Aerie Pharmaceuticals announced that enrollment for its phase 2 clinical trial of netarsudil ophthalmic solution in Japan is complete, a milestone reached several months earlier than previously anticipated.
The first patients to enter this prospective, double-masked, multicenter, placebo-controlled, parallel group phase 2 study were dosed in late March 2019. In approximately 3 months, a total of 215 patients were successfully randomized across four treatment arms: netarsudil ophthalmic solution 0.01%, netarsudil ophthalmic solution 0.02%, netarsudil ophthalmic solution 0.04%, and placebo, all administered once daily in the evening.
Netarsudil ophthalmic solution 0.02% is known by the name Rhopressa in the United States where it is approved for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.
“We believe this rapid enrollment reflects the enthusiasm of the clinical investigators at the 25 centers across Japan that participated in the study and is a credit to our clinical operations teams in Tokyo and the United States,” Vicente Anido, Jr., PhD, Chairman and Chief Executive Officer at Aerie, said in a company news release. “We expect to have topline data from this study in fourth-quarter 2019, allowing us to confirm the concentration of netarsudil we will take forward into phase 3 trials in Japan.”
The study was designed in accordance with the requirements of Japan’s PMDA (Pharmaceuticals and Medical Devices Agency) as a precursor to phase 3 trials supporting potential regulatory submission of netarsudil ophthalmic solution in Japan. The objective of the study is to evaluate the IOP-reducing effect and safety of the three concentrations of netarsudil ophthalmic solution over a 28-day period. Entry criteria include unmedicated baseline IOP ranges at 9 am of 15 mmHg to less than 35 mmHg for patients with open-angle glaucoma, and 22 mmHg to less than 35 mmHg for patients with ocular hypertension. Studies of glaucoma in Japan suggest that patients have baseline IOP that is generally lower than patients in other populations, hence the baseline IOP range in this study begins at 15 mmHg, lower than is typical of glaucoma studies in the United States or Europe.
As agreed with the PMDA, the design of this trial is consistent with that of a recent phase 2 pilot study that Aerie conducted in a Japanese-American population in the United States, with the addition of the netarsudil ophthalmic solution 0.01% treatment arm to confirm the concentration of netarsudil most suitable for Japanese patients. Topline results of the pilot study showed that netarsudil ophthalmic solution 0.02% reduced mean diurnal IOP by a range of 5.0 to 5.3 mmHg in patients with an average baseline IOP of 18.3 mmHg and netarsudil ophthalmic solution 0.04% reduced mean diurnal IOP by a range of 5.2 to 6.6 mmHg in patients with average baseline IOP of 20.2 mmHg. Both netarsudil arms produced significantly greater IOP reduction than placebo at Day 28. The safety findings were consistent with previous netarsudil trials.