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

Hemophilia B Clinical Trial

Official title:

A Phase 1/2 Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05441553
• Other study ID #: VGB-R04-101
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 2022
• Est. completion date: January 2025

Study information

• Verified date: June 2022
• Source: Shanghai Vitalgen BioPharma Co., Ltd.
• Contact: Min Li
• Phone: 18822167237
• Email: m.li[@]vitalgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 26
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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);

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• VGB-R04
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant

Locations

Country	Name	City	State
China	Shanghai Vitalgen Biopharma Co.,Ltd.	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Vitalgen BioPharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to Week 52
Primary	Incidence of serious adverse events	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	Baseline up to Week 52
Primary	FIX:C Antigen Level at Steady State	FIX:C activity antigen levels were characterized by post-treatment population mean.	Baseline up to Week 52
Secondary	FIX:C activity level	FIX:C activity change from baseline during each visit.	Baseline up to Week 52
Secondary	Vector- derived FIX antigen levels	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.	Baseline up to Week 52
Secondary	Annualized bleeding rate changes from baseline	The annualized numberof bleeding episodes.	Baseline up to Week 52
Secondary	Annualized FIX consumption changes from baseline	The annualized use of FIX replacement therapy will be calculated.	Baseline up to Week 52