This is a clinical study in adult participants with moderate to severe atopic dermatitis (AD).

The purpose of the study is to test a new medicine (LEO 138559) given by injection to see if it works to treat AD and what the side effects are when compared with a placebo injection with no medical ingredient.

The study will last up to 36 weeks for each participant. The study will include a treatment period of 16 weeks, during which the participants will receive the injections, followed by a period of 16 weeks without treatment with the main purpose of continuing safety evaluations. The participants will regularly visit the clinic for tests and the study doctor will evaluate their AD. The participants will also be asked to answer questions about their AD symptoms and quality of life.

Inclusion Criteria:

• 18-64 years old (both included) at screening.
• Diagnosis of atopic dermatitis (AD) (as defined by the American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year prior to screening.
• Subjects who have a recent history (within 6 months before screening) of inadequate response to treatment with topical medication, or for whom topical treatments are otherwise medically inadvisable.
• 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.
• Worst Daily Pruritus Numeric Rating Scale (NRS, weekly average) of ≥3 points at baseline.

Exclusion Criteria:

• Treatment with systemic immunosuppressive/immunomodulating medication, immunoglobulin/blood products, or phototherapy within 4 weeks or 5 half-lives prior to randomization, whichever is longer.
• Treatment with biologics within 5 half-lives (if known) or 16 weeks prior to randomization, whichever is longer.
• Treatment with topical corticosteroid(s) (TCS), topical calcineurin inhibitor(s) (TCI), topical phosphodiesterase-4 (PDE-4) inhibitor, or other topical prescription treatments within 1 week prior to randomization.
• Treatment with a live (attenuated) vaccine within 12 weeks prior to randomization.
• Clinically significant active chronic or acute infection requiring systemic treatment within 4 weeks prior to randomization that may compromise the safety of the subject.
• Skin infection within 1 week prior to the baseline visit.
• Presence of hepatitis B or C infection at screening.
• History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
• Participant has a positive or indeterminate test for tuberculosis at screening.
• Participant is pregnant or lactating.