Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug

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

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.

Inclusion Criteria of Phase 1/2/3:

1. Males ≥ 18 years of age;
2. Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
3. 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;
4. 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;
5. Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
6. Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.

Exclusion Criteria of Phase 1/2/3:

1. 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;
2. 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;
3. HIV positive patients;
4. 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;
5. Have alcohol or drug dependence, or cannot stop drinking throughout the study;
6. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.