Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor
 IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.
Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting
 Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a
 proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX
 with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding
 episodes. This clinical program will test a gene transfer approach involving the use of a
 gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate
 the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable
 plasma FIX activity between 10% and 40% of normal activity.
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