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

NCT05203679 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: BBM001-CLN1001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

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.

Conditions

Hemophilia B

Keywords

Hemophilia B;gene therapy;Adeno-Associated Virus

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

• Phase 1/2: Changes in liver function

  52 weeks post-infusion

• Phase 1/2/3: Mean FIX Padua Activity Level

  52 weeks post-infusion

• Phase 1/2/3: Other FIX Protein Product Usage

  52 weeks post-infusion

• Phase 1/2/3: Target Joint Count

  52 weeks post-infusion

• Phase 1/2/3: Joint Bleeding Episodes

  52 weeks post-infusion

Study Arms (1)

Arm of BBM-H901

EXPERIMENTAL

Single-dose treatment

Genetic: Single dose intravenous injection of BBM-H901

Interventions

Single dose intravenous injection of BBM-H901 GENETIC

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.

Arm of BBM-H901

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males ≥ 18 years of age;
• Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
• 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;
• 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;
• Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
• Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.

You may not qualify if:

• 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;
• 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;
• HIV positive patients;
• 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;
• Have alcohol or drug dependence, or cannot stop drinking throughout the study;
• Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.

Sponsors & Collaborators

• Shanghai Xinzhi BioMed Co., Ltd.: lead

Study Sites (9)

Anhui Provincial Hospital

Hefei, Anhui, 230022, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100005, China

Location

Nanfang Hospital Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

The Second People's Hospital of Shenzhen

Shenzhen, Guangdong, 518025, China

Location

North China University of Science and Technology Affiliated Hospital

Tangshan, Hebei, 063000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, Tianjin Municipality, 300020, China

Location

The second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

Location

Related Publications (5)

• 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.

  PMID: 35598604 BACKGROUND

• 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.

  PMID: 36306204 BACKGROUND

• 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.

  PMID: 40441148 RESULT

• 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.

  PMID: 41180128 RESULT

• 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.

  PMID: 41266685 RESULT

Related Links

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

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Lei Zhang, MD

  Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

  STUDY CHAIR

• Caifeng Yang, Master

  Shanghai Xinzhi BioMed Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 24, 2022
• Study Start: December 30, 2021
• Primary Completion: April 16, 2024
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)