Treatment summary of FVIII-deficient dogs
Animal . | Gender . | Age (mo) . | Weight (kg) . | Vector dose (part/kg) . | Peak FVIII plasma activity (mU/mL) . | FVIII antibody titer (BU) . | ||
---|---|---|---|---|---|---|---|---|
APTT . | Coatest . | Peak . | Pre/Post reinfusion . | |||||
Dog A (Riley) | Male | 10 | 11.8 | 3 × 1012 | 18 700 | 58 680 | 1210 | 41/51 |
Dog B (JJ) | Male | 10 | 10.0 | 3 × 1012 | 19 900 | 43 591 | 37 | 1.7/2.5 |
Dog C (Cocoa) | Female | 12 | 12.0 | 6 × 1011 | 1347 | 1335 | 1.9 | 0/0 |
Dog D (Java) | Male | 12 | 18.5 | 6 × 1011 | 1427 | 1725 | 1.4 | 0/0 |
Animal . | Gender . | Age (mo) . | Weight (kg) . | Vector dose (part/kg) . | Peak FVIII plasma activity (mU/mL) . | FVIII antibody titer (BU) . | ||
---|---|---|---|---|---|---|---|---|
APTT . | Coatest . | Peak . | Pre/Post reinfusion . | |||||
Dog A (Riley) | Male | 10 | 11.8 | 3 × 1012 | 18 700 | 58 680 | 1210 | 41/51 |
Dog B (JJ) | Male | 10 | 10.0 | 3 × 1012 | 19 900 | 43 591 | 37 | 1.7/2.5 |
Dog C (Cocoa) | Female | 12 | 12.0 | 6 × 1011 | 1347 | 1335 | 1.9 | 0/0 |
Dog D (Java) | Male | 12 | 18.5 | 6 × 1011 | 1427 | 1725 | 1.4 | 0/0 |
Four hemophilic dogs were treated with the canine FVIII-encoding adenoviral vector, Av3H8401, via cephalic vein infusion. Age and weight of the animals directly prior to vector administration is displayed. Plasma samples were analyzed for FVIII biologic activity using the one-stage FVIII coagulant assay (APTT) and the Coatest chromogenic bioassay. Peak FVIII plasma levels were obtained 2 days after vector treatment in all 4 dogs. Plasma samples collected prior to and following vector treatment were analyzed for the presence of anticanine FVIII inhibitory antibodies using the Bethesda assay. All animals displayed a Bethesda titer of 0 prior to vector treatment. Peak FVIII antibody titers were obtained 12 days after vector treatment in dogs A and B and 14 days after vector treatment in dogs C and D. Canine cryoprecipitate (20 FVIII Unit/kg) was delivered by IV administration to dogs A and B at 26 months and dogs C and D at 20 months after vector treatment. Directly prior to and 10 days following FVIII protein infusion, antibody levels were measured. Dog A received 2 infusions of cryoprecipitate (20 FVIII U/kg). Following the first infusion, antibody levels were followed for 4 weeks with no change detected. The data displayed are antibody levels following the second protein infusion.