Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER Study Year 1

doi:10.1016/j.ajo.2007.10.004

American Journal of Ophthalmology

Volume 145, Issue 2, February 2008, Pages 239-248.e5

https://doi.org/10.1016/j.ajo.2007.10.004 Get rights and content

Purpose

To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Design

Phase IIIb, multicenter, randomized, double-masked, sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions.

Methods

Patients were randomized 1:1:1 to 0.3 mg ranibizumab (n = 60), 0.5 mg ranibizumab (n = 61), or sham (n = 63) treatment groups. The primary efficacy endpoint was mean change from baseline visual acuity (VA) at month 12.

Results

Mean changes from baseline VA at 12 months were −16.3, −1.6, and −0.2 letters for the sham, 0.3 mg, and 0.5 mg groups, respectively (P ≤ .0001, each ranibizumab dose vs sham). Ranibizumab arrested CNV growth and reduced leakage from CNV. However, the treatment effect declined in the ranibizumab groups during quarterly dosing (e.g., at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses, respectively). Results of subgroups analyses of mean change from baseline VA at 12 months by baseline age, VA, and lesion characteristics were consistent with the overall results. Few serious ocular or nonocular adverse events occurred in any group.

Conclusions

Ranibizumab administered monthly for three months and then quarterly provided significant VA benefit to patients with AMD-related subfoveal CNV and was well tolerated. The incidence of serious ocular or nonocular adverse events was low.

Section snippets

Methods

PIER is a two-year, phase IIIb, multicenter, randomized, double-masked, sham injection–controlled study of the efficacy and safety of ranibizumab in patients with AMD-related subfoveal CNV, with or without classic CNV. After providing written informed consent, patients entered a screening period (≤28 days), with eligibility determined by the investigator. A central reading center (University of Wisconsin Fundus Photograph Reading Center, Madison, Wisconsin) later re-assessed the CNV types based

Results

Between September 7, 2004 and March 16, 2005, 184 subjects were enrolled at 43 investigative sites in the U.S. and were randomly assigned to study treatment: 60 to 0.3 mg ranibizumab, 61 to 0.5 mg ranibizumab, and 63 to sham injection. Subject disposition is summarized in Supplemental Table C (available at AJO.com). Treatment compliance was good in the ranibizumab groups, with 85% or more of subjects receiving each scheduled injection. In the sham group, 27% of subjects permanently discontinued

Discussion

Results of the PIER study indicate that ranibizumab administered on a schedule of monthly dosing for three months followed by quarterly dosing provides significant visual acuity benefit to patients with all angiographic subtypes of CNV (i.e., minimally or predominantly classic or occult with no classic component), with a low incidence of serious ocular and nonocular adverse events and an acceptable rate of nonserious adverse events. Both of the ranibizumab dose groups (0.3 mg and 0.5 mg)

Carl D. Regillo received his medical degree from Harvard and performed both his ophthalmology residency and vitreoretinal fellowship at Wills Eye Institute, Philadelphia, Pennsylvania. He is a prior Heed fellow and recipient of the American Academy of Ophthalmology Achievement and Senior Achievement Awards. Dr Regillo is currently the Director of the Wills Clinical Retina Research Unit, Professor of Ophthalmology at Thomas Jefferson University, and Chairman of the Academy Retina section of the

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: Supplemental Material available at AJO.com.

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Original articleRandomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER Study Year 1

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Ranibizumab for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study

Ophthalmology

Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration

Ophthalmology

A sharper Bonferroni procedure for multiple tests of significance

Biometrika

Original article
Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER Study Year 1