Lead-in Study of VGB-R04 Gene Therapy for Hemophilia B-- An Observational Survey Analysis Study

Study Overview
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Brief Summary
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This is a prospective, open, multicenter, observational lead-in study，to collect prospective efficacy and safety data of current replacement therapy in adult hemophilia B patients.

Detailed Description
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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 is a prospective, open, multicenter, observational lead-in study. To evaluate the efficacy and safety of current treatment regiments in patients with moderate to severe HB (FIX:C activity ≤2%). The efficacy and safety data collected in this study may be used as baseline data for subsequent related clinical trials of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 4 weeks. All subjects will undergo 26 weeks of efficacy and safety observation .Eligible subjects will be invited to a key clinical study（phase 2 study）of VGB-R04,and then 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.

Official Title
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Six-month lead-in Study to Collect Prospective Efficacy and Safety Data of Current Replacement Therapy in Adult Hemophilia B Patients -- An Observational Survey Analysis Study

Conditions
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Hemophilia B

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male ≥18 years and ≤65years of age; Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal); At least 50 days exposure history to FIX; Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding; Have acceptable laboratory values: Hemoglobin ≥110 g/L; Platelets ≥100×109 /L; AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory; Bilirubin ≤3× ULN ; Creatinine ≤1.5× ULN. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein; Exclusion Criteria: Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to: Preexisting diagnosis of portal hypertension; Splenomegaly; Encephalopathy; Reduction of serum albumin; Evidence of significant liver fibrosis; Have anti-VGB-R04 neutralizing antibody titers ≥1:5; Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.; Novel coronavirus infection occurred in the 6 weeks prior to entry into the group Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive); Evidence of malignant tumours or those with a previous history of malignant tumours; Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk; Any immunodeficiency; planned surgery may be required within one year; Past thromboembolic events (arterial or venous thromboembolic events); Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FIX replacement therapy.<br>Subject's previous treatment plan will be followed | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleeding rate changes from baseline | The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes. | Baseline up to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized FIX consumption changes from baseline | The use of on-demand FIX replacement therapy will be recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy will be calculated. | Baseline up to Week 26 | 
| Total number of annualized bleeding | Total number of annualized bleeding including spontaneous or traumatic bleeding. | Baseline up to Week 26 | 
| FIX:C activity level. | FIX:C activity level and its change from baseline . | Baseline up to Week 26 | 
| Number of target joints | The criterion of the target joint is a minimum of three bleeds into a single joint within a consecutive three-month period. | Baseline up to Week 26 | 
| The incidence of adverse Events of special interest | Adverse Events of special interest (serious or non-serious) are a category of events of scientific and medical concern that are particularly relevant to the sponsor's drug or research program. Adverse Events of special interest include liver dysfunction, inhibitors, thromboembolic events, and allergic reactions. | Baseline up to Week 26 |