Single dose GLP toxicity and biodistribution study of a conditionally replicative adenovirus vector, CRAd-S-pk7, administered by intracerebral injection to Syrian hamsters

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)

ISSN: 1479-5876