A Multicenter, Open-Label, Dose-Escalation and Expansion Phase Ib/II Study to Evaluate the Safety, PK, and PD of Multiple Ascending Doses of HZBio1 in Patients With Gout
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
Study YDHY (HZBio1)-001 (Ib/Ⅱ) is an open-label, dose-escalation and expansion, multicenter Phase Ib/II clinical trial conducted in China. The primary objectives were to evaluate the safety, tolerability, and PK of multiple-dose administration of HZBio1. The secondary objectives were to preliminarily explore the PD and immunogenicity of multiple-dose administration of HZBio1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase 1b: HZBio1 3 mg
Participants receive HZBio1 at doses of 3 mg every two weeks for a total of six doses
干预措施: Phase 1b: HZBio1 3mg (Drug)
Phase 1b: HZBio1 6 mg
Participants receive HZBio1 at doses of 6 mg every two weeks for a total of six doses
干预措施: Phase 1b: HZBio1 6mg (Drug)
Phase 1b: HZBio1 12 mg
Participants receive HZBio1 at doses of 12 mg every two weeks for a total of six doses
干预措施: Phase 1b: HZBio1 12mg (Drug)
Phase 2: HZBio1 6 mg
Participants receive intramuscular injections of HZBio1 at 6 mg every two weeks. Participants receive a total of 14 administrations.
干预措施: Phase 2: HZBio1 6mg (Drug)
Phase 2: HZBio1 9 mg
Participants receive intramuscular injections of HZBio1 at 9 mg every two weeks. Participants receive a total of 14 administrations.
干预措施: Phase 2: HZBio1 9mg (Drug)
Phase 2: HZBio1 12 mg
Participants receive intramuscular injections of HZBio1 at 12 mg every two weeks. Participants receive a total of 14 administrations.
干预措施: Phase 2: HZBio1 12mg (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs)
时间窗: 10 weeks
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
次要结局
未报告次要终点