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S. W. Cousins, Ophthotech Study Group; Targeting Complement Factor 5 in Combination with Vascular Endothelial Growth Factor (VEGF) Inhibition for Neovascular Age Related Macular Degeneration (AMD): Results of a Phase 1 Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1251.
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Genetic linkage and pathobiological studies have implicated activation of the complement system in AMD. Preclinical studies confirm a role for complement effector molecules in the induction and severity of choroidal neovascularization. This study assessed the safety of intravitreal injections of the aptamer ARC1905, which inhibits activation of complement factor 5, in combination with ranibizumab for the treatment of neovascular AMD.
A phase 1, prospective, noncontrolled multicenter, dose escalating study was initiated in 58 patients with all subtypes of subfoveal neovascular AMD. Best-corrected visual acuity (VA) in the study eye was 20/63 to 20/200. Subjects received 3-6 monthly administrations of ARC1905 (0.03, 0.3, 1, or 2 mg) in combination with ranibizumab (0.5mg). Secondary endpoints included visual acuity and OCT. Complement-associated SNP analysis was conducted in a cohort of patients.
Dose escalation was completed without evidence of dose-limiting toxicity. Forty-eight (48) subjects received at least 2 doses of the experimental regimen. The mean change in VA was +10.2 letters at Week 8. Thirty-five percent of patients gained ≥3 lines of VA. The mean change in OCT center point thickness was -124µm.
The combination of C5 and VEGF inhibition in neovascular AMD is well tolerated without evidence of acute toxicity.
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