A Non-randomized, Open-label Study to Evaluate the Safety, Kinetics and Efficacy of a Single Intravenous Infusion of ZS801 in Hemophilia B Subjects With Endogenous FIX ≤2%.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of participants with clinically significant change from baseline in physical examination findings
研究概览
简要总结
A non-randomized, open-label study to evaluate the safety, kinetics and efficacy of a single intravenous infusion of ZS801 in hemophilia B subjects with endogenous FIX ≤2%.
详细描述
This study will seek to determine the safety, kinetics and efficacy of a single IV infusion of ZS801.
The dose level is 5.0×10^12vg/kg; Dose addition may occur based on the safety and FIX activity on steady state.
Subjects will provide informed consent and then undergo screening assessments up to 6 weeks prior administration of ZS801. All subjects will undergo 52 weeks safety and efficacy observation. Then subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥18 years and ≤65years of age;
- •Confirmed diagnosis of hemophilia B, and endogenous FIX ≤2%:
- •Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products;
- •The subject had at least 3 or more bleeding events and/or chronic hemophilia arthritis in one or more joints in the previous 1 year requiring treatment with FIX agents;
- •Agree to use reliable barrier contraception and prohibition of sperm donation until 52 weeks after the administration of ZS
- •Subjects voluntarily participate and are fully informed, fully understand the research and can comply with the requirements of the research protocol, are willing to complete the research as planned, and voluntarily cooperate with the provision of biological samples for testing.
排除标准
- •Hypersensitivity to any component of the study drug (including immunosuppressants) or a condition that can not use;
- •Inability to tolerate immunosuppressants or steroid drugs;
- •Have FIX inhibitor as assessed by laboratory; or documented history of FIX inhibitor;
- •Who have a history or are currently suffering from any of the following serious clinical diseases:
- •History of malignancy or current presence of any malignancy;
- •Have active autoimmune disease;
- •Severe heart disease, including angina pectoris, myocardial infarction, heart failure, clinically significant congenital heart disease, heart valve disease, arrhythmia and atrioventricular block, etc.;
- •Have underlying liver disease or history of liver disease (such as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy or hepatic fibrosis);
- •Have HBsAg positive or HCV-Ab positive, or are currently receiving hepatitis B or hepatitis C antiviral therapy;
- •Diabetes mellitus that is poorly controlled after drug treatment;
- •Uncontrolled hypertension or hypotension;
- •laboratory values:
- •Hemoglobin<110g/L;
- •Platelets<100×10^9/L;
- •aspartate aminotransferase, Alanine transaminase, alkaline phosphatase>2×ULN;
- •Total bilirubin>1.5×ULN;
- •Creatinine>ULN;
- •Albumin<LLN;
- •HIV antibody positive or Treponema pallidum antibody positive.
- •Have AAV5 capsid neutralizing antibody titers >1:640;
- •Those who have received clinical trials of gene therapy before screening, or have used FIX clinical trial drugs within 1 month, or participated in other drug/device clinical trials within 3 months, or plan to participate in other clinical trials during this study;
- •Those who have planned surgery within 52 weeks after the infusion;
- •Those who lost more than 400 mL of blood within 3 months before screening;
- •Those with epilepsy, history of mental illness (such as schizophrenia, depression, mania or anxiety) or obvious mental disorder, incapacitated or incapacitated by other reasons;
- •Patients with a history of drug abuse or alcoholism;
- •Investigators believe that subjects have poor compliance or are expected to be less likely to complete follow-up;
- •There are clinically significant diseases or other reasons that the researcher and/or collaborators consider unsuitable to participate in this researcher.
结局指标
主要结局
Number of participants with clinically significant change from baseline in physical examination findings
时间窗: Time Frame: Baseline up to Week 52
Findings will be considered to be clinically significant based on the investigator's decision.
Number of participants with clinical laboratory abnormalities
时间窗: Baseline up to Week 52
Findings were considered to be clinically significant based on the investigator's decision.
Incidence of adverse events
时间窗: Baseline up to Week 52
An adverse event (AE) is any medical occurrence, the event will not relate to the treatment.
Number of participants with clinically significant change from baseline in vital signs
时间窗: Baseline up to Week 52
Vital signs will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion.
Antibody against AAV capsid protein
时间窗: Baseline up to Week 52
Immune response against AAV capsid will be evaluated by measurement of the binding antibody and neutralizing antibody against AAV capsid protein in plasma samples.
次要结局
- Vector-derived FIX:C activity levels(Baseline up to Week 52)
- Vector-derived FIX antigen levels(Baseline up to Week 52)
- Vector shedding of ZS801(Baseline up to Week 52)