Ripasudil 0.4% Eye Drops in Fuchs Endothelial Corneal Dystrophy

Study Overview
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Brief Summary
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The cornea forms our window to the world. Hence, its transparency is of utmost importance for vision. Corneal endothelium plays a central role in the maintenance of a transparent corneal stroma. It limits stromal fluid uptake from the anterior chamber of the eye through the formation of tight junctions. Simultaneously, fluid is actively transported from corneal stroma into the anterior chamber. This maintains the corneal stroma in a state of relative dehydration, thereby ensuring a constant distance of stromal collagen lamellae to each other, which in turn forms the basis for transparency of this tissue. If however corneal endothelial function is impaired, stromal swelling leads to corneal clouding and loss of vision. Fuchs endothelial corneal dystrophy represents the most common form of corneal dystrophy. It occurs sporadically, however in some cases autosomal dominant inheritance has been described. This condition leads to progressive loss of corneal endothelium (typically around the age of 50-60 years), causing visual impairment due to swelling and opacification of corneal stroma. Cell culture experiments have been able to show that chemical inhibitors of Rho-Kinase promote corneal endothelial cell proliferation and reduce apoptosis, while topical application in an animal model promoted corneal endothelial wound healing. This has prompted the notion of using topical Rho-kinase-inhibitor treatment to support endothelial cell regeneration in Fuchs endothelial corneal dystrophy. Since September 2014, Rho-kinase-inhibitor eye drops (ripasudil) are clinically available in Japan for reduction of intraocular pressure in Glaucoma patients. Ripasudil eye drops therefore represent a strong candidate for safe and effective adjunctive treatment in patients with Fuchs corneal endothelial cell dystrophy.

Official Title
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Prospective Single-centre Randomized Observer-blind Placebo-controlled Parallel-group Phase IIa Clinical Trial to Investigate the Safety and Efficacy of Ripasudil 0.4% Eye Drops After Descemetorhexis in Patients With Moderate to Advanced Fuchs Endothelial Corneal Dystrophy (FECD)

Conditions
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Fuchs' Endothelial Dystrophy, Fuchs Dystrophy, Corneal Endothelial Dystrophy, Corneal Endothelial Cell Loss, Cornea Guttata

Intervention / Treatment
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* Drug: Ripasudil eye drops
* Drug: Optive eye drops
* Procedure: Descemetorhexis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the subject Understanding of study procedures and willingness to abide by all procedures during the course of the study. Age range: 18-70 years Diagnosis of moderate to advanced FECD with central guttae and clinical relevant corneal endothelial cell loss of <1,000 cells/mm2 and clinical indication of surgical intervention (descemetorhexis) with or without accompanying cataract operation Reduced visual acuity, defined as BCVA <20/30 Woman of childbearing potential must be using a highly effective method of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glanatec<br> | Drug: Ripasudil eye drops<br>* Rho-kinase-Inhibitor (IMP)<br>Procedure: Descemetorhexis<br>* Corneal endothelial cells are removed prior to IMP administration by Descemetorhexis.<br>|
| Placebo Comparator: Placebo<br> | Drug: Optive eye drops<br>* Artificial tears (placebo)<br>Procedure: Descemetorhexis<br>* Corneal endothelial cells are removed prior to IMP administration by Descemetorhexis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of serious adverse reaction within the observation period of 3 months after descemetorhexis. |  | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of adverse event, adverse reaction, serious adverse event, serious adverse reaction and suspected unexpected serious adverse reaction |  | within the observation period of 6 months | 
| effect of ripasudil on corneal endothelial cell density (ECD) |  | within the observation period of 6 months | 
| effect of ripasudil on corneal thickness |  | within the observation period of 6 months | 
| effect of on visual acuity (BCVA) |  | within the observation period of 6 months | 
| effect of ripasudil on contrast sensitivity |  | within the observation period of 6 months | 
| assess the need of rescue therapy (DMEK) |  | within the observation period of 6 months |