Single dose intravenous injection of BBM-H803: Single dose intravenous infusion of BBM-H803, an adeno-associated viral (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII transgene in liver. The dose of BBM-H803 will be calculated according to participant's weight.
Study 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.
Eligibility
Sex
MALE
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria of Phase 1/2/3:
1. Subjects voluntarily sign informed consent form;
2. Males ≥ 18 years;
3. Subjects are clinically diagnosed with severe hemophilia A;
4. Have \> = 150 documented exposure days to a Factor VIII protein product
5. No prior history of hypersensitivity or anaphylaxis associated with any FVIII immunoglobulin;
6. Use a reliable contraception method during the study;
7. Capsid antibody negative;
8. Subjects have good compliance.
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, 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.
Primary outcome measure(s)
Phase 1/2: Incidence of dose limiting toxicity (DLT) events — 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) — 6 weeks To assess the safety of BBM-H803 Injection by AEs and SAEs.
Phase 1/2: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function] — 6 weeks To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Phase 3: Annualized bleeding rate (ABR) — 52 weeks To assess ABR, including spontaneous bleeding, traumatic bleeding and joint bleeding after administration.
Trial sites (10)
Facility
City
Region
Status
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing
Beijing Municipality
Recruiting
Southern Hospital, Southern Medical University
Guangzhou
Guangdong
Recruiting
Affiliated Hospital of Guizhou Medical University
Guiyang
Guizhou
Recruiting
Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology
Wuhan
Hubei
Recruiting
Xiangya Hospital Central South University
Changsha
Hunan
Recruiting
The First Affiliated Hospital of Soochow University
Suzhou
Jiangsu
Recruiting
The Affiliated Hospital of Northwest University Xi'an No.3 Hospital
Xi’an
Shanxi
Recruiting
Sichuan Provincial People's Hospital
Chengde
Sichuan
Recruiting
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin
Tianjin Municipality
Recruiting
The Second Affiliated Hospital of Kunming Medical University
Kunming
Yunnan
Recruiting
More Shanghai Xinzhi BioMed Co., Ltd. trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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