Evaluating the safety of VGB-R04 for treating Hemophilia B

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

This study is testing a new treatment called VGB-R04 to see if it is safe for people with Hemophilia B after they receive a single infusion.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Male
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05152732 on ClinicalTrials.gov

What this trial studies

This pilot study assesses the safety and tolerability of a single intravenous infusion of VGB-R04, a novel AAV vector designed to treat Hemophilia B by delivering a high specific activity factor IX variant. Participants will undergo screening assessments and will be monitored for 52 weeks post-infusion to evaluate any adverse effects. The study aims to provide insights into the kinetics of the treatment and its potential long-term safety through an extension study lasting up to five years.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 to 75 with a confirmed diagnosis of Hemophilia B and specific baseline factor IX activity levels.

Not a fit: Patients with significant underlying liver disease or those with a history of inhibitors to factor IX protein may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce bleeding episodes and improve the quality of life for patients with Hemophilia B.

How similar studies have performed: While gene therapy approaches for Hemophilia B are emerging, this specific treatment and its methodology are relatively novel and have not been extensively tested in prior studies.

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Blood diseases hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, Doctor — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Lei Zhang, Doctor

Conditions Hemophilia B; Hemophilia; AAV; safety; gene therapy