Early termination of a Phase 2 study of FHTR2163 in patients with geographic atrophy secondary to age-related macular degeneration

Abstract

Purpose : The serine protease HtrA1 is active in the retina and ARMS2/HTRA1 is a top locus identified in genome wide association studies imparting increased risk of age-related macular degeneration (AMD). Inhibiting HtrA1 is hypothesized to slow progression of geographic atrophy (GA). GAllego is a Phase 2 study investigating the safety, tolerability, and efficacy of intravitreal injection of FHTR2163, an anti-HtrA1 Fab, in patients with GA.

Methods : Patients were randomized 2:1:2 to receive 20 mg FHTR2163 every 4 weeks (Q4W) or every 8 weeks (Q8W), or sham Q4/8W. The primary endpoint was change in GA area from baseline to Week 72 as measured by fundus autofluorescence (FAF). A monitoring committee conducted periodic unmasked review of cumulative safety/limited efficacy data of the ongoing study, and made recommendations regarding study conduct and continuation. In these reviews, safety was assessed by frequency, severity, and timing of ocular and systemic adverse events and serious adverse events. Efficacy data were only assessed for patients with at least one post-baseline FAF for a benefit-risk analysis.

Results : A total of 360 patients were randomized, with 144 in the FHTR2163 Q4W arm, 74 in the FHTR2163 Q8W arm, and 142 in pooled sham arms. Baseline demographic and ocular characteristics among the three arms were reasonably well-balanced. In August 2022, the rate of intraocular inflammation (IOI) among FHTR2163-treated patients was 16/217 (7.4%). Most cases of IOI were mild or moderate in severity and resolved after treatment with topical steroids. There were no cases of occlusive retinal vasculitis. Among the 153 patients with GA area measurements at 72 weeks, the change in GA area from baseline was 2.67, 2.56, and 2.3 mm², respectively, for the Q4W, Q8W, and pooled sham arms. Differences between the treated and sham groups were not statistically significant.

Conclusions : Based on an assessment of high IOI rates and no observed treatment benefit from FHTR2163, the monitoring committee determined that benefit-risk assessment did not support further treatment with FHTR2163. The study sponsor announced early termination of GAllego, and patients exited the trial after completion of safety follow up. Formal analysis will follow database lock in February 2023.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.