Safety and Tolerability of VGB-R04 in Patients With Haemophilia B

Inclusion Criteria:

1. Male ≥18 years and ≤75years of age;

2. Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal ordocumented history of FIX activity ≤2%);

3. At least 100 days exposure history to FIX;

4. Currently receiving FIX Prophylaxis therapy or on-demand treatment to preventbleeding;

5. Have acceptable laboratory values:

6. Hemoglobin ≥110 g/L;

7. Platelets ≥100×10'9 cells/L;

8. AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testinglaboratory;

9. Bilirubin ≤3× ULN ;

10. Creatinine ≤1.5× ULN.

11. No measurable factor IX inhibitor as assessed by the central laboratory and have noprior history of inhibitors to factor IX protein;

12. Agree to use reliable barrier contraception until 3 consecutive samples are negativefor vector sequences;

13. Able to provide informed consent and comply with the requirements of the study.

Exclusion Criteria:

1. Have significant underlying liver disease within the past 6 months prior to or atScreening, including but not limited to:

2. Preexisting diagnosis of portal hypertension;

3. Splenomegaly;

4. Encephalopathy;

5. Reduction of serum albumin;

6. Evidence of significant liver fibrosis;

7. Have anti-VGB-R04 neutralizing antibody titers ≥1:5;

8. Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV)infection, syphilis, tuberculosis, etc.;

9. Evidence of active hepatitis B virus infection (HBV-DNA >103 IU/ml) or hepatitis Cvirus infection (HCV antigen and HCV-RNA positive);

10. Evidence of malignant tumours or those with a previous history of malignant tumours;

11. Have a history of chronic infection or other chronic diseases that the Investigatorconsiders to constitute an unacceptable risk;

12. Any immunodeficiency;

13. Participated in a gene transfer trial within the last 52 weeks or in a clinicaltrial with an investigational drug within the last 4 weeks;

14. Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within thelast 3 months;

15. Previous history of hypersensitivity or allergic reaction to any FIX products or anyimmunoglobulin;

16. Unable or unwilling to comply with the schedule of visits and study assessmentsdescribed in the clinical protocol;

17. Any concurrent clinically significant major disease or any other condition that, inthe opinion of the Investigator, makes the subject unsuitable for participation inthe study.