Lentiviral gene therapy to restore Factor IX in people with hemophilia B

Lentiviral FIX Gene Therapy for Hemophilia B

This trial tests whether infusing a patient’s own stem cells that have been changed with a lentiviral vector carrying a working Factor IX gene can safely raise Factor IX levels and reduce bleeding in people with severe hemophilia B.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 2 Years to 65 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT03961243 on ClinicalTrials.gov

What this trial studies

This Phase I, single-center protocol uses an advanced lentiviral vector (NHP/TYF) to insert a functional FIX gene into autologous hematopoietic stem cells, which are then infused back into the patient. The primary focus is safety, with monitoring for adverse events, vector-related complications, and evidence of persistent gene expression. Secondary observations include changes in circulating Factor IX activity and the frequency of bleeding events or replacement factor use. Patients undergo close, long-term follow-up at the treating center to monitor liver function, vector sequences, and clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates are males aged 2 years or older with confirmed severe hemophilia B (Factor IX ≤2% or ≤2 IU/dL), a history of frequent bleeding (about four or more treated bleeds per year), no measurable FIX inhibitor, and acceptable liver function.

Not a fit: Patients with existing FIX inhibitors, active hepatitis B or C, significant liver dysfunction, uncontrolled HIV with low CD4 counts, or those with only mild hemophilia are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, the approach could provide durable increases in Factor IX activity and reduce or eliminate the need for regular factor concentrate infusions.

How similar studies have performed: Gene therapy has produced lasting Factor IX increases in other hemophilia B programs using AAV vectors and lentiviral approaches have shown promise in preclinical models and other genetic diseases, but lentiviral ex vivo gene therapy for hemophilia B in humans remains early and not yet widely validated.

Eligibility criteria

Inclusion Criteria:

* 1\. Able to provide informed consent and comply with requirements of the study. 2. Males ≥2 years with confirmed diagnosis of hemophilia B (endogenous factor IX ≤2 IU/dL or ≤2% of normal).

  3\. A minimum average of 4 bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions.

  4\. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein.

  5\. Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences.

Exclusion Criteria:

* 1\. Significant liver dysfunction as defined by abnormal alanine transaminase, bilirubin and alkaline phosphatase.

  2\. History of inhibitor against factor IX. 3. Evidence of active hepatitis B or C and currently on antiviral therapy. 4. Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (subjects who are HIV+ and stable with CD4 count \>200/mm3 and undetectable viral load are eligible to enroll).

  5\. Any evidence of active infection or any immunosuppressive disorder. 6. Participated in a gene transfer trial within the last 6 months or in a clinical trial with an investigational drug within the last 12 weeks.

  7\. Unable or unwilling to comply with study assessments.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Lung-Ji Chang, PhD — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, PhD

Conditions Hemophilia B; factor IX; Gene therapylentiviral vector