Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

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

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Design: Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. Participants: A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. Methods: In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. Main Outcome Measures: The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining <10 and <15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. Results: At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained <10 and <15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. Conclusions: In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)1867-1873
Number of pages7
JournalOphthalmology
Volume119
Issue number9
DOIs
StatePublished - Sep 1 2012

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Macular Degeneration
Small Interfering RNA
Visual Acuity
Choroidal Neovascularization
Platelet Factor 3
Therapeutics
Disclosure
Ranibizumab
PF-04523655
Intravitreal Injections
Outcome Assessment (Health Care)
Safety

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Nguyen, Q. D., Schachar, R. A., Nduaka, C. I., Sperling, M., Klamerus, K. J., Chi-Burris, K., ... Erlich, S. S. (2012). Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study). Ophthalmology, 119(9), 1867-1873. https://doi.org/10.1016/j.ophtha.2012.03.043

Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study). / Nguyen, Quan Dong; Schachar, Ronald A.; Nduaka, Chudy I.; Sperling, Marvin; Klamerus, Karen J.; Chi-Burris, Katherine; Yan, Eric; Paggiarino, Dario A.; Rosenblatt, Irit; Aitchison, Roger; Erlich, Shai S.

In: Ophthalmology, Vol. 119, No. 9, 01.09.2012, p. 1867-1873.

Research output: Contribution to journalArticle

Nguyen, QD, Schachar, RA, Nduaka, CI, Sperling, M, Klamerus, KJ, Chi-Burris, K, Yan, E, Paggiarino, DA, Rosenblatt, I, Aitchison, R & Erlich, SS 2012, 'Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)', Ophthalmology, vol. 119, no. 9, pp. 1867-1873. https://doi.org/10.1016/j.ophtha.2012.03.043
Nguyen, Quan Dong ; Schachar, Ronald A. ; Nduaka, Chudy I. ; Sperling, Marvin ; Klamerus, Karen J. ; Chi-Burris, Katherine ; Yan, Eric ; Paggiarino, Dario A. ; Rosenblatt, Irit ; Aitchison, Roger ; Erlich, Shai S. / Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study). In: Ophthalmology. 2012 ; Vol. 119, No. 9. pp. 1867-1873.
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abstract = "Objective: To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Design: Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. Participants: A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. Methods: In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. Main Outcome Measures: The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining <10 and <15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. Results: At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained <10 and <15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. Conclusions: In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.",
author = "Nguyen, {Quan Dong} and Schachar, {Ronald A.} and Nduaka, {Chudy I.} and Marvin Sperling and Klamerus, {Karen J.} and Katherine Chi-Burris and Eric Yan and Paggiarino, {Dario A.} and Irit Rosenblatt and Roger Aitchison and Erlich, {Shai S.}",
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T1 - Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

AU - Nguyen, Quan Dong

AU - Schachar, Ronald A.

AU - Nduaka, Chudy I.

AU - Sperling, Marvin

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 - 2012/9/1

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N2 - Objective: To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Design: Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. Participants: A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. Methods: In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. Main Outcome Measures: The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining <10 and <15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. Results: At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained <10 and <15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. Conclusions: In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

AB - Objective: To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Design: Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. Participants: A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. Methods: In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. Main Outcome Measures: The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining <10 and <15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. Results: At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained <10 and <15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. Conclusions: In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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