Glenn J Jaffe1, Thomas A Ciulla2, Antonio P Ciardella3, Francois Devin4, Pravin U Dugel5, Chiara M Eandi6, Harvey Masonson2, Jordi Monés7, Joel A Pearlman8, Maddalena Quaranta-El Maftouhi9, Federico Ricci10, Keith Westby2, Samir C Patel2. 1. Department of Ophthalmology, Duke Reading Center, Duke University, Durham, North Carolina. Electronic address: jaffe001@mc.duke.edu. 2. Ophthotech Corporation, New York, NY. 3. Azienda Ospedaliero-Universitaria di Bologna-Policlinico S. Orsola-Malpighi, Unità Operativa Oftalmologia-Ciardella, Bologna, Italy. 4. Centre Paradis Monticelli, Marseilles, France. 5. Retinal Consultants of Arizona, Phoenix, Arizona, and USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. 6. Department of Surgical Science, Eye Clinic, University of Torino, Torino, Italy. 7. Institut de la Macula, Centro Medico Teknon, QuironSalud, and Barcelona Macula Foundation, Barcelona, Spain. 8. Retinal Consultants, Sacramento, California. 9. Centre Rabelais, Lyon, France. 10. Università Tor Vergata-Fondazione PTV Policlinico Tor Vergata, Unità Operativa Semplice Dipartimentale Patologie Retiniche-Dipartimento di Chirurgia, Rome, Italy.
Abstract
PURPOSE: To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti-vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial. PARTICIPANTS: Four hundred forty-nine patients with treatment-naïve nAMD. METHODS: Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks. MAIN OUTCOME MEASURES: The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks. RESULTS: No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group. CONCLUSIONS: In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.
RCT Entities:
PURPOSE: To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti-vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial. PARTICIPANTS: Four hundred forty-nine patients with treatment-naïve nAMD. METHODS:Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks. MAIN OUTCOME MEASURES: The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks. RESULTS: No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group. CONCLUSIONS: In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.
Authors: Ebenezer Daniel; Wei Pan; Gui-Shuang Ying; Benjamin J Kim; Juan E Grunwald; Frederick L Ferris; Glenn J Jaffe; Cynthia A Toth; Daniel F Martin; Stuart L Fine; Maureen G Maguire Journal: Ophthalmology Date: 2018-02-14 Impact factor: 12.079
Authors: Rehan M Hussain; Bilal A Shaukat; Lauren M Ciulla; Audina M Berrocal; Jayanth Sridhar Journal: Drug Des Devel Ther Date: 2021-06-21 Impact factor: 4.162