A Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients

Shanghai Vitalgen BioPharma Co., Ltd.26 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia B

Interventions

VGB-R04GENETIC

A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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);

Locations (1)

Shanghai Vitalgen Biopharma Co.,Ltd.

Shanghai, China

Outcomes

Primary Outcomes

Incidence of adverse events

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.