Study of Safety, PK, and Efficacy of Multiple Ascending Doses of HZBio1 in Patients With Gout

Inclusion criteria

• Fully informed and signed the Informed Consent Form (ICF);
• Diagnosed with gout per the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, with a screening serum uric acid (sUA) level ≥7.0 mg/dL, and in a non-acute phase at the time of first dose;
• Aged 18-70 years (inclusive), male or female;
• Body mass index (BMI) ≥18.5 kg/m²;
• Failure to achieve sUA <7.0 mg/dL after ≥8 weeks of standardized treatment with conventional urate-lowering therapy (ULT) (effective doses include but are not limited to: allopurinol ≥300 mg/day, febuxostat ≥40 mg/day, or benzbromarone ≥50 mg/day; investigators may adjust doses based on tolerance and renal/hepatic function) OR contraindication/intolerance to ULT; No use of oral urate-lowering drugs within 1 week prior to randomization;
• Negative serum pregnancy test for women of childbearing potential;
• Agreement by subjects and their partners of childbearing potential to use highly effective contraception or practice abstinence during the study and for 6 months after the last dose;
• Ability to understand and comply with protocol requirements; investigators anticipate completion of the entire study.

Exclusion criteria

• Intolerance to multiple intramuscular injections.
• Known hypersensitivity to the investigational drug, PEG-containing drugs, NSAIDs (e.g., ibuprofen, acetaminophen), or therapeutic protein products (e.g., fresh/frozen plasma, human serum albumin, cytokines, interleukins).
• History of severe allergic reactions or hypersensitivity to foods, inhalants, contact substances, or drugs, or being allergy-prone (multiple drug/food allergies).
• Acute gout flare within 2 weeks prior to baseline.
• History of organ transplantation requiring immunosuppressive therapy.
• Use of prednisone >10 mg/day (or equivalent) within 1 week prior to screening.
• Contraindications to antihistamine use.
• History of severe diseases (digestive, respiratory, urinary, musculoskeletal, neuropsychiatric, hematologic, or immune systems) within 3 months prior to screening.
• New or worsening coronary artery disease or congestive heart failure within 3 months prior to screening, or history of:

• Acute coronary syndrome (e.g., acute myocardial infarction [AMI], unstable angina).
• Coronary interventions (e.g., CABG, PTCA).
• Stroke or transient ischemic attack.
• Uncontrolled hypertension (resting systolic blood pressure [SBP] ≥180 mmHg and/or diastolic blood pressure [DBP] ≥110 mmHg). Exception: Subjects with controlled blood pressure after adjustment of antihypertensives per guidelines may be enrolled if rechecked during screening.
• Severe peripheral vascular disease (e.g., disabling claudication, unhealed ischemic ulcers, or conditions requiring surgery/angioplasty).
• Poorly controlled diabetes (HbA1c >9.0%).
• Vaccination within 1 month prior to baseline or plans to receive non-inactivated vaccines during the study. Note: Inactivated vaccines require a 2-week interval from study drug administration.
• Active malignancy or history of malignancy within 5 years prior to screening (exceptions: basal/squamous cell skin cancer, excised cervical intraepithelial neoplasia, or carcinoma in situ).
• History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD level below the lower limit of normal. Testing sources: Results from the study site, tertiary hospitals, or Guangzhou Kingmed Center for Clinical Laboratory Co., Ltd. are acceptable. Sample disposal: Processed by Guangdong Environmental Living Waste Disposal Center Co., Ltd.
• Laboratory abnormalities:

A. Hemoglobin <10 g/dL. B. Active hepatitis B (HBsAg+ with HBV DNA ≥500 IU/mL or 2500 copies/mL), HCV antibody+, HIV antibody+, or syphilis antibody+ (RPR/TPPA+).

C. White blood cells <3.0×10⁹/L. D. Platelets <75×10⁹/L. E. ALT/AST >3× upper limit of normal (ULN).

• Participation in conflicting clinical trials (device or PEG/uricase-based drugs) within 12 weeks prior to screening.
• Participation in other drug-intervention trials within 4 weeks prior to screening (or within 5 half-lives of the drug).
• Blood donation/loss ≥400 mL or transfusion within 3 months prior to screening (excluding physiological blood loss in females).
• Excessive alcohol consumption (>14 units/week) within 4 weeks prior to screening (1 unit = 285 mL beer [3.5%], 25 mL spirits [40%], or 100 mL wine [10%]).
• History of alcohol/drug abuse within 1 year prior to screening.
• Pregnancy, lactation, or plans for pregnancy during the study.
• Poor compliance (investigator's judgment).
• Major surgery within 8 weeks prior to baseline or planned surgery during the study posing unacceptable risks.
• Any other condition deemed by the investigator to compromise safety, validity, or suitability for the study.