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

Brief Title

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

Official Title

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

Brief Summary

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

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 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.

Study Phase

Early Phase 1

Study Type

Interventional

Primary Outcome

Incidence of adverse events

Secondary Outcome

 Vector- derived FIX:C Activity

Condition

Hemophilia B

Intervention

VGB-R04

Study Arms / Comparison Groups

 VGB-R04

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Genetic

Estimated Enrollment

Start Date

December 28, 2021

Completion Date

December 2025

Primary Completion Date

March 2025

Eligibility Criteria

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.

Gender

Male

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Lei Zhang, Doctor, +86-13502118379, zhanglei[email protected]

Location Countries

China

Location Countries

China

Administrative Informations

NCT ID

NCT05152732

Organization ID

VGB-R04-001

Responsible Party

Sponsor

Study Sponsor

Institute of Hematology & Blood Diseases Hospital

Study Sponsor

Lei Zhang, Doctor, Principal Investigator, Institute of Hematology & Blood Diseases Hospital

Verification Date

January 2023