Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial

期刊论文
发表日期：

2024年7月26日

查看全文

Mitsuru Arima,
Hirosuke Inoue,
Akiko Misumi,
Shoko Tsukamoto,
Itsuka Matsushita,
Shunsuke Araki,
Manami Ohta,
Kazumasa Takahashi,
Miyuki Imazato,
Tomoko Goto,
Yoshinori Aoki,
Koshiro Tagawa,
Masayuki Hirose,
Yuito Fujita,
Noriko Yoshida,
Shintaro Nakao,
Hiroyuki Kondo,
Koichi Kusuhara,
Kazuhiro Kimura,
Shunji Hasegawa,
Yasuhiro Ikeda,
Yuki Kodama,
Hiroshi Moritake,
Masayuki Ochiai,
Shouichi Ohga,
Junji Kishimoto,
Koji Todaka,
Ichiro Ieiri,
Koh-Hei Sonoda

摘要

Purpose

To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP).

Study design

Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial.

Methods

Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated.

Results

Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group.

Conclusion

Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.