Back to resultsA Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Primary Purpose
Hemophilia B
Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
VGB-R04
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B
Eligibility Criteria
Inclusion Criteria:
- Male ≥18 years and ≤65years of age;
- Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal);
- At least 100 days exposure history to FIX;
- Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
Have acceptable laboratory values:
- Hemoglobin ≥110 g/L;
- Platelets ≥100×109 /L;
- AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
- Bilirubin ≤3× ULN ;
- Creatinine ≤1.5× ULN.
- No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
- 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:
- Preexisting diagnosis of portal hypertension;
- Splenomegaly;
- Encephalopathy;
- Reduction of serum albumin;
- Evidence of significant liver fibrosis;
- Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
- Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
- Novel coronavirus infection occurred in the 6 weeks prior to entry into the group
- Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive);
- Evidence of malignant tumours or those with a previous history of malignant tumours;
- Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
- Any immunodeficiency;
- planned surgery may be required within one year;
- Past thromboembolic events (arterial or venous thromboembolic events);
- Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);
Sites / Locations
- Shanghai Vitalgen Biopharma Co.,Ltd.
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VGB-R04
Arm Description
Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer
Outcomes
Primary Outcome Measures
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.
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
FIX:C Antigen Level at Steady State
FIX:C activity antigen levels were characterized by post-treatment population mean.
Secondary Outcome Measures
FIX:C activity level
FIX:C activity change from baseline during each visit.
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.
Annualized bleeding rate changes from baseline
The annualized numberof bleeding episodes.
Annualized FIX consumption changes from baseline
The annualized use of FIX replacement therapy will be calculated.
Full Information
NCT ID
NCT05441553
First Posted
June 15, 2022
Last Updated
June 28, 2022
Sponsor
Shanghai Vitalgen BioPharma Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05441553
Brief Title
A Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Official Title
A Phase 1/2 Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Vitalgen BioPharma Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VGB-R04
Arm Type
Experimental
Arm Description
Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer
Intervention Type
Genetic
Intervention Name(s)
VGB-R04
Intervention Description
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
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.
Time Frame
Baseline up to Week 52
Title
Incidence of serious adverse events
Description
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
Time Frame
Baseline up to Week 52
Title
FIX:C Antigen Level at Steady State
Description
FIX:C activity antigen levels were characterized by post-treatment population mean.
Time Frame
Baseline up to Week 52
Secondary Outcome Measure Information:
Title
FIX:C activity level
Description
FIX:C activity change from baseline during each visit.
Time Frame
Baseline up to Week 52
Title
Vector- derived FIX antigen levels
Description
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.
Time Frame
Baseline up to Week 52
Title
Annualized bleeding rate changes from baseline
Description
The annualized numberof bleeding episodes.
Time Frame
Baseline up to Week 52
Title
Annualized FIX consumption changes from baseline
Description
The annualized use of FIX replacement therapy will be calculated.
Time Frame
Baseline up to Week 52
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male ≥18 years and ≤65years of age;
Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal);
At least 100 days exposure history to FIX;
Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
Have acceptable laboratory values:
Hemoglobin ≥110 g/L;
Platelets ≥100×109 /L;
AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
Bilirubin ≤3× ULN ;
Creatinine ≤1.5× ULN.
No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
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:
Preexisting diagnosis of portal hypertension;
Splenomegaly;
Encephalopathy;
Reduction of serum albumin;
Evidence of significant liver fibrosis;
Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
Novel coronavirus infection occurred in the 6 weeks prior to entry into the group
Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive);
Evidence of malignant tumours or those with a previous history of malignant tumours;
Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
Any immunodeficiency;
planned surgery may be required within one year;
Past thromboembolic events (arterial or venous thromboembolic events);
Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Min Li
Phone
18822167237
Email
m.li@vitalgen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, PhD
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Vitalgen Biopharma Co.,Ltd.
City
Shanghai
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Li, Bachelor's
Phone
18822167237
Email
m.li@vitalgen.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
A Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
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