Bridging Study of XKH001 in Healthy Adult Caucasian Participants

This is a Phase Id, randomised, double-blind, placebo-controlled, multiple-dose, bridging study conducted at a single Phase I clinical research unit in Australia. The study is designed to evaluate the pharmacokinetics, safety, tolerability, and immunogenicity of XKH001 following repeated subcutaneous administration in healthy adult Caucasian participants, and to provide an ethnic-bridging pharmacokinetic comparison with the prior Phase I dataset in Chinese participants, required for XKH001's global development programme.

Inclusion Criteria: 1. Healthy participants who voluntarily provide written informed consent and can comply with all study procedures according to the protocol. 2. Male or female participants of Caucasian ethnicity(both biological parents and all four grandparents of Caucasian origin), 18-65 years of age (inclusive). 3. Body mass index (BMI) between 18.0-32.0 kg/m² (inclusive). 4. Vital signs, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) within normal limits or considered not clinically significant by the investigator, with QTcF ≤450 ms. 5. No use of prescription or over-the-counter medications within 4 weeks prior to first dosing. 6. Participants must meet the sex- and reproductive-status-specific contraception and gamete-donation requirements specified in Appendix 2. Where contraception is required, the participant must agree to use the protocol-specified established effective contraception from the time of signing the informed consent form until 7 months after the last dose of study drug. Exclusion Criteria: 1. Pregnant or breastfeeding women. 2. Any clinically significant disease within 5 years that could affect participation (gastrointestinal, renal, hepatic, pulmonary, neurology, Haematology, endocrine, oncology, metabolic, psychiatric, or cerebrovascular). 3. History of autoimmune disease, known hereditary immunodeficiency, or recurrent infections suggesting immunodeficiency. 4. Active infection requiring hospitalisation or IV antibiotics within 3 months, or clinically symptomatic bacterial, viral, or fungal infection within 4 weeks prior to first dosing. 5. Active or latent tuberculosis infection. 6. HBsAg positive, HCV antibody positive, syphilis antibody positive, or HIV antigen/antibody positive. 7. Live or attenuated vaccine within 4 weeks prior to dosing or planned during trial. 8. Participation in any clinical trial within 3 months or 5 half-lives of the investigational drug (whichever is longer) prior to dosing. 9. History of allergy to the investigational drug, any formulation component, or protein-based drugs. 10. Alcohol consumption \>14 units/week within 6 weeks prior to screening, or alcohol-containing products within 1 day before dosing (1 unit = 8 g or 10 mL of pure alcohol). 11. Drug abuse or illicit substance use within 5 years, or positive urine drug screen(A positive cotinine result alone is not exclusionary). 12. Smoking history (\>5 cigarettes/day) within 3 months prior to screening. 13. Blood donation or loss \>450 mL within 8 weeks, or \>200 mL blood donation or \>300 mL blood loss within 1 month. 14. Unsuitable venous access or intolerance of venipuncture. 15. Prior exposure to any anti-IL-25 therapeutic agent, including XKH001 or any other investigational or approved therapeutic agent targeting IL-25. 16. Any other reason deemed unsuitable by the investigator.