AN OPEN LABEL DOSE-ESCALATION STUDY OF A SELF COMPLEMENTARY ADENO-ASSOCIATED VIRAL VECTOR (scAAV2/8-LP1-hFIXco) FOR GENE TRANSFER IN SUBJECTS WITH HEMOPHILIA B
UTSW will serve as a satellite site performing only follow-up visits including physical exams, local labs and collection of biological specimens for shipment to a central laboratory starting 1 week after the vector infusion and for up to 15 years of follow-up. Infusion of the vector will take place at St Jude Children and amp;apos;s Research Hospital.
In severe factor IX deficiency, factor IX protein is absent from the body. Patients with this deficiency cannot make a blood clot effectively and suffer from severe bleeding episodes. These episodes can lead to lifelong disabilities.
This research study will test the safety of giving the patient a normal factor IX gene, which could produce factor IX protein in the body. The gene is carried by what is called a vector. The vector used in this study has been made from an adeno-associated virus, AAV2/8. For safety, the virus is altered so that it is unable to cause infection.
At UTSW HTC - only those subjects already consented to the parent study at St Jude Children's Research Hospital will be eligible for follow-up at our center.
Full protocol inclusion criteria:
Males >= 18 years of age with established severe HB (FIX:C<1u/dl) resulting from a missense mutation in the hFIX gene which has not been associated with an inhibitor in the database (http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html) with detectable FIX in serum. Individuals with a stop codon mutation, a promoter mutation, a small insertion or deletion causing a frame shift, a small in frame insertion or deletion or a splice junction mutation may be enrolled if their mutation has not been associated with an inhibitor,
2. Treated/exposed to FIX concentrates for at least 10 years,
3. A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes,
4. Able to give informed consent and comply with requirements of the trial,
5. Currently free of inhibitor and have no history of inhibitors to FIX protein, and
6. A negative family history for the development of an inhibitor
7. Willing to practice a reliable barrier method of contraception until 3 sequential semen samples are negative for vector genomes using our PCR assay.