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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Drug: Ripasudil ophthalmic solution 0.4%


Participation Criteria
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Eligibility Criteria
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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 Zone I ROP with stage greater than or equal to 1 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

Ages Eligible for Study
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Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ripasudil eye drops<br>Ripasudil eye drops | Drug: Ripasudil ophthalmic solution 0.4%<br>* 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.<br>* Other names: GLANATEC ophthalmic solution 0.4%;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinopathy of Prematurity, ROP