Summary of hemophilia B dogs injected with AAV vectors intraportally
Dog/injection no. . | Weight,*kg . | Age,*mo . | Sex . | Vector . | Vector dose, GC/kg . | Total GC injected . | WBCT, min . | aPTT, s . | cFIX, ng/mL . | cFIX, % . | Bleeds after treatment† . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| G43 | |||||||||||
| 1‡ | 16.5 | 6.0 | M | AAV2/8 | 5.26 × 1012 | 8.7 × 1013 | 13.5 ± 2.1 | 48.0 ± 6.5 | 1297.4 ± 235.2 | 25.9 ± 4.7 | 0 |
| LSP-cFIX-W | |||||||||||
| H12 | |||||||||||
| 1§ | 8.8 | 4.0 | F | AAV2/8 | 5.25 × 1012 | 4.6 × 1013 | 14.5 ± 1.9 | 55.6 ± 6.3 | 468.0 ± 109.6 | 9.4 ± 2.2 | 0 |
| LSP-cFIX-W | |||||||||||
| D39 | |||||||||||
| 1∥¶ | 5.0 | 2.8 | F | AAV2 | 2.8 × 1012 | 1.4 × 1013 | 12.0 ± 2.6 | 59.3 ± 6.3 | 34.2 ± 9.8 | 0.7 ± 0.2 | 6 |
| LSP-cFIX-W | |||||||||||
| 2# | 16.6 | 35.4 | F | AAV2/8 | 9.28 × 1012 | 1.5 × 1014 | 12.7 ± 1.6 | 48.6 ± 5.1 | 785.4 ± 61.6 | 15.7 ± 1.2 | 0 |
| LSP-cFIX-W | |||||||||||
| C52 | |||||||||||
| 1¶** | 17.6 | 6.5 | M | AAV2 | 2.8 × 1011 | 5.0 × 1012 | 16.3 ± 3.4 | 81.6 ± 17.8 | 3.6 ± 1.1 | < 0.1 | 3 |
| LSP-cFIX | |||||||||||
| 2†† | 17.2 | 45.2 | M | AAV2/5 | 2.3 × 1013 | 4.0 × 1014 | 13.1 ± 1.7 | 47.6 ± 6.3 | 798.5 ± 84.4 | 16.0 ± 1.7 | 0 |
| LSP-cFIX-W |
Dog/injection no. . | Weight,*kg . | Age,*mo . | Sex . | Vector . | Vector dose, GC/kg . | Total GC injected . | WBCT, min . | aPTT, s . | cFIX, ng/mL . | cFIX, % . | Bleeds after treatment† . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| G43 | |||||||||||
| 1‡ | 16.5 | 6.0 | M | AAV2/8 | 5.26 × 1012 | 8.7 × 1013 | 13.5 ± 2.1 | 48.0 ± 6.5 | 1297.4 ± 235.2 | 25.9 ± 4.7 | 0 |
| LSP-cFIX-W | |||||||||||
| H12 | |||||||||||
| 1§ | 8.8 | 4.0 | F | AAV2/8 | 5.25 × 1012 | 4.6 × 1013 | 14.5 ± 1.9 | 55.6 ± 6.3 | 468.0 ± 109.6 | 9.4 ± 2.2 | 0 |
| LSP-cFIX-W | |||||||||||
| D39 | |||||||||||
| 1∥¶ | 5.0 | 2.8 | F | AAV2 | 2.8 × 1012 | 1.4 × 1013 | 12.0 ± 2.6 | 59.3 ± 6.3 | 34.2 ± 9.8 | 0.7 ± 0.2 | 6 |
| LSP-cFIX-W | |||||||||||
| 2# | 16.6 | 35.4 | F | AAV2/8 | 9.28 × 1012 | 1.5 × 1014 | 12.7 ± 1.6 | 48.6 ± 5.1 | 785.4 ± 61.6 | 15.7 ± 1.2 | 0 |
| LSP-cFIX-W | |||||||||||
| C52 | |||||||||||
| 1¶** | 17.6 | 6.5 | M | AAV2 | 2.8 × 1011 | 5.0 × 1012 | 16.3 ± 3.4 | 81.6 ± 17.8 | 3.6 ± 1.1 | < 0.1 | 3 |
| LSP-cFIX | |||||||||||
| 2†† | 17.2 | 45.2 | M | AAV2/5 | 2.3 × 1013 | 4.0 × 1014 | 13.1 ± 1.7 | 47.6 ± 6.3 | 798.5 ± 84.4 | 16.0 ± 1.7 | 0 |
| LSP-cFIX-W |
Values of WBCT, aPTT, cFIX plasma levels, and cFIX as percentage of normal levels in dogs are mean (± SD) for the time period indicated. Normal ranges for WBCT and aPTT are 8 to 12 minutes and 24 to 32 seconds, respectively. Normal cFIX level in dogs is considered as 5 μg/mL (100%).
Weight and age at time of vector injection.
Bleeds after treatment were spontaneous bleeding episodes that occurred in hemophilia B dogs after AAV vector administration and required treatment with plasma infusion.
Values are from weeks 3 to 68.
Values are from weeks 3 to 62.
Values are from weeks 3 to 142.
Data obtained within 2 weeks of bleeding episodes that required plasma infusion were excluded.
Values are from weeks 145 to 262.
Values are from weeks 3 to 168.
Values are from weeks 171 to 303.