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John A. Wells, III, Brian B. Berger, Christine Gonzales, Victor H. Gonzales, David L. Johnson, Brian D. Sippy, Manju Soni; Multicenter Phase 1 Clinical Trial Targeting Tissue Factor for the Treatment of Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2012;53(14):450.
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To evaluate the safety and tolerability of binding tissue factor with hI-con1™, alone or in combination with anti-VEGF therapy, in eyes with active neovascular AMD.
This prospective, multi-center, dose-escalating clinical study evaluated the safety and tolerability of a single, intravitreal injection of 60µg, 150µg and 300µg of hI-con1 in 18 patients (6 per cohort). Ocular inclusion criteria included active CNV with at least a 30% classic component on angiography and VA 20/63 - CF. Eyes with end-stage CNV, eyes on chronic anti-VEGF therapy and treatment naïve eyes were enrolled. Anti-VEGF therapy was allowed 2 weeks after the hI-con1 injection at the investigator’s discretion.
No ocular or systemic dose limiting toxicities were identified. No retinal or choroidal vascular, inflammatory or hemorrhagic toxicities were identified. Patients reported no drug related adverse events. hI-con1, administered alone or adjunctively with an anti-VEGF agent, showed multiple, dose-related biologic signals across the broad spectrum of treated eyes. An interim analysis of 6 eyes in the high-dose 300μg cohort at Day 57 showed:• 67% showed reduced OCT thickness, some CNV regression on angiography and ≥ 3 lines improved BCVA.• 100% of the 3 treatment naïve eyes showed reduced OCT thickness, some CNV regression on angiography and ≥ 3 lines improved BCVA.An interim analysis of all dose cohorts additionally showed:• The mean BCVA of 7 eyes on chronic anti-VEGF therapy (mean number of previous anti-VEGF injections = 6; all with persistent sub-retinal fluid; VA = 20/80 or worse) at Day 29 was +9 letters compared to baseline; at Day 57, +7 letters compared to baseline.• The mean BCVA of 9 patients receiving one hI-con1 plus one anti-VEGF injection was +11 letters 29 days after the anti-VEGF injection.• 67% of all 18 eyes went 57 days without resuming anti-VEGF therapy; 50% of all eyes went 85 days or longer without additional anti-VEGF therapy.
A single injection of hI-con1, alone or in combination with anti-VEGF agents, showed no ocular or systemic safety signals. Evidence of biologic activity with reduced OCT thickness, evidence of CNV regression, and gains in BCVA was observed in many of the treated eyes. Further studies are planned.
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