A Phase 1/2/3 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Virus Vector Containing an Expression Cassette of the Human Factor IX Transgene (BBM-H901) Injection in Patients With Hemophilia B
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 9
- 主要终点
- Phase 1/2: The incidence of dose limiting toxicity (DLT) events
研究概览
简要总结
This is a multi-center, Phase 1/2/3, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of BBM-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels.
BBM-H901 is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene and raises circulating levels of endogenous FIX.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •of Phase 1/2/3:
- •Males ≥ 18 years of age;
- •Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
- •Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories;
- •Have had bleeding events and/or injected with FIX protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records;
- •Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
- •Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.
排除标准
- •of Phase 1/2/3:
- •Being positive for hepatitis B surface antigen (HBsAg) or hepatitis B virus-DNA (HBV-DNA). Being positive for hepatitis C virus antibody (HCV-Ab) or hepatitis C virus RNA (HCV-RNA). Subjects with medical history of hepatitis B or C can be regarded as negative only when 2 required samplings are conducted at least 3 months apart and both test results of indicators aforementioned are negative, i.e. subjects with natural clearance and anti-viral therapy clearance for hepatitis B or C are eligible;
- •Have potential liver diseases, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy or liver fibrosis (fibrosis stage ≥ 3); nodules or cysts were found by B ultrasound, or elevated alpha-fetoprotein was detected by laboratory tests. Subjects who are not eligible for the study if the abnormalities are clinically significant regarding to the medical judgement of the investigator;
- •HIV positive patients;
- •Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer;
- •Have alcohol or drug dependence, or cannot stop drinking throughout the study;
- •Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.
结局指标
主要结局
Phase 1/2: The incidence of dose limiting toxicity (DLT) events
时间窗: 10 weeks post-infusion
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H901 injection infusion.
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 10 weeks post-infusion
To assess the safety of BBM-H901 Injection by AEs and SAEs.
Phase 1/2: Changes in liver function
时间窗: 10 weeks post-infusion
To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Phase 3: Annualized bleeding rate (ABR)
时间窗: 52 weeks post-infusion
To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.
次要结局
- Phase 1/2: Changes in liver function(52 weeks post-infusion)
- Phase 1/2/3: Mean FIX Padua Activity Level(52 weeks post-infusion)
- Phase 1/2/3: Other FIX Protein Product Usage(52 weeks post-infusion)
- Phase 1/2/3: Target Joint Count(52 weeks post-infusion)
- Phase 1/2/3: Joint Bleeding Episodes(52 weeks post-infusion)
- Phase 1/2/3: Bleeding-Free Subjects(52 weeks post-infusion)
- Phase 1/2/3: Adverse Event Incidence(52 weeks post-infusion)
- Phase 1/2/3: FIX Inhibitor Incidence(52 weeks post-infusion)
- Phase 1/2/3: AAV Vector Shedding(52 weeks post-infusion)