PhaseI/II Investigator-Initiated Trial to Investigate Safety and Efficacy of Ripasudil in Patients With Retinopathy of Prematurity

This is an open-label, single-arm phase I/II trial to evaluate the safety and efficacy of Rho-associated protein kinase(ROCK) inhibitor Ripasudil eye drops for preterm infants with Retinopathy of Prematurity(ROP).

Study Overview

• Status: Completed
• Conditions: Retinopathy of Prematurity
• Intervention / Treatment: Drug: Ripasudil ophthalmic solution 0.4%

Detailed Description

Ripasudil eye drops will be administrated to all enrolled preterm infants with zone I/II stage 1 or greater ROP （except for aggressive posterior ROP, Type1 ROP ）.

The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 807-8555
      • University Hospital of Occupational and Environmental Health
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-850
      • Yamaguchi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Informed consent signed by parents or legal guardians of the patient
• 2. Patients born with less than or equal to 32 weeks of gestational age and/or less than or equal to 1,500 grams of birth weight

• 3. Patients with the following types of ROP in both eyes

  1. Zone I ROP with stage greater than or equal to 1
  2. Zone II ROP with stage greater than or equal to 1

Exclusion Criteria:

• 1. Patients with aggressive posterior ROP in one or both eyes
• 2. Patients with type 1 ROP in one or both eyes
• 3. Patients with a confirmed or suspected chromosomal abnormality or genetic disorder
• 4. History of hypersensitivity to ripasudil (including drugs with similar chemical structure) in patients or their mothers
• 5. Patients or their mothers have participated in another intervention study and have used the study drug of another intervention study within 30 days prior to enrollment in this study or within 5 times the half-life of the study drug
• 6. Patients with an ocular structural abnormality that can affect the evaluation of this clinical study by investigators
• 7. Patients with a clinically significant neurological disease (e.g., intraventricular hemorrhage grade 3 or higher, severe hydrocephalus with significantly increased intracranial pressure)
• 8. Patients with inadequate blood access
• 9. Patients with complications, allergies, or worsening systemic conditions that make it difficult to conduct this trial
• 10. Patients judged unsuitable by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Ripasudil eye drops

Drug: Ripasudil ophthalmic solution 0.4%; Phase1 A total of three infants will receive ripasudil eye drops(0.4%) once daily for one week, followed by twice-daily drug administration for two weeks. The three infants who participate in Phase1 can continue to receive the eye drop treatment for additional 9 weeks(12 weeks in total)if the investigators determine that there are no safety issues with ripasudil. In addition, a data and safety monitoring board(DSMB)will be held two times to decide whether the new patients can be enrolled into phase1, and also if phase2 can begin. Phase2:A total of 21 patients will receive ripasudil eye drops(0.4%)twice daily for 12 weeks.; Other Names: GLANATEC ophthalmic solution 0.4%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with Adverse Events(AEs) and Adverse Drug Reactions(ADRs)	Safety Assessment	throughout the study duration(up to week16)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients whose ROP worsens to Type1 ROP in one or both eyes	Efficacy Assessment： ripasudil-treated patients will be assessed in comparison to the medical records of a historical control group	week12 of treatment
Proportion of patients with ROP remission in both eyes	Efficacy Assessment： ripasudil-treated patients will be assessed in comparison to the medical records of a historical control group	week12 of treatment
Concentration of ripasudil and its metabolite M1	Pharmacokinetics, the population pharmacokinetic(popPK)	throughout the study duration(up to week12)

Collaborators and Investigators

• Sponsor: Kyushu University

Publications and helpful links

General Publications

• Yamaguchi M, Nakao S, Arita R, Kaizu Y, Arima M, Zhou Y, Kita T, Yoshida S, Kimura K, Isobe T, Kaneko Y, Sonoda KH, Ishibashi T. Vascular Normalization by ROCK Inhibitor: Therapeutic Potential of Ripasudil (K-115) Eye Drop in Retinal Angiogenesis and Hypoxia. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):2264-76. doi: 10.1167/iovs.15-17411.
• Arima M, Inoue H, Nakao S, Misumi A, Suzuki M, Matsushita I, Araki S, Yamashiro C, Takahashi K, Ochiai M, Yoshida N, Hirose M, Kishimoto J, Todaka K, Hasegawa S, Kimura K, Kusuhara K, Kondo H, Ohga S, Sonoda KH. Study protocol for a multicentre, open-label, single-arm phase I/II trial to evaluate the safety and efficacy of ripasudil 0.4% eye drops for retinopathy of prematurity. BMJ Open. 2021 Jul 27;11(7):e047003. doi: 10.1136/bmjopen-2020-047003.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2020
• Primary Completion (ACTUAL): November 30, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (ACTUAL): November 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Retinopathy of Prematurity; ROP
• Additional Relevant MeSH Terms: Eye Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Retinal Diseases; Premature Birth; Retinopathy of Prematurity; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: CTR180-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No