Abstract
Purpose: :
DARPin® MP0112, a potent VEGF inhibitor with very long ocular half-life, belongs to a new class of small proteins with attractive therapeutic properties. Animal studies previously indicated that dosing frequency in patients may be reduced 3-4fold compared to current standard therapy. The clinical study with DARPin® MP0112 assessed the safety and preliminary efficacy. Our purpose is to report the imaging results of DARPin® MP0112 study in patients with wet AMD.
Methods: :
The MP0112 wet AMD study is a prospective Phase I/II, open-label, non-controlled, multicentre trial in 8 centres in Europe. Eligible patients were aged >50 years with diagnosed wet AMD who are treatment naïve and have a BCVA of 20/40 to 20/320 in the study eye at 4 meters. Four to nine patients were included per cohort and received a single dose of MP0112 as intravitreal injections. Efficacy assessments over the 16-week period included optical coherence tomography (OCT) to quantify central retinal thickness (CRT), and fluorescein angiography (FA) to assess the activity of the CNV.
Results: :
Initial results from an interim analysis conducted for the first 32 patients completing the 16-week study time point have shown clear OCT responses (mean decreases in CRT were -95 µm and -111 µm at week 4 in the highest two dose groups, respectively) and that the OCT decrease was maintained in seven of eight patients in the highest two dose groups for 12 to 16 weeks. FA results are in line with the OCT results and show a dose-related decrease in vascular leakage: 18 of 29 patients (62%) had no FA leakage at week4.
Conclusions: :
Clear OCT and FA responses were observed in the study, demonstrating the expected efficacy of DARPin MP0112. DARPin MP0112 represents a very promising new anti-VEGF treatment option with potential in wet AMD, DME, and RVO and is a showcase for a novel class of therapeutic proteins in ophthalmology.
Clinical Trial: :
http://www.clinicaltrials.gov NCT01086761
Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • vascular endothelial growth factor