Elsevier

Ophthalmology

Volume 119, Issue 8, August 2012, Pages 1658-1665
Ophthalmology

Original article
One-Year Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with Diabetic Macular Edema

Presented in part at: Asia Pacific Academy of Ophthalmology Congress, March 2011, Sydney, Australia; and Association for Research in Vision and Ophthalmology Annual Meeting, May 2011, Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2012.02.010Get rights and content

Purpose

To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME).

Design

Randomized, double-masked, multicenter, phase 2 clinical trial.

Participants

Diabetic patients (n = 221) with center-involved DME.

Methods

Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation.

Main Outcome Measures

The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline.

Results

As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus −1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were −165.4 μm, −227.4 μm, −187.8 μm, and −180.3 μm versus −58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure.

Conclusions

Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Patients and Methods

The DA VINCI study was a randomized, double-masked, active-controlled multicenter phase 2 clinical trial. Thirty-nine sites in the United States, Canada, and Austria participated in the trial, and patients were enrolled between December 2008 and June 2009. The primary objective was to assess the efficacy of various doses and dose intervals of intravitreal VEGF Trap-Eye (aflibercept injection) on BCVA. The primary end point was the change in BCVA from baseline to week 24. Secondary objectives

Patient Disposition and Demographics

A total of 221 eyes were randomized, 219 were treated, and 176 completed the 52-week study (Table 1, available at http://aaojournal.org). Forty-three patients discontinued the study after receiving at least 1 treatment for the following reasons: lost to follow-up (n = 11), withdrew consent (n = 11), death (n = 6), treatment failures (n = 2), AE (n = 7), protocol deviation (n = 2), other (n = 4). Discontinuations were distributed evenly among all the treatment groups. Demographic information and

Discussion

In this phase 2 clinical trial, all VEGF Trap-Eye doses and dosing regimens were found to be superior to macular laser photocoagulation for the treatment of DME over the course of 52 weeks and produced similar results in terms of preserving and improving visual acuity. Patients who received VEGF Trap-Eye benefited from significantly greater increases in mean visual acuity at 1 year (+9.7 to +13.1 letters of improvement) compared with laser treatment alone (−1.3 letters change; P<0.0001).

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    Manuscript no. 2011-1202.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): Diana V. Do, Financial support, Genentech, Regeneron Pharmaceuticals; Quan Dong Nguyen, Financial support, Genentech, Regeneron Pharmaceuticals; David Boyer, Consultant, Genentech, Regeneron Pharmaceuticals, IÇO, Allergan; Lecturer, Genentech, Regeneron Pharmaceuticals, Allergan; Ursula Schmidt-Erfuth, Consultant, Alcon Labs, Bayer Healthcare, Novartis; Lecturer, Alcon Labs, Bayer Healthcare, Novartis, Regeneron Pharmaceuticals, Pfizer; David Brown, Consultant, Genentech, Regeneron Pharmaceuticals, Allergan; Lecturer, Genentech, Regeneron Pharmaceuticals, Allergan; Robert Vitti, Employee, Equity owner, Regeneron Pharmaceuticals; Alyson Berliner, Employee, Equity owner, Regeneron Pharmaceuticals; Oliver Zeitz, Employee, Bayer Healthcare; Rene Ruckert, Employee, Bayer Healthcare; Thomas Schmelter, Employee, Bayer Healthcare; Rupert Sandbrink, Employee, Bayer Healthcare; Jeff S. Heier, Consultant, Genentech, Regeneron Pharmaceuticals, Fovea; Lecturer, Genentech, Regeneron Pharmaceuticals.

    Sponsored by Regeneron Pharmaceuticals, Inc, Tarrytown, New York, and Bayer Healthcare, Berlin, Germany.

    A list of principal investigators of the DME And VEGF Trap-Eye: INvestigation of Clinical Impact Study is available at http://aaojournal.org.

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