Gene Therapy for Hemophilia B Patients Aged 12-18 Years Old

Prior treatment

• Currently on antiviral therapy for hepatitis B or C;
• Had immunosuppressive therapy other than steroid and other suggested IST agents within 30 days prior to screening;
• Had vaccine 30 days prior to screening or have scheduled vaccination plan during the study (up to 52 weeks);
• Have surgery plan within 52 weeks after gene therapy;
• Had participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the last 12 weeks;
• Had any herb that may affect the liver function within 4 weeks prior to screening;
• 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;

Other illness

• Hepatitis B surface antigen antibody (HBSAg-Ab) or HBV-DNA positive; hepatitis C antibody or HCV-RNA positive;
• With coagulation disorders other than hemophilia B;
• Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, etc; other liver conditions unsuitable to gene therapy judged by investigator;
• Have history of chronic infection or high rish of infection that the Investigator considers to constitute an unacceptable risk;
• Have history of fatal bleeding episode, eg intracranial hemorrhage, etc;

• Subjects and statutory guardian must be able to understand the purpose and risks of the study and provide signed and dated informed consent;
• Be male and 12≤ age \<18 years of age, body wight ≥ 50kg;
• Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels as documented by a certified clinical laboratory at the time of screening. If the screening result is \>2% due to insufficient washout from FIX protein product, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤2% FIX coagulant activity (FIX:C) ;
• Had had ≥75 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
• With ≤ 1:4 neutralizing antibodies and ≤1:200 binding antibodies against BBM-H901 capsid;
• Subjects with bleeding episode and/ or FIX agents infusion events within 12 weeks prior to screening;
• Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
• Have no measurable FIX inhibitor as assessed by laboratory; or documented no prior history of FIX inhibitor (family history of inhibitors will not exclude the subject) and no clinical signs or symptoms of decreased response to FIX administration;
• Have acceptable laboratory values:
  • Hemoglobin ≥11 g/dL ;
  • Platelets ≥100,000 cells/μL;
  • AST, ALT ≤1.5x upper limit of normal at the testing laboratory;
  • Bilirubin ≤1.5x ULN ;
  • glomerular filtration rate eGFR ≥ 60ml/min.
• For those subjects with sexual maturity, subject and statutory guardian must know that subjects must agree to use reliable barrier contraception until 52 weeks;
• with good compliance to the schedule of visit and fill in the subject diary.