Enfoque de Transferencia Génica para la Hemofilia B Utilizando un Vector de Entrega del Gen FIX

Fecha de inicio: 11 de febrero de 2013

Inclusion Criteria: Males age 18-75 years, inclusive Established hemophilia B with ≥3 hemorrhages per year requiring treatment with exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding episodes Plasma FIX activity ≤2% (<1% for first cohort; then per protocol) Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative (undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at screening Exclusion Criteria: Family history of inhibitor to FIX protein or personal laboratory evidence of having developed inhibitors to FIX protein at any time (>0.6 Bethesda Units on any single test) Documented prior allergic reaction to any FIX product Detectable AAV8 neutralizing antibodies Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following: Platelet count <175,000/μL Albumin ≤3.5 g/dL Total bilirubin >1.5 x ULN and direct bilirubin ≥0.5 mg/dL Alkaline phosphatase >2.0 x ULN ALT or AST >2.0 x ULN (except for subjects who are HIV infected) Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging of 2 or greater) History of ascites, varices, variceal hemorrhage or hepatic encephalopathy