Gene therapy for treating Hemophilia A

A Clinical Study of AAV Vector Expressing Human Coagulation Factor FVIII Gene Therapy for Hemophilia A

This study is testing a new gene therapy to see if a single injection can help men with Hemophilia A increase their factor VIII levels and reduce bleeding.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05454774 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and tolerability of a single intravenous injection of BBM 002, an adeno-associated virus vector designed to increase levels of factor VIII in patients with Hemophilia A. It targets individuals with low endogenous FVIII activity levels and requires participants to have a history of bleeding events and prior exposure to FVIII products. The study is open-label and involves a single-arm design, focusing on adult males with specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates for this study are adult males with Hemophilia A and low endogenous FVIII levels who have had significant prior exposure to FVIII products.

Not a fit: Patients with a history of FVIII inhibitors or those who do not meet the specific eligibility criteria 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 increasing FVIII levels and reducing bleeding episodes.

How similar studies have performed: While gene therapy for Hemophilia A is a novel approach, there have been other studies exploring similar methodologies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Subjects are fully aware of the purpose, nature, methods and possible adverse reactions of the trial and voluntarily sign informed consent.
2. Males ≥ 18 years of age.
3. Have hemophilia A with ≤2 IU/dL (≤2 %) endogenous FVIII activity levels.
4. Have had ≥150 prior exposure days (EDs) to any recombinant and/or plasma-derived FVIII protein products.
5. Have had bleeding events and/or infusions with FVIII protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records.
6. Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
7. Have no FVIII inhibitor. (eg \<0.6BU/ml Bethesda Units; or the patient's FVIII inhibitor titer was detected \<0.6BU/ml in 2 consecutive times within 1-4 weeks using Bethesda method or Nijmegen method), or no prior medical history of FVIII inhibitor after 150 EDs of FVIII products; no clinical signs or symptoms of decreased response to FVIII products infusion.
8. Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after BBM002 infusion.
9. Compliance is good, patients and their families have the will of 'gene therapy' clinical trials.

Exclusion Criteria:

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).
2. Currently on antiviral therapy for hepatitis B or C.
3. Patients with coagulation disorders in addition to hemophilia A.
4. Use of any other systematic immunosuppressant other than glucocorticoids within 30 days prior to enrollment.
5. Patients with vaccination history within 30 days prior to screening.
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 by researchers.
7. Patients with known planned major surgery schedule during the 52-week study period aren't eligible.
8. 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.
9. Have alcohol or drug dependence, or cannot stop drinking throughout the study. 10.Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Lei Zhang, MD

Conditions: Hemophilia A, gene therapy, Adeno-Associated Virus