Abstract
Background
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).
Methods
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.
Results
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.
Conclusion
A single IVT injection of PF-0523655 ≤3000 μg seems safe and well tolerated in eyes with neovascular AMD.
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Acknowledgements
This study was supported by Pfizer Inc. San Diego, California, USA.
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RA Schachar, CI Nduaka, M Sperling, AS Basile, K Chi-Burris, KJ Klamerus, E Yan, DA Paggiarino were employees of Pfizer at the time of the study; QD Nguyen and I Rosenblatt were investigators; and A Khan, R Aitchison, and SS Erlich were employees of Quark Phamaceuticals Inc. at the time of the study.
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Appendix
Tom S Chang, Retina Institute of California, Pasadena, CA, USA; Michaella Goldstein, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Peter Kaiser, Cole Eye Institute, Cleveland, OH, USA; James M Klancnik, Vitreous-Retina-Macula, Consultants of New York, New York, NY, USA; Gregg Kokame, Retina Consultants of Hawaii, Aiea, Hawaii; Quan Dong Nguyen, Wilmer Eye Institute, Baltimore, MD, USA; Roger L Novack, Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA; Anat Pilpul, Kaplan Medical Center, Rehovot, Israel; Irit Rosenblatt, Rabin Medical Center, Petah Tikva, Israel; Philip J Rosenfeld, Bascom Palmer Eye Institute, Miami, FL, USA; Daniel Ting, Bay Area Retina Associates, Walnut Creek, CA, USA.
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Nguyen, Q., Schachar, R., Nduaka, C. et al. Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients. Eye 26, 1099–1105 (2012). https://doi.org/10.1038/eye.2012.106
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DOI: https://doi.org/10.1038/eye.2012.106
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