Universität zu Köln

Liao, David S., Grossi, Federico, V, El Mehdi, Delphine, Gerber, Monica R., Brown, David M., Heier, Jeffrey S., Wykoff, Charles C., Singerman, Lawrence J., Abraham, Prema, Grassmann, Felix ORCID: 0000-0003-1390-7528, Nuernberg, Peter, Weber, Bernhard H. F., Deschatelets, Pascal, Kim, Robert Y., Chung, Carol Y., Ribeiro, Ramiro M., Hamdani, Mohamed, Rosenfeld, Philip J., Boyer, David S., Slakter, Jason S. and Francois, Cedric G. (2020). Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration A Randomized Phase 2 Trial. Ophthalmology, 127 (2). S. 186 - 196. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1549-4713

Full text not available from this repository.

Abstract

Purpose: Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. Design: Prospective, multicenter, randomized, sham-controlled phase 2 study. Participants: Two hundred forty-six patients with GA. Methods: Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. Main Outcome Measures: The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. Results: In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). Conclusions: Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further. (C) 2019 by the American Academy of Ophthalmology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liao, David S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grossi, Federico, V UNSPECIFIED UNSPECIFIED UNSPECIFIED El Mehdi, Delphine UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerber, Monica R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brown, David M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heier, Jeffrey S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wykoff, Charles C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Singerman, Lawrence J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abraham, Prema UNSPECIFIED UNSPECIFIED UNSPECIFIED Grassmann, Felix UNSPECIFIED orcid.org/0000-0003-1390-7528 UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Bernhard H. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Deschatelets, Pascal UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Robert Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chung, Carol Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ribeiro, Ramiro M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamdani, Mohamed UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenfeld, Philip J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyer, David S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Slakter, Jason S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Francois, Cedric G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-347775
DOI:	10.1016/j.ophtha.2019.07.011
Journal or Publication Title:	Ophthalmology
Volume:	127
Number:	2
Page Range:	S. 186 - 196
Date:	2020
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1549-4713
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VISION-RELATED FUNCTION; CHOROIDAL NEOVASCULARIZATION; MACROPHAGE POLARIZATION; RANIBIZUMAB TREATMENT; EYE DISEASE; ABNORMALITIES; INFLAMMATION; ECULIZUMAB; PLASTICITY; FEATURES Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34777