Clinical trial NCT04621136: PhaseI/II Investigator-Initiated Trial to Investigate Safety and Efficacy of Ripasudil in Patients With Retinopathy of Prematurity
Official title: PhaseI/II Investigator-Initiated Trial to Investigate Safety and Efficacy of Ripasudil in Patients With Retinopathy of Prematurity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of Prematurity
ROP
Lead sponsor: Kyushu University
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 24
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with Adverse Events(AEs) and Adverse Drug Reactions(ADRs)
timeFrame: throughout the study duration(up to week16)
Secondary outcomes:
measure: Proportion of patients whose ROP worsens to Type1 ROP in one or both eyes
timeFrame: week12 of treatment
measure: Proportion of patients with ROP remission in both eyes
timeFrame: week12 of treatment
measure: Concentration of ripasudil and its metabolite M1
timeFrame: throughout the study duration(up to week12)
Other outcomes:
Locations:
city: Kitakyushu
country: Japan
facility: University Hospital of Occupational and Environmental Health
state: Fukuoka
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
Study officials:
affiliation: Kyushu University Hospital
name: Mitsuru Arima, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.