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

Launched by INSTITUTE OF HEMATOLOGY & BLOOD DISEASES HOSPITAL, CHINA · Jan 31, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new gene therapy called BBM-H901 for young boys aged 12 to 18 years who have hemophilia B, a condition that affects blood clotting. The goal of the study is to see if a single infusion of this gene therapy is safe and effective for increasing the levels of a protein called factor IX (FIX) that helps blood to clot. To participate, boys must have very low levels of FIX in their blood and have had enough prior treatments for hemophilia. They also need to be in generally good health, with certain lab test results meeting specific criteria.

Participants in the trial will receive one infusion of the gene therapy and will be monitored closely to track how well they tolerate the treatment and if it helps improve their FIX levels. It’s important for families to know that this is an early-stage study, meaning it's one of the first steps in testing this treatment, and it is not yet known if it will work as hoped. Additionally, participants will need to agree to some guidelines, such as using effective birth control if they are sexually mature, and they should not have any major health issues that could complicate the trial.

Gender

MALE

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;