Preliminary Baseline Characteristics of Patients with Leber Hereditary Optic Neuropathy (LHON) Enrolled in the RESCUE and REVERSE Clinical Gene Therapy Trials

Abstract

Purpose : RESCUE (NCT02652767) and REVERSE (NCT02652780) are Phase III, randomized, double-masked, sham-controlled trials of rAAV2/2-ND4, an intravitreally-injected gene therapy vector for the treatment of ND4 LHON. RESCUE patients have vision loss for ≤6 months and REVERSE patients from >6 months to 1-year.

Methods : Inclusion criteria included age ≥15-years, presence of the G11778A-ND4 mutation and at least CF vision. Concurrent idebenone use was prohibited. We compared baseline characteristics of the first consecutively-recruited 10 RESCUE and 11 REVERSE patients.

Results : 16/21 were men (RESCUE 8/10, REVERSE 8/11). Mean (range) age (years): RESCUE 39.4 (20-69); REVERSE 36.2 (20-64); (p=0.7312). Mean (range) vision loss duration (days) for all eyes: RESCUE 128 (0-179); REVERSE 294.9 (184-364); p<0.0001. 5/21 patients had simultaneous onset. Two eyes had >20/20 vision at baseline in RESCUE; all eyes were <20/400 in REVERSE. Mean (range) LogMAR at baseline for all eyes: RESCUE 1.109 (-0.2-2.11); REVERSE 1.696 (1-2.26). For best-/worst-seeing eyes: RESCUE: best 0.78 (-0.2-1.5), worst 1.438 (0.6-2.11); REVERSE best 1.586 (1-2.16), worst 1.806 (1.5-2.26). Combining all eyes of RESCUE/REVERSE patients revealed a significant positive correlation (squarerootR²=0.571) between vision loss duration and baseline LogMAR (p<0.0001). Of 82 baseline HVF, 34% were reliable; mean MD was -12.2 (RESCUE) and -27.8 (REVERSE); p=0.0002. Mean (SD) total macular volume (mm³) was smaller in REVERSE (7.7 (0.3) vs. 8.5 (0.4); p< 0.0001) driven by thinning of the RNFL and GCL. A statistically significant relationship existed between retinal metrics and vision, with decreases in RNFL and GCL associated with worse vision (RNFL: p=0.0005; GCL: p=0.0004).

Conclusions : In these preliminary analyses, no age/gender differences were seen between the studies, but there were clinically significant differences in baseline LogMAR for all and best-/worst-seeing eyes, with the expected positive correlation between vision loss duration and worse baseline visual acuities. REVERSE patients demonstrated thinner RNFL, GCL and macular volumes and worse acuity at baseline.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.