RNAi-based treatment for neovascular age-related macular degeneration by Sirna-027

Am J Ophthalmol. 2010 Jul;150(1):33-39.e2. doi: 10.1016/j.ajo.2010.02.006.


Purpose: To assess the safety, tolerability, pharmacokinetics, and dose-limiting toxicity of single intravitreal injection of Sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor-1, in patients with choroidal neovascularization (CNV) resulting from neovascular age-related macular degeneration (AMD). Secondary objectives included assessment of anatomic changes in retinal thickness, size of CNV, and changes in visual acuity.

Design: Prospective, open-label, single-dose, dose-escalation phase 1 study.

Methods: Twenty-six eyes of 26 patients with a median age of 82 years and CNV resulting from AMD who had previous treatments with other therapies were treated at 2 academic retinal practices. Patients received a single dose of Sirna-027 (100, 200, 400, 800, 1200, or 1600 microg/eye). Blood was sampled for pharmacokinetic analysis at 1, 4, and 24 hours after injection and on day 7. Patients underwent ophthalmic examinations including visual acuity, fluorescein angiography, and optical coherence tomography at screening and days 7, 14, 28, and 84. The main outcome measures were adverse reactions and dose-limiting toxicities.

Results: Intravitreal injection of a single dose of Sirna-027 from 100 to 1600 microg was well tolerated in patients with AMD, with no dose-limiting toxicity found. Adverse events were mild to moderate in severity. Adjusted mean foveal thickness decreased within 2 weeks after study treatment. The decrease was most pronounced in the 100- and 200-microg doses.

Conclusions: A single intravitreal dose of Sirna-027 up to 1600 microg/eye was well tolerated in patients with CNV resulting from neovascular AMD that had been refractory to other therapies. Stabilization or improvement in visual acuity and foveal thickness was observed. No dose-response or dose-limiting effects were noted.

Trial registration: ClinicalTrials.gov NCT00363714.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism
  • Female
  • Fluorescein Angiography
  • Fovea Centralis / pathology
  • Humans
  • Injections
  • Macular Degeneration / complications
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / metabolism
  • Male
  • Prospective Studies
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / pharmacokinetics
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Visual Acuity / physiology
  • Vitreous Body


  • RNA, Messenger
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor Receptor-1

Associated data

  • ClinicalTrials.gov/NCT00363714