Urticaria
Conditions
Interventions
Group A:HZ-A-018 50 mg tablet, once daily, orally for 12 consecutive weeks.
Group B:HZ-A-018 75 mg tablet, once daily, orally for 12 consecutive weeks.
Group C:HZ-A-018 100 mg tablet, once daily, orally for 12 consecutive weeks.
Group D :Placebo, once daily, orally for 12 consecutive weeks.
Sponsors
The First People's Hospital of Hangzhou
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 75 years old (inclusive), regardless of gender. 2. Diagnosed with CSU inadequately controlled by second-generation H1 antihistamines at randomization, meeting all of the following criteria: •Confirmed diagnosis of chronic spontaneous urticaria with recurrent episodes for >= 6 months at screening (the duration of CSU episodes is determined by the investigator based on available suporting documents). •Pruritus and wheals persisted for >= 6 weeks prior to screening despite treatment with second-generation H1 antihistamines in accordance with treatment guidelines. •Within 7 days before randomization (Day 1): 7-Day Urticaria Activity Score (UAS7, range: 0–42) >= 16; 7-Day Hive Severity Score (HSS7, range: 0–21) >= 6; 7-Day Itch Severity Score (ISS7, range: 0–21) >= 6. 3. Relevant medical records documenting urticaria within 3 months prior to screening. 4. Willing and able to complete the Urticaria Patient Daily Diary (UPDD) as required throughout the study. 5. No missing entries in the UPDD within 7 days before randomization. 6. Willing to take background medications (mandatory) and rescue medications (when necessary) as specified in the study protocol. 7. Adequate organ function: •White blood cell count >= 3.0×10^9/L; neutrophil count >= 1.5×10^9/L; hemoglobin >= 100 g/L; platelet count >= 100×10^9/L. •Serum creatinine = 60 mL/min (calculated by the Cockcroft-Gault formula). •Alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) <= 1.5×ULN. •International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5×ULN. •Fridericia-corrected QT interval (QTcF) < 470 msec [QTcF = QT/(RR^0.33), where RR is the standardized heart rate (RR = 60/heart rate)]. 8. Female participants of childbearing potential and male participants with reproductive capacity must have no plan to conceive with their partners during the study and within 3 months after treatment discontinuation. They must adopt one of the following effective contraceptive measures throughout the study and for 3 months after treatment cessation: abstinence, barrier contraception (e.g., sterilization, condoms), or hormonal contraceptives initiated at least 3 months prior to the first study drug administration. Male participants are prohibited from sperm donation during treatment and for 3 months after treatment discontinuation. 9. Voluntarily participate in this clinical trial, understand the study procedures, and provide written informed consent.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with HZ-A-018 or other BTK inhibitors. 2. Known history of allergy to any component of the study drug or drugs with similar chemical structures. 3. Chronic inducible urticaria or chronic urticaria with definite triggering factors, including: dermographism, cold urticaria, heat urticaria, solar urticaria, pressure urticaria, delayed pressure urticaria, aquagenic urticaria, cholinergic urticaria or contact urticaria. 4. Other diseases accompanied by urticaria or angioedema symptoms, including but not limited to: urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria or drug-induced urticaria. 5. Large-area tattoos on the body surface that may interfere with UAS7 assessment or wheal counting as judged by the investigator. 6. Other skin diseases accompanied by chronic pruritus that may affect study evaluations as judged by the investigator, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis. 7. Current or history of malignant tumors, except for non-metastatic basal cell carcinoma, cutaneous squamous cell carcinoma or cervical carcinoma in situ with no signs of recurrence after adequate treatment. 8. Progressive or uncontrolled diseases involving cardiac, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, rheumatic and immunological, neurological, psychiatric or other systems (including but not limited to): myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia, uncontrolled hypertension (systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg despite standard antihypertensive treatment) within 12 months prior to screening; asthma or inflammatory bowel disease requiring oral or injectable corticosteroids for acute episodes; or other chronic diseases deemed unsuitable for participation in this trial. 9. High risk of major bleeding, coagulation disorders, or clinically significant gastrointestinal diseases requiring hospitalization or blood transfusion. 10. Use or planned use of the following medications within the specified time windows before randomization or during the study (excluding background and rescue medications): •Biologics for CSU treatment within 4 months (e.g., omalizumab). •Vaccination with live vaccines within 6 weeks prior to screening, or planned live vaccine administration during the study or after the last study drug dose. •Regular use of systemic corticosteroids within 4 weeks (once daily or every other day for consecutive = 5 days). •Use of other immunosuppressants or immunomodulators/extracts within 4 weeks or 5 half-lives (whichever is longer), including but not limited to hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, mycophenolate mofetil, Tripterygium wilfordii, compound glycyrrhizin, BCG polysaccharide and nucleic acid, etc. •Intravenous immunoglobulin administration, plasmapheresis, or transfusion of blood/blood products within 4 weeks. •Participation in other interventional clinical trials (drugs, vaccines, medical devices, etc.) and receipt of interventional treatments within 4 weeks. •Oral administration of traditional Chinese medicines or proprietary Chinese medicines for urticaria (excluding Tripterygium wilfordii and compound glycyrrhizin) within 2 weeks or 5 half-lives (whichever is longer). •Regular use of doxepin hydrochloride within 2 weeks. •Concomitant us
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Security evaluation;Weekly Urticaria Activity Score (UAS7); | — |
Secondary
| Measure | Time frame |
|---|---|
| Weekly Itch Severity Score(ISS7);Weekly Hive Severity Score (HSS7);Weekly Angioedema Activity Score(AAS7);Dermatology Life Quality Index(DLQI);Pharmacokinetic evaluation;Pharmacodynamics evaluation; | — |
Countries
China
Contacts
Public ContactLiming Wu
The First People's Hospital of Hangzhou
Outcome results
None listed