Phase I/II Safety Study in Patients with Severe Hemophilia B

Stanford University, Stanford CA

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Abstract

AAV-2 mediated liver gene transfer for hemophilia B has been used to safely cure dogs of the disease in preclinical trials. While we have shown that AAV-2 vectors can transduce efficacious amounts of the factor IX gene into human hepatocytes, unpredicted human immune response has limited efficacy. While the promise of gene therapy for this disease is real, we plan a trial, which we believe addresses the limitations of the previous trial and will ultimately lead to a successful therapy for hemophilia. To do this, we plan to use pseudotyped vectors based on AAV-8. The potential advantages of AAV-8 over AAV-2 are: (1) Greater efficiency; (2) Simpler delivery route; (3) Lack of pre-existing humoral immunity; (4) Potential for lack of a T cell mediated immune response directed against capsid containing hepatocytes. The structure of the trial is similar in design to the previous AAV-2 liver based approach funded during the previous PEGT granting period. During the first two years, we plan to perform the appropriate preclinical studies that will allow for FDA approval to begin the phase I/II clinical trial in the beginning of year 03. During this period we anticipate treating 9 patients. We believe that hemophilia B may be treatable using AAV-8 vectors and the information learned from the proposed trial will provide data relevant for treating many hepatodeficiency states.