Gene therapy for teenagers with Hemophilia B

A Pilot Study Evaluating the Safety, Tolerability and Efficacy of Gene Therapy With BBM-H901 in Hemophilia B Patients Aged 12-18 Years Old

This study is testing a new gene therapy for teenagers with Hemophilia B to see if a single treatment can help their bodies produce more of the factor IX protein they need.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 12 Years to 18 Years
• Sex: Male
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05709288 on ClinicalTrials.gov

What this trial studies

This Phase 1 pilot study evaluates the safety, tolerability, and efficacy of a single intravenous infusion of BBM-H901 in male patients aged 12-18 years with Hemophilia B and low levels of factor IX. The study will enroll nine subjects who will receive a dose of 5x10^12 vg/Kg of BBM-H901, an adeno-associated viral vector designed to enhance the expression of the human factor IX transgene. Participants will undergo screening assessments and will be monitored for safety over a period of 52 weeks, with long-term follow-up extending up to ten years to assess the treatment's effects. The study is open-label and non-randomized, focusing on a single dose administration.

Who should consider this trial

Good fit: Ideal candidates are male patients aged 12 to 18 years with Hemophilia B and very low endogenous factor IX levels.

Not a fit: Patients with higher levels of endogenous factor IX or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with Hemophilia B by increasing their factor IX levels and reducing bleeding episodes.

How similar studies have performed: While gene therapy approaches for Hemophilia B are emerging, this specific method using BBM-H901 is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Subjects and statutory guardian must be able to understand the purpose and risks of the study and provide signed and dated informed consent;
2. Be male and 12≤ age \<18 years of age, body wight ≥ 50kg;
3. Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels as documented by a certified clinical laboratory at the time of screening. If the screening result is \>2% due to insufficient washout from FIX protein product, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤2% FIX coagulant activity (FIX:C) ;
4. Had had ≥75 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
5. With ≤ 1:4 neutralizing antibodies and ≤1:200 binding antibodies against BBM-H901 capsid;
6. Subjects with bleeding episode and/ or FIX agents infusion events within 12 weeks prior to screening;
7. Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
8. Have no measurable FIX inhibitor as assessed by laboratory; or documented no prior history of FIX inhibitor (family history of inhibitors will not exclude the subject) and no clinical signs or symptoms of decreased response to FIX administration;
9. Have acceptable laboratory values:

   1. Hemoglobin ≥11 g/dL ;
   2. Platelets ≥100,000 cells/μL;
   3. AST, ALT ≤1.5x upper limit of normal at the testing laboratory;
   4. Bilirubin ≤1.5x ULN ;
   5. glomerular filtration rate eGFR ≥ 60ml/min.
10. For those subjects with sexual maturity, subject and statutory guardian must know that subjects must agree to use reliable barrier contraception until 52 weeks;
11. with good compliance to the schedule of visit and fill in the subject diary.

Exclusion Criteria:

1. Hepatitis B surface antigen antibody (HBSAg-Ab) or HBV-DNA positive; hepatitis C antibody or HCV-RNA positive;
2. Currently on antiviral therapy for hepatitis B or C;
3. With coagulation disorders other than hemophilia B;
4. Had immunosuppressive therapy other than steroid and other suggested IST agents within 30 days prior to screening;
5. Had vaccine 30 days prior to screening or have scheduled vaccination plan during the study (up to 52 weeks);
6. Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, etc; other liver conditions unsuitable to gene therapy judged by investigator;
7. Have surgery plan within 52 weeks after gene therapy;
8. Have history of chronic infection or high rish of infection that the Investigator considers to constitute an unacceptable risk;
9. Had participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the last 12 weeks;
10. Had any herb that may affect the liver function within 4 weeks prior to screening;
11. Have history of fatal bleeding episode, eg intracranial hemorrhage, etc;
12. Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study;

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of haematology and Blood diseases hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, MD — Insitute of haematology and blood diseases hospital, chinese academy of medical sciences
• Study coordinator: Feng Xue, MD

Conditions Hemophilia B; gene therapy; AAV