Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B

Prior treatment

• Documented prior allergic reaction to any FIX product
• Detectable AAV8 neutralizing antibodies

Lab values

• 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)
• 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

• 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