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Eye (Lond). 2012 Aug;26(8):1099-105. doi: 10.1038/eye.2012.106. Epub 2012 May 25.

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

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Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.



To 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).


Prospective, 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 μg 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 μg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655.


Doses of PF-04523655 ≥ 400 μg 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 μg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities.


A single IVT injection of PF-0523655 ≤ 3000 μg seems safe and well tolerated in eyes with neovascular AMD.

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