Safety of a New Type of Treatment Called Gene Transfer for the Treatment of Severe Hemophilia B

A Phase I Safety Study in Subjects With Severe Hemophilia B (Factor IX Deficiency) Using Adeno-Associated Viral Vector to Deliver the Gene for Human Factor IX Into the Liver

Stanford University, Children's Hospital of Philadelphia, The Hemophilia Center of Western Pennsylvania, University of Washington, The University of Texas Health Science Center, Houston, University of Campinas, Brazil, Christian Medical College, Vellore, India, Royal Prince Alfred Hospital, Sydney, Australia

In this study a modified virus called adeno-associated virus (AAV) will be used to transfer a normal gene for human clotting factor IX into patients with severe hemophilia B (AAV human Factor IX vector). Gene therapy is a very new medical technique being used in a number of clinical studies for diseases such as cancer and cystic fibrosis. At this time, the U.S. Food and Drug Administration has approved no gene transfer products for commercial use. To date, 8 subjects have received AAV vector in the muscle for a hemophilia B trial by intramuscular injection, and, to date, 6 subjects have been treated with AAV vector in the current hemophilia B liver trial. Eleven cystic fibrosis subjects have received AAV vector into their nasal sinuses or lungs to date. In this study, AAV human Factor IX vector will be injected into the liver using a catheter inserted into a large blood vessel (called the proper hepatic artery or the right hepatic artery).

Males with severe hemophilia B with Factor IX activity level < 1% of normal. Life expectancy of > 1 year. Age > 18 years old. Ability to give informed consent. Greater than twenty exposure days of treatment with Factor IX protein. No history or presence of an inhibitor to Factor IX protein. Subjects must be able to receive Factor IX protein on a home infusion protocol. Subjects must have a normal protime (PT). Hepatitis C infected subjects will be evaluated for liver fibrosis based on liver biopsy data graded on a scale of 0-4 (Poynard et. al., 1997). Subjects who are Hepatitis C antibody and RNA positive and have not had a liver biopsy within the last 36 months will be required to have one. Subjects must have low AAV titer.