A Phase 1/2/3 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Viral Vector Containing an Expression Cassette of the Human Factor VIII Transgene (BBM-H803) Injection in Participants With Hemophilia A
Overview
- Phase
- Phase 2
- Intervention
- Single dose intravenous injection of BBM-H803
- Conditions
- Hemophilia A
- Sponsor
- Shanghai Xinzhi BioMed Co., Ltd.
- Enrollment
- 55
- Locations
- 11
- Primary Endpoint
- Phase 1/2: Incidence of dose limiting toxicity (DLT) events
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
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-H803 injection in severe Hemophilia A subjects.
BBM-H803 is an adeno-associated viral (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII transgene and raises circulating levels of endogenous FVIII.
Investigators
Eligibility Criteria
Inclusion Criteria
- •of Phase 1/2/3:
- •Subjects voluntarily sign informed consent form;
- •Males ≥ 18 years;
- •Subjects are clinically diagnosed with severe hemophilia A;
- •Have \> = 150 documented exposure days to a Factor VIII protein product
- •No prior history of hypersensitivity or anaphylaxis associated with any FVIII immunoglobulin;
- •Use a reliable contraception method during the study;
- •Capsid antibody negative;
- •Subjects have good compliance.
Exclusion Criteria
- •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, HIV positive patients or Syphilis seropositive patients;
- •Currently on antiviral therapy for hepatitis B or C;
- •Suffer from coagulation disorders other than hemophilia A;
- •In addition to glucocorticoids, any other immunosuppressants are being used before selection;
- •Have vaccination history within 2 months before administration, or vaccination schedule during immunomodulatory therapy;
- •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;
- •Scheduling of elective major surgery known or planned during the insertion period or the 52-week study period following BBM-H803 infusion;
- •Have participated in a previous gene therapy research trial before screening or have used other test drugs within 4 weeks before screening, or within 5 half-life of the test drug, whichever is longer; Have received emesezumab within 6 months before screening; Or drugs evaluated by the researcher to affect the study;
Arms & Interventions
Arm of BBM-H803
1×10\^13 vg/kg, Single-dose treatment
Intervention: Single dose intravenous injection of BBM-H803
Outcomes
Primary Outcomes
Phase 1/2: Incidence of dose limiting toxicity (DLT) events
Time Frame: 6 weeks
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H803 injection infusion
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 6 weeks
To assess the safety of BBM-H803 Injection by AEs and SAEs.
Phase 3: Annualized bleeding rate (ABR)
Time Frame: 52 weeks
To assess ABR, including spontaneous bleeding, traumatic bleeding and joint bleeding after administration.
Phase 1/2: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function]
Time Frame: 6 weeks
To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Secondary Outcomes
- Phase 1/2/3: Plasma FVIII activity level(52 weeks)
- Phase 1/2/3: The incidence of adverse events (AEs) and serious adverse events (SAEs)(52 weeks)
- Phase 1/2/3: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function](52 weeks)