Evaluation of the Safety and Efficacy of Hemophilia A Gene Therapy Drugs

A Phase 1/2/3 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Viral Vector Containing an Expression Cassette of the Human Factor VIII Transgene (BBM-H803) Injection in Participants With Hemophilia A

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-H803 injection in severe Hemophilia A subjects.

BBM-H803 is an adeno-associated viral (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII transgene and raises circulating levels of endogenous FVIII.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Genetic: Single dose intravenous injection of BBM-H803

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Wenqi Shao, Master; Phone Number: 13636317441; Email: ra@beliefbiomed.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100005
      • Recruiting
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Contact: Tienan Zhu, MD; Phone Number: 18611743292; Email: Zhutn@pumch.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Southern Hospital, Southern Medical University
      • Contact: Jing Sun, MD; Phone Number: 13316202696; Email: jsun_cn@hotmail.com
      • Contact: Chongyuan Xu, MD; Phone Number: 13926186470; Email: nfyygcp@126.com
  • Guizhou
    • Guiyang, Guizhou, China, 550001
      • Recruiting
      • Affiliated Hospital of Guizhou Medical University
      • Contact: Jiao Jin, Bachelor; Phone Number: 15180802411; Email: jinjiao999@163.com
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology
      • Contact: Yu Hu, MD; Phone Number: 13986183871; Email: dr_huyu387@163.com
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Xiangya Hospital Central South University
      • Contact: Xielan Zhao, MD; Phone Number: 13707489198; Email: zhaoxl9198@163.com
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • the First Affiliated Hospital of Soochow University
      • Contact: Ziqiang Yu, MD; Phone Number: 13913518032; Email: yuziqiang@suda.edu.cn
  • Shanxi
    • Xi’an, Shanxi, China, 710000
      • Recruiting
      • The Affiliated Hospital of Northwest University Xi'an No.3 Hospital
      • Contact: Xiequn Chen, MD; Phone Number: 13991832567; Email: cxq@nwu.edu.cn
  • Sichuan
    • Chengde, Sichuan, China, 610031
      • Recruiting
      • Sichuan Provincial People's Hospital
      • Contact: Xiaobing Huang, MD; Phone Number: 18981838236; Email: hxb_trial@163.com
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
      • Contact: Lei Zhang, MD; Phone Number: 0086-22-23909095; Email: zhanglei1@ihcams.ac.cn
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Recruiting
      • The Second Affiliated Hospital of Kunming Medical University
      • Contact: Zeping Zhou, MD; Phone Number: 18788571605; Email: zhouzeping@kmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria of Phase 1/2/3:

1. Subjects voluntarily sign informed consent form;
2. Males ≥ 18 years;
3. Subjects are clinically diagnosed with severe hemophilia A;
4. Have > = 150 documented exposure days to a Factor VIII protein product
5. No prior history of hypersensitivity or anaphylaxis associated with any FVIII immunoglobulin;
6. Use a reliable contraception method during the study;
7. Capsid antibody negative;
8. Subjects have good compliance.

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, HIV positive patients or Syphilis seropositive patients;

2. Currently on antiviral therapy for hepatitis B or C;
3. Suffer from coagulation disorders other than hemophilia A;
4. In addition to glucocorticoids, any other immunosuppressants are being used before selection;
5. Have vaccination history within 2 months before administration, or vaccination schedule during immunomodulatory therapy;
6. 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;
7. Scheduling of elective major surgery known or planned during the insertion period or the 52-week study period following BBM-H803 infusion;
8. Have participated in a previous gene therapy research trial before screening or have used other test drugs within 4 weeks before screening, or within 5 half-life of the test drug, whichever is longer; Have received emesezumab within 6 months before screening; Or drugs evaluated by the researcher to affect the study;
9. Any herbal preparations (herbal supplements or traditional Chinese medicines of plant, mineral or animal origin) used during the 4 weeks prior to or during the study that may affect liver function, except topical use; Or any Chinese herbal medicine that the researcher evaluates to affect the study;
10. Have alcohol or drug addiction, or cannot stop drinking as advised by the researcher throughout the study;
11. Have acute/chronic infections or other chronic diseases that may pose a risk for the study, or have a major illness, who have a current or previous history of malignant tumors, or who have other unstable medical conditions, including poor mental state and risk of suicide, that the investigator deems unsuitable for participation in the study;
12. Any other conditions 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-H803; 1×10^13 vg/kg, Single-dose treatment	Genetic: Single dose intravenous injection of BBM-H803; Single dose intravenous infusion of BBM-H803, an adeno-associated viral (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII transgene in liver. The dose of BBM-H803 will be calculated according to participant's weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2: 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-H803 injection infusion	6 weeks
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)	To assess the safety of BBM-H803 Injection by AEs and SAEs.	6 weeks
Phase 3: Annualized bleeding rate (ABR)	To assess ABR, including spontaneous bleeding, traumatic bleeding and joint bleeding after administration.	52 weeks
Phase 1/2: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function]	To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2/3: Plasma FVIII activity level	All samples collected from participants for plasma FVIII activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FVIII activity levels.	52 weeks
Phase 1/2/3: The incidence of adverse events (AEs) and serious adverse events (SAEs)	To assess the safety of BBM-H803 Injection by AEs and SAEs.	52 weeks
Phase 1/2/3: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function]	To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT)and aspartate aminotransferase (AST).	52 weeks

Collaborators and Investigators

• Sponsor: Shanghai Xinzhi BioMed Co., Ltd.
• Collaborators: Shanghai Mianyi Biopharmaceutical Co., Ltd.
• Investigators: Study Chair: Lei Zhang, MD, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2031

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: gene therapy; Hemophilia A; Adeno-Associated Virus
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: BBM002-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