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

Summary

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 (AUC_0-24). At 8 mg/kg in the multiple dose cohort, the Day 4 geometric mean AUC_0-24 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 AUC_0-24 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.

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