This study aims to evaluate the efficacy and safety of lesigercept in approximately 150 participants with CSU. By enrolling participants with an inadequate response to H1-antihistamines, including those previously treated with omalizumab, this study is expected to provide evidence for the clinical utility of lesigercept and to further characterize its benefit-risk profile in the target participant population.

A total of 150 participants will be randomized in a 2:1 ratio to either the lesigercept or placebo group. The study will proceed with a 12-week treatment period, during which the IP will be administered every 4 weeks for a total of three doses, followed by a 4-week follow-up. In total, participants will be observed for 16 weeks to evaluate efficacy, safety, PK, PD, and immunogenicity.

Inclusion Criteria:

• Chronic spontaneous urticaria for ≥6 months, uncontrolled on 2nd-generation H1-antihistamines (UAS7≥16, ISS7≥8, HSS7≥8).
• Stable dose of 2nd-generation H1-antihistamines for ≥7 days; symptom diary compliance ≥80%.
• Adults 18-75 years; informed consent signed; contraception and pregnancy test requirements for both genders.
• ≥80% adherence to antihistamines during screening.

Exclusion Criteria:

• Any medical or lab findings suggesting risk of worsening co-existing conditions during the study.
• Clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematologic, gastrointestinal, or immunodeficiency disorders that may compromise safety or study results.
• History of malignancy within 5 years (except certain cured skin/cervical cancers) or chronic urticaria with known etiology other than CSU (e.g., inducible urticaria, autoimmune diseases).
• Active or high-risk parasitic infections, chronic/recurrent infections (e.g., TB, HBV, HCV, HIV), or hypersensitivity/anaphylaxis to study drugs or related classes.
• Skin diseases affecting assessments (e.g., atopic dermatitis, psoriasis) or history of drug/alcohol abuse within 6 months.

De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to jieon.lee@yuhan.co.kr.

A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

Beginning 1 year and ending 5 years after all trial endpoints were assessed.

Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to jieon.lee@yuhan.co.kr.