Elsevier

Ophthalmology

Volume 110, Issue 12, December 2003, Pages 2372-2383
Ophthalmology

Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration: twelve-month clinical outcomes

https://doi.org/10.1016/j.ophtha.2003.08.020Get rights and content

Abstract

Purpose

To evaluate safety and efficacy of the angiostatic agent anecortave acetate, compared with a placebo, for treatment of subfoveal choroidal neovascularization (CNV).

Design

Ongoing masked, randomized, placebo-controlled, parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a placebo.

Participants

There were 128 eyes of 128 patients with subfoveal CNV secondary to age-related macular degeneration who were enrolled and treated, with 80% (102/128) of eyes presenting with predominantly classic lesions at baseline.

Methods

All eyes received a posterior juxtascleral depot application of masked study medication or a placebo, with retreatment at 6-month intervals if the masked investigator believed the patient could benefit. Patients received periodic detailed ophthalmic examinations with both fluorescein and indocyanine green angiography, general physical examinations with electrocardiograms, and hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data were periodically reviewed by the Independent Safety Committee overseeing the study.

Main outcome measures

Best-corrected logarithm of the minimum angle of resolution (logMAR) vision and fluorescein angiographic lesion characteristics were compared over time and among treatment groups.

Results

At month 12, anecortave acetate (15 mg) administered at 6-month intervals was statistically superior to the placebo for 3 measures of clinical efficacy: mean change from baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P = 0.0323), and prevention of severe vision loss (decrease of ≥6 logMAR lines from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions revealed that anecortave acetate (15 mg) was also superior to the placebo at 1 year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and 0.0299, respectively). Anecortave acetate (15 mg) trended toward significance over the placebo at month 12 for inhibition of total lesion growth and for inhibition of both the total CNV component and the classic CNV component in both the overall and subgroup analyses. The Independent Safety Committee identified no clinically relevant treatment-related safety issues.

Conclusions

Anecortave acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion growth.

Section snippets

Materials and methods

Before patient enrollment, each participating clinical center obtained approval from its institutional review board or independent ethics committee. An institutional review board– or independent ethics committee–approved informed consent document was reviewed and signed by all potential study patients before the start of screening procedures. The principal investigator, subinvestigators, study coordinator(s), and support personnel at each clinical center were trained in specific study

Patient disposition

As demonstrated in Table 2, the 4 treatment groups were similar at baseline regarding numbers of patients, patient demographics, logMAR vision, and lesion characteristics. Clinical data from all patients were analyzed after completion of the 12-month study visit by the last study patient on April 30, 2002. Of the 128 patients enrolled and treated, 76 patients (59.4%) completed their month 12 visit. Patients were to be re-treated with their masked study medication if, in the masked

Discussion

The primary efficacy variable for this study was mean change from baseline in logMAR visual acuity. The 12-month data analysis demonstrates that anecortave acetate (15 mg) is safe and clinically efficacious compared with a placebo for both stabilization of vision (<3 logMAR line change) and inhibition of lesion growth. Statistically significant differences between anecortave acetate (15 mg) and the placebo were demonstrated for mean change from baseline logMAR vision, stabilization of vision,

Acknowledgements

The Writing Committee was responsible for preparation of the manuscript on behalf of the Anecortave Acetate Clinical Study Group. This Committee was composed of the following: Donald J. D'Amico, MD, Chairman, Independent Safety Committee; Morton F. Goldberg, MD, The Wilmer Eye Institute, Baltimore, MD, Consultant to Alcon Research, Ltd.; Henry Hudson, MD, Principal Investigator; Janice A. Jerdan, PhD, Alcon Research, Ltd.; D. Scott Krueger, PhD, Alcon Research, Ltd.; Susan P. Luna, MS, Alcon

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Manuscript no. 220690.

Financial support: grant research support, travel expenses, and honoraria.

Proprietary interest: none.

Portions of these data presented at: 2002 Retina Congress, October, 2002; San Francisco.

The 6-month results from this study have been published (Retina 2003;23:14–23).

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