Cursiefen, Claus, Viaud, Eric, Bock, Felix, Geudelin, Bernard, Ferry, Antoine, Kadlecova, Pavla, Levy, Michel, Al Mahmood, Salman, Colin, Sylvie, Thorin, Eric, Majo, Francois, Frueh, Beatrice, Wilhelm, Frank, Meyer-Ter-Vehn, Tobias, Geerling, Gerd, Boehringer, Daniel, Reinhard, Thomas, Meller, Daniel, Pleyer, Uwe, Bachmann, Bjoern, Seitz, Berthold, Cursiefen, Claus, Viaud, Eric, Bock, Felix, Geudelin, Bernard, Ferry, Antoine, Kadlecova, Pavla, Levy, Michel, Al Mahmood, Salman, Colin, Sylvie, Thorin, Eric, Majo, Francois, Frueh, Beatrice, Wilhelm, Frank, Meyer-Ter-Vehn, Tobias, Geerling, Gerd, Boehringer, Daniel, Reinhard, Thomas, Meller, Daniel, Pleyer, Uwe, Bachmann, Bjoern, and Seitz, Berthold
Objective: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Design: Multicenter, double-masked, randomized, placebo-controlled phase III study. Participants: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 mu g/day/eye) or placebo twice daily for 90 days and were followed up to day 180. Main Outcome Measures: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Results: Although no significant differences in VAscores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20%(P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious T