title: Safety and Efficacy Clinical Trials for SYL1001, a Novel Short Interfering RNA for the Treatment of Dry Eye Disease.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.).
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Benitez-Del-Castillo
authors.affiliation: Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno-Montañés
authors.affiliation: Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Jiménez-Alfaro
authors.affiliation: Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Muñoz-Negrete
authors.affiliation: Eye Clinic Dr. Krista Turman, Tallin, Estonia.
authors.forename: Krista
authors.initials: K
authors.lastname: Turman
authors.affiliation: East-Tallinn Central Hospital, Tallin, Estonia.
authors.forename: Kadi
authors.initials: K
authors.lastname: Palumaa
authors.affiliation: Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Sádaba
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: González
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Ruz
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Vargas
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Covadonga
authors.initials: C
authors.lastname: Pañeda
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Martínez
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bleau
authors.affiliation: Sylentis, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Jimenez
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011446:Prospective Studies; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D013666:Tears / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009883:Ophthalmic Solutions; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C494484:TRPV1 receptor