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

Phase 1

Not yet recruiting

• Conditions: Hemophilia B
• Interventions: Genetic: VGB-R04

• Registration Number: NCT05441553
• Lead Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.

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.

Study Timeline

• Status Verified: 2022-06
• Study First Submitted: 2022-06-15
• Study First Submitted QC: 2022-06-28
• Last Update Submitted: 2022-06-28
• Study Start: 2022-07
• Study First Posted: 2022-07-01
• Last Update Posted: 2022-07-01
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 26

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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
VGB-R04	VGB-R04	Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer

Primary Outcome Measures

Name	Time	Method
FIX:C Antigen Level at Steady State	Baseline up to Week 52	FIX:C activity antigen levels were characterized by post-treatment population mean.
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
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.

Secondary Outcome Measures

Name	Time	Method
FIX:C activity level	Baseline up to Week 52	FIX:C activity 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.
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.

Trial Locations

Locations (1)

Shanghai Vitalgen Biopharma Co.,Ltd.; 🇨🇳 Shanghai, China