A Phase 1 Study of Intravitreous E10030 in Combination with Ranibizumab in Neovascular Age-Related Macular Degeneration

Ophthalmology

Volumn 123, Issue 1, 2016, Pages 78-85

  Jaffe, Glenn J ^a   Eliott, Dean ^b   Wells, John A ^c   Prenner, Jonathan L ^d   Papp, Andras ^e   Patel, Samir ^f  

^a DUKE UNIVERSITY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Palmetto Retina Center   (United States)

^d RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^e SEMMELWEIS UNIVERSITY   (Hungary)

^f Ophthotech Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; PEGPLERANIB; RANIBIZUMAB; ANGIOGENESIS INHIBITOR; PLATELET DERIVED GROWTH FACTOR; VASCULOTROPIN A;

ADULT; AGE RELATED MACULAR DEGENERATION; AGED; ARTICLE; CENTRAL CORNEAL THICKNESS; CHEMOSIS; CLINICAL ARTICLE; CONJUNCTIVAL HEMORRHAGE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EYE EXAMINATION; EYE IRRITATION; FEMALE; FOREIGN BODY; HUMAN; LABORATORY TEST; LOW DRUG DOSE; MACULAR DEGENERATION; MALE; MULTICENTER STUDY; NEOVASCULAR AGE RELATED MACULAR DEGENERATION; OPTICAL COHERENCE TOMOGRAPHY; OPTOMETRY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; PUNCTATE KERATITIS; RETINA FLUORESCEIN ANGIOGRAPHY; RISK REDUCTION; SIDE EFFECT; SUBRETINAL NEOVASCULARIZATION; TREATMENT DURATION; VISUAL ACUITY; VISUAL FIELD; VITAL SIGN; WET MACULAR DEGENERATION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DOSE RESPONSE; EYE FUNDUS; FLUORESCENCE ANGIOGRAPHY; INTRAVITREAL DRUG ADMINISTRATION; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; RETINAL NEOVASCULARIZATION; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANGIOGENESIS INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; FEMALE; FLUORESCEIN ANGIOGRAPHY; FUNDUS OCULI; HUMANS; INTRAVITREAL INJECTIONS; MACULAR DEGENERATION; MALE; MIDDLE AGED; PLATELET-DERIVED GROWTH FACTOR; PROSPECTIVE STUDIES; RANIBIZUMAB; RETINAL NEOVASCULARIZATION; TREATMENT OUTCOME; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VISUAL ACUITY;

EID: 84952991578     PISSN: 01616420     EISSN: 15494713     Source Type: Journal    
DOI: 10.1016/j.ophtha.2015.09.004     Document Type: Article

References (25)

1. Klein R, Chou CF, Klein BE, et al. Prevalence of age-related macular degeneration in the US population. Arch Ophthalmol 2011;129:75-80.
2. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267: 10931-4.
3. Comparison of Age-related Macular Degeneration Treatments Trials Research Group; Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 2012;119:1388-98.
4. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology 2014;121:193-201.
5. Busbee BG, Ho AC, Brown DM, et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2013;120:1046-56.
6. Holekamp NM, Liu Y, Yeh WS, et al. Clinical utilization of anti-VEGF agents and disease monitoring in neovascular agerelated macular degeneration. Am J Ophthalmol 2014;157: 825-833.e1.
7. Rasmussen A, Bloch SB, Fuchs J, et al. A 4-year longitudinal study of 555 patients treated with ranibizumab for neovascular age-related macular degeneration. Ophthalmology 2013;120: 2630-6.
8. Kang HM, Kwon HJ, Yi JH, et al. Subfoveal choroidal thickness as a potential predictor of visual outcome and treatment response after intravitreal ranibizumab injections for typical exudative age-related macular degeneration. Am J Ophthalmol 2014;157:1013-21.
9. Sizmaz S, Kucukerdonmez C, Kal A, et al. Retinal and choroidal thickness changes after single anti-VEGF injection in neovascular age-related macular degeneration: ranibizumab vs bevacizumab. Eur J Ophthalmol 2014;24:904-10.
10. Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 2009;116:57-65.e5.
11. Humphreys BD, Lin SL, Kobayashi A, et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010;176:85-97.
12. Lin SL, Kisseleva T, Brenner DA, Duffield JS. Pericytes and perivascular fibroblasts are the primary source of collagenproducing cells in obstructive fibrosis of the kidney. Am J Pathol 2008;173:1617-27.
13. Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 1998;125:1591-8.
14. Hellstrom M, Kalen M, Lindahl P, et al. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 1999;126:3047-55.
15. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res 2005;97:512-23.
16. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7:987-9.
17. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003;111:1287-95.
18. Jo N, Mailhos C, Ju M, et al. Inhibition of platelet-derived growth factor B signaling enhances the efficacy of antivascular endothelial growth factor therapy in multiple models of ocular neovascularization. Am J Pathol 2006;168: 2036-53.
19. Balasubramanian SA, Krishna Kumar K, Baird PN. The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance. Transl Res 2014;164:179-92.
20. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22:1276-312.
21. Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997;277:242-5.
22. Erber R, Thurnher A, Katsen AD, et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 2004;18:338-40.
23. Akiyama H, Kachi S, Silva RL, et al. Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies. J Cell Physiol 2006;207:407-12.
24. Hall AP. Review of the pericyte during angiogenesis and its role in cancer and diabetic retinopathy. Toxicol Pathol 2006;34:763-75.
25. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.