A Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VGB-R04 Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer |
Genetic: VGB-R04
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- FIX:C activity level [Baseline up to Week 52]
FIX:C activity change from baseline during each visit.
- 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.
- Annualized FIX consumption changes from baseline [Baseline up to Week 52]
The annualized use of FIX replacement therapy will be calculated.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male ≥18 years and ≤65years of age;
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Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal);
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At least 100 days exposure history to FIX;
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Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
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Have acceptable laboratory values:
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Hemoglobin ≥110 g/L;
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Platelets ≥100×109 /L;
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AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
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Bilirubin ≤3× ULN ;
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Creatinine ≤1.5× ULN.
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No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
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Agree to use reliable contraception until 2 consecutive samples are negative for vector sequences;
Exclusion Criteria:
- Have significant underlying liver disease within the past 6 months prior to or at
Screening, including but not limited to:
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Preexisting diagnosis of portal hypertension;
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Splenomegaly;
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Encephalopathy;
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Reduction of serum albumin;
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Evidence of significant liver fibrosis;
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Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
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Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
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Novel coronavirus infection occurred in the 6 weeks prior to entry into the group
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Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive);
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Evidence of malignant tumours or those with a previous history of malignant tumours;
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Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
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Any immunodeficiency;
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planned surgery may be required within one year;
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Past thromboembolic events (arterial or venous thromboembolic events);
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Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Vitalgen Biopharma Co.,Ltd. | Shanghai | China |
Sponsors and Collaborators
- Shanghai Vitalgen BioPharma Co., Ltd.
Investigators
- Principal Investigator: Lei Zhang, PhD, Institute of Hematology & Blood Diseases Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VGB-R04-101