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

NCTID	NCT00076557 (View at clinicaltrials.gov)
Description	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). (Show More)
Development Status	Inactive
Indication	Hemophilia B
Disease Ontology Term	DOID:12259
Compound Name	AAV2-hFIX16
Compound Description	adeno-associated virus serotype 2 capsid carrying optimized human F9 cDNA, under the control of the APOE enhancer and SERPINA1 promotor
Sponsor	Avigen
Funder Type	Industry
Recruitment Status	Terminated
Enrollment Count	15
Results Posted	Not Available

Target Gene/Variant	F9
Therapy Type	Gene transfer
Therapy Route	In-vivo
Mechanism of Action	Functional gene replacement
Route of Administration	Hepatic artery infusion
Drug Product Type	Viral vector
Target Tissue/Cell	Hepatocyte
Delivery System	Viral transduction
Vector Type	AAV2
Dose 1	8E10 vg/kg (n=2)
Dose 2	4E11 vg/kg (n=3)
Dose 3	2E12 vg/kg (n=2)

Eligible Age	>=18 Years
Standard Ages	Adult, Older adult
Sexes Eligible for Study	MALE
Eligibility Criteria	* 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. View Inclusion and Exclusion Criteria at ClinicalTrials.gov

No.of Trial Sites	3
Locations	United States

Has US IND	True
FDA Designations	Orphan Drug Designation
Recent Updates	Avigen suspended enrollment in May 2004; transferred AAV-based product rights to Genzyme Corporation in December 2005, LTFU was sponsored by CHOP from 2009-2013, then Spark Therapeutics afterwards