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

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

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.

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Incidence of adverse events

Secondary Outcome

 FIX:C activity level

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

July 2022

Completion Date

January 2025

Primary Completion Date

January 2025

Eligibility Criteria

        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);

Gender

Male

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Lei Zhang, PhD, 18822167237, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations

NCT ID

NCT05441553

Organization ID

VGB-R04-101

Responsible Party

Sponsor

Study Sponsor

Shanghai Vitalgen BioPharma Co., Ltd.

Study Sponsor

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

Verification Date

June 2022