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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophilia B
• Intervention / Treatment: Genetic: VGB-R04

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 Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Min Li; Phone Number: 18822167237; Email: m.li@vitalgen.com

Study Locations

• China
  • Shanghai, China
    • Shanghai Vitalgen Biopharma Co.,Ltd.
    • Contact: Min Li, Bachelor's; Phone Number: 18822167237; Email: m.li@vitalgen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
FIX:C activity level	FIX:C activity change from baseline during each visit.	Baseline up to Week 52
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
Annualized bleeding rate changes from baseline	The annualized numberof bleeding episodes.	Baseline up to Week 52
Annualized FIX consumption changes from baseline	The annualized use of FIX replacement therapy will be calculated.	Baseline up to Week 52

Collaborators and Investigators

• Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.
• Investigators: Principal Investigator: Lei Zhang, PhD, Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: June 15, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: VGB-R04-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD will be shared with other researchers when VGB-R04 is fully approved.
• IPD Sharing Time Frame: IPD will be shared with other researchers when VGB-R04 is fully approved.
• IPD Sharing Access Criteria: IPD will be shared with other researchers when VGB-R04 is fully approved.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No