Hemophilia B
Conditions
Keywords
Hemophilia B;gene therapy;Adeno-Associated Virus
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-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels. BBM-H901 is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene and raises circulating levels of endogenous FIX.
Interventions
Single dose intravenous infusion of BBM-H901, an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene in liver.
Sponsors
Shanghai Xinzhi BioMed Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
of Phase 1/2/3: 1. Males ≥ 18 years of age; 2. Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels; 3. Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories; 4. Have had bleeding events and/or injected with FIX protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records; 5. Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration; 6. Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.
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, i.e. subjects with natural clearance and anti-viral therapy clearance for hepatitis B or C are eligible; 2. 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; 3. HIV positive patients; 4. Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer; 5. Have alcohol or drug dependence, or cannot stop drinking throughout the study; 6. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1/2: The incidence of dose limiting toxicity (DLT) events | 10 weeks post-infusion | To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H901 injection infusion. |
| Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs) | 10 weeks post-infusion | To assess the safety of BBM-H901 Injection by AEs and SAEs. |
| Phase 1/2: Changes in liver function | 10 weeks post-infusion | 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 post-infusion | To assess ABR, including spontaneous bleeding and traumatic bleeding after administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1/2: Changes in liver function | 52 weeks post-infusion | To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST). |
| Phase 1/2/3: Mean FIX Padua Activity Level | 52 weeks post-infusion | Measurement of mean FIX Padua activity levels over the 52-week period following BBM-H901 injection. |
| Phase 1/2/3: Other FIX Protein Product Usage | 52 weeks post-infusion | Number and total volume of infusions of exogenous FIX protein products (recombinant or plasma-derived) administered within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: Target Joint Count | 52 weeks post-infusion | Number of target joints recorded within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: Joint Bleeding Episodes | 52 weeks post-infusion | Total number of joint bleeding events occurring within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: Bleeding-Free Subjects | 52 weeks post-infusion | Proportion of subjects experiencing no bleeding events within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: Adverse Event Incidence | 52 weeks post-infusion | Incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: FIX Inhibitor Incidence | 52 weeks post-infusion | Incidence of FIX inhibitors measured by Bethesda or Nijmegen-Bethesda assays within 52 weeks post-BBM-H901 injection. |
| Phase 1/2/3: AAV Vector Shedding | 52 weeks post-infusion | Changes in AAV vector shedding in plasma, urine, semen, saliva, and PBMCs within 52 weeks post-BBM-H901 injection. |
Countries
China
Contacts
STUDY_CHAIRLei Zhang, MD
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
STUDY_DIRECTORCaifeng Yang, Master
Shanghai Xinzhi BioMed Co., Ltd.
Outcome results
None listed