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

Jpn J Ophthalmol. 2024 Sep;68(5):490-499. doi: 10.1007/s10384-024-01100-3. Epub 2024 Jul 26.

Abstract

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.

Keywords: Drug repositioning; Eye drops; Preterm infants; Retinopathy of prematurity; Ripasudil.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Clinical Trial, Phase I

MeSH terms

  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Gestational Age*
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Isoquinolines* / administration & dosage
  • Isoquinolines* / adverse effects
  • Male
  • Ophthalmic Solutions*
  • Retinopathy of Prematurity* / diagnosis
  • Retinopathy of Prematurity* / drug therapy
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Treatment Outcome

Substances

  • K-115
  • Ophthalmic Solutions
  • Isoquinolines
  • Sulfonamides