Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 2 (ECZema TRAlokinumab Trial no. 2)

Exclusion Criteria

• •1. Concurrent enrolment in another clinical trial where the subject is receiving an IMP.
• •2. Previous randomisation in tralokinumab trials.
• •3. Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or psoriasis.
• •4. Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
• •5. Use of tanning beds or phototherapy (narrow band ultraviolet B \[NBUVB\], ultraviolet B \[UVB\], ultraviolet A1 \[UVA1\], psoralen + ultraviolet A \[PUVA\]), within 6 weeks prior to randomisation.
• •6. Treatment with the following medications within 4 weeks prior to randomisation:
• •* Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, Janus kinase inhibitors etc.).
• •* Systemic corticosteroid use (excludes topical, inhaled, or intranasal delivery).
• •* Three or more bleach baths during any week within the 4 weeks.
• •7. Treatment with the following medications within 2 weeks prior to randomisation
• •* TCS.
• •* TCI.
• •* Topical PDE 4 inhibitor.
• •8. Initiation of treatment of AD with prescription emollients or emollients containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (subjects may continue using stable doses of such emollients if initiated before the screening visit).
• •9. Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the trial including the safety follow-up period.
• •• Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed, provided they are not administered within 5 days before/after any study visit.
• •10. Receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent, including dupilumab:
• •* Any cell-depleting agents including but not limited to rituximab: within 6 months prior to randomisation, or until lymphocyte count returns to normal, whichever is longer.
• •* Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to randomisation.
• •11. Receipt of any investigational non-biologic agent within 5 half-lives prior to randomisation.
• •12. Receipt of blood products within 4 weeks prior to screening.
• •13. Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period.
• •14. Known or suspected allergy or reaction to any component of the IMP formulation.
• •15. History of any active skin infection within 1 week prior to randomisation.
• •16. History of a clinically significant infection within 4 weeks prior to randomisation which, in the opinion of the investigator or sponsor's medical expert, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as:
• •* a systemic infection.
• •* a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.
• •17. A helminth 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.
• •18. History of anaphylaxis following any biologic therapy.
• •19. History of immune complex disease.
• •20. History of cancer:
• •* Subjects who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
• •* Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• •21. Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care.
• •22. 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.
• •23. 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.
• •24. History of attempted suicide or is at significant risk of suicide (either in the opinion of the investigator or defined as a "yes" to suicidal ideation questions no. 4 or 5 or answering "yes" to suicidal behaviour on the Columbia-Suicide Severity Rating Scale \[C-SSRS\] Screening version).
• •25. Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could:
• •* Affect the safety of the subject throughout the trial.
• •* Influence the findings of the trial or their interpretations.
• •* Impede the subject's ability to complete the entire duration of trial.
• •26. Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis 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.
• •27. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the ULN (upper limit of normal) at screening.
• •28. 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. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.
• •29. Subjects who are not willing to abstain from donating blood and/or plasma from the time of informed consent and for 16 weeks (5 half-lives) after last dose of IMP.
• •30. Subjects who are legally institutionalised.
• •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.