Gene therapy for treating Hemophilia A

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 study is testing a new gene therapy to see if it can safely boost factor VIII levels in people with severe Hemophilia A.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Shanghai Xinzhi BioMed Co., Ltd. (Industry-sponsored)
• Drugs / interventions: emesezumab
• Locations: 10 sites (Beijing, Beijing Municipality and 9 other locations)
• Trial ID: NCT06111638 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a single intravenous dose of BBM-H803, a gene therapy designed to increase levels of factor VIII in patients with severe Hemophilia A. The study is multi-center and open-label, focusing on heavy Hemophilia A subjects who meet specific inclusion criteria. Participants will be monitored for safety, tolerability, and the effectiveness of the treatment in raising endogenous FVIII levels.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 and older with a clinical diagnosis of severe Hemophilia A.

Not a fit: Patients with other coagulation disorders or those with a history of hepatitis B or C may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could significantly improve the management of Hemophilia A by reducing the need for regular factor replacement therapies.

How similar studies have performed: Other studies have shown promise with gene therapy approaches for Hemophilia A, indicating potential for success in this novel treatment.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality and 9 other locations

• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)
• Southern Hospital, Southern Medical University — Guangzhou, Guangdong, China (Recruiting)
• Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (Recruiting)
• Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital Central South University — Changsha, Hunan, China (Recruiting)
• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• The Affiliated Hospital of Northwest University Xi'an No.3 Hospital — Xi’an, Shanxi, China (Recruiting)
• Sichuan Provincial People's Hospital — Chengde, Sichuan, China (Recruiting)
• Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College — Tianjin, Tianjin Municipality, China (Recruiting)
• The Second Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Recruiting)

Study contacts

• Study coordinator: Wenqi Shao, Master

Conditions Hemophilia A; gene therapy; Adeno-Associated Virus