Clinical trial NCT05203679: Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug
Official title: A Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Virus Vector Containing an Expression Cassette of the Human Factor IX Transgene (BBM-H901) Injection in Patients with Hemophilia B
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia B
Keywords: Hemophilia B;gene therapy;Adeno-Associated Virus
Lead sponsor: Shanghai Belief-Delivery BioMed Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-01-24
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center, 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.


Eligibility criteria: Inclusion Criteria:

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:

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.

Primary outcomes:
measure: Annualized bleeding rate (ABR)
timeFrame: 52 weeks post-infusion
Secondary outcomes:
measure: Mean FIX Padua Activity Level
timeFrame: 52 weeks post-infusion
measure: Other FIX Protein Product Usage
timeFrame: 52 weeks post-infusion
measure: Target Joint Count
timeFrame: 52 weeks post-infusion
measure: Joint Bleeding Episodes
timeFrame: 52 weeks post-infusion
measure: Bleeding-Free Subjects
timeFrame: 52 weeks post-infusion
measure: Adverse Event Incidence
timeFrame: 52 weeks post-infusion
measure: FIX Inhibitor Incidence
timeFrame: 52 weeks post-infusion
measure: AAV Vector Shedding
timeFrame: 52 weeks post-infusion
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The Second People's Hospital of Shenzhen
state: Guangdong
city: Tangshan
country: China
facility: North China University of Science and Technology Affiliated Hospital
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
state: Tianjin
city: Kunming
country: China
facility: The second Affiliated Hospital of Kunming Medical University
state: Yunnan
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
name: Lei Zhang, MD
role: STUDY_CHAIR
affiliation: Shanghai Belief-Delivery BioMed Co., Ltd
name: Caifeng Yang, Master
role: STUDY_DIRECTOR
References: