A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration

Quan Dong Nguyen, Syed Mahmood Shah, David J. Browning, Henry Hudson, Peter Sonkin, Seenu M. Hariprasad, Peter Kaiser, Jason S. Slakter, Julia Haller, Diana V. Do, William F. Mieler, Karen Chu, Ke Yang, Avner Ingerman, Robert L. Vitti, Alyson J. Berliner, Jesse M. Cedarbaum, Peter A. Campochiaro

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Purpose: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). Design: Dose-escalation, multicenter, interventional clinical trial. Participants: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions ≤12 disc areas in size and ≥50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) ≤20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. Methods: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. Main Outcome Measure: Safety assessments. Results: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 μm at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. Conclusions: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)2141-2148.e1
JournalOphthalmology
Volume116
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Macular Degeneration
Vascular Endothelial Growth Factor A
Visual Acuity
Choroidal Neovascularization
Intravitreal Injections
Disclosure
Safety
Intraocular Injections
Inflammation
Vascular Endothelial Growth Factor Receptor-1
Maximum Tolerated Dose
Vital Signs
Fluorescein Angiography
Optical Coherence Tomography
Fluorescein
Protein Binding
Immunoglobulin G
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Nguyen, Q. D., Shah, S. M., Browning, D. J., Hudson, H., Sonkin, P., Hariprasad, S. M., ... Campochiaro, P. A. (2009). A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration. Ophthalmology, 116(11), 2141-2148.e1. https://doi.org/10.1016/j.ophtha.2009.04.030

A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration. / Nguyen, Quan Dong; Shah, Syed Mahmood; Browning, David J.; Hudson, Henry; Sonkin, Peter; Hariprasad, Seenu M.; Kaiser, Peter; Slakter, Jason S.; Haller, Julia; Do, Diana V.; Mieler, William F.; Chu, Karen; Yang, Ke; Ingerman, Avner; Vitti, Robert L.; Berliner, Alyson J.; Cedarbaum, Jesse M.; Campochiaro, Peter A.

In: Ophthalmology, Vol. 116, No. 11, 11.2009, p. 2141-2148.e1.

Research output: Contribution to journalArticle

Nguyen, QD, Shah, SM, Browning, DJ, Hudson, H, Sonkin, P, Hariprasad, SM, Kaiser, P, Slakter, JS, Haller, J, Do, DV, Mieler, WF, Chu, K, Yang, K, Ingerman, A, Vitti, RL, Berliner, AJ, Cedarbaum, JM & Campochiaro, PA 2009, 'A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration', Ophthalmology, vol. 116, no. 11, pp. 2141-2148.e1. https://doi.org/10.1016/j.ophtha.2009.04.030
Nguyen, Quan Dong ; Shah, Syed Mahmood ; Browning, David J. ; Hudson, Henry ; Sonkin, Peter ; Hariprasad, Seenu M. ; Kaiser, Peter ; Slakter, Jason S. ; Haller, Julia ; Do, Diana V. ; Mieler, William F. ; Chu, Karen ; Yang, Ke ; Ingerman, Avner ; Vitti, Robert L. ; Berliner, Alyson J. ; Cedarbaum, Jesse M. ; Campochiaro, Peter A. / A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration. In: Ophthalmology. 2009 ; Vol. 116, No. 11. pp. 2141-2148.e1.
@article{0a7f76dcc6234ea7b887f427d15bb389,
title = "A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration",
abstract = "Purpose: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). Design: Dose-escalation, multicenter, interventional clinical trial. Participants: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions ≤12 disc areas in size and ≥50{\%} active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) ≤20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. Methods: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. Main Outcome Measure: Safety assessments. Results: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 μm at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. Conclusions: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.",
author = "Nguyen, {Quan Dong} and Shah, {Syed Mahmood} and Browning, {David J.} and Henry Hudson and Peter Sonkin and Hariprasad, {Seenu M.} and Peter Kaiser and Slakter, {Jason S.} and Julia Haller and Do, {Diana V.} and Mieler, {William F.} and Karen Chu and Ke Yang and Avner Ingerman and Vitti, {Robert L.} and Berliner, {Alyson J.} and Cedarbaum, {Jesse M.} and Campochiaro, {Peter A.}",
year = "2009",
month = "11",
doi = "10.1016/j.ophtha.2009.04.030",
language = "English (US)",
volume = "116",
pages = "2141--2148.e1",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration

AU - Nguyen, Quan Dong

AU - Shah, Syed Mahmood

AU - Browning, David J.

AU - Hudson, Henry

AU - Sonkin, Peter

AU - Hariprasad, Seenu M.

AU - Kaiser, Peter

AU - Slakter, Jason S.

AU - Haller, Julia

AU - Do, Diana V.

AU - Mieler, William F.

AU - Chu, Karen

AU - Yang, Ke

AU - Ingerman, Avner

AU - Vitti, Robert L.

AU - Berliner, Alyson J.

AU - Cedarbaum, Jesse M.

AU - Campochiaro, Peter A.

PY - 2009/11

Y1 - 2009/11

N2 - Purpose: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). Design: Dose-escalation, multicenter, interventional clinical trial. Participants: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions ≤12 disc areas in size and ≥50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) ≤20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. Methods: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. Main Outcome Measure: Safety assessments. Results: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 μm at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. Conclusions: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

AB - Purpose: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). Design: Dose-escalation, multicenter, interventional clinical trial. Participants: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions ≤12 disc areas in size and ≥50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) ≤20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. Methods: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. Main Outcome Measure: Safety assessments. Results: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 μm at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. Conclusions: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

UR - http://www.scopus.com/inward/record.url?scp=70350757650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350757650&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2009.04.030

DO - 10.1016/j.ophtha.2009.04.030

M3 - Article

C2 - 19700196

AN - SCOPUS:70350757650

VL - 116

SP - 2141-2148.e1

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 11

ER -