Safety and efficacy clinical trials for SYL1001, a novel short interfering RNA for the treatment of dry eye disease
AuthorBenitez-Del-Castillo, José Manuel; Moreno-Montañés, Javier; Jiménez-Alfaro, Ignacio; Muñoz-Negrete, Francisco José; Turman, Krista; Palumaa, Kadi; Sádaba, Belén; González, María Victoria; Ruz, Verónica; Vargas, Beatriz; Pañeda, Covadonga; Martínez, Tamara; Bleau, Anne Marie; Jimenez, Ana Isabel
EntityUAM. Departamento de Cirugía; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
PublisherAssociation for Research in Vision and Ophthalmology
10.1167/ iovs.16-20303Investigative Ophthalmology & Visual Science 57.14 (2016): 6447-6454
Funded bySupported by a grant from the 2012 INNPACTO program of the Spanish Ministry of Science and Innovation: INDREYE (Innovative solutions for the treatment and diagnosis of dry eye disease) grant number IPT-2012-0438-010000 (Madrid, Spain).
ProjectGobierno de España. IPT-2012-0438-010000; Gobierno de España. INNPACTO 2012
Editor's Versionhttps://doi.org/10.1167/ iovs.16-20303
SubjectsDry eye disease; Ocular pain; siRNA; Visual analogue scale; Medicina
Rights© 2016, Association for Research in Vision and Ophthalmology Inc.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
PURPOSE. To evaluate the efficacy and safety of SYL1001, a short interfering (si) RNA targeting the transient receptor potential cation channel subfamily V member 1 (TRPV1), for the treatment of dry eye disease (DED). METHODS. This study combines a phase I and two phase II clinical trials to test different doses of SYL1001 in a total of 156 healthy subjects and patients with DED. After 10 days of treatment, the primary efficacy endpoints were the effect on (1) the scoring in the Visual Analogue Scale (VAS) and Ocular Surface Disease Index (OSDI) questionnaires, and (2) ocular tolerance evaluated by corneal fluorescein staining and conjunctival hyperemia. Secondary endpoints included the assessment of systemic and local tolerance. RESULTS. Topical administration of SYL1001 1.125% once daily produced a significant decrease in VAS scores compared with placebo from day 4 until the end of treatment (change from baseline at day 10: -1.73 ± 0.32 vs. -0.91 ± 0.34; P = 0.013). For all treatments, OSDI scores were significantly reduced compared to their respective baseline values (P < 0.01), although no significant changes were detected between groups. Conjunctival hyperemia (quantified as normal or abnormal) significantly improved after instillation of SYL1001 1.125% compared with placebo (50% vs. 20%; P < 0.05). Excellent tolerability was reported, with no differences in the rates of occurrence of adverse events between groups. CONCLUSION. These trials achieved their primary endpoints of identifying the most effective dose of SYL1001 (1.125%). SYL1001 showed a large safety margin and may provide novel therapeutic opportunity for the relief of dry eye. (ClinicalTrials.gov numbers, NCT01438281, NCT01776658, and NCT02455999.) Eliminar seleccionado
Google Scholar:Benitez-Del-Castillo, José Manuel - Moreno-Montañés, Javier - Jiménez-Alfaro, Ignacio - Muñoz-Negrete, Francisco José - Turman, Krista - Palumaa, Kadi - Sádaba, Belén - González, María Victoria - Ruz, Verónica - Vargas, Beatriz - Pañeda, Covadonga - Martínez, Tamara - Bleau, Anne Marie - Jimenez, Ana Isabel
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