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

Quan Dong Nguyen, Ronald A. Schachar, Chudy I. Nduaka, Marvin Sperling, Anthony S. Basile, Karen J. Klamerus, Katherine Chi-Burris, Eric Yan, Dario A. Paggiarino, Irit Rosenblatt, Roger Aitchison, Shai S. Erlich

Research output: Contribution to journalArticle

Abstract

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 photoco-agulation. 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 1/4 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.

Original languageEnglish (US)
Pages (from-to)7666-7674
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number12
DOIs
StatePublished - Nov 2012

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Macular Edema
Small Interfering RNA
Visual Acuity
Lasers
Platelet Factor 3
Medical Futility
PF-04523655
Intravitreal Injections
Gene Targeting
Therapeutics
Nucleotides
Outcome Assessment (Health Care)
Clinical Trials
Safety

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Nguyen, Q. D., Schachar, R. A., Nduaka, C. I., Sperling, M., Basile, A. S., Klamerus, K. J., ... Erlich, S. S. (2012). Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study). Investigative Ophthalmology and Visual Science, 53(12), 7666-7674. https://doi.org/10.1167/iovs.12-9961

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

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 12, 11.2012, p. 7666-7674.

Research output: Contribution to journalArticle

Nguyen, QD, Schachar, RA, Nduaka, CI, Sperling, M, Basile, AS, Klamerus, KJ, Chi-Burris, K, Yan, E, Paggiarino, DA, Rosenblatt, I, Aitchison, R & Erlich, SS 2012, 'Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study)', Investigative Ophthalmology and Visual Science, vol. 53, no. 12, pp. 7666-7674. https://doi.org/10.1167/iovs.12-9961
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. / Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study). In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 12. pp. 7666-7674.
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abstract = "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 photoco-agulation. 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 1/4 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.",
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T1 - Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study)

AU - Nguyen, Quan Dong

AU - Schachar, Ronald A.

AU - Nduaka, Chudy I.

AU - Sperling, Marvin

AU - Basile, Anthony S.

AU - Klamerus, Karen J.

AU - Chi-Burris, Katherine

AU - Yan, Eric

AU - Paggiarino, Dario A.

AU - Rosenblatt, Irit

AU - Aitchison, Roger

AU - Erlich, Shai S.

PY - 2012/11

Y1 - 2012/11

N2 - 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 photoco-agulation. 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 1/4 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.

AB - 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 photoco-agulation. 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 1/4 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.

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