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

NCT06111638 | Recruiting Phase 2

• 1 other identifier: BBM002-CLN1001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 10

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-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.

Conditions

Hemophilia A

Keywords

Hemophilia A; gene therapy; Adeno-Associated Virus

Outcome Measures

Primary Outcomes (4)

• 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 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

• Phase 3: Annualized bleeding rate (ABR)

  To assess ABR, including spontaneous bleeding, traumatic bleeding and joint bleeding after administration.

  52 weeks

Secondary Outcomes (3)

• Phase 1/2/3: Plasma FVIII activity level

  52 weeks

• Phase 1/2/3: The incidence of adverse events (AEs) and serious adverse events (SAEs)

  52 weeks

• Phase 1/2/3: Number of participants with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [liver function]

  52 weeks

Study Arms (1)

Arm of BBM-H803

EXPERIMENTAL

1×10\^13 vg/kg, Single-dose treatment

Genetic: Single dose intravenous injection of BBM-H803

Interventions

Single dose intravenous injection of BBM-H803 GENETIC

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.

Arm of BBM-H803

Eligibility Criteria

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

You may qualify if:

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

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, HIV positive patients or Syphilis seropositive patients;
• Currently on antiviral therapy for hepatitis B or C;
• Suffer from coagulation disorders other than hemophilia A;
• In addition to glucocorticoids, any other immunosuppressants are being used before selection;
• Have vaccination history within 2 months before administration, or vaccination schedule during immunomodulatory therapy;
• 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;
• Scheduling of elective major surgery known or planned during the insertion period or the 52-week study period following BBM-H803 infusion;
• 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;
• 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;
• Have alcohol or drug addiction, or cannot stop drinking as advised by the researcher throughout the study;
• 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;
• Any other conditions that the investigator deems unsuitable for participation in the study.

Sponsors & Collaborators

• Shanghai Xinzhi BioMed Co., Ltd.: lead
• Shanghai Mianyi Biopharmaceutical Co., Ltd.: collaborator

Study Sites (10)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100005, China

RECRUITING

Southern Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550001, China

RECRUITING

Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

The Affiliated Hospital of Northwest University Xi'an No.3 Hospital

Xi’an, Shanxi, 710000, China

RECRUITING

Sichuan Provincial People's Hospital

Chengde, Sichuan, 610031, China

RECRUITING

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

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

RECRUITING

MeSH Terms

Conditions

Hemophilia A

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

Study Officials

• Lei Zhang, MD

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

  STUDY CHAIR

Central Study Contacts

Wenqi Shao, Master

CONTACT

13636317441; ra@beliefbiomed.com

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: October 27, 2023
• First Posted: November 1, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2031
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)