Safety and Tolerability of VGB-R04 in Patients With Haemophilia B

Hemophilia B Clinical Trial

Official title:

Safety and Tolerability of VGB-R04 in Patients With Haemophilia B

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05152732
• Other study ID #: VGB-R04-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 28, 2021
• Est. completion date: December 2025

Study information

• Verified date: January 2023
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Lei Zhang, Doctor
• Phone: +86-13502118379
• Email: zhanglei1[@]ihcams.as.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.

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 kinetics 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(±2) weeks of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGB-R04 for a total of five years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3
• Est. completion date: December 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male =18 years and =75years of age;

2. Confirmed diagnosis of hemophilia B (baseline FIX activity = 2% of normal or documented history of FIX activity =2%);

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 =100×10'9 cells/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 barrier contraception until 3 consecutive samples are negative for vector sequences;

8. Able to provide informed consent and comply with the requirements of the study.

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. Evidence of active hepatitis B virus infection (HBV-DNA >103 IU/ml) or hepatitis C virus infection (HCV antigen and HCV-RNA positive);

5. Evidence of malignant tumours or those with a previous history of malignant tumours;

6. Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;

7. Any immunodeficiency;

8. Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 4 weeks;

9. Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within the last 3 months;

10. Previous history of hypersensitivity or allergic reaction to any FIX products or any immunoglobulin;

11. Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;

12. Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.

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	Blood diseases hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

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	Number of Participants with Clinically Significant Change from Baseline in Vital Signs	Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion	Baseline up to Week 52
Primary	Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings	The physical examination will include examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination will assess the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings will be considered to be clinically significant based on the investigator's decision	Baseline up to Week 52
Primary	Number of Participants with Clinical Laboratory Abnormalities	Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings were considered to be clinically significant based on the investigator's decision.	Baseline up to Week 52
Secondary	Vector- derived FIX:C Activity	All samples collected from participants for plasma FIX activity levels will be analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels	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	Baseline up to Week 52
Secondary	Annualized bleeding rate changes from baseline	The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated	Baseline up to Week 52
Secondary	Annualized FIX consumption changes from baseline	The use of on-demand FIX replacement therapy will be recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy will be calculated.	Baseline up to Week 52
Secondary	Number of target joints	The criterion of the target joint is a minimum of three bleeds into a single joint within a consecutive three-month period.	Baseline up to Week 52
Secondary	Vector shedding of VGB-R04	Saliva, urine and semen will be collected to assess clearance of vector genomes.	Baseline up to Week 52