{"title":"利帕苏地滴眼液对早产儿视网膜病变的安全性和有效性：1/2 期开放标签单臂试验。","authors":"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","doi":"10.1007/s10384-024-01100-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP).</p><p><strong>Study design: </strong>Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"490-499"},"PeriodicalIF":2.1000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial.\",\"authors\":\"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\",\"doi\":\"10.1007/s10384-024-01100-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP).</p><p><strong>Study design: </strong>Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.</p>\",\"PeriodicalId\":14563,\"journal\":{\"name\":\"Japanese Journal of Ophthalmology\",\"volume\":\" \",\"pages\":\"490-499\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Japanese Journal of Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10384-024-01100-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Japanese Journal of Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10384-024-01100-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：评估利帕苏地治疗早产儿视网膜病变（ROP）的安全性和有效性：研究设计：1/2期、多中心、开放标签、单臂、12周临床试验：方法：研究对象为胎龄（GA）≤ 32 周或体重≤ 1500 克、双眼视网膜病变 I 区或 II 区、≥ 1 期的婴儿。患者双眼均使用瑞帕素地尔滴眼液。第一阶段为剂量递增研究（每天1次，持续1周，然后每天2次，持续2周）；如果没有出现安全问题，允许增加剂量至9周。在第2阶段，瑞帕素地尔每天用药两次，持续12周。对不良事件进行了评估。对1型ROP进展患者的比例、1型ROP进展的天数以及ROP进展到最晚期的情况进行了估计：24名婴儿入选（第一阶段，n = 3；第二阶段，n = 21）。分别有19名和4名患者出现全身和眼部不良反应。里帕斯地尔组和历史对照组的疗效终点没有差异。然而，在GA≤27周亚组中，瑞帕素地尔组进展为1型ROP的患者少于历史对照组（P = 0.09）。在GA≤27周亚组中，历史对照组1型ROP进展天数的第25百分位数为22天，而利帕斯地尔组为44天：结论：利帕旭地尔是安全的，它能抑制/延缓1型ROP的进展，尤其是对GA较短的婴儿。
Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial.
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.
期刊介绍：
The Japanese Journal of Ophthalmology (JJO) was inaugurated in 1957 as a quarterly journal published in English by the Ophthalmology Department of the University of Tokyo, with the aim of disseminating the achievements of Japanese ophthalmologists worldwide. JJO remains the only Japanese ophthalmology journal published in English. In 1997, the Japanese Ophthalmological Society assumed the responsibility for publishing the Japanese Journal of Ophthalmology as its official English-language publication.
Currently the journal is published bimonthly and accepts papers from authors worldwide. JJO has become an international interdisciplinary forum for the publication of basic science and clinical research papers.
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