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S. Kaushal, F. Grossi, C. Francois, J. Slakter, ASaP Study Group; Complement C3 inhibitor POT-4: Clinical Safety of Intravitreal Administration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5010.
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Over the last few years, several reports have suggested that complement activation is a key player in the pathogenesis of age-related macular degeneration (AMD). Complement inhibition is now being considered as a promising new therapeutic approach for the treatment of AMD. POT-4 is a potent inhibitor of complement factor C3 activation and, as such, it has the potential to inhibit the pathogenic process of AMD. A Clinical Phase I study was designed to assess the safety and tolerability of intravitreal injections of POT-4 (ClinicalTrials.gov Identifier: NCT00473928).
This prospective, first-in-human, uncontrolled, non-randomized, single-masked, single dose escalation study includes patients older than 50 years with an active choroidal neovascular lesion or prior active choroidal neovascularization with secondary fibrovascular changes and some evidence of leakage or exudation and best corrected visual acuity (BCVA) by EDTRS of 20/60 or worse. Prior treatment for neovascular AMD is allowed after a washout period of 30 days. Patients receive a single 50 µl intravitreal injection of POT-4, ranging from 1 to 1050 µg/dose. Acute safety is assessed after 30 days with BCVA, OCT, fundus photography, fluorescein angiography, IOP, b-scan, detailed eye exams, and laboratory tests. All subjects are followed for up for 52 weeks.
Safety evaluations in patients treated with up to 450 µg/dose of POT-4 revealed no drug-related toxicity based on clinical signs, ophthalmic examinations or laboratory results at any time point monitored up to date. No serious adverse events and no identifiable intraocular inflammation have been reported. A significant improvement in BCVA could not be identified, although there was no significant loss of vision either.
POT-4 is the first complement inhibitor to be tested in patients with AMD.Conclusions: POT-4 is the first complement inhibitor to be tested in patients with AMD. Preliminary results indicate that intravitreal POT-4 is safe and well tolerated and support its administration in larger randomized clinical trials to further define its efficacy profile.
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