A Randomized Sham-Controlled Phase 2/3 Trial of QPI-1007 for Acute Nonarteritic Anterior Ischemic Optic Neuropathy.

Purpose: Nonarteritic anterior ischemic optic neuropathy (NAION), the most common acute optic neuropathy in patients > 50 years of age, has no proven therapy. We report the results of a phase 2/3 clinical trial studying the safety and efficacy of intravitreal injection of QPI-1007, a small interfering RNA against the apoptotic protein caspase 2, in participants with acute-onset NAION.

Design: International, multicenter, double-masked, sham-controlled randomized trial.

Participants: Seven hundred twenty-five participants with acute unilateral NAION enrolled within 14 days of visual symptoms.

Methods: Intravitreal injection of QPI-1007 into the study eye of a single dose, multiple dose, or sham injection. Participants were randomized in a 1:1:1:1:1 ratio to 5 treatment groups (down to 3 treatment groups after a preplanned interim analysis): 1 intravitreal injection of 1.5 mg, 1 intravitreal injection of 3 mg, 3 bimonthly intravitreal injections of 1.5 mg each, 3 bimonthly intravitreal injections of 3.0 mg each, or sham injection.

Main outcome measures: The primary end points were safety and the proportion of patients losing at least 15 Early Treatment Diabetic Retinopathy Study letters of best-corrected visual acuity (BCVA) between day 1 and month 6. Secondary outcome measures were mean change in BCVA and mean change in visual field (VF) sensitivity from day 1 to month 6.

Results: At 6 months, no difference was found in the proportion of participants who lost 15 letters or more of BCVA in the multidose groups compared with the sham group. A subanalysis of participants with baseline BCVA of ≤ 60 letters or fewer (Snellen equivalent, ≤ 20/63) demonstrated a significantly lower proportion losing 10 letters of BCVA (P = 0.045 for the 1.5 mg × 3 group and P = 0.0104 for the 3.0 mg × 3 group) compared to sham. Significant prevention of 7-dB loss of VF mean deviation was seen in participants with ≤ 60 letters or fewer at baseline (P = 0.023). No significant differences were found in the frequency of adverse events between groups other than expected side-effects of intravitreal injection.

Conclusions: Intravitreal injection of QPI-1007 in eyes with acute NAION was well tolerated. Although the primary outcome measure was not met, significant effects on preserving vision were observed in the subgroup of participants with baseline BCVA of 20/63 or worse.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.