A Trial to Evaluate Efficacy, Safety, and Pharmacokinetics of Delgocitinib Cream in Chinese Adults and Adolescents With Moderate to Severe Chronic Hand Eczema

Inclusion Criteria:

1. Age 18 years or above at screening for adult participants and age 12-17 years atscreening and baseline for adolescent participants.

2. Diagnosis of CHE, defined as hand eczema that has persisted for more than 3 monthsor returned twice or more within the last 12 months. Disease severity graded asmoderate to severe at screening and baseline according to IGA-CHE (i.e. an IGA-CHEscore of 3 or 4).

3. HESD itch score (weekly average) of ≥4 points at baseline. The baseline weeklyaverage will be calculated from daily assessments of itch severity during the 7 daysimmediately preceding the baseline visit (Day -7 to Day -1). A minimum of 4 itchscores out of the 7 days is required to calculate the baseline average score.

4. Participants who have a documented recent history of inadequate response totreatment with topical corticosteroids (TCS) (at any time within 1 year before thescreening visit) or for whom TCS are documented to be otherwise medicallyinadvisable (e.g. due to important side effects or safety risks).

• Inadequate response is defined as a history of failure to achieve and maintaina low disease activity state (comparable to an IGACHE score of ≤2) despitetreatment with a daily regimen of TCS of class III-IV (potent to very potent),applied for at least 28 days or for the maximum duration recommended by theproduct prescribing information, whichever is shorter.

• Important side effects or safety risks are those that outweigh the potentialtreatment benefits and include intolerance to treatment, hypersensitivityreactions, and significant skin atrophy as assessed by the physician.

5. Participants adherent to standard non-medicated skin care including avoidance ofknown and relevant irritants and allergens.

6. A woman of childbearing potential (WOCBP) must use an acceptable method of birthcontrol throughout the trial up until the last application of investigationalmedicinal product (IMP).

Exclusion Criteria:

1. Active atopic dermatitis (AD) requiring medical treatment in regions other than thehands and feet.

2. Hyperkeratotic hand eczema in combination with a history of psoriasis on any part ofthe body.

3. Clinically significant infection (e.g. impetiginized hand eczema) on the hands.

4. Clinically significant infection within 28 days prior to baseline which, in theopinion of the investigator, may compromise the safety of the participant in thetrial, interfere with evaluation of the investigational medicinal product (IMP), orreduce the participant's ability to participate in the trial. Clinically significantinfections are defined as:

• A systemic infection.

• A serious skin infection requiring parenteral (intravenous or intramuscular)antibiotics, antiviral, or antifungal medication.

5. History of any known primary immunodeficiency disorder including a positive humanimmunodeficiency virus (HIV) test at screening, or the participant takingantiretroviral medications as determined by medical history and/or participant'sverbal report.

6. History of cancer:

• Participants who have had basal cell carcinoma, localized squamous cellcarcinoma of the skin or in situ carcinoma of the cervix are eligible providedthat the participant is in remission and curative therapy was completed atleast 12 months prior to screening.

• Participants who have had other malignancies are eligible provided that theparticipant is in remission and curative therapy was completed at least 5 yearsprior to screening.

7. Any disorder which is not stable and could:

• Affect the safety of the participant throughout the trial.

• Impede the participant's ability to complete the trial. Examples include butare not limited to cardiovascular, gastrointestinal, hepatic, renal,neurological, musculoskeletal, infectious, endocrine, metabolic, hematologic,immunological, and psychiatric disorders, and major physical impairment.

8. Any abnormal finding which may:

• Put the participant at risk because of their participation in the trial.

• Influence the participant's ability to complete the trial. The abnormal findingmust be clinically significant and observed during the screening period.Examples include abnormal findings in physical examination, vital signs, ECG,hematology, clinical chemistry, or urinalysis.

9. Positive hepatitis B surface antigen or hepatitis C virus antibody serology atscreening.

10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0×ULN atscreening.

11. Known or suspected hypersensitivity to any component(s) of the IMP.

12. Systemic treatment with immunosuppressive drugs (e.g. methotrexate, cyclosporine,azathioprine), immunomodulating drugs, retinoids (e.g. alitretinoin), traditionalChinese medicines (TCMs) (including herbals), or corticosteroids within 28 daysprior to baseline (steroid eyedrops and inhaled or intranasal steroids correspondingto up to 1 mg prednisolone for allergic conjunctivitis, asthma, or rhinitis areallowed).

13. Use of tanning beds, phototherapy (e.g. UVB, UVA1, PUVA), or bleach baths on thehandswithin 28 days prior to baseline.

14. Previous or current treatment with Janus Kinase (JAK) inhibitors (includingdelgocitinib/LEO 124249),systemic or topical.

15. Cutaneously applied treatment with immunomodulators (e.g. PDE-4 inhibitors,pimecrolimus, tacrolimus), TCMs (including herbals), or TCS on the hands within 14days prior to baseline.

16. Use of systemic antibiotics or cutaneously applied antibiotics on the hands within 14 days prior to baseline.

17. Other transdermal or cutaneously applied therapy on the hands (except for the use ofparticipant's own emollients) within 7 days prior to baseline.

18. Cutaneously applied treatments in regions other than the hands, which couldinterfere with clinical trial evaluations or pose a safety concern within 7 daysprior to baseline.

19. Treatment with any marketed biological therapy or investigational biologic agents (including immunoglobulin, anti-IgE, and dupilumab):

• Any cell-depleting agents including but not limited to rituximab: within 6 monthsprior to baseline, or until lymphocyte count returns to normal, whichever is longer.

• Other biologics: within 3 months or 5 half-lives, whichever is longer, prior tobaseline.

20. Treatment with any non-marketed drug substance (that is, an agent that has not yetbeen made available for clinical use following registration) within the last 28 daysprior to baseline or 5 half-lives, whichever is longer.

21. Major surgery within 8 weeks prior to screening, or planned in-patient surgery orhospitalization during the trial period.

22. Current participation in any other interventional clinical trial.

23. Previously randomized in this clinical trial.

24. Concurrent skin diseases on the hands, e.g. tinea manuum.

25. Active psoriasis on any part of the body.

26. Current or recent chronic alcohol or drug abuse, or any other condition associatedwith poor compliance as judged by the investigator.

27. Employees of the trial site, or any other individuals directly involved with theplanning or conduct of the trial, or immediate family members of such individuals.

28. Participants who are legally institutionalized.

29. Women who are pregnant or lactating.