April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Phase 2 of bamosiran (SYL040012), a novel RNAi based compound for the treatment of increased intraocular pressure associated to glaucoma
Author Affiliations & Notes
  • Victoria Gonzalez
    Sylentis, Madrid, Spain
  • Kadi Palumaa
    Eastt Tallinn Central Hospital, Tallinn, Estonia
  • Krista Turman
    Eye Clinic Dr. Krista Turman, Tallinn, Estonia
  • Francisco José Muñoz
    Hospital Universitario Ramón y Cajal, Madrid, Spain
  • Jens Jordan
    Universitaetsklinikum Freiburg, Freiburg, Germany
  • Julian García
    Hospital Universitario Clínico San Carlos, Madrid, Spain
  • Fernando Ussa
    Instituto de Oftalmobiología Aplicada, Valladolid, Spain
  • Alfonso Antón
    Institut Catala de Retina, Barcelona, Spain
  • Esperanza Gutierrez
    Hospital Universitario 12 de Octubre, Madrid, Spain
  • Javier Moreno-Montanes
    Clinica Universidad de Navarra, Pamplona, Spain
  • Footnotes
    Commercial Relationships Victoria Gonzalez, Sylentis (E), Sylentis (I); Kadi Palumaa, None; Krista Turman, None; Francisco José Muñoz, None; Jens Jordan, None; Julian García, None; Fernando Ussa, None; Alfonso Antón, None; Esperanza Gutierrez, None; Javier Moreno-Montanes, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 564. doi:
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      Victoria Gonzalez, Kadi Palumaa, Krista Turman, Francisco José Muñoz, Jens Jordan, Julian García, Fernando Ussa, Alfonso Antón, Esperanza Gutierrez, Javier Moreno-Montanes; Phase 2 of bamosiran (SYL040012), a novel RNAi based compound for the treatment of increased intraocular pressure associated to glaucoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):564.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The aim of this study was to assess the tolerability and intraocular pressure (IOP) lowering effect of three different doses of SYL040012 eye drops administered QD over a period of 14 days to subjects with increased IOP or glaucoma.

Methods: This phase 2 study was a multi-center, randomized, parallel-design, placebo-controlled, double masked clinical trial. 89 patients were randomized to one of following groups: 80 µg/eye/day (0.2%), 300 µg/eye/day (0.75%), 900 µg/eye/day (2.25%) SYL040012 or placebo. Local and systemic tolerability as well as effect on IOP were evaluated. Local tolerability was assessed by performing conjunctival and corneal examinations on a daily basis; full ophthalmic examinations were performed prior to the first and after the last administration. The effect on IOP was evaluated by performing a 24h IOP curve prior to the first administration and on day 14. The study was conducted in accordance with the ICH Guidelines on Good Clinical Practices and following national regulations as well as the tenets that had their origin on the Declaration of Helsinki. The study was registered on www.clinicaltrials.gov (NCT01739244) and EU Clinical Trial Register (EudraCT Number:2011-001849-33). Subjects signed a written consent form stating they understood and agreed to participate in the study.

Results: SYL040012 at the dose of 300 µg/eye/day caused a statistically significant reduction in IOP at day 14 when compared to placebo. This reduction was also statistically significant when compared to the IOP curve performed during the screening period. The compound was very well tolerated with only a 14.6% of the patients reporting an adverse event; most of these events (80%) were of mild intensity. No differences among groups were observed in terms of adverse events. The most frequent adverse event was headache. The only severe adverse event registered throughout the clinical trial was hyponatremia in one patient treated with SYL040012 at the dose of 300 µg/eye/day; this event was not considered to be related to the investigational product.

Conclusions: In conclusion, the results of this phase 2 study indicate that the dose of 300 µg/eye/day of SYL040012 significantly reduced IOP when compared to basal values and to placebo. Systemic and local tolerance to all studied doses of SYL040012 was good; with a very low rate of adverse events.

Keywords: 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials  
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