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

• Published in: Investigative ophthalmology & visual science Vol. 53; no. 12; pp. 7666 - 7674
• Main Authors: Nguyen, Quan Dong, Schachar, Ronald A, Nduaka, Chudy I, Sperling, Marvin, Basile, Anthony S, Klamerus, Karen J, Chi-Burris, Katherine, Yan, Eric, Paggiarino, Dario A, Rosenblatt, Irit, Aitchison, Roger, Erlich, Shai S
• Format: Journal Article
• Language: English
• Published: United States 15-11-2012
• Subjects: 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
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.12-9961

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.
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.
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.
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. (ClinicalTrials.gov number, NCT00701181.).