An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular oedema

被引:73
作者
Do, D. V. [1 ]
Nguyen, Q. D. [1 ]
Shah, S. M. [1 ]
Browning, D. J. [2 ]
Haller, J. A. [1 ]
Chu, K. [3 ]
Yang, K. [3 ]
Cedarbaum, J. M. [3 ,4 ]
Vitti, R. L. [3 ]
Ingerman, A. [3 ]
Campochiaro, P. A. [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA
[2] Charlotte Eye Ear Nose & Throat Associates, PA, Charlotte, NC USA
[3] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA
[4] Elan Pharmaceut Inc, San Francisco, CA USA
关键词
BLOOD-RETINAL BARRIER; CHOROIDAL NEOVASCULARIZATION; BREAKDOWN;
D O I
10.1136/bjo.2008.138271
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Aim: The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO). Methods: Five subjects with DMO, foveal thickness >= 250 mu m measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT. Results: Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 mu m. At 4 weeks after injection, the median excess FTH was 59 mm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 mu m; 31% reduction from baseline, p=0.0625) and four of the five showed improvement in BCVA (median improvement of three letters). Conclusions: A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.
引用
收藏
页码:144 / 149
页数:6
相关论文
共 15 条
[1]  
[Anonymous], ARCH OPHTHALMOL
[2]  
[Anonymous], 1987, INTOPHTHALMOLCIIN, P265, DOI DOI 10.1097/00004397-198702740-00006
[3]   Normal macular thickness measurements in healthy eyes using stratus optical coherence tomography [J].
Chan, A ;
Duker, JS ;
Ko, TH ;
Fujimoto, JG ;
Schuman, JS .
ARCHIVES OF OPHTHALMOLOGY, 2006, 124 (02) :193-198
[4]  
Derevjanik NL, 2002, INVEST OPHTH VIS SCI, V43, P2462
[5]   Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration [J].
Gaudreault, J ;
Fei, D ;
Rusit, J ;
Suboc, P ;
Shiu, V .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2005, 46 (02) :726-733
[6]   VEGF-Trap: A VEGF blocker with potent antitumor effects [J].
Holash, J ;
Davis, S ;
Papadopoulos, N ;
Croll, SD ;
Ho, L ;
Russell, M ;
Boland, P ;
Leidich, R ;
Hylton, D ;
Burova, E ;
Ioffe, E ;
Huang, T ;
Radziejewski, C ;
Bailey, K ;
Fandl, JP ;
Daly, T ;
Wiegand, SJ ;
Yancopoulos, GD ;
Rudge, JS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (17) :11393-11398
[7]  
Klein R, 1992, Trans Am Ophthalmol Soc, V90, P561
[8]   Supplemental oxygen improves diabetic macular edema: A pilot study [J].
Nguyen, QD ;
Shah, SM ;
Van Anden, E ;
Sung, JU ;
Vitale, S ;
Campochiaro, PA .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (02) :617-624
[9]  
NGUYEN QD, 1522, OPHTHALMOLOGY, V113
[10]   Vascular endothelial growth factor is a critical stimulus for diabetic macular edema [J].
Nguyen, Quan Dong ;
Tatlipinar, Sinan ;
Shah, Syed Mahmood ;
Haller, Julia A. ;
Quinlan, Edward ;
Sung, Jennifer ;
Zimmer-Galler, Ingrid ;
Do, Diana V. ;
Campochiaro, Peter A. .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 2006, 142 (06) :961-969