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

Q. D. Nguyen, R. A. Schachar, C. I. Nduaka, M. Sperling, A. S. Basile, K. J. Klamerus, K. Chi-Burris, E. Yan, D. A. Paggiarino, I. Rosenblatt, A. Khan, R. Aitchison, S. S. Erlich

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1099-1105
Number of pages7
JournalEye (Basingstoke)
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2012

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Keywords

  • neovascular age-related macular degeneration
  • phase 1
  • siRNA

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Nguyen, Q. D., Schachar, R. A., Nduaka, C. I., Sperling, M., Basile, A. S., Klamerus, K. J., ... Erlich, S. S. (2012). Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients. Eye (Basingstoke), 26(8), 1099-1105. https://doi.org/10.1038/eye.2012.106