Lentiviral FVIII Gene Therapy

This study is a Phase I trial using an advanced lentiviral vector to deliver a functional gene for human clotting factor VIII into patients with hemophilia A, to evaluate the safety and efficacy of infusion of lentiviral gene modified autologous stem cells in patients.

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.