Phase 3 Clinical Trial Comparing the Safety and Efficacy of Netarsudil to Ripasudil in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: Japan Rho Kinase Elevated Intraocular Pressure Treatment Trial (J-ROCKET)

Abstract

Introduction: A clinical trial evaluated ocular hypotensive efficacy and safety of netarsudil 0.02% once daily (QD) relative to ripasudil 0.4% twice daily (BID).

Methods: This was a single-masked, randomized, phase 3, superiority study. Japanese patients were randomized to either the netarsudil 0.02% group or the ripasudil 0.4% group in a 1:1 ratio and treated for 4 weeks. The primary efficacy variable was mean diurnal intraocular pressure (IOP) (average of diurnal time points at 09:00, 11:00, and 16:00) at Week 4.

Results: A total of 245 patients were included in the primary analysis. At Week 4, least squares (LS) mean of diurnal IOP adjusted for baseline was 15.96 and 17.71 mmHg in the netarsudil 0.02% and ripasudil 0.4% groups, respectively, demonstrating the superiority of netarsudil 0.02% QD over ripasudil 0.4% BID by a margin of - 1.74 mmHg (p < 0.0001). Mean reduction from baseline in mean diurnal IOP at Week 4 was 4.65 and 2.98 mmHg, respectively. Adverse events (AEs) occurred less frequently in netarsudil 0.02% than in ripasudil 0.4%, with the incidence of ocular AEs being 59.8% and 66.7%, respectively. The most frequently reported AE was conjunctival hyperemia in both groups, with an incidence of 54.9% and 62.6%, respectively. No serious eye-related AEs were reported.

Conclusion: Netarsudil ophthalmic solution 0.02% dosed QD (p.m.) was well tolerated and more effective in reducing IOP than ripasudil ophthalmic solution 0.4% dosed BID. Netarsudil 0.02% QD may become an important option for the treatment of Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Trial registration: ClinicalTrials.gov identifier, NCT04620135.

Keywords: Conjunctival hyperemia; Glaucoma; Intraocular pressure; Netarsudil; Rho-associated protein kinase; Ripasudil.

Fig. 1

Study disposition. N total number of patients in the given treatment, n number of patients in a given category. ITT intent-to-treat, PP per protocol

Fig. 2

Mean IOP ± SE of study eye at each timepoint (09:00, 11:00, and 16:00) at baseline, Week 1, Week 2, and Week 4 (ITT population, observed data). IOP intraocular pressure, ITT intent-to-treat, SE standard error, **p value < 0.01, ***p value < 0.001

Fig. 3

Percentage of patients with (A) mean diurnal IOP ≤ 17 mmHg at Week 4, B mean diurnal IOP reduction ≥ 4 mmHg from baseline at Week 4, C) mean diurnal IOP ≥ 20% reduction from baseline at Week 4 in the study eye. IOP intraocular pressure

Fig. 4

Efficacy of netarsudil 0.02% in patient subgroups stratified by baseline mean diurnal IOP of ≥ 20 mmHg or < 20 mmHg. Mean and mean change/mean percent change from baseline in mean diurnal IOP (mean ± SE) at Week 4 (ITT population, observed data). BL baseline, IOP intraocular pressure, ITT intent-to-treat, SE standard error

Fig. 5

Mean conjunctival hyperemia score in the study eye at each timepoint (09:00, 11:00, and 16:00) at baseline, Week 1, Week 2, and Week 4, N.S. not significant, SE standard error, *p value < 0.05, **p value < 0.01, ***p value < 0.001