A Study of Efficacy and Safety of TLL-018 in CSU Participants

This is a randomized, double-blind, single-dummy, placebo-parallel-group, phase 3 study to assess the safety and efficacy of TLL-018 in Moderate-to-Severe Chronic Spontaneous Urticaria (CSU) participants who had an Inadequate Controll to Second Generation H1-antihistamines.

Inclusion criteria

• Aged between 18 and 75.
• Diagnosis of CSU refractory to secomd-generation H1-AH.
• CSU diagnosis for ≥ 6 months.
• The presence of itch and hivese despite current use of an approved dose of H1-AH prior to screening visit.
• UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1).
• 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 for the duration of the study.
• 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 (whether male or female) should 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.

Exclusion criteria

• Participants meeting Chinese Guidelines for Urticaria Diagnosis and Treatment with the following concomitant diseases cannot be enrolled:

• 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 judgment of efficacy results, such as psoriasis, atopic dermatitis, etc.
• Previous malignancy, herpes zoster, active tuberculosis.
• Other symptoms of progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, or cerebral disease.
• Taking part in this study, in the opinion of the investigator, places the patient at unacceptable risk.
• Participants with any of the following prior therapies or concomitant medications cannot be enrolled:

• Have received any study drug within 4 weeks or less than 5 elimination of half-life period before randomization (whichever is longer).
• Have received biological agent within 3 months or 5 elimination of half-life period prior to randomization (whichever is longer).
• Have received immunosuppressive/modulatory drug within 4 weeks before randomization.
• Have received any live vaccine within 2 months before randomization or plan to receive a live vaccine during the study.
• Have experienced major surgery within 4 weeks before randomization, or expected to receive major surgical treatment after enrollment;
• Have donated blood more than 400 ml or received blood transfusion within 3 months prior to the study.
• History of drug or alcohol abuse within 6 months prior to screening.
• Allergy to ingredients or excipients of H1-AH or TLL-018.
• Laboratory test results are abnormal and may interfere the study judged by investigators.
• Participants are not appropriate for participation in any other situation or condition in this study.