Bridging Study of XKH001 in Healthy Adult Caucasian Participants

The study will consist of two cohorts of healthy adult Caucasian participants. Cohort 1 will receive XKH001 300 mg subcutaneously once every 4 weeks (Q4W) on Day 1, Day 29, and Day 57... Cohort 2 will receive XKH001 600 mg subcutaneously Q4W on Day 1, Day 29, and Day 57. Dosing will be initiated sequentially, with Cohort 1 (300 mg) dosed first, followed by Cohort 2 (600 mg). Dosing in Cohort 2 will not commence earlier than 21 days after the first participant in Cohort 1 receives the first dose and may proceed only following joint review of the available Cohort 1 safety data and unanimous agreement by the Sponsor's medical representative, the Medical Monitor, and the Principal Investigator A total of 16 healthy adult Caucasian participants will be enrolled in the study, with 8 participants per cohort. Within each cohort, participants will be randomised in a 3:1 ratio (6 active drug XKH001; 2 placebo) in a double-blind manner. Randomisation will be performed using a cohort-specific block randomisation schedule to maintain allocation concealment and treatment balance within each cohort. Enrolment will not be stratified by sex; however, at least 3 female participants will be enrolled in each cohort to ensure adequate female representation and to ensure that at least 1 female participant receives the investigational drug.

Inclusion criteria

• Healthy participants who voluntarily provide written informed consent and can comply with all study procedures according to the protocol.
• Male or female participants of Caucasian ethnicity(both biological parents and all four grandparents of Caucasian origin), 18-65 years of age (inclusive).
• Body mass index (BMI) between 18.0-32.0 kg/m² (inclusive).
• 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.
• No use of prescription or over-the-counter medications within 4 weeks prior to first dosing.
• 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

• Pregnant or breastfeeding women.
• Any clinically significant disease within 5 years that could affect participation (gastrointestinal, renal, hepatic, pulmonary, neurology, Haematology, endocrine, oncology, metabolic, psychiatric, or cerebrovascular).
• History of autoimmune disease, known hereditary immunodeficiency, or recurrent infections suggesting immunodeficiency.
• 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.
• Active or latent tuberculosis infection.
• HBsAg positive, HCV antibody positive, syphilis antibody positive, or HIV antigen/antibody positive.
• Live or attenuated vaccine within 4 weeks prior to dosing or planned during trial.
• Participation in any clinical trial within 3 months or 5 half-lives of the investigational drug (whichever is longer) prior to dosing.
• History of allergy to the investigational drug, any formulation component, or protein-based drugs.
• 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).
• Drug abuse or illicit substance use within 5 years, or positive urine drug screen(A positive cotinine result alone is not exclusionary).
• Smoking history (>5 cigarettes/day) within 3 months prior to screening.
• Blood donation or loss >450 mL within 8 weeks, or >200 mL blood donation or >300 mL blood loss within 1 month.
• Unsuitable venous access or intolerance of venipuncture.
• Prior exposure to any anti-IL-25 therapeutic agent, including XKH001 or any other investigational or approved therapeutic agent targeting IL-25.
• Any other reason deemed unsuitable by the investigator.