Table 6.
AMG 181 immunogenicity rate in percentage (n animal positive/n animal tested) in male and female cynomolgus monkeys after single or multiple s.c. or i.v. administrations
| Dosing phase | Recovery phase | ||||
|---|---|---|---|---|---|
| Study | Regimen (mg kg−1) | Binding antibodies (%) | Neutralizing antibodies (%) | Binding antibodies (%) | Neutralizing antibodies (%) |
| Single dose | 0.01 i.v. | 100 (3/3) | – | – | – |
| 0.1 i.v. | 100 (3/3) | – | – | – | |
| 1 i.v. | 100 (3/3) | – | – | – | |
| 3 i.v. | 100 (3/3) | – | – | – | |
| 3 s.c. | 100 (3/3) | – | – | – | |
| 9 i.v. | 100 (6/6) | – | – | – | |
| 9 s.c. | 100 (6/6) | – | – | – | |
| All dosed | 100 (27/27) | – | – | ||
| Two-dose non-GLP weekly dosing ×2 | 0.5 s.c. | 100 (8/8) | – | 100 (4/4) | – |
| 80 s.c. | 0 (0/8) | – | 75 (3/4) | – | |
| All dosed | N/A | 88 (7/8) | – | ||
| 3 month GLP weekly dosing ×13 | 5 s.c. | 92 (11/12) | 82 (9/11) | 100 (4/4) | 100 (4/4) |
| 20 s.c. | 75 (9/12) | 22 (2/9) | 100 (4/4) | 75 (3/4) | |
| 80 s.c. | 67 (8/12) | 0 (0/8) | 25 (1/4) | 100 (1/1) | |
| 80 i.v. | 42 (5/12) | 0 (0/5) | 100 (4/4) | 75 (3/4) | |
| All dosed | N/A | N/A | 81 (13/16) | 85 (11/13) | |
–, dose group not part of the assay plan; N/A, not applicable due to possible drug interference with the assay preventing the detection of anti-AMG 181 antibodies in some animals at high doses, making combined low and high dose values unreliable.