Ripasudil 0.4% Eye Drops in Fuchs Endothelial Corneal Dystrophy

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)

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.

Study Overview

• Status: Unknown
• Conditions: Fuchs' Endothelial Dystrophy; Fuchs Dystrophy; Corneal Endothelial Dystrophy; Corneal Endothelial Cell Loss; Cornea Guttata
• Intervention / Treatment: Drug: Ripasudil eye drops; Procedure: Descemetorhexis; Drug: Optive eye drops

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Recruiting
    • Department of Ophthalmology, University of Erlangen-Nürnberg
    • Contact: Friedrich E Kruse, Prof.; Phone Number: 34477 +49913185; Email: friedrich.kruse@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent obtained from the subject
2. Understanding of study procedures and willingness to abide by all procedures during the course of the study.
3. Age range: 18-70 years
4. 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
5. Reduced visual acuity, defined as BCVA <20/30
6. Woman of childbearing potential must be using a highly effective method of birth control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): July 12, 2018
• Last Update Submitted That Met QC Criteria: July 10, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Postoperative Complications; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Corneal Diseases; Eye Manifestations; Corneal Dystrophies, Hereditary; Fuchs' Endothelial Dystrophy; Corneal Endothelial Cell Loss; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 2017-002490-19

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
• product manufactured in and exported from the U.S.: No