This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX.
This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX. Nine subjects will be enrolled and administered with single infusion of BBM-H901, an AAV at one dose level of 5x10'12 vg/Kg. Subjects and statutory guardian must provide informed consent and then undergo screening assessments up to 4-8weeks prior administration of BBM-H901. All subjects will undergo 52(+- 2) weeks safety observation and will be continuously followed up to evaluate long- term safety and efficacy of BBM-H901 up to ten years. The first subject will be dosed at 5x10'12 vg/Kg and undergo 8 weeks safety observation of which the data will undergo review by an independent safety committee.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of an hyper active human factor IX mutant(FIX Padua) transgene in liver. The dose of BBM-H901 is 5x10'12 vg/Kg.
Institute of haematology and Blood diseases hospital
Tianjin, Tianjin Municipality, China
RECRUITINGThe incidence of treatment related adverse events deemed related to BBM-H901 within 10 weeks after vector administration
the type and incidence of TRAE after BBM-H901 infusion according to the CTCAE(v5.0)
Time frame: infusion to 10 weeks after vector infusion.
The incidence of adverse events and serious adverse events within 52 weeks after BBM-H901 administration
Number of patients experiencing treatment-related adverse events from vector infusion to 52 weeks after vector infusion.
Time frame: Vector infusion to 52 weeks after gene therapy.
Change from baseline aspartate amino transferase
number of subjects with elevation of AST. Number of episodes of elevating AST
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose
Change from baseline alanine aminotransferase
number of subjects with elevation of ALT. Number of episodes of elevating ALT
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose
Vector shedding after BBM-H901 infusion
Vector genome in plasma, urea, stool, saliva will be monitored
Time frame: multiple timepoints until 2 consecutive negative results achieved usually within 52 weeks
Vector derived Factor IX(FIX) activity
FIX:C measured using one- stage APTT based method
Time frame: infusion to 52 weeks after gene therapy
Annualized bleeding rate(ABR) after gene therapy
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ABR will be prospectively collected at each visit.
Time frame: vector infusion to 52 weeks after gene therapy
Times of infusion of factor IX agents
Times of infusion of factor IX agents, eg FIX concentrates, prothrombin complex concentrate, fresh- frozen plasma.
Time frame: vector infusion to 52 weeks after gene therapy
number of target joint
target joint is defined as a joint with ≥bleeding during the last 6 months
Time frame: vector infusion to 52 weeks after gene therapy
factor IX inhibitor
factor IX inhibitor will be measured using bethesda method
Time frame: vector infusion to 52 weeks after gene therapy