Gene Therapy for Hemophilia B Patients Aged 12-18 Years Old

Plain-language summary

This Phase 1, open-label, non-randomized, single-dose pilot study evaluates the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in people aged 12 to 18 with hemophilia B and residual FIX levels of 2 IU/dL or below. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating FIX levels. Participants must be male, weigh at least 50 kg, and provide consent together with a legal guardian.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Recruiting

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Intervention

BBM-H901

Start date

3/23/2023

Estimated completion

11/1/2035

Countries

China

Related genes

Locations

• Tianjin, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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;