Antonia M Joussen1, Sebastian Wolf2, Peter K Kaiser3, David Boyer4,5, Thomas Schmelter6, Rupert Sandbrink6,7, Oliver Zeitz1,6, Gesa Deeg6, Annett Richter6, Torsten Zimmermann6, Joachim Hoechel6, Ulf Buetehorn6, Walter Schmitt6, Brigitte Stemper6,8, Michael K Boettger6,9. 1. Department of Ophthalmology, Charité - University Medicine Berlin, Berlin, Germany. 2. Bern Photographic Reading Center and Department of Ophthalmology, Inselspital, University Hospital, University of Bern, Bern, Switzerland. 3. Cole Eye Institute, Cleveland, OH, USA. 4. Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA. 5. USC/Keck School of Medicine, Los Angeles, CA, USA. 6. Bayer AG, Division Pharma, Berlin and Wuppertal, Germany. 7. Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany. 8. Department of Neurology, University Erlangen-Nürnberg, Erlangen, Germany. 9. Department of Sports Medicine, Bergische Universität, Wuppertal, Germany.
Abstract
AIMS: This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD). METHODS:Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml-1 ) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12. RESULTS: In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) -0.61, 2.97] and -2.4 (90% CI -4.18, -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab). CONCLUSIONS: The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
RCT Entities:
AIMS: This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD). METHODS: Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml-1 ) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12. RESULTS: In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) -0.61, 2.97] and -2.4 (90% CI -4.18, -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab). CONCLUSIONS: The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
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