3 years ago

Safety, Tolerability, and Pharmacokinetics of Radavirsen (AVI-7100), an Antisense Oligonucleotide Targeting Influenza A M1/M2 translation

Richard T. Davey, Michael Wong, Alison Heald, Kristina M. Brooks, Parag Kumar, Patrick Iversen, Paula Muñoz, Jocelyn Voell, John H. Beigel, Jianbo Zhang
Aims To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults. Methods A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0.5 to 8 mg/kg or placebo. The second was a multiple dose study of 16 subjects randomized 12:4 to receive 8 mg/kg or placebo once daily for 5 days. Results 66 subjects were screened and 56 subjects were dosed between 2013 and 2015. At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo. The most common adverse events were headache and proteinuria, and were similar among those receiving radavirsen or placebo. Single dose PK demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC0-24). At 8 mg/kg in the multiple dose cohort, the Day 4 geometric mean AUC0-24 was 57.9 μg*h/mL. Conclusion Single infusions of radavirsen up to 8 mg/kg, and multi-dosing at 8 mg/kg once daily for 5 days, appear to be safe and well-tolerated in healthy subjects. The multi-dose Day 4 AUC0-24 this study is comparable to the AUC which was associated with protection from viral infection in a preclinical ferret influenza model. Further evaluation of radavirsen for the treatment of influenza infections is warranted.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13405

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