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`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER S…
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`ORIGINAL ARTICLE
`
`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab
`for Neovascular Age-related Macular Degeneration: PIER Study Year
`1
`
`
`
`•
`•
`Carl D. Regillo David M. Brown Prema Abraham
`The PIER Study Group •
`Published: December 03, 2007 • DOI: https://doi.org/10.1016/j.ajo.2007.10.004
`
`• ...
`
`•
`Susan Schneider Naveed Shams
`
`References
`
`Biography
`
`Article info
`
`Related Articles
`
`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.
`
`To read this article in full you will need to make a payment
`Purchase one-time access:
`
`Academic & Personal: 24 hour online access
`
`Corporate R&D Professionals: 24 hour online access
`
`One-time access price info
`
`Subscribe:
`
`Subscribe to American Journal of Ophthalmology
`
`Already a print subscriber? Claim online access
`
`Already an online subscriber? Sign in
`
`Register: Create an account
`
`Institutional Access: Sign in to ScienceDirect
`
`References
`Rosenfeld P.J. • Brown D.M. • Heier J.S. • et al.
`Ranibizumab for neovascular age-related macular degeneration.
`N Engl J Med. 2006; 355: 1419-1431
`
`1.
`
`View in Article
`Scopus (4740) • PubMed • Crossref • Google Scholar
`
`https://www.ajo.com/article/S0002-9394(07)00881-1/fulltext
`
`1/4
`
`|
`
` VOLUME 145, ISSUE 2
`
`,
`
`P239-248.E5,
`
`FEBRUARY 2008
`
`Show all authors
`
`Celltrion Exhibit 1023
`Page 1
`
`
`
`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER S…
`
`AAO Member Access Submit
`
`Log in
`
`Register
`
`Subscribe
`
`Claim
`
`
`Reprints
`
`
`Request
`
`
`Share
`
` S
`
`ave
`
`
`Subscribe
`
`
`Purchase
`
`
`
`PlumX Metrics
`
`ORIGINAL ARTICLE
`
`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab
`for Neovascular Age-related Macular Degeneration: PIER Study Year
`1
`
`
`
`•
`•
`Carl D. Regillo David M. Brown Prema Abraham
`The PIER Study Group •
`Published: December 03, 2007 • DOI: https://doi.org/10.1016/j.ajo.2007.10.004
`
`• ...
`
`•
`Susan Schneider Naveed Shams
`
`References
`
`Biography
`
`Article info
`
`Related Articles
`
`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.
`
`To read this article in full you will need to make a payment
`Purchase one-time access:
`
`Academic & Personal: 24 hour online access
`
`Corporate R&D Professionals: 24 hour online access
`
`One-time access price info
`
`Subscribe:
`
`Subscribe to American Journal of Ophthalmology
`
`Already a print subscriber? Claim online access
`
`Already an online subscriber? Sign in
`
`Register: Create an account
`
`Institutional Access: Sign in to ScienceDirect
`
`References
`Rosenfeld P.J. • Brown D.M. • Heier J.S. • et al.
`Ranibizumab for neovascular age-related macular degeneration.
`N Engl J Med. 2006; 355: 1419-1431
`
`1.
`
`View in Article
`Scopus (4740) • PubMed • Crossref • Google Scholar
`
`https://www.ajo.com/article/S0002-9394(07)00881-1/fulltext
`
`1/4
`
`|
`
` VOLUME 145, ISSUE 2
`
`,
`
`P239-248.E5,
`
`FEBRUARY 2008
`
`Show all authors
`
`Celltrion Exhibit 1023
`Page 1
`
`
`
`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER S…
`3/13/23, 8:58 PM
`Brown D.M. • Kaiser P.K. • Michels M. • et al.
`Ranibizumab versus verteporfin for neovascular age-related macular degeneration.
`N Engl J Med. 2006; 355: 1432-1444
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`Heier J.S. • Antoszyk A.N. • Pavan P.R. • et al.
`Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II
`multicenter, controlled, multidose study.
`Ophthalmology. 2006; 113: 633-642
`
`View in Article
`Scopus (353) • PubMed • Abstract • Full Text • Full Text PDF • Google Scholar
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`Rosenfeld P.J. • Heier J.S. • Hantsbarger G. • Shams N.
`Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular
`age-related macular degeneration.
`Ophthalmology. 2006; 113: 623-632
`
`View in Article
`Scopus (168) • PubMed • Abstract • Full Text • Full Text PDF • Google Scholar
`
`Hochberg Y.
`A sharper Bonferroni procedure for multiple tests of significance.
`Biometrika. 1988; 75: 800-802
`
`View in Article
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`Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular
`degeneration with verteporfin: one-year results of two randomized clinical trials—TAP report 1.
`Arch Ophthalmol. 1999; 117: 1329-1345
`
`View in Article
`Scopus (1738) • PubMed • Crossref • Google Scholar
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`Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with
`verteporfin.
`Ophthalmology. 2001; 108: 841-852
`
`View in Article
`Scopus (462) • PubMed • Abstract • Full Text • Full Text PDF • Google Scholar
`
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`
`Visudyne. Novartis Pharmaceuticals Corp, East Hanover, New Jersey2005 ([package insert])
`
`View in Article
`Google Scholar
`
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`
`Collaborative overview of randomized trials of antiplatelet therapy—I: Prevention of death,
`myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of
`patients.
`BMJ. 1994; 308: 81-106
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`
`Fung A.E. • Lalwani G.A. • Rosenfeld P.J. • et al.
`An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab
`(Lucentis) for neovascular age-related macular degeneration.
`Am J Ophthalmol. 2007; 143: 566-583
`
`View in Article
`Scopus (868) • PubMed • Abstract • Full Text • Full Text PDF • Google Scholar
`
`Biography
`
`https://www.ajo.com/article/S0002-9394(07)00881-1/fulltext
`
`2/4
`
`Celltrion Exhibit 1023
`Page 2
`
`
`
`3/13/23, 8:58 PM
`
`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER S…
`
`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 Basic and Clinical Science
`Course.
`
`Article info
`Publication history
`Published online: December 03, 2007
`Accepted: October 5, 2007
`Footnotes
`Supplemental Material available at AJO.com.
`
`Identification
`DOI: https://doi.org/10.1016/j.ajo.2007.10.004
`
`Copyright
`© 2008 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
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`
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`Celltrion Exhibit 1023
`Page 3
`
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`
`3/13/23, 8:58 PM
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`Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER S…
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