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Victoria Gonzalez, Javier Moreno-Montanes, Maris Oll, Kenneth N Sall, Kadi Palumaa, Harvey Dubiner, Krista Turman, Francisco Muñoz-Negrete, Veronica Ruz, Ana Isabel Jimenez; Results of Phase IIB SYLTAG clinical trial with bamosiran in patients with glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3023.
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© ARVO (1962-2015); The Authors (2016-present)
To present the results of SYLTAG Study (NCT02250612, EudraCT No: 2013-002947-27). This phase IIB trial evaluated the safety and effect of 4 doses of bamosiran (SYL040012) against elevated intraocular pressure (IOP) in patients with open-angle glaucoma.
Bamosiran eye drops is a Sylentis RNAi based drug. SYLTAG was a multi-center, randomized, parallel-design, active-controlled, observer masked clinical trial conducted in 4 countries (USA, Spain, Estonia, Germany). Its primary objective was to determine the most effective concentration of bamosiran in the reduction of IOP after 28 days. The secondary objective was to compare the effect on IOP vs Timolol and evaluate its safety on the following parameters: ocular discomfort, systemic tolerability, vital signs, laboratory parameters, electrocardiograms and adverse events (AEs) occurrence. Efficacy endpoints were analyzed using an ANCOVA model. Statistical significance was assessed for two-sided probability values <0.05.
184 patients were randomized into five arms (0.375%, 0.75%, 1.125% and 1.5% of bamosiran q.d and 0.5% Timolol b.i.d). IOP was reduced in all groups at Day 28. Bamosiran (0.75%) showed the highest reduction at Day 28 when compared with baseline value. No statistically significant differences were found among the concentrations of bamosiran. Bamosiran (1.125%) was non inferior to Timolol (p=0.071) in those patients with a basal PIO>25 mmHg. No deaths, no AEs leading to study discontinuation, no unexpected or serious AEs related to bamosiran have occurred. No grade 3 or 4 AEs (CTCAE: version 4.0) have been reported. A total of 34 related AEs were reported. The related AEs in bamosiran groups (8%, 15%, 11% and 12% for the 0.375%, 0.75%, 1.125% and 1.5% bamosiran respectively) were lower than dose reported with Timolol (24%). The hyperemia was <8% in all bamosiran groups. Vital signs, physical examination, biomicroscopy, ophthalmoscopy assessment and electrocardiogram did not show significant abnormalities.
SYLTAG clinical trial compared 4 doses of bamosiran against timolol. Among the study doses, 0.75% bamosiran showed the highest reduction in IOP after 28 days with a good tolerability and safety profile, and could be the targeted dose for future studies. Bamosiran is an RNAi based drug with very low local and systemic toxicity and it is a promising drug for the management of glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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