evaluation of the safety and efficacy of hemophilia a gene therapy drugs

Conditions: Hemophilia A

Summary: this is a multi-center, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of bbm-h803 injection in heavy 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.


Eligibility criteria:
inclusion criteria: 1. subjects voluntarily sign informed consent form; 2. males ≥ 18 years; 3. subjects are clinically diagnosed with severe hemophilia a; 4. no prior history of hypersensitivity or anaphylaxis associated with any fviii immunoglobulin; 5. use a reliable contraception method during the study; 6. capsid antibody negative; 7. subjects have good compliance. exclusion criteria: 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, hiv positive patients or syphilis seropositive patients; 2. currently on antiviral therapy for hepatitis b or c; 3. suffer from coagulation disorders other than hemophilia a; 4. in addition to glucocorticoids, any other immunosuppressants are being used before selection; 5. have vaccination history within 2 months before administration, or vaccination schedule during immunomodulatory therapy; 6. 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; 7. scheduling of elective major surgery known or planned during the insertion period or the 52-week study period following bbm-h803 infusion; 8. 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; 9. any herbal preparations (herbal supplements or traditional chinese medicines of plant, mineral or animal origin) used during the 4 weeks prior to or during the study that may affect liver function, except topical use; or any chinese herbal medicine that the researcher evaluates to affect the study; 10. have alcohol or drug addiction, or cannot stop drinking as advised by the researcher throughout the study; 11. have acute/chronic infections or other chronic diseases that may pose a risk for the study, or have a major illness, who have a current or previous history of malignant tumors, or who have other unstable medical conditions, including poor mental state and risk of suicide, that the investigator deems unsuitable for participation in the study; 12. any other conditions that the investigator deems unsuitable for participation in the study.

Keywords: hemophilia a gene therapy adeno-associated virus