The purpose of this trial is to test different doses of the trial medicine (LEO 138559) at treating moderate to severe atopic dermatitis in adults. There will be 4 different doses, that will also be compared to a placebo (a dummy medicine that doesn't contain the active ingredient of LEO 138559). Each participant will be randomly assigned to one of the 4 doses of LEO 138559 or placebo. In all arms, injections of placebo may be used to mask the different doses.

The trial will last up to 36 weeks, including a screening/washout period (up to 4 weeks), a treatment period (16 weeks), and a follow up period (16 weeks). The participants will visit the clinic 17 times. For the first 4 weeks of the treatment period, participants will visit the clinic every week. For the next 12 weeks of the treatment period, participants will visit the clinic every 2 weeks. For the 16 week follow up period, participants will visit the clinic every 4 weeks.

The treatments will be given to the participants by staff at the clinic. They are given as an injection just under the skin.

At each visit the doctor will check the participants atopic dermatitis and if they have had any side effects. Participants will also complete an electronic diary every day about their atopic dermatitis and quality of life.

Inclusion Criteria:

• Signed and dated informed consent has been obtained prior to any protocol related procedures.
• 18-75 years old (both included) at screening (Visit 1).
• Willingness to comply with the clinical trial protocol.
• At screening, diagnosis of atopic dermatitis (AD) as defined by the Hanifin and Rajka (1980) criteria for AD.
  • History of AD for ≥1 year.
• Subjects who have a recent history (within 12 months before screening) with documented inadequate response to treatment with topical corticosteroid(s) (TCS) (±topical calcineurin inhibitor(s) (TCI) as appropriate) or for whom these topical AD treatments are medically inadvisable (e.g. due to important side effects or safety risks).
• Eczema Area and Severity Index (EASI) score ≥12 at screening and ≥16 at baseline.
• validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score ≥3 at screening and baseline.
• Body Surface Area (BSA) of AD involvement ≥10% at screening and baseline.
• Atopic Dermatitis Symptom Diary (ADSD) Worst Itch score (weekly average) ≥4 at baseline.
• A woman of childbearing potential must use a highly effective form of birth control throughout the trial and for at least 18 weeks after last administration of IMP.

Exclusion Criteria:

• Major surgery within 8 weeks prior to screening, or planned inpatient surgery or hospitalization during the trial period.
• Active dermatologic condition that could confound the diagnosis of AD or interfere with assessment of the treatment (e.g. scabies, contact dermatitis, rosacea, urticaria, or psoriasis).
• History of cancer, with the following exceptions:
  • Subjects who have had basal cell carcinoma, localized 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 screening.
  • 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 screening
• History of or current immunodeficiency syndrome.
• History of anaphylaxis following any biologic therapy.
• History of clinically significant infection within 4 weeks prior to baseline which, in the opinion of the investigator, 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.
• Skin infection within 7 days prior to baseline
• Positive HBsAg or positive anti-HCV AND positive HCV RNA at screening.
• History of HIV infection or positive HIV serology at screening.
• Evidence of active or latent tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment.
• ALT or AST level ≥2.0 times the ULN at screening.
• 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 behavior on the C-SSRS Screening version).
• Known or suspected hypersensitivity to any component(s) of the IMP.
• Any disorder at screening and/or baseline, which is not stable in the opinion of the investigator, and could:
  • Affect the safety of the subject throughout the trial.
  • Influence the results of the trial.
  • Impede the subject's ability to complete the trial.
• Any significant abnormal finding at screening and/or baseline which may, in the opinion of the investigator:
  • Put the subject at risk because of their participation in the trial.
  • Influence the results of the trial.
  • Influence the subject's ability to complete the trial.
• Current or recent chronic alcohol or drug abuse, or any other condition associated with poor compliance as judged by the investigator.
• Women who are pregnant or breastfeeding.
• Previous treatment with LEO 138559.
• Previous exposure to fezakinumab (anti-IL-22 Ab).
• Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, corticosteroids (steroid eyedrops and inhaled or intranasal steroids are allowed), or JAK inhibitors within 28 days or 5 half-lives prior to baseline, whichever is longer.
• Use of tanning beds or phototherapy, within 4 weeks prior to baseline.
• Receipt of blood products within 28 days prior to screening.
• Treatment with:
  • Any marketed or investigational biologic agents within 3 months or 5 half-lives, whichever is longer, prior to baseline.
  • Any cell-depleting agents including but not limited to rituximab: within 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is longer.
• Treatment with TCS, TCI, topical PDE-4 inhibitors, topical JAK inhibitors, or other medicated topical treatments within 7 days prior to baseline.
• Receipt of live attenuated vaccines 30 days prior to baseline.
• Treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within the last 4 weeks or 5 half lives prior to randomization, whichever is longer.
• Current participation in any other interventional clinical trial.
• Previously randomized in this clinical trial.
• 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.
• Subjects who are legally institutionalized.