Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: A Phase I/II study

American Journal of Ophthalmology

Volumn 158, Issue 4, 2014, Pages 724-732.e2

  Souied, Eric H ^a   Devin, François ^b   Mauget Faÿsse, Martine ^c   Kolár, Petr ^d   Wolf Schnurrbusch, Ute ^e   Framme, Carsten ^h   Gaucher, David ^f   Querques, Giuseppe ^a   Stumpp, Michael T ^g   Wolf, Sebastian ^e  

^a CENTRE HOSPITALIER INTERCOMMUNAL DE CRÉTEIL   (France)

^b Centre d'Ophtalmologie Monticelli Paradis   (France)

^c Centre Ophtalmologique Rabelais   (France)

^d UNIVERSITY HOSPITAL BRNO   (Czech Republic)

^e UNIVERSITY OF BERN   (Switzerland)

^f UNIVERSITY HOSPITAL OF STRASBOURG   (France)

^g MOLECULAR PARTNERS AG   (Switzerland)

^h HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS ACTING ON THE EYE; CEFTRIAXONE; MP 0112; PREDNISOLONE; RANIBIZUMAB; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG; VANCOMYCIN; ANKYRIN; MP0112; PEPTIDE; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

AGE RELATED MACULAR DEGENERATION; AGED; ARTICLE; CENTRAL RETINAL THICKNESS; CLINICAL ARTICLE; DOSE RESPONSE; DRUG BINDING; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; EYE INFLAMMATION; FEMALE; FLUORESCENCE ANGIOGRAPHY; FOLLOW UP; HUMAN; HYPERTENSION; HYPOPYON; IMMUNOGENICITY; LIMIT OF QUANTITATION; MALE; MAXIMUM TOLERATED DOSE; MULTICENTER STUDY; OPEN STUDY; OPTICAL COHERENCE TOMOGRAPHY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RETINAL THICKNESS; TREATMENT OUTCOME; VERY ELDERLY; VISUAL ACUITY; VITREOUS BODY DETACHMENT; VITRITIS; WET MACULAR DEGENERATION; BIOAVAILABILITY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; EXUDATIVE MACULAR DEGENERATION; INTRAVITREAL DRUG ADMINISTRATION; METABOLISM; PHYSIOLOGY; PROTEIN BINDING; RANDOMIZED CONTROLLED TRIAL; TISSUE DISTRIBUTION;

AGED; AGED, 80 AND OVER; ANKYRIN REPEAT; BIOLOGICAL AVAILABILITY; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FLUORESCEIN ANGIOGRAPHY; HUMANS; INTRAVITREAL INJECTIONS; MALE; MAXIMUM TOLERATED DOSE; PEPTIDES; PROTEIN BINDING; TISSUE DISTRIBUTION; TOMOGRAPHY, OPTICAL COHERENCE; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VISUAL ACUITY; WET MACULAR DEGENERATION;

EID: 84908499507     PISSN: 00029394     EISSN: 18791891     Source Type: Journal    
DOI: 10.1016/j.ajo.2014.05.037     Document Type: Article

References (23)

1. Klein R. Overview of progress in the epidemiology of age related macular degeneration. Ophthalmic Epidemiol 2007; 14(4):184-187.
2. Munoz B, West SK, Rubin GS, et al. Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study. Arch Ophthalmol 2000; 118(6):819-825.
3. Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004; 137(3):486-495.
4. Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: The Beaver Dam Eye Study. Ophthalmology 1997;104(1):7-21.
5. Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep 2006;58(3): 353-363.
6. Ciulla TA, Rosenfeld PJ. Anti vascular endothelial growth factor therapy for neo vascular age-related macular degeneration. Curr Opin Ophthalmol 2009;20(3):158-165.
7. Stewart MW. Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept. Clin Ophthalmol 2012;6:1175-1186.
8. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A multicenter cohort study (SEVEN-UP). Ophthalmology 2013;120(11): 2292-2299.
9. Kaiser PK, Brown DM, Zhang K, et al. Ranibizumab for predominantly classic neo vascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 2007;144(6):850-857.
10. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neo vascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology 2009; 116(1):57-65.
11. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1419-1431.
12. Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351(27):2805-2816.
13. Heier JS, Brown DM, Chong V, et al. Intra vitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012;119(12):2537-2548.
14. Stewart MW. The expanding role of vascular endothelial growth factor inhibitors in ophthalmology. Mayo Clin Proc 2012;87(1):77-88.
15. Stumpp MT, Binz HK, Amstutz P. DARPins: A new generation of protein therapeutics. Drug Discov Today 2008; 13(15-16):695-701.
16. Forrer P, Stumpp MT, Binz HK, Pluckthun A. A novel strategy to design binding molecules harnessing the modular nature of repeat proteins. FEBS Lett 2003;539(1-3):2-6.
17. Binz HK, Stumpp MT, Forrer P, Amstutz P, Pluckthun A. Designing repeat proteins: well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins. J Mol Biol 2003;332(2):489-503.
18. Theurillat JP, Dreier B, Nagy-Davidescu G, et al. Designed ankyrin repeat proteins: A novel tool for testing epidermal growth factor receptor 2 expression in breast cancer. Mod Pathol 2010;23(9):1289-1297.
19. Zahnd C, Kawe M, Stumpp MT, et al. Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size. Cancer Res 2010;70(4): 1595-1605.
20. Munch RC, Muhlebach MD, Schaser T, et al. DARPins: An efficient targeting domain for lentiviral vectors. Mol Ther 2011;19(4):686-693.
21. Seeger MA, Mittal A, Velamakanni S, et al. Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders. PLoS One 2012;7(6): e37845.
22. Stahl A, Stumpp MT, Schlegel A, et al. Highly potent VEGFA- Antagonistic DARP ins as anti-angiogenic agents for topical and intravitreal applications. Angiogenesis 2013; 16(1):101-111.
23. Campochiaro PA, Channa R, Berger BB, et al. Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor: Aphase I/IIstudy. Am J Ophthalmol 2013;155(4): 697-704.