Preclinical Testing of Adenoviral Vectors

In the development of a new adenoviral vector for gene transfer, the preclinical pharmacology and toxicology programs are typically conducted in conjunction with the development of the product manufacturing. The overall purpose of preclinical animal and in vitro studies is to support the safety and rationale for use of the product in human subjects. Although not unique to gene therapy vectors in general, or more specifically, to adenoviral vector development, there are several basic goals to be achieved by preclinical testing which contribute to the design and conduct of the initial clinical trials. These include, but are not limited to, (i) identification of dose(s) which confer the desired biologic effect; (ii) definition of a safe starting dose and escalation scheme; (iii) identification of pharmacodynamic measures of biologic activity; (iv) identification of safety and toxicity parameters to monitor in the clinical trial; (v) definition of inclusion and/or exclusion criteria based on observed toxicities, and, finally, (vi) designated stopping rules for the clinical trial based on the toxicity profile observed in animals.

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