Ripasudil 0.4% Eye Drops in Fuchs Endothelial Corneal Dystrophy

Fuchs' Endothelial Dystrophy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03575130
• Other study ID #: 2017-002490-19
• Status: Recruiting
• Phase: Phase 2
• Start date: June 5, 2018
• Est. completion date: December 31, 2018

Study information

• Verified date: July 2018
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cornea Guttata
• Corneal Dystrophies, Hereditary
• Corneal Endothelial Cell Loss
• Corneal Endothelial Dystrophy
• Fuchs Dystrophy
• Fuchs' Endothelial Dystrophy
• Iridocorneal Endothelial Syndrome

Intervention

Drug:
• Ripasudil eye drops
Rho-kinase-Inhibitor (IMP)
• Optive eye drops
Artificial tears (placebo)

Procedure:
• Descemetorhexis
Corneal endothelial cells are removed prior to IMP administration by Descemetorhexis.

Locations

Country	Name	City	State
Germany	Department of Ophthalmology, University of Erlangen-Nürnberg	Erlangen

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The occurrence of serious adverse reaction within the observation period of 3 months after descemetorhexis.		3 Months
Secondary	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
Secondary	effect of ripasudil on corneal endothelial cell density (ECD)		within the observation period of 6 months
Secondary	effect of ripasudil on corneal thickness		within the observation period of 6 months
Secondary	effect of on visual acuity (BCVA)		within the observation period of 6 months
Secondary	effect of ripasudil on contrast sensitivity		within the observation period of 6 months
Secondary	assess the need of rescue therapy (DMEK)		within the observation period of 6 months