Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial.
Journal Article (Multicenter Study;Journal Article)
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.Full Text
Duke Authors
Cited Authors
- Jaffe, GJ; Ciulla, TA; Ciardella, AP; Devin, F; Dugel, PU; Eandi, CM; Masonson, H; Monés, J; Pearlman, JA; Quaranta-El Maftouhi, M; Ricci, F; Westby, K; Patel, SC
Published Date
- February 2017
Published In
Volume / Issue
- 124 / 2
Start / End Page
- 224 - 234
PubMed ID
- 28029445
Electronic International Standard Serial Number (EISSN)
- 1549-4713
International Standard Serial Number (ISSN)
- 0161-6420
Digital Object Identifier (DOI)
- 10.1016/j.ophtha.2016.10.010
Language
- eng