Table 1.
Assignment of hamsters to study groups
| Group | Treatment | CRAd-S-pk7 dose (vp/animal)a | Number of animals | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Core groups | Satellite groups | ||||||||
| Day 6 necropsy | Day 34 necropsy | Day 62 necropsy | Day 1 | Day 6 necropsy | Day 34 necropsy | Day 62 necropsy | |||
| 1 | Untreated | 0 | – | – | – | 5 M/5 F | – | – | – |
| 2 | Vehicle | 0 | 5 M/5 F | 5 M/5 F | 5 M/5 F | – | 5 M/5 F | 5 M/5 F | 5 M/5 F |
| 3 | Vector low | 2.5 × 107 | 5 M/5 F | 5 M/5 F | 5 M/5 F | – | 5 M/5 F | 5 M/5 F | 5 M/5 F |
| 4 | Vector mid | 2.5 × 108 | 5 M/5 F | 5 M/5 F | 5 M/5 F | – | 5 M/5 F | 5 M/5 F | 5 M/5 F |
| 5 | Vector high | 2.5 × 109 | 5 M/5 F | 5 M/5 F | 5 M/5 F | – | 5 M/5 F | 5 M/5 F | 5 M/5 F |
Thirty hamsters per sex were assigned to each of four dose groups, and were administered one intracerebral injection on day 1 of either vehicle (group 2) or the test article at 2.5 × 107, 2.5 × 108, or 2.5 × 109 viral particles (vp)/animal (groups 3, 4, and 5, respectively). Of these animals, 15 animals/sex/group (core groups) were used for toxicology evaluations including hematology and clinical chemistry, and the remaining animals (satellite groups) were used for assessment of the biodistribution and immunogenicity of the test article as well as the effect on coagulation parameters. In addition, five untreated animals per sex (group 1) were used on day 1 for collection of baseline immunogenicity samples, after which they were removed from the study without further evaluation
VP viral particles, M males, F females
aThe low, mid, and high vector doses were selected to bracket the expected human clinical range of 6.8 × 1010 to 2.06 × 1011 vp/dose, with doses scaled based on the relative brain weights of the two species (hamster ≈ 0.001 × human)