Elsevier

Ophthalmology

Volume 118, Issue 6, June 2011, Pages 1098-1106
Ophthalmology

Original article
The 1-year Results of CLEAR-IT 2, a Phase 2 Study of Vascular Endothelial Growth Factor Trap-Eye Dosed As-needed After 12-week Fixed Dosing

Presented at: The Retina Society, October, 2009; American Academy of Ophthalmology Annual Meeting, October, 2009; International Symposium on Ocular Pharmacology and Therapeutics, December 2009; Association for Research in Vision and Ophthalmology Annual Meeting, April, 2010.
https://doi.org/10.1016/j.ophtha.2011.03.020Get rights and content

Objective

To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD).

Design

Multicenter, randomized, double-masked trial.

Participants

We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD.

Methods

Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1–12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg).

Main Outcome Measures

Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52.

Results

The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (−130 μm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm2 at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events.

Conclusions

PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

The primary objectives of the study were to assess the effect of intravitreal VEGF Trap-Eye on CR/LT and to assess the ocular and systemic safety and tolerability of repeated doses of VEGF Trap-Eye in patients with choroidal neovascularization (CNV) associated with wet AMD. A key secondary objective was to assess the effect of VEGF Trap-Eye on BCVA.

This study was a double-masked, prospective, randomized, dose- and interval-ranging study in which 5 groups of approximately 30 patients each were

Patient Disposition

Of 159 patients who were randomized, 157 were treated and 134 (85.4%) completed 52 weeks in the study (Table 1 available online at http://aaojournal.org). For the 23 patients (14.6%) who were withdrawn before completion of 52 weeks, 6 (3.8%) withdrawals were at the request of the patient.

Baseline Characteristics

The study population was representative of the AMD population in the United States. Patients ranged in age from 53 to 94 years (mean, 78.3) and the majority were women (62%; Table 2). The mean time from

Discussion

Among patients with neovascular AMD, PRN dosing with VEGF Trap-Eye maintained efficacy established during a 12-week monthly or quarterly fixed-dosing phase for an additional 40 weeks. For all groups combined, a clinically significant improvement in visual acuity achieved at 12 weeks (5.7-letter gain) was maintained to 52 weeks (5.3-letter gain), accompanied by a decrease in CR/LT (−119 μm at week 12 and −130 μm at week 52). Among patients in all treatment groups combined, 22% experienced a gain

Acknowledgment

Technical writing and editorial assistance was provided by Meher Dustoor, PhD.

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    Financial Disclosure(s): The authors have made the following disclosures:

    Jeffrey S. Heier – Regeneron (C,S), Alcon (C), Genentech (C), Glaxosmithkline (C), Paloma (C), Neovista (C), Oraya (C).

    David Boyer – Alcon (C,L), Genentech (C,L), Regeneron (C), Novartis (C), Pfizer (C), Eyetech (C), Allergan (C,L).

    Quan Dong Nguyen – Genetech (S), Regeneron (S), Novartis (S), Pfizer (S), Lux Biosciences (S), Macu Sight (S), Bausch & Lomb (C).

    Dennis Marcus – Genentech (C,S), Regeneron (S), Allergan (S), Neovista (S), Pfizer (S), Ophthotech (S), Alimaera (S).

    Daniel B. Roth – Regeneron (C), Allergan (C), Notal Vision (C).

    George Yancopoulos – Regeneron (E,O).

    Neil Stahl – Regeneron Pharmaceuticals (E).

    Avner Ingerman – Regeneron Pharmaceuticals (E).

    Robert Vitti – Regeneron Pharmaceuticals (E).

    Alyson J. Berliner – Regeneron Pharmaceuticals (E).

    Ke Yang – Regeneron Pharmaceuticals (E, O).

    David M. Brown – Thrombogenics(S), Molecular Partners (C,S), Schering Plough (S), Paloma (C,S), Alimaera (S), Ophthotech (S).

    Supported by Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG. The sponsors participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, and the preparation, review and approval of the manuscript.

    Manuscript no. 2010-1500.

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