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

A Phase 1/2/3 Open-label 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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia B
• Intervention / Treatment: Genetic: Single dose intravenous injection of BBM-H901

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100005
      • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital Southern Medical University
    • Shenzhen, Guangdong, China, 518025
      • The Second People's Hospital of Shenzhen
  • Hebei
    • Tangshan, Hebei, China, 063000
      • North China University of Science and Technology Affiliated Hospital
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • The Second Hospital of Shanxi Medical University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • The Second Affiliated Hospital of Kunming Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm of BBM-H901; Single-dose treatment	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2: The incidence of dose limiting toxicity (DLT) events	To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H901 injection infusion.	10 weeks post-infusion
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)	To assess the safety of BBM-H901 Injection by AEs and SAEs.	10 weeks post-infusion
Phase 1/2: Changes in liver function	To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).	10 weeks post-infusion
Phase 3: Annualized bleeding rate (ABR)	To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.	52 weeks post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2: Changes in liver function	To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).	52 weeks post-infusion
Phase 1/2/3: Mean FIX Padua Activity Level	Measurement of mean FIX Padua activity levels over the 52-week period following BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: Other FIX Protein Product Usage	Number and total volume of infusions of exogenous FIX protein products (recombinant or plasma-derived) administered within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: Target Joint Count	Number of target joints recorded within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: Joint Bleeding Episodes	Total number of joint bleeding events occurring within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: Bleeding-Free Subjects	Proportion of subjects experiencing no bleeding events within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: Adverse Event Incidence	Incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: FIX Inhibitor Incidence	Incidence of FIX inhibitors measured by Bethesda or Nijmegen-Bethesda assays within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion
Phase 1/2/3: AAV Vector Shedding	Changes in AAV vector shedding in plasma, urine, semen, saliva, and PBMCs within 52 weeks post-BBM-H901 injection.	52 weeks post-infusion

Collaborators and Investigators

• Sponsor: Shanghai Xinzhi BioMed Co., Ltd.
• Investigators: Study Chair: Lei Zhang, MD, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College; Study Director: Caifeng Yang, Master, Shanghai Xinzhi BioMed Co., Ltd.

Publications and helpful links

General Publications

• Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19.
• Xue F, Wang P, Yuan Z, Shi C, Fang Y, Liu W, Wang Y, Xiao X, Yang R, George LA, Zhang L. Total Knee Arthroplasty after Gene Therapy for Hemophilia B. N Engl J Med. 2022 Oct 27;387(17):1622-1624. doi: 10.1056/NEJMc2211173. No abstract available.
• Wei H, Xiao W, Dai J. China's first approved gene therapy for hemophilia B: A new era for global AAV-based treatments. Mol Ther. 2025 Jun 4;33(6):2312-2313. doi: 10.1016/j.ymthe.2025.05.014. Epub 2025 May 28. No abstract available.
• Xue F, Hu Y, Yang R, Sun J, Yang L, Wang X, Yu Z, Zhu T, Zhou H, Zhou Z, Yan Z, Du X, Zheng C, Liu W, Zhou R, Dai J, Yin J, Wang H, Tang LV, Chen S, Cheng H, Zhu M, Wang S, Song Y, Zhang P, Zhang L. Chinese guidance for the clinical application of adeno-associated virus vector-based gene therapy for hemophilia B (2025). Blood Sci. 2025 Oct 29;7(4):e00257. doi: 10.1097/BS9.0000000000000257. eCollection 2025 Dec.
• Xue F, Ju M, Zhu T, Zhou Z, Sun J, Yang L, Yan Z, Zhou H, Du X, Zheng C, Zheng J, Wu X, Du Z, Jiang W, Yang C, Xiao X, Liu W, Yang R, Zhang L. Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials. Nat Med. 2026 Jan;32(1):93-102. doi: 10.1038/s41591-025-04012-y. Epub 2025 Nov 20.

Helpful Links

• Prevalence of neutralizing antibodies against AAV8,AAV9, and AAV843 in a Chinese population

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): April 16, 2024
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hemophilia B;gene therapy;Adeno-Associated Virus
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia B
• Other Study ID Numbers: BBM001-CLN1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No