Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study).
OBJECTIVE
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. (ClinicalTrials.gov number, NCT00701181.).
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
Quan Dong
QD
Nguyen
Ronald A
RA
Schachar
Chudy I
CI
Nduaka
Marvin
M
Sperling
Anthony S
AS
Basile
Karen J
KJ
Klamerus
Katherine
K
Chi-Burris
Eric
E
Yan
Dario A
DA
Paggiarino
Irit
I
Rosenblatt
Roger
R
Aitchison
Shai S
SS
Erlich
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008266:Macula Lutea / Q000187:drug effects / Q000473:pathology; D008269:Macular Edema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity
C576360:PF-04523655; D034741:RNA, Small Interfering