A Phase 1/2 Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- FIX:C Antigen Level at Steady State
研究概览
简要总结
A multicenter, open, non-randomized, phase I/II, two-phase clinical study. The dose exploration phase was phase I, and the dose extension phase was phase II.
详细描述
Hemophilia B is a genetic bleeding disorder caused by pathogenic variants (eg, mutations, deletion) in the FIX gene. HB patients have frequent and potentially life-threatening bleeding and often develop progressive physical disability and pain from chronic haemarthropathy. Current replacement therapy needs regular treatment in the life-long time, bringing heavy economic and social burdens.
VGB-R04 is a novel AAV vector carrying a high specific activity factor IX variant. This study is intended to evaluate the safety, tolerability and efficacy of a single IV infusion of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 6 weeks before administration of VGB-R04. All subjects will undergo 52 weeks of safety observation and will be encouraged to enroll in an Long-term follow-up study to evaluate the long-term safety of VGB-R04 for a total of five years.
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 (baseline FIX activity ≤ 2% of normal);
- •At least 100 days exposure history to FIX;
- •Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
- •Have acceptable laboratory values:
- •Hemoglobin ≥110 g/L;
- •Platelets ≥100×109 /L;
- •AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
- •Bilirubin ≤3× ULN ;
- •Creatinine ≤1.5× ULN.
- •No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
- •Agree to use reliable contraception until 2 consecutive samples are negative for vector sequences;
排除标准
- •Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to:
- •Preexisting diagnosis of portal hypertension;
- •Splenomegaly;
- •Encephalopathy;
- •Reduction of serum albumin;
- •Evidence of significant liver fibrosis;
- •Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
- •Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
- •Novel coronavirus infection occurred in the 6 weeks prior to entry into the group
- •Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive);
- •Evidence of malignant tumours or those with a previous history of malignant tumours;
- •Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
- •Any immunodeficiency;
- •planned surgery may be required within one year;
- •Past thromboembolic events (arterial or venous thromboembolic events);
- •Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);
结局指标
主要结局
FIX:C Antigen Level at Steady State
时间窗: Baseline up to Week 52
FIX:C activity antigen levels were characterized by post-treatment population mean.
Incidence of serious adverse events
时间窗: Baseline up to Week 52
A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect
Incidence of adverse events
时间窗: Baseline up to Week 52
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.
次要结局
- FIX:C activity level(Baseline up to Week 52)
- Annualized bleeding rate changes from baseline(Baseline up to Week 52)
- Annualized FIX consumption changes from baseline(Baseline up to Week 52)
- Vector- derived FIX antigen levels(Baseline up to Week 52)