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G. Stoller, F. Lapierre-Holme, J. Peterkin, W. Garland, R. Sabbadini; iSONEPTM , an Anti-Sphingosine-1-Phosphate (Anti-S1P) Monoclonal Antibody for Investigation in Exudative AMD: Results From a Phase 1 Prospective Open-Label Dose-Escalating Multi-Center Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1253.
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To evaluate the safety, maximum tolerated dose (MTD) and preliminary biologic activity of escalating doses of iSONEP in subjects with exudative AMD.
Subjects with all sub-types of CNV secondary to AMD were eligible. Fifteen subjects (3 subjects/dose group) received a single intravitreal (ivt) injection of iSONEP (0.2, 0.6, 1.0, 1.4 or 1.8 mg/eye) in one eye. The study duration was 30 days with 11 months of safety follow-up. Primary outcome measures were safety and tolerability. Secondary outcome measures included assessments of preliminary biologic activity as determined by OCT and FA (area of CNV).
Nine females and 6 males were enrolled. Median age was 76. Most subjects had received prior AMD treatment including anti-VEGF and triple therapy. No SAEs related to iSONEP were reported. Only 3 AEs occurred: subconjunctival hemorrhage, post-injection eye pain, and a 3 msec increase in the QTcB interval in a subject (0.2 mg) with a history of arrhythmia. All AEs resolved without sequelae.Ten subjects were evaluable for biologic activity, as 3 were deemed to have disciform scars at screening as determined by an independent reading center and 2 were excluded from analysis due to protocol violation. Of the 10 evaluable subjects, 8 demonstrated signs of biologic activity by OCT and/or FA. The 5 subjects that had a component of occult CNV demonstrated a mean regression of total CNV area of 7.4 mm2 or 76% by Day 45. Two subjects with PEDs were enrolled; both demonstrated complete resolution by Day 45.
While the MTD was not reached, a single dose of ivt iSONEP up to 1.8 mg was well tolerated. Although the study is limited by a small sample size and lack of a control group, results suggest biologic activity. S1P appears to be a mediator of exudative AMD.
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