Abstract：
OBJECTIVE: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP).
METHODS: 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.
CONCLUSIONS: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.
METHODS: 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.
CONCLUSIONS: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.
摘要：
目的：评价瑞帕舒地尔治疗早产儿视网膜病变（ROP）的安全性和有效性。
方法：阶段1/2，多中心，开放标签，单臂,12周临床试验。
方法：胎龄（GA）≤32周或体重≤1500g且具有I区或II区的婴儿，≥1期，纳入双眼ROP。对双眼患者施用利帕舒地尔滴眼液。第一阶段是剂量递增研究（每天一次，持续1周，然后每天两次，共2周）；如果没有发生安全问题，则允许再给药9周。在第2阶段，每天两次给药rapasudil，持续12周。评估不良事件。1型ROP进展的患者比例，1型ROP进展的天数，并估计进展到最晚期的ROP阶段。
结果：24名婴儿入组（1期，n=3；2期，n=21）。19例和4例患者出现全身和眼部不良事件，分别。利帕舒地尔和历史对照组之间的疗效终点没有差异。然而,在GA≤27周亚组中，与历史对照组相比,瑞帕舒地尔组进展为1型ROP的患者较少(P=0.09).在GA≤27周亚组中，1型ROP进展天数的第25百分位数在历史对照组为22天,在利帕舒地尔组为44天.
结论：利帕舒地尔是安全的，可抑制/延迟1型ROP进展，特别是在短GA的婴儿中。
方法：阶段1/2，多中心，开放标签，单臂,12周临床试验。
方法：胎龄（GA）≤32周或体重≤1500g且具有I区或II区的婴儿，≥1期，纳入双眼ROP。对双眼患者施用利帕舒地尔滴眼液。第一阶段是剂量递增研究（每天一次，持续1周，然后每天两次，共2周）；如果没有发生安全问题，则允许再给药9周。在第2阶段，每天两次给药rapasudil，持续12周。评估不良事件。1型ROP进展的患者比例，1型ROP进展的天数，并估计进展到最晚期的ROP阶段。
结果：24名婴儿入组（1期，n=3；2期，n=21）。19例和4例患者出现全身和眼部不良事件，分别。利帕舒地尔和历史对照组之间的疗效终点没有差异。然而,在GA≤27周亚组中，与历史对照组相比,瑞帕舒地尔组进展为1型ROP的患者较少(P=0.09).在GA≤27周亚组中，1型ROP进展天数的第25百分位数在历史对照组为22天,在利帕舒地尔组为44天.
结论：利帕舒地尔是安全的，可抑制/延迟1型ROP进展，特别是在短GA的婴儿中。
