Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients

Abstract

BackgroundTo evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD).MethodsProspective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) 20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 g of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of 20/100 and 20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 g of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655.ResultsDoses of PF-04523655 400 g were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 g of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities.ConclusionA single IVT injection of PF-0523655 3000 g seems safe and well tolerated in eyes with neovascular AMD. © 2012 Macmillan Publishers Limited All rights reserved.