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

Retinopathy of Prematurity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04621136
• Other study ID #: CTR180-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2023
• Source: Kyushu University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 31, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 4 Months

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

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.

Locations

Country	Name	City	State
Japan	Kyushu University Hospital	Fukuoka
Japan	University Hospital of Occupational and Environmental Health	Kitakyushu	Fukuoka
Japan	Yamaguchi University Hospital	Ube	Yamaguchi

Sponsors (1)

Lead Sponsor	Collaborator
Kyushu University

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with Adverse Events(AEs) and Adverse Drug Reactions(ADRs)	Safety Assessment	throughout the study duration(up to week16)
Secondary	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
Secondary	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
Secondary	Concentration of ripasudil and its metabolite M1	Pharmacokinetics, the population pharmacokinetic(popPK)	throughout the study duration(up to week12)