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The Developing Regorafenib Eye drops for neovascular Age‐related Macular degeneration (DREAM) study: an open‐label phase II trial
Author(s) -
Joussen Antonia M.,
Wolf Sebastian,
Kaiser Peter K.,
Boyer David,
Schmelter Thomas,
Sandbrink Rupert,
Zeitz Oliver,
Deeg Gesa,
Richter Annett,
Zimmermann Torsten,
Hoechel Joachim,
Buetehorn Ulf,
Schmitt Walter,
Stemper Brigitte,
Boettger Michael K.
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13794
Subject(s) - macular degeneration , medicine , regorafenib , choroidal neovascularization , ophthalmology , ranibizumab , visual acuity , phases of clinical research , adverse effect , confidence interval , fluorescein angiography , bevacizumab , clinical trial , surgery , chemotherapy , colorectal cancer , cancer
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).