Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05203679
• Other study ID #: BBM001-CLN1001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 30, 2021
• Est. completion date: June 30, 2028

Study information

• Verified date: August 2023
• Source: Shanghai Belief-Delivery BioMed Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• Single dose intravenous injection of BBM-H901
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. The dose of BBM-H901 will be 1×10^13 vg/ kg

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Nanfang Hospital Southern Medical University	Guangzhou	Guangdong
China	Anhui Provincial Hospital	Hefei	Anhui
China	The second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	The Second People's Hospital of Shenzhen	Shenzhen	Guangdong
China	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	North China University of Science and Technology Affiliated Hospital	Tangshan	Hebei
China	Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Belief-Delivery BioMed Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicity (DLT) events.	To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) within 6 or 10 weeks after administration.	6 or 10 weeks
Primary	The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	To assess the safety of BBM-H901 Injection by TEAEs and SAEs.	52 weeks
Primary	Changes in liver function	To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT).	52 weeks
Secondary	FIX activity	All samples collected from participants for plasma FIX activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels.	52 weeks
Secondary	FIX antigen level	To assess FIX antigen level within 52 weeks after administration.	52 weeks
Secondary	The viral load of AAV vector	To assess the viral load of AAV vector within 52 weeks after administration.	52 weeks
Secondary	Annualized bleeding rate (ABR)	To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.	52 weeks
Secondary	Improvement in patient's quality of life	To assess the proportion of subjects with life improvement from baseline through Hemophilia Joint Health Score (HJHS), Hemophilic Early Arthropathy Detection with UltraSound in China (HEAD-US-C) and the Medical Outcomes Study (MOS) item short from health survey (SF-36) at 4, 12, 26 and 52 weeks.	52 weeks