A Study of Efficacy and Safety of TLL-018 in CSU Participants With Inadequate Response to 2nd-generation H1-AHs

Inclusion criteria

• Aged between 18 and 75.
• Diagnosis of CSU refractory to second-generation H1-AH.
• CSU diagnosis for ≥ 6 months.
• The presence of itch and hives despite current use of an approved dose of H1-AH prior to randomization.
• UAS7 score (range 0-42) ≥ 16 and ISS7 (range 0-21) ≥ 8 during 7 days prior to randomization.
• Participants were required to take a stable standard dose of a second generation H1-AH concomitantly according to local guidelines.
• Willing and able to complete UPDD during the study; participants must not have more than one missing UPDD symptom score (either morning or evening) within the 7-day period prior to randomization.
• Evidence of urticaria confirmed by the investigator prior to randomization.
• Women of Child Bearing Potential (WOCBP) should not be pregnant or breastfeeding and the pregnancy test should be negative before randomization.
• Participants and their partners must agree to have adequate barrier contraception during the whole treatment period and at least 90 days after treatment; subjects should avoid the sperm or ovum donation for at least six months after treatment.
• The trial participant understands the informed consent form and voluntarily agrees to participate in the study.

Exclusion criteria

• Participants meeting diagnosis criteria of chronic spontaneous urticaria with the following concomitant diseases cannot be enrolled:

• Progressive or uncontrolled signs or symptoms of renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiovascular, neurologic, psychiatric, or cerebral disease, as judged by the investigator to place the subject at unacceptable risk by study participation.
• Clearly defined underlying etiology for chronic urticarias other than CSU. E.g. induced urticaria, including but not limited to artificial urticaria.
• Any disease, which may have symptoms of urticaria and/or angioedema, including but not limited to urticaria and vasculitis.
• Suffering from other chronic pruritic diseases that may affect the assessment of efficacy, such as psoriasis, atopic dermatitis, etc.
• Previous malignancy, herpes zoster, active tuberculosis.
• Participants with any of the following prior therapies or medications cannot be enrolled:

• Have received treatment with JAK inhibitors (e.g., tofacitinib, baricitinib, ruxolitinib, etc.) or BTK inhibitors (e.g., remibrutinib) within 4 weeks prior to randomization;
• Have received any investigational product within 4 weeks prior to randomization or within 5 elimination half-lives, whichever is longer;
• Have received omalizumab/omalizumab biosimilar treatment within 4 months prior to randomization;
• Have received biologics with potential therapeutic effects for chronic spontaneous urticaria (e.g., dupilumab, etc.) within 3 months prior to randomization or within 5 elimination half-lives, whichever is longer;
• Have received immunosuppressive or immunomodulatory drug therapy within 4 weeks prior to randomization, e.g., systemic corticosteroids, etc.
• Known allergy to any active ingredients or excipients of H1-AH or TLL-018.
• Abnormal laboratory test results that may interfere with the conduct of the study by the assessment from the investigator.
• Any other situation or condition that, in the investigator's judgment, would render the participant unsuitable for study participation.