Hemophilia B
Conditions
Brief summary
A multicenter, open, non-randomized, phase I/II, two-phase clinical study. The dose exploration phase was phase I, and the dose extension phase was phase II.
Detailed description
Hemophilia B is a genetic bleeding disorder caused by pathogenic variants (eg, mutations, deletion) in the FIX gene. HB patients have frequent and potentially life-threatening bleeding and often develop progressive physical disability and pain from chronic haemarthropathy. Current replacement therapy needs regular treatment in the life-long time, bringing heavy economic and social burdens. VGB-R04 is a novel AAV vector carrying a high specific activity factor IX variant. This study is intended to evaluate the safety, tolerability and efficacy of a single IV infusion of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 6 weeks before administration of VGB-R04. All subjects will undergo 52 weeks of safety observation and will be encouraged to enroll in an Long-term follow-up study to evaluate the long-term safety of VGB-R04 for a total of five years.
Interventions
GENETICVGB-R04
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant
Sponsors
Shanghai Vitalgen BioPharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male ≥18 years and ≤65years of age; 2. Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal); 3. At least 100 days exposure history to FIX; 4. Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding; 5. Have acceptable laboratory values: 1. Hemoglobin ≥110 g/L; 2. Platelets ≥100×109 /L; 3. AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory; 4. Bilirubin ≤3× ULN ; 5. Creatinine ≤1.5× ULN. 6. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein; 7. Agree to use reliable contraception until 2 consecutive samples are negative for vector sequences;
Exclusion criteria
1. Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to: 1. Preexisting diagnosis of portal hypertension; 2. Splenomegaly; 3. Encephalopathy; 4. Reduction of serum albumin; 5. Evidence of significant liver fibrosis; 2. Have anti-VGB-R04 neutralizing antibody titers ≥1:5; 3. Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.; 4. Novel coronavirus infection occurred in the 6 weeks prior to entry into the group 5. Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive); 6. Evidence of malignant tumours or those with a previous history of malignant tumours; 7. Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk; 8. Any immunodeficiency; 9. planned surgery may be required within one year; 10. Past thromboembolic events (arterial or venous thromboembolic events); 11. Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Baseline up to Week 52 | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment. |
| Incidence of serious adverse events | Baseline up to Week 52 | A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect |
| FIX:C Antigen Level at Steady State | Baseline up to Week 52 | FIX:C activity antigen levels were characterized by post-treatment population mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FIX:C activity level | Baseline up to Week 52 | FIX:C activity change from baseline during each visit. |
| Annualized FIX consumption changes from baseline | Baseline up to Week 52 | The annualized use of FIX replacement therapy will be calculated. |
| Vector- derived FIX antigen levels | Baseline up to Week 52 | The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity antigen levels will be characterized by post-treatment population mean, and its change from baseline during each visit. |
| Annualized bleeding rate changes from baseline | Baseline up to Week 52 | The annualized numberof bleeding episodes. |
Countries
China
Contacts
Primary ContactMin Li
Outcome results
None listed