April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Antisense Oligonucleotide Eye Drops Against IRS-1 Inhibit Corneal Neovascularization: Interim Results of a Randomized Phase II Clinical Trial
Author Affiliations & Notes
  • C. Cursiefen
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • F. Bock
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • F. E. Kruse
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • F. Horn
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • B. Seitz
    Dept of Ophthalmology, University of Homburg, Homburg, Germany
  • V. Borderie
    Dept of Ophthalmology, National Hospital of Ophthalmology, Paris, France
  • B. Früh
    Dept of Ophthalmology, University of Bern, Bern, Switzerland
  • M. A. Thiel
    Dept of Ophthalmology, University of Zuerich, Zuerich, Switzerland
  • B. Geudelin
    Mediante GmbH, Basel, Switzerland
  • D. Meller
    Dept of Ophthalmology, University of Essen, Essen, Germany
  • Footnotes
    Commercial Relationships  C. Cursiefen, Gene Signal, C; F. Bock, None; F.E. Kruse, None; F. Horn, None; B. Seitz, None; V. Borderie, None; B. Früh, None; M.A. Thiel, None; B. Geudelin, Gene Signal, E; D. Meller, None.
  • Footnotes
    Support  This study was sponsored by GENE SIGNAL, Billancourt, France; German Research Foundation (DFG: Priority Research Grant 643 [B10]) and the Interdisciplinary Center for Clinical Research (IZKF) Erlangen
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4953. doi:
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      C. Cursiefen, F. Bock, F. E. Kruse, F. Horn, B. Seitz, V. Borderie, B. Früh, M. A. Thiel, B. Geudelin, D. Meller; Antisense Oligonucleotide Eye Drops Against IRS-1 Inhibit Corneal Neovascularization: Interim Results of a Randomized Phase II Clinical Trial. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4953.

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Abstract

Purpose: : Pathologic corneal neovascularization not only reduces corneal transparency and visual acuity, but also is one of the strongest pre- and postoperative risk factors for graft rejection after corneal transplantation. Aim of this study was to test efficacy and tolerability of GS-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1 (IRS-1), versus placebo, on inhibition of progressive corneal neovascularization.

Methods: : Randomized, double-blind, multicentre phase II clinical study. Interim analysis on 40 patients with progressive corneal neovascularization due to various underlying diseases being non-responsive to conventional therapy. Four groups of 10 patients were treated for three months in this dose finding study comparing 3 doses of GS-101 (eye drops: 2x/day; 43, 86 and 172 mg/day total) to placebo (10 patients per group). Primary endpoint was the area covered by pathologic corneal blood vessels, which was measured morphometrically on digitized slit-lamp pictures using image analysis techniques.

Results: : GS101 eye drops were well tolerated: All serious and 95% of all other adverse events were unrelated. In 3 patients there was a potentially related side effect of ocular surface discomfort. At a dose of 86 mg/day (43 µg/drop) GS-101 eye drops produced a significant inhibition and regression of corneal neovascularization (-2.04±1.57% of total corneal area; p=0.0047), while the low dose tended to stabilize it (0.07±2.94; p=0.2088) compared to placebo (0.89±2.15) where corneal neovascularization progressed in all patients. The high dose was of no additional benefit (1.60±7.63).

Conclusions: : The interim results of this phase II study suggest GS-101 eye drops at an optimal dose of 86 mg/day to be an effective, safe, and non-invasive approach to specifically inhibit and regress active corneal angiogenesis, a major risk factor for corneal graft transplantation and graft rejection. These promising results support the start of a phase III clinical study in this orphan drug indication.

Clinical Trial: : Eudract database: 2004-005015-29 GS101-P2-CG

Keywords: neovascularization • cornea: clinical science • vascular endothelial growth factor 
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