TY - JOUR T1 - RV568, a narrow spectrum kinase inhibitor (NSKI), inhibits virus induced nasal interleukin-8 (IL8) in the human viral challenge model where healthy adult male volunteers were experimentally inoculated with live respiratory syncytial virus JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 1970 AU - Lindsey Cass AU - Kazuhiro Ito AU - Catherine Charron AU - Pete Strong AU - Chantelle Norton AU - Anthony Gilbert AU - Rob Lambkin-Williams AU - Alex Mann AU - Garth Rapeport Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/1970.abstract N2 - RATIONALERV568 inhibits respiratory syncytial virus (RSV) induced IL8 release in nasal epithelial cells in vitro by targeting host cell signalling. The primary aim was to assess the effects of RV568 on nasal IL8 following inoculation with RSV Memphis 37 in human subjects and demonstrate translation of the preclinical data to support progression of RV568 in patients with respiratory disease.METHODS 42 subjects aged 18–45 years were recruited into this randomised, single-blind, placebo-controlled, parallel-group quarantine study. RV568 (400µg) was administered intranasally twice daily from Day (D) -1 to 8 inclusive. Subjects were inoculated with RSV on D0 and remained in quarantine until D12. Nasal wash samples were collected daily, except for D0 and 1, for the assessment of IL8 (Luminex); secondary endpoints included nasal IL6, viral load (RT-PCR), infectivity rate, clinical symptoms and nasal secretion (tissue weight) in infected subjects.RESULTS 71% of subjects (30/42) had laboratory confirmed RSV. There was a 46% inhibition of the mean area under the profile-time curve from D2 to 12 (AUC2-12) for IL8 in the RV568 group compared to placebo (p=0.07). There was no observed difference between the groups for IL6 (AUC2-12), viral load, infectivity, or clinical symptoms. For nasal secretion the mean AUC0-12 was 304.3 g/h in the RV568 group vs 107.5 g/h in the placebo group.CONCLUSIONUsing the RSV Human Viral Challenge Model subjects treated with RV568 reduced IL8 inflammatory response compared with placebo, consistent with preclinical findings. ER -