Lentiviral gene therapy to restore factor VIII for people with Hemophilia A

Lentiviral FVIII Gene Therapy for Hemophilia A

This will try a lentiviral treatment that modifies a person's own stem cells so their body can make factor VIII for people with severe Hemophilia A.

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: NCT03217032 on ClinicalTrials.gov

What this trial studies

In this Phase I program, researchers collect a patient's autologous hematopoietic stem cells, modify them outside the body with an advanced lentiviral vector (NHP/TYF) carrying a functional FVIII gene, and infuse the gene-modified cells back into the patient. The primary focus is on safety and early signals of efficacy, including monitoring factor VIII levels, bleeding frequency, and adverse events. Eligible participants are males aged two years and older with severe Hemophilia A and no history of inhibitors. Participants will undergo close clinical and laboratory follow-up at the treating center to monitor liver function, immune responses, and any vector-related findings.

Who should consider this trial

Good fit: Ideal candidates are males aged ≥2 years with confirmed severe Hemophilia A (FVIII ≤2%), a history of at least four bleeding events per year or on prophylaxis, no measurable FVIII inhibitors, and ability to consent and comply with contraception and follow-up.

Not a fit: People with significant liver dysfunction, active hepatitis, uncontrolled HIV with low CD4 counts, a history of FVIII inhibitors, females (not eligible), or those unable to travel to and comply with Shenzhen-based procedures and contraception requirements are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could lead to durable or long-term production of factor VIII, reducing or eliminating the need for regular factor infusions and lowering bleeding risk.

How similar studies have performed: AAV-based in vivo FVIII gene therapies have shown promising results and ex vivo lentiviral modification has been successful in other genetic diseases, but lentiviral FVIII therapy for Hemophilia A remains relatively novel and early-stage.

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 A (endogenous factor VIII ≤2 IU/dL or ≤2% of normal).
3. A minimum average of 4 bleeding events per year requiring episodic treatment of factor VIII infusions or prophylactic factor VIII infusions.
4. No measurable factor VIII inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor VIII 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 VIII.
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 — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, PhD

Conditions Hemophilia A; factor VIII; Gene therapy; lentiviral vector