipating in this study, she should inform her treating physician immediately.
13. Medication that is known to interfere with any of the agents applied in the trial.
14. Receipt of live attenuated vaccines 30 days prior to the date of baseline and duringthe trial including the safety follow-up period. a. Receipt of inactive/killed vaccinations (e.g. inactive influenza) is allowed,provided they are not administered within 5 days before/after any trial visit.
15. Receipt of any marketed biological therapy (i.e. immunoglobulin, anti-IgE) includingdupilumab or investigational biologic agents:
16. Any cell-depleting agents including but not limited to rituximab: within 6 monthsprior to baseline or until lymphocyte count returns to normal whichever islonger.
17. Other biologics: within 3 months or 5 half-lives, whichever is longer prior tobaseline.
18. Receipt of any investigational non-biologic agent within 5 half-lives prior tobaseline.
19. Receipt of blood products within 4 weeks prior to screening.
20. Major surgery within 8 weeks prior to screening, or planned in-patient surgery orhospitalization during the trial period.
21. History of any active skin infection within 1 week prior to baseline.
22. History of a clinically significant infection within 4 weeks prior to baseline which,in the opinion of the investigator or sponsor, may compromise the safety of thesubject in the trial, interfere with evaluation of the IMP, or reduce the subject'sability to participate in the trial. Clinically significant infections are defined as:
23. A systemic infection.
24. A serious skin infection requiring parenteral (intravenous or intramuscular)antibiotics, antiviral, or antifungal medication.
25. History of a helminthic parasitic infection within 6 months prior to the date informedconsent is obtained that has not been treated with, or has failed to respond to,standard of care therapy.
26. History of anaphylaxis following any biological therapy.
27. History of immune complex disease.
28. History of cancer:
29. Subjects who have had basal cell carcinoma, localized squamous cell carcinoma ofthe skin or in situ carcinoma of the cervix are eligible provided that thesubject is in remission and curative therapy was completed at least 12 monthsprior to the date informed consent was obtained.
30. Subjects who have had other malignancies are eligible provided that the subjectis in remission and curative therapy was completed at least 5 years prior to thedate informed consent was obtained.
31. History of tuberculosis requiring treatment within the 12 months prior to screening.Evaluation will be according to local guidelines as per local standard of care.
32. History of any known primary immunodeficiency disorder including a positive humanimmunodeficiency virus (HIV) test at screening, or the subject taking antiretroviralmedications as determined by medical history and/or subject's verbal report.
33. History of chronic alcohol or drug abuse within 12 months prior to screening, or anycondition associated with poor compliance as judged by the investigator.
34. 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 theopinion of the investigator, and could:
35. Affect the safety of the subject throughout the trial.
36. Influence the findings of the trial or their interpretations.
37. Impede the subject's ability to complete the entire duration of trial.
38. Any clinically significant abnormal findings in physical examination, vital signs,hematology or clinical chemistry during the screening period, which in the opinion ofthe investigator, may put the subject at risk because of his/her participation in thetrial, or may influence the results of the trial, or the subject's ability to completeentire duration of the trial.
39. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb),hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology atscreening.
40. Pregnant, breastfeeding, or lactating women.
41. Employees of the trial site or any other individuals directly involved