Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study)

Invest Ophthalmol Vis Sci. 2012 Nov 15;53(12):7666-74. doi: 10.1167/iovs.12-9961.


Purpose: To evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation.

Methods: This multicenter, prospective, masked, randomized, active-controlled, phase 2 interventional clinical trial enrolled 184 DME patients with best corrected visual acuity (BCVA) of 20/40 to 20/320 inclusive in the study eye. Patients were randomly assigned to 0.4-mg, 1-mg, 3-mg PF-04523655 intravitreal injections or laser. The main outcome measure was the change in BCVA from baseline to month 12.

Results: All doses of PF-04523655 improved BCVA from baseline through month 12. At month 12, the PF-04523655 3-mg group showed a trend for greater improvement in BCVA from baseline than laser (respectively 5.77 vs. 2.39 letters; P = 0.08; 2-sided α = 0.10). The study was terminated early at month 12 based on predetermined futility criteria for efficacy and discontinuation rates. PF-04523655 was generally safe and well-tolerated, with few adverse events considered treatment-related. By month 12, the discontinuation rates in the PF-04523655 groups were higher than the laser group and were inversely related to dose levels.

Conclusions: PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients. Studies of higher doses are planned to determine the optimal efficacious dose of PF-04523655. PF-04523655 may offer a new mode of therapeutic action in the management of DME. ( number, NCT00701181.).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / pathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Macula Lutea / drug effects
  • Macula Lutea / pathology
  • Macular Edema / drug therapy*
  • Macular Edema / etiology
  • Macular Edema / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / therapeutic use
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Visual Acuity


  • PF-04523655
  • RNA, Small Interfering

Associated data