Safety and Tolerability of VGB-R04 in Patients With Haemophilia B
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.
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 kinetics 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(±2) weeks of safety observation and will be encouraged to enroll in an extension 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 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥18 years and ≤75years of age;
- •Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%);
- •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 ≥100×10'9 cells/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 barrier contraception until 3 consecutive samples are negative for vector sequences;
- •Able to provide informed consent and comply with the requirements of the study.
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.;
- •Evidence of active hepatitis B virus infection (HBV-DNA >103 IU/ml) or hepatitis C virus infection (HCV antigen and 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;
- •Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 4 weeks;
- •Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within the last 3 months;
- •Previous history of hypersensitivity or allergic reaction to any FIX products or any immunoglobulin;
- •Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
- •Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
结局指标
主要结局
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.
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
Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings
时间窗: Baseline up to Week 52
The physical examination will include examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination will assess the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings will be considered to be clinically significant based on the investigator's decision
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
时间窗: Baseline up to Week 52
Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) 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
Number of Participants with Clinical Laboratory Abnormalities
时间窗: Baseline up to Week 52
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings were considered to be clinically significant based on the investigator's decision.
次要结局
- Vector- derived FIX antigen levels(Baseline up to Week 52)
- Vector shedding of VGB-R04(Baseline up to Week 52)
- Vector- derived FIX:C Activity(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)
- Number of target joints(Baseline up to Week 52)